Aerobic training increases skin perfusion by a nitric oxide mechanism in type 2 diabetes

Directory of Open Access Journals (Sweden)

Sheri R Colberg

2010-08-01

Full Text Available Sheri R Colberg1, Laura C Hill2, Henri K Parson3, Kathleen S Thomas1, Aaron I Vinik31Old Dominion University, Norfolk; 2State University of New York at Cortland, New York; 3Eastern Virginia Medical School, Norfolk, VirginiaAbstract: It is well known that a number of locally released vasodilatory and ­vasoconstrictive ­compounds can affect skin perfusion. This study investigated the effects of aerobic training on the contribution of nitric oxide (NO, prostaglandins (PG, and endothelial-derived ­hyperpolarizing factor (EDHF in stimulated dorsal foot skin perfusion in individuals with type 2 diabetes (T2DM. Ten previously sedentary, older individuals with T2DM (57.0 ± 3.1 years and nine sedentary controls (53.5 ± 3.2 years were tested before and after undertaking six months of moderate a­erobic training three times weekly in a supervised setting. All subjects underwent measurement of ­baseline (32°C and heat-stimulated (40°C and 44°C dorsal foot skin perfusion starting one hour after ­ingestion of a single, oral 325 mg dose of aspirin, a known inhibitor of PG synthesis. Before aspirin ­ingestion, a subcutaneous microdialysis probe was inserted into each foot dorsum to administer either saline (PG pathway only blocked by aspirin in the left foot or L-NAME (N(G-nitro-l-arginine methyl ester; thereby inhibiting both PG and NO pathways in the right foot. Normative data collected previously on subjects undergoing saline administration via ­microdialysis without aspirin ingestion served as a control group. Significantly lower responsiveness of maximal perfusion was found with the EDHF pathway alone unblocked compared with NO and EDHF unblocked after training. Maximal suppression attributable directly to NO, PG, and EDHF was not significantly different when examined by subject group and training status. However, ­contributions of NO, PG, and EDHF to maximal perfusion were significantly increased, decreased, and unchanged by aerobic training

23 CFR 710.309 - Acquisition.

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2010-04-01

... 23 Highways 1 2010-04-01 2010-04-01 false Acquisition. 710.309 Section 710.309 Highways FEDERAL HIGHWAY ADMINISTRATION, DEPARTMENT OF TRANSPORTATION RIGHT-OF-WAY AND ENVIRONMENT RIGHT-OF-WAY AND REAL ESTATE Project Development § 710.309 Acquisition. The process of acquiring real property includes...

16 CFR 309.17 - Labels.

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2010-01-01

... 16 Commercial Practices 1 2010-01-01 2010-01-01 false Labels. 309.17 Section 309.17 Commercial... ALTERNATIVE FUELS AND ALTERNATIVE FUELED VEHICLES Requirements for Alternative Fuels Label Specifications § 309.17 Labels. All labels must meet the following specifications: (a) Layout: (1) Non-liquid...

22 CFR 309.2 - Scope.

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2010-04-01

... thereof, or any public international organization. (2) Debts arising out of acquisitions contracts subject... 22 Foreign Relations 2 2010-04-01 2010-04-01 true Scope. 309.2 Section 309.2 Foreign Relations PEACE CORPS DEBT COLLECTION General Provisions § 309.2 Scope. (a) Applicability of Federal Claims...

31 CFR 595.309 - Person.

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2010-07-01

... 31 Money and Finance: Treasury 3 2010-07-01 2010-07-01 false Person. 595.309 Section 595.309 Money and Finance: Treasury Regulations Relating to Money and Finance (Continued) OFFICE OF FOREIGN ASSETS CONTROL, DEPARTMENT OF THE TREASURY TERRORISM SANCTIONS REGULATIONS General Definitions § 595.309 Person...

309 plutonium recycle test reactor ion exchanger vault deactivitation report

International Nuclear Information System (INIS)

Griffin, P.W.

1996-03-01

This report documents the deactivation of the ion exchanger vault at the 309 Plutonium Recycle Test Reactor (PRTR) Facility in the 300 Area. The vault deactivation began in May 1995 and was completed in June 1995. The final site restoration and shipment of the low-level waste for disposal was finished in September 1995. The ion exchanger vault deactivation project involved the removal and disposal of twelve ion exchangers and decontaminating and fixing of residual smearable contamination on the ion exchanger vault concrete surfaces

10 CFR 590.309 - Settlements.

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2010-01-01

... 10 Energy 4 2010-01-01 2010-01-01 false Settlements. 590.309 Section 590.309 Energy DEPARTMENT OF... RESPECT TO THE IMPORT AND EXPORT OF NATURAL GAS Procedures § 590.309 Settlements. The parties may conduct settlement negotiations. If settlement negotiations are conducted during a conference, at the request of one...

Role of the Mdm2 SNIP 309 Polymorphism in Gastric Mucosal Morphologic Patterns of Patients with Helicobacter pylori Associated Gastritis.

Science.gov (United States)

Tongtawee, Taweesak; Dechsukhum, Chavaboon; Leeanansaksiri, Wilairat; Kaewpitoon, Soraya; Kaewpitoon, Natthawut; Loyd, Ryan A; Matrakool, Likit; Panpimanmas, Sukij

2016-01-01

The tumor suppressor p53 is as a regulator of cell proliferation, apoptosis and many other biological processes as well as external and internal stress responses. Mdm2 SNIP309 is a negative regulator of 53. Therefore, this study aimed to determine the role of the Mdm2 SNIP 309 polymorphism in the gastric mucosal morphological patterns in patients with Helicobacter pylori associated gastritis. A prospective cross-sectional study was carried out from November 2014 through November 2015. Biopsy specimens were obtained from patients and infection was proven by positive histology. Gastric mucosa specimens were sent to the Molecular Genetics Unit, Institute of Medicine, Suranaree University of Technology where they were tested by molecular methods to detect the patterns of Mdm2 SNIP 309 polymorphism using the real-time PCR hybridization probe method. The results were analyzed and correlated with gastric mucosal morphological patterns by using C-NBI endoscopy. A total of 300 infected patients were enrolled and gastric mucosa specimens were collected. In this study the percentage of Mdm2 SNIP 309 T/T homozygous and Mdm2 SNIP309 G/T heterozygous was 78% and 19 % respectively whereas Mdm2 SNIP309 G/G homozygous was 3%. Mdm2 SNIP 309 T/T homozygous and Mdm2 SNIP309 G/T heterozygosity correlated with type 1 to type 3 gastric mucosal morphological patterns (P<0.01) whereas Mdm2 SNIP309 G/G homozygous correlated with type 4 and type 5 (P<0.01). Our study finds the frequency of Mdm2 SNIP309 G/G in a Thai population is very low, and suggests that this can explain ae Thailand enigma. Types 1 to type 3 are the most common gastric mucosal morphological patterns according to the unique genetic polymorphism of MDM2 SNIP 309 in the Thai population.

21 CFR 520.309 - Carprofen.

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2010-04-01

... 21 Food and Drugs 6 2010-04-01 2010-04-01 false Carprofen. 520.309 Section 520.309 Food and Drugs..., AND RELATED PRODUCTS ORAL DOSAGE FORM NEW ANIMAL DRUGS § 520.309 Carprofen. (a) Specifications. (1) Each caplet contains 25, 75, or 100 milligrams (mg) carprofen. (2) Each chewable tablet contains 25, 75...

22 CFR 309.16 - Review.

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2010-04-01

... 22 Foreign Relations 2 2010-04-01 2010-04-01 true Review. 309.16 Section 309.16 Foreign Relations PEACE CORPS DEBT COLLECTION Salary Offset § 309.16 Review. (a) Request for outside hearing. Except as... hearing or a review of the documentary evidence is requested. If an oral hearing is desired, the request...

31 CFR 309.4 - Taxation.

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2010-07-01

... 31 Money and Finance: Treasury 2 2010-07-01 2010-07-01 false Taxation. 309.4 Section 309.4 Money... OF THE TREASURY BUREAU OF THE PUBLIC DEBT ISSUE AND SALE OF TREASURY BILLS § 309.4 Taxation. The... taxes, whether Federal or State, but shall be exempt from all taxation now or hereafter imposed on the...

The effect of chronic hyperthyroidism and restored euthyroid state by methimazole therapy in rat small mesenteric arteries.

Science.gov (United States)

Khorshidi-Behzadi, Mahdi; Alimoradi, Houman; Haghjoo-Javanmard, Shaghayegh; Reza Sharifi, Mohammad; Rahimi, Nastaran; Dehpour, Ahmad Reza

2013-02-15

Not much has been reported about the effects of hyperthyroidism and its correction on resistance vessels, and just two inconsistent studies have investigated the impacts of restored euthyroidism on vascular reactivity. In this regard, we designed the current study to evaluate the vascular reactivity of the mesenteric arteries of hyperthyroid and restore euthyroid rats. Hyperthyroidism was induced by administration of triiodothyronine (T3; 300μg/kg, i.p., for 12 weeks in T3 group). Euthyroidism was restored by administration of T3 for 8 weeks and then T3+Methimazole (0.003% in drinking water) for 4 weeks (T3+MMI group). According to the McGregor method, vascular relaxation and contractility response were measured in response to acetylcholine or phenylephrine respectively. We found that maximal contractility response (Emax) to phenylephrine in the T3 group was significantly decreased (P0.05). In conclusion, synthesis of both nitric oxide (NO) and endothelium-derived hyperpolarizing factor (EDHF) in mesenteric arteries significantly increased as a consequence of hyperthyroidism, and this abnormal vascular reactivity is corrected by methimazole therapy. Copyright © 2012 Elsevier B.V. All rights reserved.

33 CFR 117.309 - Nassau Sound.

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2010-07-01

... 33 Navigation and Navigable Waters 1 2010-07-01 2010-07-01 false Nassau Sound. 117.309 Section 117.309 Navigation and Navigable Waters COAST GUARD, DEPARTMENT OF HOMELAND SECURITY BRIDGES DRAWBRIDGE OPERATION REGULATIONS Specific Requirements Florida § 117.309 Nassau Sound. The draw of the Fernandina Port...

49 CFR 374.309 - Terminal facilities.

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2010-10-01

... 49 Transportation 5 2010-10-01 2010-10-01 false Terminal facilities. 374.309 Section 374.309... REGULATIONS Adequacy of Intercity Motor Common Carrier Passenger Service § 374.309 Terminal facilities. (a... attendants and be regularly patrolled. (b) Outside facilities. At terminals and stations that are closed when...

9 CFR 309.11 - Vaccine livestock.

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2010-01-01

... 9 Animals and Animal Products 2 2010-01-01 2010-01-01 false Vaccine livestock. 309.11 Section 309.11 Animals and Animal Products FOOD SAFETY AND INSPECTION SERVICE, DEPARTMENT OF AGRICULTURE AGENCY... CERTIFICATION ANTE-MORTEM INSPECTION § 309.11 Vaccine livestock. Vaccine livestock with unhealed lesions of...

31 CFR 551.309 - United States.

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2010-07-01

... 31 Money and Finance: Treasury 3 2010-07-01 2010-07-01 false United States. 551.309 Section 551.309 Money and Finance: Treasury Regulations Relating to Money and Finance (Continued) OFFICE OF....309 United States. The term United States means the United States, its territories and possessions...

47 CFR 69.309 - Other investment.

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2010-10-01

... 47 Telecommunication 3 2010-10-01 2010-10-01 false Other investment. 69.309 Section 69.309... Apportionment of Net Investment § 69.309 Other investment. Investment that is not apportioned pursuant to §§ 69... category and access elements in the same proportions as the combined investment that is apportioned...

14 CFR 1262.309 - Judicial review.

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2010-01-01

... 14 Aeronautics and Space 5 2010-01-01 2010-01-01 false Judicial review. 1262.309 Section 1262.309... PROCEEDINGS Procedures for Considering Applications § 1262.309 Judicial review. Judicial review of final... the determination to the court of the United States having jurisdiction to review the merits of the...

Novel nucleotide and amino acid covariation between the 5'UTR and the NS2/NS3 proteins of hepatitis C virus: bioinformatic and functional analyses.

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Hung-Yu Sun

Full Text Available Molecular covariation of highly polymorphic viruses is thought to have crucial effects on viral replication and fitness. This study employs association rule data mining of hepatitis C virus (HCV sequences to search for specific evolutionary covariation and then tests functional relevance on HCV replication. Data mining is performed between nucleotides in the untranslated regions 5' and 3'UTR, and the amino acid residues in the non-structural proteins NS2, NS3 and NS5B. Results indicate covariance of the 243(rd nucleotide of the 5'UTR with the 14(th, 41(st, 76(th, 110(th, 211(th and 212(th residues of NS2 and with the 71(st, 175(th and 621(st residues of NS3. Real-time experiments using an HCV subgenomic system to quantify viral replication confirm replication regulation for each covariant pair between 5'UTR₂₄₃ and NS2-41, -76, -110, -211, and NS3-71, -175. The HCV subgenomic system with/without the NS2 region shows that regulatory effects vanish without NS2, so replicative modulation mediated by HCV 5'UTR₂₄₃ depends on NS2. Strong binding of the NS2 variants to HCV RNA correlates with reduced HCV replication whereas weak binding correlates with restoration of HCV replication efficiency, as determined by RNA-protein immunoprecipitation assay band intensity. The dominant haplotype 5'UTR₂₄₃-NS2-41-76-110-211-NS3-71-175 differs according to the HCV genotype: G-Ile-Ile-Ile-Gly-Ile-Met for genotype 1b and A-Leu-Val-Leu-Ser-Val-Leu for genotypes 1a, 2a and 2b. In conclusion, 5'UTR₂₄₃ co-varies with specific NS2/3 protein amino acid residues, which may have significant structural and functional consequences for HCV replication. This unreported mechanism involving HCV replication possibly can be exploited in the development of advanced anti-HCV medication.

Role of ferrite and phosphorus plus sulphur in the crack sensitivity of autogenously welded type 309 stainless steel

International Nuclear Information System (INIS)

Lambert, F.J. Jr.

1976-07-01

A study on autogenous welding of Type 309 thin stainless steel sheet was made after experiencing cracking difficulties on several commercial heats. A relationship exists between the sum of the phosphorus plus sulfur, the ferrite control of the weld metal, and the crack sensitivity of autogenously made welds. A new simple weld test for thin-gage sheet is utilized for studying the susceptibility to cracking. A chemistry modification is suggested to alleviate possible weld cracking when autogenously welding this grade. The principles of crack sensitivity prediction could apply to other austenitic stainless steel types where chemistry limits are such that ferrite is possible

22 CFR 309.1 - General purpose.

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2010-04-01

... 22 Foreign Relations 2 2010-04-01 2010-04-01 true General purpose. 309.1 Section 309.1 Foreign Relations PEACE CORPS DEBT COLLECTION General Provisions § 309.1 General purpose. This part prescribes the procedures to be used by the United States Peace Corps (Peace Corps) in the collection and/or disposal of non...

Flavivirus NS3 and NS5 proteins interaction network: a high-throughput yeast two-hybrid screen

Directory of Open Access Journals (Sweden)

Canard Bruno

2011-10-01

Full Text Available Abstract Background The genus Flavivirus encompasses more than 50 distinct species of arthropod-borne viruses, including several major human pathogens, such as West Nile virus, yellow fever virus, Japanese encephalitis virus and the four serotypes of dengue viruses (DENV type 1-4. Each year, flaviviruses cause more than 100 million infections worldwide, some of which lead to life-threatening conditions such as encephalitis or haemorrhagic fever. Among the viral proteins, NS3 and NS5 proteins constitute the major enzymatic components of the viral replication complex and are essential to the flavivirus life cycle. Results We report here the results of a high-throughput yeast two-hybrid screen to identify the interactions between human host proteins and the flavivirus NS3 and NS5 proteins. Using our screen results and literature curation, we performed a global analysis of the NS3 and NS5 cellular targets based on functional annotation with the Gene Ontology features. We finally created the first flavivirus NS3 and NS5 proteins interaction network and analysed the topological features of this network. Our proteome mapping screen identified 108 human proteins interacting with NS3 or NS5 proteins or both. The global analysis of the cellular targets revealed the enrichment of host proteins involved in RNA binding, transcription regulation, vesicular transport or innate immune response regulation. Conclusions We proposed that the selective disruption of these newly identified host/virus interactions could represent a novel and attractive therapeutic strategy in treating flavivirus infections. Our virus-host interaction map provides a basis to unravel fundamental processes about flavivirus subversion of the host replication machinery and/or immune defence strategy.

5 CFR 179.309 - Additional administrative procedures.

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2010-01-01

... 5 Administrative Personnel 1 2010-01-01 2010-01-01 false Additional administrative procedures. 179.309 Section 179.309 Administrative Personnel OFFICE OF PERSONNEL MANAGEMENT CIVIL SERVICE REGULATIONS CLAIMS COLLECTION STANDARDS Administrative Offset § 179.309 Additional administrative procedures. Nothing...

9 CFR 309.14 - Brucellosis-reactor goats.

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2010-01-01

... 9 Animals and Animal Products 2 2010-01-01 2010-01-01 false Brucellosis-reactor goats. 309.14 Section 309.14 Animals and Animal Products FOOD SAFETY AND INSPECTION SERVICE, DEPARTMENT OF AGRICULTURE... INSPECTION AND CERTIFICATION ANTE-MORTEM INSPECTION § 309.14 Brucellosis-reactor goats. Goats which have...

31 CFR 587.309 - Transfer.

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2010-07-01

... 31 Money and Finance: Treasury 3 2010-07-01 2010-07-01 false Transfer. 587.309 Section 587.309 Money and Finance: Treasury Regulations Relating to Money and Finance (Continued) OFFICE OF FOREIGN...; the appointment of any agent, trustee, or fiduciary; the creation or transfer of any lien; the...

31 CFR 542.309 - Transfer.

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2010-07-01

... 31 Money and Finance: Treasury 3 2010-07-01 2010-07-01 false Transfer. 542.309 Section 542.309 Money and Finance: Treasury Regulations Relating to Money and Finance (Continued) OFFICE OF FOREIGN... setting off of any obligation or credit; the appointment of any agent, trustee, or fiduciary; the creation...

31 CFR 547.309 - Transfer.

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2010-07-01

... 31 Money and Finance: Treasury 3 2010-07-01 2010-07-01 false Transfer. 547.309 Section 547.309 Money and Finance: Treasury Regulations Relating to Money and Finance (Continued) OFFICE OF FOREIGN...; the creation or transfer of any lien; the issuance, docketing, filing, or levy of or under any...

31 CFR 543.309 - Transfer.

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2010-07-01

... 31 Money and Finance: Treasury 3 2010-07-01 2010-07-01 false Transfer. 543.309 Section 543.309 Money and Finance: Treasury Regulations Relating to Money and Finance (Continued) OFFICE OF FOREIGN... creation or transfer of any lien; the issuance, docketing, filing, or levy of or under any judgment, decree...

31 CFR 548.309 - Transfer.

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2010-07-01

... 31 Money and Finance: Treasury 3 2010-07-01 2010-07-01 false Transfer. 548.309 Section 548.309 Money and Finance: Treasury Regulations Relating to Money and Finance (Continued) OFFICE OF FOREIGN... setting off of any obligation or credit; the appointment of any agent, trustee, or fiduciary; the creation...

31 CFR 588.309 - Transfer.

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2010-07-01

... 31 Money and Finance: Treasury 3 2010-07-01 2010-07-01 false Transfer. 588.309 Section 588.309 Money and Finance: Treasury Regulations Relating to Money and Finance (Continued) OFFICE OF FOREIGN... creation or transfer of any lien; the issuance, docketing, filing, or levy of or under any judgment, decree...

31 CFR 541.309 - Transfer.

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2010-07-01

... 31 Money and Finance: Treasury 3 2010-07-01 2010-07-01 false Transfer. 541.309 Section 541.309 Money and Finance: Treasury Regulations Relating to Money and Finance (Continued) OFFICE OF FOREIGN... setting off of any obligation or credit; the appointment of any agent, trustee, or fiduciary; the creation...

31 CFR 544.309 - Transfer.

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2010-07-01

... 31 Money and Finance: Treasury 3 2010-07-01 2010-07-01 false Transfer. 544.309 Section 544.309 Money and Finance: Treasury Regulations Relating to Money and Finance (Continued) OFFICE OF FOREIGN... appointment of any agent, trustee, or fiduciary; the creation or transfer of any lien; the issuance, docketing...

31 CFR 546.309 - Transfer.

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2010-07-01

... 31 Money and Finance: Treasury 3 2010-07-01 2010-07-01 false Transfer. 546.309 Section 546.309 Money and Finance: Treasury Regulations Relating to Money and Finance (Continued) OFFICE OF FOREIGN... setting off of any obligation or credit; the appointment of any agent, trustee, or fiduciary; the creation...

31 CFR 515.309 - Transactions.

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2010-07-01

... 31 Money and Finance: Treasury 3 2010-07-01 2010-07-01 false Transactions. 515.309 Section 515.309 Money and Finance: Treasury Regulations Relating to Money and Finance (Continued) OFFICE OF FOREIGN... national thereof, has any interest of any nature whatsoever, direct or indirect, includes, but not by way...

31 CFR 500.309 - Transactions.

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2010-07-01

... 31 Money and Finance: Treasury 3 2010-07-01 2010-07-01 false Transactions. 500.309 Section 500.309 Money and Finance: Treasury Regulations Relating to Money and Finance (Continued) OFFICE OF FOREIGN..., but not by way of limitation: (a) Any payment or transfer to any such designated foreign country or...

Assessment of Drug Binding Potential of Pockets in the NS2B/NS3 Dengue Virus Protein

Science.gov (United States)

Amelia, F.; Iryani; Sari, P. Y.; Parikesit, A. A.; Bakri, R.; Toepak, E. P.; Tambunan, U. S. F.

2018-04-01

Every year an endemic dengue fever estimated to affect over 390 million cases in over 128 countries occurs. However, the antigen types which stimulate the human immune response are variable, as a result, neither effective vaccines nor antiviral treatments have been successfully developed for this disease. The NS2B/NS3 protease of the dengue virus (DENV) responsible for viral replication is a potential drug target. The ligand-enzyme binding site determination is a key role in the success of virtual screening of new inhibitors. The NS2B/NS3 protease of DENV (PDB ID: 2FOM) has two pockets consisting of 37 (Pocket 1) and 27 (Pocket 2) amino acid residues in each pocket. In this research, we characterized the amino acid residues for binding sites in NS3/NS2B based on the hydrophobicity, the percentage of charged residues, volume, depth, ΔGbinding, hydrogen bonding and bond length. The hydrophobic percentages of both pockets are high, 59 % (Pocket 1) and 41% (Pocket 2) and the percentage of charged residues in Pocket 1 and 2 are 22% and 48%, and the pocket volume is less than 700 Å3. An interaction analysis using molecular docking showed that interaction between the ligand complex and protein in Pocket 1 is more negative than Pocket 2. As a result, Pocket 1 is the better potential target for a ligand to inhibit the action of NS2B/NS3 DENV.

29 CFR 780.309 - Man-day exclusion.

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2010-07-01

... 29 Labor 3 2010-07-01 2010-07-01 false Man-day exclusion. 780.309 Section 780.309 Labor...) Statutory Provisions § 780.309 Man-day exclusion. Section 3(e)(1) specifically excludes from the employer's man-day total (as defined in section 3(u)) employees who qualify for exemption under section 13(a)(6...

12 CFR 309.7 - Service of process.

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2010-01-01

... 12 Banks and Banking 4 2010-01-01 2010-01-01 false Service of process. 309.7 Section 309.7 Banks... INFORMATION § 309.7 Service of process. (a) Service. Any subpoena or other legal process to obtain information... is named as a party, service of process shall be made pursuant to the Federal Rules of Civil...

Interference of transcription across H-NS binding sites and repression by H-NS.

Science.gov (United States)

Rangarajan, Aathmaja Anandhi; Schnetz, Karin

2018-05-01

Nucleoid-associated protein H-NS represses transcription by forming extended DNA-H-NS complexes. Repression by H-NS operates mostly at the level of transcription initiation. Less is known about how DNA-H-NS complexes interfere with transcription elongation. In vitro H-NS has been shown to enhance RNA polymerase pausing and to promote Rho-dependent termination, while in vivo inhibition of Rho resulted in a decrease of the genome occupancy by H-NS. Here we show that transcription directed across H-NS binding regions relieves H-NS (and H-NS/StpA) mediated repression of promoters in these regions. Further, we observed a correlation of transcription across the H-NS-bound region and de-repression. The data suggest that the transcribing RNA polymerase is able to remodel the H-NS complex and/or dislodge H-NS from the DNA and thus relieve repression. Such an interference of transcription and H-NS mediated repression may imply that poorly transcribed AT-rich loci are prone to be repressed by H-NS, while efficiently transcribed loci escape repression. © 2018 John Wiley & Sons Ltd.

40 CFR 63.309 - Performance tests and procedures.

Science.gov (United States)

2010-07-01

... 40 Protection of Environment 9 2010-07-01 2010-07-01 false Performance tests and procedures. 63.309 Section 63.309 Protection of Environment ENVIRONMENTAL PROTECTION AGENCY (CONTINUED) AIR PROGRAMS... Standards for Coke Oven Batteries § 63.309 Performance tests and procedures. (a) Except as otherwise...

Resistance Analyses of HCV NS3/4A Protease and NS5B Polymerase from Clinical Studies of Deleobuvir and Faldaprevir.

Directory of Open Access Journals (Sweden)

Kristi L Berger

Full Text Available The resistance profile of anti-hepatitis C virus (HCV agents used in combination is important to guide optimal treatment regimens. We evaluated baseline and treatment-emergent NS3/4A and NS5B amino-acid variants among HCV genotype (GT-1a and -1b-infected patients treated with faldaprevir (HCV protease inhibitor, deleobuvir (HCV polymerase non-nucleoside inhibitor, and ribavirin in multiple clinical studies.HCV NS3/4A and NS5B population sequencing (Sanger method was performed on all baseline plasma samples (n = 1425 NS3; n = 1556 NS5B and on post-baseline plasma samples from patients with virologic failure (n = 113 GT-1a; n = 221 GT-1b. Persistence and time to loss of resistance-associated variants (RAVs was estimated using Kaplan-Meier analysis.Faldaprevir RAVs (NS3 R155 and D168 and deleobuvir RAVs (NS5B 495 and 496 were rare (90%. Virologic relapse was associated with RAVs in both NS3 and NS5B (53% GT-1b; 52% GT-1b; some virologic relapses had NS3 RAVs only (47% GT-1a; 17% GT-1b. Median time to loss of GT-1b NS5B P495 RAVs post-treatment (5 months was less than that of GT-1b NS3 D168 (8.5 months and GT-1a R155 RAVs (11.5 months.Faldaprevir and deleobuvir RAVs are more prevalent among virologic failures than at baseline. Treatment response was not compromised by common NS3 polymorphisms; however, alanine at NS5B amino acid 499 at baseline (wild-type in GT-1a, polymorphism in GT-1b may reduce response to this deleobuvir-based regimen.

22 CFR 309.17 - Procedures for salary offset.

Science.gov (United States)

2010-04-01

... 22 Foreign Relations 2 2010-04-01 2010-04-01 true Procedures for salary offset. 309.17 Section 309.17 Foreign Relations PEACE CORPS DEBT COLLECTION Salary Offset § 309.17 Procedures for salary offset. Unless otherwise provided by statute or contract, the following procedures apply to salary offset: (a...

31 CFR 540.309 - Natural uranium.

Science.gov (United States)

2010-07-01

... 31 Money and Finance: Treasury 3 2010-07-01 2010-07-01 false Natural uranium. 540.309 Section 540... FOREIGN ASSETS CONTROL, DEPARTMENT OF THE TREASURY HIGHLY ENRICHED URANIUM (HEU) AGREEMENT ASSETS CONTROL REGULATIONS General Definitions § 540.309 Natural uranium. The term natural uranium means uranium found in...

Silencing by H-NS potentiated the evolution of Salmonella.

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Sabrina S Ali

2014-11-01

Full Text Available The bacterial H-NS protein silences expression from sequences with higher AT-content than the host genome and is believed to buffer the fitness consequences associated with foreign gene acquisition. Loss of H-NS results in severe growth defects in Salmonella, but the underlying reasons were unclear. An experimental evolution approach was employed to determine which secondary mutations could compensate for the loss of H-NS in Salmonella. Six independently derived S. Typhimurium hns mutant strains were serially passaged for 300 generations prior to whole genome sequencing. Growth rates of all lineages dramatically improved during the course of the experiment. Each of the hns mutant lineages acquired missense mutations in the gene encoding the H-NS paralog StpA encoding a poorly understood H-NS paralog, while 5 of the mutant lineages acquired deletions in the genes encoding the Salmonella Pathogenicity Island-1 (SPI-1 Type 3 secretion system critical to invoke inflammation. We further demonstrate that SPI-1 misregulation is a primary contributor to the decreased fitness in Salmonella hns mutants. Three of the lineages acquired additional loss of function mutations in the PhoPQ virulence regulatory system. Similarly passaged wild type Salmonella lineages did not acquire these mutations. The stpA missense mutations arose in the oligomerization domain and generated proteins that could compensate for the loss of H-NS to varying degrees. StpA variants most able to functionally substitute for H-NS displayed altered DNA binding and oligomerization properties that resembled those of H-NS. These findings indicate that H-NS was central to the evolution of the Salmonellae by buffering the negative fitness consequences caused by the secretion system that is the defining characteristic of the species.

49 CFR 1016.309 - Agency review.

Science.gov (United States)

2010-10-01

... 49 Transportation 8 2010-10-01 2010-10-01 false Agency review. 1016.309 Section 1016.309... Agency review. In the event the adjudicative officer is not the entire Board, the applicant or agency counsel may seek review of the initial decision on the fee application, or the Board may review the...

Two-year clinical comparison of a flowable-type nano-hybrid composite and a paste-type composite in posterior restoration.

Science.gov (United States)

Hirata-Tsuchiya, Shizu; Yoshii, Shinji; Ichimaru-Suematsu, Miki; Washio, Ayako; Saito, Noriko; Urata, Mariko; Hanada, Kaori; Morotomi, Takahiko; Kitamura, Chiaki

2017-08-01

The purpose of the present study was to compare the clinical efficacy between a flowable-type nano-hybrid composite and a paste-type composite for posterior restoration. Of 62 posterior teeth in 33 patients (mean age: 34.1 years), 31 were filled with a paste-type composite (Heliomolar [HM] group), and another 31 with a flowable nano-hybrid composite (MI FIL [MI] group). Clinical efficacy was evaluated at 2 years after the restoration. There were no differences for retention, surface texture deterioration, anatomical form change, deterioration of marginal adaptation, and secondary caries, while a statistical difference was found for marginal discoloration, which was significantly greater in the HM group (P < 0.05). Furthermore, color matching in the MI group was superior to that in the HM group immediately after the restoration throughout the study period. The present 2-year clinical evaluation of different composites showed that the flowable nano-hybrid composite could be an effective esthetic material for posterior restoration. © 2016 John Wiley & Sons Australia, Ltd.

40 CFR 90.309 - Engine intake air temperature measurement.

Science.gov (United States)

2010-07-01

... 40 Protection of Environment 20 2010-07-01 2010-07-01 false Engine intake air temperature measurement. 90.309 Section 90.309 Protection of Environment ENVIRONMENTAL PROTECTION AGENCY (CONTINUED) AIR... Emission Test Equipment Provisions § 90.309 Engine intake air temperature measurement. (a) The measurement...

Mutagenesis of Dengue Virus Protein NS2A Revealed a Novel Domain Responsible for Virus-Induced Cytopathic Effect and Interactions between NS2A and NS2B Transmembrane Segments.

Science.gov (United States)

Wu, Ren-Huang; Tsai, Ming-Han; Tsai, Kuen-Nan; Tian, Jia Ni; Wu, Jian-Sung; Wu, Su-Ying; Chern, Jyh-Haur; Chen, Chun-Hong; Yueh, Andrew

2017-06-15

The NS2A protein of dengue virus (DENV) has eight predicted transmembrane segments (pTMS1 to -8) and participates in RNA replication, virion assembly, and host antiviral response. However, the roles of specific amino acid residues within the pTMS regions of NS2A during the viral life cycle are not clear. Here, we explore the function of DENV NS2A by introducing a series of alanine substitutions into the N-terminal half (pTMS1 to -4) of the protein in the context of a DENV infectious clone or subgenomic replicon. Six NS2A mutants (NM5, -7, -9, and -17 to -19) around pTMS1 and -2 displayed a novel phenotype showing a >1,000-fold reduction in virus yield, an absence of plaque formation despite wild-type-like replicon activity, and infectious-virus-like particle yields. HEK-293 cells infected with the six NS2A mutant viruses failed to cause a virus-induced cytopathic effect (CPE) by MitoCapture staining, cell proliferation, and lactate dehydrogenase release assays. Sequencing analyses of pseudorevertant viruses derived from lethal-mutant viruses revealed two consensus reversion mutations, leucine to phenylalanine at codon 181 (L181F) within pTMS7 of NS2A and isoleucine to threonine at codon 114 (I114T) within NS2B. The introduction of an NS2A-L181F mutation into the lethal (NM15, -16, -25, and -33) and CPE-defective (NM7, -9, and -19) mutants substantially rescued virus infectivity and virus-induced CPE, respectively, whereas the NS2B-L114T mutation rescued the NM16, -25, and -33 mutants. In conclusion, the results revealed the essential roles of the N-terminal half of NS2A in RNA replication and virus-induced CPE. Intramolecular interactions between pTMSs of NS2A and intermolecular interactions between the NS2A and NS2B proteins were also implicated. IMPORTANCE The characterization of the N-terminal (current study) and C-terminal halves of DENV NS2A is the most comprehensive mutagenesis study to date to investigate the function of NS2A during the flaviviral life cycle

9 CFR 381.309 - Finished product inspection.

Science.gov (United States)

2010-01-01

... Section 381.309 Animals and Animal Products FOOD SAFETY AND INSPECTION SERVICE, DEPARTMENT OF AGRICULTURE AGENCY ORGANIZATION AND TERMINOLOGY; MANDATORY MEAT AND POULTRY PRODUCTS INSPECTION AND VOLUNTARY INSPECTION AND CERTIFICATION POULTRY PRODUCTS INSPECTION REGULATIONS Canning and Canned Products § 381.309...

40 CFR 91.309 - Engine intake air temperature measurement.

Science.gov (United States)

2010-07-01

... measurement. 91.309 Section 91.309 Protection of Environment ENVIRONMENTAL PROTECTION AGENCY (CONTINUED) AIR... Provisions § 91.309 Engine intake air temperature measurement. (a) Engine intake air temperature measurement must be made within 100 cm of the air-intake of the engine. The measurement location must be either in...

Identification of drug resistance and immune-driven variations in hepatitis C virus (HCV) NS3/4A, NS5A and NS5B regions reveals a new approach toward personalized medicine.

Science.gov (United States)

Ikram, Aqsa; Obaid, Ayesha; Awan, Faryal Mehwish; Hanif, Rumeza; Naz, Anam; Paracha, Rehan Zafar; Ali, Amjad; Janjua, Hussnain Ahmed

2017-01-01

Cellular immune responses (T cell responses) during hepatitis C virus (HCV) infection are significant factors for determining the outcome of infection. HCV adapts to host immune responses by inducing mutations in its genome at specific sites that are important for HLA processing/presentation. Moreover, HCV also adapts to resist potential drugs that are used to restrict its replication, such as direct-acting antivirals (DAAs). Although DAAs have significantly reduced disease burden, resistance to these drugs is still a challenge for the treatment of HCV infection. Recently, drug resistance mutations (DRMs) observed in HCV proteins (NS3/4A, NS5A and NS5B) have heightened concern that the emergence of drug resistance may compromise the effectiveness of DAAs. Therefore, the NS3/4A, NS5A and NS5B drug resistance variations were investigated in this study, and their prevalence was examined in a large number of protein sequences from all HCV genotypes. Furthermore, potential CD4 + and CD8 + T cell epitopes were predicted and their overlap with genetic variations was explored. The findings revealed that many reported DRMs within NS3/4A, NS5A and NS5B are not drug-induced; rather, they are already present in HCV strains, as they were also detected in HCV-naïve patients. This study highlights several hot spots in which HLA and drug selective pressure overlap. Interestingly, these overlapping mutations were frequently observed among many HCV genotypes. This study implicates that knowledge of the host HLA type and HCV subtype/genotype can provide important information in defining personalized therapy. Copyright © 2016 Elsevier B.V. All rights reserved.

9 CFR 318.309 - Finished product inspection.

Science.gov (United States)

2010-01-01

... Section 318.309 Animals and Animal Products FOOD SAFETY AND INSPECTION SERVICE, DEPARTMENT OF AGRICULTURE AGENCY ORGANIZATION AND TERMINOLOGY; MANDATORY MEAT AND POULTRY PRODUCTS INSPECTION AND VOLUNTARY... Canning and Canned Products § 318.309 Finished product inspection. (a) Finished product inspections must...

NS19504

DEFF Research Database (Denmark)

Nausch, Bernhard; Rode, Frederik; Jørgensen, Susanne

2014-01-01

channel activators and identified a small-molecule positive modulator, NS19504 (5-[(4-bromophenyl)methyl]-1,3-thiazol-2-amine), which activated the BK channel with an EC50 value of 11.0 ± 1.4 µM. Hit validation was performed using high-throughput electrophysiology (QPatch), and further characterization......19504 activated BK channels in native smooth muscle cells from guinea pig urinary bladder. In guinea pig urinary bladder strips, NS19504 (1 µM) reduced spontaneous phasic contractions, an effect that was significantly inhibited by the specific BK channel blocker iberiotoxin. In contrast, NS19504 (1 µ......M) only modestly inhibited nerve-evoked contractions and had no effect on contractions induced by a high K(+) concentration consistent with a K(+) channel-mediated action. Collectively, these results show that NS19504 is a positive modulator of BK channels and provide support for the role of BK channels...

Different Types of nsP3-Containing Protein Complexes in Sindbis Virus-Infected Cells▿

Science.gov (United States)

Gorchakov, Rodion; Garmashova, Natalia; Frolova, Elena; Frolov, Ilya

2008-01-01

Alphaviruses represent a serious public health threat and cause a wide variety of diseases, ranging from severe encephalitis, which can result in death or neurological sequelae, to mild infection, characterized by fever, skin rashes, and arthritis. In the infected cells, alphaviruses express only four nonstructural proteins, which function in the synthesis of virus-specific RNAs and in modification of the intracellular environment. The results of our study suggest that Sindbis virus (SINV) infection in BHK-21 cells leads to the formation of at least two types of nsP3-containing complexes, one of which was found in association with the plasma membrane and endosome-like vesicles, while the second was coisolated with cell nuclei. The latter complexes could be solubilized only with the cytoskeleton-destabilizing detergent. Besides viral nsPs, in the mammalian cells, both complexes contained G3BP1 and G3BP2 (which were found in different ratios), YBX1, and HSC70. Rasputin, an insect cell-specific homolog of G3BP1, was found in the nsP3-containing complexes isolated from mosquito cells, which was suggestive of a high conservation of the complexes in the cells of both vertebrate and invertebrate origin. The endosome- and plasma membrane-associated complexes contained a high concentration of double-stranded RNAs (dsRNAs), which is indicative of their function in viral-RNA synthesis. The dsRNA synthesis is likely to efficiently proceed on the plasma membrane, and at least some of the protein-RNA complexes would then be transported into the cytosol in association with the endosome-like vesicular organelles. These findings provide new insight into the mechanism of SINV replication and virus-host cell interactions. PMID:18684830

Different types of nsP3-containing protein complexes in Sindbis virus-infected cells.

Science.gov (United States)

Gorchakov, Rodion; Garmashova, Natalia; Frolova, Elena; Frolov, Ilya

2008-10-01

Alphaviruses represent a serious public health threat and cause a wide variety of diseases, ranging from severe encephalitis, which can result in death or neurological sequelae, to mild infection, characterized by fever, skin rashes, and arthritis. In the infected cells, alphaviruses express only four nonstructural proteins, which function in the synthesis of virus-specific RNAs and in modification of the intracellular environment. The results of our study suggest that Sindbis virus (SINV) infection in BHK-21 cells leads to the formation of at least two types of nsP3-containing complexes, one of which was found in association with the plasma membrane and endosome-like vesicles, while the second was coisolated with cell nuclei. The latter complexes could be solubilized only with the cytoskeleton-destabilizing detergent. Besides viral nsPs, in the mammalian cells, both complexes contained G3BP1 and G3BP2 (which were found in different ratios), YBX1, and HSC70. Rasputin, an insect cell-specific homolog of G3BP1, was found in the nsP3-containing complexes isolated from mosquito cells, which was suggestive of a high conservation of the complexes in the cells of both vertebrate and invertebrate origin. The endosome- and plasma membrane-associated complexes contained a high concentration of double-stranded RNAs (dsRNAs), which is indicative of their function in viral-RNA synthesis. The dsRNA synthesis is likely to efficiently proceed on the plasma membrane, and at least some of the protein-RNA complexes would then be transported into the cytosol in association with the endosome-like vesicular organelles. These findings provide new insight into the mechanism of SINV replication and virus-host cell interactions.

24 CFR 5.309 - Prohibition against discrimination.

Science.gov (United States)

2010-04-01

.... 5.309 Section 5.309 Housing and Urban Development Office of the Secretary, Department of Housing and Urban Development GENERAL HUD PROGRAM REQUIREMENTS; WAIVERS Pet Ownership for the Elderly or Persons... any tenant of such housing from owning common household pets or having such pets living in the tenant...

The texture, structure and nutrient availability of artificial soil on cut slopes restored with OSSS - Influence of restoration time.

Science.gov (United States)

Huang, Zhiyu; Chen, Jiao; Ai, Xiaoyan; Li, Ruirui; Ai, Yingwei; Li, Wei

2017-09-15

Outside soil spray seeding (OSSS) is widely used to restore cut slopes in southwest of China, and artificial soil is often sprayed onto cut slopes to establish a soil layer for revegetation. The stability of artificial soil layer and its supply of water and nutrients for plants is crucial for successful restoration. To evaluate the long-term effectiveness of OSSS, the texture, structure and nutrient availability of artificial soil were studied, various soil samples were obtained from three cut slopes with different restoration time (restored with OSSS in 1996, 2003 and 2007 respectively) and one natural developed slope (NS). The properties measured including soil particle size distribution (PSD), texture, fractal dimension of PSD (D m ), the bias (C S ) and peak convex (C E ) coefficients of aggregate size distribution, structure failure rate, bulk density, moisture, pH, soil organic carbon (SOC), calcium carbonate content, Available nitrogen (N A ), Available phosphorus (P A ), and Available potassium (K A ). The results showed that different restoration time resulted in significant differences in soil PSD, D m , C S , C E , structure failure rate, bulk density, moisture, pH, N A , and K A . And these properties improved with increasing restoration age. However, there is still a huge disparity in soil texture, structure, and the availability of nutrients and moisture between the cut slopes and NS over a restoration period of up to 17 years, and this is caused by the little fine particles and the lack of slow release fertilizers and organic fertilizers in the artificial soil, resulting in poorer soil structure stability, retention and availability of moisture and nutrients on the cut slopes. Overall, the OSSS technique shows a long-term effectiveness in southwest of China, but there is still room for improvement. Copyright © 2017 Elsevier Ltd. All rights reserved.

50 ns Backup Solution

CERN Document Server

Kain, V; Bartosik, H; Goddard, B; Höfle, W; Iadarola, G; Meddahi, M; Pieloni, T; Rumolo, G; Salvant, B; Wenninger, J

2014-01-01

The baseline bunch spacing for LHC high luminosity proton-proton operation after LS3 is 25 ns to maximize the integrated luminosity while keeping the pile-up low. The success of this mode of operation is not guaranteed. Electron cloud, UFOs, long-range beambeam, heating and other effects might make 25 ns operation in the LHC and/or the injectors difficult. This talk will review possible showstoppers in the LHC and injectors for 25 ns operation and discuss possible remedies. An alternative would be re-considering 50 ns operation. An estimate of the 50 ns performance will be given. The question of whether a different upgrade path would have to be chosen in case of 50 ns operation will also be addressed.

50 ns Backup Solution

International Nuclear Information System (INIS)

Kain, V; Arduini, G; Bartosik, H; Goddard, B; Höfle, W; Iadarola, G; Meddahi, M; Pieloni, T; Rumolo, G; Salvant, B; Wenninger, J

2014-01-01

The baseline bunch spacing for LHC high luminosity proton-proton operation after LS3 is 25 ns to maximize the integrated luminosity while keeping the pile-up low. The success of this mode of operation is not guaranteed. Electron cloud, UFOs, long-range beambeam, heating and other effects might make 25 ns operation in the LHC and/or the injectors difficult. This talk will review possible showstoppers in the LHC and injectors for 25 ns operation and discuss possible remedies. An alternative would be re-considering 50 ns operation. An estimate of the 50 ns performance will be given. The question of whether a different upgrade path would have to be chosen in case of 50 ns operation will also be addressed

28 CFR 24.309 - Payment of award.

Science.gov (United States)

2010-07-01

... 28 Judicial Administration 1 2010-07-01 2010-07-01 false Payment of award. 24.309 Section 24.309 Judicial Administration DEPARTMENT OF JUSTICE IMPLEMENTATION OF THE EQUAL ACCESS TO JUSTICE ACT IN... decision is not being sought in the United States courts, or that the process for seeking review of the...

31 CFR 598.309 - Narcotic drug; controlled substance; listed chemical.

Science.gov (United States)

2010-07-01

...; listed chemical. 598.309 Section 598.309 Money and Finance: Treasury Regulations Relating to Money and... SANCTIONS REGULATIONS General Definitions § 598.309 Narcotic drug; controlled substance; listed chemical. The terms narcotic drug, controlled substance, and listed chemical have the meanings given those terms...

Construction and analysis of a plant non-specific lipid transfer protein database (nsLTPDB).

Science.gov (United States)

Wang, Nai-Jyuan; Lee, Chi-Ching; Cheng, Chao-Sheng; Lo, Wei-Cheng; Yang, Ya-Fen; Chen, Ming-Nan; Lyu, Ping-Chiang

2012-01-01

Plant non-specific lipid transfer proteins (nsLTPs) are small and basic proteins. Recently, nsLTPs have been reported involved in many physiological functions such as mediating phospholipid transfer, participating in plant defence activity against bacterial and fungal pathogens, and enhancing cell wall extension in tobacco. However, the lipid transfer mechanism of nsLTPs is still unclear, and comprehensive information of nsLTPs is difficult to obtain. In this study, we identified 595 nsLTPs from 121 different species and constructed an nsLTPs database--nsLTPDB--which comprises the sequence information, structures, relevant literatures, and biological data of all plant nsLTPs http://nsltpdb.life.nthu.edu.tw/. Meanwhile, bioinformatics and statistics methods were implemented to develop a classification method for nsLTPs based on the patterns of the eight highly-conserved cysteine residues, and to suggest strict Prosite-styled patterns for Type I and Type II nsLTPs. The pattern of Type I is C X2 V X5-7 C [V, L, I] × Y [L, A, V] X8-13 CC × G X12 D × [Q, K, R] X2 CXC X16-21 P X2 C X13-15C, and that of Type II is C X4 L X2 C X9-11 P [S, T] X2 CC X5 Q X2-4 C[L, F]C X2 [A, L, I] × [D, N] P X10-12 [K, R] X4-5 C X3-4 P X0-2 C. Moreover, we referred the Prosite-styled patterns to the experimental mutagenesis data that previously established by our group, and found that the residues with higher conservation played an important role in the structural stability or lipid binding ability of nsLTPs. Taken together, this research has suggested potential residues that might be essential to modulate the structural and functional properties of plant nsLTPs. Finally, we proposed some biologically important sites of the nsLTPs, which are described by using a new Prosite-styled pattern that we defined.

Construction and analysis of a plant non-specific lipid transfer protein database (nsLTPDB

Directory of Open Access Journals (Sweden)

Wang Nai-Jyuan

2012-01-01

Full Text Available Abstract Background Plant non-specific lipid transfer proteins (nsLTPs are small and basic proteins. Recently, nsLTPs have been reported involved in many physiological functions such as mediating phospholipid transfer, participating in plant defence activity against bacterial and fungal pathogens, and enhancing cell wall extension in tobacco. However, the lipid transfer mechanism of nsLTPs is still unclear, and comprehensive information of nsLTPs is difficult to obtain. Methods In this study, we identified 595 nsLTPs from 121 different species and constructed an nsLTPs database -- nsLTPDB -- which comprises the sequence information, structures, relevant literatures, and biological data of all plant nsLTPs http://nsltpdb.life.nthu.edu.tw/. Results Meanwhile, bioinformatics and statistics methods were implemented to develop a classification method for nsLTPs based on the patterns of the eight highly-conserved cysteine residues, and to suggest strict Prosite-styled patterns for Type I and Type II nsLTPs. The pattern of Type I is C X2 V X5-7 C [V, L, I] × Y [L, A, V] X8-13 CC × G X12 D × [Q, K, R] X2 CXC X16-21 P X2 C X13-15C, and that of Type II is C X4 L X2 C X9-11 P [S, T] X2 CC X5 Q X2-4 C[L, F]C X2 [A, L, I] × [D, N] P X10-12 [K, R] X4-5 C X3-4 P X0-2 C. Moreover, we referred the Prosite-styled patterns to the experimental mutagenesis data that previously established by our group, and found that the residues with higher conservation played an important role in the structural stability or lipid binding ability of nsLTPs. Conclusions Taken together, this research has suggested potential residues that might be essential to modulate the structural and functional properties of plant nsLTPs. Finally, we proposed some biologically important sites of the nsLTPs, which are described by using a new Prosite-styled pattern that we defined.

Borneo: The new NS sunflower confectionary type hybrid

Directory of Open Access Journals (Sweden)

Hladni Nada

2009-01-01

Full Text Available At the Institute of Field and Vegetable Crops in Novi Sad, beside the basic direction in sunflower breeding, the creation of standard hybrids with high oil content with high seed and oil yield, hybrids are being created for special confectionery purposes directed towards the final kernel products. In this program, apart from breeding in order to improve main seed yield components, special attention is given to the increase of protein content and the quality with the decrease of seed oil content, to the increase of the weight of 1000 seeds and to the decrease of content of the shell. Two-line SC hybrid was created by crossing the cytoplasmatic male sterile line of the mother with a father line with fertility restoration genes. Borneo is a high protein confectionary type hybrid that has been registered in Slovakia (EU in 2009. It contains successfully combined genes responsible for high genetic potential for yield and valuable technical and technological seed traits. The hybrid is adequate for nutrition, dehuling and kernel production. Borneo is a medium early hybrid with the genetic potential for yield of over 4,5t/ha and its seed oil content is under 43%. .

Giant magnons under NS-NS and Melvin fields

International Nuclear Information System (INIS)

Huang, W.-H.

2006-01-01

The giant magnon is a rotating spiky string configuration which has the same dispersion relation between the energy and angular momentum as that of a spin magnon. In this paper we investigate the effects of the NS-NS and Melvin fields on the giant magnon. We first analyze the energy and angular momenta of the two-spin spiky D-string moving on the AdS 3 x S 1 with the NS-NS field. Due to the infinite boundary of the AdS spacetime the D-string solution will extend to infinity and it appears the divergences. After adding the counter terms we obtain the dispersion relation of the corresponding giant magnon. The result shows that there will appear a prefactor before the angular momentum, in addition to some corrections in the sine function. We also see that the spiky profile of a rotating D-string plays an important role in mapping it to a spin magnon. We next investigate the energy and angular momentum of the one-spin spiky fundamental string moving on the R x S 2 with the electric or magnetic Melvin field. The dispersion relation of the corresponding deformed giant magnon is also obtained. We discuss some properties of the correction terms and their relations to the spin chain with deformations

Host cell killing by the West Nile Virus NS2B-NS3 proteolytic complex: NS3 alone is sufficient to recruit caspase-8-based apoptotic pathway

International Nuclear Information System (INIS)

Ramanathan, Mathura P.; Chambers, Jerome A.; Pankhong, Panyupa; Chattergoon, Michael; Attatippaholkun, Watcharee; Dang, Kesen; Shah, Neelima; Weiner, David B.

2006-01-01

The West Nile Virus (WNV) non-structural proteins 2B and 3 (NS2B-NS3) constitute the proteolytic complex that mediates the cleavage and processing of the viral polyprotein. NS3 recruits NS2B and NS5 proteins to direct protease and replication activities. In an effort to investigate the biology of the viral protease, we cloned cDNA encoding the NS2B-NS3 proteolytic complex from brain tissue of a WNV-infected dead crow, collected from the Lower Merion area (Merion strain). Expression of the NS2B-NS3 gene cassette induced apoptosis within 48 h of transfection. Electron microscopic analysis of NS2B-NS3-transfected cells revealed ultra-structural changes that are typical of apoptotic cells including membrane blebbing, nuclear disintegration and cytoplasmic vacuolations. The role of NS3 or NS2B in contributing to host cell apoptosis was examined. NS3 alone triggers the apoptotic pathways involving caspases-8 and -3. Experimental results from the use of caspase-specific inhibitors and caspase-8 siRNA demonstrated that the activation of caspase-8 was essential to initiate apoptotic signaling in NS3-expressing cells. Downstream of caspase-3 activation, we observed nuclear membrane ruptures and cleavage of the DNA-repair enzyme, PARP in NS3-expressing cells. Nuclear herniations due to NS3 expression were absent in the cells treated with a caspase-3 inhibitor. Expression of protease and helicase domains themselves was sufficient to trigger apoptosis generating insight into the apoptotic pathways triggered by NS3 from WNV

Opening of small and intermediate calcium-activated potassium channels induces relaxation mainly mediated by nitric-oxide release in large arteries and endothelium-derived hyperpolarizing factor in small arteries from rat

DEFF Research Database (Denmark)

Stankevicius, Edgaras; Dalsgaard, Thomas; Kroigaard, Christel

2011-01-01

This study was designed to investigate whether calcium-activated potassium channels of small (SK(Ca) or K(Ca)2) and intermediate (IK(Ca) or K(Ca)3.1) conductance activated by 6,7-dichloro-1H-indole-2,3-dione 3-oxime (NS309) are involved in both nitric oxide (NO) and endothelium-derived hyperpolar......This study was designed to investigate whether calcium-activated potassium channels of small (SK(Ca) or K(Ca)2) and intermediate (IK(Ca) or K(Ca)3.1) conductance activated by 6,7-dichloro-1H-indole-2,3-dione 3-oxime (NS309) are involved in both nitric oxide (NO) and endothelium...... in human umbilical vein endothelial cells (HUVECs), and calcium concentrations were investigated in both HUVECs and mesenteric arterial endothelial cells. In both superior (∼1093 μm) and small mesenteric (∼300 μm) arteries, NS309 evoked endothelium- and concentration-dependent relaxations. In superior....... In small mesenteric arteries, NS309 relaxations were reduced slightly by ADMA, whereas apamin plus an IK(Ca) channel blocker almost abolished relaxation. Iberiotoxin did not change NS309 relaxation. HUVECs expressed mRNA for SK(Ca) and IK(Ca) channels, and NS309 induced increases in calcium, outward...

MDM2 SNP309 and SNP285 Act as Negative Prognostic Markers for Non-small Cell Lung Cancer Adenocarcinoma Patients

Science.gov (United States)

Deben, Christophe; Op de Beeck, Ken; Van den Bossche, Jolien; Jacobs, Julie; Lardon, Filip; Wouters, An; Peeters, Marc; Van Camp, Guy; Rolfo, Christian; Deschoolmeester, Vanessa; Pauwels, Patrick

2017-01-01

Objectives: Two functional polymorphisms in the MDM2 promoter region, SNP309T>G and SNP285G>C, have been shown to impact MDM2 expression and cancer risk. Currently available data on the prognostic value of MDM2 SNP309 in non-small cell lung cancer (NSCLC) is contradictory and unavailable for SNP285. The goal of this study was to clarify the role of these MDM2 SNPs in the outcome of NSCLC patients. Materials and Methods: In this study we genotyped SNP309 and SNP285 in 98 NSCLC adenocarcinoma patients and determined MDM2 mRNA and protein levels. In addition, we assessed the prognostic value of these common SNPs on overall and progression free survival, taking into account the TP53 status of the tumor. Results and Conclusion: We found that the SNP285C allele, but not the SNP309G allele, was significantly associated with increased MDM2 mRNA expression levels (p = 0.025). However, we did not observe an association with MDM2 protein levels for SNP285. The SNP309G allele was significantly associated with the presence of wild type TP53 (p = 0.047) and showed a strong trend towards increased MDM2 protein levels (p = 0.068). In addition, patients harboring the SNP309G allele showed a worse overall survival, but only in the presence of wild type TP53. The SNP285C allele was significantly associated with an early age of diagnosis and metastasis. Additionally, the SNP285C allele acted as an independent predictor for worse progression free survival (HR = 3.97; 95% CI = 1.51 - 10.42; p = 0.005). Our data showed that both SNP309 (in the presence of wild type TP53) and SNP285 act as negative prognostic markers for NSCLC patients, implicating a prominent role for these variants in the outcome of these patients. PMID:28819417

The effect of provisional restoration type on micromovement of implants.

Science.gov (United States)

Holst, Stefan; Geiselhoeringer, Hans; Wichmann, Manfred; Holst, Alexandra Ioana

2008-09-01

The osseointegration or fibrous encapsulation of immediately loaded dental implants depends largely on the extent of implant micromovement. The impact of acrylic resin or metal-reinforced acrylic resin provisional restorations on this movement is currently unknown. The purpose of this study was to isolate and measure the effect of provisional restoration type on the vertical displacement of adjacent implants under load at 2 locations. Vertical loads ranging from 10-200 N were applied to polymethyl methacrylate resin (n=56) or metal-reinforced acrylic resin provisional restorations (n=56) supported by 4 implants inserted into homogenous artificial bone in a "u-shaped" alignment. Provisional restorations were first loaded in the anterior segment where the provisional restoration was supported by a mesial and distal implant, followed by loading on an extension 8 mm distal to the last implant. Vertical displacement of the 2 implants nearest the load application was measured and recorded using an optical image correlation technique based on photogrammetric principles. Data were subjected to a nonparametric multivariate analysis (generalized Wilcoxon test) and a Mann-Whitney test with a 2-tailed P value (alpha=.05). There was no significant difference in the vertical implant displacement of the 2 provisional restoration groups when they were loaded in the anterior segment. However, when loads were applied to the distal cantilever, metal reinforcement resulted in less vertical displacement of the next-to-last implant. The mean vertical displacement of the next-to-last implant when supporting an acrylic resin provisional restoration increased from 20 microm +/-3 microm (pooled loads of 10-50 N) to 130 microm +/-21 microm (pooled loads of 160-200 N), while the vertical displacement of the implant when retaining a metal-reinforced acrylic resin provisional restoration increased from 10 microm +/-2 microm to 69 microm +/-13 microm under the same loads (Pprovisional

Restoration of lumbopelvic sagittal alignment and its maintenance following transforaminal lumbar interbody fusion (TLIF): comparison between straight type versus curvilinear type cage.

Science.gov (United States)

Kim, Jong-Tae; Shin, Myung-Hoon; Lee, Ho-Jin; Choi, Du-Yong

2015-11-01

To evaluate a radiological and clinical difference between the curvilinear type cages compared to the straight type cages for the restoration of lumbopelvic sagittal alignment and its maintenance after transforaminal lumbar interbody fusion (TLIF) procedure. 68 patients who underwent single-level TLIF using either the straight type or curvilinear type cage were retrospectively reviewed. Assessment of the lumbopelvic parameters and the height of disc space was performed before surgery as well as 2 days, 6 and 12 months after surgery. Clinical outcome was assessed using VAS and ODI. The curvilinear type cages were positioned more anteriorly than the straight type. Restoration of the segmental lordosis (SL) in the curvilinear group was significantly greater than the straight group and at 12 months of follow-up, the straight group showed greater decrease in the disc height than the curvilinear group. The straight group failed to show improvement of lumbar lordosis (LL), while the curvilinear group showed significant restoration of LL and could maintain it to the 6 months of follow-up. In both groups, pelvic tilt was significantly decreased and it lasted to 6 months in the straight group; whereas in the curvilinear group, it was maintained to the last follow-up of 12 months. There were no significant differences between the two groups in mean VAS and ODI score over the follow-up period. This study demonstrates that the curvilinear type cage is superior to the straight type cage in improving the SL and maintaining both the restored lumbopelvic parameters and elevated disc height. These results could be attributable to the anterior position of the curvilinear cage which permits easy restoration of segmental lordosis and less sinking of cages.

5 CFR 2634.309 - Spouses and dependent children.

Science.gov (United States)

2010-01-01

... 5 Administrative Personnel 3 2010-01-01 2010-01-01 false Spouses and dependent children. 2634.309....309 Spouses and dependent children. (a) Special disclosure rules. Each report required by the... or dependent children of the reporting individual: (1) Income. For purposes of § 2634.302 of this...

31 CFR 309.6 - Public notice of offering.

Science.gov (United States)

2010-07-01

... 31 Money and Finance: Treasury 2 2010-07-01 2010-07-01 false Public notice of offering. 309.6 Section 309.6 Money and Finance: Treasury Regulations Relating to Money and Finance (Continued) FISCAL... Public notice of offering. When Treasury bills are to be offered, tenders therefor will be invited...

Effects of NS lactobacillus strains on lipid metabolism of rats fed a high-cholesterol diet

Science.gov (United States)

2013-01-01

Background Elevated serum cholesterol level is generally considered to be a risk factor for the development of cardiovascular diseases which seriously threaten human health. The cholesterol-lowering effects of lactic acid bacteria have recently become an area of great interest and controversy for many researchers. In this study, we investigated the effects of two NS lactobacillus strains, Lactobacillus plantarum NS5 and Lactobacillus delbrueckii subsp. bulgaricus NS12, on lipid metabolism of rats fed a high cholesterol diet. Methods Thirty-two SD rats were assigned to four groups and fed either a normal or a high-cholesterol diet. The NS lactobacillus treated groups received the high-cholesterol diet supplemented with Lactobacillus plantarum NS5 or Lactobacillus delbrueckii subsp. bulgaricus NS12 in drinking water. The rats were sacrificed after a 6-week feeding period. Body weights, visceral organ and fat weights, serum and liver cholesterol and lipid levels, intestinal microbiota and liver mRNA expression levels related to cholesterol metabolism were analyzed. Liver lipid deposition and adipocyte size were evaluated histologically. Results Compared with rats fed a high cholesterol diet, serum total cholesterol, low-density lipoprotein cholesterol, apolipoprotein B and free fatty acids levels were decreased and apolipoprotein A-I level was increased in NS5 or NS12 strain treated rats, and with no significant change in high-density lipoprotein cholesterol level. Liver cholesterol and triglyceride levels were also significantly decreased in NS lactobacillus strains treated groups. Meanwhile, the NS lactobacillus strains obviously alleviated hepatic injuries, decreased liver lipid deposition and reduced adipocyte size of high cholesterol diet fed rats. NS lactobacillus strains restored the changes in intestinal microbiota compositions, such as the increase in Bacteroides and the decrease in Clostridium. NS lactobacillus strains also regulated the mRNA expression

9 CFR 309.17 - Livestock used for research.

Science.gov (United States)

2010-01-01

... 9 Animals and Animal Products 2 2010-01-01 2010-01-01 false Livestock used for research. 309.17... INSPECTION AND CERTIFICATION ANTE-MORTEM INSPECTION § 309.17 Livestock used for research. (a) No livestock... of such biological product, drug, or chemical will not result in the products of such livestock being...

30 CFR 77.309-1 - Control stations; location.

Science.gov (United States)

2010-07-01

... 30 Mineral Resources 1 2010-07-01 2010-07-01 false Control stations; location. 77.309-1 Section 77... MINES Thermal Dryers § 77.309-1 Control stations; location. Thermal dryer system control stations constructed after June 30, 1971, shall be installed at a location which will give to the operator of the...

Characterization of the 309 fuel examination facility

International Nuclear Information System (INIS)

Greenhalgh, W.O.; Cornwell, B.C.

1997-01-01

This document identifies radiological, chemical and physical conditions inside the Fuel Examination Facility. It is located inside the Plutonium Recycle Test Reactor containment structure (309 Building.) The facility was a hot cell used for examination of PRTR fuel and equipment during the 1960's. Located inside the cell is a PRTR shim rod assembly, reported are radiological conditions of the sample. The conditions were assessed as part of overall 309 Building transition

MDM2 SNP309, gene-gene interaction, and tumor susceptibility: an updated meta-analysis

Directory of Open Access Journals (Sweden)

Wu Wei

2011-05-01

Full Text Available Abstract Background The tumor suppressor gene p53 is involved in multiple cellular pathways including apoptosis, transcriptional control, and cell cycle regulation. In the last decade it has been demonstrated that the single nucleotide polymorphism (SNP at codon 72 of the p53 gene is associated with the risk for development of various neoplasms. MDM2 SNP309 is a single nucleotide T to G polymorphism located in the MDM2 gene promoter. From the time that this well-characterized functional polymorphism was identified, a variety of case-control studies have been published that investigate the possible association between MDM2 SNP309 and cancer risk. However, the results of the published studies, as well as the subsequent meta-analyses, remain contradictory. Methods To investigate whether currently published epidemiological studies can clarify the potential interaction between MDM2 SNP309 and the functional genetic variant in p53 codon72 (Arg72Pro and p53 mutation status, we performed a meta-analysis of the risk estimate on 27,813 cases with various tumor types and 30,295 controls. Results The data we reviewed indicated that variant homozygote 309GG and heterozygote 309TG were associated with a significant increased risk of all tumor types (homozygote comparison: odds ratio (OR = 1.25, 95% confidence interval (CI = 1.13-1.37; heterozygote comparison: OR = 1.10, 95% CI = 1.03-1.17. We also found that the combination of GG and Pro/Pro, TG and Pro/Pro, GG and Arg/Arg significantly increased the risk of cancer (OR = 3.38, 95% CI = 1.77-6.47; OR = 1.88, 95% CI = 1.26-2.81; OR = 1.96, 95% CI = 1.01-3.78, respectively. In a stratified analysis by tumor location, we also found a significant increased risk in brain, liver, stomach and uterus cancer (OR = 1.47, 95% CI = 1.06-2.03; OR = 2.24, 95%CI = 1.57-3.18; OR = 1.54, 95%CI = 1.04-2.29; OR = 1.34, 95%CI = 1.07-1.29, respectively. However, no association was seen between MDM2 SNP309 and tumor susceptibility

“Evaluation of fracture strength of teeth restored with different types ...

African Journals Online (AJOL)

Evaluation of fracture strength of teeth restored with different types of posts luted with different luting ... Nigerian Journal of Clinical Practice ... metal posts and glass‑fiber posts luted with resin‑based luting cement and glass ionomer cement.

Cleavage preference distinguishes the two-component NS2B-NS3 serine proteinases of Dengue and West Nile viruses.

Science.gov (United States)

Shiryaev, Sergey A; Kozlov, Igor A; Ratnikov, Boris I; Smith, Jeffrey W; Lebl, Michal; Strongin, Alex Y

2007-02-01

Regulated proteolysis of the polyprotein precursor by the NS2B-NS3 protease is required for the propagation of infectious virions. Unless the structural and functional parameters of NS2B-NS3 are precisely determined, an understanding of its functional role and the design of flaviviral inhibitors will be exceedingly difficult. Our objectives were to define the substrate recognition pattern of the NS2B-NS3 protease of West Nile and Dengue virises (WNV and DV respectively). To accomplish our goals, we used an efficient, 96-well plate format, method for the synthesis of 9-mer peptide substrates with the general P4-P3-P2-P1-P1'-P2'-P3'-P4'-Gly structure. The N-terminus and the constant C-terminal Gly of the peptides were tagged with a fluorescent tag and with a biotin tag respectively. The synthesis was followed by the proteolytic cleavage of the synthesized, tagged peptides. Because of the strict requirement for the presence of basic amino acid residues at the P1 and the P2 substrate positions, the analysis of approx. 300 peptide sequences was sufficient for an adequate representation of the cleavage preferences of the WNV and DV proteinases. Our results disclosed the strict substrate specificity of the WNV protease for which the (K/R)(K/R)R/GG amino acid motifs was optimal. The DV protease was less selective and it tolerated well the presence of a number of amino acid residue types at either the P1' or the P2' site, as long as the other position was occupied by a glycine residue. We believe that our data represent a valuable biochemical resource and a solid foundation to support the design of selective substrates and synthetic inhibitors of flaviviral proteinases.

Introduction to Network Simulator NS2

CERN Document Server

Issariyakul, Teerawat

2012-01-01

"Introduction to Network Simulator NS2" is a primer providing materials for NS2 beginners, whether students, professors, or researchers for understanding the architecture of Network Simulator 2 (NS2) and for incorporating simulation modules into NS2. The authors discuss the simulation architecture and the key components of NS2 including simulation-related objects, network objects, packet-related objects, and helper objects. The NS2 modules included within are nodes, links, SimpleLink objects, packets, agents, and applications. Further, the book covers three helper modules: timers, ra

Molecular dynamic simulation of complex NS2B-NS3 DENV2 ...

African Journals Online (AJOL)

Several vaccines have been developed against the disease, but they only ... a two component NS2B-NS3 protease that cleaves viral precursor proteins, and ... The results provide conformational changes of enzyme-inhibitor complex that is ...

Functional Evolution of Influenza Virus NS1 Protein in Currently Circulating Human 2009 Pandemic H1N1 Viruses.

Science.gov (United States)

Clark, Amelia M; Nogales, Aitor; Martinez-Sobrido, Luis; Topham, David J; DeDiego, Marta L

2017-09-01

In 2009, a novel H1N1 influenza virus emerged in humans, causing a global pandemic. It was previously shown that the NS1 protein from this human 2009 pandemic H1N1 (pH1N1) virus was an effective interferon (IFN) antagonist but could not inhibit general host gene expression, unlike other NS1 proteins from seasonal human H1N1 and H3N2 viruses. Here we show that the NS1 protein from currently circulating pH1N1 viruses has evolved to encode 6 amino acid changes (E55K, L90I, I123V, E125D, K131E, and N205S) with respect to the original protein. Notably, these 6 residue changes restore the ability of pH1N1 NS1 to inhibit general host gene expression, mainly by their ability to restore binding to the cellular factor CPSF30. This is the first report describing the ability of the pH1N1 NS1 protein to naturally acquire mutations that restore this function. Importantly, a recombinant pH1N1 virus containing these 6 amino acid changes in the NS1 protein (pH1N1/NSs-6mut) inhibited host IFN and proinflammatory responses to a greater extent than that with the parental virus (pH1N1/NS1-wt), yet virus titers were not significantly increased in cell cultures or in mouse lungs, and the disease was partially attenuated. The pH1N1/NSs-6mut virus grew similarly to pH1N1/NSs-wt in mouse lungs, but infection with pH1N1/NSs-6mut induced lower levels of proinflammatory cytokines, likely due to a general inhibition of gene expression mediated by the mutated NS1 protein. This lower level of inflammation induced by the pH1N1/NSs-6mut virus likely accounts for the attenuated disease phenotype and may represent a host-virus adaptation affecting influenza virus pathogenesis. IMPORTANCE Seasonal influenza A viruses (IAVs) are among the most common causes of respiratory infections in humans. In addition, occasional pandemics are caused when IAVs circulating in other species emerge in the human population. In 2009, a swine-origin H1N1 IAV (pH1N1) was transmitted to humans, infecting people then and up

7 CFR 51.309 - Condition after storage or transit.

Science.gov (United States)

2010-01-01

... 7 Agriculture 2 2010-01-01 2010-01-01 false Condition after storage or transit. 51.309 Section 51... STANDARDS) United States Standards for Grades of Apples Condition After Storage Or Transit § 51.309 Condition after storage or transit. Decay, scald, or any other deterioration which may have developed on...

33 CFR 159.309 - Limitations on discharge of treated sewage or graywater.

Science.gov (United States)

2010-07-01

... treated sewage or graywater. 159.309 Section 159.309 Navigation and Navigable Waters COAST GUARD... Certain Alaskan Waters by Cruise Vessel Operations § 159.309 Limitations on discharge of treated sewage or graywater. (a) No person shall discharge treated sewage or graywater from a cruise vessel into the...

49 CFR 30.9 - Citizenship: Direct or indirect control.

Science.gov (United States)

2010-10-01

... 49 Transportation 1 2010-10-01 2010-10-01 false Citizenship: Direct or indirect control. 30.9 Section 30.9 Transportation Office of the Secretary of Transportation DENIAL OF PUBLIC WORKS CONTRACTS TO... title to 50 percent or more of the stock of the contractor or subcontractor is held subject to trust or...

Structure-Based Mutational Analysis of the Hepatitis C Virus NS3 Helicase

Science.gov (United States)

Tai, Chun-Ling; Pan, Wen-Ching; Liaw, Shwu-Huey; Yang, Ueng-Cheng; Hwang, Lih-Hwa; Chen, Ding-Shinn

2001-01-01

The carboxyl terminus of the hepatitis C virus (HCV) nonstructural protein 3 (NS3) possesses ATP-dependent RNA helicase activity. Based on the conserved sequence motifs and the crystal structures of the helicase domain, 17 mutants of the HCV NS3 helicase were generated. The ATP hydrolysis, RNA binding, and RNA unwinding activities of the mutant proteins were examined in vitro to determine the functional role of the mutated residues. The data revealed that Lys-210 in the Walker A motif and Asp-290, Glu-291, and His-293 in the Walker B motif were crucial to ATPase activity and that Thr-322 and Thr-324 in motif III and Arg-461 in motif VI significantly influenced ATPase activity. When the pairing between His-293 and Gln-460, referred to as gatekeepers, was replaced with the Asp-293/His-460 pair, which makes the NS3 helicase more like the DEAD helicase subgroup, ATPase activity was not restored. It thus indicated that the whole microenvironment surrounding the gatekeepers, rather than the residues per se, was important to the enzymatic activities. Arg-461 and Trp-501 are important residues for RNA binding, while Val-432 may only play a coadjutant role. The data demonstrated that RNA helicase activity was possibly abolished by the loss of ATPase activity or by reduced RNA binding activity. Nevertheless, a low threshold level of ATPase activity was found sufficient for helicase activity. Results in this study provide a valuable reference for efforts under way to develop anti-HCV therapeutic drugs targeting NS3. PMID:11483774

NMR analysis of the dynamic exchange of the NS2B cofactor between open and closed conformations of the West Nile virus NS2B-NS3 protease.

Directory of Open Access Journals (Sweden)

Xun-Cheng Su

Full Text Available BACKGROUND: The two-component NS2B-NS3 proteases of West Nile and dengue viruses are essential for viral replication and established targets for drug development. In all crystal structures of the proteases to date, the NS2B cofactor is located far from the substrate binding site (open conformation in the absence of inhibitor and lining the substrate binding site (closed conformation in the presence of an inhibitor. METHODS: In this work, nuclear magnetic resonance (NMR spectroscopy of isotope and spin-labeled samples of the West Nile virus protease was used to investigate the occurrence of equilibria between open and closed conformations in solution. FINDINGS: In solution, the closed form of the West Nile virus protease is the predominant conformation irrespective of the presence or absence of inhibitors. Nonetheless, dissociation of the C-terminal part of the NS2B cofactor from the NS3 protease (open conformation occurs in both the presence and the absence of inhibitors. Low-molecular-weight inhibitors can shift the conformational exchange equilibria so that over 90% of the West Nile virus protease molecules assume the closed conformation. The West Nile virus protease differs from the dengue virus protease, where the open conformation is the predominant form in the absence of inhibitors. CONCLUSION: Partial dissociation of NS2B from NS3 has implications for the way in which the NS3 protease can be positioned with respect to the host cell membrane when NS2B is membrane associated via N- and C-terminal segments present in the polyprotein. In the case of the West Nile virus protease, discovery of low-molecular-weight inhibitors that act by breaking the association of the NS2B cofactor with the NS3 protease is impeded by the natural affinity of the cofactor to the NS3 protease. The same strategy can be more successful in the case of the dengue virus NS2B-NS3 protease.

9 CFR 309.3 - Dead, dying, disabled, or diseased and similar livestock.

Science.gov (United States)

2010-01-01

... similar livestock. 309.3 Section 309.3 Animals and Animal Products FOOD SAFETY AND INSPECTION SERVICE... diseased and similar livestock. (a) Livestock found to be dead or in a dying condition on the premises of... § 309.13. (b) Livestock plainly showing on ante-mortem inspection any disease or condition that, under...

31 CFR 596.309 - Specific license.

Science.gov (United States)

2010-07-01

... FOREIGN ASSETS CONTROL, DEPARTMENT OF THE TREASURY TERRORISM LIST GOVERNMENTS SANCTIONS REGULATIONS General Definitions § 596.309 Specific license. The term specific license means any license or...

Mechanisms underlying epithelium-dependent relaxation in rat bronchioles

DEFF Research Database (Denmark)

Kroigaard, Christel; Dalsgaard, Thomas; Simonsen, Ulf

2010-01-01

This study investigated the mechanisms underlying epithelium-derived hyperpolarizing factor (EpDHF)-type relaxation in rat bronchioles. Immunohistochemistry was performed, and rat bronchioles and pulmonary arteries were mounted in microvascular myographs for functional studies. An opener of small...... (SK(Ca)) and intermediate (IK(Ca))-conductance calcium-activated potassium channels, NS309 (6,7-dichloro-1H-indole-2,3-dione 3-oxime) was used to induce EpDHF-type relaxation. IK(Ca) and SK(Ca)3 positive immunoreactions were observed mainly in the epithelium and endothelium of bronchioles and arteries......, respectively. In 5-hydroxytryptamine (1 microM)-contracted bronchioles (828 +/- 20 microm, n = 84) and U46619 (0.03 microM)-contracted arteries (720 +/- 24 microm, n = 68), NS309 (0.001-10 microM) induced concentration-dependent relaxations that were reduced by epithelium/endothelium removal and by blocking IK...

Dengue Virus NS2B/NS3 Protease Inhibitors Exploiting the Prime Side.

Science.gov (United States)

Lin, Kuan-Hung; Ali, Akbar; Rusere, Linah; Soumana, Djade I; Kurt Yilmaz, Nese; Schiffer, Celia A

2017-05-15

The mosquito-transmitted dengue virus (DENV) infects millions of people in tropical and subtropical regions. Maturation of DENV particles requires proper cleavage of the viral polyprotein, including processing of 8 of the 13 substrate cleavage sites by dengue virus NS2B/NS3 protease. With no available direct-acting antiviral targeting DENV, NS2/NS3 protease is a promising target for inhibitor design. Current design efforts focus on the nonprime side of the DENV protease active site, resulting in highly hydrophilic and nonspecific scaffolds. However, the prime side also significantly modulates DENV protease binding affinity, as revealed by engineering the binding loop of aprotinin, a small protein with high affinity for DENV protease. In this study, we designed a series of cyclic peptides interacting with both sides of the active site as inhibitors of dengue virus protease. The design was based on two aprotinin loops and aimed to leverage both key specific interactions of substrate sequences and the entropic advantage driving aprotinin's high affinity. By optimizing the cyclization linker, length, and amino acid sequence, the tightest cyclic peptide achieved a K i value of 2.9 μM against DENV3 wild-type (WT) protease. These inhibitors provide proof of concept that both sides of DENV protease active site can be exploited to potentially achieve specificity and lower hydrophilicity in the design of inhibitors targeting DENV. IMPORTANCE Viruses of the flaviviral family, including DENV and Zika virus transmitted by Aedes aegypti , continue to be a threat to global health by causing major outbreaks in tropical and subtropical regions, with no available direct-acting antivirals for treatment. A better understanding of the molecular requirements for the design of potent and specific inhibitors against flaviviral proteins will contribute to the development of targeted therapies for infections by these viruses. The cyclic peptides reported here as DENV protease inhibitors

Analysis of hepatitis C virus core/NS5A protein co-localization using novel cell culture systems expressing core-NS2 and NS5A of genotypes 1-7

DEFF Research Database (Denmark)

Galli, Andrea; Scheel, Troels K H; Prentoe, Jannick C

2013-01-01

Hepatitis C virus (HCV) is an important human pathogen infecting hepatocytes. With the advent of infectious cell culture systems, the HCV particle assembly and release processes are finally being uncovered. The HCV core and NS5A proteins co-localize on cytoplasmic lipid droplets (c......LDs) or on the endoplasmic reticulum (ER) at different stages of particle assembly. Current knowledge on assembly and release is primarily based on studies in genotype 2a cell culture systems; however, given the high genetic heterogeneity of HCV, variations might exist among genotypes. Here, we developed novel HCV strain...... JFH1-based recombinants expressing core-NS2 and NS5A from genotypes 1-7, and analysed core and NS5A co-localization in infected cells. Huh7.5 cells were transfected with RNA of core-NS2/NS5A recombinants and putative adaptive mutations were analysed by reverse genetics. Adapted core-NS2/NS5A...

Effect of Dental Restorative Material Type and Shade on Characteristics of Two-Layer Dental Composite Systems

Directory of Open Access Journals (Sweden)

Atefeh Karimzadeh

Full Text Available Abstract The purpose of this study was to investigate the effects of shade and material type and shape in dental polymer composites on the hardness and shrinkage stress of bulk and two-layered restoration systems. For this purpose, some bulk and layered specimens from three different shades of dental materials were prepared and light-cured. The experiments were carried out on three types of materials: conventional restorative composite, nanohybrid composite and nanocomposite. Micro-indentation experiment was performed on the bulk and also on each layer of layered restoration specimens using a Vicker's indenter. The interface between the two layers was studied by scanning electron microscopy (SEM. The results revealed significant differences between the values of hardness for different shades in the conventional composite and also in the nanohybrid composite. However, no statistically significant difference was observed between the hardness values for different shades in the nanocomposite samples. The layered restoration specimens of different restorative materials exhibited lower hardness values with respect to their bulk specimens. The reduction in the hardness value of the layered conventional composite samples was higher than those of the nanocomposite and nanohybrid composite specimens indicating more shrinkage stresses generated in the conventional composite restorations. According to the SEM images, a gap was observed between the two layers in the layered restorations.

Achievements in NS rapeseed hybrids breeding

Directory of Open Access Journals (Sweden)

Marjanović-Jeromela Ana

2016-01-01

Full Text Available The increased production of oilseed rape (Brassica napus L. is evident on a global scale, but also in Serbia in the last decade. Rapeseed is used primarily for vegetable oil and processing industry, but also as a source of protein for animal feed and green manure. Following the cultivation of varieties, breeding and cultivation of hybrid rapeseed started in the 1990's, to take advantage of heterosis in F1 generation, while protecting the breeder's rights during seed commercialization. The breeding of hybrid oilseed rape requires high quality starting material (lines with good combining abilities for introduction of male sterility. Ogura sterility system is primarily used at the Institute of Field and Vegetable Crops, Novi Sad, Serbia. To use this system, separate lines are modified with genes for cytoplasmic male sterility (cms female line - mother line and restoration of fertility (Rf male lines - father line. In order to maintain the sterility of the mother line it is necessary to produce a maintainer line of cytoplasmic male sterility. Creation of these lines and hybrids at the Institute of Field and Vegetable Crops was successfully monitored with intense use of cytogenetic laboratory methods. The structure and vitality of pollen, including different phases during meiosis were checked so that cms stability was confirmed during the introduction of these genes into different lines. Rapeseed breeding program in Serbia resulted in numerous varieties through collaboration of researchers engaged in breeding and genetics of this plant species. So far, in addition to 12 varieties of winter rapeseed and two varieties of spring rapeseed, a new hybrid of winter rapeseed NS Ras was registered in Serbia. NS Ras is an early-maturing hybrid characterized by high seed yield and oil content. Average yield of NS Ras for two seasons and three sites was 4256 kg ha-1 of seed and 1704 kg ha-1 of oil. Three promising winter rapeseed hybrids are in the process of

Survival of extensively damaged endodontically treated incisors restored with different types of posts-and-core foundation restoration material.

Science.gov (United States)

Lazari, Priscilla Cardoso; de Carvalho, Marco Aurélio; Del Bel Cury, Altair A; Magne, Pascal

2018-05-01

Which post-and-core combination will best improve the performance of extensively damaged endodontically treated incisors without a ferrule is still unclear. The purpose of this in vitro study was to investigate the restoration of extensively damaged endodontically treated incisors without a ferrule using glass-ceramic crowns bonded to various composite resin foundation restorations and 2 types of posts. Sixty decoronated endodontically treated bovine incisors without a ferrule were divided into 4 groups and restored with various post-and-core foundation restorations. NfPfB=no-ferrule (Nf) with glass-fiber post (Pf) and bulk-fill resin foundation restoration (B); NfPfP=no-ferrule (Nf) with glass-fiber post (Pf) and dual-polymerized composite resin core foundation restoration (P); NfPt=no-ferrule (Nf) with titanium post (Pt) and resin core foundation restoration; and NfPtB=no-ferrule (Nf) with titanium post (Pt) and bulk-fill resin core foundation restoration (B). Two additional groups from previously published data from the same authors (FPf=2mm of ferrule (F) and glass-fiber post (Pf) and composite resin core foundation restoration; and NfPf=no-ferrule (Nf) with glass-fiber post (Pf) and composite resin core foundation restoration), which were tested concomitantly and using the same experimental arrangement, were included for comparison. All teeth were prepared to receive bonded glass-ceramic crowns luted with dual-polymerized resin cement and were subjected to accelerated fatigue testing under submerged conditions at room temperature. Cyclic isometric loading was applied to the incisal edge at an angle of 30 degrees with a frequency of 5 Hz, beginning with a load of 100 N (5000 cycles). A 100-N load increase was applied every 15000 cycles. The specimens were loaded until failure or to a maximum of 1000 N (140000 cycles). The 6 groups (4 groups from the present study and 2 groups from the previously published study) were compared using the Kaplan-Meier survival

Effects of CMS types and restorer alleles on plant performance in Plantago lanceolata L.: an indication for cost of restoration

NARCIS (Netherlands)

De Haan, A.A.; Hundscheid, M.P.J.; Van Hinsberg, A.

1997-01-01

In gynodioecious species, male steriles co-occur with hermaphrodites. Usually, the male sterile trait is maternally inherited, hence it is called Cytoplasmic Male Sterility (CMS). Nuclear loci restore male fertility in combination with their 'own' specific cytoplasmic types. In theory, two fitness

15 CFR 30.9 - Transmitting and correcting Electronic Export Information.

Science.gov (United States)

2010-01-01

... 15 Commerce and Foreign Trade 1 2010-01-01 2010-01-01 false Transmitting and correcting Electronic Export Information. 30.9 Section 30.9 Commerce and Foreign Trade Regulations Relating to Commerce and Foreign Trade BUREAU OF THE CENSUS, DEPARTMENT OF COMMERCE FOREIGN TRADE REGULATIONS General Requirements...

Computer Aided Screening of Phytochemicals from Garcinia against the Dengue NS2B/NS3 Protease.

Science.gov (United States)

Qamar, Tahir Ul; Mumtaz, Arooj; Ashfaq, Usman Ali; Azhar, Samia; Fatima, Tabeer; Hassan, Muhammad; Hussain, Syed Sajid; Akram, Waheed; Idrees, Sobia

2014-01-01

Dengue virus NS2/NS3 protease because of its ability to cleave viral proteins is considered as an attractive target to screen antiviral agents. Medicinal plants contain a variety of phytochemicals that can be used as drug against different diseases and infections. Therefore, this study was designed to uncover possible phytochemical of different classes (Aromatic, Carbohydrates, Lignin, Saponins, Steroids, Tannins, Terpenoids, Xanthones) that could be used as inhibitors against the NS2B/NS3 protease of DENV. With the help of molecular docking, Garcinia phytochemicals found to be bound deeply inside the active site of DENV NS2B/NS3 protease among all tested phytochemicals and had interactions with catalytic triad (His51, Asp75, Ser135). Thus, it can be concluded from the study that these Gracinia phytochemicals could serve as important inhibitors to inhibit the viral replication inside the host cell. Further in-vitro investigations require confirming their efficacy.

25 CFR 309.16 - What are examples of regalia that are Indian products?

Science.gov (United States)

2010-04-01

...? 309.16 Section 309.16 Indians INDIAN ARTS AND CRAFTS BOARD, DEPARTMENT OF THE INTERIOR PROTECTION OF INDIAN ARTS AND CRAFTS PRODUCTS § 309.16 What are examples of regalia that are Indian products? (a... traditional dances, participate in traditional socials, used for dance competitions, and worn on special...

A trade-off in replication in mosquito versus mammalian systems conferred by a point mutation in the NS4B protein of dengue virus type 4

International Nuclear Information System (INIS)

Hanley, Kathryn A.; Manlucu, Luella R.; Gilmore, Lara E.; Blaney, Joseph E.; Hanson, Christopher T.; Murphy, Brian R.; Whitehead, Stephen S.

2003-01-01

An acceptable live-attenuated dengue virus vaccine candidate should have low potential for transmission by mosquitoes. We have identified and characterized a mutation in dengue virus type 4 (DEN4) that decreases the ability of the virus to infect mosquitoes. A panel of 1248 mutagenized virus clones generated previously by chemical mutagenesis was screened for decreased replication in mosquito C6/36 cells but efficient replication in simian Vero cells. One virus met these criteria and contained a single coding mutation: a C-to-U mutation at nucleotide 7129 resulting in a Pro-to-Leu change in amino acid 101 of the nonstructural 4B gene (NS4B P101L). This mutation results in decreased replication in C6/36 cells relative to wild-type DEN4, decreased infectivity for mosquitoes, enhanced replication in Vero and human HuH-7 cells, and enhanced replication in SCID mice implanted with HuH-7 cells (SCID-HuH-7 mice). A recombinant DEN4 virus (rDEN4) bearing this mutation exhibited the same set of phenotypes. Addition of the NS4B P101L mutation to rDEN4 bearing a 30 nucleotide deletion (Δ30) decreased the ability of the double-mutant virus to infect mosquitoes but increased its ability to replicate in SCID-HuH-7 mice. Although the NS4B P101L mutation decreases infectivity of DEN4 for mosquitoes, its ability to enhance replication in SCID-HuH-7 mice suggests that it might not be advantageous to include this specific mutation in an rDEN4 vaccine. The opposing effects of the NS4B P101L mutation in mosquito and vertebrate systems suggest that the NS4B protein is involved in maintaining the balance between efficient replication in the mosquito vector and the human host

25 CFR 309.6 - When does a commercial product become an Indian product?

Science.gov (United States)

2010-04-01

...? 309.6 Section 309.6 Indians INDIAN ARTS AND CRAFTS BOARD, DEPARTMENT OF THE INTERIOR PROTECTION OF INDIAN ARTS AND CRAFTS PRODUCTS § 309.6 When does a commercial product become an Indian product? In addressing Indian embellishments to originally commercial products, the Indian labor expended to add art or...

NS simulator for beginners

CERN Document Server

Altman, Eitan

2012-01-01

NS-2 is an open-source discrete event network simulator which is widely used by both the research community as well as by the people involved in the standardization protocols of IETF. The goal of this book is twofold: on one hand to learn how to use the NS-2 simulator, and on the other hand, to become acquainted with and to understand the operation of some of the simulated objects using NS-2 simulations. The book is intended to help students, engineers or researchers who need not have much background in programming or who want to learn through simple examples how to analyse some simulated obje

46 CFR 308.529 - Surety Bond B, Form MA-309.

Science.gov (United States)

2010-10-01

... Shipping MARITIME ADMINISTRATION, DEPARTMENT OF TRANSPORTATION EMERGENCY OPERATIONS WAR RISK INSURANCE War Risk Cargo Insurance Ii-Open Policy War Risk Cargo Insurance § 308.529 Surety Bond B, Form MA-309. An Assured who elects to substitute a surety bond for a collateral deposit fund shall submit Form MA-309...

22 CFR 309.18 - Voluntary repayment agreements as an alternative to salary offset.

Science.gov (United States)

2010-04-01

... to salary offset. 309.18 Section 309.18 Foreign Relations PEACE CORPS DEBT COLLECTION Salary Offset § 309.18 Voluntary repayment agreements as an alternative to salary offset. (a) In response to a notice of intent, an employee may propose a written agreement to repay the debt as an alternative to salary...

25 CFR 309.15 - What are examples of apparel that are Indian products?

Science.gov (United States)

2010-04-01

...? 309.15 Section 309.15 Indians INDIAN ARTS AND CRAFTS BOARD, DEPARTMENT OF THE INTERIOR PROTECTION OF INDIAN ARTS AND CRAFTS PRODUCTS § 309.15 What are examples of apparel that are Indian products? (a... products. (b) Specific examples include, but are not limited to: seal skin parkas, ribbon appliqué dance...

45 CFR 309.150 - What start-up costs are allowable for Tribal IV-D programs carried out under § 309.65(b) of this...

Science.gov (United States)

2010-10-01

... 45 Public Welfare 2 2010-10-01 2010-10-01 false What start-up costs are allowable for Tribal IV-D... ENFORCEMENT (IV-D) PROGRAM Tribal IV-D Program Funding § 309.150 What start-up costs are allowable for Tribal... $500,000, unless additional funding is provided pursuant to § 309.16(c). Allowable start-up costs and...

Specific Mutations in the PB2 Protein of Influenza A Virus Compensate for the Lack of Efficient Interferon Antagonism of the NS1 Protein of Bat Influenza A-Like Viruses.

Science.gov (United States)

Aydillo, Teresa; Ayllon, Juan; Pavlisin, Amzie; Martinez-Romero, Carles; Tripathi, Shashank; Mena, Ignacio; Moreira-Soto, Andrés; Vicente-Santos, Amanda; Corrales-Aguilar, Eugenia; Schwemmle, Martin; García-Sastre, Adolfo

2018-04-01

Recently, two new influenza A-like viruses have been discovered in bats, A/little yellow-shouldered bat/Guatemala/060/2010 (HL17NL10) and A/flat-faced bat/Peru/033/2010 (HL18NL11). The hemagglutinin (HA)-like (HL) and neuraminidase (NA)-like (NL) proteins of these viruses lack hemagglutination and neuraminidase activities, despite their sequence and structural homologies with the HA and NA proteins of conventional influenza A viruses. We have now investigated whether the NS1 proteins of the HL17NL10 and HL18NL11 viruses can functionally replace the NS1 protein of a conventional influenza A virus. For this purpose, we generated recombinant influenza A/Puerto Rico/8/1934 (PR8) H1N1 viruses containing the NS1 protein of the PR8 wild-type, HL17NL10, and HL18NL11 viruses. These viruses (r/NS1PR8, r/NS1HL17, and r/NS1HL18, respectively) were tested for replication in bat and nonbat mammalian cells and in mice. Our results demonstrate that the r/NS1HL17 and r/NS1HL18 viruses are attenuated in vitro and in vivo However, the bat NS1 recombinant viruses showed a phenotype similar to that of the r/NS1PR8 virus in STAT1 -/- human A549 cells and mice, both in vitro and in vivo systems being unable to respond to interferon (IFN). Interestingly, multiple mouse passages of the r/NS1HL17 and r/NS1HL18 viruses resulted in selection of mutant viruses containing single amino acid mutations in the viral PB2 protein. In contrast to the parental viruses, virulence and IFN antagonism were restored in the selected PB2 mutants. Our results indicate that the NS1 protein of bat influenza A-like viruses is less efficient than the NS1 protein of its conventional influenza A virus NS1 counterpart in antagonizing the IFN response and that this deficiency can be overcome by the influenza virus PB2 protein. IMPORTANCE Significant gaps in our understanding of the basic features of the recently discovered bat influenza A-like viruses HL17NL10 and HL18NL11 remain. The basic biology of these unique

Highly pathogenic avian influenza virus H5N1 controls type I IFN induction in chicken macrophage HD-11 cells: a polygenic trait that involves NS1 and the polymerase complex

Science.gov (United States)

2012-01-01

Background Influenza A viruses are well characterized to antagonize type I IFN induction in infected mammalian cells. However, limited information is available for avian cells. It was hypothesised that avian influenza viruses (AIV) with distinct virulence may interact differently with the avian innate immune system. Therefore, the type I IFN responses induced by highly virulent and low virulent H5N1 AIV and reassortants thereof were analysed in chicken cells. Results The highly pathogenic (HP) AIV A/chicken/Yamaguchi/7/04 (H5N1) (Yama) did not induce type I IFN in infected chicken HD-11 macrophage-like cells. This contrasted with an NS1 mutant Yama virus (Yama-NS1A144V) and with the attenuated H5N1 AIV A/duck/Hokkaido/Vac-1/04 (Vac) carrying the haemagglutinin (HA) of the Yama virus (Vac-Yama/HA), that both induced type I IFN in these cells. The substitution of the NS segment from Yama with that from Vac in the Yama backbone resulted in induction of type I IFN secretion in HD-11 cells. However, vice versa, the Yama NS segment did not prevent type I IFN induction by the Vac-Yama/HA virus. This was different with the PB1/PB2/PA segment reassortant Yama and Vac-Yama/HA viruses. Whereas the Yama virus with the Vac PB1/PB2/PA segments induced type I IFN in HD-11 cells, the Vac-Yama/HA virus with the Yama PB1/PB2/PA segments did not. As reported for mammalian cells, the expression of H5N1 PB2 inhibited the activation of the IFN-β promoter in chicken DF-1 fibroblast cells. Importantly, the Yama PB2 was more potent at inhibiting the IFN-β promoter than the Vac PB2. Conclusions The present study demonstrates that the NS1 protein and the polymerase complex of the HPAIV Yama act in concert to antagonize chicken type I IFN secretion in HD-11 cells. PB2 alone can also exert a partial inhibitory effect on type I IFN induction. In conclusion, the control of type I IFN induction by H5N1 HPAIV represents a complex phenotype that involves a particular viral gene constellation

Improved Bunch Splitting for the 75ns LHC Beam

CERN Document Server

Damerau, H

2011-01-01

The 75ns variant was added to the PS arsenal of LHC-type beams by adapting the 20MHz cavity used to produce the 25 and 50ns variants to operate at a switchable 13MHz. This permitted splitting from harmonic 14 to 28, but at a cost in adiabaticity compared with the h=2142 splitting of the other two cases. Consequently, a delicate empirical optimization was necessary to bring the 75ns beam inside specification. More recently the speed at which the bunches, once fully distinct, are moved apart has been revisited and further optimization achieved. As a by-product, deliberately degrading the splitting by moving the bunches apart too quickly led to sufficient coherent motion in the resultant bunch pair to permit a voltage calibration of the 13MHz cavity by means of the influence on convergence of the rf voltage input into the iterative algorithm of the Tomoscope [1,2].

Multiple Sensing Application on Wireless Sensor Network Simulation using NS3

Science.gov (United States)

Kurniawan, I. F.; Bisma, R.

2018-01-01

Hardware enhancement provides opportunity to install various sensor device on single monitoring node which then enables users to acquire multiple data simultaneously. Constructing multiple sensing application in NS3 is a challenging task since numbers of aspects such as wireless communication, packet transmission pattern, and energy model must be taken into account. Despite of numerous types of monitoring data available, this study only considers two types such as periodic, and event-based data. Periodical data will generate monitoring data follows configured interval, while event-based transmit data when certain determined condition is met. Therefore, this study attempts to cover mentioned aspects in NS3. Several simulations are performed with different number of nodes on arbitrary communication scheme.

Identification of novel small molecule inhibitors against NS2B/NS3 serine protease from Zika virus

Energy Technology Data Exchange (ETDEWEB)

Lee, Hyun; Ren, Jinhong; Nocadello, Salvatore; Rice, Amy J.; Ojeda, Isabel; Light, Samuel; Minasov, George; Vargas, Jason; Nagarathnam, Dhanapalan; Anderson, Wayne F.; Johnson, Michael E. (UIC); (NWU); (Novalex); (DNSK)

2016-12-26

Zika flavivirus infection during pregnancy appears to produce higher risk of microcephaly, and also causes multiple neurological problems such as Guillain–Barré syndrome. The Zika virus is now widespread in Central and South America, and is anticipated to become an increasing risk in the southern United States. With continuing global travel and the spread of the mosquito vector, the exposure is expected to accelerate, but there are no currently approved treatments against the Zika virus. The Zika NS2B/NS3 protease is an attractive drug target due to its essential role in viral replication. Our studies have identified several compounds with inhibitory activity (IC50) and binding affinity (KD) of ~5–10 μM against the Zika NS2B-NS3 protease from testing 71 HCV NS3/NS4A inhibitors that were initially discovered by high-throughput screening of 40,967 compounds. Competition surface plasmon resonance studies and mechanism of inhibition analyses by enzyme kinetics subsequently determined the best compound to be a competitive inhibitor with a Ki value of 9.5 μM. We also determined the X-ray structure of the Zika NS2B-NS3 protease in a “pre-open conformation”, a conformation never observed before for any flavivirus proteases. This provides the foundation for new structure-based inhibitor design.

NS1-binding protein abrogates the elevation of cell viability by the influenza A virus NS1 protein in association with CRKL

Energy Technology Data Exchange (ETDEWEB)

Miyazaki, Masaya [Department of Cancer Pathology, Hokkaido University Graduate School of Medicine, N15W7, Kita-ku, Sapporo 060-8638 (Japan); Nishihara, Hiroshi, E-mail: hnishihara@med.hokudai.ac.jp [Department of Translational Pathology, Hokkaido University Graduate School of Medicine, N15W7, Kita-ku, Sapporo 060-8638 (Japan); Hasegawa, Hideki [Department of Pathology, National Institute of Infectious Diseases, Sinjuku-ku, Tokyo (Japan); Tashiro, Masato [Influenza Virus Research Center, National Institute of Infectious Diseases, Sinjuku-ku, Tokyo (Japan); Wang, Lei [Department of Translational Pathology, Hokkaido University Graduate School of Medicine, N15W7, Kita-ku, Sapporo 060-8638 (Japan); Kimura, Taichi; Tanino, Mishie; Tsuda, Masumi [Department of Cancer Pathology, Hokkaido University Graduate School of Medicine, N15W7, Kita-ku, Sapporo 060-8638 (Japan); Tanaka, Shinya [Department of Cancer Pathology, Hokkaido University Graduate School of Medicine, N15W7, Kita-ku, Sapporo 060-8638 (Japan); Department of Translational Pathology, Hokkaido University Graduate School of Medicine, N15W7, Kita-ku, Sapporo 060-8638 (Japan)

2013-11-29

Highlights: •NS1 induced excessive phosphorylation of ERK and elevated cell viability. •NS1-BP expression and CRKL knockdown abolished survival effect of NS1. •NS1-BP and NS1 formed the complex through the interaction with CRKL-SH3(N). -- Abstract: The influenza A virus non-structural protein 1 (NS1) is a multifunctional virulence factor consisting of an RNA binding domain and several Src-homology (SH) 2 and SH3 binding motifs, which promotes virus replication in the host cell and helps to evade antiviral immunity. NS1 modulates general host cell physiology in association with various cellular molecules including NS1-binding protein (NS1-BP) and signaling adapter protein CRK-like (CRKL), while the physiological role of NS1-BP during influenza A virus infection especially in association with NS1 remains unclear. In this study, we analyzed the intracellular association of NS1-BP, NS1 and CRKL to elucidate the physiological roles of these molecules in the host cell. In HEK293T cells, enforced expression of NS1 of A/Beijing (H1N1) and A/Indonesia (H5N1) significantly induced excessive phosphorylation of ERK and elevated cell viability, while the over-expression of NS1-BP and the abrogation of CRKL using siRNA abolished such survival effect of NS1. The pull-down assay using GST-fusion CRKL revealed the formation of intracellular complexes of NS1-BP, NS1 and CRKL. In addition, we identified that the N-terminus SH3 domain of CRKL was essential for binding to NS1-BP using GST-fusion CRKL-truncate mutants. This is the first report to elucidate the novel function of NS1-BP collaborating with viral protein NS1 in modulation of host cell physiology. In addition, an alternative role of adaptor protein CRKL in association with NS1 and NS1-BP during influenza A virus infection is demonstrated.

Mechanisms of endothelial dysfunction in resistance arteries from patients with end-stage renal disease.

Directory of Open Access Journals (Sweden)

Leanid Luksha

Full Text Available The study focuses on the mechanisms of endothelial dysfunction in the uremic milieu. Subcutaneous resistance arteries from 35 end-stage renal disease (ESRD patients and 28 matched controls were studied ex-vivo. Basal and receptor-dependent effects of endothelium-derived factors, expression of endothelial NO synthase (eNOS, prerequisites for myoendothelial gap junctions (MEGJ, and associations between endothelium-dependent responses and plasma levels of endothelial dysfunction markers were assessed. The contribution of endothelium-derived hyperpolarizing factor (EDHF to endothelium-dependent relaxation was impaired in uremic arteries after stimulation with bradykinin, but not acetylcholine, reflecting the agonist-specific differences. Diminished vasodilator influences of the endothelium on basal tone and enhanced plasma levels of asymmetrical dimethyl L-arginine (ADMA suggest impairment in NO-mediated regulation of uremic arteries. eNOS expression and contribution of MEGJs to EDHF type responses were unaltered. Plasma levels of ADMA were negatively associated with endothelium-dependent responses in uremic arteries. Preserved responses of smooth muscle to pinacidil and NO-donor indicate alterations within the endothelium and tolerance of vasodilator mechanisms to the uremic retention products at the level of smooth muscle. We conclude that both EDHF and NO pathways that control resistance artery tone are impaired in the uremic milieu. For the first time, we validate the alterations in EDHF type responses linked to kinin receptors in ESRD patients. The association between plasma ADMA concentrations and endothelial function in uremic resistance vasculature may have diagnostic and future therapeutic implications.

hnRNP A2/B1 interacts with influenza A viral protein NS1 and inhibits virus replication potentially through suppressing NS1 RNA/protein levels and NS1 mRNA nuclear export

Energy Technology Data Exchange (ETDEWEB)

Wang, Yimeng; Zhou, Jianhong; Du, Yuchun, E-mail: ydu@uark.edu

2014-01-20

The NS1 protein of influenza viruses is a major virulence factor and exerts its function through interacting with viral/cellular RNAs and proteins. In this study, we identified heterogeneous nuclear ribonucleoprotein A2/B1 (hnRNP A2/B1) as an interacting partner of NS1 proteins by a proteomic method. Knockdown of hnRNP A2/B1 by small interfering RNA (siRNA) resulted in higher levels of NS vRNA, NS1 mRNA, and NS1 protein in the virus-infected cells. In addition, we demonstrated that hnRNP A2/B1 proteins are associated with NS1 and NS2 mRNAs and that knockdown of hnRNP A2/B1 promotes transport of NS1 mRNA from the nucleus to the cytoplasm in the infected cells. Lastly, we showed that knockdown of hnRNP A2/B1 leads to enhanced virus replication. Our results suggest that hnRNP A2/B1 plays an inhibitory role in the replication of influenza A virus in host cells potentially through suppressing NS1 RNA/protein levels and NS1 mRNA nucleocytoplasmic translocation. - Highlights: • Cellular protein hnRNP A2/B1 interacts with influenza viral protein NS1. • hnRNP A2/B1 suppresses the levels of NS1 protein, vRNA and mRNA in infected cells. • hnRNP A2/B1 protein is associated with NS1 and NS2 mRNAs. • hnRNP A2/B1 inhibits the nuclear export of NS1 mRNAs. • hnRNP A2/B1 inhibits influenza virus replication.

309 Building deactivation function analysis report

International Nuclear Information System (INIS)

Lund, D.P.

1995-09-01

The document contains the functions, function definitions, function interfaces, function interface definitions, Input Computer Automated Manufacturing Definition (IDEFO) diagrams, and a function hierarchy chart that describe what needs to be performed to deactivate the 309 Building

Coronal microleakage of four temporary restorative materials in Class II-type endodontic access preparations

Directory of Open Access Journals (Sweden)

Sang-Mi Yun

2012-02-01

Full Text Available Objectives The purpose of this study was to evaluate the microleakage of 4 temporary materials in teeth with Class II-type endodontic access preparations by using a glucose penetration model. Materials and Methods Glucose reaction test was performed to rule out the presence of any reaction between glucose and temporary material. Class II-type endodontic access preparations were made in extracted human premolars with a single root (n = 10. Each experimental group was restored with Caviton (GC, Spacer (Vericom, IRM (Dentsply-Caulk, or Fuji II(GC. Microleakage of four materials used as temporary restorative materials was evaluated by using a glucose penetration model. Data were analyzed by the one-way analysis of variance followed by a multiple-comparison Tukey test. The interface between materials and tooth were examined under a scanning electron microscope (SEM. Results There was no significant reaction between glucose and temporary materials used in this study. Microleakage was significantly lower for Caviton and Spacer than for Fuji II and IRM. SEM observation showed more intimate adaptation of tooth-restoration interfaces in Caviton and Spacer than in IRM and Fuji II. Conclusions Compared to IRM and Fuji II, Caviton and Spacer can be considered better temporary sealing materials in Class II-type endodontic access cavities.

Assessment of oral hygiene and periodontal health around posterior primary molars after their restoration with various crown types.

Science.gov (United States)

Beldüz Kara, Nihal; Yilmaz, Yucel

2014-07-01

To compare the time-dependent changes in oral hygiene and periodontal health after restoring primary posterior molars with a traditional stainless steel crown (SSC) or an aesthetic crown using various measures of periodontal health and oral hygiene. This investigation was a randomized, non-blinded prospective controlled clinical trial in which 264 crowns of different types were fitted onto the first and/or second primary molars of 76 children. The oral hygiene and the gingival health of the restored teeth and the antagonistic teeth were evaluated clinically and radiographically at 3- and 6-month intervals for 18 months after fitting the crowns. The periodontal health of the control teeth was better than that of the remaining 215 restored teeth. The oral hygiene, as measured by the simplified oral hygiene index, and gingival health, as measured by the gingival index and the volume of gingival crevicular fluid, of the restored teeth, irrespective of crown type, progressively increased during the 18-month study period. Oral hygiene and gingival health around a restored primary tooth deteriorate with time. Our results suggest that SSC, an open-faced SSC, or a NuSmile(®) pediatric crown should be the preferred crown type for restoring posterior primary teeth. © 2013 BSPD, IAPD and John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

Genetic Polymorphism of MDM2 SNP309 in Patients with Helicobacter Pylori-Associated Gastritis.

Science.gov (United States)

Tongtawee, Taweesak; Dechsukhum, Chavaboon; Leeanansaksiri, Wilairat; Kaewpitoon, Soraya; Kaewpitoon, Natthawut; Loyd, Ryan A; Matrakool, Likit; Panpimanmas, Sukij

2015-01-01

Helicobacter pylori plays an important role in gastric cancer, which has a relatively low inciduence in Thailand. MDM2 is a major negative regulator of p53, the key tumor suppressor involved in tumorigenesis of the majority of human cancers. Whether its expression might explain the relative lack of gastric cancer in Thailand was assessed here. This single-center study was conducted in the northeast region of Thailand. Gastric mucosa from 100 patients with Helicobacter pylori associated gastritis was analyzed for MDM2 SNP309 using real-time PCR hybridization (light-cycler) probes. In the total 100 Helicobacter pylori associated gastritis cases the incidence of SNP 309 T/T homozygous was 78 % with SNP309 G/T heterozygous found in 19% and SNP309 G/G homozygous in 3%. The result show SNP 309 T/T and SNP 309 G/T to be rather common in the Thai population. Our study indicates that the MDM2 SNP309 G/G homozygous genotype might be a risk factor for gastric cancer in Thailand and the fact that it is infrequent could explain to some extent the low incidence of gastric cancer in the Thai population.

A Unique T-Cell Receptor Amino Acid Sequence Selected by Human T-Cell Lymphotropic Virus Type 1 Tax301-309-Specific Cytotoxic T Cells in HLA-A24:02-Positive Asymptomatic Carriers and Adult T-Cell Leukemia/Lymphoma Patients.

Science.gov (United States)

Ishihara, Yuko; Tanaka, Yukie; Kobayashi, Seiichiro; Kawamura, Koji; Nakasone, Hideki; Gomyo, Ayumi; Hayakawa, Jin; Tamaki, Masaharu; Akahoshi, Yu; Harada, Naonori; Kusuda, Machiko; Kameda, Kazuaki; Ugai, Tomotaka; Wada, Hidenori; Sakamoto, Kana; Sato, Miki; Terasako-Saito, Kiriko; Kikuchi, Misato; Kimura, Shun-Ichi; Tanihara, Aki; Kako, Shinichi; Uchimaru, Kaoru; Kanda, Yoshinobu

2017-10-01

We previously reported that the T-cell receptor (TCR) repertoire of human T-cell lymphotropic virus type 1 (HTLV-1) Tax 301-309 -specific CD8 + cytotoxic T cells (Tax 301-309 -CTLs) was highly restricted and a particular amino acid sequence motif, the PDR motif, was conserved among HLA-A*24:02-positive (HLA-A*24:02 + ) adult T-cell leukemia/lymphoma (ATL) patients who had undergone allogeneic hematopoietic cell transplantation (allo-HSCT). Furthermore, we found that donor-derived PDR + CTLs selectively expanded in ATL long-term HSCT survivors with strong CTL activity against HTLV-1. On the other hand, the TCR repertoires in Tax 301-309 -CTLs of asymptomatic HTLV-1 carriers (ACs) remain unclear. In this study, we directly identified the DNA sequence of complementarity-determining region 3 (CDR3) of the TCR-β chain of Tax 301-309 -CTLs at the single-cell level and compared not only the TCR repertoires but also the frequencies and phenotypes of Tax 301-309 -CTLs between ACs and ATL patients. We did not observe any essential difference in the frequencies of Tax 301-309 -CTLs between ACs and ATL patients. In the single-cell TCR repertoire analysis of Tax 301-309 -CTLs, 1,458 Tax 301-309 -CTLs and 140 clones were identified in this cohort. Tax 301-309 -CTLs showed highly restricted TCR repertoires with a strongly biased usage of BV7, and PDR, the unique motif in TCR-β CDR3, was exclusively observed in all ACs and ATL patients. However, there was no correlation between PDR + CTL frequencies and HTLV-1 proviral load (PVL). In conclusion, we have identified, for the first time, a unique amino acid sequence, PDR, as a public TCR-CDR3 motif against Tax in HLA-A*24:02 + HTLV-1-infected individuals. Further investigations are warranted to elucidate the role of the PDR + CTL response in the progression from carrier state to ATL. IMPORTANCE ATL is an aggressive T-cell malignancy caused by HTLV-1 infection. The HTLV-1 regulatory protein Tax aggressively promotes the

The R35 residue of the influenza A virus NS1 protein has minimal effects on nuclear localization but alters virus replication through disrupting protein dimerization

Energy Technology Data Exchange (ETDEWEB)

Lalime, Erin N.; Pekosz, Andrew, E-mail: apekosz@jhsph.edu

2014-06-15

The influenza A virus NS1 protein has a nuclear localization sequence (NLS) in the amino terminal region. This NLS overlaps sequences that are important for RNA binding as well as protein dimerization. To assess the significance of the NS1 NLS on influenza virus replication, the NLS amino acids were individually mutated to alanines and recombinant viruses encoding these mutations were rescued. Viruses containing NS1 proteins with mutations at R37, R38 and K41 displayed minimal changes in replication or NS1 protein nuclear localization. Recombinant viruses encoding NS1 R35A were not recovered but viruses containing second site mutations at position D39 in addition to the R35A mutation were isolated. The mutations at position 39 were shown to partially restore NS1 protein dimerization but had minimal effects on nuclear localization. These data indicate that the amino acids in the NS1 NLS region play a more important role in protein dimerization compared to nuclear localization. - Highlights: • Mutations were introduced into influenza NS1 NLS1. • NS1 R37A, R38A, K41A viruses had minimal changes in replication and NS1 localization. • Viruses from NS1 R35A rescue all contained additional mutations at D39. • NS1 R35A D39X mutations recover dimerization lost in NS1 R35A mutations. • These results reaffirm the importance of dimerization for NS1 protein function.

The R35 residue of the influenza A virus NS1 protein has minimal effects on nuclear localization but alters virus replication through disrupting protein dimerization

International Nuclear Information System (INIS)

Lalime, Erin N.; Pekosz, Andrew

2014-01-01

The influenza A virus NS1 protein has a nuclear localization sequence (NLS) in the amino terminal region. This NLS overlaps sequences that are important for RNA binding as well as protein dimerization. To assess the significance of the NS1 NLS on influenza virus replication, the NLS amino acids were individually mutated to alanines and recombinant viruses encoding these mutations were rescued. Viruses containing NS1 proteins with mutations at R37, R38 and K41 displayed minimal changes in replication or NS1 protein nuclear localization. Recombinant viruses encoding NS1 R35A were not recovered but viruses containing second site mutations at position D39 in addition to the R35A mutation were isolated. The mutations at position 39 were shown to partially restore NS1 protein dimerization but had minimal effects on nuclear localization. These data indicate that the amino acids in the NS1 NLS region play a more important role in protein dimerization compared to nuclear localization. - Highlights: • Mutations were introduced into influenza NS1 NLS1. • NS1 R37A, R38A, K41A viruses had minimal changes in replication and NS1 localization. • Viruses from NS1 R35A rescue all contained additional mutations at D39. • NS1 R35A D39X mutations recover dimerization lost in NS1 R35A mutations. • These results reaffirm the importance of dimerization for NS1 protein function

Boron tolerance in NS wheat lines

Directory of Open Access Journals (Sweden)

Brdar Milka

2006-01-01

Full Text Available Boron is an essential micronutrient for higher plants. Present in excessive amounts boron becomes toxic and can limit plant growth and yield. Suppression of root growth is one of the symptoms of boron toxicity in wheat. This study was undertaken to investigate the response of 10 perspective NS lines of wheat to high concentrations of boron. Analysis of root growth was done on young plants, germinated and grown in the presence of different concentrations of boric acid (0, 50,100 and 150 mg/1. Significant differences occurred between analyzed genotypes and treatments regarding root length. Average suppression of root growth was between 11,6 and 34,2%, for line NS 252/02 are even noted 61,4% longer roots at treatments in relation to the control. Lines with mean suppression of root growth less than 20% (NS 101/02, NS 138/01, NS 53/03 and NS 73/02 may be considered as boron tolerant. Spearmans coefficients showed high level of agreement regarding rang of root length for genotypes treated with 100 and 150 mg H3BO3/l.

16 CFR 309.1 - Definitions.

Science.gov (United States)

2010-01-01

... ALTERNATIVE FUELS AND ALTERNATIVE FUELED VEHICLES General § 309.1 Definitions. As used in subparts B and C of... derivative) capable of seating 12 passengers or less; or (2) A dedicated or dual fueled motor vehicle (other.... It also means any person, except a common carrier, who receives an electric vehicle fuel dispensing...

The influence of DOCA-salt hypertension and chronic administration of the FAAH inhibitor URB597 on KCa2.3/KCa3.1-EDH-type relaxation in rat small mesenteric arteries.

Science.gov (United States)

Kloza, Monika; Baranowska-Kuczko, Marta; Malinowska, Barbara; Karpińska, Olga; Harasim-Symbor, Ewa; Kasacka, Irena; Kozłowska, Hanna

2017-12-01

The aim of this study was to examine the influence of deoxycorticosterone acetate-salt (DOCA-salt) hypertension and chronic treatment with the fatty acid amide hydrolase inhibitor, URB597, on small and intermediate conductance calcium-activated potassium channels and endothelium-dependent hyperpolarization (K Ca 2.3/K Ca 3.1-EDH) in rat small mesenteric arteries (sMAs). The EDH-type response was investigated, in endothelium-intact sMAs using a wire myograph, by examining acetylcholine-evoked vasorelaxation in the presence of N ω -nitro-L-arginine methyl ester and indomethacin (inhibitors of nitric oxide synthase and cyclooxygenase, respectively). In normo- and hypertension the efficacy of EDH-type relaxation was similar and inhibition of K Ca 2.3 and K Ca 3.1 by UCL1684 and TRAM-34, respectively, given alone or in combination, attenuated EDH-mediated vasorelaxation. K Ca 3.1 expression and NS309 (K Ca 2.3/K Ca 3.1 activator)-induced relaxation was reduced in sMAs of DOCA-salt rats. Endothelium denudation and incubation with UCL1684 and TRAM-34 attenuated the maximal NS309-evoked vasorelaxation in both groups. URB597 had no effect in functional studies, but increased the expression of K Ca 3.1 in the sMAs. K Ca 2.3/K Ca 3.1-EDH-mediated relaxation was maintained in the sMAs of DOCA-salt rats despite endothelial dysfunction and down-regulation of K Ca 3.1. Furthermore, K Ca 3.1 played a key role in the EDH-type dilator response of sMAs in normo- and hypertension. The hypotensive effect of URB597 is independent of K Ca 2.3/K Ca 3.1-EDH-type relaxation. Copyright © 2017 Elsevier Inc. All rights reserved.

9 CFR 309.8 - Cattle affected with anasarca and generalized edema.

Science.gov (United States)

2010-01-01

... generalized edema. 309.8 Section 309.8 Animals and Animal Products FOOD SAFETY AND INSPECTION SERVICE... anasarca and generalized edema. All cattle found on ante-mortem inspection to be affected with anasarca in advanced stages and characterized by an extensive and generalized edema shall be identified as U.S...

Diagnostic accuracy of different display types in detection of recurrent caries under restorations by using CBCT.

Science.gov (United States)

Baltacıoĝlu, İsmail H; Eren, Hakan; Yavuz, Yasemin; Kamburoğlu, Kıvanç

To assess the in vitro diagnostic ability of CBCT images using seven different display types in the detection of recurrent caries. Our study comprised 128 extracted human premolar and molar teeth. 8 groups each containing 16 teeth were obtained as follows: (1) Black Class I (Occlusal) amalgam filling without caries; (2) Black Class I (Occlusal) composite filling without caries; (3) Black Class II (Proximal) amalgam filling without caries; (4) Black Class II (Proximal) composite filling without caries; (5) Black Class I (Occlusal) amalgam filling with caries; (6) Black Class I (Occlusal) composite filling with caries; (7) Black Class II (Proximal) amalgam filling with caries; and (8) Black Class II (Proximal) composite filling with caries. Teeth were imaged using 100 × 90 mm field of view at three different voxel sizes of a CBCT unit (Planmeca ProMax(®) 3D ProFace™; Planmeca, Helsinki, Finland). CBCT TIFF images were opened and viewed using custom-designed software for computers on different display types. Intra- and interobserver agreements were calculated. The highest area under the receiver operating characteristic curve (Az) values for each image type, observer, reading and restoration were compared using z-tests against Az = 0.5. The significance level was set at p = 0.05. We found poor and moderate agreements. In general, Az values were found when software and medical diagnostic monitor were utilized. For Observer 2, Az values were statistically significantly higher when software was used on medical monitor [p = 0.036, p = 0.015 and p = 0.002, for normal-resolution mode (0.200 mm(3) voxel size), high-resolution mode (0.150 mm(3) voxel size) and low-resolution mode (0.400 mm(3) voxel size), respectively]. No statistically significant differences were found among other display types for all modes (p > 0.05). In general, no difference was found among 3 different voxel sizes (p > 0.05). In general, higher Az values were

Diagnostic accuracy of different display types in detection of recurrent caries under restorations by using CBCT

Science.gov (United States)

Baltacıoĝlu, İsmail H; Eren, Hakan; Yavuz, Yasemin

2016-01-01

Objectives: To assess the in vitro diagnostic ability of CBCT images using seven different display types in the detection of recurrent caries. Methods: Our study comprised 128 extracted human premolar and molar teeth. 8 groups each containing 16 teeth were obtained as follows: (1) Black Class I (Occlusal) amalgam filling without caries; (2) Black Class I (Occlusal) composite filling without caries; (3) Black Class II (Proximal) amalgam filling without caries; (4) Black Class II (Proximal) composite filling without caries; (5) Black Class I (Occlusal) amalgam filling with caries; (6) Black Class I (Occlusal) composite filling with caries; (7) Black Class II (Proximal) amalgam filling with caries; and (8) Black Class II (Proximal) composite filling with caries. Teeth were imaged using 100 × 90 mm field of view at three different voxel sizes of a CBCT unit (Planmeca ProMax® 3D ProFace™; Planmeca, Helsinki, Finland). CBCT TIFF images were opened and viewed using custom-designed software for computers on different display types. Intra- and interobserver agreements were calculated. The highest area under the receiver operating characteristic curve (Az) values for each image type, observer, reading and restoration were compared using z-tests against Az = 0.5. The significance level was set at p = 0.05. Results: We found poor and moderate agreements. In general, Az values were found when software and medical diagnostic monitor were utilized. For Observer 2, Az values were statistically significantly higher when software was used on medical monitor [p = 0.036, p = 0.015 and p = 0.002, for normal-resolution mode (0.200 mm3 voxel size), high-resolution mode (0.150 mm3 voxel size) and low-resolution mode (0.400 mm3 voxel size), respectively]. No statistically significant differences were found among other display types for all modes (p > 0.05). In general, no difference was found among 3 different voxel sizes (p > 0.05). In general

Supersymmetric non-singular fractional D2-branes and NS-NS 2-branes

International Nuclear Information System (INIS)

Cvetic, M.; Gibbons, G.W.; Lue, H.; Pope, C.N.

2001-01-01

We obtain regular deformed D2-brane solutions with fractional D2-branes arising as wrapped D4-branes. The space transverse to the D2-brane is a complete Ricci-flat 7-manifold of G 2 holonomy, which is asymptotically conical with principal orbits that are topologically CP 3 or the flag manifold SU(3)/(U(1)xU(1)). We obtain the solution by first constructing an L 2 normalisable harmonic 3-form. We also review a previously-obtained regular deformed D2-brane whose transverse space is a different 7-manifold of G 2 holonomy, with principal orbits that are topologically S 3 xS 3 . This describes D2-branes with fractional NS-NS 2-branes coming from the wrapping of 5-branes, which is supported by a non-normalisable harmonic 3-form on the 7-manifold. We prove that both types of solutions are supersymmetric, preserving 1/16 of the maximal supersymmetry and hence that they are dual to N=1 three-dimensional gauge theories. In each case, the spectrum for minimally-coupled scalars is discrete, indicating confinement in the infrared region of the dual gauge theories. We examine resolutions of other branes, and obtain necessary conditions for their regularity. The resolution of many of these seems to lie beyond supergravity. In the process of studying these questions, we construct new explicit examples of complete Ricci-flat metrics

Ability of Rf5 and Rf6 to Restore Fertility of Chinsurah Boro II-type Cytoplasmic Male Sterile Oryza Sativa (ssp. Japonica) Lines.

Science.gov (United States)

Zhang, Honggen; Che, Jianlan; Ge, Yongshen; Pei, Yan; Zhang, Lijia; Liu, Qiaoquan; Gu, Minghong; Tang, Shuzhu

2017-12-01

Three-line Oryza sativa (ssp. japonica) hybrids have been developed mainly using Chinsurah Boro II (BT)-type cytoplasmic male sterility (CMS). The Rf1 gene restores the fertility of BT-type CMS lines, and is the only fertility restorer gene (Rf) that has been used to produce three-line japonica hybrids. Using more Rf genes to breed BT-type restorer lines may broaden the genetic diversity of the restorer lines, and represents a viable approach to improve the heterosis level of BT-type japonica hybrids. We identified two major Rf genes from '93-11' that are involved in restoring the fertility of BT-type CMS plants. These genes were identified from resequenced chromosome segment substitution lines derived from a cross between the japonica variety 'Nipponbare' and the indica variety '93-11'. Molecular mapping results revealed that these genes were Rf5 and Rf6, which are the Rf genes that restore fertility to Honglian-type CMS lines. The BT-type F 1 hybrids with either Rf5 or Rf6 exhibited normal seed setting rates, but F 1 plants carrying Rf6 showed more stable seed setting rates than those of plants carrying Rf5 under heat-stress conditions. Furthermore, the seed setting rates of F 1 hybrids carrying both Rf5 and Rf6 were more stable than that of F 1 plants carrying only one Rf gene. Rf6 is an important genetic resource for the breeding of BT-type japonica restorer lines. Our findings may be useful for breeders interested in developing BT-type japonica hybrids.

Evaluation of the Genetic Response of U937 and Jurkat Cells to 10-Nanosecond Electrical Pulses (nsEP.

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Caleb C Roth

Full Text Available Nanosecond electrical pulse (nsEP exposure activates signaling pathways, produces oxidative stress, stimulates hormone secretion, causes cell swelling and induces apoptotic and necrotic death. The underlying biophysical connection(s between these diverse cellular reactions and nsEP has yet to be elucidated. Using global genetic analysis, we evaluated how two commonly studied cell types, U937 and Jurkat, respond to nsEP exposure. We hypothesized that by studying the genetic response of the cells following exposure, we would gain direct insight into the stresses experienced by the cell and in turn better understand the biophysical interaction taking place during the exposure. Using Ingenuity Systems software, we found genes associated with cell growth, movement and development to be significantly up-regulated in both cell types 4 h post exposure to nsEP. In agreement with our hypothesis, we also found that both cell lines exhibit significant biological changes consistent with mechanical stress induction. These results advance nsEP research by providing strong evidence that the interaction of nsEPs with cells involves mechanical stress.

Predicting deleterious nsSNPs: an analysis of sequence and structural attributes

Directory of Open Access Journals (Sweden)

Saqi Mansoor AS

2006-04-01

Full Text Available Abstract Background There has been an explosion in the number of single nucleotide polymorphisms (SNPs within public databases. In this study we focused on non-synonymous protein coding single nucleotide polymorphisms (nsSNPs, some associated with disease and others which are thought to be neutral. We describe the distribution of both types of nsSNPs using structural and sequence based features and assess the relative value of these attributes as predictors of function using machine learning methods. We also address the common problem of balance within machine learning methods and show the effect of imbalance on nsSNP function prediction. We show that nsSNP function prediction can be significantly improved by 100% undersampling of the majority class. The learnt rules were then applied to make predictions of function on all nsSNPs within Ensembl. Results The measure of prediction success is greatly affected by the level of imbalance in the training dataset. We found the balanced dataset that included all attributes produced the best prediction. The performance as measured by the Matthews correlation coefficient (MCC varied between 0.49 and 0.25 depending on the imbalance. As previously observed, the degree of sequence conservation at the nsSNP position is the single most useful attribute. In addition to conservation, structural predictions made using a balanced dataset can be of value. Conclusion The predictions for all nsSNPs within Ensembl, based on a balanced dataset using all attributes, are available as a DAS annotation. Instructions for adding the track to Ensembl are at http://www.brightstudy.ac.uk/das_help.html

7 CFR 900.309 - Confidential information.

Science.gov (United States)

2010-01-01

... Conduct of Referenda To Determine Producer Approval of Milk Marketing Orders To Be Made Effective Pursuant to Agricultural Marketing Agreement Act of 1937, as Amended § 900.309 Confidential information. The... Agriculture Regulations of the Department of Agriculture (Continued) AGRICULTURAL MARKETING SERVICE (Marketing...

31 CFR 597.309 - Foreign terrorist organization.

Science.gov (United States)

2010-07-01

... REGULATIONS General Definitions § 597.309 Foreign terrorist organization. The term foreign terrorist... respect to which the Secretary of State has notified Congress of the intention to designate as a foreign...

Purification and crystallization of dengue and West Nile virus NS2B–NS3 complexes

Energy Technology Data Exchange (ETDEWEB)

D’Arcy, Allan, E-mail: allan.darcy@novartis.com; Chaillet, Maxime; Schiering, Nikolaus; Villard, Frederic [Novartis Institutes of Biomedical Research, Protease Platform, Klybeckstrasse 144, CH 4002 Basel (Switzerland); Lim, Siew Pheng [Novartis Institutes of Tropical Diseases (Singapore); Lefeuvre, Peggy [Novartis Institutes of Biomedical Research, Protease Platform, Klybeckstrasse 144, CH 4002 Basel (Switzerland); Erbel, Paul [Novartis Institutes of Biomedical Research, Protease Platform, Klybeckstrasse 144, CH 4002 Basel (Switzerland); Novartis Institutes of Tropical Diseases (Singapore)

2006-02-01

Crystals of dengue serotype 2 and West Nile virus NS2B–NS3 protease complexes have been obtained and the crystals of both diffract to useful resolution. Sample homogeneity was essential for obtaining X-ray-quality crystals of the dengue protease. Controlled proteolysis produced a crystallizable fragment of the apo West Nile virus NS2B–NS3 and crystals were also obtained in the presence of a peptidic inhibitor. Both dengue and West Nile virus infections are an increasing risk to humans, not only in tropical and subtropical areas, but also in North America and parts of Europe. These viral infections are generally transmitted by mosquitoes, but may also be tick-borne. Infection usually results in mild flu-like symptoms, but can also cause encephalitis and fatalities. Approximately 2799 severe West Nile virus cases were reported this year in the United States, resulting in 102 fatalities. With this alarming increase in the number of West Nile virus infections in western countries and the fact that dengue virus already affects millions of people per year in tropical and subtropical climates, there is a real need for effective medicines. A possible therapeutic target to combat these viruses is the protease, which is essential for virus replication. In order to provide structural information to help to guide a lead identification and optimization program, crystallizations of the NS2B–NS3 protease complexes from both dengue and West Nile viruses have been initiated. Crystals that diffract to high resolution, suitable for three-dimensional structure determinations, have been obtained.

Purification and crystallization of dengue and West Nile virus NS2B–NS3 complexes

International Nuclear Information System (INIS)

D’Arcy, Allan; Chaillet, Maxime; Schiering, Nikolaus; Villard, Frederic; Lim, Siew Pheng; Lefeuvre, Peggy; Erbel, Paul

2006-01-01

Crystals of dengue serotype 2 and West Nile virus NS2B–NS3 protease complexes have been obtained and the crystals of both diffract to useful resolution. Sample homogeneity was essential for obtaining X-ray-quality crystals of the dengue protease. Controlled proteolysis produced a crystallizable fragment of the apo West Nile virus NS2B–NS3 and crystals were also obtained in the presence of a peptidic inhibitor. Both dengue and West Nile virus infections are an increasing risk to humans, not only in tropical and subtropical areas, but also in North America and parts of Europe. These viral infections are generally transmitted by mosquitoes, but may also be tick-borne. Infection usually results in mild flu-like symptoms, but can also cause encephalitis and fatalities. Approximately 2799 severe West Nile virus cases were reported this year in the United States, resulting in 102 fatalities. With this alarming increase in the number of West Nile virus infections in western countries and the fact that dengue virus already affects millions of people per year in tropical and subtropical climates, there is a real need for effective medicines. A possible therapeutic target to combat these viruses is the protease, which is essential for virus replication. In order to provide structural information to help to guide a lead identification and optimization program, crystallizations of the NS2B–NS3 protease complexes from both dengue and West Nile viruses have been initiated. Crystals that diffract to high resolution, suitable for three-dimensional structure determinations, have been obtained

Image Restoration Based on the Hybrid Total-Variation-Type Model

OpenAIRE

Shi, Baoli; Pang, Zhi-Feng; Yang, Yu-Fei

2012-01-01

We propose a hybrid total-variation-type model for the image restoration problem based on combining advantages of the ROF model with the LLT model. Since two ${L}^{1}$ -norm terms in the proposed model make it difficultly solved by using some classically numerical methods directly, we first employ the alternating direction method of multipliers (ADMM) to solve a general form of the proposed model. Then, based on the ADMM and the Moreau-Yosida decomposition theory, a more efficient method call...

Performance of commercial dengue NS1 ELISA and molecular analysis of NS1 gene of dengue viruses obtained during surveillance in Indonesia.

Science.gov (United States)

Aryati, Aryati; Trimarsanto, Hidayat; Yohan, Benediktus; Wardhani, Puspa; Fahri, Sukmal; Sasmono, R Tedjo

2013-12-29

Early diagnosis of dengue infection is crucial for better management of the disease. Diagnostic tests based on the detection of dengue virus (DENV) Non Structural Protein 1 (NS1) antigen are commercially available with different sensitivities and specificities observed in various settings. Dengue is endemic in Indonesia and clinicians are increasingly using the NS1 detection for dengue confirmation. This study described the performance of Panbio Dengue Early NS1 and IgM Capture ELISA assays for dengue detection during our surveillance in eight cities in Indonesia as well as the genetic diversity of DENV NS1 genes and its relationship with the NS1 detection. The NS1 and IgM/IgG ELISA assays were used for screening and confirmation of dengue infection during surveillance in 2010-2012. Collected serum samples (n = 440) were subjected to RT-PCR and virus isolation, in which 188 samples were confirmed for dengue infection. The positivity of the ELISA assays were correlated with the RT-PCR results to obtain the sensitivity of the assays. The NS1 genes of 48 Indonesian virus isolates were sequenced and their genetic characteristics were studied. Using molecular data as gold standard, the sensitivity of NS1 ELISA assay for samples from Indonesia was 56.4% while IgM ELISA was 73.7%. When both NS1 and IgM results were combined, the sensitivity increased to 89.4%. The NS1 sensitivity varied when correlated with city/geographical origins and DENV serotype, in which the lowest sensitivity was observed for DENV-4 (19.0%). NS1 sensitivity was higher in primary (67.6%) compared to secondary infection (48.2%). The specificity of NS1 assay for non-dengue samples were 100%. The NS1 gene sequence analysis of 48 isolates revealed the presence of polymorphisms of the NS1 genes which apparently did not influence the NS1 sensitivity. We observed a relatively low sensitivity of NS1 ELISA for dengue detection on RT-PCR-positive dengue samples. The detection rate increased significantly

Characterization of the 309 building fuel transfer pit and storage basin

International Nuclear Information System (INIS)

Hale, N.S.

1998-01-01

This document identifies radiological, chemical and physical conditions inside the Fuel Transfer Pit and Fuel Storage Basins. These spaces are located inside the Plutonium Recycle Test Reactor structure (309 Building.) The fuel handling and storage feature of the PRTR were primarily located in these spaces. The conditions were assessed as part of overall 309 Building transition

Unexpected Functional Divergence of Bat Influenza Virus NS1 Proteins.

Science.gov (United States)

Turkington, Hannah L; Juozapaitis, Mindaugas; Tsolakos, Nikos; Corrales-Aguilar, Eugenia; Schwemmle, Martin; Hale, Benjamin G

2018-03-01

Recently, two influenza A virus (FLUAV) genomes were identified in Central and South American bats. These sequences exhibit notable divergence from classical FLUAV counterparts, and functionally, bat FLUAV glycoproteins lack canonical receptor binding and destroying activity. Nevertheless, other features that distinguish these viruses from classical FLUAVs have yet to be explored. Here, we studied the viral nonstructural protein NS1, a virulence factor that modulates host signaling to promote efficient propagation. Like all FLUAV NS1 proteins, bat FLUAV NS1s bind double-stranded RNA and act as interferon antagonists. Unexpectedly, we found that bat FLUAV NS1s are unique in being unable to bind host p85β, a regulatory subunit of the cellular metabolism-regulating enzyme, phosphoinositide 3-kinase (PI3K). Furthermore, neither bat FLUAV NS1 alone nor infection with a chimeric bat FLUAV efficiently activates Akt, a PI3K effector. Structure-guided mutagenesis revealed that the bat FLUAV NS1-p85β interaction can be reengineered (in a strain-specific manner) by changing two to four NS1 residues (96L, 99M, 100I, and 145T), thereby creating a hydrophobic patch. Notably, ameliorated p85β-binding is insufficient for bat FLUAV NS1 to activate PI3K, and a chimeric bat FLUAV expressing NS1 with engineered hydrophobic patch mutations exhibits cell-type-dependent, but species-independent, propagation phenotypes. We hypothesize that bat FLUAV hijacking of PI3K in the natural bat host has been selected against, perhaps because genes in this metabolic pathway were differentially shaped by evolution to suit the unique energy use strategies of this flying mammal. These data expand our understanding of the enigmatic functional divergence between bat FLUAVs and classical mammalian and avian FLUAVs. IMPORTANCE The potential for novel influenza A viruses to establish infections in humans from animals is a source of continuous concern due to possible severe outbreaks or pandemics. The

41 CFR 101-26.309 - Cancellation of orders for GSA stock items.

Science.gov (United States)

2010-07-01

... 41 Public Contracts and Property Management 2 2010-07-01 2010-07-01 true Cancellation of orders for GSA stock items. 101-26.309 Section 101-26.309 Public Contracts and Property Management Federal Property Management Regulations System FEDERAL PROPERTY MANAGEMENT REGULATIONS SUPPLY AND PROCUREMENT 26...

Rationalizing meat consumption. The 4Ns.

Science.gov (United States)

Piazza, Jared; Ruby, Matthew B; Loughnan, Steve; Luong, Mischel; Kulik, Juliana; Watkins, Hanne M; Seigerman, Mirra

2015-08-01

Recent theorizing suggests that the 4Ns - that is, the belief that eating meat is natural, normal, necessary, and nice - are common rationalizations people use to defend their choice of eating meat. However, such theorizing has yet to be subjected to empirical testing. Six studies were conducted on the 4Ns. Studies 1a and 1b demonstrated that the 4N classification captures the vast majority (83%-91%) of justifications people naturally offer in defense of eating meat. In Study 2, individuals who endorsed the 4Ns tended also to objectify (dementalize) animals and included fewer animals in their circle of moral concern, and this was true independent of social dominance orientation. Subsequent studies (Studies 3-5) showed that individuals who endorsed the 4Ns tend not to be motivated by ethical concerns when making food choices, are less involved in animal-welfare advocacy, less driven to restrict animal products from their diet, less proud of their animal-product decisions, tend to endorse Speciesist attitudes, tend to consume meat and animal products more frequently, and are highly committed to eating meat. Furthermore, omnivores who strongly endorsed the 4Ns tended to experience less guilt about their animal-product decisions, highlighting the guilt-alleviating function of the 4Ns. Copyright © 2015 Elsevier Ltd. All rights reserved.

Fracture Resistance of Premolars Restored by Various Types and Placement Techniques of Resin Composites

Directory of Open Access Journals (Sweden)

Horieh Moosavi

2012-01-01

Full Text Available To verify the fracture resistance of premolars with mesioocclusodistal preparations restored by different resin composites and placement techniques. Sixty premolars were randomly divided into two groups based on type of composite resin: Filtek P60 or Nulite F, and then each group was separated into three subgroups: bulk, centripetal, and fiber insert according to the type of placement method (n=10. Single-bond adhesive system was used as composite bonding according to the manufacturer's instructions. Specimens were restored in Groups 1, 2, and 3 with Filtek P60 and in Groups 4, 5, and 6 with Nulite F. After being stored 24 hours at 37∘C, a 4 mm diameter steel sphere in a universal testing machine was applied on tooth buccal and lingual cusps at a cross-head speed of 5 mm/min until fracture occurred. Groups 3 and 6 showed higher fracture resistance than Groups 1, 2, 4, and 5. Among the placement techniques, the fiber insert method had a significant effect, but the type of composite was ineffective. The insertion technique in contrast to the type of material had a significant influence on the fracture resistance of premolar teeth.

Leptin-induced endothelium-dependent vasorelaxation of peripheral arteries in lean and obese rats: role of nitric oxide and hydrogen sulfide.

Directory of Open Access Journals (Sweden)

Anna Jamroz-Wiśniewska

Full Text Available Adipose tissue hormone leptin induces endothelium-dependent vasorelaxation mediated by nitric oxide (NO and endothelium-derived hyperpolarizing factors (EDHF. Previously it has been demonstrated that in short-term obesity the NO-dependent and the EDHF-dependent components of vascular effect of leptin are impaired and up-regulated, respectively. Herein we examined the mechanism of the EDHF-dependent vasodilatory effect of leptin and tested the hypothesis that alterations of acute vascular effects of leptin in obesity are accounted for by chronic hyperleptinemia. The study was performed in 5 groups of rats: (1 control, (2 treated with exogenous leptin for 1 week to induce hyperleptinemia, (3 obese, fed highly-palatable diet for 4 weeks, (4 obese treated with pegylated superactive rat leptin receptor antagonist (PEG-SRLA for 1 week, (5 fed standard chow and treated with PEG-SRLA. Acute effect of leptin on isometric tension of mesenteric artery segments was measured ex vivo. Leptin relaxed phenylephrine-preconstricted vascular segments in NO- and EDHF-dependent manner. The NO-dependent component was impaired and the EDHF-dependent component was increased in the leptin-treated and obese groups and in the latter group both these effects were abolished by PEG-SRLA. The EDHF-dependent vasodilatory effect of leptin was blocked by either the inhibitor of cystathionine γ-lyase, propargylglycine, or a hydrogen sulfide (H2S scavenger, bismuth (III subsalicylate. The results indicate that NO deficiency is compensated by the up-regulation of EDHF in obese rats and both effects are accounted for by chronic hyperleptinemia. The EDHF-dependent component of leptin-induced vasorelaxation is mediated, at least partially, by H2S.

Polymorphism of MDM2 promoter 309 (rs 2279744) and the risk of PCOS.

Science.gov (United States)

Chan, Ying; Jiang, Hongguo; Yang, Xiaoling; Li, Dongya; Ma, Lan; Luo, Ying; Tang, Wenru

2016-01-01

This study aimed at evaluating possible association between MDM2 SNP309 polymorphism (rs 2279744) and polycystic ovary syndrome (PCOS). One hundred and twenty-five women with PCOS and two hundred and fifty women without PCOS were collected from the department of reproductive medicine of college hospital in this case-control study. Peripheral blood samples were collected from all participants and DNA was extracted, MDM2 SNP309 polymorphism (rs 2279744) was determined from the 125 cases and 250 controls. Women were grouped into PCOS (n = 125) group and control group (n = 250). Odds ratios (OR) and 95% confidence intervals (CI) were used to evaluate the association between MDM2 SNP309 polymorphism (rs 2279744) and PCOS. The distribution of T allele was significant higher in PCOS cases than controls. MDM2 SNP 309 T allele is associated with PCOS.

48 CFR 1545.309 - Providing Government production and research property under special restrictions.

Science.gov (United States)

2010-10-01

... improvements necessary for installing special tooling, special test equipment, or plant equipment, shall not be... production and research property under special restrictions. 1545.309 Section 1545.309 Federal Acquisition Regulations System ENVIRONMENTAL PROTECTION AGENCY CONTRACT MANAGEMENT GOVERNMENT PROPERTY Providing...

Design Concept of a Seal-off Type 14 MeV Neutron Generator of 10''1''1n/s Range

Energy Technology Data Exchange (ETDEWEB)

In, S. R.; Oh, B. H. [KAERI, Daejeon (Korea, Republic of)

2015-05-15

The total neutron fluence during the life time is expected to be around 10MW·yr/m''2 which may cause a damage of -100 dpa in materials. To estimate the adaptability of candidate materials in a few years, a 14MeV neutron source with a flux level of 3 - 5 x 10''1''8 n/s·m''2, which is the goal of the IFMIF facility costing more than ¤1000M, is necessitated. The problem in making an intense neutron generator of beam target type is really not on the neutron production rate, but on the huge heat generated in the target, because the fusion power is only one of thousands of beam power exerted on the target. We have a plan to develop neutron generators step by step from a 10''8 n/s level. The final goal is establishing a 14MeV neutron irradiation facility at 10''1''4 intensity level.. Up to the 10''1''0 n/s level, there occurs basically no critical thermal problem, because beam power density is in the range of tens W/cm''2. The neutron generator designed in a sealed-off type because of tritium safety is mainly composed of an ion source, target, reaction chamber, and getter pump.. The major design concepts for the neutron generator with the neutron production rate of 10''1''1 n/s range were presented. The specifications of the ion source, target and getter have been determined for attaining the goal of the neutron generation rate.

49 CFR 385.309 - What is the purpose of the safety audit?

Science.gov (United States)

2010-10-01

... 49 Transportation 5 2010-10-01 2010-10-01 false What is the purpose of the safety audit? 385.309... SAFETY FITNESS PROCEDURES New Entrant Safety Assurance Program § 385.309 What is the purpose of the safety audit? The purpose of a safety audit is to: (a) Provide educational and technical assistance to...

25 CFR 309.13 - What are examples of other weaving and textiles that are Indian products?

Science.gov (United States)

2010-04-01

... Indian products? 309.13 Section 309.13 Indians INDIAN ARTS AND CRAFTS BOARD, DEPARTMENT OF THE INTERIOR PROTECTION OF INDIAN ARTS AND CRAFTS PRODUCTS § 309.13 What are examples of other weaving and textiles that..., star quilts, pictorial appliqué wall hangings, fiber woven bags, embroidered dance shawls, rabbit skin...

Application of the Ceditest FMDV type O and FMDV-NS enzyme-linked immunosorbent assays for detection of antibodies against Foot-and-mouth disease virus in selected livestock and wildlife species in Uganda

DEFF Research Database (Denmark)

Ayebazibwe, Chrisostom; Mwiine, Frank Norbert; Balinda, Sheila Nina

2012-01-01

Diagnosis and control of Foot-and-mouth disease virus (FMDV) requires rapid and sensitive diagnostic tests. Two antibody enzyme-linked immunosorbent assay (ELISA) kits, Ceditest FMDV-NS for the detection of antibodies against the nonstructural proteins of all FMDV serotypes and Ceditest FMDV type O......, and selected samples were tested not only in serotype-specific ELISAs for antibodies against primarily FMDV serotype O, but also against other serotypes. The FMDV-NS assay detected far more positive samples (93%) than the FMDV type O assay (30%) in buffalo (P ... the South African Territories (SAT) serotypes, while the seroprevalence was generally comparable in cattle with antibodies against serotype O elicited by infection and/or vaccination. However, some districts had higher seroprevalence using the FMDV type O assay indicating vaccination without infection...

The F309S mutation increases factor VIII secretion in human cell line

Directory of Open Access Journals (Sweden)

Daianne Maciely Carvalho Fantacini

2016-06-01

Full Text Available ABSTRACT OBJECTIVES: The capacity of a human cell line to secrete recombinant factor VIII with a F309S point mutation was investigated, as was the effect of the addition of chemical chaperones (betaine and sodium-4-phenylbutyrate on the secretion of factor VIII. METHODS: This work used a vector with a F309S mutation in the A1 domain to investigate FVIII production in the HEK 293 human cell line. Factor VIII activity was measured by chromogenic assay. Furthermore, the effects of chemical drugs on the culture were evaluated. RESULTS: The addition of the F309S mutation to a previously described FVIII variant increased FVIII secretion by 4.5 fold. Moreover, the addition of betaine or sodium-4-phenylbutyrate increased the secretion rate of FVIIIΔB proteins in HEK 293 cells, but the same effect was not seen for FVIIIΔB-F309S indicating that all the recombinant protein produced had been efficiently secreted. CONCLUSION: Bioengineering factor VIII expressed in human cells may lead to an efficient production of recombinant factor VIII and contribute toward low-cost coagulation factor replacement therapy for hemophilia A. FVIII-F309S produced in human cells can be effective in vivo.

Advanced Power Batteries for Renewable Energy Applications 3.09

Energy Technology Data Exchange (ETDEWEB)

Shane, Rodney [East Penn Manufacturing Company, Inc., Lyon Station, PA (United States)

2011-12-01

This report describes the research that was completed under project title Advanced Power Batteries for Renewable Energy Applications 3.09, Award Number DE-EE0001112. The report details all tasks described in the Statement of Project Objectives (SOPO). The SOPO includes purchasing of test equipment, designing tooling, building cells and batteries, testing all variables and final evaluation of results. The SOPO is included. There were various types of tests performed during the project, such as; gas collection, float current monitoring, initial capacity, high rate partial state of charge (HRPSoC), hybrid pulse power characterization (HPPC), high rate capacity, corrosion, software modeling and solar life cycle tests. The grant covered a period of two years starting October 1, 2009 and ending September 30, 2011.

Pulmonary hypertension in wild type mice and animals with genetic deficit in KCa2.3 and KCa3.1 channels.

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Christine Wandall-Frostholm

Full Text Available In vascular biology, endothelial KCa2.3 and KCa3.1 channels contribute to arterial blood pressure regulation by producing membrane hyperpolarization and smooth muscle relaxation. The role of KCa2.3 and KCa3.1 channels in the pulmonary circulation is not fully established. Using mice with genetically encoded deficit of KCa2.3 and KCa3.1 channels, this study investigated the effect of loss of the channels in hypoxia-induced pulmonary hypertension.Male wild type and KCa3.1-/-/KCa2.3T/T(+DOX mice were exposed to chronic hypoxia for four weeks to induce pulmonary hypertension. The degree of pulmonary hypertension was evaluated by right ventricular pressure and assessment of right ventricular hypertrophy. Segments of pulmonary arteries were mounted in a wire myograph for functional studies and morphometric studies were performed on lung sections. Chronic hypoxia induced pulmonary hypertension, right ventricular hypertrophy, increased lung weight, and increased hematocrit levels in either genotype. The KCa3.1-/-/KCa2.3T/T(+DOX mice developed structural alterations in the heart with increased right ventricular wall thickness as well as in pulmonary vessels with increased lumen size in partially- and fully-muscularized vessels and decreased wall area, not seen in wild type mice. Exposure to chronic hypoxia up-regulated the gene expression of the KCa2.3 channel by twofold in wild type mice and increased by 2.5-fold the relaxation evoked by the KCa2.3 and KCa3.1 channel activator NS309, whereas the acetylcholine-induced relaxation - sensitive to the combination of KCa2.3 and KCa3.1 channel blockers, apamin and charybdotoxin - was reduced by 2.5-fold in chronic hypoxic mice of either genotype.Despite the deficits of the KCa2.3 and KCa3.1 channels failed to change hypoxia-induced pulmonary hypertension, the up-regulation of KCa2.3-gene expression and increased NS309-induced relaxation in wild-type mice point to a novel mechanism to counteract pulmonary

Hepatitis C virus NS3/4A protease inhibits complement activation by cleaving complement component 4.

Directory of Open Access Journals (Sweden)

Seiichi Mawatari

Full Text Available BACKGROUND: It has been hypothesized that persistent hepatitis C virus (HCV infection is mediated in part by viral proteins that abrogate the host immune response, including the complement system, but the precise mechanisms are not well understood. We investigated whether HCV proteins are involved in the fragmentation of complement component 4 (C4, composed of subunits C4α, C4β, and C4γ, and the role of HCV proteins in complement activation. METHODS: Human C4 was incubated with HCV nonstructural (NS 3/4A protease, core, or NS5. Samples were separated by sodium dodecyl sulfate-polyacrylamide gel electrophoresis and then subjected to peptide sequencing. The activity of the classical complement pathway was examined using an erythrocyte hemolysis assay. The cleavage pattern of C4 in NS3/4A-expressing and HCV-infected cells, respectively, was also examined. RESULTS: HCV NS3/4A protease cleaved C4γ in a concentration-dependent manner, but viral core and NS5 did not. A specific inhibitor of NS3/4A protease reduced C4γ cleavage. NS3/4A protease-mediated cleavage of C4 inhibited classical pathway activation, which was abrogated by a NS3/4A protease inhibitor. In addition, co-transfection of cells with C4 and wild-type NS3/4A, but not a catalytic-site mutant of NS3/4A, produced cleaved C4γ fragments. Such C4 processing, with a concomitant reduction in levels of full-length C4γ, was also observed in HCV-infected cells expressing C4. CONCLUSIONS: C4 is a novel cellular substrate of the HCV NS3/4A protease. Understanding disturbances in the complement system mediated by NS3/4A protease may provide new insights into the mechanisms underlying persistent HCV infection.

The Influenza NS1 Protein: What Do We Know in Equine Influenza Virus Pathogenesis?

Directory of Open Access Journals (Sweden)

Marta Barba

2016-08-01

Full Text Available Equine influenza virus remains a serious health and potential economic problem throughout most parts of the world, despite intensive vaccination programs in some horse populations. The influenza non-structural protein 1 (NS1 has multiple functions involved in the regulation of several cellular and viral processes during influenza infection. We review the strategies that NS1 uses to facilitate virus replication and inhibit antiviral responses in the host, including sequestering of double-stranded RNA, direct modulation of protein kinase R activity and inhibition of transcription and translation of host antiviral response genes such as type I interferon. Details are provided regarding what it is known about NS1 in equine influenza, especially concerning C-terminal truncation. Further research is needed to determine the role of NS1 in equine influenza infection, which will help to understand the pathophysiology of complicated cases related to cytokine imbalance and secondary bacterial infection, and to investigate new therapeutic and vaccination strategies.

9 CFR 317.309 - Nutrition label content.

Science.gov (United States)

2010-01-01

... consumed,” provided that preparation and cooking instructions are clearly stated. (4) For products in... method of cooking and other preparation shall be specified prominently on the label. (c) The declaration... Section 317.309 Animals and Animal Products FOOD SAFETY AND INSPECTION SERVICE, DEPARTMENT OF AGRICULTURE...

Central leptin action on euglycemia restoration in type 1 diabetes: Restraining responses normally induced by fasting?

Science.gov (United States)

Xu, Yuanzhong; Tong, Qingchun

2017-07-01

Leptin monotherapy is sufficient to restore euglycemia in insulinopenic type 1 diabetes (T1D), yet the underlying mechanism remains poorly understood. Accumulating evidence demonstrates that the brain mediates the leptin action on euglycemia restoration. Here, we first review evidence supporting that symptoms in T1D resemble an uncontrolled response to fasting. Then, we discuss recent research progress on brain neurons and their neurotransmitters that potentially mediate the leptin action. Finally, peripheral effective pathways, which are normally involved in fasting responses and associated with leptin action on euglycemia restoration in T1D, will also be discussed. This summary complements several previous excellent reviews on this topic (Meek and Morton, 2016; Perry et al., 2016; Fujikawa and Coppari, 2015). A deep understanding of neurocircuitry and the peripheral effective pathways that mediate the leptin action on euglycemia restoration will likely lead to novel targets for an insulin-independent therapeutics against T1D. Copyright © 2016 Elsevier Ltd. All rights reserved.

Localisation system in wireless sensor networks using ns-2

CSIR Research Space (South Africa)

Abu-Mahfouz, Adnan M

2012-04-01

Full Text Available -1 /************************************************************************** ********** * * File: readme.asn * * Author: Adnan Abu-Mahfouz * * Date: March 2012 * * Description: Localisation system in wireless sensor networks using ns-2... *************************************************************************** *********/ /************************************************************************** *************************************************************************** *****/ 1. Introduction: ns-2 contains several flexible features that encourage researchers to use ns-2 to investigate the characteristics of wireless sensor networks (WSNs). However, to implement and evaluate localisation algorithms, the current ns- 2...

309 Building deactivation mission analysis report

International Nuclear Information System (INIS)

Lund, D.P.

1995-01-01

This report presents the results of the 309 Building (Plutonium Fuels Utilization Program) Deactivation Project mission analysis. Hanford systems engineering (SE) procedures call for a mission analysis. The mission analysis is an important first step in the SE process. The functions and requirements to successfully accomplish this mission, the selected alternatives and products will later be defined using the SE process

9 CFR 309.7 - Livestock affected with anthrax; cleaning and disinfection of infected livestock pens and driveways.

Science.gov (United States)

2010-01-01

...; cleaning and disinfection of infected livestock pens and driveways. 309.7 Section 309.7 Animals and Animal... INSPECTION § 309.7 Livestock affected with anthrax; cleaning and disinfection of infected livestock pens and... followed immediately by a thorough disinfection of the exposed premises by soaking the ground, fences...

Functional investigation of grass carp reovirus nonstructural protein NS80

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Shao Ling

2011-04-01

Full Text Available Abstract Background Grass Carp Reovirus (GCRV, a highly virulent agent of aquatic animals, has an eleven segmented dsRNA genome encased in a multilayered capsid shell, which encodes twelve proteins including seven structural proteins (VP1-VP7, and five nonstructural proteins (NS80, NS38, NS31, NS26, and NS16. It has been suggested that the protein NS80 plays an important role in the viral replication cycle that is similar to that of its homologous protein μNS in the genus of Orthoreovirus. Results As a step to understanding the basis of the part played by NS80 in GCRV replication and particle assembly, we used the yeast two-hybrid (Y2H system to identify NS80 interactions with proteins NS38, VP4, and VP6 as well as NS80 and NS38 self-interactions, while no interactions appeared in the four protein pairs NS38-VP4, NS38-VP6, VP4-VP4, and VP4-VP6. Bioinformatic analyses of NS80 with its corresponding proteins were performed with all currently available homologous protein sequences in ARVs (avian reoviruses and MRVs (mammalian reoviruses to predict further potential functional domains of NS80 that are related to VFLS (viral factory-like structures formation and other roles in viral replication. Two conserved regions spanning from aa (amino acid residues of 388 to 433, and 562 to 580 were discovered in this study. The second conserved region with corresponding conserved residues Tyr565, His569, Cys571, Asn573, and Glu576 located between the two coiled-coils regions (aa ~513-550 and aa ~615-690 in carboxyl-proximal terminus were supposed to be essential to form VFLS, so that aa residues ranging from 513 to 742 of NS80 was inferred to be the smallest region that is necessary for forming VFLS. The function of the first conserved region including Ala395, Gly419, Asp421, Pro422, Leu438, and Leu443 residues is unclear, but one-third of the amino-terminal region might be species specific, dominating interactions with other viral components. Conclusions Our

24 CFR 3282.309 - Formal and informal presentations of views held by SAAs.

Science.gov (United States)

2010-04-01

... 24 Housing and Urban Development 5 2010-04-01 2010-04-01 false Formal and informal presentations of views held by SAAs. 3282.309 Section 3282.309 Housing and Urban Development Regulations Relating... held by SAAs. (a) When an SAA is the appropriate agency to hold a Formal or Informal Presentation of...

Maternal nutrient restriction during pregnancy impairs an endothelium-derived hyperpolarizing factor-like pathway in sheep fetal coronary arteries.

Science.gov (United States)

Shukla, Praveen; Ghatta, Srinivas; Dubey, Nidhi; Lemley, Caleb O; Johnson, Mary Lynn; Modgil, Amit; Vonnahme, Kimberly; Caton, Joel S; Reynolds, Lawrence P; Sun, Chengwen; O'Rourke, Stephen T

2014-07-15

The mechanisms underlying developmental programming are poorly understood but may be associated with adaptations by the fetus in response to changes in the maternal environment during pregnancy. We hypothesized that maternal nutrient restriction during pregnancy alters vasodilator responses in fetal coronary arteries. Pregnant ewes were fed a control [100% U.S. National Research Council (NRC)] or nutrient-restricted (60% NRC) diet from days 50 to 130 of gestation (term = 145 days); fetal tissues were collected at day 130. In coronary arteries isolated from control fetal lambs, relaxation to bradykinin was unaffected by nitro-l-arginine (NLA). Iberiotoxin or contraction with KCl abolished the NLA-resistant response to bradykinin. In fetal coronary arteries from nutrient-restricted ewes, relaxation to bradykinin was fully suppressed by NLA. Large-conductance, calcium-activated potassium channel (BKCa) currents did not differ in coronary smooth muscle cells from control and nutrient-restricted animals. The BKCa openers, BMS 191011 and NS1619, and 14,15-epoxyeicosatrienoic acid [a putative endothelium-derived hyperpolarizing factor (EDHF)] each caused fetal coronary artery relaxation and BKCa current activation that was unaffected by maternal nutrient restriction. Expression of BKCa-channel subunits did not differ in fetal coronary arteries from control or undernourished ewes. The results indicate that maternal undernutrition during pregnancy results in loss of the EDHF-like pathway in fetal coronary arteries in response to bradykinin, an effect that cannot be explained by a decreased number or activity of BKCa channels or by decreased sensitivity to mediators that activate BKCa channels in vascular smooth muscle cells. Under these conditions, bradykinin-induced relaxation is completely dependent on nitric oxide, which may represent an adaptive response to compensate for the absence of the EDHF-like pathway. Copyright © 2014 the American Physiological Society.

An NS5A single optimized method to determine genotype, subtype and resistance profiles of Hepatitis C strains.

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Elisabeth Andre-Garnier

Full Text Available The objective was to develop a method of HCV genome sequencing that allowed simultaneous genotyping and NS5A inhibitor resistance profiling. In order to validate the use of a unique RT-PCR for genotypes 1-5, 142 plasma samples from patients infected with HCV were analysed. The NS4B-NS5A partial region was successfully amplified and sequenced in all samples. In parallel, partial NS3 sequences were analyzed obtained for genotyping. Phylogenetic analysis showed concordance of genotypes and subtypes with a bootstrap >95% for each type cluster. NS5A resistance mutations were analyzed using the Geno2pheno [hcv] v0.92 tool and compared to the list of known Resistant Associated Substitutions recently published. In conclusion, this tool allows determination of HCV genotypes, subtypes and identification of NS5A resistance mutations. This single method can be used to detect pre-existing resistance mutations in NS5A before treatment and to check the emergence of resistant viruses while undergoing treatment in major HCV genotypes (G1-5 in the EU and the US.

A Regulatory Polymorphism at Position -309 in PTPRCAP Is Associated with Susceptibility to Diffuse-type Gastric Cancer and Gene Expression

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Hyoungseok Ju

2009-12-01

Full Text Available PTPRCAP (CD45-AP is a positive regulator of protein tyrosine phosphatase PTPRC (CD45, which activates Src family kinases implicated in tumorigenesis. Single-nucleotide polymorphism (SNP rs869736 located at position -309 of the PTPRCAP promoter was associated with susceptibility to diffuse-type gastric cancer in the current case-control study. The minor-allele homozygote was significantly associated with a 2.5-fold increased susceptibility to diffuse-type gastric cancer (P = .0021, n = 252, but not to intestinal-type (P = .30, n = 178, versus the major-allele homozygote, when comparing unrelated Korean patients with healthy controls (n = 406. Nine other SNPs were in nearly perfect linkage disequilibrium (r2 ≥ 0.97 with this SNP, exhibiting the same association, and spread out for 26 kb on chromosome 11q13.1 covering RPS6KB2, PTPRCAP, CORO1B, and GPR152. Among the four genes, however, only PTPRCAP expression was affected by haplotypes of the 10 SNPs. Endogenous transcript levels of PTPRCAP were linearly correlated with copy numbers (0, 1, and 2 of the risk-haplotype (P = .0060 in 12 lymphoblastoid cells derived from blood samples, but those of the other three genes were not. Furthermore, the cancer-risk, minor-allele T of rs869736 increased both promoter activity and specific nuclear protein-binding affinity than the nonrisk, major-allele G in luciferase reporter and electrophoretic mobility shift assays, respectively. Accordingly, the minor allele of rs869736 in the PTPRCAP promoter is associated with increased susceptibility to diffuse-type gastric cancer by increasing PTPRCAP expression, possibly leading to activation of the oncogenic Src family kinases.

14 CFR 61.309 - What aeronautical knowledge must I have to apply for a sport pilot certificate?

Science.gov (United States)

2010-01-01

... apply for a sport pilot certificate? 61.309 Section 61.309 Aeronautics and Space FEDERAL AVIATION... GROUND INSTRUCTORS Sport Pilots § 61.309 What aeronautical knowledge must I have to apply for a sport pilot certificate? Except as specified in § 61.329, to apply for a sport pilot certificate you must...

25 CFR 309.24 - How will statements about Indian origin of art or craft products be interpreted?

Science.gov (United States)

2010-04-01

... 25 Indians 2 2010-04-01 2010-04-01 false How will statements about Indian origin of art or craft products be interpreted? 309.24 Section 309.24 Indians INDIAN ARTS AND CRAFTS BOARD, DEPARTMENT OF THE INTERIOR PROTECTION OF INDIAN ARTS AND CRAFTS PRODUCTS § 309.24 How will statements about Indian origin of...

25 CFR 309.23 - Does this part apply to products made before 1935?

Science.gov (United States)

2010-04-01

... 25 Indians 2 2010-04-01 2010-04-01 false Does this part apply to products made before 1935? 309.23 Section 309.23 Indians INDIAN ARTS AND CRAFTS BOARD, DEPARTMENT OF THE INTERIOR PROTECTION OF INDIAN ARTS... part do not apply to any art or craft products made before 1935. [68 FR 35170, June 12, 2003] ...

In-Silico Computing of the Most Deleterious nsSNPs in HBA1 Gene.

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Sayed AbdulAzeez

Full Text Available α-Thalassemia (α-thal is a genetic disorder caused by the substitution of single amino acid or large deletions in the HBA1 and/or HBA2 genes.Using modern bioinformatics tools as a systematic in-silico approach to predict the deleterious SNPs in the HBA1 gene and its significant pathogenic impact on the functions and structure of HBA1 protein was predicted.A total of 389 SNPs in HBA1 were retrieved from dbSNP database, which includes: 201 non-coding synonymous (nsSNPs, 43 human active SNPs, 16 intronic SNPs, 11 mRNA 3' UTR SNPs, 9 coding synonymous SNPs, 9 5' UTR SNPs and other types. Structural homology-based method (PolyPhen and sequence homology-based tool (SIFT, SNPs&Go, PROVEAN and PANTHER revealed that 2.4% of the nsSNPs are pathogenic.A total of 5 nsSNPs (G60V, K17M, K17T, L92F and W15R were predicted to be responsible for the structural and functional modifications of HBA1 protein. It is evident from the deep comprehensive in-silico analysis that, two nsSNPs such as G60V and W15R in HBA1 are highly deleterious. These "2 pathogenic nsSNPs" can be considered for wet-lab confirmatory analysis.

Lyso-myristoyl phosphatidylcholine micelles sustain the activity of Dengue non-structural (NS) protein 3 protease domain fused with the full-length NS2B.

Science.gov (United States)

Huang, Qiwei; Li, Qingxin; Joy, Joma; Chen, Angela Shuyi; Ruiz-Carrillo, David; Hill, Jeffrey; Lescar, Julien; Kang, Congbao

2013-12-01

Dengue virus (DENV), a member of the flavivirus genus, affects 50-100 million people in tropical and sub-tropical regions. The DENV protease domain is located at the N-terminus of the NS3 protease and requires for its enzymatic activity a hydrophilic segment of the NS2B that acts as a cofactor. The protease is an important antiviral drug target because it plays a crucial role in virus replication by cleaving the genome-coded polypeptide into mature functional proteins. Currently, there are no drugs to inhibit DENV protease activity. Most structural and functional studies have been conducted using protein constructs containing the NS3 protease domain connected to a soluble segment of the NS2B membrane protein via a nine-residue linker. For in vitro structural and functional studies, it would be useful to produce a natural form of the DENV protease containing the NS3 protease domain and the full-length NS2B protein. Herein, we describe the expression and purification of a natural form of DENV protease (NS2BFL-NS3pro) containing the full-length NS2B protein and the protease domain of NS3 (NS3pro). The protease was expressed and purified in detergent micelles necessary for its folding. Our results show that this purified protein was active in detergent micelles such as lyso-myristoyl phosphatidylcholine (LMPC). These findings should facilitate further structural and functional studies of the protease and will facilitate drug discovery targeting DENV. Copyright © 2013 Elsevier Inc. All rights reserved.

Identification and subcellular localization of porcine deltacoronavirus accessory protein NS6

International Nuclear Information System (INIS)

Fang, Puxian; Fang, Liurong; Liu, Xiaorong; Hong, Yingying; Wang, Yongle; Dong, Nan; Ma, Panpan; Bi, Jing; Wang, Dang; Xiao, Shaobo

2016-01-01

Porcine deltacoronavirus (PDCoV) is an emerging swine enteric coronavirus. Accessory proteins are genus-specific for coronavirus, and two putative accessory proteins, NS6 and NS7, are predicted to be encoded by PDCoV; however, this remains to be confirmed experimentally. Here, we identified the leader-body junction sites of NS6 subgenomic RNA (sgRNA) and found that the actual transcription regulatory sequence (TRS) utilized by NS6 is non-canonical and is located upstream of the predicted TRS. Using the purified NS6 from an Escherichia coli expression system, we obtained two anti-NS6 monoclonal antibodies that could detect the predicted NS6 in cells infected with PDCoV or transfected with NS6-expressing plasmids. Further studies revealed that NS6 is always localized in the cytoplasm of PDCoV-infected cells, mainly co-localizing with the endoplasmic reticulum (ER) and ER-Golgi intermediate compartments, as well as partially with the Golgi apparatus. Together, our results identify the NS6 sgRNA and demonstrate its expression in PDCoV-infected cells. -- Highlights: •The leader-body fusion site of NS6 sgRNA is identified. •NS6 sgRNA uses a non-canonical transcription regulatory sequence (TRS). •NS6 can be expressed in PDCoV-infected cell. •NS6 predominantly localize to the ER complex and ER-Golgi intermediate compartment.

Identification and subcellular localization of porcine deltacoronavirus accessory protein NS6

Energy Technology Data Exchange (ETDEWEB)

Fang, Puxian; Fang, Liurong; Liu, Xiaorong; Hong, Yingying; Wang, Yongle; Dong, Nan; Ma, Panpan [State Key Laboratory of Agricultural Microbiology, College of Veterinary Medicine, Huazhong Agricultural University, Wuhan 430070 (China); The Cooperative Innovation Center for Sustainable Pig Production, Wuhan 430070 (China); Bi, Jing [State Key Laboratory of Agricultural Microbiology, College of Veterinary Medicine, Huazhong Agricultural University, Wuhan 430070 (China); Department of Immunology and Aetology, College of Basic Medicine, Hubei University of Chinese Medicine, Wuhan 430065 (China); Wang, Dang [State Key Laboratory of Agricultural Microbiology, College of Veterinary Medicine, Huazhong Agricultural University, Wuhan 430070 (China); The Cooperative Innovation Center for Sustainable Pig Production, Wuhan 430070 (China); Xiao, Shaobo, E-mail: vet@mail.hzau.edu.cn [State Key Laboratory of Agricultural Microbiology, College of Veterinary Medicine, Huazhong Agricultural University, Wuhan 430070 (China); The Cooperative Innovation Center for Sustainable Pig Production, Wuhan 430070 (China)

2016-12-15

Porcine deltacoronavirus (PDCoV) is an emerging swine enteric coronavirus. Accessory proteins are genus-specific for coronavirus, and two putative accessory proteins, NS6 and NS7, are predicted to be encoded by PDCoV; however, this remains to be confirmed experimentally. Here, we identified the leader-body junction sites of NS6 subgenomic RNA (sgRNA) and found that the actual transcription regulatory sequence (TRS) utilized by NS6 is non-canonical and is located upstream of the predicted TRS. Using the purified NS6 from an Escherichia coli expression system, we obtained two anti-NS6 monoclonal antibodies that could detect the predicted NS6 in cells infected with PDCoV or transfected with NS6-expressing plasmids. Further studies revealed that NS6 is always localized in the cytoplasm of PDCoV-infected cells, mainly co-localizing with the endoplasmic reticulum (ER) and ER-Golgi intermediate compartments, as well as partially with the Golgi apparatus. Together, our results identify the NS6 sgRNA and demonstrate its expression in PDCoV-infected cells. -- Highlights: •The leader-body fusion site of NS6 sgRNA is identified. •NS6 sgRNA uses a non-canonical transcription regulatory sequence (TRS). •NS6 can be expressed in PDCoV-infected cell. •NS6 predominantly localize to the ER complex and ER-Golgi intermediate compartment.

31 CFR 309.3 - Denominations and exchange.

Science.gov (United States)

2010-07-01

... 31 Money and Finance: Treasury 2 2010-07-01 2010-07-01 false Denominations and exchange. 309.3... Denominations and exchange. Treasury bills will be issued in denominations (maturity value) of $10,000, $15,000, $50,000, $100,000, $500,000, and $1,000,000. Exchanges from higher to lower and lower to higher...

Otolith analysis of pre-restoration habitat use by Chinook salmon in the delta-flats and nearshore regions of the Nisqually River Estuary

Science.gov (United States)

Lind-Null, Angie; Larsen, Kim

2010-01-01

The Nisqually Fall Chinook population is one of 27 salmon stocks in the Puget Sound (Washington) evolutionarily significant unit listed as threatened under the federal Endangered Species Act (ESA). Extensive restoration of the Nisqually River delta ecosystem is currently taking place to assist in recovery of the stock as juvenile Fall Chinook salmon are dependent on the estuary. A pre-restoration baseline that includes the characterization of life history strategies, estuary residence times, growth rates, and habitat use is needed to evaluate the potential response of hatchery and natural origin Chinook salmon to restoration efforts and to determine restoration success. Otolith analysis was selected as a tool to examine Chinook salmon life history, growth, and residence in the Nisqually River estuary. Previously funded work on samples collected in 2004 (marked and unmarked) and 2005 (unmarked only) partially established a juvenile baseline on growth rates and length of residence associated with various habitats (freshwater, forested riverine tidal, emergent forested transition, estuarine emergent marsh, delta-flats and nearshore). However, residence times and growth rates for the delta-flats (DF) and nearshore (NS) habitats have been minimally documented due to small sample sizes. The purpose of the current study is to incorporate otolith microstructural analysis using otoliths from fish collected within the DF and NS habitats during sampling years 2004-08 to increase sample size and further evaluate between-year variation in otolith microstructure. Our results from this analysis indicated the delta-flats check (DFCK) on unmarked and marked Chinook samples in 2005-08 varied slightly in appearance from that seen on samples previously analyzed only from 2004. A fry migrant life history was observed on otoliths of unmarked Chinook collected in 2005, 2007, and 2008. Generally, freshwater mean increment width of unmarked fish, on average, was smaller compared to marked

Rab5 Enhances Classical Swine Fever Virus Proliferation and Interacts with Viral NS4B Protein to Facilitate Formation of NS4B Related Complex

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Jihui Lin

2017-08-01

Full Text Available Classical swine fever virus (CSFV is a fatal pig pestivirus and causes serious financial losses to the pig industry. CSFV NS4B protein is one of the most important viral replicase proteins. Rab5, a member of the small Rab GTPase family, is involved in infection and replication of numerous viruses including hepatitis C virus and dengue virus. Until now, the effects of Rab5 on the proliferation of CSFV are poorly defined. In the present study, we showed that Rab5 could enhance CSFV proliferation by utilizing lentivirus-mediated constitutive overexpression and eukaryotic plasmid transient overexpression approaches. On the other hand, lentivirus-mediated short hairpin RNA knockdown of Rab5 dramatically inhibited virus production. Co-immunoprecipitation, glutathione S-transferase pulldown and laser confocal microscopy assays further confirmed the interaction between Rab5 and CSFV NS4B protein. In addition, intracellular distribution of NS4B-Red presented many granular fluorescent signals (GFS in CSFV infected PK-15 cells. Inhibition of basal Rab5 function with Rab5 dominant negative mutant Rab5S34N resulted in disruption of the GFS. These results indicate that Rab5 plays a critical role in facilitating the formation of the NS4B related complexes. Furthermore, it was observed that NS4B co-localized with viral NS3 and NS5A proteins in the cytoplasm, suggesting that NS3 and NS5A might be components of the NS4B related complex. Taken together, these results demonstrate that Rab5 positively modulates CSFV propagation and interacts with NS4B protein to facilitate the NS4B related complexes formation.

Image Restoration Based on the Hybrid Total-Variation-Type Model

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Baoli Shi

2012-01-01

Full Text Available We propose a hybrid total-variation-type model for the image restoration problem based on combining advantages of the ROF model with the LLT model. Since two L1-norm terms in the proposed model make it difficultly solved by using some classically numerical methods directly, we first employ the alternating direction method of multipliers (ADMM to solve a general form of the proposed model. Then, based on the ADMM and the Moreau-Yosida decomposition theory, a more efficient method called the proximal point method (PPM is proposed and the convergence of the proposed method is proved. Some numerical results demonstrate the viability and efficiency of the proposed model and methods.

A new approach to dengue fatal cases diagnosis: NS1 antigen capture in tissues.

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Monique da Rocha Queiroz Lima

Full Text Available UNLABELLED: / BACKGROUND: Dengue is the most important arthropod borne viral disease worldwide in terms of morbidity and mortality and is caused by any of the four serotypes of dengue virus (DENV-1 to 4. Brazil is responsible for approximately 80% of dengue cases in the Americas, and since the introduction of dengue in 1986, a total of 5,944,270 cases have been reported including 21,596 dengue hemorrhagic fever and 874 fatal cases. DENV can infect many cell types and cause diverse clinical and pathological effects. The goal of the study was to investigate the usefulness of NS1 capture tests as an alternative tool to detect DENV in tissue specimens from previously confirmed dengue fatal cases (n = 23 that occurred in 2002 in Brazil. METHODOLOGY/PRINCIPAL FINDINGS: A total of 74 tissue specimens were available: liver (n = 23, lung (n = 14, kidney (n = 04, brain (n = 10, heart (n = 02, skin (n = 01, spleen (n = 15, thymus (n = 03 and lymph nodes (n = 02. We evaluated three tests for NS1 antigen capture: first generation Dengue Early ELISA (PanBio Diagnostics, Platelia NS1 (BioRad Laboratories and the rapid test NS1 Ag Strip (BioRad Laboratories. The overall dengue fatal case diagnosis based on the tissues analyzed by Dengue Early ELISA, Platelia NS1 and the NS1 Ag Strip was 34.7% (08/23, 60.8% (14/23 and 91.3% (21/23, respectively. The Dengue Early ELISA detected NS1 in 22.9% (17/74 of the specimens analyzed and the Platelia NS1 in 45.9% (34/74. The highest sensitivity (78.3%; 58/74 was achieved by the NS1 Ag Strip, and the differences in the sensitivities were statistically significant (p<0.05. The NS1 Ag Strip was the most sensitive in liver (91.3%; 21/23, lung (71.4%; 10/14, kidney (100%; 4/4, brain (80%; 8/10, spleen (66.6%, 10/15 and thymus (100%, 3/3 when compared to the other two ELISA assays. CONCLUSIONS/SIGNIFICANCE: This study shows the DENV NS1 capture assay as a rapid and valuable approach to postmortem dengue confirmation. With an

16 CFR 309.10 - Alternative vehicle fuel rating.

Science.gov (United States)

2010-01-01

... 16 Commercial Practices 1 2010-01-01 2010-01-01 false Alternative vehicle fuel rating. 309.10... LABELING REQUIREMENTS FOR ALTERNATIVE FUELS AND ALTERNATIVE FUELED VEHICLES Requirements for Alternative Fuels Duties of Importers, Producers, and Refiners of Non-Liquid Alternative Vehicle Fuels (other Than...

The NS1 polypeptide of the murine parvovirus minute virus of mice binds to DNA sequences containing the motif [ACCA]2-3.

Science.gov (United States)

Cotmore, S F; Christensen, J; Nüesch, J P; Tattersall, P

1995-03-01

A DNA fragment containing the minute virus of mice 3' replication origin was specifically coprecipitated in immune complexes containing the virally coded NS1, but not the NS2, polypeptide. Antibodies directed against the amino- or carboxy-terminal regions of NS1 precipitated the NS1-origin complexes, but antibodies directed against NS1 amino acids 284 to 459 blocked complex formation. Using affinity-purified histidine-tagged NS1 preparations, we have shown that the specific protein-DNA interaction is of moderate affinity, being stable in 0.1 M salt but rapidly lost at higher salt concentrations. In contrast, generalized (or nonspecific) DNA binding by NS1 could be demonstrated only in low salt. Addition of ATP or gamma S-ATP enhanced specific DNA binding by wild-type NS1 severalfold, but binding was lost under conditions which favored ATP hydrolysis. NS1 molecules with mutations in a critical lysine residue (amino acid 405) in the consensus ATP-binding site bound to the origin, but this binding could not be enhanced by ATP addition. DNase I protection assays carried out with wild-type NS1 in the presence of gamma S-ATP gave footprints which extended over 43 nucleotides on both DNA strands, from the middle of the origin bubble sequence to a position some 14 bp beyond the nick site. The DNA-binding site for NS1 was mapped to a 22-bp fragment from the middle of the 3' replication origin which contains the sequence ACCAACCA. This conforms to a reiterated motif (ACCA)2-3, which occurs, in more or less degenerate form, at many sites throughout the minute virus of mice genome (J. W. Bodner, Virus Genes 2:167-182, 1989). Insertion of a single copy of the sequence (ACCA)3 was shown to be sufficient to confer NS1 binding on an otherwise unrecognized plasmid fragment. The functions of NS1 in the viral life cycle are reevaluated in the light of this result.

25 CFR 309.22 - What are examples of painting and other fine art forms that are Indian products?

Science.gov (United States)

2010-04-01

... 25 Indians 2 2010-04-01 2010-04-01 false What are examples of painting and other fine art forms that are Indian products? 309.22 Section 309.22 Indians INDIAN ARTS AND CRAFTS BOARD, DEPARTMENT OF THE INTERIOR PROTECTION OF INDIAN ARTS AND CRAFTS PRODUCTS § 309.22 What are examples of painting and other...

14 CFR 152.309 - Availability of sponsor's records.

Science.gov (United States)

2010-01-01

... (CONTINUED) AIRPORTS AIRPORT AID PROGRAM Accounting and Reporting Requirements § 152.309 Availability of... the purposes of accounting and audit. (b) The sponsor or planning agency shall allow appropriate FAA...-term retention value, the FAA may require transfer of custody of those records to the FAA. ...

NS Pudarka: A new winter wheat cultivar

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Hristov Nikola

2014-01-01

Full Text Available The high-yielding, medium late winter wheat cultivar NS Pudarka was developed by crossing genetic divergent parents: line NMNH-07 and cv. NS 40S and Simonida. In cultivar NS Pudarka genes responsible for high yield potential, very good technological quality, resistance to lodging, low temperature and diseases, were successfully combined. It was registered by Ministry of agriculture, forestry and water management of Serbia Republic in 2013. This cultivar has wide adaptability and stability of yield that enable growing in different environments with optimal agricultural practice. On the base of technological quality this cultivar belongs to the second quality class, A2 farinograph subgroup and second technological group.

The interactomes of influenza virus NS1 and NS2 proteins identify new host factors and provide insights for ADAR1 playing a supportive role in virus replication.

Science.gov (United States)

de Chassey, Benoît; Aublin-Gex, Anne; Ruggieri, Alessia; Meyniel-Schicklin, Laurène; Pradezynski, Fabrine; Davoust, Nathalie; Chantier, Thibault; Tafforeau, Lionel; Mangeot, Philippe-Emmanuel; Ciancia, Claire; Perrin-Cocon, Laure; Bartenschlager, Ralf; André, Patrice; Lotteau, Vincent

2013-01-01

Influenza A NS1 and NS2 proteins are encoded by the RNA segment 8 of the viral genome. NS1 is a multifunctional protein and a virulence factor while NS2 is involved in nuclear export of viral ribonucleoprotein complexes. A yeast two-hybrid screening strategy was used to identify host factors supporting NS1 and NS2 functions. More than 560 interactions between 79 cellular proteins and NS1 and NS2 proteins from 9 different influenza virus strains have been identified. These interacting proteins are potentially involved in each step of the infectious process and their contribution to viral replication was tested by RNA interference. Validation of the relevance of these host cell proteins for the viral replication cycle revealed that 7 of the 79 NS1 and/or NS2-interacting proteins positively or negatively controlled virus replication. One of the main factors targeted by NS1 of all virus strains was double-stranded RNA binding domain protein family. In particular, adenosine deaminase acting on RNA 1 (ADAR1) appeared as a pro-viral host factor whose expression is necessary for optimal viral protein synthesis and replication. Surprisingly, ADAR1 also appeared as a pro-viral host factor for dengue virus replication and directly interacted with the viral NS3 protein. ADAR1 editing activity was enhanced by both viruses through dengue virus NS3 and influenza virus NS1 proteins, suggesting a similar virus-host co-evolution.

The interactomes of influenza virus NS1 and NS2 proteins identify new host factors and provide insights for ADAR1 playing a supportive role in virus replication.

Directory of Open Access Journals (Sweden)

Benoît de Chassey

Full Text Available Influenza A NS1 and NS2 proteins are encoded by the RNA segment 8 of the viral genome. NS1 is a multifunctional protein and a virulence factor while NS2 is involved in nuclear export of viral ribonucleoprotein complexes. A yeast two-hybrid screening strategy was used to identify host factors supporting NS1 and NS2 functions. More than 560 interactions between 79 cellular proteins and NS1 and NS2 proteins from 9 different influenza virus strains have been identified. These interacting proteins are potentially involved in each step of the infectious process and their contribution to viral replication was tested by RNA interference. Validation of the relevance of these host cell proteins for the viral replication cycle revealed that 7 of the 79 NS1 and/or NS2-interacting proteins positively or negatively controlled virus replication. One of the main factors targeted by NS1 of all virus strains was double-stranded RNA binding domain protein family. In particular, adenosine deaminase acting on RNA 1 (ADAR1 appeared as a pro-viral host factor whose expression is necessary for optimal viral protein synthesis and replication. Surprisingly, ADAR1 also appeared as a pro-viral host factor for dengue virus replication and directly interacted with the viral NS3 protein. ADAR1 editing activity was enhanced by both viruses through dengue virus NS3 and influenza virus NS1 proteins, suggesting a similar virus-host co-evolution.

PRTR/309 building nuclear facility preliminary

International Nuclear Information System (INIS)

Cornwell, B.C.

1994-01-01

The hazard classification of the Plutonium Recycle Test Reactor (PRTR)/309 building as a ''Radiological Facility'' and the office portions as ''Other Industrial Facility'' are documented by this report. This report provides: a synopsis of the history and facility it's uses; describes major area of the facility; and assesses the radiological conditions for the facility segments. The assessment is conducted using the hazard category threshold values, segmentation methodology, and graded approach guidance of DOE-STD-1027-92

Pre-Restoration Habitat Use by Chinook Salmon in the Nisqually Estuary Using Otolith Analysis: An Additional Year

Science.gov (United States)

Lind-Null, Angie; Larsen, Kim

2009-01-01

The Nisqually Fall Chinook population is one of 27 stocks in the Puget Sound evolutionarily significant unit listed as threatened under the Federal Endangered Species Act (ESA). Preservation and extensive restoration of the Nisqually delta ecosystem is currently taking place to assist in recovery of the stock as juvenile Fall Chinook salmon are dependent upon the estuary. A pre-restoration baseline that includes characterization of life history types, estuary residence times, growth rates, and habitat use is needed to evaluate the potential response of hatchery and natural origin Chinook salmon to restoration efforts and determine restoration success. Otolith analysis was selected to examine Chinook salmon life history, growth, and residence in the Nisqually Estuary. Previously funded work on wild samples collected in 2004 established the growth rate and length of residence associated with various habitats. The purpose of the current study is to build on the previous work by incorporating otolith microstructure analysis from 2005 (second sampling year), to verify findings from 2004, and to evaluate between-year variation in otolith microstructure. Our results from this second year of analysis indicated no inter-annual variation in the appearance of the tidal delta check (TDCK) and delta-flats check (DFCK). However, a new life history type (fry migrant) was observed on samples collected in 2005. Fish caught in the tidal delta regardless of capture date spent an average of 17 days in the tidal delta. There was a corresponding increase in growth rate as the fish migrated from freshwater (FW) to tidal delta to nearshore (NS) habitats. Fish grew 33 percent faster in the tidal delta than in FW habitat and slightly faster (14 percent) in the delta flats (DF) habitat compared to the tidal delta.

NS&T Management Observations

Energy Technology Data Exchange (ETDEWEB)

Gianotto, David [Idaho National Laboratory (INL), Idaho Falls, ID (United States)

2014-09-01

The INL Management Observation Program (MOP) is designed to improve managers and supervisors understanding of work being performed by employees and the barriers impacting their success. The MOP also increases workers understanding of managements’ expectations as they relate to safety, security, quality, and work performance. Management observations (observations) are designed to improve the relationship and trust between employees and managers through increased engagement and interactions between managers and researchers in the field. As part of continuous improvement, NS&T management took initiative to focus on the participation and quality of observations in FY 14. This quarterly report is intended to (a) summarize the participation and quality of management’s observations, (b) assess observations for commonalities or trends related to facility or process barriers impacting research, and (c) provide feedback and make recommendations for improvements NS&T’s MOP.

Restoration of muscle mitochondrial function and metabolic flexibility in type 2 diabetes by exercise training is paralleled by increased myocellular fat storage and improved insulin sensitivity.

Science.gov (United States)

Meex, Ruth C R; Schrauwen-Hinderling, Vera B; Moonen-Kornips, Esther; Schaart, Gert; Mensink, Marco; Phielix, Esther; van de Weijer, Tineke; Sels, Jean-Pierre; Schrauwen, Patrick; Hesselink, Matthijs K C

2010-03-01

Mitochondrial dysfunction and fat accumulation in skeletal muscle (increased intramyocellular lipid [IMCL]) have been linked to development of type 2 diabetes. We examined whether exercise training could restore mitochondrial function and insulin sensitivity in patients with type 2 diabetes. Eighteen male type 2 diabetic and 20 healthy male control subjects of comparable body weight, BMI, age, and VO2max participated in a 12-week combined progressive training program (three times per week and 45 min per session). In vivo mitochondrial function (assessed via magnetic resonance spectroscopy), insulin sensitivity (clamp), metabolic flexibility (indirect calorimetry), and IMCL content (histochemically) were measured before and after training. Mitochondrial function was lower in type 2 diabetic compared with control subjects (P = 0.03), improved by training in control subjects (28% increase; P = 0.02), and restored to control values in type 2 diabetic subjects (48% increase; P type 2 diabetic subjects (delta Rd 63% increase; P type 2 diabetic subjects was restored (delta respiratory exchange ratio 63% increase; P = 0.01) but was unchanged in control subjects (delta respiratory exchange ratio 7% increase; P = 0.22). Starting with comparable pretraining IMCL levels, training tended to increase IMCL content in type 2 diabetic subjects (27% increase; P = 0.10), especially in type 2 muscle fibers. Exercise training restored in vivo mitochondrial function in type 2 diabetic subjects. Insulin-mediated glucose disposal and metabolic flexibility improved in type 2 diabetic subjects in the face of near-significantly increased IMCL content. This indicates that increased capacity to store IMCL and restoration of improved mitochondrial function contribute to improved muscle insulin sensitivity.

Recombinant HCV variants with NS5A from genotypes 1-7 have different sensitivities to an NS5A inhibitor but not interferon-a

DEFF Research Database (Denmark)

Scheel, Troels K H; Gottwein, Judith M; Mikkelsen, Lotte S

2011-01-01

Heterogeneity in the hepatitis C virus (HCV) protein NS5A influences its sensitivity to interferon-based therapy. Furthermore, NS5A is an important target for development of HCV-specific inhibitors. We aimed to develop recombinant infectious cell culture systems that express NS5A from isolates...

41 CFR 301-71.309 - What internal policies and procedures must we establish governing travel advances?

Science.gov (United States)

2010-07-01

... and procedures must we establish governing travel advances? 301-71.309 Section 301-71.309 Public Contracts and Property Management Federal Travel Regulation System TEMPORARY DUTY (TDY) TRAVEL ALLOWANCES AGENCY RESPONSIBILITIES 71-AGENCY TRAVEL ACCOUNTABILITY REQUIREMENTS Accounting for Travel Advances § 301...

Cloning and expression of NS3 gene of Pakistani isolate type 2 dengue virus

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Yasmin Farkhanda

2018-03-01

Full Text Available Introduction: Dengue is one of the major emerging viral diseases in the world, with dramatic increases in reported cases in the last few decades and annual worldwide occurrence of approximately 390 million infections. It is a highly important mosquito-vectored disease and is a problem in tropical and subtropical areas of the world. The major aim of this study was to clone and express the dengue NS3 gene, in service to its therapeutic importance for the development of stable cell lines.

In Vitro and in Vivo Evaluation of Mutations in the NS Region of Lineage 2 West Nile Virus Associated with Neuroinvasiveness in a Mammalian Model

Directory of Open Access Journals (Sweden)

Katalin Szentpáli-Gavallér

2016-02-01

Full Text Available West Nile virus (WNV strains may differ significantly in neuroinvasiveness in vertebrate hosts. In contrast to genetic lineage 1 WNVs, molecular determinants of pathogenic lineage 2 strains have not been experimentally confirmed so far. A full-length infectious clone of a neurovirulent WNV lineage 2 strain (578/10; Central Europe was generated and amino acid substitutions that have been shown to attenuate lineage 1 WNVs were introduced into the nonstructural proteins (NS1 (P250L, NS2A (A30P, NS3 (P249H NS4B (P38G, C102S, E249G. The mouse neuroinvasive phenotype of each mutant virus was examined following intraperitoneal inoculation of C57BL/6 mice. Only the NS1-P250L mutation was associated with a significant attenuation of virulence in mice compared to the wild-type. Multiplication kinetics in cell culture revealed significantly lower infectious virus titres for the NS1 mutant compared to the wild-type, as well as significantly lower amounts of positive and negative stranded RNA.

Power conditioning using dynamic voltage restorers under different voltage sag types.

Science.gov (United States)

Saeed, Ahmed M; Abdel Aleem, Shady H E; Ibrahim, Ahmed M; Balci, Murat E; El-Zahab, Essam E A

2016-01-01

Voltage sags can be symmetrical or unsymmetrical depending on the causes of the sag. At the present time, one of the most common procedures for mitigating voltage sags is by the use of dynamic voltage restorers (DVRs). By definition, a DVR is a controlled voltage source inserted between the network and a sensitive load through a booster transformer injecting voltage into the network in order to correct any disturbance affecting a sensitive load voltage. In this paper, modelling of DVR for voltage correction using MatLab software is presented. The performance of the device under different voltage sag types is described, where the voltage sag types are introduced using the different types of short-circuit faults included in the environment of the MatLab/Simulink package. The robustness of the proposed device is evaluated using the common voltage sag indices, while taking into account voltage and current unbalance percentages, where maintaining the total harmonic distortion percentage of the load voltage within a specified range is desired. Finally, several simulation results are shown in order to highlight that the DVR is capable of effective correction of the voltage sag while minimizing the grid voltage unbalance and distortion, regardless of the fault type.

Role of nonstructural protein NS2A in flavivirus assembly

NARCIS (Netherlands)

Leung, J.Y.; Pijlman, G.P.; Kondratieva, N.; Hyde, J.; Mackenzie, J.M.; Khromykh, A.A.

2008-01-01

Flavivirus nonstructural (NS) proteins are involved in RNA replication and modulation of the host antiviral response; however, evidence is mounting that some NS proteins also have essential roles in virus assembly. Kunjin virus (KUN) NS2A is a small, hydrophobic, transmembrane protein that is part

Surgical Treatment of Cervical Spondylotic Myelopathy Associated Hypertension--A Retrospective Study of 309 Patients.

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Ze-qun Li

Full Text Available Hypertension is the most prevalent cardiovascular disease, and various risk factors are known to be involved in it. Cervical spondylotic myelopathy (CSM is the most common non-traumatic cause of myelopathy, which displays neurological symptoms and may induce systemic symptoms. To date, it is still unknown whether CSM is associated with hypertension, and if so, whether the decompression operations can attenuate CSM associated hypertension. Here, a total of 309 patients with CSM who received anterior or posterior decompression surgery were enrolled as subjects. Blood pressure measurements were performed before and within one week after the surgery. Among the 309 subjects, 144 (46.6% of them exhibited hypertension before surgery, a significantly higher ratio than that of the whole population. One week after surgery, blood pressure of 106 (73.6% patients turned back to normal. Blood pressure of another 37(25.7% patients decreased with different degrees, although still higher than normal. Moreover, it appears that both approaches were effective in improving blood pressure, while the posterior approach was more effective in decreasing systolic blood pressure. We speculate this type of hypertension might result from hyperactivity of sympathetic nervous system as the heart rate of these patients decreased after surgery as well. Collectively, compression of spinal cord in CSM patients might be associated with hypertension, and decompression surgery largely attenuated this type of hypertension. These findings prove CSM to be a potential associated factor of high blood pressure and may shed light on therapies of hypertension in clinics.

Influence of the MDM2 single nucleotide polymorphism SNP309 on tumour development in BRCA1 mutation carriers

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Johnson Peter W

2006-03-01

Full Text Available Abstract Background The MDM2 gene encodes a negative regulator of the p53 tumour suppressor protein. A single nucleotide polymorphism (SNP in the MDM2 promoter (a T to G exchange at nucleotide 309 has been reported to produce accelerated tumour formation in individuals with inherited p53 mutations. We have investigated the effect of the MDM2 SNP309 on clinical outcome in a cohort of patients with germline mutations of BRCA1. Methods Genomic DNA was obtained for 102 healthy controls and 116 patients with established pathogenic mutations of BRCA1 and Pyrosequencing technology™ was used to determine the genotype at the MDM2 SNP309 locus. Results The polymorphism was present in 52.9% of the controls (G/T in 37.3% and G/G in 15.6% and 58.6% of the BRCA1 mutation carriers (47.4% G/T and 11.2% G/G. Incidence of malignancy in female BRCA1 carriers was not significantly higher in SNP309 carriers than in wildtype (T/T individuals (72.7% vs. 75.6%, p = 1.00. Mean age of diagnosis of first breast cancer was 41.2 years in the SNP309 G/G genotype carriers, 38.6 years in those with the SNP309 G/T genotype and 39.0 years in wildtype subjects (p = 0.80. Conclusion We found no evidence that the MDM2 SNP309 accelerates tumour development in carriers of known pathogenic germline mutations of BRCA1.

Characterization of microstructure of A508III/309L/308L weld and oxide films formed in deaerated high-temperature water

Science.gov (United States)

Xiong, Qi; Li, Hongjuan; Lu, Zhanpeng; Chen, Junjie; Xiao, Qian; Ma, Jiarong; Ru, Xiangkun

2018-01-01

The microstructure of A508III/309L/308L weld clad and the properties of the oxide films formed in simulated pressurized water reactor primary water at 290 °C were characterized. The A508III heat-affected zone (HAZ) consisted primarily of a decarburization zone with ferrite near the fusion line and a following pearlite structure with fine grains. A high hardness region in the HAZ could be the result of C-enrichment. M23C6 and M7C3 precipitates were observed in element transition zone. 308L stainless steel (SS) containing ∼ 12% ferrites exhibited both ferritic-austenitic solidification mode (FA mode, δ→γ) and austenitic-ferritic solidification mode (AF mode, γ→δ), whereas 309L SS containing ∼ 9% ferrites exhibited only FA mode. The A508III surface oxide film was mainly Fe3O4 in deaerated high-temperature water. The coarse grain zone covered with few oxide particles was different from other types of film on the other region of HAZ and the bulk zone. More pitting appears on 309L SS after immersion in deaerated high-temperature water due to the dissolution of inclusions. SS surface oxide films consisted primarily of spinels. The oxide film on SS was divided into two layers. Ni was concentrated mainly at the oxide/substrate interface. The oxide film formed on 309L was thicker than that on the 308L. The ferrite in the stainless steel could improve the oxidation resistance.

Bearing restoration by grinding

Science.gov (United States)

Hanau, H.; Parker, R. J.; Zaretsky, E. V.; Chen, S. M.; Bull, H. L.

1976-01-01

A joint program was undertaken by the NASA Lewis Research Center and the Army Aviation Systems Command to restore by grinding those rolling-element bearings which are currently being discarded at aircraft engine and transmission overhaul. Three bearing types were selected from the UH-1 helicopter engine (T-53) and transmission for the pilot program. No bearing failures occurred related to the restoration by grinding process. The risk and cost of a bearing restoration by grinding programs was analyzed. A microeconomic impact analysis was performed.

Effect of type of cavity preparation (bur,Er:YAG laser and restorative materials on prevention of caries lesion

Directory of Open Access Journals (Sweden)

Masumeh Hasani Tabatabaei

2017-03-01

Full Text Available Background and Aims: Despite the reduction of incidence of dental caries in recent years, this disease is common and many efforts were conducted to decrease the prevalence of dental caries. On the other hand secondary caries lesions are the main reason for replacement of direct restorations. Therefore, the aim of the current study was to evaluate suitable methods of preparation and restorative materials to reduce caries recurrence. Materials and Methods: In this experimental study, eighty human teeth were collected and stored in normal saline. The teeth were soft-tissue debrided and cleaned with water/pumice slurry and rubber cups in a low-speed handpiece. Speciments were randomly divided in two main groups. Cavities were prepared with diamond burs or Er:YAG laser (10 Hz, 300 mJ, 3W. Each group was divided into 4 sub-groups, and restored with a glass-ionomer cement (Fuji IX, resin modified glass-ionomer (Fuji II LC, total etch bonding + composite resin or self-etch bonding + composite resin. The specimens were submitted to pH cycling. Speciments were then sectioned, polished and Vickers microhardness measurements were performed on each specimen. Differences among the medians were analyzed using two way ANOVA test at a 95% confidence level and Tukey test. Results: Statistical analysis showed significant difference in the type of substrate (enamel, dentin in both main groups (P<0.0001 but no differences in the caries lesion development between the cavities restored with the same material and prepared with diamond burs or Er:YAG laser. Conclusion: The Er:YAG laser used for cavity preparation and different types of restorative materials used did not show the ability to guarantee significantly more acid-resistance tooth structure against demineralization.

Ecological restoration [book review

Science.gov (United States)

Eric J. Gustafson

2010-01-01

Ecological restoration has increased in prominence in recent years as environmental policies have slowed the rate of environmental degradation in many parts of the world and practitioners have looked for active ways to reverse the damage. Because of the vast number of types and contexts of degraded ecological systems, the field of ecological restoration is still very...

EFSA Panel on Food Contact Materials, Enzymes, Flavourings and Processing Aids (CEF); Scientific Opinion on Flavouring Group Evaluation 309 (FGE.309): Sodium Diacetate

DEFF Research Database (Denmark)

Larsen, John Christian; Nørby, Karin Kristiane; Beltoft, Vibe Meister

The Panel on Food Contact Materials, Enzymes, Flavourings and Processing Aids of the European Food Safety Authority was requested to evaluate sodium diacetate [FL-no: 16.073] in the Flavouring Group Evaluation 309, using the Procedure in Commission Regulation (EC) No 1565/2000. However, although...

A conformational switch high-throughput screening assay and allosteric inhibition of the flavivirus NS2B-NS3 protease.

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Matthew Brecher

2017-05-01

Full Text Available The flavivirus genome encodes a single polyprotein precursor requiring multiple cleavages by host and viral proteases in order to produce the individual proteins that constitute an infectious virion. Previous studies have revealed that the NS2B cofactor of the viral NS2B-NS3 heterocomplex protease displays a conformational dynamic between active and inactive states. Here, we developed a conformational switch assay based on split luciferase complementation (SLC to monitor the conformational change of NS2B and to characterize candidate allosteric inhibitors. Binding of an active-site inhibitor to the protease resulted in a conformational change of NS2B and led to significant SLC enhancement. Mutagenesis of key residues at an allosteric site abolished this induced conformational change and SLC enhancement. We also performed a virtual screen of NCI library compounds to identify allosteric inhibitors, followed by in vitro biochemical screening of the resultant candidates. Only three of these compounds, NSC135618, 260594, and 146771, significantly inhibited the protease of Dengue virus 2 (DENV2 in vitro, with IC50 values of 1.8 μM, 11.4 μM, and 4.8 μM, respectively. Among the three compounds, only NSC135618 significantly suppressed the SLC enhancement triggered by binding of active-site inhibitor in a dose-dependent manner, indicating that it inhibits the conformational change of NS2B. Results from virus titer reduction assays revealed that NSC135618 is a broad spectrum flavivirus protease inhibitor, and can significantly reduce titers of DENV2, Zika virus (ZIKV, West Nile virus (WNV, and Yellow fever virus (YFV on A549 cells in vivo, with EC50 values in low micromolar range. In contrast, the cytotoxicity of NSC135618 is only moderate with CC50 of 48.8 μM on A549 cells. Moreover, NSC135618 inhibited ZIKV in human placental and neural progenitor cells relevant to ZIKV pathogenesis. Results from binding, kinetics, Western blot, mass spectrometry and

Survival Rates from Fracture of Endodontically Treated Premolars Restored with Full-coverage Crowns or Direct Resin Composite Restorations: A Retrospective Study.

Science.gov (United States)

Suksaphar, Warattama; Banomyong, Danuchit; Jirathanyanatt, Titalee; Ngoenwiwatkul, Yaowaluk

2018-02-01

The aim of the present study was to compare the survival rates against fracture of premolar endodontically treated teeth (ETT) restored with resin composite or crowns and to identify risk factors associated with the fracture. Data from dental records and radiographs of premolar ETT with postendodontic restorations (ie, resin composite or crowns) were collected between 2012 and 2016 and selected following selected inclusion and exclusion criteria. Tooth location, type of restoration, number of proximal contacts, and amount of tooth surface loss were recorded. The incidence and restorability of postendodontic fractures were identified. Survival rates against fracture of the 2 restoration types were calculated using Kaplan-Meier survival analysis. Any potential factors associated with fractures were identified using Cox proportional hazards models. The survival rate against fracture of ETT restored with crowns (95.1%) was higher than resin composite (77.0%). ETT restored with resin composite with 1 or 2 tooth surface losses and 2 proximal contacts had a high survival rate of 88.5% that was not significantly different from ETT with crowns. A higher incidence of restorability after fracture was observed in teeth restored with resin composite than crowns. The type of restoration and number of proximal contacts were identified as potential risk factors associated with fracture incidence. The survival rate against fracture of ETT restored with crowns was higher than resin composite. However, ETT with 1 or 2 tooth surface losses and 2 proximal contacts and restored with resin composite showed a high survival rate that was comparable with ETT restored with crowns. Copyright © 2017 American Association of Endodontists. Published by Elsevier Inc. All rights reserved.

25 CFR 309.9 - When can non-Indians make and sell products in the style of Indian arts and crafts?

Science.gov (United States)

2010-04-01

... of Indian arts and crafts? 309.9 Section 309.9 Indians INDIAN ARTS AND CRAFTS BOARD, DEPARTMENT OF THE INTERIOR PROTECTION OF INDIAN ARTS AND CRAFTS PRODUCTS § 309.9 When can non-Indians make and sell products in the style of Indian arts and crafts? A non-Indian can make and sell products in the style of...

Modifying Cement Hydration with NS@PCE Core-Shell Nanoparticles

Directory of Open Access Journals (Sweden)

Yue Gu

2017-01-01

Full Text Available It is generally accepted that fine particles could accelerate cement hydration process, or, more specifically, this accelerating effect can be attributed to additional surface area introduced by fine particles. In addition to this view, the surface state of fine particles is also an important factor, especially for nanoparticles. In the previous study, a series of nano-SiO2-polycarboxylate superplasticizer core-shell nanoparticles (NS@PCE were synthesized, which have a similar particle size distribution but different surface properties. In this study, the impact of NS@PCE on cement hydration was investigated by heat flow calorimetry, mechanical property measurement, XRD, and SEM. Results show that, among a series of NS@PCE, NS@PCE-2 with a moderate shell-core ratio appeared to be more effective in accelerating cement hydration. As dosage increases, the efficiency of NS@PCE-2 would reach a plateau which is quantified by various characteristic values. Compressive strength results indicate that strength has a linear correlation with cumulative heat release. A hypothesis was proposed to explain the modification effect of NS@PCE, which highlights a balance between initial dispersion and pozzolanic reactivity. This paper provides a new understanding for the surface modification of supplementary cementitious materials and their application and also sheds a new light on nano-SiO2 for optimizing cement-based materials.

Secreted NS1 of dengue virus attaches to the surface of cells via interactions with heparan sulfate and chondroitin sulfate E.

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Panisadee Avirutnan

2007-11-01

Full Text Available Dengue virus (DENV nonstructural protein-1 (NS1 is a secreted glycoprotein that is absent from viral particles but accumulates in the supernatant and on the plasma membrane of cells during infection. Immune recognition of cell surface NS1 on endothelial cells has been hypothesized as a mechanism for the vascular leakage that occurs during severe DENV infection. However, it has remained unclear how NS1 becomes associated with the plasma membrane, as it contains no membrane-spanning sequence motif. Using flow cytometric and ELISA-based binding assays and mutant cell lines lacking selective glycosaminoglycans, we show that soluble NS1 binds back to the surface of uninfected cells primarily via interactions with heparan sulfate and chondroitin sulfate E. DENV NS1 binds directly to the surface of many types of epithelial and mesenchymal cells yet attaches poorly to most peripheral blood cells. Moreover, DENV NS1 preferentially binds to cultured human microvascular compared to aortic or umbilical cord vein endothelial cells. This binding specificity was confirmed in situ as DENV NS1 bound to lung and liver but not intestine or brain endothelium of mouse tissues. Differential binding of soluble NS1 by tissue endothelium and subsequent recognition by anti-NS1 antibodies could contribute to the selective vascular leakage syndrome that occurs during severe secondary DENV infection.

Gene therapy restores auditory and vestibular function in a mouse model of Usher syndrome type 1c.

Science.gov (United States)

Pan, Bifeng; Askew, Charles; Galvin, Alice; Heman-Ackah, Selena; Asai, Yukako; Indzhykulian, Artur A; Jodelka, Francine M; Hastings, Michelle L; Lentz, Jennifer J; Vandenberghe, Luk H; Holt, Jeffrey R; Géléoc, Gwenaëlle S

2017-03-01

Because there are currently no biological treatments for hearing loss, we sought to advance gene therapy approaches to treat genetic deafness. We focused on Usher syndrome, a devastating genetic disorder that causes blindness, balance disorders and profound deafness, and studied a knock-in mouse model, Ush1c c.216G>A, for Usher syndrome type IC (USH1C). As restoration of complex auditory and balance function is likely to require gene delivery systems that target auditory and vestibular sensory cells with high efficiency, we delivered wild-type Ush1c into the inner ear of Ush1c c.216G>A mice using a synthetic adeno-associated viral vector, Anc80L65, shown to transduce 80-90% of sensory hair cells. We demonstrate recovery of gene and protein expression, restoration of sensory cell function, rescue of complex auditory function and recovery of hearing and balance behavior to near wild-type levels. The data represent unprecedented recovery of inner ear function and suggest that biological therapies to treat deafness may be suitable for translation to humans with genetic inner ear disorders.

Infection of Common Marmosets with GB Virus B Chimeric Virus Encoding the Major Nonstructural Proteins NS2 to NS4A of Hepatitis C Virus.

Science.gov (United States)

Zhu, Shaomei; Li, Tingting; Liu, Bochao; Xu, Yuxia; Sun, Yachun; Wang, Yilin; Wang, Yuanzhan; Shuai, Lifang; Chen, Zixuan; Allain, Jean-Pierre; Li, Chengyao

2016-09-15

A lack of immunocompetent-small-primate models has been an obstacle for developing hepatitis C virus (HCV) vaccines and affordable antiviral drugs. In this study, HCV/GB virus B (GBV-B) chimeric virus carrying the major nonstructural proteins NS2 to NS4A (HCV NS2 to -4A chimera) was produced and used to infect common marmosets, since HCV NS2 to NS4A proteins are critical proteases and major antigens. Seven marmosets were inoculated intrahepatically with HCV NS2 to -4A chimera RNA for primary infection or intravenously injected with chimera-containing serum for passage infection. Three animals used as controls were injected with phosphate-buffered saline (PBS) or GBV-B, respectively. Six of seven HCV NS2 to -4A chimera-infected marmosets exhibited consistent viremia and one showed transient viremia during the course of follow-up detection. All six infected animals with persistent circulating viremia presented characteristics typical of viral hepatitis, including viral RNA and proteins in hepatocytes and histopathological changes in liver tissue. Viremia was consistently detected for 5 to 54 weeks of follow-up. FK506 immunosuppression facilitated the establishment of persistent chimera infection in marmosets. An animal with chimera infection spontaneously cleared the virus in blood 7 weeks following the first inoculation, but viral-RNA persistence, low-level viral protein, and mild necroinflammation remained in liver tissue. The specific antibody and T-cell response to HCV NS3 in this viremia-resolved marmoset was boosted by rechallenging, but no viremia was detected during 57 weeks of follow-up. The chimera-infected marmosets described can be used as a suitable small-primate animal model for studying novel antiviral drugs and T-cell-based vaccines against HCV infection. HCV infection causes approximately 70% of chronic hepatitis and is frequently associated with primary liver cancer globally. Chimpanzees have been used as a reliable primate model for HCV infection

Dengue NS1 Antigen - for Early Detection of Dengue Virus Infection

Directory of Open Access Journals (Sweden)

Amol Hartalkar

2015-08-01

Full Text Available Objectives: To evaluate the efficacy of NS1 antigen assay for early diagnosis of dengue virus infection in a tertiary care hospital. Methods: This cross sectional study was carried out in department of Medicine from August to December 2013. Total 100 patients with dengue fever were included. Complete blood count, alanine aminotransferase (ALT, aspartate aminotransferase (AST, Dengue NS1 antigen and IgM and IgG antibodies of dengue virus were done in all cases. Results: Of the 100 sera tested, 75% were positive for dengue virus infection based on dengue NS1 antigen, IgM antibody and IgG antibody. Dengue NS1 antigen and IgM, IgG antibody were able to detect dengue virus infection between day 1 to day 8 in 92% of samples, 86.7% of samples and 82.6% of samples respectively. Sixty nine percent (69% were found positive for dengue NS1 antigen, 65% were IgM positive and 62% were IgG positive. Based on the dengue NS1 antigen and IgM antibody combination, 74% were positive for dengue virus infections. Sensitivity of Dengue NS1 antigen was 92.3% and specificity of 74.28% in comparison to IgM antibody. Detection rate increased to 75%, based on the antigen and IgG antibody combination. Sensitivity of dengue NS1 antigen was 90.3% and specificity of 65.8% in comparison to IgG antibody. Conclusion: Dengue NS1 antigen is a useful, sensitive and specific test for early diagnosis of dengue virus infection and it improves diagnostic efficiency in combination with antibody test. Key words: Dengue fever, NS1 antigen. Introduction: Dengue fever (DF is the most common arboviral illness in humans. Each year, an estimated 50-100 million cases of dengue fever and 500,000 cases of dengue hemorrhagic fever occur worldwide, with 30000 deaths (mainly in children. Globally 2.5-3 billion people in approximately 112 tropical and subtropical countries are at risk of dengue.of samples respectively. Sixty nine percent (69% were found positive for dengue NS1 antigen, 65% were Ig

The NS segment of H5N1 avian influenza viruses (AIV) enhances the virulence of an H7N1 AIV in chickens.

Science.gov (United States)

Vergara-Alert, Júlia; Busquets, Núria; Ballester, Maria; Chaves, Aida J; Rivas, Raquel; Dolz, Roser; Wang, Zhongfang; Pleschka, Stephan; Majó, Natàlia; Rodríguez, Fernando; Darji, Ayub

2014-01-25

Some outbreaks involving highly pathogenic avian influenza viruses (HPAIV) of subtypes H5 and H7 were caused by avian-to-human transmissions. In nature, different influenza A viruses can reassort leading to new viruses with new characteristics. We decided to investigate the impact that the NS-segment of H5 HPAIV would have on viral pathogenicity of a classical avian H7 HPAIV in poultry, a natural host. We focussed this study based on our previous work that demonstrated that single reassortment of the NS-segment from an H5 HPAIV into an H7 HPAIV changes the ability of the virus to replicate in mammalian hosts. Our present data show that two different H7-viruses containing an NS-segment from H5-types (FPV NS GD or FPV NS VN) show an overall highly pathogenic phenotype compared with the wild type H7-virus (FPV), as characterized by higher viral shedding and earlier manifestation of clinical signs. Correlating with the latter, higher amounts of IFN-β mRNA were detected in the blood of NS-reassortant infected birds, 48 h post-infection (pi). Although lymphopenia was detected in chickens from all AIV-infected groups, also 48 h pi those animals challenged with NS-reassortant viruses showed an increase of peripheral monocyte/macrophage-like cells expressing high levels of IL-1β, as determined by flow cytometry. Taken together, these findings highlight the importance of the NS-segment in viral pathogenicity which is directly involved in triggering antiviral and pro-inflammatory cytokines found during HPAIV pathogenesis in chickens.

NS Otto Hahn

International Nuclear Information System (INIS)

Schafstall, H.G.

1983-01-01

For the bulk cargo ship had been chosen the advanced PWR, the secial characteristic of which is an integrated primary loop with automatic pressurisation. Altogether the Otto Hahn covered over half a million sea-miles. In-service inspections and examinations of the reactor plant were effected by control authorities every year. During the whole operating period the NS Otto Hahn showed a safe and reliable behaviour even from the view of radiation protection. (DG) [de

Efficient hepatitis c virus genotype 1b core-NS5A recombinants permit efficacy testing of protease and NS5A inhibitors

DEFF Research Database (Denmark)

Pham, Long V.; Ramirez Almeida, Santseharay; Carlsen, Thomas H R

2017-01-01

Hepatitis C virus (HCV) strains belong to seven genotypes with numerous subtypes that respond differently to antiviral therapies. Genotype 1, and primarily subtype 1b, is the most prevalent genotype worldwide. The development of recombinant HCV infectious cell culture systems for different variants......, permitted by the high replication capacity of strain JFH1 (genotype 2a), has advanced efficacy and resistance testing of antivirals. However, efficient infectious JFH1-based cell cultures of subtype 1b are limited and comprise only the 5= untranslated region (5=UTR)-NS2, NS4A, or NS5A regions. Importantly...

45 CFR 309.145 - What costs are allowable for Tribal IV-D programs carried out under § 309.65(a) of this part?

Science.gov (United States)

2010-10-01

... 45 Public Welfare 2 2010-10-01 2010-10-01 false What costs are allowable for Tribal IV-D programs... ENFORCEMENT (IV-D) PROGRAM Tribal IV-D Program Funding § 309.145 What costs are allowable for Tribal IV-D... maintenance of essential Office Automation capability; (4) Establishment of Intergovernmental Service...

Evolutionary dynamics of hepatitis C virus NS3 protease domain during and following treatment with narlaprevir, a potent NS3 protease inhibitor

NARCIS (Netherlands)

de Bruijne, J.; Thomas, X. V.; Rebers, S. P.; Weegink, C. J.; Treitel, M. A.; Hughes, E.; Bergmann, J. F.; de Knegt, R. J.; Janssen, H. L. A.; Reesink, H. W.; Molenkamp, R.; Schinkel, J.

2013-01-01

Narlaprevir, a hepatitis C virus (HCV) NS3/4A serine protease inhibitor, has demonstrated robust antiviral activity in a placebo-controlled phase 1 study. To study evolutionary dynamics of resistant variants, the NS3 protease sequence was clonally analysed in thirty-two HCV genotype 1-infected

Rangeland restoration for Hirola, the world's most endangered antelope

Science.gov (United States)

Rangeland restoration can improve habitat for threatened species such as the hirola antelope (Beatragus hunteri) that inhabit savannas of eastern Kenya. However, restoration success likely varies across soil types and target restoration species, as well as according to restoration approach. We teste...

Influenza virus sequence feature variant type analysis: evidence of a role for NS1 in influenza virus host range restriction.

Science.gov (United States)

Noronha, Jyothi M; Liu, Mengya; Squires, R Burke; Pickett, Brett E; Hale, Benjamin G; Air, Gillian M; Galloway, Summer E; Takimoto, Toru; Schmolke, Mirco; Hunt, Victoria; Klem, Edward; García-Sastre, Adolfo; McGee, Monnie; Scheuermann, Richard H

2012-05-01

Genetic drift of influenza virus genomic sequences occurs through the combined effects of sequence alterations introduced by a low-fidelity polymerase and the varying selective pressures experienced as the virus migrates through different host environments. While traditional phylogenetic analysis is useful in tracking the evolutionary heritage of these viruses, the specific genetic determinants that dictate important phenotypic characteristics are often difficult to discern within the complex genetic background arising through evolution. Here we describe a novel influenza virus sequence feature variant type (Flu-SFVT) approach, made available through the public Influenza Research Database resource (www.fludb.org), in which variant types (VTs) identified in defined influenza virus protein sequence features (SFs) are used for genotype-phenotype association studies. Since SFs have been defined for all influenza virus proteins based on known structural, functional, and immune epitope recognition properties, the Flu-SFVT approach allows the rapid identification of the molecular genetic determinants of important influenza virus characteristics and their connection to underlying biological functions. We demonstrate the use of the SFVT approach to obtain statistical evidence for effects of NS1 protein sequence variations in dictating influenza virus host range restriction.

Hepatitis C Virus NS3 Inhibitors: Current and Future Perspectives

Directory of Open Access Journals (Sweden)

Kazi Abdus Salam

2013-01-01

Full Text Available Currently, hepatitis C virus (HCV infection is considered a serious health-care problem all over the world. A good number of direct-acting antivirals (DAAs against HCV infection are in clinical progress including NS3-4A protease inhibitors, RNA-dependent RNA polymerase inhibitors, and NS5A inhibitors as well as host targeted inhibitors. Two NS3-4A protease inhibitors (telaprevir and boceprevir have been recently approved for the treatment of hepatitis C in combination with standard of care (pegylated interferon plus ribavirin. The new therapy has significantly improved sustained virologic response (SVR; however, the adverse effects associated with this therapy are still the main concern. In addition to the emergence of viral resistance, other targets must be continually developed. One such underdeveloped target is the helicase portion of the HCV NS3 protein. This review article summarizes our current understanding of HCV treatment, particularly with those of NS3 inhibitors.

48 CFR 46.309 - Research and development contracts (short form).

Science.gov (United States)

2010-10-01

... 48 Federal Acquisition Regulations System 1 2010-10-01 2010-10-01 false Research and development... REGULATION CONTRACT MANAGEMENT QUALITY ASSURANCE Contract Clauses 46.309 Research and development contracts... Development (Short Form), in solicitations and contracts for research and development when the clause...

25 CFR 309.1 - How do the regulations in this part carry out the Indian Arts and Crafts Act of 1990?

Science.gov (United States)

2010-04-01

... Arts and Crafts Act of 1990? 309.1 Section 309.1 Indians INDIAN ARTS AND CRAFTS BOARD, DEPARTMENT OF THE INTERIOR PROTECTION OF INDIAN ARTS AND CRAFTS PRODUCTS § 309.1 How do the regulations in this part carry out the Indian Arts and Crafts Act of 1990? These regulations define the nature and Indian origin...

CIAE 600 kV ns pulse neutron generator

International Nuclear Information System (INIS)

Shen Guanren; Guan Xialing; Chen Hongtao

2001-01-01

The overall composition of CIAE 600 kV ns Pulse Neutron Generator (CPNG) are introduced, and its characteristic, main technological performance and application were also given. CPNG consists of high voltage power supply with highest output voltage 600 kV, direct current 15 mA, stability and ripple ≤0.1%, 2214 mm x 1604 mm x 1504 mm stainless steel high voltage electrode, built in head equipment uniform field accelerating tube, ns pulsed installation, turbomolecular vacuum pump system and drift pipes at 0 degree and 45 degree. Its characteristics are: (1) high current beam; (2) high current beam ns pulsed installation made use of low energy for chopper and high energy for buncher; (3) compactly laid out and simple in structure

[11C]NS8880, a promising PET radiotracer targeting the norepinephrine transporter

DEFF Research Database (Denmark)

Vase, Karina Højrup; Peters, Dan; Nielsen, Elsebeth Ø

2014-01-01

-azabicyclo[3.2.1]octane (NS8880), targeting NET. NS8880 has an in vitro binding profile comparable to desipramine and is structurally not related to reboxetine. METHODS: Labeling of NS8880 with [11C] was achieved by a non-conventional technique: substitution of pyridinyl fluorine with [11C]methanolate...... yields with high purity. The PET in vivo evaluation in pig and rat revealed a rapid brain uptake of [11C]NS8880 and fast obtaining of equilibrium. Highest binding was observed in thalamic and hypothalamic regions. Pretreatment with desipramine efficiently reduced binding of [11C]NS8880. CONCLUSION: Based...... on the pre-clinical results obtained so far [11C]NS8880 displays promising properties for PET imaging of NET....

[Posterior ceramic bonded partial restorations].

Science.gov (United States)

Mainjot, Amélie; Vanheusden, Alain

2006-01-01

Posterior ceramic bonded partial restorations are conservative and esthetic approaches for compromised teeth. Overlays constitute a less invasive alternative for tooth tissues than crown preparations. With inlays and onlays they are also indicated in case of full arch or quadrant rehabilitations including several teeth. This article screens indications and realization of this type of restorations.

Mosquito densonucleosis virus non-structural protein NS2 is necessary for a productive infection

International Nuclear Information System (INIS)

Azarkh, Eugene; Robinson, Erin; Hirunkanokpun, Supanee; Afanasiev, Boris; Kittayapong, Pattamaporn; Carlson, Jonathan; Corsini, Joe

2008-01-01

Mosquito densonucleosis viruses synthesize two non-structural proteins, NS1 and NS2. While NS1 has been studied relatively well, little is known about NS2. Antiserum was raised against a peptide near the N-terminus of NS2, and used to conduct Western blot analysis and immuno-fluorescence assays. Western blots revealed a prominent band near the expected size (41 kDa). Immuno-fluorescence studies of mosquito cells transfected with AeDNV indicate that NS2 has a wider distribution pattern than does NS1, and the distribution pattern appears to be a function of time post-infection. Nuclear localization of NS2 requires intact C-terminus but does not require additional viral proteins. Mutations ranging from complete NS2 knock-out to a single missense amino acid substitution in NS2 can significantly reduce viral replication and production of viable progeny

AGILE Observations of the Gravitational-wave Source GW170817: Constraining Gamma-Ray Emission from an NS-NS Coalescence

Science.gov (United States)

Verrecchia, F.; Tavani, M.; Donnarumma, I.; Bulgarelli, A.; Evangelista, Y.; Pacciani, L.; Ursi, A.; Piano, G.; Pilia, M.; Cardillo, M.; Parmiggiani, N.; Giuliani, A.; Pittori, C.; Longo, F.; Lucarelli, F.; Minervini, G.; Feroci, M.; Argan, A.; Fuschino, F.; Labanti, C.; Marisaldi, M.; Fioretti, V.; Trois, A.; Del Monte, E.; Antonelli, L. A.; Barbiellini, G.; Caraveo, P.; Cattaneo, P. W.; Colafrancesco, S.; Costa, E.; D'Amico, F.; Ferrari, A.; Giommi, P.; Morselli, A.; Paoletti, F.; Pellizzoni, A.; Picozza, P.; Rappoldi, A.; Soffitta, P.; Vercellone, S.; Baroncelli, L.; Zollino, G.

2017-12-01

The LIGO-Virgo Collaboration (LVC) detected, on 2017 August 17, an exceptional gravitational-wave (GW) event temporally consistent within ˜ 1.7 {{s}} with the GRB 1708117A observed by Fermi-GBM and INTEGRAL. The event turns out to be compatible with a neutron star-neutron star (NS-NS) coalescence that subsequently produced a radio/optical/X-ray transient detected at later times. We report the main results of the observations by the AGILE satellite of the GW170817 localization region (LR) and its electromagnetic (EM) counterpart. At the LVC detection time T 0, the GW170817 LR was occulted by the Earth. The AGILE instrument collected useful data before and after the GW/GRB event because in its spinning observation mode it can scan a given source many times per hour. The earliest exposure of the GW170817 LR by the gamma-ray imaging detector started about 935 s after T 0. No significant X-ray or gamma-ray emission was detected from the LR that was repeatedly exposed over timescales of minutes, hours, and days before and after GW170817, also considering Mini-calorimeter and Super-AGILE data. Our measurements are among the earliest ones obtained by space satellites on GW170817 and provide useful constraints on the precursor and delayed emission properties of the NS-NS coalescence event. We can exclude with high confidence the existence of an X-ray/gamma-ray emitting magnetar-like object with a large magnetic field of {10}15 {{G}}. Our data are particularly significant during the early stage of evolution of the EM remnant.

Mapping of Leaf Rust Resistance Genes and Molecular Characterization of the 2NS/2AS Translocation in the Wheat Cultivar Jagger.

Science.gov (United States)

Xue, Shulin; Kolmer, James A; Wang, Shuwen; Yan, Liuling

2018-04-19

Winter wheat cultivar 'Jagger' was recently found to have an alien chromosomal segment 2NS that has Lr37 , a gene conferring resistance against leaf rust caused by Puccinia triticina The objective of this study was to map and characterize the gene(s) for seedling leaf rust resistance in Jagger. The recombinant inbred line (RIL) population of Jagger × '2174' was inoculated with leaf rust pathogen THBJG and BBBDB, and evaluated for infection type (IT) response. A major quantitative trait locus (QTL) for THBJG and BBBDB was coincidently mapped to chromosome arm 2AS, and the QTL accounted for 56.6% - 66.2% of total phenotypic variation in infection type (IT) response to THBJG, and 72.1% - 86.9% to BBBDB. The causal gene for resistance to these rust races was mapped to the 2NS segment in Jagger. The 2NS segment was located in a region of approximately 27.8 Mb starting from the telomere of chromosome arm 2AS, based on the sequences of the A genome in tetraploid wheat. The Lr17a gene on chromosome arm 2AS was delimited to 3.1 Mb in the genomic region, which was orthologous to the 2NS segment. Therefore, the Lr37 gene in the 2NS segment can be pyramided with other effective resistance genes, rather than Lr17a in wheat, to improve resistance to rust diseases. Copyright © 2018, G3: Genes, Genomes, Genetics.

[Clinical significance of NS1-BP expression in esophageal squamous cell carcinoma].

Science.gov (United States)

Ren, K; Qian, D; Wang, Y W; Pang, Q S; Zhang, W C; Yuan, Z Y; Wang, P

2018-01-23

Objective: To investigate the clinical significance of NS1-BP expression in patients with esophageal squamous cell carcinoma (ESCC), and to study the roles of NS1-BP in proliferation and apoptosis of ESCC cells. Methods: A total of 98 tumor tissues and 30 adjacent normal tissues from 98 ESCC patients were used as study group and control group, and these samples were collected in Sun Yat-Sen University Cancer Center between 2002 and 2008. In addition, 46 ESCC tissues which were collected in Cancer Institute and Hospital of Tianjin Medical University were used as validation group. Expression of mucosal NS1-BP was detected by immunohistochemistry. Kaplan-Meier curve and log-rank test were used to analyze the survival rate. Multivariate Cox proportional hazard model was used to analyze the prognostic factors. Furthermore, NS1-BP was over expressed or knocked down in ESCC cells by transient transfection. Protein levels of c-Myc were detected by western blot. Cell viability and apoptosis was analyzed by MTT assay and flow cytometry. Results: Among all of tested samples, NS1-BP were down-regulated in 9 out of 30 non-tumorous normal esophageal tissues (30.0%) and 85 out of 144 ESCC tissues (59.0%), respectively, showing a statistically significant difference ( P =0.012). In the study group, three-year disease-free survival rate of NS1-BP high expression group (53.2%) was significantly higher than that of NS1-BP low expression group (27.6%; P =0.009). In the validation group, the three-year disease-free survival rates were 57.8% and 25.5% in NS1-BP high and low levels groups, respectively, showing a similar results ( P =0.016). Importantly, multivariate analyses showed that low expression of NS1-BP was an independent predictor for chemoradiotherapy sensitivity and shorter disease-free survival time in ESCC patients( P <0.05 for all). Furthermore, overexpressed NS1-BP in TE-1 cells repressed c-Myc expression, inhibited cell proliferation and promoted apoptosis. In contrast

Structure-based discovery of clinically approved drugs as Zika virus NS2B-NS3 protease inhibitors that potently inhibit Zika virus infection in vitro and in vivo.

Science.gov (United States)

Yuan, Shuofeng; Chan, Jasper Fuk-Woo; den-Haan, Helena; Chik, Kenn Ka-Heng; Zhang, Anna Jinxia; Chan, Chris Chung-Sing; Poon, Vincent Kwok-Man; Yip, Cyril Chik-Yan; Mak, Winger Wing-Nga; Zhu, Zheng; Zou, Zijiao; Tee, Kah-Meng; Cai, Jian-Piao; Chan, Kwok-Hung; de la Peña, Jorge; Pérez-Sánchez, Horacio; Cerón-Carrasco, José Pedro; Yuen, Kwok-Yung

2017-09-01

Zika virus (ZIKV) infection may be associated with severe complications in fetuses and adults, but treatment options are limited. We performed an in silico structure-based screening of a large chemical library to identify potential ZIKV NS2B-NS3 protease inhibitors. Clinically approved drugs belonging to different drug classes were selected among the 100 primary hit compounds with the highest predicted binding affinities to ZIKV NS2B-NS3-protease for validation studies. ZIKV NS2B-NS3 protease inhibitory activity was validated in most of the selected drugs and in vitro anti-ZIKV activity was identified in two of them (novobiocin and lopinavir-ritonavir). Molecular docking and molecular dynamics simulations predicted that novobiocin bound to ZIKV NS2B-NS3-protease with high stability. Dexamethasone-immunosuppressed mice with disseminated ZIKV infection and novobiocin treatment had significantly (P < 0.05) higher survival rate (100% vs 0%), lower mean blood and tissue viral loads, and less severe histopathological changes than untreated controls. This structure-based drug discovery platform should facilitate the identification of additional enzyme inhibitors of ZIKV. Copyright © 2017 Elsevier B.V. All rights reserved.

Psychological Restoration Practices among College Students

Science.gov (United States)

Altaher, Yara; Runnerstrom, Miryha G.

2018-01-01

This study investigates the restoration practices and the different types of environments sought out by college students during times of stress and also explores the potential for restorative experiences in built environments. In February 2015, 407 matriculated undergraduates at a large public research university voluntarily participated in this…

Antiviral Activity and Resistance Analysis of NS3/4A Protease Inhibitor Grazoprevir and NS5A Inhibitor Elbasvir in Hepatitis C Virus GT4 Replicons.

Science.gov (United States)

Asante-Appiah, Ernest; Curry, Stephanie; McMonagle, Patricia; Ingravallo, Paul; Chase, Robert; Nickle, David; Qiu, Ping; Howe, Anita; Lahser, Frederick C

2017-07-01

Although genotype 4 (GT4)-infected patients represent a minor overall percentage of the global hepatitis C virus (HCV)-infected population, the high prevalence of the genotype in specific geographic regions coupled with substantial sequence diversity makes it an important genotype to study for antiviral drug discovery and development. We evaluated two direct-acting antiviral agents-grazoprevir, an HCV NS3/4A protease inhibitor, and elbasvir, an HCV NS5A inhibitor-in GT4 replicons prior to clinical studies in this genotype. Following a bioinformatics analysis of available GT4 sequences, a set of replicons bearing representative GT4 clinical isolates was generated. For grazoprevir, the 50% effective concentration (EC 50 ) against the replicon bearing the reference GT4a (ED43) NS3 protease and NS4A was 0.7 nM. The median EC 50 for grazoprevir against chimeric replicons encoding NS3/4A sequences from GT4 clinical isolates was 0.2 nM (range, 0.11 to 0.33 nM; n = 5). The difficulty in establishing replicons bearing NS3/4A resistance-associated substitutions was substantially overcome with the identification of a G162R adaptive substitution in NS3. Single NS3 substitutions D168A/V identified from de novo resistance selection studies reduced grazoprevir antiviral activity by 137- and 47-fold, respectively, in the background of the G162R replicon. For elbasvir, the EC 50 against the replicon bearing the reference full-length GT4a (ED43) NS5A gene was 0.0002 nM. The median EC 50 for elbasvir against chimeric replicons bearing clinical isolates from GT4 was 0.0007 nM (range, 0.0002 to 34 nM; n = 14). De novo resistance selection studies in GT4 demonstrated a high propensity to suppress the emergence of amino acid substitutions that confer high-potency reductions to elbasvir. Phenotypic characterization of the NS5A amino acid substitutions identified (L30F, L30S, M31V, and Y93H) indicated that they conferred 15-, 4-, 2.5-, and 7.5-fold potency losses, respectively, to elbasvir

Epitope Sequences in Dengue Virus NS1 Protein Identified by Monoclonal Antibodies

Directory of Open Access Journals (Sweden)

Leticia Barboza Rocha

2017-10-01

Full Text Available Dengue nonstructural protein 1 (NS1 is a multi-functional glycoprotein with essential functions both in viral replication and modulation of host innate immune responses. NS1 has been established as a good surrogate marker for infection. In the present study, we generated four anti-NS1 monoclonal antibodies against recombinant NS1 protein from dengue virus serotype 2 (DENV2, which were used to map three NS1 epitopes. The sequence 193AVHADMGYWIESALNDT209 was recognized by monoclonal antibodies 2H5 and 4H1BC, which also cross-reacted with Zika virus (ZIKV protein. On the other hand, the sequence 25VHTWTEQYKFQPES38 was recognized by mAb 4F6 that did not cross react with ZIKV. Lastly, a previously unidentified DENV2 NS1-specific epitope, represented by the sequence 127ELHNQTFLIDGPETAEC143, is described in the present study after reaction with mAb 4H2, which also did not cross react with ZIKV. The selection and characterization of the epitope, specificity of anti-NS1 mAbs, may contribute to the development of diagnostic tools able to differentiate DENV and ZIKV infections.

Restoring degraded tropical forests for carbon and biodiversity

International Nuclear Information System (INIS)

Budiharta, Sugeng; Meijaard, Erik; Wilson, Kerrie A; Erskine, Peter D; Rondinini, Carlo; Pacifici, Michela

2014-01-01

The extensive deforestation and degradation of tropical forests is a significant contributor to the loss of biodiversity and to global warming. Restoration could potentially mitigate the impacts of deforestation, yet knowledge on how to efficiently allocate funding for restoration is still in its infancy. We systematically prioritize investments in restoration in the tropical landscape of East Kalimantan, Indonesia, and through this application demonstrate the capacity to account for a diverse suite of restoration techniques and forests of varying condition. To achieve this we develop a map of forest degradation for the region, characterized on the basis of aboveground biomass and differentiated by broad forest types. We estimate the costs of restoration as well as the benefits in terms of carbon sequestration and improving the suitability of habitat for threatened mammals through time. When the objective is solely to enhance carbon stocks, then restoration of highly degraded lowland forest is the most cost-effective activity. However, if the objective is to improve the habitat of threatened species, multiple forest types should be restored and this reduces the accumulated carbon by up to 24%. Our analysis framework provides a transparent method for prioritizing where and how restoration should occur in heterogeneous landscapes in order to maximize the benefits for carbon and biodiversity. (letter)

Restoring degraded tropical forests for carbon and biodiversity

Science.gov (United States)

Budiharta, Sugeng; Meijaard, Erik; Erskine, Peter D.; Rondinini, Carlo; Pacifici, Michela; Wilson, Kerrie A.

2014-11-01

The extensive deforestation and degradation of tropical forests is a significant contributor to the loss of biodiversity and to global warming. Restoration could potentially mitigate the impacts of deforestation, yet knowledge on how to efficiently allocate funding for restoration is still in its infancy. We systematically prioritize investments in restoration in the tropical landscape of East Kalimantan, Indonesia, and through this application demonstrate the capacity to account for a diverse suite of restoration techniques and forests of varying condition. To achieve this we develop a map of forest degradation for the region, characterized on the basis of aboveground biomass and differentiated by broad forest types. We estimate the costs of restoration as well as the benefits in terms of carbon sequestration and improving the suitability of habitat for threatened mammals through time. When the objective is solely to enhance carbon stocks, then restoration of highly degraded lowland forest is the most cost-effective activity. However, if the objective is to improve the habitat of threatened species, multiple forest types should be restored and this reduces the accumulated carbon by up to 24%. Our analysis framework provides a transparent method for prioritizing where and how restoration should occur in heterogeneous landscapes in order to maximize the benefits for carbon and biodiversity.

The effect of glycosylation on cytotoxicity of Ibaraki virus nonstructural protein NS3

Science.gov (United States)

URATA, Maho; WATANABE, Rie; IWATA, Hiroyuki

2015-01-01

The cytotoxicity of Ibaraki virus nonstructural protein NS3 was confirmed, and the contribution of glycosylation to this activity was examined by using glycosylation mutants of NS3 generated by site-directed mutagenesis. The expression of NS3 resulted in leakage of lactate dehydrogenase to the culture supernatant, suggesting the cytotoxicity of this protein. The lack of glycosylation impaired the transport of NS3 to the plasma membrane and resulted in reduced cytotoxicity. Combined with the previous observation that NS3 glycosylation was specifically observed in mammalian cells (Urata et al., Virus Research 2014), it was suggested that the alteration of NS3 cytotoxicity through modulating glycosylation is one of the strategies to achieve host specific pathogenisity of Ibaraki virus between mammals and vector arthropods. PMID:26178820

MD421: Electron cloud studies on 25 ns beam variants (BCMS, 8b+4e)

CERN Document Server

Iadarola, Giovanni; Belli, Eleonora; Carver, Lee Robert; Dijkstal, Philipp; Li, Kevin Shing Bruce; Mether, Lotta; Romano, Annalisa; Rumolo, Giovanni; CERN. Geneva. ATS Department

2017-01-01

This note describes a Machine Development session performed with the main goal of studying the e-cloud mitigation that can be obtained by injecting mixed trains of 8b+4e beam type and trains having the standard 25 ns structure. Additionally, in the course of the MD, the pure 8b+4e beam was also checked to be stable when injected with low chromaticity and octupole current settings. Subsequently, the operational BCMS 25 ns beam was also injected with the 8b+4e settings and found to be unstable. The operational settings for injection were re-found by gradually increasing the chromaticity and octupole knobs until all the bunches of the injected beam could remain stable after injection.

The DNA-mimic antirestriction proteins ArdA ColIB-P9, Arn T4, and Ocr T7 as activators of H-NS-dependent gene transcription.

Science.gov (United States)

Melkina, Olga E; Goryanin, Ignatiy I; Zavilgelsky, Gennadii B

2016-11-01

The antirestriction proteins ArdA ColIb-P9, Arn T4 and Ocr T7 specifically inhibit type I and type IV restriction enzymes and belong to the family of DNA-mimic proteins because their three-dimensional structure is similar to the double-helical B-form DNA. It is proposed that the DNA-mimic proteins are able to bind nucleoid protein H-NS and alleviate H-NS-silencing of the transcription of bacterial genes. Escherichia coli lux biosensors were constructed by inserting H-NS-dependent promoters into a vector, thereby placing each fragment upstream of the promoterless Photorhabdus luminescens luxCDABE operon. It was demonstrated that the DNA-mimic proteins ArdA, Arn and Ocr activate the transcription of H-NS-dependent promoters of the lux operon of marine luminescent bacteria (mesophilic Aliivibrio fischeri and psychrophilic Aliivibrio logei), and the dps gene from E. coli. It was also demonstrated that the ArdA antirestriction protein, the genes of which are located on transmissive plasmids ColIb-P9, R64, PK101, decreases levels of H-NS silencing of the PluxC promoter during conjugation in the recipient bacteria. Copyright © 2016 Elsevier GmbH. All rights reserved.

Remote sensing for restoration ecology: Application for restoring degraded, damaged, transformed, or destroyed ecosystems.

Science.gov (United States)

Reif, Molly K; Theel, Heather J

2017-07-01

Restoration monitoring is generally perceived as costly and time consuming, given the assumptions of successfully restoring ecological functions and services of a particular ecosystem or habitat. Opportunities exist for remote sensing to bolster the restoration science associated with a wide variety of injured resources, including resources affected by fire, hydropower operations, chemical releases, and oil spills, among others. In the last decade, the role of remote sensing to support restoration monitoring has increased, in part due to the advent of high-resolution satellite sensors as well as other sensor technology, such as lidar. Restoration practitioners in federal agencies require monitoring standards to assess restoration performance of injured resources. This review attempts to address a technical need and provides an introductory overview of spatial data and restoration metric considerations, as well as an in-depth review of optical (e.g., spaceborne, airborne, unmanned aerial vehicles) and active (e.g., radar, lidar) sensors and examples of restoration metrics that can be measured with remotely sensed data (e.g., land cover, species or habitat type, change detection, quality, degradation, diversity, and pressures or threats). To that end, the present article helps restoration practitioners assemble information not only about essential restoration metrics but also about the evolving technological approaches that can be used to best assess them. Given the need for monitoring standards to assess restoration success of injured resources, a universal monitoring framework should include a range of remote sensing options with which to measure common restoration metrics. Integr Environ Assess Manag 2017;13:614-630. Published 2016. This article is a US Government work and is in the public domain in the USA. Published 2016. This article is a US Government work and is in the public domain in the USA.

Evaluation of ball and roller bearings restored by grinding

Science.gov (United States)

Parker, R. J.; Zaretsky, E. V.; Chen, S. M.

1976-01-01

A joint program was undertaken to restore by grinding those rolling-element bearings which are currently being discarded at aircraft engine and transmission overhaul. Three bearing types were selected from the UH-1 helicopter engine (T-53) and transmission for the pilot program. Groups of each of these bearings were visually and dimensionally inspected for suitability for restoration. A total of 250 bearings were restored by grinding. Of this number, 30 bearings from each type were endurance tested to a TBO of 1600 hours. No bearing failures occurred related to the restoration by grinding process. The two bearing failures which occurred were due to defective rolling elements and were typical of those which may occur in new bearings. The restorable component yield to the three groups was in excess of 90 percent.

An updated meta-analysis on the association of MDM2 SNP309 polymorphism with colorectal cancer risk.

Directory of Open Access Journals (Sweden)

Xue Qin

Full Text Available The mouse double minute 2 (MDM2 gene encodes a phosphoprotein that interacts with P53 and negatively regulates its activity. The SNP309 polymorphism (T-G in the promoter of MDM2 gene has been reported to be associated with enhanced MDM2 expression and tumor development. Studies investigating the association between MDM2 SNP309 polymorphism and colorectal cancer (CRC risk reported conflicting results. We performed a meta-analysis of all available studies to explore the association of this polymorphism with CRC risk.All studies published up to July 2013 on the association between MDM2 SNP309 polymorphism and CRC risk were identified by searching electronic databases PubMed, EMBASE, and Chinese Biomedical Literature database (CBM databases. The association between the MDM2 SNP309 polymorphism and CRC risk was assessed by odds ratios (ORs together with their 95% confidence intervals (CIs.A total of 14 case-control studies including 4460 CRC cases and 4828 controls were identified. We did not find a significant association between the MDM2 SNP309 polymorphism and CRC risk in all genetic models in overall population. However, in subgroup analysis by ethnicity, significant associations were found in Asians (TG vs. TT: OR = 1.197, 95% CI = 1.055-1.358, P=0.005; GG+TG vs. TT: OR = 1.246, 95% CI = 1.106-1.404, P=0.000 and Africans. When stratified by HWE in controls, significantly increased risk was also found among the studies consistent with HWE (TG vs. TT: OR = 1.166, 95% CI = 1.037-1.311, P= 0.010. In subgroup analysis according to p53 mutation status, and gender, no any significant association was detected.The present meta-analysis suggests that the MDM2 is a candidate gene for CRC susceptibility. The MDM2 SNP309 polymorphism may be a risk factor for CRC in Asians.

The Future of HCV Therapy: NS4B as an Antiviral Target

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Hadas Dvory-Sobol

2010-11-01

Full Text Available Chronic hepatitis C virus (HCV infection is a major worldwide cause of liver disease, including cirrhosis and hepatocellular carcinoma. It is estimated that more than 170 million individuals are infected with HCV, with three to four million new cases each year. The current standard of care, combination treatment with interferon and ribavirin, eradicates the virus in only about 50% of chronically infected patients. Notably, neither of these drugs directly target HCV. Many new antiviral therapies that specifically target hepatitis C (e.g. NS3 protease or NS5B polymerase inhibitors are therefore in development, with a significant number having advanced into clinical trials. The nonstructural 4B (NS4B protein, is among the least characterized of the HCV structural and nonstructural proteins and has been subjected to few pharmacological studies. NS4B is an integral membrane protein with at least four predicted transmembrane (TM domains. A variety of functions have been postulated for NS4B, such as the ability to induce the membranous web replication platform, RNA binding and NTPase activity. This review summarizes potential targets within the nonstructural protein NS4B, with a focus on novel classes of NS4B inhibitors.

Uncoupling of Protease trans-Cleavage and Helicase Activities in Pestivirus NS3.

Science.gov (United States)

Zheng, Fengwei; Lu, Guoliang; Li, Ling; Gong, Peng; Pan, Zishu

2017-11-01

The nonstructural protein NS3 from the Flaviviridae family is a multifunctional protein that contains an N-terminal protease and a C-terminal helicase, playing essential roles in viral polyprotein processing and genome replication. Here we report a full-length crystal structure of the classical swine fever virus (CSFV) NS3 in complex with its NS4A protease cofactor segment (PCS) at a 2.35-Å resolution. The structure reveals a previously unidentified ∼2,200-Å 2 intramolecular protease-helicase interface comprising three clusters of interactions, representing a "closed" global conformation related to the NS3-NS4A cis -cleavage event. Although this conformation is incompatible with protease trans -cleavage, it appears to be functionally important and beneficial to the helicase activity, as the mutations designed to perturb this conformation impaired both the helicase activities in vitro and virus production in vivo Our work reveals important features of protease-helicase coordination in pestivirus NS3 and provides a key basis for how different conformational states may explicitly contribute to certain functions of this natural protease-helicase fusion protein. IMPORTANCE Many RNA viruses encode helicases to aid their RNA genome replication and transcription by unwinding structured RNA. Being naturally fused to a protease participating in viral polyprotein processing, the NS3 helicases encoded by the Flaviviridae family viruses are unique. Therefore, how these two enzyme modules coordinate in a single polypeptide is of particular interest. Here we report a previously unidentified conformation of pestivirus NS3 in complex with its NS4A protease cofactor segment (PCS). This conformational state is related to the protease cis -cleavage event and is optimal for the function of helicase. This work provides an important basis to understand how different enzymatic activities of NS3 may be achieved by the coordination between the protease and helicase through different

The effects of non-synonymous single nucleotide polymorphisms (nsSNPs) on protein-protein interactions.

Science.gov (United States)

Yates, Christopher M; Sternberg, Michael J E

2013-11-01

Non-synonymous single nucleotide polymorphisms (nsSNPs) are single base changes leading to a change to the amino acid sequence of the encoded protein. Many of these variants are associated with disease, so nsSNPs have been well studied, with studies looking at the effects of nsSNPs on individual proteins, for example, on stability and enzyme active sites. In recent years, the impact of nsSNPs upon protein-protein interactions has also been investigated, giving a greater insight into the mechanisms by which nsSNPs can lead to disease. In this review, we summarize these studies, looking at the various mechanisms by which nsSNPs can affect protein-protein interactions. We focus on structural changes that can impair interaction, changes to disorder, gain of interaction, and post-translational modifications before looking at some examples of nsSNPs at human-pathogen protein-protein interfaces and the analysis of nsSNPs from a network perspective. © 2013.

Restoration in Its Natural Context: How Ecological Momentary Assessment Can Advance Restoration Research

Directory of Open Access Journals (Sweden)

Femke Beute

2016-04-01

Full Text Available More and more people use self-tracking technologies to track their psychological states, physiology, and behaviors to gain a better understanding of themselves or to achieve a certain goal. Ecological Momentary Assessment (EMA also offers an excellent opportunity for restorative environments research, which examines how our physical environment (especially nature can positively influence health and wellbeing. It enables investigating restorative health effects in everyday life, providing not only high ecological validity but also opportunities to study in more detail the dynamic processes playing out over time on recovery, thereby bridging the gap between laboratory (i.e., short-term effects and epidemiological (long-term effects research. We have identified four main areas in which self-tracking could help advance restoration research: (1 capturing a rich set of environment types and restorative characteristics; (2 distinguishing intra-individual from inter-individual effects; (3 bridging the gap between laboratory and epidemiological research; and (4 advancing theoretical insights by measuring a more broad range of effects in everyday life. This paper briefly introduces restorative environments research, then reviews the state of the art of self-tracking technologies and methodologies, discusses how these can be implemented to advance restoration research, and presents some examples of pioneering work in this area.

9 CFR 309.5 - Swine; disposal because of hog cholera.

Science.gov (United States)

2010-01-01

... 9 Animals and Animal Products 2 2010-01-01 2010-01-01 false Swine; disposal because of hog cholera... INSPECTION AND CERTIFICATION ANTE-MORTEM INSPECTION § 309.5 Swine; disposal because of hog cholera. (a) All swine found by an inspector to be affected with hog cholera shall be identified as U.S. Condemned and...

31 CFR 309.10 - Tenders; reservation of right to reject.

Science.gov (United States)

2010-07-01

... 31 Money and Finance: Treasury 2 2010-07-01 2010-07-01 false Tenders; reservation of right to... BILLS § 309.10 Tenders; reservation of right to reject. In considering the acceptance of tenders, the highest prices offered will be accepted in full down to the amount required, and if the same price appears...

Nodding syndrome (NS) and Onchocerca Volvulus (OV) in Northern Uganda.

Science.gov (United States)

Lagoro, David Kitara; Arony, Denis Anywar

2017-01-01

Nodding Syndrome (NS) is a childhood neurological disorder characterized by atonic seizures, cognitive decline, school dropout, muscle weakness, thermal dysfunction, wasting and stunted growth. There are recent published information suggesting associations between Nodding Syndrome (NS) with cerebrospinal fluid (CSF) VGKC antibodies and serum leiomidin-1 antibody cross reacting with Onchocerca Volvulus ( OV ). These findings suggest a neuro-inflammatory cause of NS and they are important findings in the search for the cause of Nodding Syndrome. These observations perhaps provide further, the unique explanation for the association between Nodding Syndrome and Onchocerca Volvulus . Many clinical and epidemiological studies had shown a significant correlation between NS and infestation with a nematode, Onchocerca volvulus which causes a disease, Onchocerciasis , some of which when left untreated can develop visual defect ("River Blindness"). While these studies conducted in Northern Uganda and Southern Sudan indicate a statistically significant association with ( OV infection (using positive skin snips), we observe that ( OV is generally endemic in many parts of Sub Saharan Africa and Latin America and that to date, no NS cases have been recorded in those regions. This letter to the Editor is to provide additional information on the current view about the relationship between Nodding Syndrome and Onchocerca Volvulus as seen in Northern Uganda.

Early diagnosis of dengue in travelers: comparison of a novel real-time RT-PCR, NS1 antigen detection and serology.

Science.gov (United States)

Huhtamo, Eili; Hasu, Essi; Uzcátegui, Nathalie Y; Erra, Elina; Nikkari, Simo; Kantele, Anu; Vapalahti, Olli; Piiparinen, Heli

2010-01-01

The increased traveling to dengue endemic regions and the numerous epidemics have led to a rise in imported dengue. The laboratory diagnosis of acute dengue requires several types of tests and often paired samples are needed for obtaining reliable results. Although several diagnostic methods are available, proper comparative data on their performance are lacking. To compare the performance of novel methods including a novel pan-DENV real-time RT-PCR and a commercially available NS1 capture-EIA in regard to IgM detection for optimizing the early diagnosis of DENV in travelers. A panel of 99 selected early phase serum samples of dengue patients was studied by real-time RT-PCR, NS1 antigen ELISA, IgM-EIA, IgG-IFA and cell culture virus isolation. The novel real-time RT-PCR was shown specific and sensitive for detection of DENV-1-4 RNA and suitable for diagnostic use. The diagnostic rate using combination of RNA and IgM detection was 99% and using NS1 and IgM detection 95.9%. The results of RNA and NS1 antigen detection disagreed in 15.5% of samples that had only RNA or NS1 antigen detected. The diagnostic rates of early samples are higher when either RNA or NS1 antigen detection is combined with IgM detection. Besides the differences in the RNA and NS1 detection assays, the observed discrepancy of results could suggest individual variation or differences in timing of these markers in patient serum. Copyright (c) 2009 Elsevier B.V. All rights reserved.

Genetic Defects Underlie the Non-syndromic Autosomal Recessive Intellectual Disability (NS-ARID

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Saleha Shamim

2017-05-01

Full Text Available Intellectual disability (ID is a neurodevelopmental disorder which appears frequently as the result of genetic mutations and may be syndromic (S-ID or non-syndromic (NS-ID. ID causes an important economic burden, for patient's family, health systems, and society. Identifying genes that cause S-ID can easily be evaluated due to the clinical symptoms or physical anomalies. However, in the case of NS-ID due to the absence of co-morbid features, the latest molecular genetic techniques can be used to understand the genetic defects that underlie it. Recent studies have shown that non-syndromic autosomal recessive (NS-ARID is extremely heterogeneous and contributes much more than X-linked ID. However, very little is known about the genes and loci involved in NS-ARID relative to X-linked ID, and whose complete genetic etiology remains obscure. In this review article, the known genetic etiology of NS-ARID and possible relationships between genes and the associated molecular pathways of their encoded proteins has been reviewed which will enhance our understanding about the underlying genes and mechanisms in NS-ARID.

Production of recombinant dengue non-structural 1 (NS1) proteins from clinical virus isolates.

Science.gov (United States)

Yohan, Benediktus; Wardhani, Puspa; Aryati; Trimarsanto, Hidayat; Sasmono, R Tedjo

2017-01-01

Dengue is a febrile disease caused by infection of dengue virus (DENV). Early diagnosis of dengue infection is important for better management of the disease. The DENV Non-Structural Protein 1 (NS1) antigen has been routinely used for the early dengue detection. In dengue epidemic countries such as Indonesia, clinicians are increasingly relying on the NS1 detection for confirmation of dengue infection. Various NS1 diagnostic tests are commercially available, however different sensitivities and specificities were observed in various settings. This study was aimed to generate dengue NS1 recombinant protein for the development of dengue diagnostic tests. Four Indonesian DENV isolates were used as the source of the NS1 gene cloning, expression, and purification in bacterial expression system. Recombinant NS1 proteins were successfully purified and their antigenicities were assessed. Immunization of mice with recombinant proteins observed the immunogenicity of the NS1 protein. The generated recombinant proteins can be potentially used in the development of NS1 diagnostic test. With minimal modifications, this method can be used for producing NS1 recombinant proteins from isolates obtained from other geographical regions. Copyright © 2016 Elsevier Inc. All rights reserved.

Gelatin nanoparticles enhance delivery of hepatitis C virus recombinant NS2 gene.

Science.gov (United States)

Sabet, Salwa; George, Marina A; El-Shorbagy, Haidan M; Bassiony, Heba; Farroh, Khaled Y; Youssef, Tareq; Salaheldin, Taher A

2017-01-01

Development of an effective non-viral vaccine against hepatitis C virus infection is of a great importance. Gelatin nanoparticles (Gel.NPs) have an attention and promising approach as a viable carrier for delivery of vaccine, gene, drug and other biomolecules in the body. The present study aimed to develop stable Gel.NPs conjugated with nonstructural protein 2 (NS2) gene of Hepatitis C Virus genotype 4a (HCV4a) as a safe and an efficient vaccine delivery system. Gel.NPs were synthesized and characterized (size: 150±2 nm and zeta potential +17.6 mv). NS2 gene was successfully cloned and expressed into E. coli M15 using pQE-30 vector. Antigenicity of the recombinant NS2 protein was confirmed by Western blotting to verify the efficiency of NS2 as a possible vaccine. Then NS2 gene was conjugated to gelatin nanoparticles and a successful conjugation was confirmed by labeling and imaging using Confocal Laser Scanning Microscope (CLSM). Interestingly, the transformation of the conjugated NS2/Gel.NPs complex into E. coli DH5-α was 50% more efficient than transformation with the gene alone. In addition, conjugated NS2/Gel.NPs with ratio 1:100 (w/w) showed higher transformation efficiency into E. coli DH5-α than the other ratios (1:50 and 2:50). Gel.NPs effectively enhanced the gene delivery in bacterial cells without affecting the structure of NS2 gene and could be used as a safe, easy, rapid, cost-effective and non-viral vaccine delivery system for HCV.

Comparison Of Internal Adaptation Of Fixed Restorations Fabricated From Four Different Materials By A Three Axis Mill

Science.gov (United States)

2016-06-26

COMP ARIS ON OF INTERNAL ADAPTATION OF FIXED RESTO RA TIO NS FABRICATED FROM FOUR DIFFERENT MATERIALS BY A THREE-AXIS MILL by Bryan Paul...MATERIALS BY A THREE-AXIS MILL is appropriately acknowledged and, beyond brief excerpts, is with the permission of the copyright owner. ~r2L~ Bryan Paul...RESTORATIONS FABRICATED FROM FOUR DIFFERENT MATERIALS BY A THREE-AXIS MILL LCDR Bryan Paul Rasmussen, DC USN Prosthodontics Dept., 2016 Directed by

D-Branes in the Background of NS Fivebranes

CERN Document Server

Elitzur, Shmuel; Rabinovici, Eliezer; Sarkisian, G; Kutasov, D; Elitzur, Shmuel; Giveon, Amit; Kutasov, David; Rabinovici, Eliezer; Sarkissian, Gor

2000-01-01

We study the dynamics of $D$-branes in the near-horizon geometry of $NS$ fivebranes. This leads to a holographically dual description of the physics of $D$-branes ending on and/or intersecting $NS5$-branes. We use it to verify some properties of such $D$-branes which were deduced indirectly in the past, and discuss some instabilities of non-supersymmetric brane configurations. Our construction also describes vacua of Little String Theory which are dual to open plus closed string theory in asymptotically linear dilaton spacetimes.

Oncolytic effects of a novel influenza A virus expressing interleukin-15 from the NS reading frame.

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Marijke van Rikxoort

Full Text Available Oncolytic influenza A viruses with deleted NS1 gene (delNS1 replicate selectively in tumour cells with defective interferon response and/or activated Ras/Raf/MEK/ERK signalling pathway. To develop a delNS1 virus with specific immunostimulatory properties, we used an optimised technology to insert the interleukin-15 (IL-15 coding sequence into the viral NS gene segment (delNS1-IL-15. DelNS1 and delNS1-IL-15 exerted similar oncolytic effects. Both viruses replicated and caused caspase-dependent apoptosis in interferon-defective melanoma cells. Virus replication was required for their oncolytic activity. Cisplatin enhanced the oncolytic activity of delNS1 viruses. The cytotoxic drug increased delNS1 replication and delNS1-induced caspase-dependent apoptosis. Interference with MEK/ERK signalling by RNAi-mediated depletion or the MEK inhibitor U0126 did not affect the oncolytic effects of the delNS1 viruses. In oncolysis sensitive melanoma cells, delNS1-IL-15 (but not delNS1 infection resulted in the production of IL-15 levels ranging from 70 to 1140 pg/mL in the cell culture supernatants. The supernatants of delNS1-IL-15-infected (but not of delNS1-infected melanoma cells induced primary human natural killer cell-mediated lysis of non-infected tumour cells. In conclusion, we constructed a novel oncolytic influenza virus that combines the oncolytic activity of delNS1 viruses with immunostimulatory properties through production of functional IL-15. Moreover, we showed that the oncolytic activity of delNS1 viruses can be enhanced in combination with cytotoxic anti-cancer drugs.

Pollution characteristics of surface runoff under different restoration types in manganese tailing wasteland.

Science.gov (United States)

Wang, Jun; Cheng, Qingyu; Xue, Shengguo; Rajendran, Manikandan; Wu, Chuan; Liao, Jiaxin

2018-04-01

A great deal of manganese and associated heavy metals (such as Ni, Cu, Zn, Cd, Pb, etc.) was produced in manganese mining, smelting, and other processes and weathering and leaching of waste slag, which entered rainwater runoff by different means under the action of rainfall runoff. It caused heavy metal pollution in water environment to surrounding areas, and then environmental and human health risks were becoming increasingly serious. In the Xiangtan manganese mine, we studied the characteristics of nutritional pollutants and heavy metals by using the method of bounded runoff plots on the manganese tailing wasteland after carrying out some site treatments using three different approaches, such as (1) exposed tailings, the control treatment (ET), (2) external-soil amelioration and colonization of Cynodon dactylon (Linn.) Pers. turf (EC), and (3) external-soil amelioration and seedling seeding propagation of Cynodon dactylon (Linn.) Pers. (ES). The research showed that the maximum runoff occurred in 20,140,712 rainfall events, and the basic law of runoff was EC area > ET area > ES area in the same rainfall event. The concentration of total suspended solids (TSS) and chemical oxygen demand (COD) of three ecological restoration areas adopted the following rule: ET area > EC area > ES area. Nitrogen (N) existed mainly in the form of water soluble while phosphorus (P) was particulate. The highest concentrations of total nitrogen (TN) and total phosphorus (TP) were 11.57 ± 2.99 mg/L in the EC area and 1.42 ± 0.56 mg/L in the ET area, respectively. Cr, Ni, Pb, Zn, Mn, and Cu in surface runoff from three restoration types all exceeded the class V level of the environmental quality standard for surface water except Cu in EC and ES areas. Pollution levels of heavy metals in surface runoff from three restoration areas are shown as follows: ET area > EC area > ES area. There was a significant positive correlation between TSS and runoff, COD, and TP. And this

309 Building transition plan

International Nuclear Information System (INIS)

Graves, C.E.

1994-01-01

The preparation for decontamination and decommissioning (transition) of the 309 Building is projected to be completed by the end of the fiscal year (FY) 1998. The major stabilization and decontamination efforts include the Plutonium Recycle Test Reactor (PRTR), fuel storage and transfer pits, Transfer Waste (TW) tanks and the Ion Exchange Vaults. In addition to stabilizing contaminated areas, equipment, components, records, waste products, etc., will be dispositioned. All nonessential systems, i.e., heating, ventilation, and air conditioning (HVAC), electrical, monitoring, fluids, etc., will be shut down and drained/de-energized. This will allow securing of the process, laboratory, and office areas of the facility. After that, the facility will be operated at a level commensurate with its surveillance needs while awaiting D ampersand D. The implementation costs for FY 1995 through FY 1998 for the transition activities are estimated to be $1,070K, $2,115K, $2,939K, and $4,762K, respectively. Costs include an assumed company overhead of 20% and a 30% out year contingency

5 CFR 352.309 - Retirement, health benefits, and group life insurance.

Science.gov (United States)

2010-01-01

... Organizations § 352.309 Retirement, health benefits, and group life insurance. (a) Agency action. An employee... entitled to retain coverage for retirement, health benefits, and group life insurance purposes if he or she... he or she wishes to retain coverage under the retirement, health benefits, and group life insurance...

Mechanistic Characterization of GS-9190 (Tegobuvir), a Novel Nonnucleoside Inhibitor of Hepatitis C Virus NS5B Polymerase▿

Science.gov (United States)

Shih, I-hung; Vliegen, Inge; Peng, Betty; Yang, Huiling; Hebner, Christy; Paeshuyse, Jan; Pürstinger, Gerhard; Fenaux, Martijn; Tian, Yang; Mabery, Eric; Qi, Xiaoping; Bahador, Gina; Paulson, Matthew; Lehman, Laura S.; Bondy, Steven; Tse, Winston; Reiser, Hans; Lee, William A.; Schmitz, Uli; Neyts, Johan; Zhong, Weidong

2011-01-01

GS-9190 (Tegobuvir) is a novel imidazopyridine inhibitor of hepatitis C virus (HCV) RNA replication in vitro and has demonstrated potent antiviral activity in patients chronically infected with genotype 1 (GT1) HCV. GS-9190 exhibits reduced activity against GT2a (JFH1) subgenomic replicons and GT2a (J6/JFH1) infectious virus, suggesting that the compound's mechanism of action involves a genotype-specific viral component. To further investigate the GS-9190 mechanism of action, we utilized the susceptibility differences between GT1b and GT2a by constructing a series of replicon chimeras where combinations of 1b and 2a nonstructural proteins were encoded within the same replicon. The antiviral activities of GS-9190 against the chimeric replicons were reduced to levels comparable to that of the wild-type GT2a replicon in chimeras expressing GT2a NS5B. GT1b replicons in which the β-hairpin region (amino acids 435 to 455) was replaced by the corresponding sequence of GT2a were markedly less susceptible to GS-9190, indicating the importance of the thumb subdomain of the polymerase in this effect. Resistance selection in GT1b replicon cells identified several mutations in NS5B (C316Y, Y448H, Y452H, and C445F) that contributed to the drug resistance phenotype. Reintroduction of these mutations into wild-type replicons conferred resistance to GS-9190, with the number of NS5B mutations correlating with the degree of resistance. Analysis of GS-9190 cross-resistance against previously reported NS5B drug-selected mutations showed that the resistance pattern of GS-9190 is different from other nonnucleoside inhibitors. Collectively, these data demonstrate that GS-9190 represents a novel class of nonnucleoside polymerase inhibitors that interact with NS5B likely through involvement of the β-hairpin in the thumb subdomain. PMID:21746939

49 CFR 40.309 - What are the employer's responsibilities with respect to the SAP's directions for follow-up tests?

Science.gov (United States)

2010-10-01

... respect to the SAP's directions for follow-up tests? 40.309 Section 40.309 Transportation Office of the... responsibilities with respect to the SAP's directions for follow-up tests? (a) As the employer, you must carry out the SAP's follow-up testing requirements. You may not allow the employee to continue to perform safety...

A Model of H-NS Mediated Compaction of Bacterial DNA

NARCIS (Netherlands)

Joyeux, M.; Vreede, J.

2013-01-01

The histone-like nucleoid structuring protein (H-NS) is a nucleoid-associated protein, which is involved in both gene regulation and DNA compaction. H-NS can bind to DNA in two different ways: in trans, by binding to two separate DNA duplexes, or in cis, by binding to different sites on the same

The science and practice of river restoration

Science.gov (United States)

Wohl, Ellen; Lane, Stuart N.; Wilcox, Andrew C.

2015-08-01

River restoration is one of the most prominent areas of applied water-resources science. From an initial focus on enhancing fish habitat or river appearance, primarily through structural modification of channel form, restoration has expanded to incorporate a wide variety of management activities designed to enhance river process and form. Restoration is conducted on headwater streams, large lowland rivers, and entire river networks in urban, agricultural, and less intensively human-altered environments. We critically examine how contemporary practitioners approach river restoration and challenges for implementing restoration, which include clearly identified objectives, holistic understanding of rivers as ecosystems, and the role of restoration as a social process. We also examine challenges for scientific understanding in river restoration. These include: how physical complexity supports biogeochemical function, stream metabolism, and stream ecosystem productivity; characterizing response curves of different river components; understanding sediment dynamics; and increasing appreciation of the importance of incorporating climate change considerations and resiliency into restoration planning. Finally, we examine changes in river restoration within the past decade, such as increasing use of stream mitigation banking; development of new tools and technologies; different types of process-based restoration; growing recognition of the importance of biological-physical feedbacks in rivers; increasing expectations of water quality improvements from restoration; and more effective communication between practitioners and river scientists.

2′-O Methylation of Internal Adenosine by Flavivirus NS5 Methyltransferase

Science.gov (United States)

Dong, Hongping; Chang, David C.; Hua, Maggie Ho Chia; Lim, Siew Pheng; Chionh, Yok Hian; Hia, Fabian; Lee, Yie Hou; Kukkaro, Petra; Lok, Shee-Mei; Dedon, Peter C.; Shi, Pei-Yong

2012-01-01

RNA modification plays an important role in modulating host-pathogen interaction. Flavivirus NS5 protein encodes N-7 and 2′-O methyltransferase activities that are required for the formation of 5′ type I cap (m7GpppAm) of viral RNA genome. Here we reported, for the first time, that flavivirus NS5 has a novel internal RNA methylation activity. Recombinant NS5 proteins of West Nile virus and Dengue virus (serotype 4; DENV-4) specifically methylates polyA, but not polyG, polyC, or polyU, indicating that the methylation occurs at adenosine residue. RNAs with internal adenosines substituted with 2′-O-methyladenosines are not active substrates for internal methylation, whereas RNAs with adenosines substituted with N6-methyladenosines can be efficiently methylated, suggesting that the internal methylation occurs at the 2′-OH position of adenosine. Mass spectroscopic analysis further demonstrated that the internal methylation product is 2′-O-methyladenosine. Importantly, genomic RNA purified from DENV virion contains 2′-O-methyladenosine. The 2′-O methylation of internal adenosine does not require specific RNA sequence since recombinant methyltransferase of DENV-4 can efficiently methylate RNAs spanning different regions of viral genome, host ribosomal RNAs, and polyA. Structure-based mutagenesis results indicate that K61-D146-K181-E217 tetrad of DENV-4 methyltransferase forms the active site of internal methylation activity; in addition, distinct residues within the methyl donor (S-adenosyl-L-methionine) pocket, GTP pocket, and RNA-binding site are critical for the internal methylation activity. Functional analysis using flavivirus replicon and genome-length RNAs showed that internal methylation attenuated viral RNA translation and replication. Polymerase assay revealed that internal 2′-O-methyladenosine reduces the efficiency of RNA elongation. Collectively, our results demonstrate that flavivirus NS5 performs 2′-O methylation of internal adenosine of

Euglycemia Restoration by Central Leptin in Type 1 Diabetes Requires STAT3 Signaling but Not Fast-Acting Neurotransmitter Release.

Science.gov (United States)

Xu, Yuanzhong; Chang, Jeffrey T; Myers, Martin G; Xu, Yong; Tong, Qingchun

2016-04-01

Central leptin action is sufficient to restore euglycemia in insulinopenic type 1 diabetes (T1D); however, the underlying mechanism remains poorly understood. To examine the role of intracellular signal transducer and activator of transcription 3 (STAT3) pathways, we used LepRs/s mice with disrupted leptin-phosphorylated STAT3 signaling to test the effect of central leptin on euglycemia restoration. These mice developed streptozocin-induced T1D, which was surprisingly not associated with hyperglucagonemia, a typical manifestation in T1D. Further, leptin action on euglycemia restoration was abrogated in these mice, which was associated with refractory hypercorticosteronemia. To examine the role of fast-acting neurotransmitters glutamate and γ-aminobutyric acid (GABA), two major neurotransmitters in the brain, from leptin receptor (LepR) neurons, we used mice with disrupted release of glutamate, GABA, or both from LepR neurons. Surprisingly, all mice responded normally to leptin-mediated euglycemia restoration, which was associated with expected correction from hyperglucagonemia and hyperphagia. In contrast, mice with loss of glutamate and GABA appeared to develop an additive obesity effect over those with loss of single neurotransmitter release. Thus, our study reveals that STAT3 signaling, but not fast-acting neurotransmitter release, is required for leptin action on euglycemia restoration and that hyperglucagonemia is not required for T1D. © 2016 by the American Diabetes Association. Readers may use this article as long as the work is properly cited, the use is educational and not for profit, and the work is not altered.

Implementation of the Save and Restoration application for KOMAC operation

Energy Technology Data Exchange (ETDEWEB)

Kim, Jae-Ha; Song, Young-Gi; Kwon, Hyeok-Jung; Cho, Yong-Sub [Korea Atomic Energy Research Institute, Gyeongju (Korea, Republic of)

2016-10-15

KOMAC has been operating a 100 MeV proton linear Accelerator. There are about 10,000 PVs for operating the 100 MeV proton linac. It is important to archive the operating parameters for operating beam lines and machine study. The parameters are reported manually and with screenshot. There not fixed reporting type so it is difficult to compare archived data. To improve and compensate the reporting system, a Save and Restoration application, which is based on JAVA has been implemented and connected with KOMAC Control system based on EPICS with JCA library. The operating data are saved in Save and Restoration Server in file type, and are restored to the required values using the saved files. This paper presents Implementation of the Save and Restoration application and its function. The group list is shown in restore page using reload button. The saved value of the PVs in group is shown as selecting a group which clients require and current values are appeared beside the restore value table to compare with saved data. The set restore button input the values in restore value table to each PV. The Save and Restore application save and restore the value of the PVs that clients require. The application is installed in client PC but data are archived in save and restore server in file format.

Invertebrate succession on open coast coal post mining sites in response to the type of restoration

OpenAIRE

Hromádková, Šárka

2014-01-01

This review deals with development of invertebrates on sites after brown coal mining in response to the type of restoration. When the soil properties are improved, it is then necessary to mitigate negative threats such as landslides and erosion or low pH. The following is an overlap of fertile soil. Soil characteristics can be locally modified by diversifying of plantations of fast and slow growing wood species. After a succession of plants and the subsequent increase in litter layer, the dev...

Measuring energy conservation on Nova Scotia (NS) farms: A 2004 to 2011 comparison

International Nuclear Information System (INIS)

Bailey, J.A.; Duinker, P.; Amyotte, P.; Adams, M.; Khan, F.

2016-01-01

Many jurisdictions, including Nova Scotia (NS), have implemented policies and programs around energy. The NS government has targeted energy efficiency and more renewable energy as two main policy areas. The NS Department of Agriculture has taken initiative to provide support to implement energy conservation, energy efficiency and renewable energy opportunities in recent years but have these programs and policies been effective? A baseline energy use survey was conducted in 2005 and responses from mail surveys in 2012 (n = 273, 11.4% response rate) were used to measure the change in NS farm energy use data reported for 2004 and 2011. There have been significant reductions in energy use on NS farms. On average, NS farmers spent $8790 on energy expenses in 2011 compared to $11,228 in 2004. Adjusting for inflation, this is a 32% decrease, despite energy commodity pricing increases beyond the inflation rate. This is likely due to a decrease in energy use and a shift from gasoline use to diesel use. By the end of 2012, 36.0% of NS farmers (more than 860) had received some level of support to evaluate their energy options. This includes 410 energy audits compared to only 36 by the end of 2005. - Highlights: • Nova Scotia farmers decreased their energy costs by 32% between 2004 and 2011. • Energy reductions were likely due to decreased energy use and a shift in fuel use. • An estimated 374 NS farms had an energy audit between 2005 and 2012.

Expression of NS1 of PPV in E.coli%猪细小病毒NS1基因的原核表达

Institute of Scientific and Technical Information of China (English)

冉旭华; 闻晓波; 孟凡; 周恩民

2007-01-01

根据GenBank发表的猪细小病毒(porcine parvovirus, PPV)中国株基因序列设计引物,通过PCR方法扩增到了PPV LJL12株NS1全长基因,将其克隆到原核表达载pET30a(+)上,成功构建原核表达载体pET30a-NS1,将其转化到大肠杆菌BL21(DE3)感受态细胞.经IPTG诱导表达后,进行SDS-PAGE和Western blot分析.SDS-PAGE电泳显示NS1在大肠杆菌中得到成功表达,重组蛋白大小约为86 ku,与预期大小相符;Western blot分析表明,该蛋白能与PPV阳性血清发生特异性反应,证明该蛋白具有良好生物学活性.NS1在大肠杆菌中成功表达,具有免疫原性,可作为鉴别诊断抗原用于PPV的临床检测.

Simulasi Kinerja Jaringan Nirkabel IEEE-802.11a dan IEEE-802.11g Menggunakan NS-2

Directory of Open Access Journals (Sweden)

Helm Fitriawan

2014-03-01

Full Text Available Wireless network uses transmission media based on radio waves. This type of networks is mainly useddue to its efficiency and mobility in data exchanging. This paper reports the modeling and simulation of wirelessnetworks based on Cisco Aironet 1130ag access point devices with IEEE 802.11a and IEEE 802.11g standards. Themodeling and simulation are performed using network simulator version 2 (NS-2 that is installed on operationsystem Linux Ubuntu v.10.10. The NS-2 is commonly used and works well in numerous types of network simulation. From simulation, we obtain quality of service parameters by employing several simulation scenarios in terms ofnumber of nodes, distances, and packet data sizes. It can be concluded from simulation results that the IEEE 802.11gnetworks transfer data with better quality than those of IEEE 802.11a networks.  Furthermore, the IEEE 802.11gnetworks provide a higher throughput, with smaller amount of delay and packet loss percentage compared to thoseof IEEE 802.11a networks.

LHC experience with different bunch spacings in 2011 (25, 50 and 75 ns)

International Nuclear Information System (INIS)

Rumolo, G.; Iadarola, G.; Dominguez, O.; Arduini, G.; Bartosik, H.; Claudet, S.; Esteban-Mueller, J.; Roncarolo, F.; Shaposhnikova, E.; Tavian, L.

2012-01-01

LHC operation in 2011 had a smooth start in March with 75 ns beams and only one month later moved to 50 ns beam, after a successful dedicated scrubbing run. Several observables, such as pressure rise, heat load in the arcs, beam instability, emittance growth and synchronous phase shift, clearly pointed to the presence of an electron cloud inside the machine during the first days of operation with 50 ns beams. The gradual reduction of all these effects, and their eventual disappearance, over the days of the scrubbing run, indicated electron cloud mitigation and allowed physics production to shift to 50 ns beams. Up to the end of the run the quality of the 50 ns beams was increased by regular stages (first lower transverse emittances, then higher intensities), so that these beams could provide steadily improving peak luminosities. Furthermore, five MD sessions with 25 ns beams took place in the period June-October, but the quality of these beams was always deteriorated by severe electron cloud effects. However, a clear improvement was noticed also with the 25 ns runs. An estimation of the present state of conditioning of the machine and the required scrubbing time can be inferred from electron cloud simulations compared with measured data. (authors)

Dresden 1 Radiation Level Reduction Program. Intergranular corrosion tests of sensitized Type-304 stainless steel in Dow NS-1, and stress corrosion cracking tests of Type-304 stainless steel and carbon and low alloy steels in Dow copper rinse solution

International Nuclear Information System (INIS)

Walker, W.L.

1978-09-01

Corrosion tests were performed to evaluate the extent of intergranular attack on sensitized Type-304 stainless steel by a proprietary Dow Chemical solvent, NS-1, which is to be used in the chemical cleaning of the Dresden 1 primary system. In addition, tests were performed to evaluate stress corrosion cracking of sensitized Type-304 stainless steel and post-weld heat-treated ASTM A336-F1, A302-B, and A106-B carbon and low alloy steels in a solution to be used to remove residual metallic copper from the Dresden 1 primary system surfaces following the chemical cleaning. No evidence of deleterious corrosion was observed in either set of tests

Utility of dengue NS1 antigen rapid diagnostic test for use in difficult to reach areas and its comparison with dengue NS1 ELISA and qRT-PCR.

Science.gov (United States)

Shukla, Mohan K; Singh, Neeru; Sharma, Ravendra K; Barde, Pradip V

2017-07-01

The objective of this study was to demonstrate the utility of dengue virus (DENV) non structural protein 1 (NS1) based rapid diagnostic test (RDT) for use in tribal and difficult to reach areas for early dengue (DEN) diagnosis in acute phase patients and evaluate its sensitivity and specificity against DENV NS1 enzyme linked immune sorbent assay (ELISA) and real time reverse transcriptase polymerase chain reaction (qRT-PCR). The DENV NS1 RDT was used for preliminary diagnosis during outbreaks in difficult to reach rural and tribal areas. The diagnosis was confirmed by DENV NS1 ELISA in the laboratory. The samples were also tested and serotyped by qRT-PCR. The results were evaluated using statistical tests. The DENV NS1 RDT showed 99.2% sensitivity and 96.0% specificity when analyzed using DENV NS1 ELISA as standard. The specificity and sensitivity of the RDT when compared with qRT-PCR was 93.6% and 91.1%, respectively. The serotype specific evaluation showed more than 90% sensitivity and specificity for DENV-1, 2, and 3. The RDT proved a good diagnostic tool in difficult to reach rural and tribal areas. Further evaluation studies with different commercially available RDTs in different field conditions are essential, that will help clinicians and patients for treatment and programme managers for timely intervention. © 2017 Wiley Periodicals, Inc.

H-NS Facilitates Sequence Diversification of Horizontally Transferred DNAs during Their Integration in Host Chromosomes.

Directory of Open Access Journals (Sweden)

Koichi Higashi

2016-01-01

Full Text Available Bacteria can acquire new traits through horizontal gene transfer. Inappropriate expression of transferred genes, however, can disrupt the physiology of the host bacteria. To reduce this risk, Escherichia coli expresses the nucleoid-associated protein, H-NS, which preferentially binds to horizontally transferred genes to control their expression. Once expression is optimized, the horizontally transferred genes may actually contribute to E. coli survival in new habitats. Therefore, we investigated whether and how H-NS contributes to this optimization process. A comparison of H-NS binding profiles on common chromosomal segments of three E. coli strains belonging to different phylogenetic groups indicated that the positions of H-NS-bound regions have been conserved in E. coli strains. The sequences of the H-NS-bound regions appear to have diverged more so than H-NS-unbound regions only when H-NS-bound regions are located upstream or in coding regions of genes. Because these regions generally contain regulatory elements for gene expression, sequence divergence in these regions may be associated with alteration of gene expression. Indeed, nucleotide substitutions in H-NS-bound regions of the ybdO promoter and coding regions have diversified the potential for H-NS-independent negative regulation among E. coli strains. The ybdO expression in these strains was still negatively regulated by H-NS, which reduced the effect of H-NS-independent regulation under normal growth conditions. Hence, we propose that, during E. coli evolution, the conservation of H-NS binding sites resulted in the diversification of the regulation of horizontally transferred genes, which may have facilitated E. coli adaptation to new ecological niches.

H-NS Facilitates Sequence Diversification of Horizontally Transferred DNAs during Their Integration in Host Chromosomes.

Science.gov (United States)

Higashi, Koichi; Tobe, Toru; Kanai, Akinori; Uyar, Ebru; Ishikawa, Shu; Suzuki, Yutaka; Ogasawara, Naotake; Kurokawa, Ken; Oshima, Taku

2016-01-01

Bacteria can acquire new traits through horizontal gene transfer. Inappropriate expression of transferred genes, however, can disrupt the physiology of the host bacteria. To reduce this risk, Escherichia coli expresses the nucleoid-associated protein, H-NS, which preferentially binds to horizontally transferred genes to control their expression. Once expression is optimized, the horizontally transferred genes may actually contribute to E. coli survival in new habitats. Therefore, we investigated whether and how H-NS contributes to this optimization process. A comparison of H-NS binding profiles on common chromosomal segments of three E. coli strains belonging to different phylogenetic groups indicated that the positions of H-NS-bound regions have been conserved in E. coli strains. The sequences of the H-NS-bound regions appear to have diverged more so than H-NS-unbound regions only when H-NS-bound regions are located upstream or in coding regions of genes. Because these regions generally contain regulatory elements for gene expression, sequence divergence in these regions may be associated with alteration of gene expression. Indeed, nucleotide substitutions in H-NS-bound regions of the ybdO promoter and coding regions have diversified the potential for H-NS-independent negative regulation among E. coli strains. The ybdO expression in these strains was still negatively regulated by H-NS, which reduced the effect of H-NS-independent regulation under normal growth conditions. Hence, we propose that, during E. coli evolution, the conservation of H-NS binding sites resulted in the diversification of the regulation of horizontally transferred genes, which may have facilitated E. coli adaptation to new ecological niches.

ns-2 extension to simulate localization system in wireless sensor networks

CSIR Research Space (South Africa)

Abu-Mahfouz, Adnan M

2011-09-01

Full Text Available The ns-2 network simulator is one of the most widely used tools by researchers to investigate the characteristics of wireless sensor networks. Academic papers focus on results and rarely include details of how ns-2 simulations are implemented...

Clinical evaluation of combined surgical/ restorative treatment of gingival recession-type defects using different restorative materials: A randomized clinical trial

Directory of Open Access Journals (Sweden)

Sila Cagri Isler

2018-03-01

Full Text Available Background/purpose: An ideal therapeutic procedure for the treatment of gingival recession associated with an NCCL has presented a challenge to clinicians. Various dental materials and surgical approaches have been used to manage gingival recessions associated with NCCLs for the most predictable combined surgical/restorative treatment. The objective of this study was to evaluate the treatment of gingival recessions associated with non-carious cervical lesions (NCCL using a modified coronally advanced flap (MCAF in combination with a connective tissue graft (CTG on restored root surfaces. Materials and methods: Twenty-three systemically healthy subjects, who were positive for the presence of three cervical lesions associated with gingival recessions in three different adjacent teeth, were enrolled in the study. The NCCL were each restored prior to surgery by using one of three different materials: nanofilled composite resin (NCR, resin-modified glass ionomer cement (RMGI or giomer. The gingival recession defects were treated by CTG. Results: Inter-group differences were not statistically significant for probing depth (PD, relative recession height (rRH, relative clinical attachment level (rCAL, keratinized tissue width (KTW or keratinized tissue thickness (KTT (p > 0.05 among the groups at any time. The mean percentage of defect coverage was 71.18 ± 23.16% for NCR + CTG group; 71.33 ± 22.33% for RMGI + CTG group; and 64.23 ± 20.33% for giomer + CTG group at 1 year postoperatively (p > 0.05. Conclusion: The combined surgical/restorative treatments provided successful clinical results. Giomer + CTG may be less effective compared to other groups for treatment of gingival recession associated with NCCL. Keywords: cervical lesions, connective tissue grafts, gingival recession, restorative materials

Spiky strings on AdS3 x S3 with NS-NS flux

CERN Document Server

Banerjee, Aritra; Pradhan, Pabitra M.

2014-01-01

We study rigidly rotating strings in the background of AdS3 x S3 with Neveu-Schwarz (NS) fluxes. We find two interesting limiting cases corresponding to the known giant magnon and the new single spike solution of strings in the above background and write down the dispersion relations among various conserved charges. We use proper regularization to find the correct relations among them. We further study the circular and infinite spiky strings on AdS and study their properties.

Adapted J6/JFH1-based Hepatitis C virus recombinants with genotype-specific NS4A show similar efficacies against lead protease inhibitors, alpha interferon, and a putative NS4A inhibitor

DEFF Research Database (Denmark)

Gottwein, Judith M; Jensen, Sanne B; Serre, Stéphanie B N

2013-01-01

To facilitate studies of hepatitis C virus (HCV) NS4A, we aimed at developing J6/JFH1-based recombinants with genotype 1- to 7-specific NS4A proteins. We developed efficient culture systems expressing NS4A proteins of genotypes (isolates) 1a (H77 and TN), 1b (J4), 2a (J6), 4a (ED43), 5a (SA13), 6a...... (HK6a), and 7a (QC69), with peak infectivity titers of ∼3.5 to 4.5 log10 focus-forming units per ml. Except for genotype 2a (J6), growth depended on adaptive mutations identified in long-term culture. Genotype 1a, 1b, and 4a recombinants were adapted by amino acid substitutions F772S (p7) and V1663A...... (NS4A), while 5a, 6a, and 7a recombinants required additional substitutions in the NS3 protease and/or NS4A. We demonstrated applicability of the developed recombinants for study of antivirals. Genotype 1 to 7 NS4A recombinants showed similar responses to the protease inhibitors telaprevir (VX-950...

Electron paramagnetic resonance of the ns1 centers in crystals

International Nuclear Information System (INIS)

Nistor, S.V.; Ursu, I.

1993-05-01

The results of the EPR studies concerning the paramagnetic centers with ns 1 (N=n>2) outer electronic configuration contained in crystals are reviewed. Such centers, with 2 S 1/2 ground state, are produced by electron trapping at impurities of the IB and IIB group or by hole trapping at impurities of the IIIB and IV group of elements. The production and structural properties of such centers consisting of ns 1 ions (atoms) at various sites in the crystal lattice with different configurations of neighbouring defects are discussed in connection with their EPR characteristics. Tables containing the spin Hamiltonian parameters of all ns 1 centers reported in the literature until the end of year 1992 are given. (author). 146 refs, 14 tabs

Ecological and Social Dimensions of Ecosystem Restoration in the Nordic Countries

Directory of Open Access Journals (Sweden)

Dagmar Hagen

2013-12-01

Full Text Available An international overview of the extent and type of ecological restoration can offer new perspectives for understanding, planning, and implementation. The Nordic countries, with a great range of natural conditions but historically similar social and political structures, provide an opportunity to compare restoration approaches and efforts across borders. The aim of this study was to explore variation in ecological restoration using the Nordic countries as an example. We used recent national assessments and expert evaluations of ecological restoration. Restoration efforts differed among countries: forest and peatland restoration was most common in Finland, freshwater restoration was most common in Sweden, restoration of natural heathlands and grasslands was most common in Iceland, restoration of natural and semi-cultural heathlands was most common in Norway, and restoration of cultural ecosystems, mainly abandoned agricultural land, was most common in Denmark. Ecological restoration currently does not occur on the Faroe Islands. Economic incentives influence ecological restoration and depend on laws and policies in each country. Our analyses suggest that habitat types determine the methods of ecological restoration, whereas socio-economic drivers are more important for the decisions concerning the timing and location of restoration. To improve the understanding, planning, and implementation of ecological restoration, we advocate increased cooperation and knowledge sharing across disciplines and among countries, both in the Nordic countries and internationally. An obvious advantage of such cooperation is that a wider range of experiences from different habitats and different socio-economic conditions becomes available and thus provides a more solid basis for developing practical solutions for restoration methods and policies.

In Vitro Antiviral Activity and Resistance Profile Characterization of the Hepatitis C Virus NS5A Inhibitor Ledipasvir.

Science.gov (United States)

Cheng, Guofeng; Tian, Yang; Doehle, Brian; Peng, Betty; Corsa, Amoreena; Lee, Yu-Jen; Gong, Ruoyu; Yu, Mei; Han, Bin; Xu, Simin; Dvory-Sobol, Hadas; Perron, Michel; Xu, Yili; Mo, Hongmei; Pagratis, Nikos; Link, John O; Delaney, William

2016-01-11

Ledipasvir (LDV; GS-5885), a component of Harvoni (a fixed-dose combination of LDV with sofosbuvir [SOF]), is approved to treat chronic hepatitis C virus (HCV) infection. Here, we report key preclinical antiviral properties of LDV, including in vitro potency, in vitro resistance profile, and activity in combination with other anti-HCV agents. LDV has picomolar antiviral activity against genotype 1a and genotype 1b replicons with 50% effective concentration (EC50) values of 0.031 nM and 0.004 nM, respectively. LDV is also active against HCV genotypes 4a, 4d, 5a, and 6a with EC50 values of 0.11 to 1.1 nM. LDV has relatively less in vitro antiviral activity against genotypes 2a, 2b, 3a, and 6e, with EC50 values of 16 to 530 nM. In vitro resistance selection with LDV identified the single Y93H and Q30E resistance-associated variants (RAVs) in the NS5A gene; these RAVs were also observed in patients after a 3-day monotherapy treatment. In vitro antiviral combination studies indicate that LDV has additive to moderately synergistic antiviral activity when combined with other classes of HCV direct-acting antiviral (DAA) agents, including NS3/4A protease inhibitors and the nucleotide NS5B polymerase inhibitor SOF. Furthermore, LDV is active against known NS3 protease and NS5B polymerase inhibitor RAVs with EC50 values equivalent to those for the wild type. Copyright © 2016, American Society for Microbiology. All Rights Reserved.

25 CFR 309.7 - How should a seller disclose the nature and degree of Indian labor when selling, offering, or...

Science.gov (United States)

2010-04-01

... Indian labor when selling, offering, or displaying art and craft work for sale? 309.7 Section 309.7 Indians INDIAN ARTS AND CRAFTS BOARD, DEPARTMENT OF THE INTERIOR PROTECTION OF INDIAN ARTS AND CRAFTS..., or displaying art and craft work for sale? The Indian Arts and Crafts Act is a truth-in-marketing law...

Identification of Hydroxyanthraquinones as Novel Inhibitors of Hepatitis C Virus NS3 Helicase

Science.gov (United States)

Furuta, Atsushi; Tsubuki, Masayoshi; Endoh, Miduki; Miyamoto, Tatsuki; Tanaka, Junichi; Abdus Salam, Kazi; Akimitsu, Nobuyoshi; Tani, Hidenori; Yamashita, Atsuya; Moriishi, Kohji; Nakakoshi, Masamichi; Sekiguchi, Yuji; Tsuneda, Satoshi; Noda, Naohiro

2015-01-01

Hepatitis C virus (HCV) is an important etiological agent of severe liver diseases, including cirrhosis and hepatocellular carcinoma. The HCV genome encodes nonstructural protein 3 (NS3) helicase, which is a potential anti-HCV drug target because its enzymatic activity is essential for viral replication. Some anthracyclines are known to be NS3 helicase inhibitors and have a hydroxyanthraquinone moiety in their structures; mitoxantrone, a hydroxyanthraquinone analogue, is also known to inhibit NS3 helicase. Therefore, we hypothesized that the hydroxyanthraquinone moiety alone could also inhibit NS3 helicase. Here, we performed a structure–activity relationship study on a series of hydroxyanthraquinones by using a fluorescence-based helicase assay. Hydroxyanthraquinones inhibited NS3 helicase with IC50 values in the micromolar range. The inhibitory activity varied depending on the number and position of the phenolic hydroxyl groups, and among different hydroxyanthraquinones examined, 1,4,5,8-tetrahydroxyanthraquinone strongly inhibited NS3 helicase with an IC50 value of 6 µM. Furthermore, hypericin and sennidin A, which both have two hydroxyanthraquinone-like moieties, were found to exert even stronger inhibition with IC50 values of 3 and 0.8 µM, respectively. These results indicate that the hydroxyanthraquinone moiety can inhibit NS3 helicase and suggest that several key chemical structures are important for the inhibition. PMID:26262613

Identification of Hydroxyanthraquinones as Novel Inhibitors of Hepatitis C Virus NS3 Helicase

Directory of Open Access Journals (Sweden)

Atsushi Furuta

2015-08-01

Full Text Available Hepatitis C virus (HCV is an important etiological agent of severe liver diseases, including cirrhosis and hepatocellular carcinoma. The HCV genome encodes nonstructural protein 3 (NS3 helicase, which is a potential anti-HCV drug target because its enzymatic activity is essential for viral replication. Some anthracyclines are known to be NS3 helicase inhibitors and have a hydroxyanthraquinone moiety in their structures; mitoxantrone, a hydroxyanthraquinone analogue, is also known to inhibit NS3 helicase. Therefore, we hypothesized that the hydroxyanthraquinone moiety alone could also inhibit NS3 helicase. Here, we performed a structure–activity relationship study on a series of hydroxyanthraquinones by using a fluorescence-based helicase assay. Hydroxyanthraquinones inhibited NS3 helicase with IC50 values in the micromolar range. The inhibitory activity varied depending on the number and position of the phenolic hydroxyl groups, and among different hydroxyanthraquinones examined, 1,4,5,8-tetrahydroxyanthraquinone strongly inhibited NS3 helicase with an IC50 value of 6 µM. Furthermore, hypericin and sennidin A, which both have two hydroxyanthraquinone-like moieties, were found to exert even stronger inhibition with IC50 values of 3 and 0.8 µM, respectively. These results indicate that the hydroxyanthraquinone moiety can inhibit NS3 helicase and suggest that several key chemical structures are important for the inhibition.

Decreasing the infusion rate reduces the proarrhythmic risk of NS-7

DEFF Research Database (Denmark)

Detre, Elke; Thomsen, Morten Bækgaard; Beekman, Jet D

2005-01-01

1 The rate of infusion has been suggested to be important for drug-induced torsades de pointes (TdP) arrhythmias. We investigated the repolarisation-prolonging effects and proarrhythmic properties of NS-7, a neuroprotective drug in development, using two different infusion rates. 2 A fast (5 min...... intravenously (i.v.)) escalating dosing regimen (0.3 and 3.0 mg kg(-1), n=4) of NS-7 was investigated in anaesthetised control dogs in sinus rhythm (SR). This was compared to a slow infusion (60 min i.v.) of one dose (3.0 mg kg(-1), n=4) NS-7. The similar dosing regimens were investigated in anaesthetised dogs...... with chronic, complete AV block (CAVB), an animal model of TdP (n=6). 3 No electrophysiological effects were seen after 0.3 mg kg(-1) NS-7. Fast infusion of 3.0 mg kg(-1) caused prolongation of repolarisation, for example, heart rate corrected QT interval (QT(c)): in SR: 6+/-1%; in CAVB: 10+/-7%, which...

Hepatitis C virus NS4B carboxy terminal domain is a membrane binding domain

Directory of Open Access Journals (Sweden)

Spaan Willy JM

2009-05-01

Full Text Available Abstract Background Hepatitis C virus (HCV induces membrane rearrangements during replication. All HCV proteins are associated to membranes, pointing out the importance of membranes for HCV. Non structural protein 4B (NS4B has been reported to induce cellular membrane alterations like the membranous web. Four transmembrane segments in the middle of the protein anchor NS4B to membranes. An amphipatic helix at the amino-terminus attaches to membranes as well. The carboxy-terminal domain (CTD of NS4B is highly conserved in Hepaciviruses, though its function remains unknown. Results A cytosolic localization is predicted for the NS4B-CTD. However, using membrane floatation assays and immunofluorescence, we now show targeting of the NS4B-CTD to membranes. Furthermore, a profile-profile search, with an HCV NS4B-CTD multiple sequence alignment, indicates sequence similarity to the membrane binding domain of prokaryotic D-lactate dehydrogenase (d-LDH. The crystal structure of E. coli d-LDH suggests that the region similar to NS4B-CTD is located in the membrane binding domain (MBD of d-LDH, implying analogy in membrane association. Targeting of d-LDH to membranes occurs via electrostatic interactions of positive residues on the outside of the protein with negative head groups of lipids. To verify that anchorage of d-LDH MBD and NS4B-CTD is analogous, NS4B-CTD mutants were designed to disrupt these electrostatic interactions. Membrane association was confirmed by swopping the membrane contacting helix of d-LDH with the corresponding domain of the 4B-CTD. Furthermore, the functionality of these residues was tested in the HCV replicon system. Conclusion Together these data show that NS4B-CTD is associated to membranes, similar to the prokaryotic d-LDH MBD, and is important for replication.

Characterization of Pressure Transients Generated by Nanosecond Electrical Pulse (nsEP) Exposure

Science.gov (United States)

Roth, Caleb C.; Barnes Jr., Ronald A.; Ibey, Bennett L.; Beier, Hope T.; Christopher Mimun, L.; Maswadi, Saher M.; Shadaram, Mehdi; Glickman, Randolph D.

2015-01-01

The mechanism(s) responsible for the breakdown (nanoporation) of cell plasma membranes after nanosecond pulse (nsEP) exposure remains poorly understood. Current theories focus exclusively on the electrical field, citing electrostriction, water dipole alignment and/or electrodeformation as the primary mechanisms for pore formation. However, the delivery of a high-voltage nsEP to cells by tungsten electrodes creates a multitude of biophysical phenomena, including electrohydraulic cavitation, electrochemical interactions, thermoelastic expansion, and others. To date, very limited research has investigated non-electric phenomena occurring during nsEP exposures and their potential effect on cell nanoporation. Of primary interest is the production of acoustic shock waves during nsEP exposure, as it is known that acoustic shock waves can cause membrane poration (sonoporation). Based on these observations, our group characterized the acoustic pressure transients generated by nsEP and determined if such transients played any role in nanoporation. In this paper, we show that nsEP exposures, equivalent to those used in cellular studies, are capable of generating high-frequency (2.5 MHz), high-intensity (>13 kPa) pressure transients. Using confocal microscopy to measure cell uptake of YO-PRO®-1 (indicator of nanoporation of the plasma membrane) and changing the electrode geometry, we determined that acoustic waves alone are not responsible for poration of the membrane. PMID:26450165

Characterization of Pressure Transients Generated by Nanosecond Electrical Pulse (nsEP) Exposure.

Science.gov (United States)

Roth, Caleb C; Barnes, Ronald A; Ibey, Bennett L; Beier, Hope T; Christopher Mimun, L; Maswadi, Saher M; Shadaram, Mehdi; Glickman, Randolph D

2015-10-09

The mechanism(s) responsible for the breakdown (nanoporation) of cell plasma membranes after nanosecond pulse (nsEP) exposure remains poorly understood. Current theories focus exclusively on the electrical field, citing electrostriction, water dipole alignment and/or electrodeformation as the primary mechanisms for pore formation. However, the delivery of a high-voltage nsEP to cells by tungsten electrodes creates a multitude of biophysical phenomena, including electrohydraulic cavitation, electrochemical interactions, thermoelastic expansion, and others. To date, very limited research has investigated non-electric phenomena occurring during nsEP exposures and their potential effect on cell nanoporation. Of primary interest is the production of acoustic shock waves during nsEP exposure, as it is known that acoustic shock waves can cause membrane poration (sonoporation). Based on these observations, our group characterized the acoustic pressure transients generated by nsEP and determined if such transients played any role in nanoporation. In this paper, we show that nsEP exposures, equivalent to those used in cellular studies, are capable of generating high-frequency (2.5 MHz), high-intensity (>13 kPa) pressure transients. Using confocal microscopy to measure cell uptake of YO-PRO®-1 (indicator of nanoporation of the plasma membrane) and changing the electrode geometry, we determined that acoustic waves alone are not responsible for poration of the membrane.

Discovery of Dengue Virus NS4B Inhibitors

Science.gov (United States)

Wang, Qing-Yin; Dong, Hongping; Zou, Bin; Karuna, Ratna; Wan, Kah Fei; Zou, Jing; Susila, Agatha; Yip, Andy; Shan, Chao; Yeo, Kim Long; Xu, Haoying; Ding, Mei; Chan, Wai Ling; Gu, Feng; Seah, Peck Gee; Liu, Wei; Lakshminarayana, Suresh B.; Kang, CongBao; Lescar, Julien; Blasco, Francesca; Smith, Paul W.

2015-01-01

ABSTRACT The four serotypes of dengue virus (DENV-1 to -4) represent the most prevalent mosquito-borne viral pathogens in humans. No clinically approved vaccine or antiviral is currently available for DENV. Here we report a spiropyrazolopyridone compound that potently inhibits DENV both in vitro and in vivo. The inhibitor was identified through screening of a 1.8-million-compound library by using a DENV-2 replicon assay. The compound selectively inhibits DENV-2 and -3 (50% effective concentration [EC50], 10 to 80 nM) but not DENV-1 and -4 (EC50, >20 μM). Resistance analysis showed that a mutation at amino acid 63 of DENV-2 NS4B (a nonenzymatic transmembrane protein and a component of the viral replication complex) could confer resistance to compound inhibition. Genetic studies demonstrate that variations at amino acid 63 of viral NS4B are responsible for the selective inhibition of DENV-2 and -3. Medicinal chemistry improved the physicochemical properties of the initial “hit” (compound 1), leading to compound 14a, which has good in vivo pharmacokinetics. Treatment of DENV-2-infected AG129 mice with compound 14a suppressed viremia, even when the treatment started after viral infection. The results have proven the concept that inhibitors of NS4B could potentially be developed for clinical treatment of DENV infection. Compound 14a represents a potential preclinical candidate for treatment of DENV-2- and -3-infected patients. IMPORTANCE Dengue virus (DENV) threatens up to 2.5 billion people and is now spreading in many regions in the world where it was not previously endemic. While there are several promising vaccine candidates in clinical trials, approved vaccines or antivirals are not yet available. Here we describe the identification and characterization of a spiropyrazolopyridone as a novel inhibitor of DENV by targeting the viral NS4B protein. The compound potently inhibits two of the four serotypes of DENV (DENV-2 and -3) both in vitro and in vivo. Our

Rapid detection of SNP (c.309T>G in the MDM2 gene by the Duplex SmartAmp method.

Directory of Open Access Journals (Sweden)

Yasuaki Enokida

Full Text Available BACKGROUND: Genetic polymorphisms in the human MDM2 gene are suggested to be a tumor susceptibility marker and a prognostic factor for cancer. It has been reported that a single nucleotide polymorphism (SNP c.309T>G in the MDM2 gene attenuates the tumor suppressor activity of p53 and accelerates tumor formation in humans. METHODOLOGY: In this study, to detect the SNP c.309T>G in the MDM2 gene, we have developed a new SNP detection method, named "Duplex SmartAmp," which enabled us to simultaneously detect both 309T and 309G alleles in one tube. To develop this new method, we introduced new primers i.e., nBP and oBPs, as well as two different fluorescent dyes that separately detect those genetic polymorphisms. RESULTS AND CONCLUSIONS: By the Duplex SmartAmp method, the genetic polymorphisms of the MDM2 gene were detected directly from a small amount of genomic DNA or blood samples. We used 96 genomic DNA and 24 blood samples to validate the Duplex SmartAmp by comparison with results of the conventional PCR-RFLP method; consequently, the Duplex SmartAmp results agreed totally with those of the PCR-RFLP method. Thus, the new SNP detection method is considered useful for detecting the SNP c.309T>G in the MDM2 gene so as to judge cancer susceptibility against some cellular stress in the clinical setting, and also to handle a large number of samples and enable rapid clinical diagnosis.

Quantum restoration of broken symmetry in onedimensional loop ...

Indian Academy of Sciences (India)

Home; Journals; Pramana – Journal of Physics; Volume 82; Issue 6. Quantum restoration of broken symmetry in ... Keywords. Non-local transformation; broken symmetry; sine-Gordon; sech interaction. ... A specific type of classically broken symmetry is restored in quantum theory. One-dimensional sine-Gordon system and ...

Influence of Si content on the intergranular corrosion of SUS 309L stainless steels

International Nuclear Information System (INIS)

Lin, D.-Y.; Chang, T.-C.

2003-01-01

The effect of Si content on the intergranular corrosion resistance of SUS 309L stainless steels was investigated by 10 wt.% oxalic acid test, 65 wt.% boiling nitric acid test, double loop electrochemical potential reactivation (DLEPR) method, optical microscope (OM) and scanning electronic microscope (SEM). A maximum corrosion rate, weight loss of 2.80 g m -1 h, was obtained when SUS 309L stainless steel containing 0.73 wt.% Si was subjected to heat treatment at 800 deg. C for 1 h. It shows that the Cr depletion zone formed due to σ phase precipitation. The same result is obtained in DLEPR test and the ditch microstructure after oxalic test was found in samples that showed the minimum corrosion rate

Experimental voyages of N.S. Mutsu

International Nuclear Information System (INIS)

Ochiai, Masaaki

1993-01-01

The first Japanese nuclear ship, N.S. MUTSU was commissioned by the Government on February 14 1991, after power up test and official sea trial with much success. Four experimental voyages of the ship were taken in the Pacific Ocean from March to December 1991 to study the performance of the nuclear power plant when it was influenced by marine conditions. In such an environment, incessant ship motion and load changes due to wave, wind, maneuvering, etc. are experienced. The ship sailed for a total of 110 days, a total distance of 64,180 km and for a total reactor operating time of 2,321 hours. Integrated reactor power was about 2,250 efph (effective full power hour) including that during the power up test. Zero power experiments were done again in Jan. 1992 to measure the core characteristics after finishing all the N.S. MUTSU plant operation program. Thus the most essential parts in the R ampersand D program on N.S. MUTSU was completed. The voyages demonstrated that the nuclear power plant worked well in any case and that the plant system had excellent capability as a marine engine. The data acquired through the experiments will contribute to the research and development program of the advanced marine reactor in Japan Atomic Energy Research Institute. This paper describes the technical informations obtained through the experimental voyages, such as load following abilities, system performances during the high sea sailing and the tropical sea sailing and behavior of system parameters accompanied with steering. The latest technical results yielded by the program are also summarized here

New NS varieties of six-rowed winter barley

Directory of Open Access Journals (Sweden)

Pržulj Novo

2009-01-01

Full Text Available The paper describes the characteristics of several new NS varieties of winter six-rowed barley released in Serbia between 2004 and 2007. These are Somborac, Ozren, Javor, Novosadski 773, Sremac and Leotar. In the official variety trials in the country, all six of these varieties outyielded the check variety, and the margins were as follows: Somborac - 3.4%, Ozren - 5.0%, Javor - 7.3%, Novosadski 773 - 3.4%, Sremac - 7.4%, and Leotar - 7.2%. Yield levels in absolute terms depended on the variety as well as year. All six-rowed NS varieties headed earlier than the check and had better resistance to lodging than the check has. The test weight of the new varieties was 70.2-73.8 kg/hl and the 1000-grain weight 33.4-50.2 g. The cellulose content was 4.4-4.8%, the fat content 1.4%, and the protein content 13.3-14.6%. The high variability of the new NS varieties of winter six-rowed barley makes it possible to choose the most suitable genotype for each barley-growing area in the country. .

31 CFR 309.7 - Tenders; submission through Federal Reserve Banks and branches and to the Bureau of the Public Debt.

Science.gov (United States)

2010-07-01

... Reserve Banks and branches and to the Bureau of the Public Debt. 309.7 Section 309.7 Money and Finance... Reserve Banks and branches and to the Bureau of the Public Debt. Tenders in response to any such public notice will be received at the Federal Reserve Banks, or Branches thereof and at the Bureau of the Public...

Direct binding of ledipasvir to HCV NS5A: mechanism of resistance to an HCV antiviral agent.

Directory of Open Access Journals (Sweden)

Hyock Joo Kwon

Full Text Available Ledipasvir, a direct acting antiviral agent (DAA targeting the Hepatitis C Virus NS5A protein, exhibits picomolar activity in replicon cells. While its mechanism of action is unclear, mutations that confer resistance to ledipasvir in HCV replicon cells are located in NS5A, suggesting that NS5A is the direct target of ledipasvir. To date co-precipitation and cross-linking experiments in replicon or NS5A transfected cells have not conclusively shown a direct, specific interaction between NS5A and ledipasvir. Using recombinant, full length NS5A, we show that ledipasvir binds directly, with high affinity and specificity, to NS5A. Ledipasvir binding to recombinant NS5A is saturable with a dissociation constant in the low nanomolar range. A mutant form of NS5A (Y93H that confers resistance to ledipasvir shows diminished binding to ledipasvir. The current study shows that ledipasvir inhibits NS5A through direct binding and that resistance to ledipasvir is the result of a reduction in binding affinity to NS5A mutants.

[Dental implant restoration abutment selection].

Science.gov (United States)

Bin, Shi; Hao, Zeng

2017-04-01

An increasing number of implant restoration abutment types are produced with the rapid development of dental implantology. Although various abutments can meet different clinical demands, the selection of the appropriate abutment is both difficult and confusing. This article aims to help clinicians select the appropriate abutment by describing abutment design, types, and selection criteria.

Designing cyclopentapeptide inhibitor as potential antiviral drug for dengue virus ns5 methyltransferase.

Science.gov (United States)

Idrus, Syarifuddin; Tambunan, Usman Sumo Friend; Zubaidi, Ahmad Ardilla

2012-01-01

NS5 methyltransferase (Mtase) has a crucial role in the replication of dengue virus. There are two active sites on NS5 Mtase i.e., SAM and RNA-cap binding sites. Inhibition of the NS5 Mtase activity is expected to prevent the propagation of dengue virus. This study was conducted to design cyclic peptide ligands as enzyme inhibitors of dengue virus NS5 Mtase through computational approach. Cyclopentapeptides were designed as ligand of SAM binding site as much as 1635 and 736 cyclopentpeptides were designed as ligand of RNA-cap binding site. Interaction between ligand and NS5 Mtase has been conducted on the Docking simulation. The result shows that cyclopentapeptide CTWYC was the best peptide candidate on SAM binding site, with estimated free binding energy -30.72 kca/mol. Cyclopentapeptide CYEFC was the best peptide on RNA-cap binding site with estimated free binding energy -22.89 kcal/mol. Both peptides did not have tendency toward toxicity properties. So it is expected that both CTWYC and CYEFC ligands could be used as a potential antiviral drug candidates, which can inhibit the SAM and RNA-cap binding sites of dengue virus NS5 Mtase.

Electron Cloud Observations during LHC Operation with 25 ns Beams

CERN Document Server

Li, Kevin; Iadarola, Giovanni; Mether, Lotta; Romano, Annalisa; Rumolo, Giovanni; Schenk, Michael

2016-01-01

While during the Run 1 (2010-2012) of the Large Hadron Collider (LHC) most of the integrated luminosity was produced with 50 ns bunch spacing, for the Run 2 start-up (2015) it was decided to move to the nominal bunch spacing of 25 ns. As expected, with this beam configuration strong electron cloud effects were observed in the machine, which had to be mitigated with dedicated 'scrubbing' periods at injection energy. This enabled to start the operation with 25 ns beams at 6.5 TeV, but e-cloud effects continued to pose challenges while gradually increasing the number of circulating bunch trains. This contribution will review the encountered limitations and the mitigation measures that where put in place and will discuss possible strategies for further performance gain.

Social Science Methods Used in the RESTORE Project

Science.gov (United States)

Lynne M. Westphal; Cristy Watkins; Paul H. Gobster; Liam Heneghan; Kristen Ross; Laurel Ross; Madeleine Tudor; Alaka Wali; David H. Wise; Joanne Vining; Moira. Zellner

2014-01-01

The RESTORE (Rethinking Ecological and Social Theories of Restoration Ecology) project is an interdisciplinary, multi-institutional research endeavor funded by the National Science Foundation's Dynamics of Coupled Natural Human Systems program. The goal of the project is to understand the links between organizational type, decision making processes, and...

Naturally occurring mutations associated with resistance to HCV NS5B polymerase and NS3 protease inhibitors in treatment-naïve patients with chronic hepatitis C.

Science.gov (United States)

Costantino, Angela; Spada, Enea; Equestre, Michele; Bruni, Roberto; Tritarelli, Elena; Coppola, Nicola; Sagnelli, Caterina; Sagnelli, Evangelista; Ciccaglione, Anna Rita

2015-11-14

The detection of baseline resistance mutations to new direct-acting antivirals (DAAs) in HCV chronically infected treatment-naïve patients could be important for their management and outcome prevision. In this study, we investigated the presence of mutations, which have been previously reported to be associated with resistance to DAAs in HCV polymerase (NS5B) and HCV protease (NS3) regions, in sera of treatment-naïve patients. HCV RNA from 152 naïve patients (84 % Italian and 16 % immigrants from various countries) infected with different HCV genotypes (21,1a; 21, 1b; 2, 2a; 60, 2c; 22, 3a; 25, 4d and 1, 4k) was evaluated for sequence analysis. Amplification and sequencing of fragments in the NS5B (nt 8256-8640) and NS3 (nt 3420-3960) regions of HCV genome were carried out for 152 and 28 patients, respectively. The polymorphism C316N/H in NS5B region, associated with resistance to sofosbuvir, was detected in 9 of the 21 (43 %) analysed sequences from genotype 1b-infected patients. Naturally occurring mutations V36L, and M175L in the NS3 protease region were observed in 100 % of patients infected with subtype 2c and 4. A relevant proportion of treatment naïve genotype 1b infected patients evaluated in this study harboured N316 polymorphism and might poorly respond to sofosbuvir treatment. As sofosbuvir has been approved for treatment of HCV chronic infection in USA and Europe including Italy, pre-treatment testing for N316 polymorphism on genotype 1b naïve patients should be considered for this drug.

The Nucleoid Binding Protein H-NS Biases Genome-Wide Transposon Insertion Landscapes

Directory of Open Access Journals (Sweden)

Satoshi Kimura

2016-08-01

Full Text Available Transposon insertion sequencing (TIS; also known as TnSeq is a potent approach commonly used to comprehensively define the genetic loci that contribute to bacterial fitness in diverse environments. A key presumption underlying analyses of TIS datasets is that loci with a low frequency of transposon insertions contribute to fitness. However, it is not known whether factors such as nucleoid binding proteins can alter the frequency of transposon insertion and thus whether TIS output may systematically reflect factors that are independent of the role of the loci in fitness. Here, we investigated whether the histone-like nucleoid structuring (H-NS protein, which preferentially associates with AT-rich sequences, modulates the frequency of Mariner transposon insertion in the Vibrio cholerae genome, using comparative analysis of TIS results from wild-type (wt and Δhns V. cholerae strains. These analyses were overlaid on gene classification based on GC content as well as on extant genome-wide identification of H-NS binding loci. Our analyses revealed a significant dearth of insertions within AT-rich loci in wt V. cholerae that was not apparent in the Δhns insertion library. Additionally, we observed a striking correlation between genetic loci that are overrepresented in the Δhns insertion library relative to their insertion frequency in wt V. cholerae and loci previously found to physically interact with H-NS. Collectively, our findings reveal that factors other than genetic fitness can systematically modulate the frequency of transposon insertions in TIS studies and add a cautionary note to interpretation of TIS data, particularly for AT-rich sequences.

Evolutionary restoration of fertility in an interspecies hybrid yeast, by whole-genome duplication after a failed mating-type switch.

Directory of Open Access Journals (Sweden)

Raúl A Ortiz-Merino

2017-05-01

Full Text Available Many interspecies hybrids have been discovered in yeasts, but most of these hybrids are asexual and can replicate only mitotically. Whole-genome duplication has been proposed as a mechanism by which interspecies hybrids can regain fertility, restoring their ability to perform meiosis and sporulate. Here, we show that this process occurred naturally during the evolution of Zygosaccharomyces parabailii, an interspecies hybrid that was formed by mating between 2 parents that differed by 7% in genome sequence and by many interchromosomal rearrangements. Surprisingly, Z. parabailii has a full sexual cycle and is genetically haploid. It goes through mating-type switching and autodiploidization, followed by immediate sporulation. We identified the key evolutionary event that enabled Z. parabailii to regain fertility, which was breakage of 1 of the 2 homeologous copies of the mating-type (MAT locus in the hybrid, resulting in a chromosomal rearrangement and irreparable damage to 1 MAT locus. This rearrangement was caused by HO endonuclease, which normally functions in mating-type switching. With 1 copy of MAT inactivated, the interspecies hybrid now behaves as a haploid. Our results provide the first demonstration that MAT locus damage is a naturally occurring evolutionary mechanism for whole-genome duplication and restoration of fertility to interspecies hybrids. The events that occurred in Z. parabailii strongly resemble those postulated to have caused ancient whole-genome duplication in an ancestor of Saccharomyces cerevisiae.

Nanosecond pulsed electric fields (nsPEFs) low cost generator design using power MOSFET and Cockcroft-Walton multiplier circuit as high voltage DC source

International Nuclear Information System (INIS)

Sulaeman, M. Y.; Widita, R.

2014-01-01

Purpose: Non-ionizing radiation therapy for cancer using pulsed electric field with high intensity field has become an interesting field new research topic. A new method using nanosecond pulsed electric fields (nsPEFs) offers a novel means to treat cancer. Not like the conventional electroporation, nsPEFs able to create nanopores in all membranes of the cell, including membrane in cell organelles, like mitochondria and nucleus. NsPEFs will promote cell death in several cell types, including cancer cell by apoptosis mechanism. NsPEFs will use pulse with intensity of electric field higher than conventional electroporation, between 20–100 kV/cm and with shorter duration of pulse than conventional electroporation. NsPEFs requires a generator to produce high voltage pulse and to achieve high intensity electric field with proper pulse width. However, manufacturing cost for creating generator that generates a high voltage with short duration for nsPEFs purposes is highly expensive. Hence, the aim of this research is to obtain the low cost generator design that is able to produce a high voltage pulse with nanosecond width and will be used for nsPEFs purposes. Method: Cockcroft-Walton multiplier circuit will boost the input of 220 volt AC into high voltage DC around 1500 volt and it will be combined by a series of power MOSFET as a fast switch to obtain a high voltage with nanosecond pulse width. The motivation using Cockcroft-Walton multiplier is to acquire a low-cost high voltage DC generator; it will use capacitors and diodes arranged like a step. Power MOSFET connected in series is used as voltage divider to share the high voltage in order not to damage them. Results: This design is expected to acquire a low-cost generator that can achieve the high voltage pulse in amount of −1.5 kV with falltime 3 ns and risetime 15 ns into a 50Ω load that will be used for nsPEFs purposes. Further detailed on the circuit design will be explained at presentation

Restoration of Muscle Mitochondrial Function and Metabolic Flexibility in Type 2 Diabetes by Exercise Training Is Paralleled by Increased Myocellular Fat Storage and Improved Insulin Sensitivity

NARCIS (Netherlands)

Meex, R.C.R.; Schrauwen-Hinderling, V.B.; Moonen-Kornips, E.; Schaart, G.; Mensink, M.R.; Phielix, E.; Weijer, van de T.; Sels, J.P.; Schrauwen, P.; Hesselink, M.K.C.

2010-01-01

OBJECTIVE-Mitochondrial dysfunction and fat accumulation in skeletal muscle (increased intramyocellular lipid [IMCL]) have been linked to development of type 2 diabetes. We examined whether exercise training could restore mitochondrial function and insulin sensitivity in patients with type 2

X-ray structure of the pestivirus NS3 helicase and its conformation in solution.

Science.gov (United States)

Tortorici, M Alejandra; Duquerroy, Stéphane; Kwok, Jane; Vonrhein, Clemens; Perez, Javier; Lamp, Benjamin; Bricogne, Gerard; Rümenapf, Till; Vachette, Patrice; Rey, Félix A

2015-04-01

Pestiviruses form a genus in the Flaviviridae family of small enveloped viruses with a positive-sense single-stranded RNA genome. Viral replication in this family requires the activity of a superfamily 2 RNA helicase contained in the C-terminal domain of nonstructural protein 3 (NS3). NS3 features two conserved RecA-like domains (D1 and D2) with ATPase activity, plus a third domain (D3) that is important for unwinding nucleic acid duplexes. We report here the X-ray structure of the pestivirus NS3 helicase domain (pNS3h) at a 2.5-Å resolution. The structure deviates significantly from that of NS3 of other genera in the Flaviviridae family in D3, as it contains two important insertions that result in a narrower nucleic acid binding groove. We also show that mutations in pNS3h that rescue viruses from which the core protein is deleted map to D3, suggesting that this domain may be involved in interactions that facilitate particle assembly. Finally, structural comparisons of the enzyme in different crystalline environments, together with the findings of small-angle X-ray-scattering studies in solution, show that D2 is mobile with respect to the rest of the enzyme, oscillating between closed and open conformations. Binding of a nonhydrolyzable ATP analog locks pNS3h in a conformation that is more compact than the closest apo-form in our crystals. Together, our results provide new insight and bring up new questions about pNS3h function during pestivirus replication. Although pestivirus infections impose an important toll on the livestock industry worldwide, little information is available about the nonstructural proteins essential for viral replication, such as the NS3 helicase. We provide here a comparative structural and functional analysis of pNS3h with respect to its orthologs in other viruses of the same family, the flaviviruses and hepatitis C virus. Our studies reveal differences in the nucleic acid binding groove that could have implications for understanding the

Simultaneous removal of chlorothalonil and nitrate by Bacillus cereus strain NS1

International Nuclear Information System (INIS)

Zhang Yiqiang; Lu Jianhang; Wu Laosheng; Chang, Andrew; Frankenberger, William T.

2007-01-01

Elevated NO 3 - and chlorothalonil (CTN) have been found in production nursery recycling ponds. Bacillus cereus strain NS1 isolated from nursery recycling pond sediment was assessed for its ability to reduce NO 3 - and degrade CTN in a mineral medium. The results showed that the efficiency of NO 3 - reduction and CTN degradation by B. cereus strain NS1 were related to the nature of organic carbon sources added to the medium. In the medium amended with 100 mg/L yeast extract, 86% of NO 3 - (100 mg/L) and 99% of CTN (78 μg/L) were simultaneously removed by B. cereus strain NS1 during the first day of the experiment. It took 6 days for the removal of 82-93% of NO 3 - and 87-91% of CTN in the media containing glucose and acetate. B. cereus strain NS1 needed organic carbon as energy sources and electron donors to respire NO 3 - , and simultaneously degrade CTN. These results suggest that B. cereus strain NS1 may have great potential to remediate NO 3 - and CTN contaminated water in nursery recycling ponds

Restoring proximal caries lesions conservatively with tunnel restorations.

Science.gov (United States)

Chu, Chun-Hung; Mei, May L; Cheung, Chloe; Nalliah, Romesh P

2013-07-30

The tunnel restoration has been suggested as a conservative alternative to the conventional box preparation for treating proximal caries. The main advantage of tunnel restoration over the conventional box or slot preparation includes being more conservative and increasing tooth integrity and strength by preserving the marginal ridge. However, tunnel restoration is technique-sensitive and can be particularly challenging for inexperienced restorative dentists. Recent advances in technology, such as the contemporary design of dental handpieces with advanced light-emitting diode (LED) and handheld comfort, offer operative dentists better vision, illumination, and maneuverability. The use of magnifying loupes also enhances the visibility of the preparation. The advent of digital radiographic imaging has improved dental imaging and reduced radiation. The new generation of restorative materials has improved mechanical properties. Tunnel restoration can be an option to restore proximal caries if the dentist performs proper case selection and pays attention to the details of the restorative procedures. This paper describes the clinical technique of tunnel restoration and reviews the studies of tunnel restorations.

The N-Terminal of Aquareovirus NS80 Is Required for Interacting with Viral Proteins and Viral Replication.

Directory of Open Access Journals (Sweden)

Jie Zhang

Full Text Available Reovirus replication and assembly occurs within viral inclusion bodies that formed in specific intracellular compartments of cytoplasm in infected cells. Previous study indicated that aquareovirus NS80 is able to form inclusion bodies, and also can retain viral proteins within its inclusions. To better understand how NS80 performed in viral replication and assembly, the functional regions of NS80 associated with other viral proteins in aquareovirus replication were investigated in this study. Deletion mutational analysis and rotavirus NSP5-based protein association platform were used to detect association regions. Immunofluorescence images indicated that different N-terminal regions of NS80 could associate with viral proteins VP1, VP4, VP6 and NS38. Further co-immunoprecipitation analysis confirmed the interaction between VP1, VP4, VP6 or NS38 with different regions covering the N-terminal amino acid (aa, 1-471 of NS80, respectively. Moreover, removal of NS80 N-terminal sequences required for interaction with proteins VP1, VP4, VP6 or NS38 not only prevented the capacity of NS80 to support viral replication in NS80 shRNA-based replication complementation assays, but also inhibited the expression of aquareovirus proteins, suggesting that N-terminal regions of NS80 are necessary for viral replication. These results provided a foundational basis for further understanding the role of NS80 in viral replication and assembly during aquareovirus infection.

Effect of subchronic exposure to mainstream cigarette smoke on endothelium-dependent vasodilation in rat arteries

Directory of Open Access Journals (Sweden)

Helena Lenasi

2005-07-01

Full Text Available Background: Cigarette smoking is reported to impair endothelium-dependent vasodilation. The aim of the present study was to assess the effect of 30-day exposure to mainstream cigarette smoke on vascular reactivity of rat abdominal aorta, carotid, renal and mesenteric artery. Separately, the NO-mediated and the EDHF-mediated, endothelium-dependent vascular relaxations were determined.Methods: Two groups of »Whistar Kyoto« rats were exposed to mainstream cigarette smoke (2 hours/day, 5 days/week for 30 days and to fresh conditioned air, respectively. Rats were sacrificed on the second day after the last exposition to cigarette smoke. Vascular reactivity studies were performed on isolated, endothelium-intact, phenylephrine-preconstricted rat artery rings. Cumulative concentration-relaxation curves to acetylcholine (ACh were obtained in the absence and presence of the endothelial NO synthase (eNOS inhibitor N ω nitro L-arginine (L-NA and the cyclo-oxygenase (COX inhibitor diclofenac, respectively. After washing period of 1 hour, vessels were exposed either to the intracellular superoxide scavenger tiron, to the cytochrome P450 (CYP inhibitor miconazole or the Na-K-ATPase inhibitor ouabain before being preconstricted with phenylephrine and determining the concentration-response curve to ACh.Results: ACh induced concentration-dependent relaxations. In none of the vessels investigated did we observe a significant difference in the relaxations obtained in arteries from control rats and rats exposed to cigarettee smoke. Although smoking is known to cause an increase in oxidative stress, treatment of the vessels with tiron did not affect the NOmediated relaxations. To evaluate the contribution of EDHF to endothelium-dependent vasodilation rings were preincubated with L-NA. The EDHF-mediated relaxations were significantly attenuated compared to the NO-mediated relaxations in renal and mesenteric artery and almost completely abolished in aorta and

Fate of the H-NS-repressed bgl operon in evolution of Escherichia coli.

Directory of Open Access Journals (Sweden)

T Sabari Sankar

2009-03-01

Full Text Available In the enterobacterial species Escherichia coli and Salmonella enterica, expression of horizontally acquired genes with a higher than average AT content is repressed by the nucleoid-associated protein H-NS. A classical example of an H-NS-repressed locus is the bgl (aryl-beta,D-glucoside operon of E. coli. This locus is "cryptic," as no laboratory growth conditions are known to relieve repression of bgl by H-NS in E. coli K12. However, repression can be relieved by spontaneous mutations. Here, we investigated the phylogeny of the bgl operon. Typing of bgl in a representative collection of E. coli demonstrated that it evolved clonally and that it is present in strains of the phylogenetic groups A, B1, and B2, while it is presumably replaced by a cluster of ORFans in the phylogenetic group D. Interestingly, the bgl operon is mutated in 20% of the strains of phylogenetic groups A and B1, suggesting erosion of bgl in these groups. However, bgl is functional in almost all B2 isolates and, in approximately 50% of them, it is weakly expressed at laboratory growth conditions. Homologs of bgl genes exist in Klebsiella, Enterobacter, and Erwinia species and also in low GC-content Gram-positive bacteria, while absent in E. albertii and Salmonella sp. This suggests horizontal transfer of bgl genes to an ancestral Enterobacterium. Conservation and weak expression of bgl in isolates of phylogenetic group B2 may indicate a functional role of bgl in extraintestinal pathogenic E. coli.

NS&T Management Observations - 3rd Quarter

Energy Technology Data Exchange (ETDEWEB)

Gianotto, David [Idaho National Lab. (INL), Idaho Falls, ID (United States)

2014-07-01

The INL Management Observation Program (MOP) is designed to improve managers and supervisors understanding of work being performed by employees and the barriers impacting their success. The MOP also increases workers understanding of managements’ expectations as they relate to safety, security, quality, and work performance. Management observations are designed to improve the relationship and trust between employees and managers through increased engagement and interactions between managers and researchers in the field. As part of continuous improvement, NS&T management took initiative to focus on the participation and quality of observations in FY 14. This quarterly report is intended to (a) summarize the participation and quality of management’s observations, (b) assess observations for commonalities or trends related to facility or process barriers impacting research, and (c) provide feedback and make recommendations for improvements NS&T’s MOP.

NS&T Management Observations: Quarterly Performance Analysis

Energy Technology Data Exchange (ETDEWEB)

Gianotto, David [Idaho National Lab. (INL), Idaho Falls, ID (United States)

2014-09-01

The INL Management Observation Program (MOP) is designed to improve managers and supervisors understanding of work being performed by employees and the barriers impacting their success. The MOP also increases workers understanding of managements’ expectations as they relate to safety, security, quality, and work performance. Management observations (observations) are designed to improve the relationship and trust between employees and managers through increased engagement and interactions between managers and researchers in the field. As part of continuous improvement, NS&T management took initiative to focus on the participation and quality of observations in FY-14. This quarterly report is intended to (a) summarize the participation and quality of management’s observations, (b) assess observations for commonalities or trends related to facility or process barriers impacting research, and (c) provide feedback and make recommendations for improvements NS&T’s MOP.

NS&T Managment Observations - 1st Quarter

Energy Technology Data Exchange (ETDEWEB)

David Gianotto

2014-06-01

The INL Management Observation Program (MOP) is designed to improve managers and supervisors understanding of work being performed by employees and the barriers impacting their success. The MOP also increases workers understanding of managements’ expectations as they relate to safety, security, quality, and work performance. Management observations (observations) are designed to improve the relationship and trust between employees and managers through increased engagement and interactions between managers and researchers in the field. As part of continuous improvement, NS&T management took initiative to focus on the participation and quality of observations in FY 14. This quarterly report is intended to (a) summarize the participation and quality of management’s observations, (b) assess observations for commonalities or trends related to facility or process barriers impacting research, and (c) provide feedback and make recommendations for improvements NS&T’s MOP.

The inhibition of cAMP-dependent protein kinase by full-length hepatitis C virus NS3/4A complex is due to ATP hydrolysis.

Science.gov (United States)

Aoubala, M; Holt, J; Clegg, R A; Rowlands, D J; Harris, M

2001-07-01

Hepatitis C virus (HCV) is an important cause of chronic liver disease, but the molecular mechanisms of viral pathogenesis remain to be established. The HCV non-structural protein NS3 complexes with NS4A and has three enzymatic activities: a proteinase and a helicase/NTPase. Recently, catalytically inactive NS3 fragments containing an arginine-rich motif have been reported to interact with, and inhibit, the catalytic subunit of cAMP-dependent protein kinase (PKA C-subunit). Here we demonstrate that full-length, catalytically active NS3/4A, purified from recombinant baculovirus-infected insect cells, is also able to inhibit PKA C-subunit in vitro. This inhibition was abrogated by mutation of either the arginine-rich motif or the conserved helicase motif II, both of which also abolished NTPase activity. As PKA C-subunit inhibition was also enhanced by poly(U) (an activator of NS3 NTPase activity), we hypothesized that PKA C-subunit inhibition could be due to NS3/4A-mediated ATP hydrolysis. This was confirmed by experiments in which a constant ATP concentration was maintained by addition of an ATP regeneration system--under these conditions PKA C-subunit inhibition was not observed. Interestingly, the mutations also abrogated the ability of wild-type NS3/4A to inhibit the PKA-regulated transcription factor CREB in transiently transfected hepatoma cells. Our data are thus not consistent with the previously proposed model in which the arginine-rich motif of NS3 was suggested to act as a pseudosubstrate inhibitor of PKA C-subunit. However, in vivo effects of NS3/4A suggest that ATPase activity may play a role in viral pathology in the infected liver.

NS OTTO HAHN - the first German nuclear ship

International Nuclear Information System (INIS)

1981-01-01

The NS OTTO HAHN is the first and only European nuclear propelled cargo and research vessel. She entered service in 1968 and was operated for 11 years without any technical failure. The essential experience and know-how about the nuclear propulsion unit is available now. Therefore the ship was decommissioned in 1979. Until the end of 1981 all activated and contaminated components will be removed and decontaminated. The ship can then be released for conventional utilization. In this book the NS OTTO HAHN is described in detail and the experiences of operation as well as research and development activities are reported. All earlier publications of GKSS on the same subject are listed. (orig.) [de

The quest for restoring hearing: Understanding ear development more completely.

Science.gov (United States)

Jahan, Israt; Pan, Ning; Elliott, Karen L; Fritzsch, Bernd

2015-09-01

Neurosensory hearing loss is a growing problem of super-aged societies. Cochlear implants can restore some hearing, but rebuilding a lost hearing organ would be superior. Research has discovered many cellular and molecular steps to develop a hearing organ but translating those insights into hearing organ restoration remains unclear. For example, we cannot make various hair cell types and arrange them into their specific patterns surrounded by the right type of supporting cells in the right numbers. Our overview of the topologically highly organized and functionally diversified cellular mosaic of the mammalian hearing organ highlights what is known and unknown about its development. Following this analysis, we suggest critical steps to guide future attempts toward restoration of a functional organ of Corti. We argue that generating mutant mouse lines that mimic human pathology to fine-tune attempts toward long-term functional restoration are needed to go beyond the hope generated by restoring single hair cells in postnatal sensory epithelia. © 2015 WILEY Periodicals, Inc.

Governing Forest Landscape Restoration: Cases from Indonesia

Directory of Open Access Journals (Sweden)

Cora van Oosten

2014-05-01

Full Text Available Forest landscape restoration includes both the planning and implementation of measures to restore degraded forests within the perspective of the wider landscape. Governing forest landscape restoration requires fundamental considerations about the conceptualisation of forested landscapes and the types of restoration measures to be taken, and about who should be engaged in the governance process. A variety of governance approaches to forest landscape restoration exist, differing in both the nature of the object to be governed and the mode of governance. This paper analyses the nature and governance of restoration in three cases of forest landscape restoration in Indonesia. In each of these cases, both the original aim for restoration and the initiators of the process differ. The cases also differ in how deeply embedded they are in formal spatial planning mechanisms at the various political scales. Nonetheless, the cases show similar trends. All cases show a dynamic process of mobilising the landscape’s stakeholders, plus a flexible process of crafting institutional space for conflict management, negotiation and decision making at the landscape level. As a result, the landscape focus changed over time from reserved forests to forested mosaic lands. The cases illustrate that the governance of forest landscape restoration should not be based on strict design criteria, but rather on a flexible governance approach that stimulates the creation of novel public-private institutional arrangements at the landscape level.

31 CFR 309.9 - Tenders; acceptance by the Secretary of the Treasury.

Science.gov (United States)

2010-07-01

... 31 Money and Finance: Treasury 2 2010-07-01 2010-07-01 false Tenders; acceptance by the Secretary... TREASURY BILLS § 309.9 Tenders; acceptance by the Secretary of the Treasury. At the time fixed for closing... acceptable prices offered and will make public announcement thereof those submitting tenders will be advised...

The relationship between ecological restoration and the ecosystem services concept

Directory of Open Access Journals (Sweden)

Sasha Alexander

2016-03-01

Full Text Available Ecological restoration and the mainstreaming of the concept of ecosystem services will be critical if global society is to move toward sustainability. Conference of the Parties 21 (COP21 of the United Nations Framework Convention on Climate Change and COP12 of the Convention on Biological Diversity should help foster support for vastly increased investment in the better management and restoration of natural capital. Large-scale restoration demonstrably improves ecological functioning to sustain both biodiversity and human well-being. However, much progress is needed to improve the effectiveness and cost efficiency of any restoration. The ecosystem services concept provides a framework for identifying the types of restorative interventions needed to target different forms and degrees of degradation, and achieve goals related to both ecosystem health and delivery of services to people. Moreover, it can strengthen the argument for, and planning of, large-scale restoration and conservation of natural capital. We use case studies from four continents to help demonstrate how the interconnection between ecological restoration and the ecosystem services concept is being utilized in land-use planning and enlightened ecosystem management. We offer ways in which this relationship can be better understood and communicated to support the scaling up of restoration activities to the landscape and regional scales across the full spectrum of land uses and ecosystem types.

Restoring proximal caries lesions conservatively with tunnel restorations

Directory of Open Access Journals (Sweden)

Chu CH

2013-07-01

Full Text Available Chun-Hung Chu1, May L Mei,1 Chloe Cheung,1 Romesh P Nalliah2 1Faculty of Dentistry, The University of Hong Kong, Hong Kong, People's Republic of China; 2Department of Restorative Dentistry and Biomaterials Sciences, Harvard School of Dental Medicine, Boston, MA, USA Abstract: The tunnel restoration has been suggested as a conservative alternative to the conventional box preparation for treating proximal caries. The main advantage of tunnel restoration over the conventional box or slot preparation includes being more conservative and increasing tooth integrity and strength by preserving the marginal ridge. However, tunnel restoration is technique-sensitive and can be particularly challenging for inexperienced restorative dentists. Recent advances in technology, such as the contemporary design of dental handpieces with advanced light-emitting diode (LED and handheld comfort, offer operative dentists better vision, illumination, and maneuverability. The use of magnifying loupes also enhances the visibility of the preparation. The advent of digital radiographic imaging has improved dental imaging and reduced radiation. The new generation of restorative materials has improved mechanical properties. Tunnel restoration can be an option to restore proximal caries if the dentist performs proper case selection and pays attention to the details of the restorative procedures. This paper describes the clinical technique of tunnel restoration and reviews the studies of tunnel restorations. Keywords: operative, practice, tunnel preparation, composite, amalgam, glass ionomer

Crystal structure of full-length Zika virus NS5 protein reveals a conformation similar to Japanese encephalitis virus NS5

Energy Technology Data Exchange (ETDEWEB)

Upadhyay, Anup K.; Cyr, Matthew; Longenecker, Kenton; Tripathi, Rakesh; Sun, Chaohong; Kempf, Dale J. (AbbVie)

2017-02-21

The rapid spread of the recentZika virus(ZIKV) epidemic across various countries in the American continent poses a major health hazard for the unborn fetuses of pregnant women. To date, there is no effective medical intervention. The nonstructural protein 5 ofZika virus(ZIKV-NS5) is critical for ZIKV replication through the 5'-RNA capping and RNA polymerase activities present in its N-terminal methyltransferase (MTase) and C-terminal RNA-dependent RNA polymerase (RdRp) domains, respectively. The crystal structure of the full-length ZIKV-NS5 protein has been determined at 3.05 Å resolution from a crystal belonging to space groupP2₁2₁2 and containing two protein molecules in the asymmetric unit. The structure is similar to that reported for the NS5 protein fromJapanese encephalitis virusand suggests opportunities for structure-based drug design targeting either its MTase or RdRp domain.

Characterization of purified Sindbis virus nsP4 RNA-dependent RNA polymerase activity in vitro

International Nuclear Information System (INIS)

Rubach, Jon K.; Wasik, Brian R.; Rupp, Jonathan C.; Kuhn, Richard J.; Hardy, Richard W.; Smith, Janet L.

2009-01-01

The Sindbis virus RNA-dependent RNA polymerase (nsP4) is responsible for the replication of the viral RNA genome. In infected cells, nsP4 is localized in a replication complex along with the other viral non-structural proteins. nsP4 has been difficult to homogenously purify from infected cells due to its interactions with the other replication proteins and the fact that its N-terminal residue, a tyrosine, causes the protein to be rapidly turned over in cells. We report the successful expression and purification of Sindbis nsP4 in a bacterial system, in which nsP4 is expressed as an N-terminal SUMO fusion protein. After purification the SUMO tag is removed, resulting in the isolation of full-length nsP4 possessing the authentic N-terminal tyrosine. This purified enzyme is able to produce minus-strand RNA de novo from plus-strand templates, as well as terminally add adenosine residues to the 3' end of an RNA substrate. In the presence of the partially processed viral replicase polyprotein, P123, purified nsP4 is able to synthesize discrete template length minus-strand RNA products. Mutations in the 3' CSE or poly(A) tail of viral template RNA prevent RNA synthesis by the replicase complex containing purified nsP4, consistent with previously reported template requirements for minus-strand RNA synthesis. Optimal reaction conditions were determined by investigating the effects of time, pH, and the concentrations of nsP4, P123 and magnesium on the synthesis of RNA

A novel cell-based assay to measure activity of Venezuelan equine encephalitis virus nsP2 protease

International Nuclear Information System (INIS)

Campos-Gomez, Javier; Ahmad, Fahim; Rodriguez, Efrain; Saeed, Mohammad F.

2016-01-01

The encephalitic alphaviruses encode nsP2 protease (nsP2pro), which because of its vital role in virus replication, represents an attractive target for therapeutic intervention. To facilitate the discovery of nsP2 inhibitors we have developed a novel assay for quantitative measurement of nsP2pro activity in a cell-based format. The assay is based on a substrate fusion protein consisting of eGFP and Gaussia luciferase (Gluc) linked together by a small peptide containing a VEEV nsp2pro cleavage sequence. The expression of the substrate protein in cells along with recombinant nsP2pro results in cleavage of the substrate protein resulting in extracellular release of free Gluc. The Gluc activity in supernatants corresponds to intracellular nsP2pro-mediated substrate cleavage; thus, providing a simple and convenient way to quantify nsP2pro activity. Here, we demonstrate potential utility of the assay in identification of nsP2pro inhibitors, as well as in investigations related to molecular characterization of nsP2pro. - Highlights: • A novel cell-based assay to measure VEEV nsP2 protease activity was developed. • Assay utility was demonstrated for antiviral screening. • .The assay also proved to be useful in basic mechanistic studies of nsP2 protease.

A novel cell-based assay to measure activity of Venezuelan equine encephalitis virus nsP2 protease

Energy Technology Data Exchange (ETDEWEB)

Campos-Gomez, Javier; Ahmad, Fahim; Rodriguez, Efrain; Saeed, Mohammad F., E-mail: saeed@southernresearch.org

2016-09-15

The encephalitic alphaviruses encode nsP2 protease (nsP2pro), which because of its vital role in virus replication, represents an attractive target for therapeutic intervention. To facilitate the discovery of nsP2 inhibitors we have developed a novel assay for quantitative measurement of nsP2pro activity in a cell-based format. The assay is based on a substrate fusion protein consisting of eGFP and Gaussia luciferase (Gluc) linked together by a small peptide containing a VEEV nsp2pro cleavage sequence. The expression of the substrate protein in cells along with recombinant nsP2pro results in cleavage of the substrate protein resulting in extracellular release of free Gluc. The Gluc activity in supernatants corresponds to intracellular nsP2pro-mediated substrate cleavage; thus, providing a simple and convenient way to quantify nsP2pro activity. Here, we demonstrate potential utility of the assay in identification of nsP2pro inhibitors, as well as in investigations related to molecular characterization of nsP2pro. - Highlights: • A novel cell-based assay to measure VEEV nsP2 protease activity was developed. • Assay utility was demonstrated for antiviral screening. • .The assay also proved to be useful in basic mechanistic studies of nsP2 protease.

Analysis of the PDZ binding specificities of Influenza A Virus NS1 proteins

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Nagasaka Kazunori

2011-01-01

Full Text Available Abstract The Influenza A virus non-structural protein 1 (NS1 is a multifunctional virulence factor with several protein-protein interaction domains, involved in preventing apoptosis of the infected cell and in evading the interferon response. In addition, the majority of influenza A virus NS1 proteins have a class I PDZ-binding motif at the C-terminus, and this itself has been shown to be a virulence determinant. In the majority of human influenza NS1 proteins the consensus motif is RSxV: in avian NS1 it is ESxV. Of the few human strains that have the avian motif, all were from very high mortality outbreaks of the disease. Previous work has shown that minor differences in PDZ-binding motifs can have major effects on the spectrum of cellular proteins targeted. In this study we analyse the effect of these differences upon the binding of Influenza A virus NS1 protein to a range of cellular proteins involved in polarity and signal transduction.

Local gene therapy durably restores vestibular function in a mouse model of Usher syndrome type 1G.

Science.gov (United States)

Emptoz, Alice; Michel, Vincent; Lelli, Andrea; Akil, Omar; Boutet de Monvel, Jacques; Lahlou, Ghizlene; Meyer, Anaïs; Dupont, Typhaine; Nouaille, Sylvie; Ey, Elody; Franca de Barros, Filipa; Beraneck, Mathieu; Dulon, Didier; Hardelin, Jean-Pierre; Lustig, Lawrence; Avan, Paul; Petit, Christine; Safieddine, Saaid

2017-09-05

Our understanding of the mechanisms underlying inherited forms of inner ear deficits has considerably improved during the past 20 y, but we are still far from curative treatments. We investigated gene replacement as a strategy for restoring inner ear functions in a mouse model of Usher syndrome type 1G, characterized by congenital profound deafness and balance disorders. These mice lack the scaffold protein sans, which is involved both in the morphogenesis of the stereociliary bundle, the sensory antenna of inner ear hair cells, and in the mechanoelectrical transduction process. We show that a single delivery of the sans cDNA by the adenoassociated virus 8 to the inner ear of newborn mutant mice reestablishes the expression and targeting of the protein to the tips of stereocilia. The therapeutic gene restores the architecture and mechanosensitivity of stereociliary bundles, improves hearing thresholds, and durably rescues these mice from the balance defects. Our results open up new perspectives for efficient gene therapy of cochlear and vestibular disorders by showing that even severe dysmorphogenesis of stereociliary bundles can be corrected.

Effect of abutment shade, ceramic thickness, and coping type on the final shade of zirconia all-ceramic restorations: in vitro study of color masking ability.

Science.gov (United States)

Oh, Seon-Hee; Kim, Seok-Gyu

2015-10-01

The aim of the study was to evaluate the effect of abutment shade, ceramic thickness, and coping type on the final shade of zirconia all-ceramic restorations. Three different types of disk-shaped zirconia coping specimens (Lava, Cercon, Zirkonzahn: ø10 mm × 0.4 mm) were fabricated and veneered with IPS e.max Press Ceram (shade A2), for total thicknesses of 1 and 1.5 mm. A total of sixty zirconia restoration specimens were divided into six groups based on their coping types and thicknesses. The abutment specimens (ø10 mm × 7 mm) were prepared with gold alloy, base metal (nickel-chromium) alloy, and four different shades (A1, A2, A3, A4) of composite resins. The average L*, a*, b* values of the zirconia specimens on the six abutment specimens were measured with a dental colorimeter, and the statistical significance in the effects of three variables was analyzed by using repeated measures analysis of variance (α=.05).The average shade difference (ΔE) values of the zirconia specimens between the A2 composite resin abutment and other abutments were also evaluated. The effects of zirconia specimen thickness (Pabutment shade (Pabutments was higher (close to the acceptability threshold of 5.5 ΔE) than th ose between the A2 composite resin and other abutments. This in-vitro study demonstrated that abutment shade, ceramic thickness, and coping type affected the resulting shade of zirconia restorations.

Influence of Genetic Drift of Restoring Gene (Rf on Seed Purity of Yuetai A, a Honglian-Type Cytoplasmic Male Sterile Line in Hybrid Rice

Directory of Open Access Journals (Sweden)

Ji-feng Wang

2008-06-01

Full Text Available The seed samples of Yuetai A, a Honglian (HL type cytoplasmic male sterile (CMS line in hybrid rice were investigated to assess the seed purity and to analyze the cause of off-type plants by imitating the biological contaminant to Yuetai A in Nanjing, Jiangsu Province and Lingshui, Hainan Province during 2004–2006. The seed impurity of Yuetai A mainly resulted from the genetic drift of restoring fertility gene (Rf after biological contamination but not from its sterility unstability. All of the ten maintainer lines, five restorer lines and three thermo-sensitive genic male sterile lines used in the study could pollinate Yuetai A and Yuetai B to produce F1 plants, directly or indirectly resulting in Rf-gene drifting into Yuetai A and generating ‘iso-cytoplasm restoring-generations’. Furthermore, high outcrossing rate and similar heading date of Yuetai A with many varieties used in rice production might easily result in the biological contamination. After removing all plants with Rf-gene mixed in Yuetai A and preventing Rf-gene drifting into Yuetai A, the seed purity of Yuetai A and Yuetai B had been raised to 100%.

Tetrahydrobiopterin restores impaired coronary microvascular dysfunction in hypercholesterolaemia

Energy Technology Data Exchange (ETDEWEB)

Wyss, Christophe A.; Koepfli, Pascal; Namdar, Mehdi; Siegrist, Patrick T.; Kaufmann, Philipp A. [University Hospital, Nuclear Cardiology, Cardiovascular Center, Zurich (Switzerland); Luscher, Thomas F. [University Hospital, Division of Cardiology, Cardiovascular Center, Zurich (Switzerland); Camici, Paolo G. [Hammersmith Hospital, MRC Clinical Sciences Centre, Faculty of Medicine, Imperial College of Science, Technology and Medicine, London (United Kingdom)

2005-01-01

Tetrahydrobiopterin (BH{sub 4}) is an essential co-factor for the synthesis of nitric oxide (NO), and BH{sub 4} deficiency may cause impaired NO synthase (NOS) activity. We studied whether BH{sub 4} deficiency contributes to the coronary microcirculatory dysfunction observed in patients with hypercholesterolaemia. Myocardial blood flow (MBF; ml min{sup -1} g{sup -1}) was measured at rest, during adenosine-induced (140 {mu}g kg{sup -1} min{sup -1} over 7 min) hyperaemia (mainly non-endothelium dependent) and immediately after supine bicycle exercise (endothelium-dependent) stress in ten healthy volunteers and in nine hypercholesterolaemic subjects using {sup 15}O-labelled water and positron emission tomography. Measurements were repeated 60 min later, after intravenous infusion of BH{sub 4} (10 mg kg{sup -1} body weight over 30 min). Adenosine-induced hyperaemic MBF is considered to represent (near) maximal flow. Flow reserve utilisation was calculated as the ratio of exercise-induced to adenosine-induced hyperaemic MBF and expressed as percent to indicate how much of the maximal (adenosine-induced) hyperaemia can be achieved by bicycle stress. BH{sub 4} increased exercise-induced hyperaemia in controls (2.96{+-}0.58 vs 3.41{+-}0.73 ml min{sup -1} g{sup -1}, p<0.05) and hypercholesterolaemic subjects (2.47{+-}0.78 vs 2.70{+-}0.72 ml min{sup -1} g{sup -1}, p<0.01) but had no influence on MBF at rest or during adenosine-induced hyperaemia in controls (4.52{+-}1.10 vs 4.85{+-}0.45 ml min{sup -1} g{sup -1}, p=NS) or hypercholesterolaemic subjects (4.86{+-}1.18 vs 4.53{+-}0.93 ml min{sup -1} g{sup -1}, p=NS). Flow reserve utilisation remained unchanged in controls (70{+-}17% vs 71{+-}19%, p=NS) but increased significantly in hypercholesterolaemic subjects (53{+-}15% vs 66{+-}14%, p<0.05). BH{sub 4} restores flow reserve utilisation of the coronary microcirculation in hypercholesterolaemic subjects, suggesting that BH{sub 4} deficiency may contribute to coronary

Broadband Fan Noise Prediction System for Turbofan Engines. Volume 2; BFaNS User's Manual and Developer's Guide

Science.gov (United States)

Morin, Bruce L.

2010-01-01

Pratt & Whitney has developed a Broadband Fan Noise Prediction System (BFaNS) for turbofan engines. This system computes the noise generated by turbulence impinging on the leading edges of the fan and fan exit guide vane, and noise generated by boundary-layer turbulence passing over the fan trailing edge. BFaNS has been validated on three fan rigs that were tested during the NASA Advanced Subsonic Technology Program (AST). The predicted noise spectra agreed well with measured data. The predicted effects of fan speed, vane count, and vane sweep also agreed well with measurements. The noise prediction system consists of two computer programs: Setup_BFaNS and BFaNS. Setup_BFaNS converts user-specified geometry and flow-field information into a BFaNS input file. From this input file, BFaNS computes the inlet and aft broadband sound power spectra generated by the fan and FEGV. The output file from BFaNS contains the inlet, aft and total sound power spectra from each noise source. This report is the second volume of a three-volume set documenting the Broadband Fan Noise Prediction System: Volume 1: Setup_BFaNS User s Manual and Developer s Guide; Volume 2: BFaNS User s Manual and Developer s Guide; and Volume 3: Validation and Test Cases. The present volume begins with an overview of the Broadband Fan Noise Prediction System, followed by step-by-step instructions for installing and running BFaNS. It concludes with technical documentation of the BFaNS computer program.

Quantification of NS1 dengue biomarker in serum via optomagnetic nanocluster detection

DEFF Research Database (Denmark)

Antunes, Paula Soares Martins; Watterson, Daniel; Parmvi, Mattias

2015-01-01

Dengue is a tropical vector-borne disease without cure or vaccine that progressively spreads into regions with temperate climates. Diagnostic tools amenable to resource-limited settings would be highly valuable for epidemiologic control and containment during outbreaks. Here, we present a novel low......-cost automated biosensing platform for detection of dengue fever biomarker NS1 and demonstrate it on NS1 spiked in human serum. Magnetic nanoparticles (MNPs) are coated with high-affinity monoclonal antibodies against NS1 via bio-orthogonal Cu-free 'click' chemistry on an anti-fouling surface molecular...... method. The resulting automated dengue fever assay takes just 8 minutes, requires 6 μL of serum sample and shows a limit of detection of 25 ng/mL with an upper detection range of 20000 ng/mL. The technology holds a great potential to be applied to NS1 detection in patient samples. As the assay...

Functional restoration of diaphragmatic paralysis: an evaluation of phrenic nerve reconstruction.

Science.gov (United States)

Kaufman, Matthew R; Elkwood, Andrew I; Colicchio, Alan R; CeCe, John; Jarrahy, Reza; Willekes, Lourens J; Rose, Michael I; Brown, David

2014-01-01

Unilateral diaphragmatic paralysis causes respiratory deficits and can occur after iatrogenic or traumatic phrenic nerve injury in the neck or chest. Patients are evaluated using spirometry and imaging studies; however, phrenic nerve conduction studies and electromyography are not widely available or considered; thus, the degree of dysfunction is often unknown. Treatment has been limited to diaphragmatic plication. Phrenic nerve operations to restore diaphragmatic function may broaden therapeutic options. An interventional study of 92 patients with symptomatic diaphragmatic paralysis assigned 68 (based on their clinical condition) to phrenic nerve surgical intervention (PS), 24 to nonsurgical (NS) care, and evaluated a third group of 68 patients (derived from literature review) treated with diaphragmatic plication (DP). Variables for assessment included spirometry, the Short-Form 36-Item survey, electrodiagnostics, and complications. In the PS group, there was an average 13% improvement in forced expiratory volume in 1 second (p Phrenic nerve operations for functional restoration of the paralyzed diaphragm should be part of the standard treatment algorithm in the management of symptomatic patients with this condition. Assessment of neuromuscular dysfunction can aid in determining the most effective therapy. Copyright © 2014 The Society of Thoracic Surgeons. Published by Elsevier Inc. All rights reserved.

The CENNS-10 liquid argon detector to measure CEvNS at the Spallation Neutron Source

Science.gov (United States)

Tayloe, R.

2018-04-01

The COHERENT collaboration is deploying a suite of low-energy detectors in a low-background corridor of the ORNL Spallation Neutron Source (SNS) to measure coherent elastic neutrino-nucleus scattering (CEvNS) on an array of nuclear targets employing different detector technologies. A measurement of CEvNS on different nuclei will test the N2-dependence of the CEvNS cross section and further the physics reach of the COHERENT effort. The first step of this program has been realized recently with the observation of CEvNS in a 14.6 kg CsI detector. Operation and deployment of Ge and NaI detectors are also underway. A 22 kg, single-phase, liquid argon detector (CENNS-10) started data-taking in Dec. 2016 and will provide results on CEvNS from a lighter nucleus. Initial results indicate that light output, pulse-shape discrimination, and background suppression are sufficient for a measurement of CEvNS on argon.

Respiratory syncytial virus mechanisms to interfere with type 1 interferons.

Science.gov (United States)

Barik, Sailen

2013-01-01

Respiratory syncytial virus (RSV) is a member of the Paramyxoviridae family that consists of viruses with nonsegmented negative-strand RNA genome. Infection by these viruses triggers the innate antiviral response of the host, mainly type I interferon (IFN). Essentially all other viruses of this family produce IFN suppressor functions by co-transcriptional RNA editing. In contrast, RSV has evolved two unique nonstructural proteins, NS1 and NS2, to effectively serve this purpose. Together, NS1 and NS2 degrade or sequester multiple signaling proteins that affect both IFN induction and IFN effector functions. While the mechanism of action of NS1 and NS2 is a subject of active research, their effect on adaptive immunity is also being recognized. In this review, we discuss various aspects of NS1 and NS2 function with implications for vaccine design.

Activation of TLR2 and TLR6 by Dengue NS1 Protein and Its Implications in the Immunopathogenesis of Dengue Virus Infection.

Directory of Open Access Journals (Sweden)

Jincheng Chen

2015-07-01

Full Text Available Dengue virus (DV infection is the most prevalent mosquito-borne viral disease and its manifestation has been shown to be contributed in part by the host immune responses. In this study, pathogen recognition receptors, Toll-like receptor (TLR 2 and TLR6 were found to be up-regulated in DV-infected human PBMC using immunofluorescence staining, flow cytometry and Western blot analyses. Using ELISA, IL-6 and TNF-α, cytokines downstream of TLR2 and TLR6 signaling pathways were also found to be up-regulated in DV-infected PBMC. IL-6 and TNF-α production by PBMC were reduced when TLR2 and TLR6 were blocked using TLR2 and TLR6 neutralizing antibodies during DV infection. These results suggested that signaling pathways of TLR2 and TLR6 were activated during DV infection and its activation contributed to IL-6 and TNF-α production. DV NS1 protein was found to significantly increase the production of IL-6 and TNF-α when added to PBMC. The amount of IL-6 and TNF-α stimulated by DV NS1 protein was reduced when TLR2 and TLR6 were blocked, suggesting that DV NS1 protein is the viral protein responsible for the activation of TLR2 and TLR6 during DV infection. Secreted alkaline phosphatase (SEAP reporter assay was used to further confirm activation of TLR2 and TLR6 by DV NS1 protein. In addition, DV-infected and DV NS1 protein-treated TLR6-/- mice have higher survivability compared to DV-infected and DV NS1 protein-treated wild-type mice. Hence, activation of TLR6 via DV NS1 protein could potentially play an important role in the immunopathogenesis of DV infection.

Nucleolar localization of influenza A NS1: striking differences between mammalian and avian cells

Directory of Open Access Journals (Sweden)

Mazel-Sanchez Beryl

2010-03-01

Full Text Available Abstract In mammalian cells, nucleolar localization of influenza A NS1 requires the presence of a C-terminal nucleolar localization signal. This nucleolar localization signal is present only in certain strains of influenza A viruses. Therefore, only certain NS1 accumulate in the nucleolus of mammalian cells. In contrast, we show that all NS1 tested in this study accumulated in the nucleolus of avian cells even in the absence of the above described C-terminal nucleolar localization signal. Thus, nucleolar localization of NS1 in avian cells appears to rely on a different nucleolar localization signal that is more conserved among influenza virus strains.

Pomegranate ( Punica granatum L.) expresses several nsLTP isoforms characterized by different immunoglobulin E-binding properties.

Science.gov (United States)

Bolla, Michela; Zenoni, Sara; Scheurer, Stephan; Vieths, Stefan; San Miguel Moncin, Maria Del Mar; Olivieri, Mario; Antico, Andrea; Ferrer, Marta; Berroa, Felicia; Enrique, Ernesto; Avesani, Linda; Marsano, Francesco; Zoccatelli, Gianni

2014-01-01

Pomegranate allergy is associated with sensitization to non-specific lipid transfer proteins (nsLTPs). Our aim was to identify and characterize the non-specific nsLTPs expressed in pomegranate at the molecular level and to study their allergenic properties in terms of immunoglobulin E (IgE)-binding and cross-reactivity with peach nsLTP (Pru p 3). A non-equilibrium two-dimensional (2-D) electrophoretic approach based on acid-urea PAGE and sodium dodecyl sulfate PAGE was set up to separate pomegranate nsLTPs. Their immunoreactivity was tested by immunoblotting carried out with anti-Pru p 3 polyclonal antibodies and sera from pomegranate-allergic patients. For final identification, pomegranate nsLTPs were purified by chromatography and subjected to trypsin digestion and mass spectrometry (MS) analysis. For this purpose, the sequences obtained by cDNA cloning of three pomegranate nsLTPs were integrated in the database that was subsequently searched for MS data interpretation. Four nsLTPs were identified by 2-D immunoblotting. The detected proteins showed different IgE-binding capacity and partial cross-reactivity with Pru p 3. cDNA cloning and MS analyses led to the identification of three nsLTP isoforms with 66-68% amino acid sequence identity named Pun g 1.0101, Pun g 1.0201 and Pun g 1.0301. By 2-D electrophoresis, we could separate different nsLTP isoforms possessing different IgE-binding properties, which might reflect peculiar allergenic potencies. The contribution of Pru p 3 to prime sensitization is not central as in other plant nsLTPs. © 2014 S. Karger AG, Basel.

47 CFR 80.309 - Watch required by the Bridge-to-Bridge Act.

Science.gov (United States)

2010-10-01

... 47 Telecommunication 5 2010-10-01 2010-10-01 false Watch required by the Bridge-to-Bridge Act. 80... Safety Watches § 80.309 Watch required by the Bridge-to-Bridge Act. In addition to the watch requirement contained in § 80.148, all vessels subject to the Bridge-to-Bridge Act must keep a watch on the designated...

Detergent-resistant membrane association of NS2 and E2 during hepatitis C virus replication.

Science.gov (United States)

Shanmugam, Saravanabalaji; Saravanabalaji, Dhanaranjani; Yi, MinKyung

2015-04-01

Previously, we demonstrated that the efficiency of hepatitis C virus (HCV) E2-p7 processing regulates p7-dependent NS2 localization to putative virus assembly sites near lipid droplets (LD). In this study, we have employed subcellular fractionations and membrane flotation assays to demonstrate that NS2 associates with detergent-resistant membranes (DRM) in a p7-dependent manner. However, p7 likely plays an indirect role in this process, since only the background level of p7 was detectable in the DRM fractions. Our data also suggest that the p7-NS2 precursor is not involved in NS2 recruitment to the DRM, despite its apparent targeting to this location. Deletion of NS2 specifically inhibited E2 localization to the DRM, indicating that NS2 regulates this process. Treatment of cells with methyl-β-cyclodextrin (MβCD) significantly reduced the DRM association of Core, NS2, and E2 and reduced infectious HCV production. Since disruption of the DRM localization of NS2 and E2, either due to p7 and NS2 defects, respectively, or by MβCD treatment, inhibited infectious HCV production, these proteins' associations with the DRM likely play an important role during HCV assembly. Interestingly, we detected the HCV replication-dependent accumulation of ApoE in the DRM fractions. Taking into consideration the facts that ApoE was shown to be a major determinant for infectious HCV particle production at the postenvelopment step and that the HCV Core protein strongly associates with the DRM, recruitment of E2 and ApoE to the DRM may allow the efficient coordination of Core particle envelopment and postenvelopment events at the DRM to generate infectious HCV production. The biochemical nature of HCV assembly sites is currently unknown. In this study, we investigated the correlation between NS2 and E2 localization to the detergent-resistant membranes (DRM) and HCV particle assembly. We determined that although NS2's DRM localization is dependent on p7, p7 was not targeted to these

Proliferation of NS0 cells in protein-free medium: the role of cell-derived proteins, known growth factors and cellular receptors.

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Spens, Erika; Häggström, Lena

2009-05-20

NS0 cells proliferate without external supply of growth factors in protein-free media. We hypothesize that the cells produce their own factors to support proliferation. Understanding the mechanisms behind this autocrine regulation of proliferation may open for the novel approaches to improve animal cell processes. The following proteins were identified in NS0 conditioned medium (CM): cyclophilin A, cyclophilin B (CypB), cystatin C, D-dopachrome tautomerase, IL-25, isopentenyl-diphosphate delta-isomerase, macrophage migration inhibitory factor (MIF), beta(2)-microglobulin, Niemann pick type C2, secretory leukocyte protease inhibitor, thioredoxin-1, TNF-alpha, tumour protein translationally controlled 1 and ubiquitin. Further, cDNA microarray analysis indicated that the genes for IL-11, TNF receptor 6, TGF-beta receptor 1 and the IFN-gamma receptor were transcribed. CypB, IFN-alpha/beta/gamma, IL-11, IL-25, MIF, TGF-beta and TNF-alpha as well as the known growth factors EGF, IGF-I/II, IL-6, leukaemia inhibitory factor and oncostatin M (OSM) were excluded as involved in autocrine regulation of NS0 cell proliferation. The receptors for TGF-beta, IGF and OSM are however present in NS0 cell membranes since TGF-beta(1) caused cell death, and IGF-I/II and OSM improved cell growth. Even though no ligand was found, the receptor subunit gp130, active in signal transduction of the IL-6 like proteins, was shown to be essential for NS0 cells as demonstrated by siRNA gene silencing.

On the meaning of NS comparisons in Israel-critical discourse

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Wilhelm Kempf

2017-04-01

Full Text Available Apart from Holocaust denial, probably nothing outrages Israelis and Jews around the world more than comparisons of Israeli Palestinian policy with National Socialist Jewish policy. Particularly, if Germans make such comparisons, the obvious suspicion is that they are an expression of secondary anti-Semitism. On the other hand, in Western democracies it is virtually part of political culture to fall back on NS comparisons whenever one wants to dramatize precarious human rights situations and justify the need for action to change them. Based on new analyses of survey data published in Kempf (2015a,b, this study shows that NS comparisons can constitute not only anti-Semitic demonization of Jews but also anti-Zionist dramatization of the Palestinian human rights situation. People who work consequently and without reservation for human rights, however, indeed see a strong need for action to change Israeli policy, but strictly refuse to equate it with NS policy.

Influence of citric acid on the surface texture of glass ionomer restorative materials

OpenAIRE

Reddy, Dappili Swami Ranga; Kumar, Ramachandran Anil; Venkatesan, Sokkalingam Mothilal; Narayan, Gopal Shankar; Duraivel, Dasarathan; Indra, Rajamani

2014-01-01

Aim: This study determined the effectiveness of G-coat plus surface protective agent over petroleum jelly on the surface texture of conventional Glass ionomer restorative materials. Materials and Methods: Three chemically cured conventional glass ionomer restorative materials type II, type IX and ketac molar were evaluated in this study. Sixty specimens were made for each restorative material. They were divided into two groups of thirty specimens each. Of the sixty specimens, thirty were...

Impact of revisions to the F-Tag 309 surveyors' interpretive guidelines on pain management among nursing home residents.

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Lapane, Kate L; Quilliam, Brian J; Chow, Wing; Kim, Myoung S

2012-05-01

On 31 March 2009, the US Centers for Medicare & Medicaid Services (CMS) provided revised guidance for meeting compliance in the evaluation and management of pain in nursing home residents, known as F-Tag 309. The aim of the study was to estimate the extent to which implementation of revisions to the surveyors' interpretive guidelines for F-Tag 309 improved recognition and management of pain among nursing home residents. The impact of the revisions to guidance on F-Tag 309 on pain in nursing home residents was investigated. The study was quasi-experimental in design and included 174 for-profit nursing homes in 19 US states. Nursing home residents with ≥2 Minimum Data Set (MDS) assessments between 1 January 2007 and 30 March 2009 (before the revisions to the guidelines; n = 8449) and between 31 March 2009 and 31 December 2009 (after the revisions; n = 1400) were included. The MDS assessments provided information on pain, analgesic use and cognitive, functional and emotional status. Separate logistic regression models that adjusted for clustering effects of residents residing in nursing homes provided estimates of the relationship between the implementation of the revisions to F-Tag 309 and the prevalence of pain and its management. Pain was more likely to be documented in the period after the revisions were implemented. The odds of pain being documented on at least one of two consecutive MDS assessments increased after the revisions to the guidelines were implemented (adjusted odds ratio [OR] 1.15; 95% confidence interval [CI] 1.01, 1.31). Increases in scheduled analgesic prescription were observed in the post-revision era (adjusted OR 1.38; 95% CI 1.21,1.57). The implementation of revisions to the surveyors' interpretive guidelines for F-Tag 309 improved recognition and management of pain as well as analgesic use in nursing home residents with documented non-cancer pain. Use of directed language as part of the surveyors' interpretive guidelines may be a

NS3 from Hepatitis C Virus Strain JFH-1 Is an Unusually Robust Helicase That Is Primed To Bind and Unwind Viral RNA

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Zhou, Ting; Ren, Xiaoming; Adams, Rebecca L.; Pyle, Anna Marie; Ou, J. -H. James

2017-10-25

Hepatitis C viruses (HCV) encode a helicase enzyme that is essential for viral replication and assembly (nonstructural protein 3 [NS3]). This helicase has become the focus of extensive basic research on the general helicase mechanism, and it is also of interest as a novel drug target. Despite the importance of this protein, mechanistic work on NS3 has been conducted almost exclusively on variants from HCV genotype 1. Our understanding of NS3 from the highly active HCV strains that are used to study HCV genetics and mechanism in cell culture (such as JFH-1) is lacking. We therefore set out to determine whether NS3 from the replicatively efficient genotype 2a strain JFH-1 displays novel functional or structural properties. Using biochemical assays for RNA binding and duplex unwinding, we show that JFH-1 NS3 binds RNA much more rapidly than the previously studied NS3 variants from genotype 1b. Unlike NS3 variants from other genotypes, JFH-1 NS3 binds RNA with high affinity in a functionally active form that is capable of immediately unwinding RNA duplexes without undergoing rate-limiting conformational changes that precede activation. Unlike other superfamily 2 (SF2) helicases, JFH-1 NS3 does not require long 3' overhangs, and it unwinds duplexes that are flanked by only a few nucleotides, as in the folded HCV genome. To understand the physical basis for this, we solved the crystal structure of JFH-1 NS3, revealing a novel conformation that contains an open, positively charged RNA binding cleft that is primed for productive interaction with RNA targets, potentially explaining robust replication by HCV JFH-1.

IMPORTANCEGenotypes of HCV are as divergent as different types of flavivirus, and yet mechanistic features of HCV variants are presumed to be held in common. One of the most well-studied components of the HCV replication complex is a helicase known as nonstructural protein 3 (NS3). We set out to determine whether this important

Evolution of Bacterial Global Modulators: Role of a Novel H-NS Paralogue in the Enteroaggregative Escherichia coli Strain 042.

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Prieto, A; Bernabeu, M; Aznar, S; Ruiz-Cruz, S; Bravo, A; Queiroz, M H; Juárez, A

2018-01-01

Bacterial genomes sometimes contain genes that code for homologues of global regulators, the function of which is unclear. In members of the family Enterobacteriaceae , cells express the global regulator H-NS and its paralogue StpA. In Escherichia coli , out of providing a molecular backup for H-NS, the role of StpA is poorly characterized. The enteroaggregative E. coli strain 042 carries, in addition to the hns and stpA genes, a third gene encoding an hns paralogue ( hns2 ). We present in this paper information about its biological function. Transcriptomic analysis has shown that the H-NS2 protein targets a subset of the genes targeted by H-NS. Genes targeted by H-NS2 correspond mainly with horizontally transferred (HGT) genes and are also targeted by the Hha protein, a fine-tuner of H-NS activity. Compared with H-NS, H-NS2 expression levels are lower. In addition, H-NS2 expression exhibits specific features: it is sensitive to the growth temperature and to the nature of the culture medium. This novel H-NS paralogue is widespread within the Enterobacteriaceae . IMPORTANCE Global regulators such as H-NS play key relevant roles enabling bacterial cells to adapt to a changing environment. H-NS modulates both core and horizontally transferred (HGT) genes, but the mechanism by which H-NS can differentially regulate these genes remains to be elucidated. There are several instances of bacterial cells carrying genes that encode homologues of the global regulators. The question is what the roles of these proteins are. We noticed that the enteroaggregative E. coli strain 042 carries a new hitherto uncharacterized copy of the hns gene. We decided to investigate why this pathogenic E. coli strain requires an extra H-NS paralogue, termed H-NS2. In our work, we show that H-NS2 displays specific expression and regulatory properties. H-NS2 targets a subset of H-NS-specific genes and may help to differentially modulate core and HGT genes by the H-NS cellular pool.

Suppression of Rac1 Signaling by Influenza A Virus NS1 Facilitates Viral Replication

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Jiang, Wei; Sheng, Chunjie; Gu, Xiuling; Liu, Dong; Yao, Chen; Gao, Shijuan; Chen, Shuai; Huang, Yinghui; Huang, Wenlin; Fang, Min

2016-01-01

Influenza A virus (IAV) is a major human pathogen with the potential to become pandemic. IAV contains only eight RNA segments; thus, the virus must fully exploit the host cellular machinery to facilitate its own replication. In an effort to comprehensively characterize the host machinery taken over by IAV in mammalian cells, we generated stable A549 cell lines with over-expression of the viral non-structural protein (NS1) to investigate the potential host factors that might be modulated by the NS1 protein. We found that the viral NS1 protein directly interacted with cellular Rac1 and facilitated viral replication. Further research revealed that NS1 down-regulated Rac1 activity via post-translational modifications. Therefore, our results demonstrated that IAV blocked Rac1-mediated host cell signal transduction through the NS1 protein to facilitate its own replication. Our findings provide a novel insight into the mechanism of IAV replication and indicate new avenues for the development of potential therapeutic targets. PMID:27869202

Murine Double Minute 2 SNP T309G Polymorphism and Urinary Tract Cancer Risk: A Meta-Analysis.

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Ding, Hui; Dai, Yu; Ning, Zhongyun; Fan, Ning; Wang, Zhiping; Li, Pei; Zhang, Liyuan; Tao, Yan; Wang, Hanzhang

2016-03-01

Urinary tract cancer is a common cause of cancer-related death. The etiology and pathogenesis of urinary tract cancer remain unclear, with genetic and epigenetic factors playing an important role. Studies of the polymorphism of murine double minute 2 (MDM2) have shown inconclusive trends in the risk of urinary tract cancer.To clarify this inconsistency, we conducted updated meta-analyses to evaluate the role of MDM2 T309G polymorphism in urinary tract cancer susceptibility.Data sources were Pubmed (1966-May 2015), Chinese biomedicine literature database (1978-May 2015), and hand searching of the reference lists of included studies:(1) research categories case-control study or a nested case-control study; (2) information evaluating the association between the MDM2 SNP309 and urinary tract cancer risk; (3) studies with sufficient data to perform a meta-analysis.It included the use of odds ratios (ORs) to assess the strength of the association, and 95% confidence intervals (CIs) give a sense of the precision of the estimate. We used I for the assessment of between-study heterogeneity, and publication bias was assessed using the funnel plot and the Egger test. Statistical analyses were performed by Review Manage, version 5.0 and Stata 11.0.A total of 18 studies met the eligibility criteria and were included in our analyses. Overall, there was no statistical association between MDM2 SNP309 and prostate cancer risk for the allele contrast, the GG genotype, the recessive genetic model, the dominant genetic model, and prostate cancer risk in all subjects (OR = 0.96, 95% CI 0.87-1.05, P = 0.36; OR = 0.93, 95% CI 0.75-1.15, P = 0.50; OR = 1.00, 95% CI 0.87-1.15, P = 0.99; OR = 0.93, 95% CI 0.80-1.07, P = 0.30), and between MDM2 SNP309 and bladder cancer risk (the allele contrast: OR = 1.06, 95% CI 0.89-1.27, P = 0.50; the GG genotype: OR = 1.12, 95% CI 0.79-1.61, P = 0.52; the dominant genetic model: OR = 1.03, 95% CI 0

NS maize hybrids in production regions of Serbia

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Stojaković Milisav

2010-01-01

Full Text Available Fifteen NS maize hybrids of FAO 300-700 maturity groups were evaluated in strip trials (plot size 1,120 m2 at 30 locations in Serbia. In all locations including all production regions, the most yielding hybrid was NS 6030 with average yield of 10.9 t ha-1. The additive Main Effects and Multiplicative Interaction (AMMI and the sites regression (SREG models were used to study basic structure of G x E interactions and the possible existence of different mega-environments in Serbian maize growing regions in 2009. The results of the 15 hybrids x 10 locations for grain yield in maize showed by biplot technique indicate several specific location-hybrid deviations (the AMMI biplot, and possible existence of at least one mega-environment (the GGE biplot. .

Thermal Energy Transfer Through All Ceramic Restorations

Science.gov (United States)

2016-06-01

correlate to a histological status or disease process. A positive response only expresses that there is a viable nerve fibers located within the pulp ...INTRODUCTION: The literature has demonstrated that cold testing with 1,1,1,2- tetrafluoroethane (TFE) can be used to assess the pulp vitality of teeth restored...restorative materials to natural teeth. MATERIALS AND METHODS: Thermoprobes (T-type, Omega) were inserted into the pulp chamber of 3 extracted human

How economics can further the success of ecological restoration.

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Iftekhar, Md Sayed; Polyakov, Maksym; Ansell, Dean; Gibson, Fiona; Kay, Geoffrey M

2017-04-01

Restoration scientists and practitioners have recently begun to include economic and social aspects in the design and investment decisions for restoration projects. With few exceptions, ecological restoration studies that include economics focus solely on evaluating costs of restoration projects. However, economic principles, tools, and instruments can be applied to a range of other factors that affect project success. We considered the relevance of applying economics to address 4 key challenges of ecological restoration: assessing social and economic benefits, estimating overall costs, project prioritization and selection, and long-term financing of restoration programs. We found it is uncommon to consider all types of benefits (such as nonmarket values) and costs (such as transaction costs) in restoration programs. Total benefit of a restoration project can be estimated using market prices and various nonmarket valuation techniques. Total cost of a project can be estimated using methods based on property or land-sale prices, such as hedonic pricing method and organizational surveys. Securing continuous (or long-term) funding is also vital to accomplishing restoration goals and can be achieved by establishing synergy with existing programs, public-private partnerships, and financing through taxation. © 2016 Society for Conservation Biology.

StpA and Hha stimulate pausing by RNA polymerase by promoting DNA-DNA bridging of H-NS filaments.

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Boudreau, Beth A; Hron, Daniel R; Qin, Liang; van der Valk, Ramon A; Kotlajich, Matthew V; Dame, Remus T; Landick, Robert

2018-06-20

In enterobacteria, AT-rich horizontally acquired genes, including virulence genes, are silenced through the actions of at least three nucleoid-associated proteins (NAPs): H-NS, StpA and Hha. These proteins form gene-silencing nucleoprotein filaments through direct DNA binding by H-NS and StpA homodimers or heterodimers. Both linear and bridged filaments, in which NAPs bind one or two DNA segments, respectively, have been observed. Hha can interact with H-NS or StpA filaments, but itself lacks a DNA-binding domain. Filaments composed of H-NS alone can inhibit transcription initiation and, in the bridged conformation, slow elongating RNA polymerase (RNAP) by promoting backtracking at pause sites. How the other NAPs modulate these effects of H-NS is unknown, despite evidence that they help regulate subsets of silenced genes in vivo (e.g. in pathogenicity islands). Here we report that Hha and StpA greatly enhance H-NS-stimulated pausing by RNAP at 20°C. StpA:H-NS or StpA-only filaments also stimulate pausing at 37°C, a temperature at which Hha:H-NS or H-NS-only filaments have much less effect. In addition, we report that both Hha and StpA greatly stimulate DNA-DNA bridging by H-NS filaments. Together, these observations indicate that Hha and StpA can affect H-NS-mediated gene regulation by stimulating bridging of H-NS/DNA filaments.

Potential of plant alkaloids as dengue ns3 protease inhibitors: Molecular docking and simulation approach

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Muhammad Tahir ul Qamar

2014-08-01

Full Text Available Dengue infection has become a worldwide health problem and infection rate is increasing each year. Alkaloids are important phytochemicals of medicinal plant and can be used as vaccine candidates for viruses. Therefore, present study was designed to find potential alkaloids inhibitors against the Dengue virus NS2B/NS3 protease which can inhibit the viral replication inside the host cell. Through molecular docking it was investigated that most of the alkaloids bound deeply in the binding pocket of Dengue virus NS2B/NS3 protease and had potential interactions with catalytic triad. Five alkaloids (6’-desmethylthalifaboramin; 3,5-dihydroxythalifaboramine; Betanin; Reserpic acid and Tubulosine successfully blocked the catalytic triad of NS2B/NS3 protease and these alkaloids can serve as a potential drug candidate to stop viral replication. It can be concluded from this study that these alkaloids could serve as important inhibitors to inhibit the replication of DENV and need further in-vitro investigations to confirm their efficacy and drug ability.

Comparative Analysis of Disruption Tolerant Network Routing Simulations in the One and NS-3

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2017-12-01

The added levels of simulation increase the processing required by a simulation . ns-3’s simulation of other layers of the network stack permits...NAVAL POSTGRADUATE SCHOOL MONTEREY, CALIFORNIA THESIS COMPARATIVE ANALYSIS OF DISRUPTION TOLERANT NETWORK ROUTING SIMULATIONS IN THE ONE AND NS-3...Thesis 03-23-2016 to 12-15-2017 4. TITLE AND SUBTITLE COMPARATIVE ANALYSIS OF DISRUPTION TOLERANT NETWORK ROUTING SIMULATIONS IN THE ONE AND NS-3 5

Comparative study of nanomechanical properties of cements used in teeth restoration

International Nuclear Information System (INIS)

Peluccio, M S; Bignardi, C; Lombardo, S; Montevecchi, F M; Carossa, S

2007-01-01

The discipline of dental science includes the diagnosis of disease in the mouth and teeth, its manifestations and the procedures involved in the restoration of their integrity and function. Restoration of lost tooth structure with suitable materials plays an integral part in the successful rehabilitation of oral tissues. Several factors influence the performance of dental restorations. These factors include the type of cement used to bond crown restoration to prepared teeth. The nanoindentation method was used to explore the mechanical properties of different types of resin cement polymerized using different techniques. A Nano Indenter XP (from MTS Nano Instruments, USA) was used for the experimental tests. A sample of 40 extracted human teeth were restored using two different resin cements: Variolink II (Ivoclar Vivadent, Liechtenstein) and Venus A2 (Heraeus Kulzer, Germany). Both resin cements are light-cured and one of them is self-cured so that the degree of polymerization would be higher. The data obtained for nanohardness and the Young's modulus were analysed using ANOVA to evaluate the influence of different factors (the resin cement and polymerization technique used, the position on the tooth-restoration interface) and to determine the best performance for restoration. The results obtained could give a useful indication of the choice of cementation technique and of the materials used for the restoration of lost tooth structure in different clinical cases

[Advances in Parvovirus Non-structural Protein NS1 Induced Apoptosis].

Science.gov (United States)

Tu, Mengyu; Liu, Fei; Chen, Shun; Wang, Mingshu; Cheng, Anchun

2015-11-01

Until now, more than seventeen parvovirus have been reported which can infect mammals and poultries. The infected cells appeared different properties of apoptosis and death, present a typical cytopathic effect. NS1 is a major nonstructural protein of parvovirus, with a conservative structure and function, which plays an important role in the viral life cycle. In addition to the influence on viral replication, the NS1 also participates in apoptosis induced by viruses. Parvovirus induced apoptosis which is mainly mediated by mitochondrial pathway, this review summarized the latest research progresses of parvovirus induced apoptosis.

Influenza A Virus NS1 Protein Promotes Efficient Nuclear Export of Unspliced Viral M1 mRNA.

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Pereira, Carina F; Read, Eliot K C; Wise, Helen M; Amorim, Maria J; Digard, Paul

2017-08-01

Influenza A virus mRNAs are transcribed by the viral RNA-dependent RNA polymerase in the cell nucleus before being exported to the cytoplasm for translation. Segment 7 produces two major transcripts: an unspliced mRNA that encodes the M1 matrix protein and a spliced transcript that encodes the M2 ion channel. Export of both mRNAs is dependent on the cellular NXF1/TAP pathway, but it is unclear how they are recruited to the export machinery or how the intron-containing but unspliced M1 mRNA bypasses the normal quality-control checkpoints. Using fluorescent in situ hybridization to monitor segment 7 mRNA localization, we found that cytoplasmic accumulation of unspliced M1 mRNA was inefficient in the absence of NS1, both in the context of segment 7 RNPs reconstituted by plasmid transfection and in mutant virus-infected cells. This effect was independent of any major effect on steady-state levels of segment 7 mRNA or splicing but corresponded to a ∼5-fold reduction in the accumulation of M1. A similar defect in intronless hemagglutinin (HA) mRNA nuclear export was seen with an NS1 mutant virus. Efficient export of M1 mRNA required both an intact NS1 RNA-binding domain and effector domain. Furthermore, while wild-type NS1 interacted with cellular NXF1 and also increased the interaction of segment 7 mRNA with NXF1, mutant NS1 polypeptides unable to promote mRNA export did neither. Thus, we propose that NS1 facilitates late viral gene expression by acting as an adaptor between viral mRNAs and the cellular nuclear export machinery to promote their nuclear export. IMPORTANCE Influenza A virus is a major pathogen of a wide variety of mammalian and avian species that threatens public health and food security. A fuller understanding of the virus life cycle is important to aid control strategies. The virus has a small genome that encodes relatively few proteins that are often multifunctional. Here, we characterize a new function for the NS1 protein, showing that, as well as

Forest restoration: a global dataset for biodiversity and vegetation structure.

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Crouzeilles, Renato; Ferreira, Mariana S; Curran, Michael

2016-08-01

Restoration initiatives are becoming increasingly applied around the world. Billions of dollars have been spent on ecological restoration research and initiatives, but restoration outcomes differ widely among these initiatives in part due to variable socioeconomic and ecological contexts. Here, we present the most comprehensive dataset gathered to date on forest restoration. It encompasses 269 primary studies across 221 study landscapes in 53 countries and contains 4,645 quantitative comparisons between reference ecosystems (e.g., old-growth forest) and degraded or restored ecosystems for five taxonomic groups (mammals, birds, invertebrates, herpetofauna, and plants) and five measures of vegetation structure reflecting different ecological processes (cover, density, height, biomass, and litter). We selected studies that (1) were conducted in forest ecosystems; (2) had multiple replicate sampling sites to measure indicators of biodiversity and/or vegetation structure in reference and restored and/or degraded ecosystems; and (3) used less-disturbed forests as a reference to the ecosystem under study. We recorded (1) latitude and longitude; (2) study year; (3) country; (4) biogeographic realm; (5) past disturbance type; (6) current disturbance type; (7) forest conversion class; (8) restoration activity; (9) time that a system has been disturbed; (10) time elapsed since restoration started; (11) ecological metric used to assess biodiversity; and (12) quantitative value of the ecological metric of biodiversity and/or vegetation structure for reference and restored and/or degraded ecosystems. These were the most common data available in the selected studies. We also estimated forest cover and configuration in each study landscape using a recently developed 1 km consensus land cover dataset. We measured forest configuration as the (1) mean size of all forest patches; (2) size of the largest forest patch; and (3) edge:area ratio of forest patches. Global analyses of the

[Effect of saliva contamination on microleakage around class-5 cavities restored with three different types of adhesive materials].

Science.gov (United States)

Iovan, Gianina; Stoleriu, Simona; Andrian, S; Dia, V; Căruntu, Irina Draga

2004-01-01

The recent improvement of adhesive materials should decrease the risk related to saliva contamination. The aim of this study was to evaluate the effect of saliva contamination on the microleakage within class V cavities restored with three different types of materials: conventional glass ionomer cement, composite resin and compomer. 30 human extracted teeth were randomly divided in 3 equal groups. In each group, class V cavities were prepared on both facial and lingual surfaces (but joint for glass ionomer cement and bevelled incisal margin for composite resin and compomer). The lingual cavities were contaminated with saliva prior to restoration, while the facial cavities were not contaminated, serving as control. After water storage for 24 hours, teeth were immersed in 1% methylene blue solution for 24 hours. The axial sections were viewed under an optical microscope and the extent of dye penetration along cervical, axial and incisal margins was measured in millimetres. Statistic analysis showed that under salivary contamination, microleakage increased along the cervical margin of restoration for all three tested materials. Saliva contamination resulted in microleakage within the axial wall of the cavity only for the conventional glass ionomer cement. These data indicate that composite resin and compomer used together with new adhesives seem to be less sensitive to saliva contamination compared to conventional materials. However, under saliva contamination, cervical microleakage cannot be completely prevented and proper isolation should still be mandatory.

Molecular models of NS3 protease variants of the Hepatitis C virus

Directory of Open Access Journals (Sweden)

Mello Isabel MVGC

2005-01-01

Full Text Available Abstract Background Hepatitis C virus (HCV currently infects approximately three percent of the world population. In view of the lack of vaccines against HCV, there is an urgent need for an efficient treatment of the disease by an effective antiviral drug. Rational drug design has not been the primary way for discovering major therapeutics. Nevertheless, there are reports of success in the development of inhibitor using a structure-based approach. One of the possible targets for drug development against HCV is the NS3 protease variants. Based on the three-dimensional structure of these variants we expect to identify new NS3 protease inhibitors. In order to speed up the modeling process all NS3 protease variant models were generated in a Beowulf cluster. The potential of the structural bioinformatics for development of new antiviral drugs is discussed. Results The atomic coordinates of crystallographic structure 1CU1 and 1DY9 were used as starting model for modeling of the NS3 protease variant structures. The NS3 protease variant structures are composed of six subdomains, which occur in sequence along the polypeptide chain. The protease domain exhibits the dual beta-barrel fold that is common among members of the chymotrypsin serine protease family. The helicase domain contains two structurally related beta-alpha-beta subdomains and a third subdomain of seven helices and three short beta strands. The latter domain is usually referred to as the helicase alpha-helical subdomain. The rmsd value of bond lengths and bond angles, the average G-factor and Verify 3D values are presented for NS3 protease variant structures. Conclusions This project increases the certainty that homology modeling is an useful tool in structural biology and that it can be very valuable in annotating genome sequence information and contributing to structural and functional genomics from virus. The structural models will be used to guide future efforts in the structure

Linking restoration ecology with coastal dune restoration

Science.gov (United States)

Lithgow, D.; Martínez, M. L.; Gallego-Fernández, J. B.; Hesp, P. A.; Flores, P.; Gachuz, S.; Rodríguez-Revelo, N.; Jiménez-Orocio, O.; Mendoza-González, G.; Álvarez-Molina, L. L.

2013-10-01

Restoration and preservation of coastal dunes is urgently needed because of the increasingly rapid loss and degradation of these ecosystems because of many human activities. These activities alter natural processes and coastal dynamics, eliminate topographic variability, fragment, degrade or eliminate habitats, reduce diversity and threaten endemic species. The actions of coastal dune restoration that are already taking place span contrasting activities that range from revegetating and stabilizing the mobile substrate, to removing plant cover and increasing substrate mobility. Our goal was to review how the relative progress of the actions of coastal dune restoration has been assessed, according to the ecosystem attributes outlined by the Society of Ecological Restoration: namely, integrity, health and sustainability and that are derived from the ecological theory of succession. We reviewed the peer reviewed literature published since 1988 that is listed in the ISI Web of Science journals as well as additional references, such as key books. We exclusively focused on large coastal dune systems (such as transgressive and parabolic dunefields) located on natural or seminatural coasts. We found 150 articles that included "coastal dune", "restoration" and "revegetation" in areas such as title, keywords and abstract. From these, 67 dealt specifically with coastal dune restoration. Most of the studies were performed in the USA, The Netherlands and South Africa, during the last two decades. Restoration success has been assessed directly and indirectly by measuring one or a few ecosystem variables. Some ecosystem attributes have been monitored more frequently (ecosystem integrity) than others (ecosystem health and sustainability). Finally, it is important to consider that ecological succession is a desirable approach in restoration actions. Natural dynamics and disturbances should be considered as part of the restored system, to improve ecosystem integrity, health and

25 CFR 309.17 - What are examples of woodwork that are Indian products?

Science.gov (United States)

2010-04-01

... 25 Indians 2 2010-04-01 2010-04-01 false What are examples of woodwork that are Indian products... INDIAN ARTS AND CRAFTS PRODUCTS § 309.17 What are examples of woodwork that are Indian products? (a..., hunting hats, spirit masks, bows and arrows, atlatls, redwood dug out canoes, war clubs, flutes, dance...

25 CFR 309.11 - What are examples of jewelry that are Indian products?

Science.gov (United States)

2010-04-01

... 25 Indians 2 2010-04-01 2010-04-01 false What are examples of jewelry that are Indian products... INDIAN ARTS AND CRAFTS PRODUCTS § 309.11 What are examples of jewelry that are Indian products? (a...) Specific examples include, but are not limited to: ivory and baleen scrimshaw bracelets, abalone shell...

DEB025 (Alisporivir inhibits hepatitis C virus replication by preventing a cyclophilin A induced cis-trans isomerisation in domain II of NS5A.

Directory of Open Access Journals (Sweden)

Lotte Coelmont

2010-10-01

Full Text Available DEB025/Debio 025 (Alisporivir is a cyclophilin (Cyp-binding molecule with potent anti-hepatitis C virus (HCV activity both in vitro and in vivo. It is currently being evaluated in phase II clinical trials. DEB025 binds to CypA, a peptidyl-prolyl cis-trans isomerase which is a crucial cofactor for HCV replication. Here we report that it was very difficult to select resistant replicons (genotype 1b to DEB025, requiring an average of 20 weeks (four independent experiments, compared to the typically <2 weeks with protease or polymerase inhibitors. This indicates a high genetic barrier to resistance for DEB025. Mutation D320E in NS5A was the only mutation consistently selected in the replicon genome. This mutation alone conferred a low-level (3.9-fold resistance. Replacing the NS5A gene (but not the NS5B gene from the wild type (WT genome with the corresponding sequence from the DEB025(res replicon resulted in transfer of resistance. Cross-resistance with cyclosporine A (CsA was observed, whereas NS3 protease and NS5B polymerase inhibitors retained WT-activity against DEB025(res replicons. Unlike WT, DEB025(res replicon replicated efficiently in CypA knock down cells. However, DEB025 disrupted the interaction between CypA and NS5A regardless of whether the NS5A protein was derived from WT or DEB025(res replicon. NMR titration experiments with peptides derived from the WT or the DEB025(res domain II of NS5A corroborated this observation in a quantitative manner. Interestingly, comparative NMR studies on two 20-mer NS5A peptides that contain D320 or E320 revealed a shift in population between the major and minor conformers. These data suggest that D320E conferred low-level resistance to DEB025 probably by reducing the need for CypA-dependent isomerisation of NS5A. Prolonged DEB025 treatment and multiple genotypic changes may be necessary to generate significant resistance to DEB025, underlying the high barrier to resistance.

Raising the avermectins production in Streptomyces avermitilis by utilizing nanosecond pulsed electric fields (nsPEFs)

Science.gov (United States)

Guo, Jinsong; Ma, Ruonan; Su, Bo; Li, Yinglong; Zhang, Jue; Fang, Jing

2016-05-01

Avermectins, a group of anthelmintic and insecticidal agents produced from Streptomyces avermitilis, are widely used in agricultural, veterinary, and medical fields. This study presents the first report on the potential of using nanosecond pulsed electric fields (nsPEFs) to improve avermectin production in S. avermitilis. The results of colony forming units showed that 20 pulses of nsPEFs at 10 kV/cm and 20 kV/cm had a significant effect on proliferation, while 100 pulses of nsPEFs at 30 kV/cm exhibited an obvious effect on inhibition of agents. Ultraviolet spectrophotometry assay revealed that 20 pulses of nsPEFs at 15 kV/cm increased avermectin production by 42% and reduced the time for reaching a plateau in fermentation process from 7 days to 5 days. In addition, the decreased oxidation reduction potential (ORP) and increased temperature of nsPEFs-treated liquid were evidenced to be closely associated with the improved cell growth and fermentation efficiency of avermectins in S. avermitilis. More importantly, the real-time RT-PCR analysis showed that nsPEFs could remarkably enhance the expression of aveR and malE in S. avermitilis during fermentation, which are positive regulator for avermectin biosynthesis. Therefore, the nsPEFs technology presents an alternative strategy to be developed to increase avermectin output in fermentation industry.

Broadband Fan Noise Prediction System for Turbofan Engines. Volume 1; Setup_BFaNS User's Manual and Developer's Guide

Science.gov (United States)

Morin, Bruce L.

2010-01-01

Pratt & Whitney has developed a Broadband Fan Noise Prediction System (BFaNS) for turbofan engines. This system computes the noise generated by turbulence impinging on the leading edges of the fan and fan exit guide vane, and noise generated by boundary-layer turbulence passing over the fan trailing edge. BFaNS has been validated on three fan rigs that were tested during the NASA Advanced Subsonic Technology Program (AST). The predicted noise spectra agreed well with measured data. The predicted effects of fan speed, vane count, and vane sweep also agreed well with measurements. The noise prediction system consists of two computer programs: Setup_BFaNS and BFaNS. Setup_BFaNS converts user-specified geometry and flow-field information into a BFaNS input file. From this input file, BFaNS computes the inlet and aft broadband sound power spectra generated by the fan and FEGV. The output file from BFaNS contains the inlet, aft and total sound power spectra from each noise source. This report is the first volume of a three-volume set documenting the Broadband Fan Noise Prediction System: Volume 1: Setup_BFaNS User s Manual and Developer s Guide; Volume 2: BFaNS User's Manual and Developer s Guide; and Volume 3: Validation and Test Cases. The present volume begins with an overview of the Broadband Fan Noise Prediction System, followed by step-by-step instructions for installing and running Setup_BFaNS. It concludes with technical documentation of the Setup_BFaNS computer program.

Minimizing waste in environmental restoration

International Nuclear Information System (INIS)

Moos, L.; Thuot, J.R.

1996-01-01

Environmental restoration, decontamination and decommissioning and facility dismantelment projects are not typically known for their waste minimization and pollution prevention efforts. Typical projects are driven by schedules and milestones with little attention given to cost or waste minimization. Conventional wisdom in these projects is that the waste already exists and cannot be reduced or minimized. In fact, however, there are three significant areas where waste and cost can be reduced. Waste reduction can occur in three ways: beneficial reuse or recycling; segregation of waste types; and reducing generation of secondary waste. This paper will discuss several examples of reuse, recycle, segregation, and secondary waste reduction at ANL restoration programs

Topical Retinol Restores Type I Collagen Production in Photoaged Forearm Skin within Four Weeks

Directory of Open Access Journals (Sweden)

Min Sun

2016-09-01

Full Text Available Production of type I collagen (COL1, the major structural protein of the skin, declines during aging, leading to skin thinning and becoming fragile, which increases the risk of bruising and wound healing disorders in the elderly. Topical treatments that can restore COL1 synthesis and ultimately COL1 content in aged skin hold promise to improve skin health. Much effort has been spent on developing agents that can safely and effectively enhance COL1 synthesis in aged skin. However, how fast and to what extent COL1 production in aged skin can be enhanced by a topical treatment remains unclear. Herein, we investigated a four-week topical retinol (ROL treatment. A one-day occlusion of ROL (0.4% or vehicle was applied on photoaged forearms of elderly (>65 years old subjects once a week for four weeks. Vehicle was also applied on forearms of young (23–33 years subjects in the same manner. Skin samples were obtained one week after the last treatment and analyzed for COL1 synthesis. We found that the ROL treatment increased the level of COL1 mRNA (2.3-fold and proCOL1 protein (1.8-fold in photoaged forearms to levels similar to that of young forearms within four weeks. Our study proves the concept that reduced COL1 production in aged skin can be readily restored. In addition, our study provides an evidence-based foundation for developing COL1-enhancing topical agents, and establishes a reliable and practical efficacy test for evaluating such agents.

H-NS represses transcription of the flagellin gene lafA of lateral flagella in Vibrio parahaemolyticus.

Science.gov (United States)

Wang, Yan; Zhang, Yiquan; Yin, Zhe; Wang, Jie; Zhu, Yongzhe; Peng, Haoran; Zhou, Dongsheng; Qi, Zhongtian; Yang, Wenhui

2018-01-01

Swarming motility is ultimately mediated by the proton-powered lateral flagellar (laf) system in Vibrio parahaemolyticus. Expression of laf genes is tightly regulated by a number of environmental conditions and regulatory factors. The nucleoid-associated DNA-binding protein H-NS is a small and abundant protein that is widely distributed in bacteria, and H-NS-like protein-dependent expression of laf genes has been identified in Vibrio cholerae and V. parahaemolyticus. The data presented here show that H-NS acts as a repressor of the swarming motility in V. parahaemolyticus. A single σ 28 -dependent promoter was detected for lafA encoding the flagellin of the lateral flagella, and its activity was directly repressed by H-NS. Thus, H-NS represses swarming motility by directly acting on lafA. Briefly, this work revealed a novel function for H-NS as a repressor of the expression of lafA and swarming motility in V. parahaemolyticus.

Mosquito Rasputin interacts with chikungunya virus nsP3 and determines the infection rate in Aedes albopictus.

Science.gov (United States)

Fros, Jelke J; Geertsema, Corinne; Zouache, Karima; Baggen, Jim; Domeradzka, Natalia; van Leeuwen, Daniël M; Flipse, Jacky; Vlak, Just M; Failloux, Anna-Bella; Pijlman, Gorben P

2015-09-17

Chikungunya virus (CHIKV) is an arthritogenic alphavirus (family Togaviridae), transmitted by Aedes species mosquitoes. CHIKV re-emerged in 2004 with multiple outbreaks worldwide and recently reached the Americas where it has infected over a million individuals in a rapidly expanding epidemic. While alphavirus replication is well understood in general, the specific function (s) of non-structural protein nsP3 remain elusive. CHIKV nsP3 modulates the mammalian stress response by preventing stress granule formation through sequestration of G3BP. In mosquitoes, nsP3 is a determinant of vector specificity, but its functional interaction with mosquito proteins is unclear. In this research we studied the domains required for localization of CHIKV nsP3 in insect cells and demonstrated its molecular interaction with Rasputin (Rin), the mosquito homologue of G3BP. The biological involvement of Rin in CHIKV infection was investigated in live Ae. albopictus mosquitoes. In insect cells, nsP3 localized as cytoplasmic granules, which was dependent on the central domain and the C-terminal variable region but independent of the N-terminal macrodomain. Ae. albopictus Rin displayed a diffuse, cytoplasmic localization, but was effectively sequestered into nsP3-granules upon nsP3 co-expression. Site-directed mutagenesis showed that the Rin-nsP3 interaction involved the NTF2-like domain of Rin and two conserved TFGD repeats in the C-terminal variable domain of nsP3. Although in vitro silencing of Rin did not impact nsP3 localization or CHIKV replication in cell culture, Rin depletion in vivo significantly decreased the CHIKV infection rate and transmissibility in Ae.albopictus. We identified the nsP3 hypervariable C-terminal domain as a critical factor for granular localization and sequestration of mosquito Rin. Our study offers novel insight into a conserved virus-mosquito interaction at the molecular level, and reveals a strong proviral role for G3BP homologue Rin in live mosquitoes

Restorative Justice Of Adjudication On The Household Violence

Directory of Open Access Journals (Sweden)

Srigandawati

2017-06-01

Full Text Available The essence of restorative justice in the settlement of household violence is very important as bridge for peace of the parties to restoring good relations between the perpetrator and victim both the direct and indirect victim the family of victim. The type of research is socio-legal research with the normative law method doctrinal research. The results shows that the implementation of restorative justice of adjudication on household violence cases can be applied although there is no legal arrangement. The judge may apply in its judgment based on the fact that the judge cannot refuse a case because of a law that does not exist or it is unclear. Judges are required to explore the values that live within society to discover the law. It can be concluded that restorative justice has been acknowledged by its existence in the adjudication as the purpose of punishment. Similar perceptions are required for law enforcers concern the concept of restorative justice as the purpose of punishment.

Evolutionary conservation and neuronal mechanisms of auditory perceptual restoration.

Science.gov (United States)

Petkov, Christopher I; Sutter, Mitchell L

2011-01-01

Auditory perceptual 'restoration' occurs when the auditory system restores an occluded or masked sound of interest. Behavioral work on auditory restoration in humans began over 50 years ago using it to model a noisy environmental scene with competing sounds. It has become clear that not only humans experience auditory restoration: restoration has been broadly conserved in many species. Behavioral studies in humans and animals provide a necessary foundation to link the insights being obtained from human EEG and fMRI to those from animal neurophysiology. The aggregate of data resulting from multiple approaches across species has begun to clarify the neuronal bases of auditory restoration. Different types of neural responses supporting restoration have been found, supportive of multiple mechanisms working within a species. Yet a general principle has emerged that responses correlated with restoration mimic the response that would have been given to the uninterrupted sound of interest. Using the same technology to study different species will help us to better harness animal models of 'auditory scene analysis' to clarify the conserved neural mechanisms shaping the perceptual organization of sound and to advance strategies to improve hearing in natural environmental settings. © 2010 Elsevier B.V. All rights reserved.

In vivo effects of the IKr agonist NS3623 on cardiac electrophysiology of the guinea pig

DEFF Research Database (Denmark)

Hansen, Rie Schultz; Olesen, Søren-Peter; Rønn, Lars Christian B

2008-01-01

to examining the in vivo effects of NS3623. Injection of 30 mg/kg NS3623 shortened the corrected QT interval by 25 +/- 4% in anaesthetized guinea pigs. Accordingly, 50 mg/kg of NS3623 shortened the QT interval by 30 +/- 6% in conscious guinea pigs. Finally, pharmacologically induced QT prolongation by a h......ERG channel antagonist (0.15 mg/kg E-4031) could be reverted by injection of NS3623 (50 mg/kg) in conscious guinea pigs. In conclusion, the present in vivo study demonstrates that injection of the hERG channel agonist NS3623 results in shortening of the QTc interval as well as reversal of a pharmacologically...... induced QT prolongation in both anaesthetized and conscious guinea pigs....

Partition dataset according to amino acid type improves the prediction of deleterious non-synonymous SNPs

International Nuclear Information System (INIS)

Yang, Jing; Li, Yuan-Yuan; Li, Yi-Xue; Ye, Zhi-Qiang

2012-01-01

Highlights: ► Proper dataset partition can improve the prediction of deleterious nsSNPs. ► Partition according to original residue type at nsSNP is a good criterion. ► Similar strategy is supposed promising in other machine learning problems. -- Abstract: Many non-synonymous SNPs (nsSNPs) are associated with diseases, and numerous machine learning methods have been applied to train classifiers for sorting disease-associated nsSNPs from neutral ones. The continuously accumulated nsSNP data allows us to further explore better prediction approaches. In this work, we partitioned the training data into 20 subsets according to either original or substituted amino acid type at the nsSNP site. Using support vector machine (SVM), training classification models on each subset resulted in an overall accuracy of 76.3% or 74.9% depending on the two different partition criteria, while training on the whole dataset obtained an accuracy of only 72.6%. Moreover, the dataset was also randomly divided into 20 subsets, but the corresponding accuracy was only 73.2%. Our results demonstrated that partitioning the whole training dataset into subsets properly, i.e., according to the residue type at the nsSNP site, will improve the performance of the trained classifiers significantly, which should be valuable in developing better tools for predicting the disease-association of nsSNPs.

Spatial navigation impairment is proportional to right hippocampal volume

Czech Academy of Sciences Publication Activity Database

Nedelská, Z.; Andel, R.; Laczó, J.; Vlček, Kamil; Hořínek, D.; Lisý, J.; Sheardová, K.; Bureš, Jan; Hort, J.

2012-01-01

Roč. 109, č. 7 (2012), s. 2590-2594 ISSN 0027-8424 R&D Projects: GA ČR(CZ) GA309/09/1053; GA ČR(CZ) GA309/09/0286; GA MŠk(CZ) 1M0517; GA MŠk(CZ) LC554 Grant - others:GA MZd(CZ) NS10331 Institutional research plan: CEZ:AV0Z50110509 Keywords : spatial navigation * Alzheimer’s Disease * hippocampal volume Subject RIV: FH - Neurology Impact factor: 9.737, year: 2012

Hepatitis C virus expressing reporter tagged NS5A protein

DEFF Research Database (Denmark)

2014-01-01

Hepatitis C reporter viruses containing Core through NS2 of prototype isolates of all major HCV genotypes and the remaining genes of isolate JFH1, by insertion of reporter genes in domain III of HCV NS5A were developed. A deletion upstream of the inserted reporter gene sequence conferred favorable...... growth kinetics in Huh7.5 cells to these viruses. These reporter viruses can be used for high throughput analysis of drug and vaccine candidates as well as patient samples. JFH1-based intergenotypic recombinants with genotype specific homotypic 5'UTR, or heterotypic 5'UTR (either of genotype 1a (strain H...

The Management of Dissonance in Nature Restoration

DEFF Research Database (Denmark)

Clemmensen, Thomas Juel

2016-01-01

Nature restoration is far from a neural undertaking. Just like any other type of heritage production, it can be the source of dissonance—‘our’ nature is not necessary ‘their’ nature. Often this dissonance is managed in ways, which are not particularly sensitive to site-specificity. As exemplified...... for multiple interpretations to coexist. Indications can be found in the Re-naturalization of River Aire (2002-2015)—a restoration project, which reveals approaches that could be labelled landscape architecture specific....

The Management of Dissonance in Nature Restoration

DEFF Research Database (Denmark)

Clemmensen, Thomas Juel

2014-01-01

Nature restoration is far from a neural undertaking. Just like any other type of heritage production, it can be the source of dissonance—‘our’ nature is not necessary ‘their’ nature. Often this dissonance is managed in ways, which are not particularly sensitive to site-specificity. As exemplified...... for multiple interpretations to coexist. Indications can be found in the Re-naturalization of River Aire (2002-2015)—a restoration project, which reveals approaches that could be labelled landscape architecture specific....

The μs and ns mode modulation system for grid controlled gun of the HESYRL linac

International Nuclear Information System (INIS)

Wang, Guicheng; Hong, Jun; Pei, Yuanji

1988-01-01

A μs and ns mode modulation system has been developed for the grid-controlled gun in the HESYRL. The gun drived by this system generated 1A and 500 MA pulse current for μs and ns mode respectively. In the ns mode modulation pulse formulation system, the sharper was built up using one transistor 3DA87D as avalanche switch and a shortcircuit coaxal cable as waveform sharp element. Outline of the μs mode system and details of the ns mode system are presented. (author)

31 CFR 309.12 - Relief on account of loss, theft or destruction, etc.

Science.gov (United States)

2010-07-01

... 31 Money and Finance: Treasury 2 2010-07-01 2010-07-01 false Relief on account of loss, theft or... BILLS § 309.12 Relief on account of loss, theft or destruction, etc. (a) Relief on account of the loss, theft, destruction, mutilation or defacement of Treasury bills may be given only under the authority of...

Exploring the molecular basis of dsRNA recognition by NS1 protein of influenza A virus using molecular dynamics simulation and free energy calculation.

Science.gov (United States)

Pan, Dabo; Sun, Huijun; Shen, Yulin; Liu, Huanxiang; Yao, Xiaojun

2011-12-01

The frequent outbreak of influenza pandemic and the limited available anti-influenza drugs highlight the urgent need for the development of new antiviral drugs. The dsRNA-binding surface of nonstructural protein 1 of influenza A virus (NS1A) is a promising target. The detailed understanding of NS1A-dsRNA interaction will be valuable for structure-based anti-influenza drug discovery. To characterize and explore the key interaction features between dsRNA and NS1A, molecular dynamics simulation combined with MM-GBSA calculations were performed. Based on the MM-GBSA calculations, we find that the intermolecular van der Waals interaction and the nonpolar solvation term provide the main driving force for the binding process. Meanwhile, 17 key residues from NS1A were identified to be responsible for the dsRNA binding. Compared with the wild type NS1A, all the studied mutants S42A, T49A, R38A, R35AR46A have obvious reduced binding free energies with dsRNA reflecting in the reduction of the polar and/or nonpolar interactions. In addition, the structural and energy analysis indicate the mutations have a small effect to the backbone structures but the loss of side chain interactions is responsible for the decrease of the binding affinity. The uncovering of NS1A-dsRNA recognition mechanism will provide some useful insights and new chances for the development of anti-influenza drugs. Copyright © 2011 Elsevier B.V. All rights reserved.

Isolation and sequence analysis of the complete NS1 and VP2 genes of canine parvovirus from domestic dogs in 2013 and 2014 in China.

Science.gov (United States)

Wang, Hualei; Jin, Hongli; Li, Qian; Zhao, Guoxing; Cheng, Nan; Feng, Na; Zheng, Xuexing; Wang, Jianzhong; Zhao, Yongkun; Li, Ling; Cao, Zengguo; Yan, Feihu; Wang, Lina; Wang, Tiecheng; Gao, Yuwei; Yang, Songtao; Xia, Xianzhu

2016-02-01

Canine parvovirus (CPV) can cause severe disease in animals and continuously generates new variant and recombinant strains in dogs that have a strong impact on sanitation. It is therefore necessary to investigate epidemic CPV strains to improve our understanding of CPV transmission and epidemic behavior. However, most studies have focused on the analysis of VP2, and therefore, information about recombination and relationships between strains is still lacking. Here, 14 strains of CPV were isolated from domestic dogs suspected of hosting CPV between 2013 and 2014 in China. The complete NS1 and VP2 genes were sequenced and analyzed. The results suggest that the new CPV-2a and new CPV-2b types are the prevalent strains in China. In addition to a few mutations (residues 19, 544, 545, 572 and 583 of NS1 and residues 267, 370, 377 and 440 of VP2) that were preserved during transmission, new mutations (residues 60, 630 of NS1, and residues 21, 310 of VP2) were found in the isolated strains. A phylogenetic tree based on VP2 sequences illustrated that the new CPV-2a and new CPV-2b strains from China form single clusters that are distinct from lineages from other countries. Moreover, recombination between the new CPV-2a and new CPV-2b types was also identified in the isolated strains. Due to differences in selection pressures or recombination, there were a small number of inconsistencies between the phylogenetic trees for VP2 and NS1, which indicated that phylogenetic relationships based on VP2 might not be representative of those based on NS1. The data indicated that mutations and recombination are constantly occurring along with the spread of CPV in China.

76 FR 59174 - Environmental Assessment and Finding of No Significant Impact for the N.S. Savannah; License NS-1...

Science.gov (United States)

2011-09-23

... of Federal Regulations (10 CFR) part 73 and 10 CFR 50.54(p) for the N.S. Savannah (NSS). This... security requirements from the 10 CFR Part 50 licensed site because the NSS spent fuel elements were... Carolina. There is no longer any special nuclear material (SNM) located within the NSS other than that...

Process Performances of 2 ns Pulsed Discharge Plasma

Science.gov (United States)

Matsumoto, Takao; Wang, Douyan; Namihira, Takao; Akiyama, Hidenori

2011-08-01

Pulsed discharge plasmas have been used to treat exhaust gases. Since pulse duration and the rise time of applied voltage to the discharge electrode has a strong influence on the energy efficiency of pollutant removal, the development of a short-pulse generator is of paramount importance for practical applications. In this work, it is demonstrated that the non thermal plasma produced by the 2 ns pulsed discharge has a higher energy efficiency than the 5 ns pulsed discharge plasma for NO removal and ozone generation. Typically, the NO removal efficiency was 1.0 mol kW-1 h-1 for 70% NO removal (initial NO concentration = 200 ppm, gas flow = 10 L/min). Meanwhile, the ozone yield was 500 g kW-1 h-1 for 20 g/m3 ozone concentration in the case of oxygen feeding. These energy efficiencies are the highest in the literature.

Data center network performance evaluation in ns3

DEFF Research Database (Denmark)

Andrus, Bogdan-Mihai; Vegas Olmos, Juan José

2015-01-01

In the following paper we present the analysis of highly interconnected topologies like hypercube and torus and how they can be implemented in data centers in order to cope with the rapid increase and demands for performance of the internal traffic. By replicating the topologies in NS3 and subjec......In the following paper we present the analysis of highly interconnected topologies like hypercube and torus and how they can be implemented in data centers in order to cope with the rapid increase and demands for performance of the internal traffic. By replicating the topologies in NS3...... and subjecting them to uniformly distributed traffic routed by shortest path algorithms we are able to extract statistics related to average throughput, latency and loss rate that show the decrease in the average throughput per connection is only about 5% for the hypercube compared to 16% for the 3D torus when...

Evaluation of dengue NS1 antigen rapid tests and ELISA kits using clinical samples.

Directory of Open Access Journals (Sweden)

Subhamoy Pal

Full Text Available Early diagnosis of dengue virus (DENV infection can improve clinical outcomes by ensuring close follow-up, initiating appropriate supportive therapies and raising awareness to the potential of hemorrhage or shock. Non-structural glycoprotein-1 (NS1 has proven to be a useful biomarker for early diagnosis of dengue. A number of rapid diagnostic tests (RDTs and enzyme-linked immunosorbent assays (ELISAs targeting NS1 antigen (Ag are now commercially available. Here we evaluated these tests using a well-characterized panel of clinical samples to determine their effectiveness for early diagnosis.Retrospective samples from South America were used to evaluate the following tests: (i "Dengue NS1 Ag STRIP" and (ii "Platelia Dengue NS1 Ag ELISA" (Bio-Rad, France, (iii "Dengue NS1 Detect Rapid Test (1st Generation" and (iv "DENV Detect NS1 ELISA" (InBios International, United States, (v "Panbio Dengue Early Rapid (1st generation" (vi "Panbio Dengue Early ELISA (2nd generation" and (vii "SD Bioline Dengue NS1 Ag Rapid Test" (Alere, United States. Overall, the sensitivity of the RDTs ranged from 71.9%-79.1% while the sensitivity of the ELISAs varied between 85.6-95.9%, using virus isolation as the reference method. Most tests had lower sensitivity for DENV-4 relative to the other three serotypes, were less sensitive in detecting secondary infections, and appeared to be most sensitive on Day 3-4 post symptom onset. The specificity of all evaluated tests ranged from 95%-100%.ELISAs had greater overall sensitivity than RDTs. In conjunction with other parameters, the performance data can help determine which dengue diagnostics should be used during the first few days of illness, when the patients are most likely to present to a clinic seeking care.

Resistance Patterns Associated with HCV NS5A Inhibitors Provide Limited Insight into Drug Binding

Directory of Open Access Journals (Sweden)

Moheshwarnath Issur

2014-11-01

Full Text Available Direct-acting antivirals (DAAs have significantly improved the treatment of infection with the hepatitis C virus. A promising class of novel antiviral agents targets the HCV NS5A protein. The high potency and broad genotypic coverage are favorable properties. NS5A inhibitors are currently assessed in advanced clinical trials in combination with viral polymerase inhibitors and/or viral protease inhibitors. However, the clinical use of NS5A inhibitors is also associated with new challenges. HCV variants with decreased susceptibility to these drugs can emerge and compromise therapy. In this review, we discuss resistance patterns in NS5A with focus prevalence and implications for inhibitor binding.

Activation of ERG2 potassium channels by the diphenylurea NS1643

DEFF Research Database (Denmark)

Elmedyb, Pernille; Olesen, Søren-Peter; Grunnet, Morten

2007-01-01

Three members of the ERG potassium channel family have been described (ERG1-3 or Kv 11.1-3). ERG1 is by far the best characterized subtype and it constitutes the molecular component of the cardiac I(Kr) current. All three channel subtypes are expressed in neurons but their function remains unclear....... The lack of functional information is at least partly due to the lack of specific pharmacological tools. The compound NS1643 has earlier been reported as an ERG1 channel activator. We found that NS1643 also activates the ERG2 channel; however, the molecular mechanism of the activation differs between...... the ERG1 and ERG2 channels. This is surprising since ERG1 and ERG2 channels have very similar biophysical and structural characteristics. For ERG2, NS1643 causes a left-ward shift of the activation curve, a faster time-constant of activation and a slower time-constant of inactivation as well...

Decontamination tests using an electrolytic method on NS 22 S stainless steel discs (1963); Essais de decontamination par voie electrolytique de plaquettes en acier inoxydable NS 22 S (1963)

Energy Technology Data Exchange (ETDEWEB)

Boutot, P; Schipfer, P [Commissariat a l' Energie Atomique, Centre de Production de Plutonium, Marcoule (France). Centre d' Etudes Nucleaires

1963-07-01

These tests were carried out with a view to observing the results obtained by using electrolytic polishing for the decontamination operations. The experimental equipment consists essentially of a current rectifier and adjuster, and of an electrolytic cell fitted with an automatic system for thermal regulation and agitation. The samples made of type NS 22 S stainless steel are contaminated with an active solution of fission products. The activity of the discs is measured before and after each treatment using a bell counter. For each electrolyte, the parameters studied are: - the time, - the reactant concentration, - the temperature, - the current density, - the corrosion. Taking into account the necessity of transforming as little as possible the surface of the part to be treated, the best results are generally obtained using intermediate concentrations of the reactant, low temperatures, and high current densities. (authors) [French] Ces essais ont ete effectues dans le but d'observer les resultats obtenus en utilisant le procede de polissage electrolytique pour les operations de decontamination. Le dispositif experimental consiste essentiellement en un redresseur-variateur de courant et en une cellule electrolytique munie d'un systeme automatique de regulation thermique et d'agitation. Les echantillons en acier inoxydable du type NS 22 S sont contamines par une solution active de produits de fission. L'activite des plaquettes est mesuree avant et apres chaque traitement au moyen d'un compteur cloche. Pour chaque electrolyte, les parametres etudies sont: - le temps, - la concentration du reactif, - la temperature, - la densite de courant, - la corrosion. En tenant compte de la necessite de transformer au minimum l'etat de surface de la piece a traiter, les resultats les meilleurs sont generalement obtenus pour des concentrations moyennes de reactif, des temperatures basses et des densites de courant elevees. (auteurs)

Lax-Phillips scattering theory with perturbations of the type: V(x)=(φ(x))/|x|β, where β=2-(n)/s, φ is an element of Ls(Rn), s > 2 and s ≥ (n)/2

International Nuclear Information System (INIS)

Brambila-Paz, F.; Duong Minh Duc.

1990-12-01

A scattering theory for the wave equation with compactly supported perturbations was developed by Lax-Phillips in 1967. Using Enss approach, Phillips developed a Lax-Phillips scattering theory with short range perturbations of the type: V(x)=o((1)/|x| β ), β > 2. In this paper we develop a scattering theory for more general perturbations, i.e. for V(x)=(φ(x))/|x| β , where β=2-(n)/s, φ is an element of L s (R n ), s > 2 and s ≥ (n)/2. Refs

Quantitative Analysis of Hepatitis C NS5A Viral Protein Dynamics on the ER Surface

Directory of Open Access Journals (Sweden)

Markus M. Knodel

2018-01-01

Full Text Available Exploring biophysical properties of virus-encoded components and their requirement for virus replication is an exciting new area of interdisciplinary virological research. To date, spatial resolution has only rarely been analyzed in computational/biophysical descriptions of virus replication dynamics. However, it is widely acknowledged that intracellular spatial dependence is a crucial component of virus life cycles. The hepatitis C virus-encoded NS5A protein is an endoplasmatic reticulum (ER-anchored viral protein and an essential component of the virus replication machinery. Therefore, we simulate NS5A dynamics on realistic reconstructed, curved ER surfaces by means of surface partial differential equations (sPDE upon unstructured grids. We match the in silico NS5A diffusion constant such that the NS5A sPDE simulation data reproduce experimental NS5A fluorescence recovery after photobleaching (FRAP time series data. This parameter estimation yields the NS5A diffusion constant. Such parameters are needed for spatial models of HCV dynamics, which we are developing in parallel but remain qualitative at this stage. Thus, our present study likely provides the first quantitative biophysical description of the movement of a viral component. Our spatio-temporal resolved ansatz paves new ways for understanding intricate spatial-defined processes central to specfic aspects of virus life cycles.

Quantitative Analysis of Hepatitis C NS5A Viral Protein Dynamics on the ER Surface.

Science.gov (United States)

Knodel, Markus M; Nägel, Arne; Reiter, Sebastian; Vogel, Andreas; Targett-Adams, Paul; McLauchlan, John; Herrmann, Eva; Wittum, Gabriel

2018-01-08

Exploring biophysical properties of virus-encoded components and their requirement for virus replication is an exciting new area of interdisciplinary virological research. To date, spatial resolution has only rarely been analyzed in computational/biophysical descriptions of virus replication dynamics. However, it is widely acknowledged that intracellular spatial dependence is a crucial component of virus life cycles. The hepatitis C virus-encoded NS5A protein is an endoplasmatic reticulum (ER)-anchored viral protein and an essential component of the virus replication machinery. Therefore, we simulate NS5A dynamics on realistic reconstructed, curved ER surfaces by means of surface partial differential equations (sPDE) upon unstructured grids. We match the in silico NS5A diffusion constant such that the NS5A sPDE simulation data reproduce experimental NS5A fluorescence recovery after photobleaching (FRAP) time series data. This parameter estimation yields the NS5A diffusion constant. Such parameters are needed for spatial models of HCV dynamics, which we are developing in parallel but remain qualitative at this stage. Thus, our present study likely provides the first quantitative biophysical description of the movement of a viral component. Our spatio-temporal resolved ansatz paves new ways for understanding intricate spatial-defined processes central to specfic aspects of virus life cycles.

Quantitative Analysis of Hepatitis C NS5A Viral Protein Dynamics on the ER Surface

Science.gov (United States)

Nägel, Arne; Reiter, Sebastian; Vogel, Andreas; McLauchlan, John; Herrmann, Eva; Wittum, Gabriel

2018-01-01

Exploring biophysical properties of virus-encoded components and their requirement for virus replication is an exciting new area of interdisciplinary virological research. To date, spatial resolution has only rarely been analyzed in computational/biophysical descriptions of virus replication dynamics. However, it is widely acknowledged that intracellular spatial dependence is a crucial component of virus life cycles. The hepatitis C virus-encoded NS5A protein is an endoplasmatic reticulum (ER)-anchored viral protein and an essential component of the virus replication machinery. Therefore, we simulate NS5A dynamics on realistic reconstructed, curved ER surfaces by means of surface partial differential equations (sPDE) upon unstructured grids. We match the in silico NS5A diffusion constant such that the NS5A sPDE simulation data reproduce experimental NS5A fluorescence recovery after photobleaching (FRAP) time series data. This parameter estimation yields the NS5A diffusion constant. Such parameters are needed for spatial models of HCV dynamics, which we are developing in parallel but remain qualitative at this stage. Thus, our present study likely provides the first quantitative biophysical description of the movement of a viral component. Our spatio-temporal resolved ansatz paves new ways for understanding intricate spatial-defined processes central to specfic aspects of virus life cycles. PMID:29316722

Quantitative Analysis of Hepatitis C NS5A Viral Protein Dynamics on the ER Surface

KAUST Repository

Knodel, Markus

2018-01-08

Exploring biophysical properties of virus-encoded components and their requirement for virus replication is an exciting new area of interdisciplinary virological research. To date, spatial resolution has only rarely been analyzed in computational/biophysical descriptions of virus replication dynamics. However, it is widely acknowledged that intracellular spatial dependence is a crucial component of virus life cycles. The hepatitis C virus-encoded NS5A protein is an endoplasmatic reticulum (ER)-anchored viral protein and an essential component of the virus replication machinery. Therefore, we simulate NS5A dynamics on realistic reconstructed, curved ER surfaces by means of surface partial differential equations (sPDE) upon unstructured grids. We match the in silico NS5A diffusion constant such that the NS5A sPDE simulation data reproduce experimental NS5A fluorescence recovery after photobleaching (FRAP) time series data. This parameter estimation yields the NS5A diffusion constant. Such parameters are needed for spatial models of HCV dynamics, which we are developing in parallel but remain qualitative at this stage. Thus, our present study likely provides the first quantitative biophysical description of the movement of a viral component. Our spatio-temporal resolved ansatz paves new ways for understanding intricate spatial-defined processes central to specfic aspects of virus life cycles.

Integrating ecological restoration into CDM forestry projects

International Nuclear Information System (INIS)

Ma, Maohua; Haapanen, Toni; Singh, Ram Babu; Hietala, Reija

2014-01-01

Highlights: • Concerns and issues in sustainability of CDM forestry projects are reviewed. • Ecological restoration is suggested to be integrated in the CDM framework. • As an ecosystem supporting service, soil restoration on degraded land is of primary importance. • Regenerating forests naturally rather than through monoculture plantations is suggested. • Potential social impacts of ecological restoration are discussed. - Abstract: The Clean Development Mechanism (CDM) is proposed to reduce greenhouse gas emissions and promote sustainable development. CDM forestry projects should contribute to mitigation of climate change through afforestation and reforestation (A/R) activities on degraded land in developing countries. However, like other types of CDM projects, the forestry projects have encountered a number of concerns and critiques. Appropriate approaches and concrete aims to achieve long-term sustainability have been lacking, and reforms have therefore been called for. The aims of this paper are to examine the published information relevant to these concerns, and frame appropriate approaches for a more sustainable CDM. In this review, as a first step to tackle some of these issues, ecological restoration is suggested for integration into the CDM framework. Essentially, this involves the restoration of ecosystem supporting service (soil restoration), upon which forests regenerate naturally rather than establishing monoculture plantations. In this way, forestry projects would bring cost-effective opportunities for multiple ecosystem services. Potential approaches, necessary additions to the monitoring plans, and social impacts of ecological restoration in CDM projects are discussed

Practitioner, patient and carious lesion characteristics associated with type of restorative material

DEFF Research Database (Denmark)

Makhija, Sonia K; Gordan, Valeria V; Gilbert, Gregg H

2011-01-01

The authors conducted a study to identify factors associated with the materials that dentists in The Dental Practice-Based Research Network (DPBRN) use when placing the first restoration on permanent posterior tooth surfaces....

Ecological outcomes and evaluation of success in passively restored southeastern depressional wetlands.

Energy Technology Data Exchange (ETDEWEB)

De Steven, Diane; Sharitz, Rebecca R.; Barton, Christopher, D.

2010-11-01

Abstract: Depressional wetlands may be restored passively by disrupting prior drainage to recover original hydrology and relying on natural revegetation. Restored hydrology selects for wetland vegetation; however, depression geomorphology constrains the achievable hydroperiod, and plant communities are influenced by hydroperiod and available species pools. Such constraints can complicate assessments of restoration success. Sixteen drained depressions in South Carolina, USA, were restored experimentally by forest clearing and ditch plugging for potential crediting to a mitigation bank. Depressions were assigned to alternate revegetation methods representing desired targets of herbaceous and wet-forest communities. After five years, restoration progress and revegetation methods were evaluated. Restored hydroperiods differed among wetlands, but all sites developed diverse vegetation of native wetland species. Vegetation traits were influenced by hydroperiod and the effects of early drought, rather than by revegetation method. For mitigation banking, individual wetlands were assessed for improvement from pre-restoration condition and similarity to assigned reference type. Most wetlands met goals to increase hydroperiod, herb-species dominance, and wetland-plant composition. Fewer wetlands achieved equivalence to reference types because some vegetation targets were incompatible with depression hydroperiods and improbable without intensive management. The results illustrated a paradox in judging success when vegetation goals may be unsuited to system constraints.

Synthesis of p-type nickel oxide nanosheets on n-type titanium dioxide nanorod arrays for p-n heterojunction-based UV photosensor

Science.gov (United States)

Yusoff, M. M.; Mamat, M. H.; Malek, M. F.; Abdullah, M. A. R.; Ismail, A. S.; Saidi, S. A.; Mohamed, R.; Suriani, A. B.; Khusaimi, Z.; Rusop, M.

2018-05-01

Titanium dioxide (TiO2) nanorod arrays (TNAs) were synthesized and deposited on fluorine tin oxide (FTO)-coated glass substrate using a novel and facile immersion method in a glass container. The synthesis and deposition of p-type nickel oxide (NiO) nanosheets (NS) on the n-type TNAs was investigated in the p-n heterojunction photodiode (PD) for the application of ultraviolet (UV) photosensor. The fabricated TNAs/NiO NS based UV photosensor exhibited a highly increased photocurrent of 4.3 µA under UV radiation (365 nm, 750 µW/cm2) at 1.0 V reverse bias. In this study, the fabricated TNAs/NiO NS p-n heterojunction based photodiode showed potential applications for UV photosensor based on the stable photo-generated current attained under UV radiation.

Characterization of Pressure Transients Generated by Nanosecond Electrical Pulse (nsEP) Exposure

OpenAIRE

Caleb C. Roth; Ronald A. Barnes Jr.; Bennett L. Ibey; Hope T. Beier; L. Christopher Mimun; Saher M. Maswadi; Mehdi Shadaram; Randolph D. Glickman

2015-01-01

The mechanism(s) responsible for the breakdown (nanoporation) of cell plasma membranes after nanosecond pulse (nsEP) exposure remains poorly understood. Current theories focus exclusively on the electrical field, citing electrostriction, water dipole alignment and/or electrodeformation as the primary mechanisms for pore formation. However, the delivery of a high-voltage nsEP to cells by tungsten electrodes creates a multitude of biophysical phenomena, including electrohydraulic cavitation, el...

The effect of rebonding and liner type on microleakage of Class V amalgam restorations

Directory of Open Access Journals (Sweden)

Moosavi H.

2008-10-01

Full Text Available Background and Aim: Application of varnish and dentin bonding agents can effectively reduce microleakage under amalgam restorations. Also rebonding may show some effects on microleakage and its complications. The aim of this study was to evaluate the effect of liner/ adhesives on microleakage of Class V amalgam restoration with or without rebonding. Materials and Methods: In this in vitro study Class V cavities were prepared on sixty sound human maxillary premolars with the gingival floor 1mm below the CEJ. Cases were divided into six groups of ten teeth each. Specimens in group 1 and 2 were lined with Copalite and Scotchbond Multi-Purpose (SBMP respectively. In the third group (control no liner was applied. The teeth were then restored with spherical amalgam. Specimens in group 4 to 6 received the same treatments but after filling, the interfaces of restorations and teeth were etched with 37% phosphoric acid gel, rinsed and dried. Adhesive resin of SBMP was applied over amalgam and tooth margins and polymerized (rebonding. Specimens were thermocycled, exposed to dye and sectioned. Microleakage was graded (0-3 using a stereomicroscope at X40 magnification. Data were analyzed with Kruskal-Wallis, Mann-Whitney and Wilcoxon pair wise statistical tests. P<0.05 was considered as the limit of significance. Results: The groups lined with SBMP showed the lowest and the groups without liner the highest microleakage (p= 0.001. Significant difference was observed in microleakage mean rank of enamel and dentin margins (p=0.048. Rebonding with resin did not improve the seal (p> 0.05. Conclusion: Based on the results of this study, total etch adhesive system had significant effect on microleakage of Class V amalgam restorations especially in cervical margin. Rebonding did not show a significant effect on microleakage.

Clinical decisions for anterior restorations: the concept of restorative volume.

Science.gov (United States)

Cardoso, Jorge André; Almeida, Paulo Júlio; Fischer, Alex; Phaxay, Somano Luang

2012-12-01

The choice of the most appropriate restoration for anterior teeth is often a difficult decision. Numerous clinical and technical factors play an important role in selecting the treatment option that best suits the patient and the restorative team. Experienced clinicians have developed decision processes that are often more complex than may seem. Less experienced professionals may find difficulties making treatment decisions because of the widely varied restorative materials available and often numerous similar products offered by different manufacturers. The authors reviewed available evidence and integrated their clinical experience to select relevant factors that could provide a logical and practical guideline for restorative decisions in anterior teeth. The presented concept of restorative volume is based on structural, optical, and periodontal factors. Each of these factors will influence the short- and long-term behavior of restorations in terms of esthetics, biology, and function. Despite the marked evolution of esthetic restorative techniques and materials, significant limitations still exist, which should be addressed by researchers. The presented guidelines must be regarded as a mere orientation for risk analysis. A comprehensive individual approach should always be the core of restorative esthetic treatments. The complex decision process for anterior esthetic restorations can be clarified by a systematized examination of structural, optical, and periodontal factors. The basis for the proposed thought process is the concept of restorative volume that is a contemporary interpretation of restoration categories and their application. © 2012 Wiley Periodicals, Inc.

Molecular and biochemical characterization of the NS1 protein of non-cultured influenza B virus strains circulating in Singapore

KAUST Repository

Jumat, Muhammad; Sugrue, Richard J.; Tan, Boon Huan; Maurer-Stroh, Sebastian; Lee, Raphael Tze Chuen; Wong, Puisan

2016-01-01

In this study we compared the NS1 protein of Influenza B/Lee/40 and several non-cultured Influenza B virus clinical strains detected in Singapore. In B/Lee/40 virus-infected cells and in cells expressing the recombinant B/Lee/40 NS1 protein a full-length 35 kDa NS1 protein and a 23 kDa NS1 protein species (p23) were detected. Mutational analysis of the NS1 gene indicated that p23 was generated by a novel cleavage event within the linker domain between an aspartic acid and proline at amino acid residues at positions 92 and 93 respectively (DP92–93), and that p23 contained the first 92 amino acids of the NS1 protein. Sequence analysis of the Singapore strains indicated the presence of either DP92–93 or NP92–93 in the NS1 protein, but protein expression analysis showed that p23 was only detected in NS1 proteins with DP92–93.. An additional adjacent proline residue at position 94 (P94) was present in some strains and correlated with increased p23 levels, suggesting that P94 has a synergistic effect on the cleavage of the NS1 protein. The first 145 amino acids of the NS1 protein are required for inhibition of ISG15-mediated ubiquitination, and our analysis showed that Influenza B viruses circulating in Singapore with DP92–93 expressed truncated NS1 proteins and may differ in their capacity to inhibit ISG15 activity. Thus, DP92–93 in the NS1 protein may confer a disadvantage to Influenza B viruses circulating in the human population and interestingly the low frequency of DP92–93detection in the NS1 protein since 2004 is consistent with this suggestion.

Molecular and biochemical characterization of the NS1 protein of non-cultured influenza B virus strains circulating in Singapore

KAUST Repository

Jumat, Muhammad Raihan

2016-08-04

In this study we compared the NS1 protein of Influenza B/Lee/40 and several non-cultured Influenza B virus clinical strains detected in Singapore. In B/Lee/40 virus-infected cells and in cells expressing the recombinant B/Lee/40 NS1 protein a full-length 35 kDa NS1 protein and a 23 kDa NS1 protein species (p23) were detected. Mutational analysis of the NS1 gene indicated that p23 was generated by a novel cleavage event within the linker domain between an aspartic acid and proline at amino acid residues at positions 92 and 93 respectively (DP92–93), and that p23 contained the first 92 amino acids of the NS1 protein. Sequence analysis of the Singapore strains indicated the presence of either DP92–93 or NP92–93 in the NS1 protein, but protein expression analysis showed that p23 was only detected in NS1 proteins with DP92–93.. An additional adjacent proline residue at position 94 (P94) was present in some strains and correlated with increased p23 levels, suggesting that P94 has a synergistic effect on the cleavage of the NS1 protein. The first 145 amino acids of the NS1 protein are required for inhibition of ISG15-mediated ubiquitination, and our analysis showed that Influenza B viruses circulating in Singapore with DP92–93 expressed truncated NS1 proteins and may differ in their capacity to inhibit ISG15 activity. Thus, DP92–93 in the NS1 protein may confer a disadvantage to Influenza B viruses circulating in the human population and interestingly the low frequency of DP92–93detection in the NS1 protein since 2004 is consistent with this suggestion.

Design of New Competitive Dengue Ns2b/Ns3 Protease Inhibitors—A Computational Approach

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Noorsaadah Abd. Rahman

2011-02-01

Full Text Available Dengue is a serious disease which has become a global health burden in the last decade. Currently, there are no approved vaccines or antiviral therapies to combat the disease. The increasing spread and severity of the dengue virus infection emphasizes the importance of drug discovery strategies that could efficiently and cost-effectively identify antiviral drug leads for development into potent drugs. To this effect, several computational approaches were applied in this work. Initially molecular docking studies of reference ligands to the DEN2 NS2B/NS3 serine protease were carried out. These reference ligands consist of reported competitive inhibitors extracted from Boesenbergia rotunda (i.e., 4-hydroxypanduratin A and panduratin A and three other synthesized panduratin A derivative compounds (i.e., 246DA, 2446DA and 20H46DA. The design of new lead inhibitors was carried out in two stages. In the first stage, the enzyme complexed to the reference ligands was minimized and their complexation energies (i.e., sum of interaction energy and binding energy were computed. New compounds as potential dengue inhibitors were then designed by putting various substituents successively on the benzyl ring A of the reference molecule. These substituted benzyl compounds were then computed for their enzyme-ligand complexation energies. New enzyme-ligand complexes, exhibiting the lowest complexation energies and closest to the computed energy for the reference compounds, were then chosen for the next stage manipulation and design, which involved substituting positions 4 and 5 of the benzyl ring A (positions 3 and 4 for 2446DA with various substituents.

Multiplex Outputs ns Grade High-voltage Fast Pulse Generator Study

International Nuclear Information System (INIS)

Wang Xin; Chen Kenan

2009-01-01

Using a double-grid hydrogen thyratron, a fast pulse generator with four outputs, high-voltage, low jitter, was made to use at special occasion.In this paper, the basic structure of pulser, switching theory and double-grid driving of hydrogen thyratron was introduced, and also, the effects of grids driving pulses characteristics, the delay between too grids driving, the reservoir heater voltage and cathode heater voltage on the output are carefully examined in experiments. The pulse generator with four outputs was made to producing pulses with amplitude up to 4 kV, rise-time less than 15 ns and jitter less than 3 ns. (authors)

Guidelines for evaluating performance of oyster habitat restoration

Science.gov (United States)

Baggett, Lesley P.; Powers, Sean P.; Brumbaugh, Robert D.; Coen, Loren D.; DeAngelis, Bryan M.; Greene, Jennifer K.; Hancock, Boze T.; Morlock, Summer M.; Allen, Brian L.; Breitburg, Denise L.; Bushek, David; Grabowski, Jonathan H.; Grizzle, Raymond E.; Grosholz, Edwin D.; LaPeyre, Megan K.; Luckenbach, Mark W.; McGraw, Kay A.; Piehler, Michael F.; Westby, Stephanie R.; zu Ermgassen, Philine S. E.

2015-01-01

Restoration of degraded ecosystems is an important societal goal, yet inadequate monitoring and the absence of clear performance metrics are common criticisms of many habitat restoration projects. Funding limitations can prevent adequate monitoring, but we suggest that the lack of accepted metrics to address the diversity of restoration objectives also presents a serious challenge to the monitoring of restoration projects. A working group with experience in designing and monitoring oyster reef projects was used to develop standardized monitoring metrics, units, and performance criteria that would allow for comparison among restoration sites and projects of various construction types. A set of four universal metrics (reef areal dimensions, reef height, oyster density, and oyster size–frequency distribution) and a set of three universal environmental variables (water temperature, salinity, and dissolved oxygen) are recommended to be monitored for all oyster habitat restoration projects regardless of their goal(s). In addition, restoration goal-based metrics specific to four commonly cited ecosystem service-based restoration goals are recommended, along with an optional set of seven supplemental ancillary metrics that could provide information useful to the interpretation of prerestoration and postrestoration monitoring data. Widespread adoption of a common set of metrics with standardized techniques and units to assess well-defined goals not only allows practitioners to gauge the performance of their own projects but also allows for comparison among projects, which is both essential to the advancement of the field of oyster restoration and can provide new knowledge about the structure and ecological function of oyster reef ecosystems.

The cost of wetland creation and restoration. Final report

Energy Technology Data Exchange (ETDEWEB)

King, D.; Bohlen, C.

1995-08-01

This report examines the economics of wetland creation, restoration, and enhancement projects, especially as they are used within the context of mitigation for unavoidable wetland losses. Complete engineering-cost-accounting profiles of over 90 wetland projects were developed in collaboration with leading wetland restoration and creation practitioners around the country to develop a primary source database. Data on the costs of over 1,000 wetland projects were gathered from published sources and other available databases to develop a secondary source database. Cases in both databases were carefully analyzed and a set of baseline cost per acre estimates were developed for wetland creation, restoration, and enhancement. Observations of costs varied widely, ranging from $5 per acre to $1.5 million per acre. Differences in cost were related to the target wetland type, and to site-specific and project-specific factors that affected the preconstruction, construction, and post-construction tasks necessary to carry out each particular project. Project-specific and site-specific factors had a much larger effect on project costs than wetland type for non-agricultural projects. Costs of wetland creation and restoration were also shown to differ by region, but not by as much as expected, and in response to the regulatory context. The costs of wetland creation, restoration, and enhancement were also analyzed in a broader economic context through examination of the market for wetland mitigation services, and through the development of a framework for estimating compensation ratios-the number of acres of created, restored, or enhanced wetland required to compensate for an acre of lost natural wetland. The combination of per acre creation, restoration, and enhancement costs and the compensation ratio determine the overall mitigation costs associated with alternative mitigation strategies.

Characterization of the expression and immunogenicity of the ns4b protein of human coronavirus 229E

DEFF Research Database (Denmark)

Chagnon, F; Lamarre, A; Lachance, C

1998-01-01

to demonstrate the expression of ns4b in HCV-229E-infected cells using flow cytometry. Given a previously reported contiguous five amino acid shared region between ns4b and myelin basic protein, a purified recombinant histidine-tagged ns4b protein and (or) human myelin basic protein were injected into mice......Sequencing of complementary DNAs prepared from various coronaviruses has revealed open reading frames encoding putative proteins that are yet to be characterized and are so far only described as nonstructural (ns). As a first step in the elucidation of its function, we characterized the expression...... and immunogenicity of the ns4b gene product from strain 229E of human coronavirus (HCV-229E), a respiratory virus with a neurotropic potential. The gene was cloned and expressed in bacteria. A fusion protein of ns4b with maltose-binding protein was injected into rabbits to generate specific antibodies that were used...

Effects of the small molecule HERG activator NS1643 on Kv11.3 channels.

Directory of Open Access Journals (Sweden)

Arne Bilet

Full Text Available NS1643 is one of the small molecule HERG (Kv11.1 channel activators and has also been found to increase erg2 (Kv11.2 currents. We now investigated whether NS1643 is also able to act as an activator of Kv11.3 (erg3 channels expressed in CHO cells. Activation of rat Kv11.3 current occurred in a dose-dependent manner and maximal current increasing effects were obtained with 10 µM NS1643. At this concentration, steady-state outward current increased by about 80% and the current increase was associated with a significant shift in the voltage dependence of activation to more negative potentials by about 15 mV. In addition, activation kinetics were accelerated, whereas deactivation was slowed. There was no significant effect on the kinetics of inactivation and recovery from inactivation. The strong current-activating agonistic effect of NS1643 did not result from a shift in the voltage dependence of Kv11.3 channel inactivation and was independent from external Na(+ or Ca(2+. At the higher concentration of 20 µM, NS1643 induced clearly less current increase. The left shift in the voltage dependence of activation reversed and the voltage sensitivity of activation dramatically decreased along with a slowing of Kv11.3 channel activation. These data show that, in comparison to other Kv11 family members, NS1643 exerts distinct effects on Kv11.3 channels with especially pronounced partial antagonistic effects at higher concentration.

Influenza A virus NS1 gene mutations F103L and M106I increase replication and virulence

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Ping Jihui

2011-01-01

Full Text Available Abstract Background To understand the evolutionary steps required for a virus to become virulent in a new host, a human influenza A virus (IAV, A/Hong Kong/1/68(H3N2 (HK-wt, was adapted to increased virulence in the mouse. Among eleven mutations selected in the NS1 gene, two mutations F103L and M106I had been previously detected in the highly virulent human H5N1 isolate, A/HK/156/97, suggesting a role for these mutations in virulence in mice and humans. Results To determine the selective advantage of these mutations, reverse genetics was used to rescue viruses containing each of the NS1 mouse adapted mutations into viruses possessing the HK-wt NS1 gene on the A/PR/8/34 genetic backbone. Both F103L and M106I NS1 mutations significantly enhanced growth in vitro (mouse and canine cells and in vivo (BALB/c mouse lungs as well as enhanced virulence in the mouse. Only the M106I NS1 mutation enhanced growth in human cells. Furthermore, these NS1 mutations enhanced early viral protein synthesis in MDCK cells and showed an increased ability to replicate in mouse interferon β (IFN-β pre-treated mouse cells relative to rPR8-HK-NS-wt NS1. The double mutant, rPR8-HK-NS-F103L + M106I, demonstrated growth attenuation late in infection due to increased IFN-β induction in mouse cells. We then generated a rPR8 virus possessing the A/HK/156/97 NS gene that possesses 103L + 106I, and then rescued the L103F + I106M mutant. The 103L + 106I mutations increased virulence by >10 fold in BALB/c mice. We also inserted the avian A/Ck/Beijing/1/95 NS1 gene (the source lineage of the A/HK/156/97 NS1 gene that possesses 103L + 106I, onto the A/WSN/33 backbone and then generated the L103F + I106M mutant. None of the H5N1 and H9N2 NS containing viruses resulted in increased IFN-β induction. The rWSN-A/Ck/Beijing/1/95-NS1 gene possessing 103L and 106I demonstrated 100 fold enhanced growth and >10 fold enhanced virulence that was associated with increased tropism for lung

New binding site conformations of the dengue virus NS3 protease accessed by molecular dynamics simulation.

Directory of Open Access Journals (Sweden)

Hugo de Almeida

Full Text Available Dengue fever is caused by four distinct serotypes of the dengue virus (DENV1-4, and is estimated to affect over 500 million people every year. Presently, there are no vaccines or antiviral treatments for this disease. Among the possible targets to fight dengue fever is the viral NS3 protease (NS3PRO, which is in part responsible for viral processing and replication. It is now widely recognized that virtual screening campaigns should consider the flexibility of target protein by using multiple active conformational states. The flexibility of the DENV NS3PRO could explain the relatively low success of previous virtual screening studies. In this first work, we explore the DENV NS3PRO conformational states obtained from molecular dynamics (MD simulations to take into account protease flexibility during the virtual screening/docking process. To do so, we built a full NS3PRO model by multiple template homology modeling. The model comprised the NS2B cofactor (essential to the NS3PRO activation, a glycine flexible link and the proteolytic domain. MD simulations had the purpose to sample, as closely as possible, the ligand binding site conformational landscape prior to inhibitor binding. The obtained conformational MD sample was clustered into four families that, together with principal component analysis of the trajectory, demonstrated protein flexibility. These results allowed the description of multiple binding modes for the Bz-Nle-Lys-Arg-Arg-H inhibitor, as verified by binding plots and pair interaction analysis. This study allowed us to tackle protein flexibility in our virtual screening campaign against the dengue virus NS3 protease.

MDM2 gene SNP309 T/G and p53 gene SNP72 G/C do not influence diffuse large B-cell non-Hodgkin lymphoma onset or survival in central European Caucasians

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Landt Olfert

2008-04-01

Full Text Available Abstract Background SNP309 T/G (rs2279744 causes higher levels of MDM2, the most important negative regulator of the p53 tumor suppressor. SNP72 G/C (rs1042522 gives rise to a p53 protein with a greatly reduced capacity to induce apoptosis. Both polymorphisms have been implicated in cancer. The SNP309 G-allele has recently been reported to accelerate diffuse large B-cell lymphoma (DLBCL formation in pre-menopausal women and suggested to constitute a genetic basis for estrogen affecting human tumorigenesis. Here we asked whether SNP309 and SNP72 are associated with DLBCL in women and are correlated with age of onset, diagnosis, or patient's survival. Methods SNP309 and SNP72 were PCR-genotyped in a case-control study that included 512 controls and 311 patients diagnosed with aggressive NHL. Of these, 205 were diagnosed with DLBCL. Results The age of onset was similar in men and women. The control and patients group showed similar SNP309 and SNP72 genotype frequencies. Importantly and in contrast to the previous findings, similar genotype frequencies were observed in female patients diagnosed by 51 years of age and those diagnosed later. Specifically, 3/20 female DLBCL patients diagnosed by 51 years of age were homozygous for SNP309 G and 2/20 DLBCL females in that age group were homozygous for SNP72 C. Neither SNP309 nor SNP72 had a significant influence on event-free and overall survival in multivariate analyses. Conclusion In contrast to the previous study on Ashkenazi Jewish Caucasians, DLBCL in pre-menopausal women of central European Caucasian ethnicity was not associated with SNP309 G. Neither SNP309 nor SNP72 seem to be correlated with age of onset, diagnosis, or survival of patients.

Amino Terminal Region of Dengue Virus NS4A Cytosolic Domain Binds to Highly Curved Liposomes

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Yu-Fu Hung

2015-07-01

Full Text Available Dengue virus (DENV is an important human pathogen causing millions of disease cases and thousands of deaths worldwide. Non-structural protein 4A (NS4A is a vital component of the viral replication complex (RC and plays a major role in the formation of host cell membrane-derived structures that provide a scaffold for replication. The N-terminal cytoplasmic region of NS4A(1–48 is known to preferentially interact with highly curved membranes. Here, we provide experimental evidence for the stable binding of NS4A(1–48 to small liposomes using a liposome floatation assay and identify the lipid binding sequence by NMR spectroscopy. Mutations L6E;M10E were previously shown to inhibit DENV replication and to interfere with the binding of NS4A(1–48 to small liposomes. Our results provide new details on the interaction of the N-terminal region of NS4A with membranes and will prompt studies of the functional relevance of the curvature sensitive membrane anchor at the N-terminus of NS4A.

Equivalent Young's modulus of composite resin for simulation of stress during dental restoration.

Science.gov (United States)

Park, Jung-Hoon; Choi, Nak-Sam

2017-02-01

For shrinkage stress simulation in dental restoration, the elastic properties of composite resins should be acquired beforehand. This study proposes a formula to measure the equivalent Young's modulus of a composite resin through a calculation scheme of the shrinkage stress in dental restoration. Two types of composite resins remarkably different in the polymerization shrinkage strain were used for experimental verification: the methacrylate-type (Clearfil AP-X) and the silorane-type (Filtek P90). The linear shrinkage strains of the composite resins were gained through the bonded disk method. A formula to calculate the equivalent Young's moduli of composite resin was derived on the basis of the restored ring substrate. Equivalent Young's moduli were measured for the two types of composite resins through the formula. Those values were applied as input to a finite element analysis (FEA) for validation of the calculated shrinkage stress. Both of the measured moduli through the formula were appropriate for stress simulation of dental restoration in that the shrinkage stresses calculated by the FEA were in good agreement within 3.5% with the experimental values. The concept of equivalent Young's modulus so measured could be applied for stress simulation of 2D and 3D dental restoration. Copyright © 2016 The Academy of Dental Materials. Published by Elsevier Ltd. All rights reserved.

Political and Economic Geomorphology: The Effect of Market Forces on Stream Restoration Designs

Science.gov (United States)

Singh, J.; Doyle, M. W.; Lave, R.; Robertson, M.

2013-12-01

Stream restoration in the U.S. is increasingly driven by compensatory mitigation; impacts to streams associated with typical land development activities must be offset via restoration of streams elsewhere. This policy application creates conditions in which restored stream ';credits' are traded under market-like conditions, comparable to wetland mitigation, carbon offsets, or endangered species habitat banking. The effect of this relatively new mechanism to finance stream restoration on design and construction is unknown. This research explores whether the introduction of a credit-based mitigation apparatus results in streams designed to maximize credit yields (i.e., ';credit-chasing') rather than focusing on restoring natural systems or functions. In other words, are market-based restored streams different from those designed for non-market purposes? We quantified geomorphic characteristics (e.g. hydraulic geometry, sinuosity, profile, bed sediment, LWD) of three types of streams: (1) a random sample of non-restored reaches, (2) streams restored for compensatory mitigation, and (3) streams restored under alternative funding sources (e.g., government grant programs, non-profit activities). We also compared the location of the types of stream reaches to determine whether there is a spatiality of restored streams. Physical data were complemented with a series of semi-structured interviews with key personnel in the stream restoration industry to solicit information on the influence of policy interpretation and market-driven factors on the design process. Preliminary analysis suggests that restoration is driving a directional shift in stream morphology in North Carolina. As a simple example, in the Piedmont, non-restored and restored channels had mean sinuosity of 1.17 and 1.23, respectively (p sale of restored stream credits, was seen as critically important rather than the marginal gains to be made by manipulating particular stream designs to glean more credits

NS 1231, a novel compound with neurotrophic-like effects in vitro and in vivo

DEFF Research Database (Denmark)

Dagø, Lone; Bonde, Christian; Peters, Dan

2002-01-01

reduced NMDA-induced excitotoxicity in organotypic hippocampal slice cultures. In a gerbil model of transient global ischaemia, treatment with NS 1231 reduced the delayed loss of neurons in the hippocampal CA1 layer. Furthermore, NS 1231 treatment resulted in a 43% reduction in total infarct volume...

15 CFR 990.53 - Restoration selection-developing restoration alternatives.

Science.gov (United States)

2010-01-01

... OIL POLLUTION ACT REGULATIONS NATURAL RESOURCE DAMAGE ASSESSMENTS Restoration Planning Phase § 990.53... justify restoration, trustees may proceed with the Restoration Planning Phase. Otherwise, trustees may not... discount all service quantities and/or values to the date the demand is presented to the responsible...

The NS1 Protein from Influenza Virus Stimulates Translation Initiation by Enhancing Ribosome Recruitment to mRNAs.

Science.gov (United States)

Panthu, Baptiste; Terrier, Olivier; Carron, Coralie; Traversier, Aurélien; Corbin, Antoine; Balvay, Laurent; Lina, Bruno; Rosa-Calatrava, Manuel; Ohlmann, Théophile

2017-10-27

The non-structural protein NS1 of influenza A viruses exerts pleiotropic functions during infection. Among these functions, NS1 was shown to be involved in the control of both viral and cellular translation; however, the mechanism by which this occurs remains to be determined. Thus, we have revisited the role of NS1 in translation by using a combination of influenza infection, mRNA reporter transfection, and in vitro functional and biochemical assays. Our data show that the NS1 protein is able to enhance the translation of virtually all tested mRNAs with the exception of constructs bearing the Dicistroviruses Internal ribosome entry segment (IRESes) (DCV and CrPV), suggesting a role at the level of translation initiation. The domain of NS1 required for translation stimulation was mapped to the RNA binding amino-terminal motif of the protein with residues R38 and K41 being critical for activity. Although we show that NS1 can bind directly to mRNAs, it does not correlate with its ability to stimulate translation. This activity rather relies on the property of NS1 to associate with ribosomes and to recruit them to target mRNAs. Copyright © 2017 Elsevier Ltd. All rights reserved.

Ecological and social dimensions of ecosystem restoration in the Nordic countries

DEFF Research Database (Denmark)

Hagen, Dagmar; Svavarsdottir, Kristin; Nilsson, Christer

2013-01-01

An international overview of the extent and type of ecological restoration can offer new perspectives for understanding, planning, and implementation. The Nordic countries, with a great range of natural conditions but historically similar social and political structures, provide an opportunity...... and among countries, both in the Nordic countries and internationally. An obvious advantage of such cooperation is that a wider range of experiences from different habitats and different socio-economic conditions becomes available and thus provides a more solid basis for developing practical solutions...... to compare restoration approaches and efforts across borders. The aim of this study was to explore variation in ecological restoration using the Nordic countries as an example. We used recent national assessments and expert evaluations of ecological restoration. Restoration efforts differed among countries...

Effects of nanosecond pulsed electric fields (nsPEFs) on the human fungal pathogen Candida albicans: an in vitro study

Science.gov (United States)

Guo, Jinsong; Dang, Jie; Wang, Kaile; Zhang, Jue; Fang, Jing

2018-05-01

Candida albicans is the leading human fungal pathogen that causes many life-threatening infections. Notably, the current clinical trial data indicate that Candida species shows the emerging resistance to anti-fungal drugs. The aim of this study was to evaluate the antifungal effects of nanosecond pulsed electric fields (nsPEFs) as a novel drug-free strategy in vitro. In this study, we investigated the inactivation and permeabilization effects of C. albicans under different nsPEFs exposure conditions (100 pulses, 100 ns in duration, intensities of 20, 40 kV cm‑1). Cell death was studied by annexin-V and propidium iodide staining. The changes of intracellular Ca2+ concentration after nsPEFs treatment were observed using Fluo-4 AM. Results show that C. albicans cells and biofilms were both obviously inhibited and destroyed after nsPEFs treatment. Furthermore, C. albicans cells were significantly permeabilized after nsPEFs treatment. Additionally, nsPEFs exposure led to a large amount of DNA and protein leakage. Importantly, nsPEFs induced a field strength-dependent apoptosis in C. albicans cells. Further experiments revealed that Ca2+ involved in nsPEFs induced C. albicans apoptosis. In conclusion, this proof-of-concept study provides a potential alternative drug-free strategy for killing pathogenic Candida species.

Symposium on CIAE 600 kV ns pulse neutron generator

International Nuclear Information System (INIS)

Shen Guanren

2001-01-01

CIAE 600 kV ns Pulse Neutron Generator was built by China National Nuclear Corporation, which is an important facility mainly used for experimental researches of nuclear reactions induced by 14 MeV neutrons, experimental measurements of energy spectra of secondary neutrons and charged particles and macro-checking experiments of evaluated neutron database and dosimetry researches of neutrons and γ rays. It is the first home made one, but the fourth similar facility in the world. Six articles are included in this symposium. The articles details the general structure, radio frequency ion source, high current beam ns pulsed system, etc. The main technical problems resolved during development are discussed. And attentions and experiences in the generator adjustments are introduced

Meissner effect in clean proximity-contact N-S double layer

International Nuclear Information System (INIS)

Higashitani, S.; Nagai, K.

1994-01-01

The Meissner effect in proximity-contact normal-superconducting (N-S) double layers is discussed in the clean limit. We obtain the quasi-classical Green's function linear in the vector potential such that satisfies the boundary conditions at the layer ends and also at the N-S interface with a finite reflection coefficient R. We find that, when there is no pairing interaction in the normal layer, the diamagnetic current in the normal layer is constant in space, consequently the magnetic field decreases linearly in the normal layer. To compare our theory with experiments, we calculate the screening length and find a good agreement in the temperature dependence with the experiments in the Au-Nb system. (orig.)

Charged residues in the H-NS linker drive DNA binding and gene silencing in single cells.

Science.gov (United States)

Gao, Yunfeng; Foo, Yong Hwee; Winardhi, Ricksen S; Tang, Qingnan; Yan, Jie; Kenney, Linda J

2017-11-21

Nucleoid-associated proteins (NAPs) facilitate chromosome organization in bacteria, but the precise mechanism remains elusive. H-NS is a NAP that also plays a major role in silencing pathogen genes. We used genetics, single-particle tracking in live cells, superresolution microscopy, atomic force microscopy, and molecular dynamics simulations to examine H-NS/DNA interactions in single cells. We discovered a role for the unstructured linker region connecting the N-terminal oligomerization and C-terminal DNA binding domains. In the present work we demonstrate that linker amino acids promote engagement with DNA. In the absence of linker contacts, H-NS binding is significantly reduced, although no change in chromosome compaction is observed. H-NS is not localized to two distinct foci; rather, it is scattered all around the nucleoid. The linker makes DNA contacts that are required for gene silencing, while chromosome compaction does not appear to be an important H-NS function.

Estimating the Size and Impact of the Ecological Restoration Economy.

Directory of Open Access Journals (Sweden)

Todd BenDor

Full Text Available Domestic public debate continues over the economic impacts of environmental regulations that require environmental restoration. This debate has occurred in the absence of broad-scale empirical research on economic output and employment resulting from environmental restoration, restoration-related conservation, and mitigation actions - the activities that are part of what we term the "restoration economy." In this article, we provide a high-level accounting of the size and scope of the restoration economy in terms of employment, value added, and overall economic output on a national scale. We conducted a national survey of businesses that participate in restoration work in order to estimate the total sales and number of jobs directly associated with the restoration economy, and to provide a profile of this nascent sector in terms of type of restoration work, industrial classification, workforce needs, and growth potential. We use survey results as inputs into a national input-output model (IMPLAN 3.1 in order to estimate the indirect and induced economic impacts of restoration activities. Based on this analysis we conclude that the domestic ecological restoration sector directly employs ~ 126,000 workers and generates ~ $9.5 billion in economic output (sales annually. This activity supports an additional 95,000 jobs and $15 billion in economic output through indirect (business-to-business linkages and increased household spending.