Dual inhibition of human type 4 phosphodiesterase isostates by (R, R)-(+/-)-methyl 3-acetyl-4-[3-(cyclopentyloxy)-4-methoxyphenyl]-3- methyl-1-pyrrolidinecarboxylate.

PubMed

Tian, G; Rocque, W J; Wiseman, J S; Thompson, I Z; Holmes, W D; Domanico, P L; Stafford, J A; Feldman, P L; Luther, M A

1998-05-12

Purified recombinant human type 4 phosphodiesterase B2B (HSPDE4B2B) exists in both a low- and a high-affinity state that bind (R)-rolipram with Kd's of ca. 500 and 1 nM, respectively [Rocque, W. J., Tian, G., Wiseman, J. S., Holmes, W. D., Thompson, I. Z., Willard, D. H., Patel, I. R., Wisely, G. B., Clay, W. C., Kadwell, S. H., Hoffman, C. R., and Luther, M. A. (1997) Biochemistry 36, 14250-14261]. Since the tissue distribution of the two isostates may be significantly different, development of inhibitors that effectively inhibit both forms may be advantageous pharmacologically. In this study, enzyme inhibition and binding of HSPDE4B2B by (R, R)-(+/-)-methyl 3-acetyl-4-[3-(cyclopentyloxy)-4-methoxyphenyl]-3-methyl-1-pyrrolidin ecarboxylate (1), a novel inhibitor of phosphodiesterase 4 (PDE 4), were investigated. Binding experiments demonstrated high-affinity binding of 1 to HSPDE4B2B with a stoichiometry of 1:1. Inhibition of PDE activity showed only a single transition with an observed Ki similar to the apparent Kd determined by the binding experiments. Deletional mutants of HSPDE4B2B, which have been shown to bind (R)-rolipram with low affinity, were shown to interact with 1 with high affinity, indistinguishable from the results obtained with the full-length enzyme. Bound 1 was completely displaced by (R)-rolipram, and the displacement showed a biphasic transition that resembles the biphasic inhibition of HSPDE4B2B by (R)-rolipram. Theoretical analysis of the two transitions exemplified in the interaction of (R)-rolipram with HSPDE4B2B indicated that the two isostates were nonexchangeable. Phosphorylation at serines 487 and 489 on HSPDE4B2B had no effect on the stoichiometry of binding, the affinity for binding, or the inhibition of the enzyme by 1. These data further illustrate the presence of two isostates in PDE 4 as shown previously for (R)-rolipram binding and inhibition. In contrast to (R)-rolipram, where only one of the two isostates of PDE 4 binds with

4-D OCT in Developmental Cardiology

NASA Astrophysics Data System (ADS)

Jenkins, Michael W.; Rollins, Andrew M.

Although strong evidence exists to suggest that altered cardiac function can lead to CHDs, few studies have investigated the influential role of cardiac function and biophysical forces on the development of the cardiovascular system due to a lack of proper in vivo imaging tools. 4-D imaging is needed to decipher the complex spatial and temporal patterns of biomechanical forces acting upon the heart. Numerous solutions over the past several years have demonstrated 4-D OCT imaging of the developing cardiovascular system. This chapter will focus on these solutions and explain their context in the evolution of 4-D OCT imaging. The first sections describe the relevant techniques (prospective gating, direct 4-D imaging, retrospective gating), while later sections focus on 4-D Doppler imaging and measurements of force implementing 4-D OCT Doppler. Finally, the techniques are summarized, and some possible future directions are discussed.

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

PubMed

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

2009-12-14

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

[Overexpression of miR-519d-3p inhibits the proliferation of DU-145 prostate cancer cells by reducing TRAF4].

PubMed

Li, Xiaohui; Han, Xingtao; Yang, Jinhui; Sun, Jiantao; Wei, Pengtao

2018-01-01

Objective To observe the effect of microRNA-519d-3p (miR-519d-3p) on the proliferation of prostate cancer cells and explore the possible molecular mechanism. Methods The expression level of miR-519d-3p in PC-3, DU-145, 22RV1, PC-3M, LNCaP human prostate cancer cells and RWPE-1 human normal prostate epithelial cells was detected by real-time quantitative PCR. miR-519d-3p mimics or negative control microRNAs (miR-NC) was transfected into the prostate cancer cells with the lowest level of miR-519d-3p expression. Transfection efficiency was examined. The effect of miR-519d-3p on the cell cycle of prostate cancer was detected by flow cytometry. MTT assay and plate clone formation assay were used to detect its effect on the proliferation of prostate cancer cells. Bioinformatics software was used to predict and dual luciferase reporter assay was used to validate the target gene of miR-519d-3p. Real-time quantitative PCR was used to detect the expression of miR-519d-3p target gene. Western blot analysis was used to detect the expression of target gene protein and downstream protein. Results The expression of miR-519d-3p in normal prostate epithelial cells was significantly higher than that in prostate cancer cells, and the lowest was found in DU-145 cells. After transfected with miR-519d-3p mimics, the expression level of miR-519d-3p in DU-145 cells increased significantly. Bioinformatics prediction and dual luciferase reporter gene confirmed that tumor necrosis factor receptor associated factor 4 (TRAF4) was the target gene of miR-519d-3p. Overexpression of miR-519d-3p significantly reduced the expression of TRAF4 gene and its downstream TGF-β signaling pathway proteins in the prostate cancer cells. Conclusion The expression of miR-519d-3p is down-regulated in prostate cancer cells. Overexpression of miR-519d-3p can inhibit the proliferation of prostate cancer cells. The possible mechanism is that miR-519d-3p inhibits the expression of TRAF4.

The Outstanding Investigator Award (R35)

Cancer.gov

NCI established the Outstanding Investigator Award (R35) in 2014, for principal investigators who have achieved significant research accomplishments. Featured in this video is Holly Prigerson, Ph.D., of Weill Cornell Medicine, who is among the first group of 62 researchers to receive the award. The R35 encourages these outstanding investigators to take on high-risk and potentially high-reward research projects by providing stable funding for 7 years.

ATLAS Cloud R&D

NASA Astrophysics Data System (ADS)

Panitkin, Sergey; Barreiro Megino, Fernando; Caballero Bejar, Jose; Benjamin, Doug; Di Girolamo, Alessandro; Gable, Ian; Hendrix, Val; Hover, John; Kucharczyk, Katarzyna; Medrano Llamas, Ramon; Love, Peter; Ohman, Henrik; Paterson, Michael; Sobie, Randall; Taylor, Ryan; Walker, Rodney; Zaytsev, Alexander; Atlas Collaboration

2014-06-01

The computing model of the ATLAS experiment was designed around the concept of grid computing and, since the start of data taking, this model has proven very successful. However, new cloud computing technologies bring attractive features to improve the operations and elasticity of scientific distributed computing. ATLAS sees grid and cloud computing as complementary technologies that will coexist at different levels of resource abstraction, and two years ago created an R&D working group to investigate the different integration scenarios. The ATLAS Cloud Computing R&D has been able to demonstrate the feasibility of offloading work from grid to cloud sites and, as of today, is able to integrate transparently various cloud resources into the PanDA workload management system. The ATLAS Cloud Computing R&D is operating various PanDA queues on private and public resources and has provided several hundred thousand CPU days to the experiment. As a result, the ATLAS Cloud Computing R&D group has gained a significant insight into the cloud computing landscape and has identified points that still need to be addressed in order to fully utilize this technology. This contribution will explain the cloud integration models that are being evaluated and will discuss ATLAS' learning during the collaboration with leading commercial and academic cloud providers.

Design of fluorinated 5-HT(4)R antagonists: influence of the basicity and lipophilicity toward the 5-HT(4)R binding affinities.

PubMed

Fontenelle, Clement Q; Wang, Zhong; Fossey, Christine; Cailly, Thomas; Linclau, Bruno; Fabis, Frederic

2013-12-01

Analogues of potent 5-HT(4)R antagonists possessing a fluorinated N-alkyl chain have been synthesized in order to investigate the effect of the resulting change in basicity and lipophilicity on the affinity and selectivity profile. We demonstrate that for this series, the affinity is decreased with decreased basicity of the piperidine's nitrogen atom. In contrast, the resulting increase in lipophilicity has minimal impact on binding affinity and selectivity. 3,3,3-Trifluoropropyl and 4,4,4-trifluorobutyl derivatives 6d and 6e have shown to bind to the 5-HT(4)R while maintaining their pharmacological profile and selectivity toward other 5-HT receptors. Copyright © 2013 Elsevier Ltd. All rights reserved.

76 FR 41144 - Airworthiness Directives; Pratt & Whitney Corp. (PW) JT9D-7R4H1 Turbofan Engines

Federal Register 2010, 2011, 2012, 2013, 2014

2011-07-13

...-7R4H1 turbofan engines. This proposed AD would require removing certain high-pressure compressor (HPC...) Applicability Pratt & Whitney Corp (PW) JT9D-7R4H1 turbofan engines with a high-pressure compressor (HPC) shaft... the rear shaft. These engines have the highest-thrust rating of the JT9D models, and were operating in...

The productivity crisis in pharmaceutical R&D.

PubMed

Pammolli, Fabio; Magazzini, Laura; Riccaboni, Massimo

2011-06-01

Advances in the understanding of the molecular basis of diseases have expanded the number of plausible therapeutic targets for the development of innovative agents in recent decades. However, although investment in pharmaceutical research and development (R&D) has increased substantially in this time, the lack of a corresponding increase in the output in terms of new drugs being approved indicates that therapeutic innovation has become more challenging. Here, using a large database that contains information on R&D projects for more than 28,000 compounds investigated since 1990, we examine the decline of R&D productivity in pharmaceuticals in the past two decades and its determinants. We show that this decline is associated with an increasing concentration of R&D investments in areas in which the risk of failure is high, which correspond to unmet therapeutic needs and unexploited biological mechanisms. We also investigate the potential variations in productivity with regard to the regional location of companies and find that although companies based in the United States and Europe differ in the composition of their R&D portfolios, there is no evidence of any productivity gap.

Mapping R&D within Multinational Networks: Evidence from the Electronics Industry

NASA Astrophysics Data System (ADS)

Urze, Paula; Manatos, Maria João

Based on the final results of the R&D.COM - Local R&D COMpetencies within Global Value Chains project, this paper aims at mapping the trajectories of delocalised R&D units within a multinational’s global strategy and designing the knowledge flows within the global value chain. This analysis was performed using typologies proposed in the theoretical framework, which help us to have an overview of the network. The methodology is grounded on one extended case study that involves a local R&D unit (Portugal), a foreign R&D unit (Netherlands) and the headquarters (Norway) - developed on a multinational from the electronics industry. This case is an example of a multinational company where R&D is developed mainly in the headquarters but it is also delocalised to some subsidiaries with a certain level of autonomy.

Digit ratio (2D:4D) in primary brain tumor patients: A case-control study.

PubMed

Bunevicius, Adomas; Tamasauskas, Sarunas; Deltuva, Vytenis Pranas; Tamasauskas, Arimantas; Sliauzys, Albertas; Bunevicius, Robertas

2016-12-01

The second-to-fourth digit ratio (2D:4D) reflects prenatal estrogen and testosterone exposure, and is established in utero. Sex steroids are implicated in development and progression of primary brain tumors. To investigate whether there is a link between 2D:4D ratio and primary brain tumors, and age at presentation. Digital images of the right and left palms of 85 primary brain tumor patients (age 56.96±13.68years; 71% women) and 106 (age 54.31±13.68years; 68% women) gender and age matched controls were obtained. The most common brain tumor diagnoses were meningioma (41%), glioblastoma (20%) and pituitary adenoma (16%). Right and left 2D:4D ratios, and right minus left 2D:4D (D r-l ) were compared between patients and controls, and were correlated with age. Right and left 2D:4D ratios were significantly lower in primary brain tumor patients relative to controls (t=-4.28, p<0.001 and t=-3.69, p<0.001, respectively). The D r-l was not different between brain tumor patients and controls (p=0.27). In meningioma and glioma patients, age at presentation correlated negatively with left 2D:4D ratio (rho=-0.42, p=0.01 and rho=-0.36, p=0.02, respectively) and positively with D r-l (rho=0.45, p=0.009 and rho=0.65, p=0.04, respectively). Right and left hand 2D:4D ratios are lower in primary brain tumor patients relative to healthy individuals suggesting greater prenatal testosterone and lower prenatal estrogen exposure in brain tumor patients. Greater age at presentation is associated with greater D r-l and with lower left 2D:4D ratio of meningioma and glioma patients. Due to small sample size our results should be considered preliminary and interpreted with caution. Copyright © 2016 Elsevier Ireland Ltd. All rights reserved.

Spinal Actions of Lipoxin A4 and 17(R)-Resolvin D1 Attenuate Inflammation-Induced Mechanical Hypersensitivity and Spinal TNF Release

PubMed Central

Abdelmoaty, Sally; Wigerblad, Gustaf; Bas, Duygu B.; Codeluppi, Simone; Fernandez-Zafra, Teresa; El-Awady, El-Sayed; Moustafa, Yasser; Abdelhamid, Alaa El-din S.; Brodin, Ernst; Svensson, Camilla I.

2013-01-01

Lipoxins and resolvins have anti-inflammatory and pro-resolving actions and accumulating evidence indicates that these lipid mediators also attenuate pain-like behavior in a number of experimental models of inflammation and tissue injury-induced pain. The present study was undertaken to assess if spinal administration of lipoxin A4 (LXA4) or 17 (R)-resolvin D1 (17(R)-RvD1) attenuates mechanical hypersensitivity in the carrageenan model of peripheral inflammation in the rat. Given the emerging role of spinal cytokines in the generation and maintenance of inflammatory pain we measured cytokine levels in the cerebrospinal fluid (CSF) after LXA4 or 17(R)-RvD1 administration, and the ability of these lipid metabolites to prevent stimuli-induced release of cytokines from cultured primary spinal astrocytes. We found that intrathecal bolus injection of LXA4 and17(R)-RvD1 attenuated inflammation-induced mechanical hypersensitivity without reducing the local inflammation. Furthermore, both LXA4 and 17(R)-RvD1 reduced carrageenan-induced tumor necrosis factor (TNF) release in the CSF, while only 17(R)-RvD1attenuated LPS and IFN-γ-induced TNF release in astrocyte cell culture. In conclusion, this study demonstrates that lipoxins and resolvins potently suppress inflammation-induced mechanical hypersensitivity, possibly by attenuating cytokine release from spinal astrocytes. The inhibitory effect of lipoxins and resolvins on spinal nociceptive processing puts them in an intriguing position in the search for novel pain therapeutics. PMID:24086560

FAA perspectives on historical wake turbulence R&D to recent operational implementations

DOT National Transportation Integrated Search

2017-06-03

A major intent of this presentation is to delineate why the many years of wake turbulence R&D are finally yielding beneficial operational implementations. It will highlight lessons learned from past R&D and going forward for NextGen and beyond.

Current status of final design and R&D for ITER blanket shield blocks in Korea

NASA Astrophysics Data System (ADS)

Ha, M. S.; Kim, S. W.; Jung, H. C.; Hwang, H. S.; Heo, Y. G.; Kim, D. H.; Ahn, H. J.; Lee, H. G.; Jung, K. J.

2015-07-01

them and to optimize the cooling channels. The SB #8 FSP was manufactured and tested in accordance with the pre-qualification program based on the preliminary design, and related R&D activities were implemented to resolve the fabrication issues. This paper provides the current status of the final design and relevant R&D activities of the blanket SB.

Stereochemical course and structure of the products of the enzymic action of endo-1,3-1,4-beta-D-glucan 4-glucanohydrolase from Bacillus licheniformis.

PubMed Central

Malet, C; Jiménez-Barbero, J; Bernabé, M; Brosa, C; Planas, A

1993-01-01

The stereochemical course of the reaction catalysed by endo-1,3-1,4-beta-D-glucan 4-glucanohydrolase (EC 3.2.1.73) has been determined by 1H n.m.r. The enzyme-catalysed hydrolysis of barley beta-glucan proceeds with overall retention of the anomeric configuration, indicating that the enzyme operates through a double-displacement mechanism. The structures of the final oligosaccharide products, 3-beta-O-cellobiosyl D-glucopyranoside and 3-beta-O-cellotriosyl D-glucopyranoside, have been completely assigned by 1H- and 13C-n.m.r. spectroscopy. PMID:8280073

IL-1R and MyD88 signalling in CD4+ T cells promote Th17 immunity and atherosclerosis.

PubMed

Engelbertsen, Daniel; Rattik, Sara; Wigren, Maria; Vallejo, Jenifer; Marinkovic, Goran; Schiopu, Alexandru; Björkbacka, Harry; Nilsson, Jan; Bengtsson, Eva

2018-01-01

The role of CD4+ T cells in atherosclerosis has been shown to be dependent on cytokine cues that regulate lineage commitment into mature T helper sub-sets. In this study, we tested the roles of IL-1R1 and MyD88 signalling in CD4+ T cells in atherosclerosis. We transferred apoe-/-myd88+/+ or apoe-/-myd88-/- CD4+ T cells to T- and B-cell-deficient rag1-/-apoe-/- mice fed high fat diet. Mice given apoe-/-myd88-/- CD4+ T cells exhibited reduced atherosclerosis compared with mice given apoe-/-myd88+/+ CD4+ T cells. CD4+ T cells from apoe-/-myd88-/- produced less IL-17 but similar levels of IFN-γ. Treatment of human CD4+ T cells with a MyD88 inhibitor inhibited IL-17 secretion in vitro. Transfer of il1r1-/- CD4+ T cells recapitulated the phenotype seen by transfer of myd88-/- CD4+ T cells with reduced lesion development and a reduction in Th17 and IL-17 production compared with wild type CD4+ T cell recipients. Relative collagen content of lesions was reduced in mice receiving il1r1-/- CD4+ T cells. We demonstrate that both IL1R and MyD88 signalling in CD4+ T cells promote Th17 immunity, plaque growth and may regulate plaque collagen levels. Published on behalf of the European Society of Cardiology. All rights reserved. © The Author 2017. For permissions please email: journals.permissions@oup.com.

Examining the Chirality, Conformation and Selective Kinase Inhibition of 3-((3R,4R)-4-methyl-3-(methyl(7H-pyrrolo[2,3-d]pyrimidin-4-yl)amino)piperidin-1-yl)-3-oxopropanenitrile (CP-690,550)

PubMed Central

Jiang, Jian-kang; Ghoreschi, Kamran; Deflorian, Francesca; Chen, Zhi; Perreira, Melissa; Pesu, Marko; Smith, Jeremy; Nguyen, Dac-Trung; Liu, Eric H.; Leister, William; Costanzi, Stefano; O’Shea, John J.; Thomas, Craig J.

2009-01-01

Here, we examine the significance that stereochemistry plays within the clinically relevant Janus Kinase 3 (Jak3) inhibitor CP-690,550. A synthesis of all four enantiopure stereoisomers of the drug was carried out and an examination of each compound revealed that only the enantiopure 3R, 4R isomer was capable of blocking Stat5 phosphorylation (Jak3 dependent). Each compound was profiled across a panel of over 350 kinases which revealed a high level of selectivity for the Jak family kinases for these related compounds. Each stereoisomer retained a degree of binding to Jak3 and Jak2 and the 3R, 4S and 3S, 4R stereoisomers were further revealed to have binding affinity for selected members of the STE7 and STE20 subfamily of kinases. Finally, an appraisal of the minimum energy conformation of each stereoisomer and molecular docking at Jak3 was performed in an effort to better understand each compounds selectivity and potency profiles. PMID:19053756

The Impact of Selective Dopamine D2, D3 and D4 Ligands on the Rat Gambling Task.

PubMed

Di Ciano, Patricia; Pushparaj, Abhiram; Kim, Aaron; Hatch, Jessica; Masood, Talal; Ramzi, Abby; Khaled, Maram A T M; Boileau, Isabelle; Winstanley, Catherine A; Le Foll, Bernard

2015-01-01

Gambling is an addictive disorder with serious societal and personal costs. To-date, there are no approved pharmacological treatments for gambling disorder. Evidence suggests a role for dopamine in gambling disorder and thus may provide a therapeutic target. The present study therefore aimed to investigate the effects of selective antagonists and agonists of D2, D3 and D4 receptors in a rodent analogue of the Iowa gambling task used clinically. In this rat gambling task (rGT), animals are trained to associate different response holes with different magnitudes and probabilities of food pellet rewards and punishing time-out periods. As in the Iowa gambling task, the optimal strategy is to avoid the tempting high-risk high-reward options, and instead favor those linked to smaller per-trial rewards but also lower punishments, thereby maximizing the amount of reward earned over time. Administration of those selective ligands did not affect decision making under the rGT. Only the D4 drug had modest effects on latency measures suggesting that D4 may contribute in some ways to decision making under this task.

Clinical Investigation Program, Reports Control Symbol MED-300(R1), Fiscal Year 1988

DTIC Science & Technology

1988-10-01

Dr. Venkataraman Balaraman, M.D. Department/Section: Clinical Investigation Key Words: arginine vasopressin (AVP); vascular smooth muscle responses...Kullama, Ph.D. Associate Investigators: Dr. Venkataraman Balaraman, M.D.; Dr. Kenneth T. Nakamura, M.D.; John R. Claybaugh, Ph.D. Department/Section...Harrison Hassell, MC Associate Investigators: John R. Claybaugh, Ph.D.; Arnold Siemsen, MD; Jon Streltzer, MD Department/Section: Medicine/ Nephrology

A novel MC4R deletion coexisting with FTO and MC1R gene variants, causes severe early onset obesity.

PubMed

Neocleous, Vassos; Shammas, Christos; Phelan, Marie M; Fanis, Pavlos; Pantelidou, Maria; Skordis, Nicos; Mantzoros, Christos; Phylactou, Leonidas A; Toumba, Meropi

2016-07-01

Heterozygous mutations on the melanocortin-4-receptor gene (MC4R) are the most frequent cause of monogenic obesity. We describe a novel MC4R deletion in a girl with severe early onset obesity, tall stature, pale skin and red hair. Clinical and hormonal parameters were evaluated in a girl born full-term by non-consanguineous parents. Her body mass index (BMI) at presentation (3 years) was 30 kg/m 2 (z-score: +4.5SDS). By the age of 5.2 years, she exhibited extreme linear growth acceleration and developed hyperinsulinemia. Direct sequencing of the MC4R, MC1Rand for the knownFTOsingle nucleotide polymorphism (SNP) rs9939609was performed for the patient and her family. A novel heterozygous MC4R p.Met215del (c.643_645delATG) deletion was identified in the patient, her father and her brother, both of whom exhibited a milder phenotype. 3D structural dynamic simulation studies investigated the conformational changes induced by the p.Met215del. The patient and her mother were also found to be carriers of the obesity risk associated FTOrs9939609SNP. Finally, the identification of the known p.Arg160Trp MC1Rvariant in the patient accounts for the red hair and pale skin phenotypic features. The p.Met215del causes global conformational and functional changes as it is localized at the alpha-helical transmembrane regions and the membrane spanning regions of the beta-barrel. This novel mutation produces a severe overgrowth phenotype that is apparent as from infancy and is progressive in childhood. The additional negative effect of environmental and unhealthy lifestyle habits as well as a possible co-interaction of FTOrs9939609 SNP may worsen the phenotype.

Effect of tumor amplitude and frequency on 4D modeling of Vero4DRT system.

PubMed

Miura, Hideharu; Ozawa, Shuichi; Hayata, Masahiro; Tsuda, Shintaro; Yamada, Kiyoshi; Nagata, Yasushi

2017-01-01

An important issue in indirect dynamic tumor tracking with the Vero4DRT system is the accuracy of the model predictions of the internal target position based on surrogate infrared (IR) marker measurement. We investigated the predictive uncertainty of 4D modeling using an external IR marker, focusing on the effect of the target and surrogate amplitudes and periods. A programmable respiratory motion table was used to simulate breathing induced organ motion. Sinusoidal motion sequences were produced by a dynamic phantom with different amplitudes and periods. To investigate the 4D modeling error, the following amplitudes (peak-to-peak: 10-40 mm) and periods (2-8 s) were considered. The 95th percentile 4D modeling error (4D- E 95% ) between the detected and predicted target position ( μ  + 2SD) was calculated to investigate the 4D modeling error. 4D- E 95% was linearly related to the target motion amplitude with a coefficient of determination R 2  = 0.99 and ranged from 0.21 to 0.88 mm. The 4D modeling error ranged from 1.49 to 0.14 mm and gradually decreased with increasing target motion period. We analyzed the predictive error in 4D modeling and the error due to the amplitude and period of target. 4D modeling error substantially increased with increasing amplitude and decreasing period of the target motion.

Pseudo-simple heteroclinic cycles in R4

NASA Astrophysics Data System (ADS)

Chossat, Pascal; Lohse, Alexander; Podvigina, Olga

2018-06-01

We study pseudo-simple heteroclinic cycles for a Γ-equivariant system in R4 with finite Γ ⊂ O(4) , and their nearby dynamics. In particular, in a first step towards a full classification - analogous to that which exists already for the class of simple cycles - we identify all finite subgroups of O(4) admitting pseudo-simple cycles. To this end we introduce a constructive method to build equivariant dynamical systems possessing a robust heteroclinic cycle. Extending a previous study we also investigate the existence of periodic orbits close to a pseudo-simple cycle, which depends on the symmetry groups of equilibria in the cycle. Moreover, we identify subgroups Γ ⊂ O(4) , Γ ⊄ SO(4) , admitting fragmentarily asymptotically stable pseudo-simple heteroclinic cycles. (It has been previously shown that for Γ ⊂ SO(4) pseudo-simple cycles generically are completely unstable.) Finally, we study a generalized heteroclinic cycle, which involves a pseudo-simple cycle as a subset.

Selection of recombinant MVA by rescue of the essential D4R gene.

PubMed

Ricci, Patricia S; Schäfer, Birgit; Kreil, Thomas R; Falkner, Falko G; Holzer, Georg W

2011-12-12

Modified vaccinia virus Ankara (MVA) has become a promising vaccine vector due to its immunogenicity and its proven safety in humans. As a general approach for stringent and rapid selection of recombinant MVA, we assessed marker rescue of the essential viral D4R gene in an engineered deletion mutant that is fully replication defective in wild-type cells. Recombinant, replicating virus was obtained by re-introduction of the deleted viral gene as a dominant selection marker into the deletion mutant.

3D And 4D Cloud Lifecycle Investigations Using Innovative Scanning Radar Analysis Methods. Final report

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

Kollias, Pavlos

2017-04-23

With the vast upgrades to the ARM program radar measurement capabilities in 2010 and beyond, our ability to probe the 3D structure of clouds and associated precipitation has increased dramatically. This project build on the PI's and co-I's expertisein the analysis of radar observations. The first research thrust aims to document the 3D morphological (as depicted by the radar reflectivity structure) and 3D dynamical (cloud$-$scale eddies) structure of boundary layer clouds. Unraveling the 3D dynamical structure of stratocumulus and shallow cumulus clouds requires decomposition of the environmental wind contribution and particle sedimentation velocity from the observed radial Doppler velocity. Themore » second thrust proposes to unravel the mechanism of cumulus entrainment (location, scales) and its impact on microphysics utilizing radar measurements from the vertically pointing and new scanning radars at the ARM sites. The third research thrust requires the development of a cloud$-$tracking algorithm that monitors the properties of cloud.« less

Collaborative Product Development in an R&D Environment

NASA Technical Reports Server (NTRS)

Davis, Jose M.; Keys, L. Ken; Chen, Injazz J.; Peterson, Paul L.

2004-01-01

Research and development (R&D) organizations are being required to be relevant, to be more application-oriented, and to be partners in the strategic management of the business while meeting the same challenges as the rest of the organization, namely: (1) reduced time to market; (2) reduced cost; (3) improved quality; (4) increased reliability; and (5) increased focus on customer needs. Recent advances in computer technology and the Internet have created a new paradigm of collaborative engineering or collaborative product development (CPD), from which new types of relationships among researchers and their partners have emerged. Research into the applicability and benefits of CPD in a low/no production, R&D, and/or government environment is limited. In addition, the supply chain management (SCM) aspects of these relationships have not been studied. This paper presents research conducted at the NASA Glenn Research Center (GRC) investigating the applicability of CPD and SCM in an R&D organization. The study concentrates on the management and implementation of space research activities at GRC. Results indicate that although the organization is engaged in collaborative relationships that incorporate aspects of SCM, a number of areas, such as development of trust and information sharing merit special attention.

Unravelling the resistance mechanisms to 2,4-D (2,4-dichlorophenoxyacetic acid) in corn poppy (Papaver rhoeas).

PubMed

Rey-Caballero, Jordi; Menéndez, Julio; Giné-Bordonaba, Jordi; Salas, Marisa; Alcántara, Ricardo; Torra, Joel

2016-10-01

In southern Europe, the intensive use of 2,4-D (2,4-dichlorophenoxyacetic acid) and tribenuron-methyl in cereal crop systems has resulted in the evolution of resistant (R) corn poppy (Papaver rhoeas L.) biotypes. Experiments were conducted to elucidate (1) the resistance response to these two herbicides, (2) the cross-resistant pattern to other synthetic auxins and (3) the physiological basis of the auxin resistance in two R (F-R213 and D-R703) populations. R plants were resistant to both 2,4-D and tribenuron-methyl (F-R213) or just to 2,4-D (D-R703) and both R populations were also resistant to dicamba and aminopyralid. Results from absorption and translocation experiment revealed that R plants translocated less [14C]-2,4-D than S plants at all evaluation times. There was between four and eight-fold greater ethylene production in S plants treated with 2,4-D, than in R plants. Overall, these results suggest that reduced 2,4-D translocation is the resistance mechanism in synthetic auxins R corn poppy populations and this likely leads to less ethylene production and greater survival in R plants. Copyright © 2016 Elsevier B.V. All rights reserved.

A peptide disrupting the D2R-DAT interaction protects against dopamine neurotoxicity.

PubMed

Su, Ping; Liu, Fang

2017-09-01

Dopamine reuptake from extracellular space to cytosol leads to accumulation of dopamine, which triggers neurotoxicity in dopaminergic neurons. Previous studies have shown that both dopamine D2 receptor (D2R) and dopamine transporter (DAT) are involved in dopamine neurotoxicity. However, blockade of either D2R or DAT causes side effects due to antagonism of other physiological functions of these two proteins. We previously found that DAT can form a protein complex with D2R and its cell surface expression is facilitated via D2R-DAT interaction, which regulates dopamine reuptake and intracellular dopamine levels. Here we found that an interfering peptide (DAT-S1) disrupting the D2R-DAT interaction protects neurons against dopamine neurotoxicity, and this effect is mediated by inhibiting DAT cell surface expression and inhibiting both caspase-3 and PARP-1 cleavage. This study demonstrates the role of the D2R-DAT complex in dopamine neurotoxicity and investigated the potential mechanisms, which might help better understand the mechanisms of dopamine neurotoxicity. The peptide may provide some insights to improve treatments for dopamine neurotoxicity and related diseases, such as Parkinson's disease, as well as methamphetamine- and 3,4-methsylenedioxy methamphetamine-induced neurotoxicity. Copyright © 2017. Published by Elsevier Inc.

Rebaudioside A and Rebaudioside D bitterness do not covary with Acesulfame K bitterness or polymorphisms in TAS2R9 and TAS2R31

PubMed Central

Allen, Alissa L.; McGeary, John E.; Hayes, John E.

2013-01-01

In order to reduce calories in foods and beverages, the food industry routinely uses non-nutritive sweeteners. Unfortunately, many are synthetically derived, and many consumers have a strong preference for natural sweeteners, irrespective of the safety data on synthetic non-nutritive sweeteners. Additionally, many non-nutritive sweeteners elicit aversive side tastes such as bitter and metallic in addition to sweetness. Bitterness thresholds of acesulfame-K (AceK) and saccharin are known to vary across bitter taste receptors polymorphisms in TAS2R31. RebA has shown to activate hTAS2R4 and hTAS2R14 in vitro. Here we examined bitterness and sweetness perception of natural and synthetic non-nutritive sweeteners. In a follow-up to a previous gene-association study, participants (n=122) who had been genotyped previously rated sweet, bitter and metallic sensations from rebaudioside A (RebA), rebaudioside D (RebD), aspartame, sucrose and gentiobiose in duplicate in a single session. For comparison, we also present sweet and bitter ratings of AceK collected in the original experiment for the same participants. At similar sweetness levels, aspartame elicited less bitterness than RebD, which was significantly less bitter than RebA. The bitterness of RebA and RebD showed wide variability across individuals, and bitterness ratings for these compounds were correlated. However, RebA and RebD bitterness did not covary with AceK bitterness. Likewise, single nucleotide polymorphisms (SNPs) shown previously to explain variation in the suprathreshold bitterness of AceK (rs3741845 in TAS2R9 and rs10772423 in TAS2R31) did not explain variation in RebA and RebD bitterness. Because RebA activates hT2R4 and hT2R14, a SNP in TAS2R4 previously associated with variation in bitterness perception was included here; there are no known functional SNPs for TAS2R14. In present data, a putatively functional SNP (rs2234001) in TAS2R4 did not explain variation in RebA or RebD bitterness. Collectively

Helical assembly in the MyD88-IRAK4-IRAK2 complex in TLR/IL-1R signalling

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

Lin, Su-Chang; Lo, Yu-Chih; Wu, Hao

2010-08-23

MyD88, IRAK4 and IRAK2 are critical signalling mediators of the TLR/IL1-R superfamily. Here we report the crystal structure of the MyD88-IRAK4-IRAK2 death domain (DD) complex, which surprisingly reveals a left-handed helical oligomer that consists of 6 MyD88, 4 IRAK4 and 4 IRAK2 DDs. Assembly of this helical signalling tower is hierarchical, in which MyD88 recruits IRAK4 and the MyD88-IRAK4 complex recruits the IRAK4 substrates IRAK2 or the related IRAK1. Formation of these Myddosome complexes brings the kinase domains of IRAKs into proximity for phosphorylation and activation. Composite binding sites are required for recruitment of the individual DDs in the complex,more » which are confirmed by mutagenesis and previously identified signalling mutations. Specificities in Myddosome formation are dictated by both molecular complementarity and correspondence of surface electrostatics. The MyD88-IRAK4-IRAK2 complex provides a template for Toll signalling in Drosophila and an elegant mechanism for versatile assembly and regulation of DD complexes in signal transduction.« less

High field induced magnetic transitions in the Y0.7E r0.3F e2D4.2 deuteride

NASA Astrophysics Data System (ADS)

Paul-Boncour, V.; Guillot, M.; Isnard, O.; Hoser, A.

2017-09-01

The influence of the partial Er for Y substitution on the crystal structure and magnetic properties of YF e2D4.2 has been investigated by high field magnetization and neutron diffraction experiments. Y0.7E r0.3F e2D4.2 compound crystallizes in the same monoclinic structure as YF e2D4.2 described in P c (P1c1) space group with D atoms located in 18 different tetrahedral interstitial sites. A cell volume contraction of 0.6% is observed upon Er substitution, inducing large modification of the magnetic properties. Electronic effect of D insertion as well as lowering of crystal symmetry are important factors determining the magnetic properties of Fe sublattice, which evolves towards more delocalized behavior and modifying the Er-Fe exchange interactions. In the ground state, the Er and Fe moments are arranged ferrimagnetically within the plane perpendicular to the monoclinic b axis and with average moments mEr=6.4 (3 ) μBEr-1 and mFe=2.0 (1 ) μBFe-1 at 10 K. Upon heating, mEr decreases progressively until TEr=55 K . Between 55 K and 75 K, the Fe sublattice undergoes a first-order ferromagnetic-antiferromagnetic (FM-AFM) transition with a cell volume contraction due to the itinerant metamagnetic behavior of one Fe site. In the AFM structure, mFe decreases until the Néel temperature TN=125 K . At high field, two different types of field induced transitions are observed. The Er moments become parallel to the Fe one and saturates to the E r3 + free ion value, leading to an unusual field induced FM arrangement at a transition field BTrans of only 78 kG below 30 K. Then above TM0=66 K , an AFM-FM transition of the Fe sublattice, accompanied by a cell volume increase is observed. BTrans increases linearly versus temperature and with a larger d BTrans/d T slope than for YF e2D4.2 . This has been explained by the additional contribution of Er induced moments above BTrans.

Trends & Indicators: NE Universities Still R&D Powerhouses

ERIC Educational Resources Information Center

Harney, John O.

2011-01-01

New England universities performed more than $4 billion worth of research and development (R&D) in 2009, but the region's share of total R&D performed by all U.S. universities remained at 7.3%, down from more than 10% in the 1980s. The region's university research labs have been world-famous for ideas that breed companies and whole…

Photooxidation of d(TpG) by phthalocyanines and riboflavin. Isolation and characterization of dinucleoside monophosphates containing the 4R* and 4S* diastereoisomers of 4,8-dihydro-4-hydroxy-8-oxo-2'-deoxy-guanosine.

PubMed Central

Buchko, G W; Cadet, J; Berger, M; Ravanat, J L

1992-01-01

Phthalocyanine mediated photosensitization of 2'-deoxyguanosine (dG) in oxygen saturated aqueous solution has previously been shown to result in the addition of molecular oxygen to the guanine base generating the 4R* and 4S* diastereoisomers of 4,8-dihydro-4-hydroxy-8-oxo-2'-deoxyguanosine (dO) (the asterisk denotes unambiguous assignment of the 4R and 4S diastereoisomers). The data presented here show that the same guanine modified bases are generated in a 1:1 ratio when thymidylyl-(3',5')-2'-deoxyguanosine (d(TpG)) is similarly photo-oxidized. These modified dinucleoside monophosphates, labelled d(TpO)-A and -B, have been isolated by high performance liquid chromatography and characterized by proton NMR spectrometry, fast atom bombardment mass spectrometry, and enzymatic digestions. Photosensitization in D2O instead of H2O leads to an increase in the rate of d(TpO) formation that is consistent with a type II (singlet oxygen) reaction mechanism. Three interesting properties of these modified dinucleoside monophosphates are: i) the rate of their digestion with spleen phosphodiesterase is greatly reduced relative to d(TpG), ii) they are not digested by snake venom phosphodiesterase, and iii) they are stable to 1.0 M piperidine at 90 degrees C for 30 min. The latter observation indicates that 4,8-dihydro-4-hydroxy-8-oxoguanine is not a base lesion responsible for the strand breaks observed following hot piperidine treatment of DNA exposed to type II photosensitizers or chemically generated singlet oxygen. PMID:1329029

Complete genomic sequences for hepatitis C virus subtypes 4b, 4c, 4d, 4g, 4k, 4l, 4m, 4n, 4o, 4p, 4q, 4r and 4t.

PubMed

Li, Chunhua; Lu, Ling; Wu, Xianghong; Wang, Chuanxi; Bennett, Phil; Lu, Teng; Murphy, Donald

2009-08-01

In this study, we characterized the full-length genomic sequences of 13 distinct hepatitis C virus (HCV) genotype 4 isolates/subtypes: QC264/4b, QC381/4c, QC382/4d, QC193/4g, QC383/4k, QC274/4l, QC249/4m, QC97/4n, QC93/4o, QC139/4p, QC262/4q, QC384/4r and QC155/4t. These were amplified, using RT-PCR, from the sera of patients now residing in Canada, 11 of which were African immigrants. The resulting genomes varied between 9421 and 9475 nt in length and each contains a single ORF of 9018-9069 nt. The sequences showed nucleotide similarities of 77.3-84.3 % in comparison with subtypes 4a (GenBank accession no. Y11604) and 4f (EF589160) and 70.6-72.8 % in comparison with genotype 1 (M62321/1a, M58335/1b, D14853/1c, and 1?/AJ851228) reference sequences. These similarities were often higher than those currently defined by HCV classification criteria for subtype (75.0-80.0 %) and genotype (67.0-70.0 %) division, respectively. Further analyses of the complete and partial E1 and partial NS5B sequences confirmed these 13 'provisionally assigned subtypes'.

Malware Memory Analysis for Non-specialists: Investigating Publicly Available Memory Image 0zapftis (R2D2)

DTIC Science & Technology

2013-10-01

investigators can conduct meaningful memory-based investigations on their own. This technical memorandum examines the 0zapftis (R2D2) Trojan horse , in order...TM 2013-018 and TM 2013-155, examined the Zeus Trojan horse (the former) while the latter examined the Prolaco worm and SpyEye Trojan horse . It is...necessary for a novice to conduct such memory analyses on his own. The first report in this series written by the author examined the Zeus Trojan Horse

Data assimilation of non-conventional observations using GEOS-R flash lightning: 1D+4D-VAR approach vs. assimilation of images (Invited)

NASA Astrophysics Data System (ADS)

Navon, M. I.; Stefanescu, R.

2013-12-01

Previous assimilation of lightning used nudging approaches. We develop three approaches namely, 3D-VAR WRFDA and1D+nD-VAR (n=3,4) WRFDA . The present research uses Convective Available Potential Energy (CAPE) as a proxy between lightning data and model variables. To test performance of aforementioned schemes, we assess quality of resulting analysis and forecasts of precipitation compared to those from a control experiment and verify them against NCEP stage IV precipitation. Results demonstrate that assimilating lightning observations improves precipitation statistics during the assimilation window and for 3-7 h thereafter. The 1D+4D-VAR approach yielded the best performance significantly improving precipitation rmse errors by 25% and 27.5%,compared to control during the assimilation window for two tornadic test cases. Finally we propose a new approach to assimilate 2-D images of lightning flashes based on pixel intensity, mitigating dimensionality by a reduced order method.

The FAZIA project in Europe: R&D phase

NASA Astrophysics Data System (ADS)

Bougault, R.; Poggi, G.; Barlini, S.; Borderie, B.; Casini, G.; Chbihi, A.; Le Neindre, N.; Pârlog, M.; Pasquali, G.; Piantelli, S.; Sosin, Z.; Ademard, G.; Alba, R.; Anastasio, A.; Barbey, S.; Bardelli, L.; Bini, M.; Boiano, A.; Boisjoli, M.; Bonnet, E.; Borcea, R.; Bougard, B.; Brulin, G.; Bruno, M.; Carboni, S.; Cassese, C.; Cassese, F.; Cinausero, M.; Ciolacu, L.; Cruceru, I.; Cruceru, M.; D'Aquino, B.; De Fazio, B.; Degerlier, M.; Desrues, P.; Di Meo, P.; Dueñas, J. A.; Edelbruck, P.; Energico, S.; Falorsi, M.; Frankland, J. D.; Galichet, E.; Gasior, K.; Gramegna, F.; Giordano, R.; Gruyer, D.; Grzeszczuk, A.; Guerzoni, M.; Hamrita, H.; Huss, C.; Kajetanowicz, M.; Korcyl, K.; Kordyasz, A.; Kozik, T.; Kulig, P.; Lavergne, L.; Legouée, E.; Lopez, O.; Łukasik, J.; Maiolino, C.; Marchi, T.; Marini, P.; Martel, I.; Masone, V.; Meoli, A.; Merrer, Y.; Morelli, L.; Negoita, F.; Olmi, A.; Ordine, A.; Paduano, G.; Pain, C.; Pałka, M.; Passeggio, G.; Pastore, G.; Pawłowski, P.; Petcu, M.; Petrascu, H.; Piasecki, E.; Pontoriere, G.; Rauly, E.; Rivet, M. F.; Rocco, R.; Rosato, E.; Roscilli, L.; Scarlini, E.; Salomon, F.; Santonocito, D.; Seredov, V.; Serra, S.; Sierpowski, D.; Spadaccini, G.; Spitaels, C.; Stefanini, A. A.; Tobia, G.; Tortone, G.; Twaróg, T.; Valdré, S.; Vanzanella, A.; Vanzanella, E.; Vient, E.; Vigilante, M.; Vitiello, G.; Wanlin, E.; Wieloch, A.; Zipper, W.

2014-02-01

The goal of the FAZIA Collaboration is the design of a new-generation 4 π detector array for heavy-ion collisions with radioactive beams. This article summarizes the main results of the R&D phase, devoted to the search for significant improvements of the techniques for charge and mass identification of reaction products. This was obtained by means of a systematic study of the basic detection module, consisting of two transmission-mounted silicon detectors followed by a CsI(Tl) scintillator. Significant improvements in ΔE- E and pulse-shape techniques were obtained by controlling the doping homogeneity and the cutting angles of silicon and by putting severe constraints on thickness uniformity. Purposely designed digital electronics contributed to identification quality. The issue of possible degradation related to radiation damage of silicon was also addressed. The experimental activity was accompanied by studies on the physics governing signal evolution in silicon. The good identification quality obtained with the prototypes during the R&D phase, allowed us to investigate also some aspects of isospin physics, namely isospin transport and odd-even staggering. Now, after the conclusion of the R&D period, the FAZIA Collaboration has entered the demonstrator phase, with the aim of verifying the applicability of the devised solutions for the realization of a larger-scale experimental set-up.

Gene expression in hypothalamus, liver and adipose tissues and feed intake response to melanocortin-4 receptor (MC4R) agonist in pigs expressing (MC4R) mutations

USDA-ARS?s Scientific Manuscript database

Transcriptional profiling was used to identify genes and pathways that responded to intracerebroventricular (ICV) injection of melanocortin-4 receptor (MC4R) agonist, NDP-MSH, in pigs homozygous for the missense mutation in the MC4R, D298 allele (n = 12), N298 allele (n = 12) or heterozygous (n = 12...

Digit ratio (2D:4D) and male facial attractiveness: new data and a meta-analysis.

PubMed

Hönekopp, Johannes

2013-10-01

Digit ratio (2D:4D) appears to correlate negatively with prenatal testosterone (T) effects in humans. As T probably increases facial masculinity, which in turn might be positively related to male facial attractiveness, a number of studies have looked into the relationship between 2D:4D and male facial attractiveness, showing equivocal results. Here, I present the largest and third largest samples so far, which investigate the relationship between 2D:4D and male facial attractiveness in adolescents (n = 115) and young men (n = 80). I then present random-effects meta-analyses of the available data (seven to eight samples, overall n = 362 to 469). These showed small (r ≈ -.09), statistically non-significant relationships between 2D:4D measures and male facial attractiveness. Thus, 2D:4D studies offer no convincing evidence at present that prenatal T has a positive effect on male facial attractiveness. However, a consideration of confidence intervals shows that, at present, a theoretically meaningful relationship between 2D:4D and male facial attractiveness cannot be ruled out either.

Effect of Dissemination of 2,4-Dichlorophenoxyacetic Acid (2,4-D) Degradation Plasmids on 2,4-D Degradation and on Bacterial Community Structure in Two Different Soil Horizons

PubMed Central

Dejonghe, Winnie; Goris, Johan; El Fantroussi, Saïd; Höfte, Monica; De Vos, Paul; Verstraete, Willy; Top, Eva M.

2000-01-01

Transfer of the 2,4-dichlorophenoxyacetic acid (2,4-D) degradation plasmids pEMT1 and pJP4 from an introduced donor strain, Pseudomonas putida UWC3, to the indigenous bacteria of two different horizons (A horizon, depth of 0 to 30 cm; B horizon, depth of 30 to 60 cm) of a 2,4-D-contaminated soil was investigated as a means of bioaugmentation. When the soil was amended with nutrients, plasmid transfer and enhanced degradation of 2,4-D were observed. These findings were most striking in the B horizon, where the indigenous bacteria were unable to degrade any of the 2,4-D (100 mg/kg of soil) during at least 22 days but where inoculation with either of the two plasmid donors resulted in complete 2,4-D degradation within 14 days. In contrast, in soils not amended with nutrients, inoculation of donors in the A horizon and subsequent formation of transconjugants (105 CFU/g of soil) could not increase the 2,4-D degradation rate compared to that of the noninoculated soil. However, donor inoculation in the nonamended B-horizon soil resulted in complete degradation of 2,4-D within 19 days, while no degradation at all was observed in noninoculated soil during 89 days. With plasmid pEMT1, this enhanced degradation seemed to be due only to transconjugants (105 CFU/g of soil), since the donor was already undetectable when degradation started. Denaturing gradient gel electrophoresis (DGGE) of 16S rRNA genes showed that inoculation of the donors was followed by a shift in the microbial community structure of the nonamended B-horizon soils. The new 16S rRNA gene fragments in the DGGE profile corresponded with the 16S rRNA genes of 2,4-D-degrading transconjugant colonies isolated on agar plates. This result indicates that the observed change in the community was due to proliferation of transconjugants formed in soil. Overall, this work clearly demonstrates that bioaugmentation can constitute an effective strategy for cleanup of soils which are poor in nutrients and microbial activity

Structures of exocyclic R,R- and S,S-N(6),N(6)-(2,3-dihydroxybutan-1,4-diyl)-2'-deoxyadenosine adducts induced by 1,2,3,4-diepoxybutane.

PubMed

Kowal, Ewa A; Seneviratne, Uthpala; Wickramaratne, Susith; Doherty, Kathleen E; Cao, Xiangkun; Tretyakova, Natalia; Stone, Michael P

2014-05-19

1,3-Butadiene (BD) is an industrial and environmental chemical present in urban air and cigarette smoke, and is classified as a human carcinogen. It is oxidized by cytochrome P450 to form 1,2,3,4-diepoxybutane (DEB); DEB bis-alkylates the N(6) position of adenine in DNA. Two enantiomers of bis-N(6)-dA adducts of DEB have been identified: R,R-N(6),N(6)-(2,3-dihydroxybutan-1,4-diyl)-2'-deoxyadenosine (R,R-DHB-dA), and S,S-N(6),N(6)-(2,3-dihydroxybutan-1,4-diyl)-2'-deoxyadenosine (S,S-DHB-dA) [ Seneviratne , U. , Antsypovich , S. , Dorr , D. Q. , Dissanayake , T. , Kotapati , S. , and Tretyakova , N. ( 2010 ) Chem. Res. Toxicol. 23 , 1556 -1567 ]. Herein, the R,R-DHB-dA and S,S-DHB-dA adducts have been incorporated into the 5'-d(C(1)G(2)G(3)A(4)C(5)X(6)A(7)G(8)A(9)A(10)G(11))-3':5'-d(C(12)T(13)T(14)C(15)T(16)T(17)G(18)T(19)C(20)C(21)G(22))-3' duplex [X(6) = R,R-DHB-dA (R(6)) or S,S-DHB-dA (S(6))]. The structures of the duplexes were determined by molecular dynamics calculations, which were restrained by experimental distances obtained from NMR data. Both the R,R- and S,S-DHB-dA adducts are positioned in the major groove of DNA. In both instances, the bulky 3,4-dihydroxypyrrolidine rings are accommodated by an out-of-plane rotation about the C6-N(6) bond of the bis-alkylated adenine. In both instances, the directionality of the dihydroxypyrrolidine ring is evidenced by the pattern of NOEs between the 3,4-dihydroxypyrrolidine protons and DNA. Also in both instances, the anti conformation of the glycosyl bond is maintained, which combined with the out-of-plane rotation about the C6-N(6) bond, allows the complementary thymine, T(17), to remain stacked within the duplex, and form one hydrogen bond with the modified base, between the imine nitrogen of the modified base and the T(17) N3H imino proton. The loss of the second Watson-Crick hydrogen bonding interaction at the lesion sites correlates with the lower thermal stabilities of the R,R- and S,S-DHB-dA duplexes, as

Luminescence and magnetic properties of novel nanoparticle-sheathed 3D Micro-Architectures of Fe0.5R0.5(MoO4)1.5:Ln3+ (R = Gd3+, La3+), (Ln = Eu, Tb, Dy) for bifunctional application

NASA Astrophysics Data System (ADS)

Krishnan, Rajagopalan; Thirumalai, Jagannathan; Kathiravan, Arunkumar

2015-01-01

For the first time, we report the successful synthesis of novel nanoparticle-sheathed bipyramid-like and almond-like Fe0.5R0.5(MoO4)1.5:Ln3+ (R = Gd3+, La3+), (Ln = Eu, Tb, Dy) 3D hierarchical microstructures through a simple disodium ethylenediaminetetraacetic acid (Na2EDTA) facilitated hydrothermal method. Interestingly, time-dependent experiments confirm that the assembly-disassembly process is responsible for the formation of self-aggregated 3D architectures via Ostwald ripening phenomena. The resultant products are characterized by x-ray diffraction (XRD), field emission scanning electron microscopy (FESEM), high resolution transmission electron microscopy (HRTEM), photoluminescence (PL), and magnetic measurements. The growth and formation mechanisms of the self-assembled 3D micro structures are discussed in detail. To confirm the presence of all the elements in the microstructure, the energy loss induced by the K, L shell electron ionization is observed in order to map the Fe, Gd, Mo, O, and Eu components. The photo luminescence properties of Fe0.5R0.5(MoO4)1.5 doped with Eu3+, Tb3+, Dy3+ are investigated. The room temperature and low temperature magnetic properties suggest that the interaction between the local-fields introduced by the magnetic Fe3+ ions and the R3+ (La, Gd) ions in the dodecahedral sites determine the magnetism in Fe0.5R0.5(MoO4)1.5:Eu3+. This work provides a new approach to synthesizing the novel Fe0.5R0.5(MoO4)1.5:Ln3+ for bi-functional magnetic and luminescence applications.

Output orientation in R and D: A better approach?. [decision making in R and D

NASA Technical Reports Server (NTRS)

Black, G.

1974-01-01

Research and development management is examined as it might be performed under an output-oriented approach in which the company's needs for innovations in various product and production areas were identified. It is shown that a company's R and D program is the aggregate of its needs in various areas of its business. The planning, programming and budgeting approach is applied to R and D. The state of theory on R and D decision making in economics is summarized. Abstracts of articles concerning R and D in industry are included.

Gravitational collapse in repulsive R+μ4/R gravity

NASA Astrophysics Data System (ADS)

Fathi, Mohsen; Mohseni, Morteza

2016-10-01

In this paper we work out collapsing conditions for a spherical star in the weak field limit of the R+μ4/R gravity and discuss the importance of the parameter μ to generate different criteria in the theory. Such criteria are proved to be resulting in a variety of different fates for the evolution of the outer shells of stars. Furthermore, we investigate the special case of violating the first junction condition and point out corresponding contradictions to the normal cases. These results show that the consistency of the R+μ4/R theory of gravity with the common astrophysical predictions relies highly on the adoption of the parameter μ and satisfaction/violation of the first junction condition. For those anomalous results, further observational attempts are mandatory.

ReRouting biomedical innovation: observations from a mapping of the alternative research and development (R&D) landscape.

PubMed

Greenberg, Alexandra; Kiddell-Monroe, Rachel

2016-09-14

In recent years, the world has witnessed the tragic outcomes of multiple global health crises. From Ebola to high prices to antibiotic resistance, these events highlight the fundamental constraints of the current biomedical research and development (R&D) system in responding to patient needs globally.To mitigate this lack of responsiveness, over 100 self-identified "alternative" R&D initiatives, have emerged in the past 15 years. To begin to make sense of this panoply of initiatives working to overcome the constraints of the current system, UAEM began an extensive, though not comprehensive, mapping of the alternative biomedical R&D landscape. We developed a two phase approach: (1) an investigation, via the RE:Route Mapping, of both existing and proposed initiatives that claim to offer an alternative approach to R&D, and (2) evaluation of those initiatives to determine which are in fact achieving increased access to and innovation in medicines. Through phase 1, the RE:Route Mapping, we examined 81 initiatives that claim to redress the inequity perpetuated by the current system via one of five commonly recognized mechanisms necessary for truly alternative R&D.Preliminary analysis of phase 1 provides the following conclusions: 1. No initiative presents a completely alternative model of biomedical R&D. 2. The majority of initiatives focus on developing incentives for drug discovery. 3. The majority of initiatives focus on rare diseases or diseases of the poor and marginalized. 4. There is an increasing emphasis on the use of push, pull, pool, collaboration and open mechanisms alongside the concept of delinkage in alternative R&D. 5. There is a trend towards public funding and launching of initiatives by the Global South. Given the RE:Route Mapping's inevitable limitations and the assumptions made in its methodology, it is not intended to be the final word on a constantly evolving and complex field; however, its findings are significant. The Mapping's value lies in its

Structures of Exocyclic R,R- and S,S-N6,N6-(2,3-Dihydroxybutan-1,4-diyl)-2′-Deoxyadenosine Adducts Induced by 1,2,3,4-Diepoxybutane

PubMed Central

2015-01-01

1,3-Butadiene (BD) is an industrial and environmental chemical present in urban air and cigarette smoke, and is classified as a human carcinogen. It is oxidized by cytochrome P450 to form 1,2,3,4-diepoxybutane (DEB); DEB bis-alkylates the N6 position of adenine in DNA. Two enantiomers of bis-N6-dA adducts of DEB have been identified: R,R-N6,N6-(2,3-dihydroxybutan-1,4-diyl)-2′-deoxyadenosine (R,R-DHB-dA), and S,S-N6,N6-(2,3-dihydroxybutan-1,4-diyl)-2′-deoxyadenosine (S,S-DHB-dA) [SeneviratneU., AntsypovichS., DorrD. Q., DissanayakeT., KotapatiS., and TretyakovaN. (2010) Chem. Res. Toxicol.23, 1556−156720873715]. Herein, the R,R-DHB-dA and S,S-DHB-dA adducts have been incorporated into the 5′-d(C1G2G3A4C5X6A7G8A9A10G11)-3′:5′-d(C12T13T14C15T16T17G18T19C20C21G22)-3′ duplex [X6 = R,R-DHB-dA (R6) or S,S-DHB-dA (S6)]. The structures of the duplexes were determined by molecular dynamics calculations, which were restrained by experimental distances obtained from NMR data. Both the R,R- and S,S-DHB-dA adducts are positioned in the major groove of DNA. In both instances, the bulky 3,4-dihydroxypyrrolidine rings are accommodated by an out-of-plane rotation about the C6-N6 bond of the bis-alkylated adenine. In both instances, the directionality of the dihydroxypyrrolidine ring is evidenced by the pattern of NOEs between the 3,4-dihydroxypyrrolidine protons and DNA. Also in both instances, the anti conformation of the glycosyl bond is maintained, which combined with the out-of-plane rotation about the C6-N6 bond, allows the complementary thymine, T17, to remain stacked within the duplex, and form one hydrogen bond with the modified base, between the imine nitrogen of the modified base and the T17 N3H imino proton. The loss of the second Watson–Crick hydrogen bonding interaction at the lesion sites correlates with the lower thermal stabilities of the R,R- and S,S-DHB-dA duplexes, as compared to the corresponding unmodified duplex. The reduced base stacking at the

Malat1 activates autophagy and promotes cell proliferation by sponging miR-101 and upregulating STMN1, RAB5A and ATG4D expression in glioma.

PubMed

Fu, Zhenqiang; Luo, Wenzheng; Wang, Jingtao; Peng, Tao; Sun, Guifang; Shi, Jingyu; Li, Zhihong; Zhang, Boai

2017-10-21

The long noncoding RNA Malat1 has been reported to be an oncogene that promotes tumor progress and correlates with prognosis in glioma. Growing evidence shows that autophagy plays a very important role in tumorigenesis and tumor cell survival, but whether Malat1 regulates autophagy in glioma is still unclear. In this study, we found that Malat1 expression and autophagy activity were significantly increased in glioma tissues compared with adjacent normal tissues. Additionally, Malat1 level was positively correlated with the expression of LC3-II (autophagy marker) mRNA in vivo. In vitro assays revealed that Malat1 significantly promoted autophagy activation and cell proliferation in glioma cells. More importantly, inhibition of autophagy by 3-MA relieved Malat1-induced cell proliferation. These data demonstrated that Malat1 activates autophagy and increases cell proliferation in glioma. We further investigated the molecular mechanisms whereby Malat1 functioned on glioma cell autophagy and proliferation. We found that Malat1 served as an endogenous sponge to reduce miR-101 expression by directly binding to miR-101. Moreover, Malat1 abolished the suppression effects of miR-101 on glioma cell autophagy and proliferation, which involved in upregulating the expression of miR-101 targets STMN1, RAB5A and ATG4D. Overall, our study elucidated a novel Malat1-miR-101-STMN1/RAB5A/ATG4D regulatory network that Malat1 activates autophagy and promotes cell proliferation by sponging miR-101 and upregulating STMN1, RAB5A and ATG4D expression in glioma cells. Copyright © 2017 Elsevier Inc. All rights reserved.

FY2016 Advanced Batteries R&D Annual Progress Report - Part 4 of 5

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

None, None

The Advanced Batteries research and development (R&D) subprogram within the DOE Vehicle Technologies Office (VTO) provides support and guidance for projects focusing on batteries for plug-in electric vehicles. Program targets focus on overcoming technical barriers to enable market success including: (1) significantly reducing battery cost, (2) increasing battery performance (power, energy, durability), (3) reducing battery weight & volume, and (4) increasing battery tolerance to abusive conditions such as short circuit, overcharge, and crush. This report describes the progress made on the research and development projects funded by the Battery subprogram in 2016. This section covers Advanced Battery Materials Research (BMR)more » part 1.« less

Novel Analogues of (R)-5-(Methylamino)-5,6-dihydro-4H-imidazo[4,5,1-ij]quinolin-2(1H)-one (Sumanirole) Provide Clues to Dopamine D2/D3 Receptor Agonist Selectivity

PubMed Central

2016-01-01

Novel 1-, 5-, and 8-substituted analogues of sumanirole (1), a dopamine D2/D3 receptor (D2R/D3R) agonist, were synthesized. Binding affinities at both D2R and D3R were higher when determined in competition with the agonist radioligand [3H]7-hydroxy-N,N-dipropyl-2-aminotetralin (7-OH-DPAT) than with the antagonist radioligand [3H]N-methylspiperone. Although 1 was confirmed as a D2R-preferential agonist, its selectivity in binding and functional studies was lower than previously reported. All analogues were determined to be D2R/D3R agonists in both GoBRET and mitogenesis functional assays. Loss of efficacy was detected for the N-1-substituted analogues at D3R. In contrast, the N-5-alkyl-substituted analogues, and notably the n-butyl-arylamides (22b and 22c), all showed improved affinity at D2R over 1 with neither a loss of efficacy nor an increase in selectivity. Computational modeling provided a structural basis for the D2R selectivity of 1, illustrating how subtle differences in the highly homologous orthosteric binding site (OBS) differentially affect D2R/D3R affinity and functional efficacy. PMID:27035329

78 FR 24985 - Amendment of Restricted Areas R-6703A, B, C, D; and Establishment of Restricted Areas R-6703E, F...

Federal Register 2010, 2011, 2012, 2013, 2014

2013-04-29

...-0371; Airspace Docket No. 12-ANM-14] RIN 2120-AA66 Amendment of Restricted Areas R-6703A, B, C, D; and Establishment of Restricted Areas R-6703E, F, G, H, I, and J; WA AGENCY: Federal Aviation Administration (FAA), DOT. ACTION: Final rule. SUMMARY: This action modifies the internal boundaries of R-6703 by further...

Differentiation of Forebrain and Hippocampal Dopamine 1-Class Receptors, D1R and D5R, in Spatial Learning and Memory

PubMed Central

Sariñana, Joshua; Tonegawa, Susumu

2017-01-01

Activation of prefrontal cortical (PFC), striatal, and hippocampal dopamine 1-class receptors (D1R and D5R) is necessary for normal spatial information processing. Yet the precise role of the D1R versus the D5R in the aforementioned structures, and their specific contribution to the water-maze spatial learning task remains unknown. D1R- and D5R- specific in situ hybridization probes showed that forebrain restricted D1R and D5R KO mice (F-D1R/D5R KO) displayed D1R mRNA deletion in the medial (m)PFC, dorsal and ventral striatum, and the dentate gyrus (DG) of the hippocampus. D5R mRNA deletion was limited to the mPFC, the CA1 and DG hippocampal subregions. F-D1R/D5R KO mice were given water-maze training and displayed subtle spatial latency differences between genotypes and spatial memory deficits during both regular and reversal training. To differentiate forebrain D1R from D5R activation, forebrain restricted D1R KO (F-D1R KO) and D5R KO (F-D5R KO) mice were trained on the water-maze task. F-D1R KO animals exhibited escape latency deficits throughout regular and reversal training as well as spatial memory deficits during reversal training. F-D1R KO mice also showed perseverative behavior during the reversal spatial memory probe test. In contrast, F-D5R KO animals did not present observable deficits on the water-maze task. Because F-D1R KO mice showed water-maze deficits we tested the necessity of hippocampal D1R activation for spatial learning and memory. We trained DG restricted D1R KO (DG-D1R KO) mice on the water-maze task. DG-D1R KO mice did not present detectable spatial memory deficit, but did show subtle deficits during specific days of training. Our data provides evidence that forebrain D5R activation plays a unique role in spatial learning and memory in conjunction with D1R activation. Moreover, these data suggest that mPFC and striatal, but not DG D1R activation are essential for spatial learning and memory. PMID:26174222

Investigation of the effect of mutations of rat albumin on the binding affinity to the alpha(4)beta(1) integrin antagonist, 4-[1-[3-chloro-4-[N'-(2-methylphenyl)ureido]phenylacetyl]-(4S)-fluoro-(2S)-pyrrolidine-2-yl]methoxybenzoic acid (D01-4582), using recombinant rat albumins.

PubMed

Ito, Takashi; Takahashi, Masayuki; Okazaki, Osamu; Sugiyama, Yuichi

2010-08-02

The authors reported previously rat strain differences in plasma protein binding to alpha(4)beta(1) antagonist D01-4582, resulting in a great strain difference in its pharmacokinetics (19-fold differences in the AUC). The previous study suggested that amino acid changes of V238L and/or T293I in albumin reduced the binding affinity. In order to elucidate the relative significance of these mutations, an expression system was developed to obtain recombinant rat albumins (rRSA) using Pichia pastoris, followed by a binding analysis of four rRSAs by the ultracentrifugation method. The equilibrium dissociation constant (K(d)) of wild-type rRSA was 210 nM, while K(d) of rRSA that carried both V238L and T293I mutations was 974 nM. K(d) of artificial rRSA that carried only V238L was 426 nM, and K(d) of artificial rRSA that carried only T293I was 191 nM. These results suggested that V238L would be more important in the alteration of K(d). However, since none of the single mutations were sufficient to explain the reduction of affinity, the possibility was also suggested that T293I interacted cooperatively to reduce the binding affinity of rat albumin to D01-4582. Further investigation is required to elucidate the mechanism of the possible cooperative interaction.

Biotransformation of (-)-(1R,4S)-Menthone and (+)-(1S,4R)-Menthone by the Common Cutworm Spodoptera litura Larvae.

PubMed

Marumoto, Shinsuke; Okuno, Yoshiharu; Hagiwara, Yuki; Miyazawa, Mitsuo

2017-08-01

Using biotransformation as a biocatalytic process has the advantage of being able to proceed under mild conditions and with high regio- and enantioselectivity. This study investigated the biotransformation of (-)-(1R,4S)-menthone (1) and (+)-(1S,4R)-menthone (2) by Spodoptera litura larvae. Compound 1 was converted to (-)-(1R,4S)-7-hydroxymenthone (1-1), (+)-(1R,3S,4S)-7-hydroxyneomenthol (1-2) and (-)-(1R,4S,8R)-p-menth-3-one-9-oic acid (1-3). The metabolism of substrate 2 generated three enantiomers of the above metabolites, designated as 2-1 to 2-3, respectively. The C-9 position of (-)-menthone and (+)-menthone was oxidized to carboxylic acid by S. litura, which is a metabolic pathway not observed in any other example of biocatalysis.

High glucose concentration induces endothelial cell proliferation by regulating cyclin-D2-related miR-98.

PubMed

Li, Xin-Xin; Liu, Yue-Mei; Li, You-Jie; Xie, Ning; Yan, Yun-Fei; Chi, Yong-Liang; Zhou, Ling; Xie, Shu-Yang; Wang, Ping-Yu

2016-06-01

Cyclin D2 is involved in the pathology of vascular complications of type 2 diabetes mellitus (T2DM). This study investigated the role of cyclin-D2-regulated miRNAs in endothelial cell proliferation of T2DM. Results showed that higher glucose concentration (4.5 g/l) significantly promoted the proliferation of rat aortic endothelial cells (RAOECs), and significantly increased the expression of cyclin D2 and phosphorylation of retinoblastoma 1 (p-RB1) in RAOECs compared with those under low glucose concentration. The cyclin D2-3' untranslated region is targeted by miR-98, as demonstrated by miRNA analysis software. Western blot also confirmed that cyclin D2 and p-RB1 expression was regulated by miR-98. The results indicated that miR-98 treatment can induce RAOEC apoptosis. The suppression of RAOEC growth by miR-98 might be related to regulation of Bcl-2, Bax and Caspase 9 expression. Furthermore, the expression levels of miR-98 decreased in 4.5 g/l glucose-treated cells compared with those treated by low glucose concentration. Similarly, the expression of miR-98 significantly decreased in aortas of established streptozotocin (STZ)-induced diabetic rat model compared with that in control rats; but cyclin D2 and p-RB1 levels remarkably increased in aortas of STZ-induced diabetic rats compared with those in healthy control rats. In conclusion, this study demonstrated that high glucose concentration induces cyclin D2 up-regulation and miR-98 down-regulation in the RAOECs. By regulating cyclin D2, miR-98 can inhibit human endothelial cell growth, thereby providing novel therapeutic targets for vascular complication of T2DM. © 2016 The Authors. Journal of Cellular and Molecular Medicine published by John Wiley & Sons Ltd and Foundation for Cellular and Molecular Medicine.

NEFM (Neurofilament Medium) Polypeptide, a Marker for Zona Glomerulosa Cells in Human Adrenal, Inhibits D1R (Dopamine D1 Receptor)-Mediated Secretion of Aldosterone.

PubMed

Maniero, Carmela; Garg, Sumedha; Zhao, Wanfeng; Johnson, Timothy Isaac; Zhou, Junhua; Gurnell, Mark; Brown, Morris J

2017-08-01

Heterogeneity among aldosterone-producing adenomas (APAs) has been highlighted by the discovery of somatic mutations. KCNJ5 mutations predominate in large zona fasciculata (ZF)-like APAs; mutations in CACNA1D , ATP1A1, ATP2B3 , and CTNNB1 are more likely to be found in small zona glomerulosa (ZG)-like APAs. Microarray comparison of KCNJ5 mutant versus wild-type APAs revealed significant differences in transcriptomes. NEFM , encoding a neurofilament subunit which is a D1R (dopamine D1 receptor)-interacting protein, was 4-fold upregulated in ZG-like versus ZF-like APAs and 14-fold more highly expressed in normal ZG versus ZF. Immunohistochemistry confirmed selective expression of NEFM (neurofilament medium) polypeptide in ZG and in ZG-like APAs. Silencing NEFM in adrenocortical H295R cells increased basal aldosterone secretion and cell proliferation; silencing also amplified aldosterone stimulation by the D1R agonist, fenoldopam, and inhibition by the D1R antagonist, SCH23390. NEFM coimmunoprecipitated with D1R, and its expression was stimulated by fenoldopam. Immunohistochemistry for D1R was mainly intracellular in ZG-like APAs but membranous in ZF-like APAs. Aldosterone secretion in response to fenoldopam in primary cells from ZF-like APAs was higher than in cells from ZG-like APAs. Transfection of mutant KCNJ5 caused a large reduction in NEFM expression in H295R cells. We conclude that NEFM is a negative regulator of aldosterone production and cell proliferation, in part by facilitating D1R internalization from the plasma membrane. Downregulation of NEFM in ZF-like APAs may contribute to a D1R/D2R imbalance underlying variable pharmacological responses to dopaminergic drugs among patients with APAs. Finally, taken together, our data point to the possibility that ZF-like APAs are in fact ZG in origin. © 2017 American Heart Association, Inc.

Crowdsourced 'R&D' and medical research.

PubMed

Callaghan, Christian William

2015-09-01

Crowdsourced R&D, a research methodology increasingly applied to medical research, has properties well suited to large-scale medical data collection and analysis, as well as enabling rapid research responses to crises such as disease outbreaks. Multidisciplinary literature offers diverse perspectives of crowdsourced R&D as a useful large-scale medical data collection and research problem-solving methodology. Crowdsourced R&D has demonstrated 'proof of concept' in a host of different biomedical research applications. A wide range of quality and ethical issues relate to crowdsourced R&D. The rapid growth in applications of crowdsourced R&D in medical research is predicted by an increasing body of multidisciplinary theory. Further research in areas such as artificial intelligence may allow better coordination and management of the high volumes of medical data and problem-solving inputs generated by the crowdsourced R&D process. © The Author 2015. Published by Oxford University Press. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.

R&D Jobs for BS Engineers.

ERIC Educational Resources Information Center

Basta, Nicholas

1985-01-01

Outlines opportunities for beginning engineers seeking employment in research and development (R&D). R&D spending growth, underlying factors, job categories, and divisions within an industrial firm are discussed. Above average grades and additional mathematics courses are primary requirements for an R&D position, which may later lead to…

Wall-crossing in coupled 2d-4d systems

NASA Astrophysics Data System (ADS)

Gaiotto, Davide; Moore, Gregory W.; Neitzke, Andrew

2012-12-01

We introduce a new wall-crossing formula which combines and generalizes the Cecotti-Vafa and Kontsevich-Soibelman formulas for supersymmetric 2d and 4d systems respectively. This 2d-4d wall-crossing formula governs the wall-crossing of BPS states in an {N}=2 supersymmetric 4d gauge theory coupled to a supersymmetric surface defect. When the theory and defect are compactified on a circle, we get a 3d theory with a supersymmetric line operator, corresponding to a hyperholomorphic connection on a vector bundle over a hyperkähler space. The 2d-4d wall-crossing formula can be interpreted as a smoothness condition for this hyperholomorphic connection. We explain how the 2d-4d BPS spectrum can be determined for 4d theories of class {S} , that is, for those theories obtained by compactifying the six-dimensional (0, 2) theory with a partial topological twist on a punctured Riemann surface C. For such theories there are canonical surface defects. We illustrate with several examples in the case of A 1 theories of class {S} . Finally, we indicate how our results can be used to produce solutions to the A 1 Hitchin equations on the Riemann surface C.

Intrastriatal administration of botulinum neurotoxin A normalizes striatal D2 R binding and reduces striatal D1 R binding in male hemiparkinsonian rats.

PubMed

Wedekind, Franziska; Oskamp, Angela; Lang, Markus; Hawlitschka, Alexander; Zilles, Karl; Wree, Andreas; Bauer, Andreas

2018-01-01

Cerebral administration of botulinum neurotoxin A (BoNT-A) has been shown to improve disease-specific motor behavior in a rat model of Parkinson disease (PD). Since the dopaminergic system of the basal ganglia fundamentally contributes to motor function, we investigated the impact of BoNT-A on striatal dopamine receptor expression using in vitro and in vivo imaging techniques (positron emission tomography and quantitative autoradiography, respectively). Seventeen male Wistar rats were unilaterally lesioned with 6-hydroxydopamine (6-OHDA) and assigned to two treatment groups 7 weeks later: 10 rats were treated ipsilaterally with an intrastriatal injection of 1 ng BoNT-A, while the others received vehicle (n = 7). All animals were tested for asymmetric motor behavior (apomorphine-induced rotations and forelimb usage) and for striatal expression of dopamine receptors and transporters (D 1 R, D 2 R, and DAT). The striatal D 2 R availability was also quantified longitudinally (1.5, 3, and 5 months after intervention) in 5 animals per treatment group. The 6-OHDA lesion alone induced a unilateral PD-like phenotype and a 13% increase of striatal D 2 R. BoNT-A treatment reduced the asymmetry in both apomorphine-induced rotational behavior and D 2 R expression, with the latter returning to normal values 5 months after intervention. D 1 R expression was significantly reduced, while DAT concentrations showed no alteration. Independent of the treatment, higher interhemispheric symmetry in raclopride binding to D 2 R was generally associated with reduced forelimb akinesia. Our findings indicate that striatal BoNT-A treatment diminishes motor impairment and induces changes in D 1 and D 2 binding site density in the 6-OHDA rat model of PD. © 2017 Wiley Periodicals, Inc.

Investigation of cis-4-[18F]Fluoro-D-Proline Uptake in Human Brain Tumors After Multimodal Treatment.

PubMed

Verger, Antoine; Stoffels, Gabriele; Galldiks, Norbert; Lohmann, Philipp; Willuweit, Antje; Neumaier, Bernd; Geisler, Stefanie; Langen, Karl-Josef

2018-04-23

Cis-4-[ 18 F]fluoro-D-proline (D-cis-[ 18 F]FPro) has been shown to pass the intact blood-brain barrier and to accumulate in areas of secondary neurodegeneration and necrosis in the rat brain while uptake in experimental brain tumors is low. This pilot study explores the uptake behavior of D-cis-[ 18 F]FPro in human brain tumors after multimodal treatment. In a prospective study, 27 patients with suspected recurrent brain tumor after treatment with surgery, radiotherapy, and/or chemotherapy (SRC) were investigated by dynamic positron emission tomography (PET) using D-cis-[ 18 F]FPro (22 high-grade gliomas, one unspecified glioma, and 4 metastases). Furthermore, two patients with untreated lesions were included (one glioblastoma, one reactive astrogliosis). Data were compared with the results of PET using O-(2-[ 18 F]fluoroethyl)-L-tyrosine ([ 18 F]FET) which detects viable tumor tissue. Tracer distribution, mean and maximum lesion-to-brain ratios (LBR mean , LBR max ), and time-to-peak (TTP) of the time activity curve (TAC) of tracer uptake were evaluated. Final diagnosis was determined by histology (n = 9), clinical follow-up (n = 10), or by [ 18 F]FET PET (n = 10). D-cis-[ 18 F]FPro showed high uptake in both recurrent brain tumors (n = 11) and lesions classified as treatment-related changes (TRC) only (n = 16) (LBR mean 2.2 ± 0.7 and 2.1 ± 0.6, n.s.; LBR max 3.4 ± 1.2 and 3.2 ± 1.3, n.s.). The untreated glioblastoma and the lesion showing reactive astrogliosis exhibited low D-cis-[ 18 F]FPro uptake. Distribution of [ 18 F]FET and D-cis-[ 18 F]FPro uptake was discordant in 21/29 cases indicating that the uptake mechanisms are different. The high accumulation of D-cis-[ 18 F]FPro in pretreated brain tumors and TRC supports the hypothesis that tracer uptake is related to cell death. Further studies before and after therapy are needed to assess the potential of D-cis-[ 18 F]FPro for treatment monitoring.

77 FR 1656 - Proposed Establishment of Restricted Areas R-5402, R-5403A, R-5403B, R-5403C, R-5403D, R-5403E, R...

Federal Register 2010, 2011, 2012, 2013, 2014

2012-01-11

...-0117; Airspace Docket No. 09-AGL-31] RIN 2120-AI92 Proposed Establishment of Restricted Areas R-5402, R-5403A, R- 5403B, R-5403C, R-5403D, R-5403E, R-5403F; Devils Lake, ND AGENCY: Federal Aviation... Restricted Areas R-5402, R-5403A, R-5403B, R- 5403C, R-5403D, R-5403E, R-5403F; Devils Lake, ND (76 FR 72869...

Consequences of ChemR23 Heteromerization with the Chemokine Receptors CXCR4 and CCR7

PubMed Central

de Poorter, Cédric; Baertsoen, Kevin; Lannoy, Vincent; Parmentier, Marc; Springael, Jean-Yves

2013-01-01

Recent studies have shown that heteromerization of the chemokine receptors CCR2, CCR5 and CXCR4 is associated to negative binding cooperativity. In the present study, we build on these previous results, and investigate the consequences of chemokine receptor heteromerization with ChemR23, the receptor of chemerin, a leukocyte chemoattractant protein structurally unrelated to chemokines. We show, using BRET and HTRF assays, that ChemR23 forms homomers, and provide data suggesting that ChemR23 also forms heteromers with the chemokine receptors CCR7 and CXCR4. As previously described for other chemokine receptor heteromers, negative binding cooperativity was detected between ChemR23 and chemokine receptors, i.e. the ligands of one receptor competed for the binding of a specific tracer of the other. We also showed, using mouse bone marrow-derived dendritic cells prepared from wild-type and ChemR23 knockout mice, that ChemR23-specific ligands cross-inhibited CXCL12 binding on CXCR4 in a ChemR23-dependent manner, supporting the relevance of the ChemR23/CXCR4 interaction in native leukocytes. Finally, and in contrast to the situation encountered for other previously characterized CXCR4 heteromers, we showed that the CXCR4-specific antagonist AMD3100 did not cross-inhibit chemerin binding in cells co-expressing ChemR23 and CXCR4, demonstrating that cross-regulation by AMD3100 depends on the nature of receptor partners with which CXCR4 is co-expressed. PMID:23469143

Consequences of ChemR23 heteromerization with the chemokine receptors CXCR4 and CCR7.

PubMed

de Poorter, Cédric; Baertsoen, Kevin; Lannoy, Vincent; Parmentier, Marc; Springael, Jean-Yves

2013-01-01

Recent studies have shown that heteromerization of the chemokine receptors CCR2, CCR5 and CXCR4 is associated to negative binding cooperativity. In the present study, we build on these previous results, and investigate the consequences of chemokine receptor heteromerization with ChemR23, the receptor of chemerin, a leukocyte chemoattractant protein structurally unrelated to chemokines. We show, using BRET and HTRF assays, that ChemR23 forms homomers, and provide data suggesting that ChemR23 also forms heteromers with the chemokine receptors CCR7 and CXCR4. As previously described for other chemokine receptor heteromers, negative binding cooperativity was detected between ChemR23 and chemokine receptors, i.e. the ligands of one receptor competed for the binding of a specific tracer of the other. We also showed, using mouse bone marrow-derived dendritic cells prepared from wild-type and ChemR23 knockout mice, that ChemR23-specific ligands cross-inhibited CXCL12 binding on CXCR4 in a ChemR23-dependent manner, supporting the relevance of the ChemR23/CXCR4 interaction in native leukocytes. Finally, and in contrast to the situation encountered for other previously characterized CXCR4 heteromers, we showed that the CXCR4-specific antagonist AMD3100 did not cross-inhibit chemerin binding in cells co-expressing ChemR23 and CXCR4, demonstrating that cross-regulation by AMD3100 depends on the nature of receptor partners with which CXCR4 is co-expressed.

4. Photocopy of measured drawing (from Robert R. Harvey's 'Historic ...

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

4. Photocopy of measured drawing (from Robert R. Harvey's 'Historic Stone Architecture of Winterset, Iowa, Prior To and During the Civil War Period,' Unpublished Report, Iowa State University, (Ames, IA), 1960.) FLOOR PLAN, 1944 ('Fig. 4-D') - M. R. Tidrick House, 122 South Fourth Avenue, Winterset, Madison County, IA

Enterprise Systems Value-Based R&D Portfolio Analytics: Methods, Processes, and Tools

DTIC Science & Technology

2014-01-14

Enterprise Systems Value-Based R&D Portfolio Analytics: Methods, Processes, and Tools Final Technical Report SERC -2014-TR-041-1 January 14...by the U.S. Department of Defense through the Systems Engineering Research Center ( SERC ) under Contract H98230-08-D-0171 (Task Order 0026, RT 51... SERC is a federally funded University Affiliated Research Center managed by Stevens Institute of Technology Any opinions, findings and

Analysis of various types of single-polypeptide-chain (sc) heterodimeric A{sub 2A}R/D{sub 2}R complexes and their allosteric receptor–receptor interactions

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

Kamiya, Toshio, E-mail: kamiya@z2.keio.jp; Department of Neurology, Tokyo Metropolitan Institute for Neuroscience, 2-6 Musashidai, Fuchu, Tokyo 183-8526; Cell Biology Laboratory, School of Pharmaceutical Sciences, Kinki University, 3-4-1 Kowakae, Higashi-Osaka, Osaka 577-8502

Highlights: • Various scA{sub 2A}R/D{sub 2}R constructs, with spacers between the two receptors, were created. • Using whole cell binding assay, constructs were examined for their binding activity. • Although the apparent ratio of A{sub 2A}R to D{sub 2}R binding sites should be 1, neither was 1. • Counter agonist-independent binding cooperativity occurred in context of scA{sub 2A}R/D{sub 2}R. - Abstract: Adenosine A{sub 2A} receptor (A{sub 2A}R) heteromerizes with dopamine D{sub 2} receptor (D{sub 2}R). However, these class A G protein-coupled receptor (GPCR) dimers are not fully formed, but depend on the equilibrium between monomer and dimer. In order tomore » stimulate the heteromerization, we have previously shown a successful design for a fusion receptor, single-polypeptide-chain (sc) heterodimeric A{sub 2A}R/D{sub 2}R complex. Here, using whole cell binding assay, six more different scA{sub 2A}R/D{sub 2}R constructs were examined. Not only in scA{sub 2A}R/D{sub 2}R ‘liberated’ with longer spacers between the two receptors, which confer the same configuration as the prototype, the A{sub 2A}R-odr4TM-D{sub 2L}R, but differ in size (Forms 1–3), but also in scA{sub 2A}R/D{sub 2L}R (Form 6) fused with a transmembrane (TM) of another type II TM protein, instead of odr4TM, neither of their fixed stoichiometry (the apparent ratios of A{sub 2A}R to D{sub 2}R binding sites) was 1, suggesting their compact folding. This suggests that type II TM, either odr4 or another, facilitates the equilibrial process of the dimer formation between A{sub 2A}R and D{sub 2L}R, resulting in the higher-order oligomer formation from monomer of scA{sub 2A}R/D{sub 2L}R itself. Also, in the reverse type scA{sub 2A}R/D{sub 2L}R, i.e., the D{sub 2L}R-odr4TM-A{sub 2A}R, counter agonist-independent binding cooperativity (cooperative folding) was found to occur (Forms 4 and 5). In this way, the scA{sub 2A}R/D{sub 2L}R system has unveiled the cellular phenomenon as a snapshot of the

Assessing the Need for Curriculum or Delivery Revisions to the D.A.R.E.[R] K-4 Visitation Lessons: A Qualitative Inquiry

ERIC Educational Resources Information Center

Witte, Jeffrey H.

2011-01-01

Over the last several decades, research has questioned the effectiveness of the D.A.R.E.[c] (Drug Abuse Resistance Education) program. D.A.R.E.[c] has also experienced cuts based on budget restrictions and personnel reallocations within police agencies, as well as competing demands for classroom time. Although concerted efforts have been made to…

Search for D 0 decays to invisible final states at Belle

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

Lai, Y. -T.; Wang, M. -Z.; Adachi, I.

2017-01-01

We report the result from the first search for D 0 decays to invisible final states. The analysis is performed on a data sample of 924 fb -1 collected at and near the Y(4S) and Y(5S) resonances with the Belle detector at the KEKB asymmetric-energy e +e - collider. The absolute branching fraction is determined using an inclusive D 0 sample, obtained by fully reconstructing the rest of the particle system including the other charmed particle. No significant signal yield is observed and an upper limit of 9.4 × 10 -5 is set on the branching fraction of D 0more » to invisible final states at 90% confidence level.« less

How to obtain a cosmological constant from small exotic R4

NASA Astrophysics Data System (ADS)

Asselmeyer-Maluga, Torsten; Król, Jerzy

2018-03-01

In this paper we determine the cosmological constant as a topological invariant by applying certain techniques from low dimensional differential topology. We work with a small exotic R4 which is embedded into the standard R4. Any exotic R4 is a Riemannian smooth manifold with necessary non-vanishing curvature tensor. To determine the invariant part of such curvature we deal with a canonical construction of R4 where it appears as a part of the complex surface K 3 # CP(2) bar. Such R4's admit hyperbolic geometry. This fact simplifies significantly the calculations and enforces the rigidity of the expressions. In particular, we explain the smallness of the cosmological constant with a value consisting of a combination of (natural) topological invariant. Finally, the cosmological constant appears to be a topologically supported quantity.

ECG-based 4D-dose reconstruction of cardiac arrhythmia ablation with carbon ion beams: application in a porcine model

NASA Astrophysics Data System (ADS)

Richter, Daniel; Immo Lehmann, H.; Eichhorn, Anna; Constantinescu, Anna M.; Kaderka, Robert; Prall, Matthias; Lugenbiel, Patrick; Takami, Mitsuru; Thomas, Dierk; Bert, Christoph; Durante, Marco; Packer, Douglas L.; Graeff, Christian

2017-09-01

Noninvasive ablation of cardiac arrhythmia by scanned particle radiotherapy is highly promising, but especially challenging due to cardiac and respiratory motion. Irradiations for catheter-free ablation in intact pigs were carried out at the GSI Helmholtz Center in Darmstadt using scanned carbon ions. Here, we present real-time electrocardiogram (ECG) data to estimate time-resolved (4D) delivered dose. For 11 animals, surface ECGs and temporal structure of beam delivery were acquired during irradiation. R waves were automatically detected from surface ECGs. Pre-treatment ECG-triggered 4D-CT phases were synchronized to the R-R interval. 4D-dose calculation was performed using GSI’s in-house 4D treatment planning system. Resulting dose distributions were assessed with respect to coverage (D95 and V95), heterogeneity (HI  =  D5-D95) and normal tissue exposure. Final results shown here were performed offline, but first calculations were started shortly after irradiation The D95 for TV and PTV was above 95% for 10 and 8 out of 11 animals, respectively. HI was reduced for PTV versus TV volumes, especially for some of the animals targeted at the atrioventricular junction, indicating residual interplay effects due to cardiac motion. Risk structure exposure was comparable to static and 4D treatment planning simulations. ECG-based 4D-dose reconstruction is technically feasible in a patient treatment-like setting. Further development of the presented approach, such as real-time dose calculation, may contribute to safe, successful treatments using scanned ion beams for cardiac arrhythmia ablation.

A system dynamics model of a large R&D program

NASA Astrophysics Data System (ADS)

Ahn, Namsung

Organizations with large R&D activities must deal with a hierarchy of decision regarding resource allocation. At the highest level of allocation, the decision is related to the total allocation to R&D as some portion of revenue. The middle level of allocation deals with the allocation among phases of the R&D process. The lowest level of decisions relates to the resource allocation to specific projects within a specific phase. This study focuses on developing an R&D model to deal with the middle level of allocation, i.e., the allocation among phases of research such as basic research, development, and demonstration. The methodology used to develop the R&D model is System Dynamics. Our modeling concept is innovative in representing each phase of R&D as consisting of two parts: projects under way, and an inventory of successful but not-yet- exploited projects. In a simple world, this concept can yield an exact analytical solution for allocation of resources among phases. But in a real world, the concept should be improved by adding more complex structures with nonlinear behaviors. Two particular nonlinear feedbacks are incorporated into the R&D model. The probability of success for any specific project is assumed partly dependent upon resources allocated to the project. Further, the time required to reach a conclusion regarding the success or failure of a project is also assumed dependent upon the level of resources allocated. In addition, the number of successful projects partly depends on the inventory of potential ideas in the previous stage that can be exploited. This model can provide R&D management with insights into the effect of changing allocations to phases whether those changes are internally or externally driven. With this model, it is possible to study the effectiveness of management decisions in a continuous fashion. Managers can predict payoffs for a host of different policies. In addition, as new research results accumulate, a re- assessment of program

Evaluating firms' R&D performance using best worst method.

PubMed

Salimi, Negin; Rezaei, Jafar

2018-02-01

Since research and development (R&D) is the most critical determinant of the productivity, growth and competitive advantage of firms, measuring R&D performance has become the core of attention of R&D managers, and an extensive body of literature has examined and identified different R&D measurements and determinants of R&D performance. However, measuring R&D performance and assigning the same level of importance to different R&D measures, which is the common approach in existing studies, can oversimplify the R&D measuring process, which may result in misinterpretation of the performance and consequently fallacy R&D strategies. The aim of this study is to measure R&D performance taking into account the different levels of importance of R&D measures, using a multi-criteria decision-making method called Best Worst Method (BWM) to identify the weights (importance) of R&D measures and measure the R&D performance of 50 high-tech SMEs in the Netherlands using the data gathered in a survey among SMEs and from R&D experts. The results show how assigning different weights to different R&D measures (in contrast to simple mean) results in a different ranking of the firms and allow R&D managers to formulate more effective strategies to improve their firm's R&D performance by applying knowledge regarding the importance of different R&D measures. Copyright © 2017 The Authors. Published by Elsevier Ltd.. All rights reserved.

Supplement to CCM.D-K4 'Hydrometer' report: linkage of EURAMET.M.D-K4 comparison, SIM.M.D-K4 comparison and the supplementary SIM.M.D-S2 to CCM.D-K4 'Hydrometer'

NASA Astrophysics Data System (ADS)

Lorefice, S.; Becerra, L. O.

2017-01-01

Evaluation of different types of comparisons to a common set of reference values of a CIPM key comparison is essential to satisfy the concept of the CIPM Mutual Recognition Arrangement (CIPM MRA), where the DoEs of any participant who took part in comparisons should be within the Calibration and Measurement Capability (CMC) section of the CIPM MRA Key Comparison Data Base. The subject of this supplementary report is therefore to present the equivalence of each National Metrological Institute (NMI) participant in the CCM.D-K4 'Hydrometer' key comparison, which was performed in the density range 600 kg/m3 to 2000 kg/m3 at the temperature of 20 °C, and the linkage of the European and Inter-American NMI results performed in the RMO.M.D-K4 comparisons as well as those of the supplementary SIM.M.D-S2 to the common set of KCRVs of the CCM.D-K4 'Hydrometer'. The linking procedure has been obtained by numerical simulation, based on the Monte Carlo method, in which the differences in the results of the different comparison between the intended laboratory and one or more linking laboratory/ies, which took part in both comparisons, are correlated with a continuous function describing the DoEs of the linking laboratory/ies with respect to the common set of KCRVs of the CCM.D-K4. Main text To reach the main text of this paper, click on Final Report. Note that this text is that which appears in Appendix B of the BIPM key comparison database kcdb.bipm.org/. The final report has been peer-reviewed and approved for publication by the CCM, according to the provisions of the CIPM Mutual Recognition Arrangement (CIPM MRA).

Examining the link between price regulation and pharmaceutical R&D investment.

PubMed

Vernon, John A

2005-01-01

This paper examines the link between price regulation and pharmaceutical research and development (R&D) investment. I identify two mechanisms through which price regulation may exert an influence on R&D: an expected-profit effect and a cash-flow effect. Using established models of the determinants of pharmaceutical R&D, I exploit a unique fact to quantify firm exposure to pharmaceutical price regulation: relative to the rest of the world, the U.S. pharmaceutical market is largely unregulated with respect to price. Using this fact within the context of a system of quasi-structural equations, I simulate how a new policy regulating pharmaceutical prices in the U.S. will affect R&D investment. I find that such a policy will lead to a decline in industry R&D by between 23.4 and 32.7%. This prediction, however, is accompanied by several caveats. Moreover, it says nothing about the implications for social welfare; therefore, these issues are also discussed. Copyright 2004 John Wiley & Sons, Ltd.

Overview of superconductivity in Japan Strategy road map and R&D status

NASA Astrophysics Data System (ADS)

Tsukamoto, O.

2008-09-01

Superconducting technology benefits society in broad fields; environment/energy, life science, manufacturing industry and information and communication. Superconducting equipments and devices used in various fields are divided into two categories, electric and electronic applications. Technologies in those applications are progressing remarkably owing to firm and consistent supports by various national projects. The final target of the NEDO R&D project of fundamental technology for superconductivity applications to develop 500 m long coated conductors (CCs) of the critical current 300 A/cm (at 77 K, 0 T) will be fulfilled by the end of JFY 2007 and manufacturing process to produce extremely low-cost CCs is to be developed to make the applications realistic. Preliminary works to develop power apparatuses using CCs have started in the frame of the R&D project for the fundamental technology and have produced significant results. Performance of BSCCO/Ag-sheathed wires has been improved greatly and various applications using those wires are being developed. R&D projects for SMES, power cable, flywheel energy storage and rotating machines are going to introduce those equipments to the real world. Technologies of SQUID and SFQ, basic devices of the electronic applications, are progressing dramatically also owing to various national projects. In this back ground the technology strategy map in the field of superconducting technology was formulated to prioritize investments in R&D by clearly defining the objectives and inspire autonomous R&D actives in various fields of industries. R&D activities in the superconducting technologies are to be scheduled following this strategy map.

Retrospectively gated intracardiac 4D flow MRI using spiral trajectories.

PubMed

Petersson, Sven; Sigfridsson, Andreas; Dyverfeldt, Petter; Carlhäll, Carl-Johan; Ebbers, Tino

2016-01-01

To develop and evaluate retrospectively gated spiral readout four-dimensional (4D) flow MRI for intracardiac flow analysis. Retrospectively gated spiral 4D flow MRI was implemented on a 1.5-tesla scanner. The spiral sequence was compared against conventional Cartesian 4D flow (SENSE [sensitivity encoding] 2) in seven healthy volunteers and three patients (only spiral). In addition to comparing flow values, linear regression was used to assess internal consistency of aortic versus pulmonary net volume flows and left ventricular inflow versus outflow using quantitative pathlines analysis. Total scan time with spiral 4D flow was 44% ± 6% of the Cartesian counterpart (13 ± 3 vs. 31 ± 7 min). Aortic versus pulmonary flow correlated strongly for the spiral sequence (P < 0.05, slope = 1.03, R(2) = 0.88, N = 10), whereas the linear relationship for the Cartesian sequence was not significant (P = 0.06, N = 7). Pathlines analysis indicated good data quality for the spiral (P < 0.05, slope = 1.02, R(2) = 0.90, N = 10) and Cartesian sequence (P < 0.05, slope = 1.10, R(2) = 0.93, N = 7). Spiral and Cartesian peak flow rate (P < 0.05, slope = 0.96, R(2) = 0.72, N = 14), peak velocity (P < 0.05, slope = 1.00, R(2) = 0.81, N = 14), and pathlines flow components (P < 0.05, slope = 1.04, R(2) = 0.87, N = 28) correlated well. Retrospectively gated spiral 4D flow MRI permits more than two-fold reduction in scan time compared to conventional Cartesian 4D flow MRI, while maintaining similar data quality. © 2015 Wiley Periodicals, Inc.

miR-124 radiosensitizes human esophageal cancer cell TE-1 by targeting CDK4.

PubMed

Zhang, Y H; Wang, Q Q; Li, H; Ye, T; Gao, F; Liu, Y C

2016-06-03

Radiotherapy is one of the most important treatments for esophageal cancer, but radioresistance remains a major challenge. Previous studies have shown that microRNAs (miRNAs or miRs) are involved in human cancers. miR-124 has been widely reported in various cancers and it is intimately involved in proliferation, cell cycle regulation, apoptosis, migration, and invasion of cancer cells. The aim of this study was to explore the relationship between the miR-124/cyclin-dependent kinase 4 (CDK4) axis and the radiosensitivity of esophageal cancer cells. In this study, we identified the reduced expression of miR-124 in 18 paired esophageal cancer tissues compared to their matched normal tissues. In order to investigate the physiological role of miR-124 in esophageal cancer, the cell counting kit-8 (CCK-8) assay and wound healing assay were performed, and the results suggest that miR-124 overexpression decreases tumor growth and aggression. Next, we detected the effects of ectopic miR-124 expression on the apoptosis of an esophageal cancer cell line (TE-1) following radiotherapy. Using the CCK-8 assay and Hoechst 332528 stain, we found that ectopic expression of miR-124 led to a higher percentage of apoptotic cells. Finally, we identified that CDK4 is a direct target of miR-124 in TE-1 cells using target prediction algorithms and a luciferase reporter assay. Moreover, western blot assay confirmed that CDK4 was downregulated during miR-124 transfection. Taken together, we illustrate that the miR-124/CDK4 axis plays an important role in radiation sensitivity of human esophageal cancer cells by targeting CDK4.

Agricultural R&D, technology and productivity.

PubMed

Piesse, J; Thirtle, C

2010-09-27

The relationships between basic and applied agricultural R&D, developed and developing country R&D and between R&D, extension, technology and productivity growth are outlined. The declining growth rates of public R&D expenditures are related to output growth and crop yields, where growth rates have also fallen, especially in the developed countries. However, growth in output value per hectare has not declined in the developing countries and labour productivity growth has increased except in the EU. Total factor productivity has generally increased, however it is measured. The public sector share of R&D expenditures has fallen and there has been rapid concentration in the private sector, where six multinationals now dominate. These companies are accumulating intellectual property to an extent that the public and international institutions are disadvantaged. This represents a threat to the global commons in agricultural technology on which the green revolution has depended. Estimates of the increased R&D expenditures needed to feed 9 billion people by 2050 and how these should be targeted, especially by the Consultative Group on International Agricultural Research (CGIAR), show that the amounts are feasible and that targeting sub-Saharan Africa (SSA) and South Asia can best increase output growth and reduce poverty. Lack of income growth in SSA is seen as the most insoluble problem.

Agricultural R&D, technology and productivity

PubMed Central

Piesse, J.; Thirtle, C.

2010-01-01

The relationships between basic and applied agricultural R&D, developed and developing country R&D and between R&D, extension, technology and productivity growth are outlined. The declining growth rates of public R&D expenditures are related to output growth and crop yields, where growth rates have also fallen, especially in the developed countries. However, growth in output value per hectare has not declined in the developing countries and labour productivity growth has increased except in the EU. Total factor productivity has generally increased, however it is measured. The public sector share of R&D expenditures has fallen and there has been rapid concentration in the private sector, where six multinationals now dominate. These companies are accumulating intellectual property to an extent that the public and international institutions are disadvantaged. This represents a threat to the global commons in agricultural technology on which the green revolution has depended. Estimates of the increased R&D expenditures needed to feed 9 billion people by 2050 and how these should be targeted, especially by the Consultative Group on International Agricultural Research (CGIAR), show that the amounts are feasible and that targeting sub-Saharan Africa (SSA) and South Asia can best increase output growth and reduce poverty. Lack of income growth in SSA is seen as the most insoluble problem. PMID:20713401

KEY COMPARISON: Final report of comparison of the calibrations of hydrometers for liquid density determination between SIM laboratories: SIM.M.D-K4

NASA Astrophysics Data System (ADS)

Becerra, Luis Omar

2009-01-01

This SIM comparison on the calibration of high accuracy hydrometers was carried out within fourteen laboratories in the density range from 600 kg/m3 to 1300 kg/m3 in order to evaluate the degree of equivalence among participant laboratories. This key comparison anticipates the planned key comparison CCM.D-K4, and is intended to be linked with CCM.D-K4 when results are available. Main text. To reach the main text of this paper, click on Final Report. Note that this text is that which appears in Appendix B of the BIPM key comparison database kcdb.bipm.org/. The final report has been peer-reviewed and approved for publication by the CCM, according to the provisions of the CIPM Mutual Recognition Arrangement (MRA).

Defense Conversion - Redirecting R and D. Summary

DTIC Science & Technology

1993-05-01

include cleaner can, simple or painless. The first report of this powered by electric batteries or a combination of asessment, After the Cold War: Living...govemment-owned, -operated, or -funded labs. DoD’s total 1992 budget authority for R&D, excludi expenditres for R&D plant and equipment, was about $38.8...SOURCE: Lawrence ,Jvermore National Laboratory. 14 1 Defens Conversionm: Redirectng R&D Figure 10-- Nucler Weapons and DoD Funding for Las Alamos

FY 1992 Budget committed to R&D

NASA Astrophysics Data System (ADS)

Bush, Susan

President's Bush's Fiscal Year 1992 budget for research and development is clear proof of his commitment to R&D as a long-term investment for the next American century, according to D. Allan Bromley, Assistant to the President for Science and Technology and Director, Office of Science and Technology Policy. The FY 92 budget proposes to allocate $75.6 billion for research and development, an increase of $8.4billion, or 13% over the amount appropriated for FY 91. Calling it a “good budget,” Bromley revealed the specifics of research and development in the President's budget on February 4.Bromley believes that as a nation we are underinvesting in research and development,but sees the 1992 budget increases as concrete steps to address this problem. The newly organized and revitalized Federal Coordinating Council for Science, Engineering, and Technology (FCCSET)—an interagency forum of Cabinet secretaries, deputy secretaries, and the heads of independent agencies that reviews, coordinates, and helps implement federal science and technology policy-named three high-priority cross—cutting areas of R&D and organized special interagency programs in these areas. The areas are high-performance computing and communications, global change, and mathematics and science education.

Removal of 2,4-Dichlorophenolyxacetic acid (2,4-D) herbicide in the aqueous phase using modified granular activated carbon.

PubMed

Dehghani, Mansooreh; Nasseri, Simin; Karamimanesh, Mojtaba

2014-01-10

Low cost 2,4-Dichlorophenolyxacetic acid (2,4-D) widely used in controlling broad-leafed weeds is frequently detected in water resources. The main objectives of this research were focused on evaluating the feasibility of using granular activated carbon modified with acid to remove 2,4-D from aqueous phase, determining its removal efficiency and assessing the adsorption kinetics. The present study was conducted at bench-scale method. The influence of different pH (3-9), the effect of contact time (3-90 min), the amount of adsorbent (0.1-0.4 g), and herbicide initial concentration (0.5-3 ppm) on 2,4-D removal efficiency by the granular activated carbon were investigated. Based on the data obtained in the present study, pH of 3 and contact time of 60 min is optimal for 2,4-D removal. 2,4-D reduction rate increased rapidly by the addition of the adsorbent and decreased by herbicide initial concentration (63%). The percent of 2,4-D reduction were significantly enhanced by decreasing pH and increasing the contact time. The adsorption of 2,4-D onto the granular activated carbon conformed to Langmuir and Freundlich models, but was best fitted to type II Langmuir model (R2 = 0.999). The second order kinetics was the best for the adsorption of 2,4-D by modified granular activated carbon with R2 > 0.99. Regression analysis showed that all of the variables in the process have been statistically significant effect (p < 0.001). In conclusion, granular activated carbon modified with acid is an appropriate method for reducing the herbicide in the polluted water resources.

Removal of 2,4-Dichlorophenolyxacetic acid (2,4-D) herbicide in the aqueous phase using modified granular activated carbon

PubMed Central

2014-01-01

Background Low cost 2,4-Dichlorophenolyxacetic acid (2,4-D) widely used in controlling broad-leafed weeds is frequently detected in water resources. The main objectives of this research were focused on evaluating the feasibility of using granular activated carbon modified with acid to remove 2,4-D from aqueous phase, determining its removal efficiency and assessing the adsorption kinetics. Results The present study was conducted at bench-scale method. The influence of different pH (3–9), the effect of contact time (3–90 min), the amount of adsorbent (0.1-0.4 g), and herbicide initial concentration (0.5-3 ppm) on 2,4-D removal efficiency by the granular activated carbon were investigated. Based on the data obtained in the present study, pH of 3 and contact time of 60 min is optimal for 2,4-D removal. 2,4-D reduction rate increased rapidly by the addition of the adsorbent and decreased by herbicide initial concentration (63%). The percent of 2,4-D reduction were significantly enhanced by decreasing pH and increasing the contact time. The adsorption of 2,4-D onto the granular activated carbon conformed to Langmuir and Freundlich models, but was best fitted to type II Langmuir model (R2 = 0.999). The second order kinetics was the best for the adsorption of 2,4-D by modified granular activated carbon with R2 > 0.99. Regression analysis showed that all of the variables in the process have been statistically significant effect (p < 0.001). Conclusions In conclusion, granular activated carbon modified with acid is an appropriate method for reducing the herbicide in the polluted water resources. PMID:24410737

N-Doped Dual Carbon-Confined 3D Architecture rGO/Fe3O4/AC Nanocomposite for High-Performance Lithium-Ion Batteries.

PubMed

Ding, Ranran; Zhang, Jie; Qi, Jie; Li, Zhenhua; Wang, Chengyang; Chen, Mingming

2018-04-25

To address the issues of low electrical conductivity, sluggish lithiation kinetics and dramatic volume variation in Fe 3 O 4 anodes of lithium ion battery, herein, a double carbon-confined three-dimensional (3D) nanocomposite architecture was synthesized by an electrostatically assisted self-assembly strategy. In the constructed architecture, the ultrafine Fe 3 O 4 subunits (∼10 nm) self-organize to form nanospheres (NSs) that are fully coated by amorphous carbon (AC), formatting core-shell structural Fe 3 O 4 /AC NSs. By further encapsulation by reduced graphene oxide (rGO) layers, a constructed 3D architecture was built as dual carbon-confined rGO/Fe 3 O 4 /AC. Such structure restrains the adverse reaction of the electrolyte, improves the electronic conductivity and buffers the mechanical stress of the entire electrode, thus performing excellent long-term cycling stability (99.4% capacity retention after 465 cycles relevant to the second cycle at 5 A g -1 ). Kinetic analysis reveals that a dual lithium storage mechanism including a diffusion reaction mechanism and a surface capacitive behavior mechanism coexists in the composites. Consequently, the resulting rGO/Fe 3 O 4 /AC nanocomposite delivers a high reversible capacity (835.8 mA h g -1 for 300 cycles at 1 A g -1 ), as well as remarkable rate capability (436.7 mA h g -1 at 10 A g -1 ).

Federal Life Sciences Funding and University R&D. NBER Working Paper No. 15146

ERIC Educational Resources Information Center

Blume-Kohout, Margaret E.; Kumar, Krishna B.; Sood, Neeraj

2009-01-01

This paper investigates the impact of federal extramural research funding on total expenditures for life sciences research and development (R&D) at U.S. universities, to determine whether federal R&D funding spurs funding from non-federal (private and state/local government) sources. We use a fixed effects instrumental variable approach…

4D Bioprinting for Biomedical Applications.

PubMed

Gao, Bin; Yang, Qingzhen; Zhao, Xin; Jin, Guorui; Ma, Yufei; Xu, Feng

2016-09-01

3D bioprinting has been developed to effectively and rapidly pattern living cells and biomaterials, aiming to create complex bioconstructs. However, placing biocompatible materials or cells into direct contact via bioprinting is necessary but insufficient for creating these constructs. Therefore, '4D bioprinting' has emerged recently, where 'time' is integrated with 3D bioprinting as the fourth dimension, and the printed objects can change their shapes or functionalities when an external stimulus is imposed or when cell fusion or postprinting self-assembly occurs. In this review, we highlight recent developments in 4D bioprinting technology. Additionally, we review the uses of 4D bioprinting in tissue engineering and drug delivery. Finally, we discuss the major roadblocks to this approach, together with possible solutions, to provide future perspectives on this technology. Copyright © 2016 Elsevier Ltd. All rights reserved.

R-spondin3-LGR4 signaling protects hepatocytes against DMOG-induced hypoxia/reoxygenation injury through activating β-catenin.

PubMed

Liu, Shiying; Yin, Yue; Yu, Ruili; Li, Yin; Zhang, Weizhen

2018-04-30

Leucine-rich repeat G-protein-coupled receptor 4 (LGR4) and its ligands R-spondin1-4 (Rspos) have been vastly investigated in embryonic development. The biological functions of Rspos-LGR4 system in liver remains largely unknown. Here, we explored whether it protects hepatocytes against hypoxia/reoxygenation (H/R) induced damage. H/R injury was induced by dimethyloxalylglycine (DMOG) in AML12 cells and the effects of Rspo3 on cell proliferation and apoptosis were assessed. Specific shRNAs were used to interfere LGR4 or β-catenin. DMOG caused hepatocytes damage evidenced by increase in HIF-1α, cell death and apoptosis genes p27 and Bax, with concurrent decrease of cell proliferation genes PCNA and CyclinD1. Of all the Rspos, Rspo3 is predominantly expressed in AML12 hepatocytes. Importantly, Rspo3 demonstrated an alteration in a manner similar to proliferation-related genes during H/R injury. Rspo3 pretreatment rendered hepatocytes less vulnerable to DMOG induced H/R injury. Ablation of LGR4 using shRNA attenuated the protective effects of Rspo3. Wnt3a also protected AML12 cells from damages caused by H/R, showing enhanced proliferation activity. Notably, knockdown of β-catenin in hepatocytes completely abolished the effect of Rspo3 pretreatment on the expression levels of PCNA and CyclinD1. Rspo3-LGR4 axis protects hepatocytes from H/R injury via activating β-catenin. Copyright © 2018. Published by Elsevier Inc.

Money for nothing: How firms have financed R&D-projects since the Industrial Revolution

PubMed Central

Bakker, Gerben

2013-01-01

We investigate the long-run historical pattern of R&D-outlays by reviewing aggregate growth rates and historical cases of particular R&D projects, following the historical-institutional approach of Chandler (1962), North (1981) and Williamson (1985). We find that even the earliest R&D-projects used non-insignificant cash outlays and that until the 1970s aggregate R&D outlays grew far faster than GDP, despite five well-known challenges that implied that R&D could only be financed with cash, for which no perfect market existed: the presence of sunk costs, real uncertainty, long time lags, adverse selection, and moral hazard. We then review a wide variety of organisational forms and institutional instruments that firms historically have used to overcome these financing obstacles, and without which the enormous growth of R&D outlays since the nineteenth century would not have been possible. PMID:24910477

Money for nothing: How firms have financed R&D-projects since the Industrial Revolution.

PubMed

Bakker, Gerben

2013-12-01

We investigate the long-run historical pattern of R&D-outlays by reviewing aggregate growth rates and historical cases of particular R&D projects, following the historical-institutional approach of Chandler (1962), North (1981) and Williamson (1985). We find that even the earliest R&D-projects used non-insignificant cash outlays and that until the 1970s aggregate R&D outlays grew far faster than GDP, despite five well-known challenges that implied that R&D could only be financed with cash, for which no perfect market existed: the presence of sunk costs, real uncertainty, long time lags, adverse selection, and moral hazard. We then review a wide variety of organisational forms and institutional instruments that firms historically have used to overcome these financing obstacles, and without which the enormous growth of R&D outlays since the nineteenth century would not have been possible.

Does R&D pay?

PubMed

Cavalla, David; Minhas, Raman

2010-03-01

Pharmaceutical R&D is notoriously risky, lengthy and costly; moreover, it does not always produce products of blockbuster status. The conventional route of fully discovering, developing and marketing a new chemical entity is followed by the large pharmaceutical companies, whereas other organizations in the pharmaceutical sector--such as generic or specialty companies and biotechnology companies--only operate over portions of the full R&D process. Here, we compare the ten-year financial performance of these three subsectors through their price/earnings ratios and their return on capital metrics to understand which of these strategic alternatives offered the best return to investors. 2009 Elsevier Ltd. All rights reserved.

Analyses of direct and indirect impacts of a positive list system on pharmaceutical R&D investments.

PubMed

Han, Euna; Kim, Tae Hyun; Jeung, Myung Jin; Lee, Eui-Kyung

2013-07-01

The South Korean government recently enacted a Positive List System (PLS) as a major change of the national formulary listing system and reimbursed prices for pharmaceutical products. Regardless of the primary goal of the PLS, its implementation might have spillover effects by influencing the pharmaceutical industry's research and development (R&D), potentially leading to a variety of responses by firms in relation to their R&D activities. We investigated the spillover effect of the PLS on R&D investments of the pharmaceutical industry in Korea through both direct and indirect channels, examining the influence of the PLS on sales profit and cash flow. Data from 9 years (5 before and 4 after PLS implementation) were drawn from the financial statements of firms whose stocks were exchanged in 2 official stock markets in Korea (526 firms) and additional pharmaceutical firms whose financial performance was officially audited by external reviewers (263 firms). Longitudinal analyses were conducted, using the panel nature of the data to control for permanent unobserved firm heterogeneity. Our results showed that the PLS was directly associated with R&D investments. In contrast, its indirect impacts stemming from the influence on sales profit and cash flow were minimal and statistically nonsignificant. The gross impact of the PLS on R&D investments increased moving further from the enactment year; R&D investments were reduced by 18.3% to 25.8% in 2009-2010 (compared with before PLS implementation) in the firm fixed-effects model. We also found that such negative direct and gross impacts of the PLS on R&D investments were significant only in firms without newly developed chemical entities. Considering the gross negative impact of the PLS on R&D investments of pharmaceutical firms and the heterogeneous response of these firms by the R&D activities, governmental efforts of cost-containment may need to consider the spillover impact of the PLS on pharmaceutical innovation

Oscillator strengths and branching fractions of 4d75p-4d75s Rh II transitions

NASA Astrophysics Data System (ADS)

Bouazza, Safa

2017-01-01

This work reports semi-empirical determination of oscillator strengths, transition probabilities and branching fractions for Rh II 4d75p-4d75s transitions in a wide wavelength range. The angular coefficients of the transition matrix, beforehand obtained in pure SL coupling with help of Racah algebra are transformed into intermediate coupling using eigenvector amplitudes of these two configuration levels determined for this purpose; The transition integral was treated as free parameter in the least squares fit to experimental oscillator strength (gf) values found in literature. The extracted value: <4d75s|r1|4d75p> =2.7426 ± 0.0007 is slightly smaller than that computed by means of ab-initio method. Subsequently to oscillator strength evaluations, transition probabilities and branching fractions were deduced and compared to those obtained experimentally or through another approach like pseudo-relativistic Hartree-Fock model including core-polarization effects.

Strategic Sourcing of R&D: The Determinants of Success

NASA Astrophysics Data System (ADS)

Brook, Jacques W.; Plugge, Albert

The outsourcing of the R&D function is an emerging practice of corporate firms. In their attempt to reduce the increasing cost of research and technology development, firms are strategically outsourcing the R&D function or repositioning their internal R&D organisation. By doing so, they are able to benefit from other technology sources around the world. So far, there is only limited research on how firms develop their R&D sourcing strategies and how these strategies are implemented. This study aims to identify which determinants contribute to the success of R&D sourcing strategies. The results of our empirical research indicate that a clear vision of how to manage innovation strategically on a corporate level is a determinant of an effective R&D strategy. Moreover, our findings revealed that the R&D sourcing strategy influences a firm's sourcing capabilities. These sourcing capabilities need to be developed to manage the demand as well as the supply of R&D services. The alignment between the demand capabilities and the supply capabilities contributes to the success of R&D sourcing.

Synthesis, characterization and crystal structure of (2RS,4R)-2-(2-hydroxy-3-methoxyphenyl)thiazolidine-4-carboxylic acid

NASA Astrophysics Data System (ADS)

Muche, Simon; Müller, Matthias; Hołyńska, Małgorzata

2018-03-01

The condensation reaction of ortho-vanillin and L-cysteine leads to formation of a racemic mixture of (2RS,4R)-2-(2-hydroxy-3-methoxyphenyl)thiazolidine-4-carboxylic acid and not, as reported in the available literature, to a Schiff base. The racemic mixture was fully characterized by 1D and 2D NMR techniques, ESI-MS and X-ray diffraction. Addition of ZnCl2 led to formation of crystals in form of colorless needles, suitable for X-ray diffraction studies. The measured crystals were identified as the diastereomer (2R,4R)-2-(2-hydroxy-3-methoxyphenyl)thiazolidine-4-carboxylic acid 1. The bulk material is racemic. Thiazolidine exists as zwitterion in solid state, as indicated by the crystal structure.

VS{sub 2}/rGO hybrid nanosheets prepared by annealing of VS{sub 4}/rGO

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

Mohan, Pandurangan; Yang, Jieun; Jena, Anirudha

Layered transition metal dichalcogenides and their hybrids with reduced grpahene oxide (rGO) have attracted much interest due to many potential applications for electrode materials in Li ion batteries and supercapacitors and electro-catalysts for hydrogen evolution reaction. Among them, synthesis of VS{sub 2} sheets and VS{sub 4}/rGO hybrid via a hydrothermal reaction was recently reported, whereas VS{sub 2}/rGO hybrid sheets have not been reported. In this study, we report VS{sub 2}/rGO hybrid sheets after annealing VS{sub 4}/rGO hybrid materials at 350 °C. The conversion of VS{sub 4} to VS{sub 2} on rGO sheets after annealing is attributed to a thermal cleavagemore » of VS{sub 4}. - Highlights: • VS2/rGO hybrid sheets were obtained by annealing of VS4/rGO at 350 °C. • The phase transition from monoclinic to hexagonal is occurred. • The HER performance of VS2/rGO is investigated.« less

NREL Honored with Three Top R&D Awards

Science.gov Websites

Honored with Three Top R&D Awards For more information contact: Sarah Holmes Barba, 303-275 Renewable Energy Laboratory will receive three R&D 100 awards this week for technologies judged by R& fuels. This is Ginley's second R&D 100 award. Real-time biomass analysis can help analyze wood chips

Federal R&D funding: 10-year trends

NASA Astrophysics Data System (ADS)

Bell, Peter M.

Research and development (R&D) funded by the federal government has grown steadily since 1971, according to the National Science Foundation (NSF). The total federal R&D funding gained at an annual rate of 8.6% in actual dollars. Substantial gains, on the order of 15% over 1981, had originally been planned but later revised downward, close to 0%, for the fiscal year 1982. The essential features of the 10-year trend are that federal R&D funding has been mostly directed toward the military—over twice the amount of all other types of R&D funding—and while military research funding is accelerating sharply, other research funding is on the decline. In simple terms, the 10-year increases are only for national defense.

Interaction between GPR120 p.R270H loss-of-function variant and dietary fat intake on incident type 2 diabetes risk in the D.E.S.I.R. study.

PubMed

Lamri, A; Bonnefond, A; Meyre, D; Balkau, B; Roussel, R; Marre, M; Froguel, P; Fumeron, F

2016-10-01

GPR120 (encoded by FFAR4) is a lipid sensor that plays an important role in the control of energy balance. GPR120 is activated by long chain fatty acids (FAs) including omega-3 FAs. In humans, the loss of function p.R270H variant of the gene FFAR4 has been associated with a lower protein activity, an increased risk of obesity and higher fasting plasma glucose levels. The aim of this study was to investigate whether p.R270H interacts with dietary fat intake to modulate the risk of type 2 diabetes (T2D, 198 incident; 368 prevalent cases) and overweight (787 incident and 2891 prevalent cases) in the prospective D.E.S.I.R. study (n = 5,212, 9 years follow-up). The association of p.R270H with dietary fat and total calories was assessed by linear mixed models. The interaction between p.R270H and dietary fat on T2D and overweight was assessed by logistic regression analysis. The p.R270H variant had a minor allele frequency of 1.45% and was not significantly associated with total calories intake, fat intake or the total calories derived from fat (%). However, there was a significant interaction between p.R270H and dietary fat modulating the incidence of T2D (Pinteraction = 0.02) where the H-carriers had a higher risk of T2D than RR homozygotes in the low fat intake category only. The interaction between p.R270H and fat intake modulating the incidence and prevalence of overweight was not significant. The p.R270H variant of GPR120 modulates the risk of T2D in interaction with dietary fat intake in the D.E.S.I.R. Copyright © 2016 The Italian Society of Diabetology, the Italian Society for the Study of Atherosclerosis, the Italian Society of Human Nutrition, and the Department of Clinical Medicine and Surgery, Federico II University. Published by Elsevier B.V. All rights reserved.

2D:4D, Lateralization and Strength in Handball Players

ERIC Educational Resources Information Center

Eler, Nebahat; Eler, Serdar

2018-01-01

Lateralization, which is also known as hand preference, and 2D:4D finger ratio is a sign of prenatal testosterone and known to be associated with strength. The aim of this study is to investigate the relationship between 2D:4D, lateralization and hand grip strength in relation to hand and forearm that are thought to be effective in handball in…

Industry R&D to rise in 1984

NASA Astrophysics Data System (ADS)

Research and development spending from private industry funds is expected to grow approximately 11% during 1984 to $48 billion, according to a new report by the National Science Foundation (NSF). Spurring this growth, say industry officials, are industry's need to keep abreast of rapidly advancing technology, the impact of foreign competition, and the expectation that more funds will be available as the economic recovery continues.The NSF report is based on mail response to an inquiry to the foundation's Industrial Panel on Science and Technology and on interviews with officials in several R&D-intensive industries. The panel is composed of about 90 officials, primarily corporate directors of research and development, who are responsible for R&D in their companies. The report, “Companies Plan Increases in R&D Spending Through 1984,” contains projections of R&D expenditures for 1983 and 1984 for the six largest R&D-performing industries: machinery (including computers); electrical equipment and communications; chemicals (including drugs and medicine); motor vehicles; aircraft; and professional and scientific instruments.

D4 receptor deficiency in mice has limited effects on impulsivity and novelty seeking.

PubMed

Helms, C M; Gubner, N R; Wilhelm, C J; Mitchell, S H; Grandy, D K

2008-09-01

Alleles of the human dopamine D(4) receptor (D(4)R) gene (DRD4.7) have repeatedly been found to correlate with novelty seeking, substance abuse, pathological gambling, and attention-deficit hyperactivity disorder (ADHD). If these various psychopathologies are a result of attenuated D(4)R-mediated signaling, mice lacking D(4)Rs (D(4)KO) should be more impulsive than wild-type (WT) mice and exhibit more novelty seeking. However, in our study, D(4)KO and WT mice showed similar levels of impulsivity as measured by delay discounting performance and response inhibition on a Go/No-go test, suggesting that D(4)R-mediated signaling may not affect impulsivity. D(4)KO mice were more active than WT mice in the first 5 min of a novel open field test, suggesting greater novelty seeking. For both genotypes, more impulsive mice habituated less in the novel open field. These data suggest that the absence of D(4)Rs is not sufficient to cause psychopathologies associated with heightened impulsivity and novelty seeking.

Analysis of the effectiveness of industrial R and D. [costs and impact on economic growth

NASA Technical Reports Server (NTRS)

Fisher, W. H.; Kleiman, H. S.; Moore, J. L.; Triplett, M. B.

1976-01-01

The criteria used by private industry in evaluating and selecting proposed research and development projects for implementation, and also in determining which R and D facilities are to be acquired were investigated. Conceptual and practical issues inherent in any quantitative analysis of the contribution of R and D to economic growth were identified in order to assist NASA in developing approaches for analzying the economic implication of its own R and D efforts.

Native presynaptic metabotropic glutamate receptor 4 (mGluR4) interacts with exocytosis proteins in rat cerebellum.

PubMed

Ramos, Cathy; Chardonnet, Solenne; Marchand, Christophe H; Decottignies, Paulette; Ango, Fabrice; Daniel, Hervé; Le Maréchal, Pierre

2012-06-08

The eight pre- or/and post-synaptic metabotropic glutamatergic receptors (mGluRs) modulate rapid excitatory transmission sustained by ionotropic receptors. They are classified in three families according to their percentage of sequence identity and their pharmacological properties. mGluR4 belongs to group III and is mainly localized presynaptically. Activation of group III mGluRs leads to depression of excitatory transmission, a process that is exclusively provided by mGluR4 at parallel fiber-Purkinje cell synapse in rodent cerebellum. This function relies at least partly on an inhibition of presynaptic calcium influx, which controls glutamate release. To improve the understanding of molecular mechanisms of the mGluR4 depressant effect, we decided to identify the proteins interacting with this receptor. Immunoprecipitations using anti-mGluR4 antibodies were performed with cerebellar extracts. 183 putative partners that co-immunoprecipitated with anti-mGluR4 antibodies were identified and classified according to their cellular functions. It appears that native mGluR4 interacts with several exocytosis proteins such as Munc18-1, synapsins, and syntaxin. In addition, native mGluR4 was retained on a Sepharose column covalently grafted with recombinant Munc18-1, and immunohistochemistry experiments showed that Munc18-1 and mGluR4 colocalized at plasma membrane in HEK293 cells, observations in favor of an interaction between the two proteins. Finally, affinity chromatography experiments using peptides corresponding to the cytoplasmic domains of mGluR4 confirmed the interaction observed between mGluR4 and a selection of exocytosis proteins, including Munc18-1. These results could give indications to explain how mGluR4 can modulate glutamate release at parallel fiber-Purkinje cell synapses in the cerebellum in addition to the inhibition of presynaptic calcium influx.

R D ( * ) anomaly: A possible hint for natural supersymmetry with R -parity violation

DOE PAGES

Altmannshofer, Wolfgang; Bhupal Dev, P. S.; Soni, Amarjit

2017-11-15

Recently, several B-physics experiments have reported an appreciable deviation from the standard model (SM) in the tree-level observables R D(*); the combined weighted average now stands at ≈4σ. We first show the anomaly necessarily implies model-independent collider signals of the form pp → bτν that should be expeditiously searched for at ATLAS/CMS as a complementary test of the anomaly. Next we suggest a possible interconnection of the anomaly with the radiative stability of the standard model Higgs boson and point to a minimal effective supersymmetric scenario with R-parity violation as the underlying cause. In conclusion, we also comment on themore » possibility of simultaneously explaining the recently reported R K(*) anomaly in this setup.« less

R D ( * ) anomaly: A possible hint for natural supersymmetry with R -parity violation

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

Altmannshofer, Wolfgang; Bhupal Dev, P. S.; Soni, Amarjit

Recently, several B-physics experiments have reported an appreciable deviation from the standard model (SM) in the tree-level observables R D(*); the combined weighted average now stands at ≈4σ. We first show the anomaly necessarily implies model-independent collider signals of the form pp → bτν that should be expeditiously searched for at ATLAS/CMS as a complementary test of the anomaly. Next we suggest a possible interconnection of the anomaly with the radiative stability of the standard model Higgs boson and point to a minimal effective supersymmetric scenario with R-parity violation as the underlying cause. In conclusion, we also comment on themore » possibility of simultaneously explaining the recently reported R K(*) anomaly in this setup.« less

76 FR 27281 - Airworthiness Directives; Dowty Propellers Type R212/4-30-4/22 and R251/4-30-4/49 Propeller...

Federal Register 2010, 2011, 2012, 2013, 2014

2011-05-11

... Airworthiness Directives; Dowty Propellers Type R212/4-30-4/22 and R251/4-30-4/49 Propeller Assemblies AGENCY.../22 propeller assemblies with hub and driving center assembly part number (P/N) 601022105, 601022211, 601022294, 601021426, 601021858, or 601021859 installed, and type R251/4-30-4/49 propeller assemblies with...

Awards for Photovoltaic Manufacturing R&D | Photovoltaic Research | NREL

Science.gov Websites

Awards for Photovoltaic Manufacturing R&D Awards for Photovoltaic Manufacturing R&D The following research efforts within the PV Manufacturing R&D Project were honored with prestigious industry awards. 1995-AstroPower (now GE Energy): Received an R&D 100 Award for its Silicon-Film

Building bridges from process R&D: from a customer-supplier relationship to full partnership.

PubMed

Federsel

2000-08-01

A new and forward-looking way of running process R&D is introduced that integrates this core business in an efficient manner into the network of activities in different disciplines, which constitute the arena for the development of pharmaceutical products. The interfaces with surrounding areas are discussed in addition to the novel organizational principles implemented in process R&D and the workflow emanating from this. Furthermore, the Tollgate model used to keep track of the progress in a project and the pre-study concept are presented in detail. Finally, the main differences between operating modes in the past and in the future are highlighted.

Gravitational wave memory in dS4+2n and 4D cosmology

NASA Astrophysics Data System (ADS)

Chu, Y.-Z.

2017-02-01

We argue that massless gravitons in all even dimensional de Sitter (dS) spacetimes higher than two admit a linear memory effect arising from their propagation inside the null cone. Assume that gravitational waves (GWs) are being generated by an isolated source, and over only a finite period of time {η\\text{i}}≤slant η ≤slant {η\\text{f}} . Outside of this time interval, suppose the shear-stress of the GW source becomes negligible relative to its energy-momentum and its mass quadrupole moments settle to static values. We then demonstrate, the transverse-traceless (TT) GW contribution to the perturbation of any dS4+2n written in a conformally flat form ({{a}2}{ημ ν}\\text{d}{{x}μ}\\text{d}{{x}ν} )—after the source has ceased and the primary GW train has passed—amounts to a spacetime constant shift in the flat metric proportional to the difference between the TT parts of the source’s final and initial mass quadrupole moments. As a byproduct, we present solutions to Einstein’s equations linearized about de Sitter backgrounds of all dimensions greater than three. We then point out there is a similar but approximate tail induced linear GW memory effect in 4D matter dominated universes. Our work here serves to improve upon and extend the 4D cosmological results of Chu (2015 Phys. Rev. D 92 124038), which in turn preceded complementary work by Bieri et al (2015 arXiv:1509.01296) and by Kehagias and Riotto (2016 arXiv:1602.02653).

Prescription Drug Abuse Information in D.A.R.E.

ERIC Educational Resources Information Center

Morris, Melissa C.; Cline, Rebecca J. Welch; Weiler, Robert M.; Broadway, S. Camille

2006-01-01

This investigation was designed to examine prescription drug-related content and learning objectives in Drug Abuse Resistance Education (D.A.R.E.) for upper elementary and middle schools. Specific prescription-drug topics and context associated with content and objectives were coded. The coding system for topics included 126 topics organized…

Assimilation of DMSP/SSUSI UV data into IDA4D

NASA Astrophysics Data System (ADS)

Gelinas, L. J.; Bust, G. S.; Brinkman, D. G.; Straus, P. R.; Swartz, R. L.

2014-12-01

Ionospheric Data Assimilation Four-Dimensional (IDA4D) is a continuous-time, three-dimensional imaging algorithm that can produce 4D electron density specifications for various science investigations [e.g., Bust et al., 2007]. IDA4D is based on three-dimensional variational (3DVAR) data assimilation [Daley and Barker, 2001]. The algorithm combines various data sources and their associated error covariances with a background model (in this case the IRI) and its covariances to produce an ionospheric specification with formal uncertainties. IDA4D employs a Gauss- Markov Kalman filter technique similar to that used by operational assimilation models. The model can ingest a broad spectrum of data types that are either linearly or non-linearly related to electron density, including ground-based TEC, space-based TEC as measured by GPS occultation sensors and UV emissions associated with nightside recombination of O+. IDA4D has been undergoing testing at The Aerospace Corporation to determine its performance with respect to combinations of input data sets under different conditions (solar minimum, solar maximum, geomagnetic activity). The results presented here summarize the performance of IDA4D when UV data is ingested, both with and without additional TEC measurements. The UV data used in the study summarized here are 135.6 nm emissions measured the SSUSI instruments on F16 and F18 DMSP. We discuss the process by which UV data is ingested into IDA4D, including data binning, error estimation and correction of 135.6 nm contamination from mutual neutralization of O+ and O-. Model performance is then assessed using comparisons to various ground truth data, including ISR data, Jason VTEC, CNOF/S in-situ plasma density and ionosonde-derived NmF2 values. The results of this study show that UV data improves model performance, particularly when TEC data coverage is sparse. Bust, G. S., G. Crowley, T. W. Garner, T. L. Gaussiran II, R. W. Meggs, C. N. Mitchell, P. S. J. Spencer, P

4D scattering amplitudes and asymptotic symmetries from 2D CFT

NASA Astrophysics Data System (ADS)

Cheung, Clifford; de la Fuente, Anton; Sundrum, Raman

2017-01-01

We reformulate the scattering amplitudes of 4D flat space gauge theory and gravity in the language of a 2D CFT on the celestial sphere. The resulting CFT structure exhibits an OPE constructed from 4D collinear singularities, as well as infinite-dimensional Kac-Moody and Virasoro algebras encoding the asymptotic symmetries of 4D flat space. We derive these results by recasting 4D dynamics in terms of a convenient foliation of flat space into 3D Euclidean AdS and Lorentzian dS geometries. Tree-level scattering amplitudes take the form of Witten diagrams for a continuum of (A)dS modes, which are in turn equivalent to CFT correlators via the (A)dS/CFT dictionary. The Ward identities for the 2D conserved currents are dual to 4D soft theorems, while the bulk-boundary propagators of massless (A)dS modes are superpositions of the leading and subleading Weinberg soft factors of gauge theory and gravity. In general, the massless (A)dS modes are 3D Chern-Simons gauge fields describing the soft, single helicity sectors of 4D gauge theory and gravity. Consistent with the topological nature of Chern-Simons theory, Aharonov-Bohm effects record the "tracks" of hard particles in the soft radiation, leading to a simple characterization of gauge and gravitational memories. Soft particle exchanges between hard processes define the Kac-Moody level and Virasoro central charge, which are thereby related to the 4D gauge coupling and gravitational strength in units of an infrared cutoff. Finally, we discuss a toy model for black hole horizons via a restriction to the Rindler region.

Distinct Physiological Effects of Dopamine D4 Receptors on Prefrontal Cortical Pyramidal Neurons and Fast-Spiking Interneurons

PubMed Central

Zhong, Ping; Yan, Zhen

2016-01-01

Dopamine D4 receptor (D4R), which is strongly linked to neuropsychiatric disorders, such as attention-deficit hyperactivity disorder and schizophrenia, is highly expressed in pyramidal neurons and GABAergic interneurons in prefrontal cortex (PFC). In this study, we examined the impact of D4R on the excitability of these 2 neuronal populations. We found that D4R activation decreased the frequency of spontaneous action potentials (sAPs) in PFC pyramidal neurons, whereas it induced a transient increase followed by a decrease of sAP frequency in PFC parvalbumin-positive (PV+) interneurons. D4R activation also induced distinct effects in both types of PFC neurons on spontaneous excitatory and inhibitory postsynaptic currents, which drive the generation of sAP. Moreover, dopamine substantially decreased sAP frequency in PFC pyramidal neurons, but markedly increased sAP frequency in PV+ interneurons, and both effects were partially mediated by D4R activation. In the phencyclidine model of schizophrenia, the decreasing effect of D4R on sAP frequency in both types of PFC neurons was attenuated, whereas the increasing effect of D4R on sAP in PV+ interneurons was intact. These results suggest that D4R activation elicits distinct effects on synaptically driven excitability in PFC projection neurons versus fast-spiking interneurons, which are differentially altered in neuropsychiatric disorder-related conditions. PMID:25146372

R&D on Composition and Processing of Titanium Aluminide Alloys for Turbine Engines

DTIC Science & Technology

1982-07-01

45433. AUTHORITY AFWAL ltr, 6 Feb 1987 THIS PAGE IS UNCLASSIFIED AFWAL-TR-82-4086 R&D ON COMPOSITION AND PROCESSING4 OF TITANIUM ALUMINIDE ALLOYS FOR...TR-82-4086- 4. TITLE (and Subitfle) S TYPE OF REPORT I PERIOO COVEREO R&D ON COMPOSITION AND PROCESSING OF Interim Technical Report TITANIUM ALUMINIDE ...ILLUSTRATIONS FICURE PACE 1 As-received titanium aluminide ingots supplied 9 by RMI. (a) S/N 20007; (b) left to right, S/N 20008, S/N 20009, S/N 20010

Deoxyfluoroketohexoses: 4-deoxy-4-fluoro-D-sorbose and -tagatose and 5-deoxy-5-fluoro-L-sorbose.

PubMed

Rao, G V; Que, L; Hall, L D; Fondy, T P

1975-04-01

4-Deoxy-4-fluoro-alpha-D-sorbose (6) was prepared in crystalline form by the action of potassium hydrogen fluoride on 3,4-anhydro-1,2-O-isopropylidene-beta-D-psicopyranose (3) followed by deacetonation. Under identical conditions, 3,4-anhydro-1,2-O-isopropylidene-beta-D-tagatopyranose (7) underwent epoxide migration to give 4,5-anhydro-1,2-O-isopropylidene-beta-D-fructopyranose (12), which after deacetonation yielded 4-deoxy-4-fluoro-D-tagatose (15) and 5-deoxy-5-fluoro-alpha-L-sorbopyranose (16), the latter as the crystalline, free sugar. The action of glycol-cleavage reagents on the isopropylidene acetals of the deoxyfluoro sugars was consistent with the assigned structures. The structures were established by 13-C n.m.r. studies of the free deoxyfluoro sugars 6 and 16 and of the isopropylidene acetal 13, and by 1-H n.m.r. studies on the acetylated isopropylidene acetals 5 diacetate, 13 diacetate, and 14 diacetate. 5-Deoxy-5-fluoro-L-sorbose (16) was biologically active, producing in mice effects characteristic of deoxyfluorotrioses and of fluoroacetate. 4-Deoxy-4-fluoro-D-tagatose (15) and 4-deoxy-4-fluoro-D-sorbose (6) produced no apparent effects in mice up to a dose of 500mg/kg. The implications of these findings with respect to transport, phosphorylation, and the action of aldolase on ketohexoses are discussed.

The economic impact of NASA R and D spending Appendices

NASA Technical Reports Server (NTRS)

Evans, M. K.

1976-01-01

Seven appendices related to a previous report on the economic impact of NASA R and D spending were presented. They dealt with: (1) theoretical and empirical development of aggregate production functions, (2) the calculation of the time series for the rate of technological progress, (3) the calculation of the industry mix variable, (4) the estimation of distributed lags, (5) the estimation of the equations for gamma, (6) a ten-year forecast of the U.S. economy, (7) simulations of the macroeconomic model for increases in NASA R and D spending of $1.0, $.0.5, and 0.1 billions.

Study of D J meson decays to D +π-, D 0π+ and D ∗+π- final states in pp collisions

NASA Astrophysics Data System (ADS)

Aaij, R.; Adeva, B.; Adinolfi, M.; Adrover, C.; Affolder, A.; Ajaltouni, Z.; Albrecht, J.; Alessio, F.; Alexander, M.; Ali, S.; Alkhazov, G.; Cartelle, P. Alvarez; Alves, A. A.; Amato, S.; Amerio, S.; Amhis, Y.; Anderlini, L.; Anderson, J.; Andreassen, R.; Andrews, J. E.; Appleby, R. B.; Gutierrez, O. Aquines; Archilli, F.; Artamonov, A.; Artuso, M.; Aslanides, E.; Auriemma, G.; Baalouch, M.; Bachmann, S.; Back, J. J.; Baesso, C.; Balagura, V.; Baldini, W.; Barlow, R. J.; Barschel, C.; Barsuk, S.; Barter, W.; Bauer, Th.; Bay, A.; Beddow, J.; Bedeschi, F.; Bediaga, I.; Belogurov, S.; Belous, K.; Belyaev, I.; Ben-Haim, E.; Bencivenni, G.; Benson, S.; Benton, J.; Berezhnoy, A.; Bernet, R.; Bettler, M.-O.; van Beuzekom, M.; Bien, A.; Bifani, S.; Bird, T.; Bizzeti, A.; Bjørnstad, P. M.; Blake, T.; Blanc, F.; Blouw, J.; Blusk, S.; Bocci, V.; Bondar, A.; Bondar, N.; Bonivento, W.; Borghi, S.; Borgia, A.; Bowcock, T. J. V.; Bowen, E.; Bozzi, C.; Brambach, T.; van den Brand, J.; Bressieux, J.; Brett, D.; Britsch, M.; Britton, T.; Brook, N. H.; Brown, H.; Burducea, I.; Bursche, A.; Busetto, G.; Buytaert, J.; Cadeddu, S.; Callot, O.; Calvi, M.; Gomez, M. Calvo; Camboni, A.; Campana, P.; Perez, D. Campora; Carbone, A.; Carboni, G.; Cardinale, R.; Cardini, A.; Carranza-Mejia, H.; Carson, L.; Akiba, K. Carvalho; Casse, G.; Garcia, L. Castillo; Cattaneo, M.; Cauet, Ch.; Cenci, R.; Charles, M.; Charpentier, Ph.; Chen, P.; Chiapolini, N.; Chrzaszcz, M.; Ciba, K.; Vidal, X. Cid; Ciezarek, G.; Clarke, P. E. L.; Clemencic, M.; Cliff, H. V.; Closier, J.; Coca, C.; Coco, V.; Cogan, J.; Cogneras, E.; Collins, P.; Comerma-Montells, A.; Contu, A.; Cook, A.; Coombes, M.; Coquereau, S.; Corti, G.; Couturier, B.; Cowan, G. A.; Craik, D. C.; Cunliffe, S.; Currie, R.; D'Ambrosio, C.; David, P.; David, P. N. Y.; Davis, A.; De Bonis, I.; De Bruyn, K.; De Capua, S.; De Cian, M.; De Miranda, J. M.; De Paula, L.; De Silva, W.; De Simone, P.; Decamp, D.; Deckenhoff, M.; Del Buono, L.; Déléage, N.; Derkach, D.; Deschamps, O.; Dettori, F.; Di Canto, A.; Dijkstra, H.; Dogaru, M.; Donleavy, S.; Dordei, F.; Suárez, A. Dosil; Dossett, D.; Dovbnya, A.; Dupertuis, F.; Durante, P.; Dzhelyadin, R.; Dziurda, A.; Dzyuba, A.; Easo, S.; Egede, U.; Egorychev, V.; Eidelman, S.; van Eijk, D.; Eisenhardt, S.; Eitschberger, U.; Ekelhof, R.; Eklund, L.; El Rifai, I.; Elsasser, Ch.; Falabella, A.; Färber, C.; Fardell, G.; Farinelli, C.; Farry, S.; Fave, V.; Ferguson, D.; Albor, V. Fernandez; Rodrigues, F. Ferreira; Ferro-Luzzi, M.; Filippov, S.; Fiore, M.; Fitzpatrick, C.; Fontana, M.; Fontanelli, F.; Forty, R.; Francisco, O.; Frank, M.; Frei, C.; Frosini, M.; Furcas, S.; Furfaro, E.; Torreira, A. Gallas; Galli, D.; Gandelman, M.; Gandini, P.; Gao, Y.; Garofoli, J.; Garosi, P.; Tico, J. Garra; Garrido, L.; Gaspar, C.; Gauld, R.; Gersabeck, E.; Gersabeck, M.; Gershon, T.; Ghez, Ph.; Gibson, V.; Giubega, L.; Gligorov, V. V.; Göbel, C.; Golubkov, D.; Golutvin, A.; Gomes, A.; Gordon, H.; Gándara, M. Grabalosa; Diaz, R. Graciani; Cardoso, L. A. Granado; Graugés, E.; Graziani, G.; Grecu, A.; Greening, E.; Gregson, S.; Griffith, P.; Grünberg, O.; Gui, B.; Gushchin, E.; Guz, Yu.; Gys, T.; Hadjivasiliou, C.; Haefeli, G.; Haen, C.; Haines, S. C.; Hall, S.; Hamilton, B.; Hampson, T.; Hansmann-Menzemer, S.; Harnew, N.; Harnew, S. T.; Harrison, J.; Hartmann, T.; He, J.; Head, T.; Heijne, V.; Hennessy, K.; Henrard, P.; Morata, J. A. Hernando; van Herwijnen, E.; Hicheur, A.; Hicks, E.; Hill, D.; Hoballah, M.; Hombach, C.; Hopchev, P.; Hulsbergen, W.; Hunt, P.; Huse, T.; Hussain, N.; Hutchcroft, D.; Hynds, D.; Iakovenko, V.; Idzik, M.; Ilten, P.; Jacobsson, R.; Jaeger, A.; Jans, E.; Jaton, P.; Jawahery, A.; Jing, F.; John, M.; Johnson, D.; Jones, C. R.; Joram, C.; Jost, B.; Kaballo, M.; Kandybei, S.; Kanso, W.; Karacson, M.; Karbach, T. M.; Kenyon, I. R.; Ketel, T.; Keune, A.; Khanji, B.; Kochebina, O.; Komarov, I.; Koopman, R. F.; Koppenburg, P.; Korolev, M.; Kozlinskiy, A.; Kravchuk, L.; Kreplin, K.; Kreps, M.; Krocker, G.; Krokovny, P.; Kruse, F.; Kucharczyk, M.; Kudryavtsev, V.; Kvaratskheliya, T.; La Thi, V. N.; Lacarrere, D.; Lafferty, G.; Lai, A.; Lambert, D.; Lambert, R. W.; Lanciotti, E.; Lanfranchi, G.; Langenbruch, C.; Latham, T.; Lazzeroni, C.; Le Gac, R.; van Leerdam, J.; Lees, J.-P.; Lefèvre, R.; Leflat, A.; Lefrançois, J.; Leo, S.; Leroy, O.; Lesiak, T.; Leverington, B.; Li, Y.; Gioi, L. Li; Liles, M.; Lindner, R.; Linn, C.; Liu, B.; Liu, G.; Lohn, S.; Longstaff, I.; Lopes, J. H.; Lopez-March, N.; Lu, H.; Lucchesi, D.; Luisier, J.; Luo, H.; Machefert, F.; Machikhiliyan, I. V.; Maciuc, F.; Maev, O.; Malde, S.; Manca, G.; Mancinelli, G.; Maratas, J.; Marconi, U.; Märki, R.; Marks, J.; Martellotti, G.; Martens, A.; Sánchez, A. M´ın; Martinelli, M.; Santos, D. Martinez; Tostes, D. Martins; Massafferri, A.; Matev, R.; Mathe, Z.; Matteuzzi, C.; Maurice, E.; Mazurov, A.; Skelly, B. Mc; McCarthy, J.; McNab, A.; McNulty, R.; Meadows, B.; Meier, F.; Meissner, M.; Merk, M.; Milanes, D. A.; Minard, M.-N.; Rodriguez, J. Molina; Monteil, S.; Moran, D.; Morawski, P.; Mordà, A.; Morello, M. J.; Mountain, R.; Mous, I.; Muheim, F.; Müller, K.; Muresan, R.; Muryn, B.; Muster, B.; Naik, P.; Nakada, T.; Nandakumar, R.; Nasteva, I.; Needham, M.; Neubert, S.; Neufeld, N.; Nguyen, A. D.; Nguyen, T. D.; Nguyen-Mau, C.; Nicol, M.; Niess, V.; Niet, R.; Nikitin, N.; Nikodem, T.; Nomerotski, A.; Novoselov, A.; Oblakowska-Mucha, A.; Obraztsov, V.; Oggero, S.; Ogilvy, S.; Okhrimenko, O.; Oldeman, R.; Orlandea, M.; Goicochea, J. M. Otalora; Owen, P.; Oyanguren, A.; Pal, B. K.; Palano, A.; Palutan, M.; Panman, J.; Papanestis, A.; Pappagallo, M.; Parkes, C.; Parkinson, C. J.; Passaleva, G.; Patel, G. D.; Patel, M.; Patrick, G. N.; Patrignani, C.; Pavel-Nicorescu, C.; Alvarez, A. Pazos; Pellegrino, A.; Penso, G.; Altarelli, M. Pepe; Perazzini, S.; Trigo, E. Perez; Yzquierdo, A. Pérez-Calero; Perret, P.; Perrin-Terrin, M.; Pessina, G.; Petridis, K.; Petrolini, A.; Phan, A.; Olloqui, E. Picatoste; Pietrzyk, B.; Pilař, T.; Pinci, D.; Playfer, S.; Casasus, M. Plo; Polci, F.; Polok, G.; Poluektov, A.; Polycarpo, E.; Popov, A.; Popov, D.; Popovici, B.; Potterat, C.; Powell, A.; Prisciandaro, J.; Pritchard, A.; Prouve, C.; Pugatch, V.; Navarro, A. Puig; Punzi, G.; Qian, W.; Rademacker, J. H.; Rakotomiaramanana, B.; Rangel, M. S.; Raniuk, I.; Rauschmayr, N.; Raven, G.; Redford, S.; Reid, M. M.; dos Reis, A. C.; Ricciardi, S.; Richards, A.; Rinnert, K.; Molina, V. Rives; Romero, D. A. Roa; Robbe, P.; Roberts, D. A.; Rodrigues, E.; Perez, P. Rodriguez; Roiser, S.; Romanovsky, V.; Vidal, A. Romero; Rouvinet, J.; Ruf, T.; Ruffini, F.; Ruiz, H.; Valls, P. Ruiz; Sabatino, G.; Silva, J. J. Saborido; Sagidova, N.; Sail, P.; Saitta, B.; Guimaraes, V. Salustino; Salzmann, C.; Sedes, B. Sanmartin; Sannino, M.; Santacesaria, R.; Rios, C. Santamarina; Santovetti, E.; Sapunov, M.; Sarti, A.; Satriano, C.; Satta, A.; Savrie, M.; Savrina, D.; Schaack, P.; Schiller, M.; Schindler, H.; Schlupp, M.; Schmelling, M.; Schmidt, B.; Schneider, O.; Schopper, A.; Schune, M.-H.; Schwemmer, R.; Sciascia, B.; Sciubba, A.; Seco, M.; Semennikov, A.; Senderowska, K.; Sepp, I.; Serra, N.; Serrano, J.; Seyfert, P.; Shapkin, M.; Shapoval, I.; Shatalov, P.; Shcheglov, Y.; Shears, T.; Shekhtman, L.; Shevchenko, O.; Shevchenko, V.; Shires, A.; Coutinho, R. Silva; Sirendi, M.; Skwarnicki, T.; Smith, N. A.; Smith, E.; Smith, J.; Smith, M.; Sokoloff, M. D.; Soler, F. J. P.; Soomro, F.; Souza, D.; De Paula, B. Souza; Spaan, B.; Sparkes, A.; Spradlin, P.; Stagni, F.; Stahl, S.; Steinkamp, O.; Stevenson, S.; Stoica, S.; Stone, S.; Storaci, B.; Straticiuc, M.; Straumann, U.; Subbiah, V. K.; Sun, L.; Swientek, S.; Syropoulos, V.; Szczekowski, M.; Szczypka, P.; Szumlak, T.; T'Jampens, S.; Teklishyn, M.; Teodorescu, E.; Teubert, F.; Thomas, C.; Thomas, E.; van Tilburg, J.; Tisserand, V.; Tobin, M.; Tolk, S.; Tonelli, D.; Topp-Joergensen, S.; Torr, N.; Tournefier, E.; Tourneur, S.; Tran, M. T.; Tresch, M.; Tsaregorodtsev, A.; Tsopelas, P.; Tuning, N.; Garcia, M. Ubeda; Ukleja, A.; Urner, D.; Ustyuzhanin, A.; Uwer, U.; Vagnoni, V.; Valenti, G.; Vallier, A.; Van Dijk, M.; Gomez, R. Vazquez; Regueiro, P. Vazquez; Sierra, C. Vázquez; Vecchi, S.; Velthuis, J. J.; Veltri, M.; Veneziano, G.; Vesterinen, M.; Viaud, B.; Vieira, D.; Vilasis-Cardona, X.; Vollhardt, A.; Volyanskyy, D.; Voong, D.; Vorobyev, A.; Vorobyev, V.; Voß, C.; Voss, H.; Waldi, R.; Wallace, C.; Wallace, R.; Wandernoth, S.; Wang, J.; Ward, D. R.; Watson, N. K.; Webber, A. D.; Websdale, D.; Whitehead, M.; Wicht, J.; Wiechczynski, J.; Wiedner, D.; Wiggers, L.; Wilkinson, G.; Williams, M. P.; Williams, M.; Wilson, F. F.; Wimberley, J.; Wishahi, J.; Witek, M.; Wotton, S. A.; Wright, S.; Wu, S.; Wyllie, K.; Xie, Y.; Xing, Z.; Yang, Z.; Young, R.; Yuan, X.; Yushchenko, O.; Zangoli, M.; Zavertyaev, M.; Zhang, F.; Zhang, L.; Zhang, W. C.; Zhang, Y.; Zhelezov, A.; Zhokhov, A.; Zhong, L.; Zvyagin, A.

2013-09-01

A study of D +π-, D 0π+ and D ∗+π- final states is performed using pp collision data, corresponding to an integrated luminosity of 1.0 fb-1, collected at a centre-of-mass energy of 7 TeV with the LHCb detector. The D 1(2420)0 resonance is observed in the D ∗+π- final state and the resonance is observed in the D +π-, D 0π+ and D ∗+π- final states. For both resonances, their properties and spin-parity assignments are obtained. In addition, two natural parity and two unnatural parity resonances are observed in the mass region between 2500 and 2800 MeV. Further structures in the region around 3000 MeV are observed in all the D ∗+π-, D +π- and D 0π+ final states. [Figure not available: see fulltext.

77 FR 47110 - Manufacturer of Controlled Substances; Notice of Application; R & D Systems, Inc.

Federal Register 2010, 2011, 2012, 2013, 2014

2012-08-07

... DEPARTMENT OF JUSTICE Drug Enforcement Administration Manufacturer of Controlled Substances; Notice of Application; R & D Systems, Inc. Pursuant to Title 21 Code of Federal Regulations 1301.34(a), this is notice that on May 4, 2012, R & D Systems, Inc., 614 McKinley Place NE., Minneapolis, Minnesota...

Mir-338-3p Mediates Tnf-A-Induced Hepatic Insulin Resistance by Targeting PP4r1 to Regulate PP4 Expression.

PubMed

Dou, Lin; Wang, Shuyue; Sun, Libo; Huang, Xiuqing; Zhang, Yang; Shen, Tao; Guo, Jun; Man, Yong; Tang, Weiqing; Li, Jian

2017-01-01

Insulin resistance is a critical factor contributing to the pathogenesis of type 2 diabetes and other metabolic diseases. Recent studies have indicated that miR-338-3p plays an important role in cancer. Here, we investigated whether miR-338-3p mediates tumour necrosis factor-α (TNF-α)-induced hepatic insulin resistance. The activation of the insulin signalling pathway and the level of glycogenesis were examined in the livers of the db/db and high fat diet (HFD)-fed mice and in HEP1-6 cells transfected with miR-338-3p mimic or inhibitor. Computational prediction of microRNA target, luciferase assay and Western blot were used to assess the miR-338-3p target. Chromatin immunoprecipitation (ChIP) assay was used to determine the transcriptional regulator of miR-338-3p. miR-338-3p was down-regulated in the livers of the db/db, HFD-fed and TNF-α-treated C57BL/6J mice, as well as in mouse HEP1-6 hepatocytes treated with TNF-α. Importantly the down-regulation of miR-338-3p induced insulin resistance, as indicated by impaired glucose tolerance and insulin tolerance. Further research showed that the down-regulated miR-338-3p resulted in the impaired AKT/ glycogen synthase kinase 3 beta (GSl·Gβ) signalling pathway and glycogen synthesis. In contrast, hepatic over-expression of miR-338-3p rescued the TNF-α-induced insulin resistance. Moreover, protein phosphatase 4 regulator subunit 1 (PP4R1) was identified as a direct target of miR-338-3p that mediated hepatic insulin signalling by regulating protein phosphatase 4 (PP4). Finally we identified hepatic nuclear factor 4 alpha (HNF-4α) as the transcriptional regulator of miRNA-338-3p. Our studies provide novel insight into the critical role and molecular mechanism by which miR-338-3p is involved in TNF-α-induced hepatic insulin resistance. miR-338-3p might mediate TNF-α-induced hepatic insulin resistance by targeting PP4R1 to regulate PP4 expression. © 2017 The Author(s). Published by S. Karger AG, Basel.

Motion4D-library extended

NASA Astrophysics Data System (ADS)

Müller, Thomas

2011-06-01

Chandrasekhar [6].HalilsoyWave: see Ref. [7].JaNeWi: Janis-Newman-Winicour metric, see Ref. [8].MinkowskiConformal: Minkowski metric in conformally rescaled coordinates.PTD_AI, PTD_AII, PTD_AIII, PTD_BI, PTD_BII, PTD_BIII, PTD_C Petrov-Type D - Levi-Civita spacetimes, see Ref. [7].PainleveGullstrand: Schwarzschild metric in Painlevé-Gullstrand coordinates, see Ref. [9].PlaneGravWave: Plane gravitational wave, see Ref. [10].SchwarzschildIsotropic: Schwarzschild metric in isotropic coordinates, see Ref. [11].SchwarzschildTortoise: Schwarzschild metric in tortoise coordinates, see Ref. [11].Sultana-Dyer: A black hole in the Einstein-de Sitter universe by Sultana and Dyer [12].TaubNUT: see Ref. [13]. The Christoffel symbols and the natural local tetrads of these new metrics are given in the Catalogue of Spacetimes, Ref. [14].To study the behavior of geodesics, it is often useful to determine an effective potential like in classical mechanics. For several metrics, we followed the Euler-Lagrangian approach as described by Rindler [10] and implemented an effective potential for a specific situation. As an example, consider the Lagrangian L=-αt˙+α-1r˙+r2φ˙ for timelike geodesics in the ϑ=π/2 hypersurface in the Schwarzschild spacetime with α=1-2m/r. The Euler-Lagrangian equations lead to the energy balance equation r˙+V(r)=k2 with the effective potential V(r)=(r-2m)(r2+h2)/r3 and the constants of motion k=αt˙ and h=r2φ˙. The constants of motion for a timelike geodesic that starts at (r=10m,φ=0) with initial direction ξ=π/4 with respect to the black hole direction and with initial velocity β=0.7 read k≈1.252 and h≈6.931. Then, from the energy balance equation we immediately obtain the radius of closest approach r≈5.927.Beside a standard Runge-Kutta fourth-order integrator and the integrators of the Gnu Scientific Library (GSL), we also implemented a standard Bulirsch-Stoer integrator.Running time: The test runs provided with the distribution require only a few

Leveraging R&D Resources via the Joint LLC Model

NASA Astrophysics Data System (ADS)

Ganz, Matthew W.

2008-03-01

government and commercial entities. The central themes to HRL’s business model are innovation, value and leverage. Leverage is key to the company’s success. HRL’s business model has been carefully honed to allow its parent companies to perform proprietary R&D in certain areas and joint, collaborative R&D among the LLC members in others. The intellectual property arrangements are skillfully organized so that the LLC Members receive a greater than 4:1 leverage of their research dollars in terms of the IP rights gained. This briefing will describe an overview of the current industrial research environment, HRL’s business model, and challenges to future success.

IM-16: A new microporous germanosilicate with a novel framework topology containing d4r and mtw composite building units

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

Lorgouilloux, Yannick; Dodin, Mathias; Paillaud, Jean-Louis

2009-03-15

The synthesis and the structure of IM-16 a new germanosilicate with a novel zeolitic topology prepared hydrothermally with the ionic liquid 3-ethyl-1-methyl-3H-imidazol-1-ium as the organic structure-directing agent are reported. The structure of calcined and partially rehydrated IM-16 of chemical formula |(H{sub 2}O){sub 0.16}|[Si{sub 3.47}Ge{sub 2.53}O{sub 12}] was solved from powder XRD data in space group Cmcm with a=15.0861(2) A, b=17.7719(3) A, c=19.9764(3) A, V=5355.84(12) A{sup 3} (Z=16). This new zeolite framework type contains 10-MRs channels and may be described from the d4r and mtw composite building units. - Graphical abstract: The synthesis and the structure of IM-16 a new germanosilicatemore » with a novel zeolitic topology prepared hydrothermally with the ionic liquid 3-ethyl-1-methyl-3H-imidazol-1-ium as the organic structure-directing agent are reported. This new zeolite framework type contains 10-MRs channels and may be described from the d4r and mtw composite building units.« less

R&D in Poland: Is the Country Close to a Knowledge-Driven Economy?

NASA Astrophysics Data System (ADS)

Chybowska, Dorota; Chybowski, Leszek; Souchkov, Valeri

2018-06-01

Poland has a strong ambition to evolve rapidly into a knowledge-driven economy. Since 2004, it has been the largest beneficiary of European Union cohesion policy funds among all member states. Between 2007 and 2013, Poland was allocated approximately EUR 67 billion, whereas for 2014-2020 the EU budget earmarked EUR 82.5 billion for Polish cohesion policy. This means that in the coming years, Poland's R&D intensity will grow. But the question remains: is 27 years of free market economy enough to enable a country's economy to become knowledge-based ? This paper offers an analysis of Polish R&D expenditures and investments in terms of their sources (business, government or higher education sectors), types (European Union or state aid) and areas of support (infrastructure, education or innovation). It also characterises the Polish R&D market with its strengths and weaknesses. Then, it examines the process of technology transfer in Poland, comparing it to best practice. Finally, the paper lays out the barriers to effective commercialisation that need to be overcome, and attempts to answer the question raised in its title.

Solid-State Lighting R&D Plan - 2015

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

Bardsley, Norman; Bland, Stephen; Hansen, Monica

2015-05-28

Provides analysis and direction for ongoing R&D activities to advance SSL technology and increase energy savings, reviewing SSL technology status and trends for both LEDs and OLEDs and offering an overview of the current DOE SSL R&D project portfolio.

Air/Oil Seals R and D at AlliedSignal

NASA Technical Reports Server (NTRS)

Ullah, M. Rifat

2006-01-01

AlliedSignal aerospace company is committed to significantly improving the reliabilities of air/oil seals in their gas turbine engines. One motivation for this is that aircraft cabin air quality can be affected by the performance of mainshaft air/oil seals. In the recent past, coking related failure modes have been the focus of air/oil seal R&D at AlliedSignal. Many significant advances have been made to combat coke related failures, with some more work continuing in this area. This years R&D begins to address other commin failure modes. Among them, carbon seal "blistering" has been a chronic problem facing the sealing industry for many decades. AlliedSignal has launched an aggressive effort this year to solve this problem for our aerospace rated carbon seals in a short (one to two year) timeframe. Work also continues in developing more user-friendly tools and data for seal analysis & design. Innovations in seal cooling continue. Nominally non-contacting hydropad sealing concept is being developed for aerospace applications. Finally, proprietary work is in planning stages for development of a seal with the aggressive aim of zero oil leakage.

Effect of the Yield Stress and r-value Distribution on the Earing Profile of Cup Drawing with Yld2000-2d Yield Function

NASA Astrophysics Data System (ADS)

Lou, Yanshan; Bae, Gihyun; Lee, Changsoo; Huh, Hoon

2010-06-01

This paper deals with the effect of the yield stress and r-value distribution on the earing in the cup drawing. The anisotropic yield function, Yld2000-2d yield function, is selected to describe the anisotropy of two metal sheets, 719B and AA5182-O. The tool dimension is referred from the Benchmark problem of NUMISHEET'2002. The Downhill Simplex method is applied to identify the anisotropic coefficients in Yld2000-2d yield function. Simulations of the drawing process are performed to investigate the earing profile of two materials. The earing profiles obtained from simulations are compared with the analytical model developed by Hosford and Caddell. Simulations are conducted with respect to the change of the yield stress and r-value distribution, respectively. The correlation between the anisotropy and the earing tendency is investigated based on simulation data. Finally, the earing mechanism is analyzed through the deformation process of the blank during the cup deep drawing. It can be concluded that ears locate at angular positions with lower yield stress and higher r-value while the valleys appear at the angular position with higher yield stress and lower r-value. The effect of the yield stress distribution is more important for the cup height distribution than that of the r-value distribution.

Measurement of R(D* ) with hadronic τ decays

NASA Astrophysics Data System (ADS)

Siddi, B. G.; LHCb Collaboration

2018-01-01

Lepton universality, described in the Standard Model (SM), predicts equal coupling between gauge bosons and the three lepton families. SM extensions give additional interactions, implying in some cases a stronger coupling with the third generation of leptons. Semileptonic decays of b-hadrons provide a sensitive probe to such New Physics effects. The presence of additional charged Higgs bosons, required by such SM extensions, can have significant effect on the semileptonic decay rate of B 0 → D*τν. A probe of new physics effects is the measurement of the quantities: R(D* )=\\frac{B({\\bar{B}}0\\to {D}* +{τ }-{\\bar{ν }}τ )}{B({\\bar{B}}0\\to {D}* +{μ }-{\\bar{ν }}μ )} and R(D)=\\frac{B({\\bar{B}}0\\to {D}+{τ }-{\\bar{ν }}τ )}{B({\\bar{B}}0\\to {D}+{μ }-{\\bar{ν }}μ )}. The combination of experimental measurements performed by BaBar, Belle and LHCb observing the channel where the τ decays in leptons, gives a deviation from the SM prediction of about 4 σ. It is therefore important to perform additional measurements in this sector in order to improve the precision and confirm or disprove this deviation. Another possibility is to perform this measurement using the channel where the semileptonic τ decays in 3 pions. This in LHCb allows to have e better reconstruction of vertices and other kinematic variables. Results obtained by LHCb on B 0 → D*τν decays, where the τ decays hadronically, are reported.

Characterization of recombinant Mal d 4 and its application for component-resolved diagnosis of apple allergy.

PubMed

Ma, Y; Zuidmeer, L; Bohle, B; Bolhaar, S T H; Gadermaier, G; Gonzalez-Mancebo, E; Fernandez-Rivas, M; Knulst, A C; Himly, M; Asero, R; Ebner, C; van Ree, R; Ferreira, F; Breiteneder, H; Hoffmann-Sommergruber, K

2006-08-01

Profilins are ubiquitous panallergens that have been extensively characterized; yet, their clinical relevance is still unclear. The aim of the present study was to produce recombinant apple profilin (rMal d 4) and to evaluate its allergenic activity and its potency for component-resolved allergy diagnosis. Complementary DNA-derived Mal d 4 was cloned, expressed in Escherichia coli and subsequently purified via poly (l-proline) sepharose. A total of 28 sera from apple-allergic patients were used for IgE-ELISA, immunoblot, RAST and basophil histamine release (BHR) test. In addition, skin prick tests (SPTs) were performed in five patients. Four different complementary DNA coding for apple profilin, Mal d 4, each with an open reading frame of 393 nucleotides, were identified. One isoform Mal d 4.0101 was expressed in Escherichia coli and subsequently purified. Mass spectroscopy revealed the expected mass of 13.826 for rMal d 4.0101, and circular dichroism analysis data were typical for a folded protein and small-angle X-ray scattering measurement identified the protein as a monomer. All the serum samples displayed IgE binding to rMal d 4.0101 in IgE ELISA, immunoblot and RAST. In immunoblotting, IgE binding to natural Mal d 4 was partially/completely inhibited by preincubation with rMal d 4.0101, and RAST values to apple extract were significantly reduced upon serum pretreatment with rMal d 4.0101. SPTs and BHR assays using purified rMal d 4.0101 were positive. Purified rMal d 4.0101 was destroyed within seconds when subjected to pepsin digestion. Apple profilin complementary DNAs were identified. The physicochemical and allergenic properties of purified recombinant Mal d 4.0101 were evaluated showing that the recombinant protein was equal to the natural protein as shown by inhibition assays. Thus, Mal d 4 represents another example suitable for component-resolved diagnosis of food allergy.

COX-2 Elevates Oncogenic miR-526b in Breast Cancer by EP4 Activation.

PubMed

Majumder, Mousumi; Landman, Erin; Liu, Ling; Hess, David; Lala, Peeyush K

2015-06-01

MicroRNAs (miRs) are small regulatory molecules emerging as potential biomarkers in cancer. Previously, it was shown that COX-2 expression promotes breast cancer progression via multiple mechanisms, including induction of stem-like cells (SLC), owing to activation of the prostaglandin E2 receptor EP4 (PTGER4). COX-2 overexpression also upregulated microRNA-526b (miR-526b), in association with aggressive phenotype. Here, the functional roles of miR-526b in breast cancer and the mechanistic role of EP4 signaling in miR-526b upregulation were examined. A positive correlation was noted between miR-526b and COX-2 mRNA expression in COX-2 disparate breast cancer cell lines. Stable overexpression of miR-526b in poorly metastatic MCF7 and SKBR3 cell lines resulted in increased cellular migration, invasion, EMT phenotype and enhanced tumorsphere formation in vitro, and lung colony formation in vivo in immunodeficient mice. Conversely, knockdown of miR-526b in aggressive MCF7-COX-2 and SKBR3-COX-2 cells reduced oncogenic functions and reversed the EMT phenotype, in vitro. Furthermore, it was determined that miR-526b expression is dependent on EP4 receptor activity and downstream PI3K-AKT and cyclic AMP (cAMP) signaling pathways. PI3K-AKT inhibitors blocked EP4 agonist-mediated miR-526b upregulation and tumorsphere formation in MCF7 and SKBR3 cells. NF-κB inhibitor abrogates EP agonist-stimulated miRNA expression in MCF7 and T47D cells, indicating that the NF-κB pathway is also involved in miR-526b regulation. In addition, inhibition of COX-2, EP4, PI3K, and PKA in COX-2-overexpressing cells downregulated miR-526b and its functions in vitro. Finally, miR-526b expression was significantly higher in cancerous than in noncancerous breast tissues and associated with reduced patient survival. In conclusion, miR-526b promotes breast cancer progression, SLC-phenotype through EP4-mediated signaling, and correlates with breast cancer patient survival. This study presents novel

Reward-seeking and discrimination deficits displayed by hypodopaminergic mice are prevented in mice lacking dopamine D4 receptors.

PubMed

Nemirovsky, Sergio I; Avale, M Elena; Brunner, Daniela; Rubinstein, Marcelo

2009-11-01

The dopamine D4 receptor (D4R) is predominantly expressed in the prefrontal cortex, a brain area that integrates motor, rewarding, and cognitive information. Because participation of D4Rs in executive learning is largely unknown, we challenged D4R knockout mice (Drd4(-/-)) and their wild-type (WT) littermates, neonatally treated with 6-hydroxydopamine (6-OHDA; icv) or vehicle in two operant learning paradigms. A continuous reinforcement task, in which one food-pellet was delivered after every lever press, showed that 6-OHDA-treated mice (hypodopaminergic) WT mice pressed the reinforcing lever at much lower rates than normodopaminergic WT mice. In contrast, Drd4(-/-) mice displayed increased lever pressing rates, regardless of their dopamine content. In another study, mice were trained to solve an operant two-choice task in which a first showing lever was coupled to the delivery of one food pellet only after a second lever emerged. Interval between presentation of both levers was initially 12 s and progressively shortened to 6, 2, and finally 0.5 s. Normodopaminergic WT mice obtained a pellet reward in more than 75% of the trials at 12, 6, and 2 s, whereas hypodopaminergic WT mice were severely impaired to select the reward-paired lever. Absence of D4Rs was not detrimental in this task. Moreover, hypodopaminergic Drd4(-/-) mice were as efficient as their normodopaminergic Drd4(-/-) siblings in selecting the reward-paired lever. In summary, hypodopaminergic mice exhibit severe impairments to retrieve rewards in two operant positive reinforcement tasks, but these deleterious effects are totally prevented in the absence of functional D4Rs.

Synthesis of LiFePO4/Li2SiO3/reduced Graphene Oxide (rGO) Composite via Hydrothermal Method

NASA Astrophysics Data System (ADS)

Arifin, M.; Iskandar, F.; Aimon, A. H.; Munir, M. M.; Nuryadin, B. W.

2016-08-01

LiFePO4 is a type of cathode active material used for lithium ion batteries. It has a high electrochemical performance. However, it suffers from certain disadvantages such as a very low intrinsic electronic conductivity and low ionic diffusion. This study was conducted to increase the conductivity of LiFePO4. We have investigated the addition of Li2SiO3 and reduced graphene oxide (rGO) to LiFePO4. The objective of this research was to synthesize LiFePO4/Li2SiO3/rGO via hydrothermal method. Fourier transform infrared spectroscopy (FTIR) measurement showed that the peaks corresponded to the vibration of LiFePO4/Li2SiO3. Further, X-ray diffraction (XRD) measurement confirmed a single phase of LiFePO4. Finally, scanning electron microscopy (SEM) images showed that rGO was distributed on the LiFePO4/Li2SiO3 structure.

TH-E-17A-04: Geometric Validation of K-Space Self-Gated 4D-MRI Vs. 4D-CT Using A Respiratory Motion Phantom

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

Yue, Y; Fan, Z; Yang, W

Purpose: 4D-CT is often limited by motion artifacts, low temporal resolution, and poor phase-based target definition. We recently developed a novel k-space self-gated 4D-MRI technique with high spatial and temporal resolution. The goal here is to geometrically validate 4D-MRI using a MRI-CT compatible respiratory motion phantom and comparison to 4D-CT. Methods: 4D-MRI was acquired using 3T spoiled gradient echo-based 3D projection sequences. Respiratory phases were resolved using self-gated k-space lines as the motion surrogate. Images were reconstructed into 10 temporal bins with 1.56×1.56×1.56mm3. A MRI-CT compatible phantom was designed with a 23mm diameter ball target filled with highconcentration gadolinium(Gd) gelmore » embedded in a 35×40×63mm3 plastic box stabilized with low-concentration Gd gel. The whole phantom was driven by an air pump. Human respiratory motion was mimicked using the controller from a commercial dynamic phantom (RSD). Four breathing settings (rates/depths: 10s/20mm, 6s/15mm, 4s/10mm, 3s/7mm) were scanned with 4D-MRI and 4D-CT (slice thickness 1.25mm). Motion ground-truth was obtained from input signals and real-time video recordings. Reconstructed images were imported into Eclipse(Varian) for target contouring. Volumes and target positions were compared with ground-truth. Initial human study was investigated on a liver patient. Results: 4D-MRI and 4D-CT scans for the different breathing cycles were reconstructed with 10 phases. Target volume in each phase was measured for both 4D-CT and 4D-MRI. Volume percentage difference for the 6.37ml target ranged from 6.67±5.33 to 11.63±5.57 for 4D-CT and from 1.47±0.52 to 2.12±1.60 for 4D-MRI. The Mann-Whitney U-test shows the 4D-MRI is significantly superior to 4D-CT (p=0.021) for phase-based target definition. Centroid motion error ranges were 1.35–1.25mm (4D-CT), and 0.31–0.12mm (4D-MRI). Conclusion: The k-space self-gated 4D-MRI we recently developed can accurately determine

Searches for R-parity-violating supersymmetry in pp collisions at $$\\sqrt{s}$$ = 8 TeV in final states with 0-4 leptons

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

Khachatryan, Vardan

Results are presented from searches for R-parity-violating supersymmetry in events produced inmore » $pp$ collisions at $$\\sqrt{s}$$ = 8 TeV at the LHC. Final states with 0, 1, 2, or multiple leptons are considered independently. The analysis is performed on data collected by the CMS experiment corresponding to an integrated luminosity of 19.5 fb -1. No excesses of events above the standard model expectations are observed, and 95% confidence level limits are set on supersymmetric particle masses and production cross sections. The results are interpreted in models featuring R-parity-violating decays of the lightest supersymmetric particle, which in the studied scenarios can be either the gluino, a bottom squark, or a neutralino. In a gluino pair production model with baryon number violation, gluinos with a mass less than 0.98 and 1.03 TeV are excluded, by analyses in a fully hadronic and one-lepton final state, respectively. An analysis in a dilepton final state is used to exclude bottom squarks with masses less than 307 GeV in a model considering bottom squark pair production. Multilepton final states are considered in the context of either strong or electroweak production of superpartners and are used to set limits on the masses of the lightest supersymmetric particles. Finally, these limits range from 300 to 900 GeV in models with leptonic and up to approximately 700 GeV in models with semileptonic R-parity-violating couplings.« less

Searches for R-parity-violating supersymmetry in pp collisions at $$\\sqrt{s}$$ = 8 TeV in final states with 0-4 leptons

DOE PAGES

Khachatryan, Vardan

2016-12-29

Results are presented from searches for R-parity-violating supersymmetry in events produced inmore » $pp$ collisions at $$\\sqrt{s}$$ = 8 TeV at the LHC. Final states with 0, 1, 2, or multiple leptons are considered independently. The analysis is performed on data collected by the CMS experiment corresponding to an integrated luminosity of 19.5 fb -1. No excesses of events above the standard model expectations are observed, and 95% confidence level limits are set on supersymmetric particle masses and production cross sections. The results are interpreted in models featuring R-parity-violating decays of the lightest supersymmetric particle, which in the studied scenarios can be either the gluino, a bottom squark, or a neutralino. In a gluino pair production model with baryon number violation, gluinos with a mass less than 0.98 and 1.03 TeV are excluded, by analyses in a fully hadronic and one-lepton final state, respectively. An analysis in a dilepton final state is used to exclude bottom squarks with masses less than 307 GeV in a model considering bottom squark pair production. Multilepton final states are considered in the context of either strong or electroweak production of superpartners and are used to set limits on the masses of the lightest supersymmetric particles. Finally, these limits range from 300 to 900 GeV in models with leptonic and up to approximately 700 GeV in models with semileptonic R-parity-violating couplings.« less

Investigation of histone H4 hyperacetylation dynamics in the 5S rRNA genes family by chromatin immunoprecipitation assay.

PubMed

Burlibașa, Liliana; Suciu, Ilinca

2015-12-01

Oogenesis is a critical event in the formation of female gamete, whose role in development is to transfer genomic information to the next generation. During this process, the gene expression pattern changes dramatically concomitant with genome remodelling, while genomic information is stably maintained. The aim of the present study was to investigate the presence of H4 acetylation of the oocyte and somatic 5S rRNA genes in Triturus cristatus, using chromatin immunoprecipitation assay (ChIP). Our findings suggest that some epigenetic mechanisms such as histone acetylation could be involved in the transcriptional regulation of 5S rRNA gene families.

76 FR 72869 - Proposed Establishment of Restricted Areas R-5402, R-5403A, R-5403B, R-5403C, R-5403D, R-5403E...

Federal Register 2010, 2011, 2012, 2013, 2014

2011-11-28

...-0117; Airspace Docket No. 09-AGL-31] Proposed Establishment of Restricted Areas R-5402, R-5403A, R- 5403B, R-5403C, R-5403D, R-5403E, and R-5403F; Devils Lake, ND AGENCY: Federal Aviation Administration... Camp Grafton Range, the existing R-5401 restricted area surrounding the range is inadequate to satisfy...

Building effective R&D capabilities abroad.

PubMed

Kuemmerle, W

1997-01-01

In the past, companies kept most of their research and development activities in their home country because they thought it important to have R&D close to where strategic decisions were being made. But today many companies choose to establish R&D networks in foreign countries in order to tap the knowledge there or to commercialize products for those markets at a competitive speed. Adopting a global approach entails new, complex managerial challenges. It means linking R&D strategy to a company's overall business strategy. The first step in adopting such an approach is to build a team to lead the initiative--a team whose members are sufficiently senior to be able to mobilize resources at short notice. Second, companies must determine whether an R&D site's primary objective is to augment the expertise that the home base has the offer or to exploit that knowledge for use in the foreign country. That determination affects the choice of location and staff. For example, to augment the home base laboratory, a company would want to be near a foreign university; to exploit the home base laboratory it would need to be near large markets and manufacturing facilities. The best individual for managing both types of site combines the qualities of good scientist and good manager, knows how to integrate the new site with existing sites, understand technology trends, and is good at gaining access to foreign scientific communities. As more pockets of knowledge emerge around the globe and competition in foreign markets mounts, only those companies that embrace an informed approach to global R&D will be able to meet the new challenges.

76 FR 441 - Airworthiness Directives; Airbus Model A300 B4-600, B4-600R, and F4-600R Series Airplanes, and...

Federal Register 2010, 2011, 2012, 2013, 2014

2011-01-05

... Airworthiness Directives; Airbus Model A300 B4-600, B4-600R, and F4-600R Series Airplanes, and Model C4-605R...-622, B4-605R, B4-622R, F4-605R, F4-622R, and C4-605R Variant F airplanes, certificated in any category...

Four-dimensional diffusion-weighted MR imaging (4D-DWI): a feasibility study.

PubMed

Liu, Yilin; Zhong, Xiaodong; Czito, Brian G; Palta, Manisha; Bashir, Mustafa R; Dale, Brian M; Yin, Fang-Fang; Cai, Jing

2017-02-01

Diffusion-weighted Magnetic Resonance Imaging (DWI) has been shown to be a powerful tool for cancer detection with high tumor-to-tissue contrast. This study aims to investigate the feasibility of developing a four-dimensional DWI technique (4D-DWI) for imaging respiratory motion for radiation therapy applications. Image acquisition was performed by repeatedly imaging a volume of interest (VOI) using an interleaved multislice single-shot echo-planar imaging (EPI) 2D-DWI sequence in the axial plane. Each 2D-DWI image was acquired with an intermediately low b-value (b = 500 s/mm 2 ) and with diffusion-encoding gradients in x, y, and z diffusion directions. Respiratory motion was simultaneously recorded using a respiratory bellow, and the synchronized respiratory signal was used to retrospectively sort the 2D images to generate 4D-DWI. Cine MRI using steady-state free precession was also acquired as a motion reference. As a preliminary feasibility study, this technique was implemented on a 4D digital human phantom (XCAT) with a simulated pancreas tumor. The respiratory motion of the phantom was controlled by regular sinusoidal motion profile. 4D-DWI tumor motion trajectories were extracted and compared with the input breathing curve. The mean absolute amplitude differences (D) were calculated in superior-inferior (SI) direction and anterior-posterior (AP) direction. The technique was then evaluated on two healthy volunteers. Finally, the effects of 4D-DWI on apparent diffusion coefficient (ADC) measurements were investigated for hypothetical heterogeneous tumors via simulations. Tumor trajectories extracted from XCAT 4D-DWI were consistent with the input signal: the average D value was 1.9 mm (SI) and 0.4 mm (AP). The average D value was 2.6 mm (SI) and 1.7 mm (AP) for the two healthy volunteers. A 4D-DWI technique has been developed and evaluated on digital phantom and human subjects. 4D-DWI can lead to more accurate respiratory motion measurement. This has a

C4d-the witness of humoral rejection.

PubMed

de Gouveia, R H; Vitorino, E; Ramos, S; Rebocho, M J; Queirós E Melo, J; Martins, A P; Moura, M L C

2009-04-01

Acute antibody-mediated (humoral) rejection is a major cause of morbidity, graft loss, and mortality among heart transplant patients. Herein we have presented our experience using C4d to characterize humoral rejection. All nonformalin-fixed cardiac graft biopsies (protocol or emergency) received between May 2007 and May 2008 were examined by immunofluorescence for C4d. One hundred twelve endomyocardial biopsies from 25 transplanted patients included 20 males and 5 females of ages ranging from 3 to 71 years. The number of biopsies per subject varied from 1 to 11; the timespan between transplantation and the diagnostic biopsies ranged from days to 8 years. Thirteen biopsies showed acute humoral rejection (intramyocardial capillaries positive for C4d); 31, acute cellular rejection (grades 1R, 2R); 7, both humoral and cellular rejection; and 1, acute humoral rejection and allograft vasculopathy. Some of the positive biopsies belonged to the same person, and some to transplanted individuals with signs and symptoms suggestive of rejection, while others did not. The persistence of humoral rejection, despite the disappearance of a cellular component, correlated with slower clinicoechocardiographic improvement. C4d positivity is a morphologic sign of humoral rejection. It may hasten the appearance and/or worsening of allograft vasculopathy independent of patient age or posttransplantation time.

Biosynthesis of a (1. -->. 4)-. beta. -D-glucan. [Lupinus albus

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

Brummond, D.O.

1983-01-01

An enzymatic activity isolated from Lupinus albus that produced an insoluble (1..-->..4)-..beta..-D-glucan from UDP-D-glucose has been solubilized and partially purified. Some of the properties of the enzyme system have been characterized. A proposed sequence of reactions between UDP-D-glucose and the final dextran may involve a (1..-->..4)-..beta..-linked polysaccharide bonded to UDP.

Changing R&D models in research-based pharmaceutical companies.

PubMed

Schuhmacher, Alexander; Gassmann, Oliver; Hinder, Markus

2016-04-27

New drugs serving unmet medical needs are one of the key value drivers of research-based pharmaceutical companies. The efficiency of research and development (R&D), defined as the successful approval and launch of new medicines (output) in the rate of the monetary investments required for R&D (input), has declined since decades. We aimed to identify, analyze and describe the factors that impact the R&D efficiency. Based on publicly available information, we reviewed the R&D models of major research-based pharmaceutical companies and analyzed the key challenges and success factors of a sustainable R&D output. We calculated that the R&D efficiencies of major research-based pharmaceutical companies were in the range of USD 3.2-32.3 billion (2006-2014). As these numbers challenge the model of an innovation-driven pharmaceutical industry, we analyzed the concepts that companies are following to increase their R&D efficiencies: (A) Activities to reduce portfolio and project risk, (B) activities to reduce R&D costs, and (C) activities to increase the innovation potential. While category A comprises measures such as portfolio management and licensing, measures grouped in category B are outsourcing and risk-sharing in late-stage development. Companies made diverse steps to increase their innovation potential and open innovation, exemplified by open source, innovation centers, or crowdsourcing, plays a key role in doing so. In conclusion, research-based pharmaceutical companies need to be aware of the key factors, which impact the rate of innovation, R&D cost and probability of success. Depending on their company strategy and their R&D set-up they can opt for one of the following open innovators: knowledge creator, knowledge integrator or knowledge leverager.

Development of melanoma-targeted polymer micelles by conjugation of a melanocortin 1 receptor (MC1R) specific ligand.

PubMed

Barkey, Natalie M; Tafreshi, Narges K; Josan, Jatinder S; De Silva, Channa R; Sill, Kevin N; Hruby, Victor J; Gillies, Robert J; Morse, David L; Vagner, Josef

2011-12-08

The incidence of malignant melanoma is rising faster than that of any other cancer in the United States. Because of its high expression on the surface of melanomas, MC1R has been investigated as a target for selective imaging and therapeutic agents against melanoma. Eight ligands were screened against cell lines engineered to overexpress MC1R, MC4R, or MC5R. Of these, compound 1 (4-phenylbutyryl-His-dPhe-Arg-Trp-NH(2)) exhibited high (0.2 nM) binding affinity for MC1R and low (high nanomolar) affinities for MC4R and MC5R. Functionalization of the ligand at the C-terminus with an alkyne for use in Cu-catalyzed click chemistry was shown not to affect the binding affinity. Finally, formation of the targeted polymer, as well as the targeted micelle formulation, also resulted in constructs with low nanomolar binding affinity.

Comparison of 4D flow and 2D velocity-encoded phase contrast MRI sequences for the evaluation of aortic hemodynamics

PubMed Central

Bollache, Emilie; van Ooij, Pim; Powell, Alex; Carr, James; Markl, Michael; Barker, Alex J.

2016-01-01

The purpose of this study was to compare aortic flow and velocity quantification using 4D flow MRI and 2D CINE phase-contrast (PC)-MRI with either one-directional (2D-1dir) or three-directional (2D-3dir) velocity encoding. 15 healthy volunteers (51 ± 19 years) underwent MRI including (1) breath-holding 2D-1dir and (2) free breathing 2D-3dir PC-MRI in planes orthogonal to the ascending (AA) and descending (DA) aorta, as well as (3) free breathing 4D flow MRI with full thoracic aorta coverage. Flow quantification included the co-registration of the 2D PC acquisition planes with 4D flow MRI data, AA and DA segmentation, and calculation of AA and DA peak systolic velocity, peak flow and net flow volume for all sequences. Additionally, the 2D-3dir velocity taking into account the through-plane component only was used to obtain results analogous to a free breathing 2D-1dir acquisition. Good agreement was found between 4D flow and 2D-3dir peak velocity (differences = −3 to 6 %), peak flow (−7 %) and net volume (−14 to −9 %). In contrast, breath-holding 2D-1dir measurements exhibited indices significantly lower than free breathing 2D-3dir and 2D-1dir (differences = −35 to −7 %, p < 0.05). Finally, high correlations (r ≥ 0.97) were obtained for indices estimated with or without eddy current correction, with the lowest correlation observed for net volume. 4D flow and 2D-3dir aortic hemodynamic indices were in concordance. However, differences between respiration state and 2D-1dir and 2D-3dir measurements indicate that reference values should be established according to the PC-MRI sequence, especially for the widely used net flow (e.g. stroke volume in the AA). PMID:27435230

Isoguanine quartets formed by d(T4isoG4T4): tetraplex identification and stability.

PubMed Central

Seela, F; Wei, C; Melenewski, A

1996-01-01

The self-aggregation of the oligonucleotide d(T4isoG4T4) (1) is investigated. Based on ion exchange HPLC experiments and CD spectroscopy, a tetrameric structure is identified. This structure was formed in the presence of sodium ions and shows almost the same chromatographic mobility on ion exchange HPLC as d(T4G4T4) (2). The ratio of aggregate versus monomer is temperature dependent and the tetraplex of [d(T4isoG4T4)]4 is more stable than that of [d(T4G4T4)]4. A mixture of d(T4isoG4T4) and d(T4G4T4) forms mixed tetraplexes containing strands of d(T4isoG4T4) and d(T4G4T4). PMID:9016664

Chlamydia abortus Pmp18.1 Induces IL-1β Secretion by TLR4 Activation through the MyD88, NF-κB, and Caspase-1 Signaling Pathways

PubMed Central

Pan, Qing; Zhang, Qiang; Chu, Jun; Pais, Roshan; Liu, Shanshan; He, Cheng; Eko, Francis O.

2017-01-01

The polymorphic membrane protein D (Pmp18D) is a 160-kDa outer membrane protein that is conserved and plays an important role in Chlamydia abortus pathogenesis. We have identified an N-terminal fragment of Pmp18D (designated Pmp18.1) as a possible subunit vaccine antigen. In this study, we evaluated the vaccine potential of Pmp18.1 by investigating its ability to induce innate immune responses in dendritic cells and the signaling pathway(s) involved in rPmp18.1-induced IL-1β secretion. We next investigated the immunomodulatory impact of VCG, in comparison with the more established Th1-promoting adjuvants, CpG and FL, on rPmp18.1-mediated innate immune activation. Finally, the effect of siRNA targeting TLR4, MyD88, NF-κB p50, and Caspase-1 mRNA in DCs on IL-1β cytokine secretion was also investigated. Bone marrow-derived dendritic cells (BMDCs) were stimulated with rPmp18.1 in the presence or absence of VCG or CpG or FL and the magnitude of cytokines produced was assessed using a multiplex cytokine ELISA assay. Expression of costimulatory molecules and Toll-like receptors (TLRs) was analyzed by flow cytometry. Quantitation of intracellular levels of myeloid differentiation factor 88 (MyD88), nuclear factor kappa beta (NF-κB p50/p65), and Caspase-1 was evaluated by Western immunoblotting analysis while NF-κB p65 nuclear translocation was assessed by confocal microscopy. The results showed DC stimulation with rPmp18.1 provoked the secretion of proinflammatory cytokines and upregulated expression of TLRs and co-stimulatory molecules associated with DC maturation. These responses were significantly (p ≤ 0.001) enhanced by VCG but not CpG or FL. In addition, rPmp18.1 activated the expression of MyD88, NF-κB p50, and Caspase-1 as well as the nuclear expression of NF-κB p65 in treated DCs. Furthermore, targeting TLR4, MyD88, NF-κB p50, and Caspase-1 mRNA in BMDCs with siRNA significantly reduced their expression levels, resulting in decreased IL-1β cytokine

CM and DM in an ISO R and D Environment

NASA Technical Reports Server (NTRS)

Crowley, Sandra L.

2000-01-01

ISO 9000 - a common buzz word in industry is making inroads to government agencies. The National Aeronautics and Space Agency (NASA) achieved ISO 9001 certification at each of its nine (9) Centers and Headquarters in 1998-1999. NASA Glenn Research Center (GRC) was recommended for certification in September 1999. Since then, each of the Centers has been going through the semi-annual surveillance audits. Growing out of the manufacturing industry, successful application of the international quality standard to a research and development (R&D) environment has had its challenges. This paper will address how GRC applied Configuration Management (CM) and Data (or Document) Management (DM) to meet challenges to achieve ISO certification. One of the first challenges was to fit the ISO 9001-1994 elements to the GRC environment. Some of the elements fit well-Management Responsibility (4.1), Internal Audits (4.17), Document and Data Control (4.5). Other elements were not suited or applied easily to the R&D environment-Servicing (4.19), Statistical Techniques (4.20). Since GRC "builds" only one or two items at a time, these elements were considered not applicable to the environment.

75 FR 60611 - Airworthiness Directives; Airbus Model A300 B4-600, B4-600R, and F4-600R Series Airplanes, and...

Federal Register 2010, 2011, 2012, 2013, 2014

2010-10-01

... Airworthiness Directives; Airbus Model A300 B4-600, B4-600R, and F4-600R Series Airplanes, and Model A300 C4...; Model A300 B4-601, B4- 603, B4-620, B4-622, B4-605R, B4-622R, F4-605R, F4-622R, and C4-605R Variant F...-- Dated-- A300 series airplanes......... A300-32A0447..... April 22, 2004. A300 B4-600, B4-600R, and F4...

Association of MC4R variants with obesity-related traits in Hispanic children

USDA-ARS?s Scientific Manuscript database

Melanocortin 4 receptor (MC4R) has been implicated in the regulation of appetite and energy expenditure. In children, MC4R mutations have been associated with severe obesity. The main objective of this study was to investigate the potential functional effects of variants in MC4R gene on the variatio...

National R & D Policy: An Industrial Perspective.

ERIC Educational Resources Information Center

Schmitt, Roland W.

1984-01-01

An analysis of how the government can and cannot use research and development (R&D) policy to improve the nation's industrial posture suggests four guidelines for federal R&D policy. These guidelines are outlined and discussed. Areas analyzed include federal role; competition from Japan; support for university research, immigration policy,…

75 FR 76926 - Airworthiness Directives; Airbus Model A300 B4-600, B4-600R, and F4-600R Series Airplanes, and...

Federal Register 2010, 2011, 2012, 2013, 2014

2010-12-10

... Airworthiness Directives; Airbus Model A300 B4-600, B4-600R, and F4-600R Series Airplanes, and Model C4-605R... airplanes; Model A300 B4-605R and B4-622R airplanes; Model A300 F4-605R and F4-622R airplanes; Model A300 C4...

75 FR 27956 - Airworthiness Directives; Airbus Model A300 B4-600, B4-600R, and F4-600R Series Airplanes, and...

Federal Register 2010, 2011, 2012, 2013, 2014

2010-05-19

... B4-600, B4-600R, and F4-600R Series Airplanes, and Model C4-605R Variant F Airplanes (Collectively...-203, and B4-203 airplanes; Model A300 B4-601, B4- 603, B4-620, B4-622, B4-605R, B4-622R, F4-605R, F4...

R&D Nuggets

Science.gov Websites

Origin of the Chemical Elements and Their Discoveries [added 1/2007] National Laboratories and Other to the content of DOE R&D Accomplishments. Celebrating Einstein - series of articles about Albert Einstein and his work [added 3/2005] Compact Portable Electric Power Sources [added 1/2007] History of the

Circulating levels of miR-7, miR-152 and miR-192 respond to vitamin D supplementation in adults with prediabetes and correlate with improvements in glycemic control.

PubMed

Nunez Lopez, Yury O; Pittas, Anastassios G; Pratley, Richard E; Seyhan, Attila A

2017-11-01

Vitamin D may play an important role in modifying the risk of type 2 diabetes. Supplementation with cholecalciferol has been shown to improve β cell function and to attenuate the rise in glycated hemoglobin in people at high risk of diabetes. We examined whether circulating microRNAs (miRNAs) reflect disease progression and/or respond to vitamin D supplementation. We measured plasma levels of select miRNAs implicated in diabetes in people with prediabetes treated either with placebo (n=21) or 2000 U of cholecalciferol daily (n=21) for 4 months in the Calcium and Vitamin D for Diabetes Mellitus trial and compared the baseline-adjusted changes after correcting for age, body mass index, race, time of study entry (season) and baseline disposition index. Circulating levels of miR-7 (sixfold reduction, P=.01), miR-152 (1.5-fold increase, P=.03), and miR-192 (1.7-fold reduction, P=.026) displayed significant treatment-by-time interactions between the placebo- and the vitamin-D-treated groups. Plasma levels of miR-7 were reduced in the vitamin D and increased in the placebo group. The change in miR-152 positively correlated with the change in levels of the circulating metabolite 25-hydroxyvitamin D (r=0.33, P=.046) and negatively correlated with the change in glycated hemoglobin (r=-0.37, P=.024). The change in miR-192 positively correlated with the change in fasting glucose (r=0.41, P<.011). In conclusion, reduction of circulating miR-7 and miR-192, accompanied by elevation of miR-152, reflects a beneficial metabolic response to vitamin D treatment in people with prediabetes. These miRNAs may be useful biomarkers in diabetes prevention trials and other studies of vitamin D. Copyright © 2017 Elsevier Inc. All rights reserved.

THE CIRCUMSTELLAR ENVIRONMENT OF R CORONAE BOREALIS: WHITE DWARF MERGER OR FINAL-HELIUM-SHELL FLASH?

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

Clayton, Geoffrey C.; Andrews, J. E.; Sugerman, Ben E. K.

2011-12-10

In 2007, R Coronae Borealis (R CrB) went into a historically deep and long decline. In this state, the dust acts like a natural coronagraph at visible wavelengths, allowing faint nebulosity around the star to be seen. Imaging has been obtained from 0.5 to 500 {mu}m with Gemini/GMOS, Hubble Space Telescope/WFPC2, Spitzer/MIPS, and Herschel/SPIRE. Several of the structures around R CrB are cometary globules caused by wind from the star streaming past dense blobs. The estimated dust mass of the knots is consistent with their being responsible for the R CrB declines if they form along the line of sightmore » to the star. In addition, there is a large diffuse shell extending up to 4 pc away from the star containing cool 25 K dust that is detected all the way out to 500 {mu}m. The spectral energy distribution of R CrB can be well fitted by a 150 AU disk surrounded by a very large diffuse envelope which corresponds to the size of the observed nebulosity. The total masses of the disk and envelope are 10{sup -4} and 2 M{sub Sun }, respectively, assuming a gas-to-dust ratio of 100. The evidence pointing toward a white dwarf merger or a final-helium-shell flash origin for R CrB is contradictory. The shell and the cometary knots are consistent with a fossil planetary nebula. Along with the fact that R CrB shows significant lithium in its atmosphere, this supports the final-helium-shell flash. However, the relatively high inferred mass of R CrB and its high fluorine abundance support a white dwarf merger.« less

Variable tolerance among Palmer amaranth (Amaranthus palmeri) biotypes to glyphosate, 2,4-D amine, and premix formulation of glyphosate plus 2,4-D choline (Enlist Duo®) herbicide

USDA-ARS?s Scientific Manuscript database

Adoption of soybean that is resistant to 2,4-D will result in more use of glyphosate plus 2,4-D premixes and tank-mixtures. Preliminary whole-plant greenhouse assays confirm most Palmer amaranth found in Indiana are glyphosate-resistant (GR) and some biotypes exhibit tolerance to 2,4-D amine. Dose r...

Insilico study of the A(2A)R-D (2)R kinetics and interfacial contact surface for heteromerization.

PubMed

Prakash, Amresh; Luthra, Pratibha Mehta

2012-10-01

G-protein-coupled receptors (GPCRs) are cell surface receptors. The dynamic property of receptor-receptor interactions in GPCRs modulates the kinetics of G-protein signaling and stability. In the present work, the structural and dynamic study of A(2A)R-D(2)R interactions was carried to acquire the understanding of the A(2A)R-D(2)R receptor activation and deactivation process, facilitating the design of novel drugs and therapeutic target for Parkinson's disease. The structure-based features (Alpha, Beta, SurfAlpha, and SurfBeta; GapIndex, Leakiness and Gap Volume) and slow mode model (ENM) facilitated the prediction of kinetics (K (off), K (on), and K (d)) of A(2A)R-D(2)R interactions. The results demonstrated the correlation coefficient 0.294 for K (d) and K (on) and the correlation coefficient 0.635 for K (d) and K (off), and indicated stable interfacial contacts in the formation of heterodimer. The coulombic interaction involving the C-terminal tails of the A(2A)R and intracellular loops (ICLs) of D(2)R led to the formation of interfacial contacts between A(2A)R-D(2)R. The properties of structural dynamics, ENM and KFC server-based hot-spot analysis illustrated the stoichiometry of A(2A)R-D(2)R contact interfaces as dimer. The propensity of amino acid residues involved in A(2A)R-D(2)R interaction revealed the presence of positively (R, H and K) and negatively (E and D) charged structural motif of TMs and ICL3 of A(2A)R and D(2)R at interface of dimer contact. Essentially, in silico structural and dynamic study of A(2A)R-D(2)R interactions will provide the basic understanding of the A(2A)R-D(2)R interfacial contact surface for activation and deactivation processes, and could be used as constructive model to recognize the protein-protein interactions in receptor assimilations.

cis-1,3,4,6-Tetranitrooctahydroimidazo-[4,5-d]imidazole (BCHMX), its properties and initiation reactivity.

PubMed

Klasovitý, Dusan; Zeman, Svatopluk; Růzicka, Ales; Jungová, Marcela; Rohác, Michal

2009-05-30

Using the (15)N NMR chemical shifts of nitrogen atoms in nitramino groups of cis-1,3,4,6-tetranitrooctahydroimidazo-[4,5-d]imidazole (bicyclo-HMX or BCHMX) and additional 10 nitramines, we have assessed its reactivity in detonation, under the influence of impact, and by action of electric spark. It is stated that the thermal stability of BCHMX is higher than that of 1,3,5-trinitro-1,3,5-triazinane (RDX). The longest NN bond in the BCHMX molecule (1.412(4)A) is the cause for its higher impact reactivity, which is at the level of that of penterythritol tetranitrate (PETN). In the experimentally determined detonation velocity, BCMX can be slightly better performing than RDX. From the standpoint of friction sensitivity, BCHMX is similar to 1,3,5,7-tetranitro-1,3,5,7-tetrazocane (HMX). Attention was also focused on the solubility-temperature dependence of BCHMX in acetone, acetonitrile, ethyl acetate, dimethyl sulfoxide, tetrahydrofurane, and nitromethane. X-ray crystallographic study of BCHMX (C(4)H(6)N(8)O(8), M(r)=294.17), has been carried out at the temperature of 150K with the following results: a=8.5430(8), b=6.9480(6), c=8.7780(8)A, alpha=90.0(7) degrees , beta=102.452(11) degrees , gamma=90.0(9) degrees , V=508.777(8)A(3), Z=2, D(x)=1.920 g cm(-3), lambda(Mo Ka)=0.71073A, micro=0.169 cm(-1), F(000)=856, final R=0.0414 for 1254 independent observed reflections. In the BCHMX crystal there were found more short contacts in the molecular crystal of BCHMX data of Gilardi creating extensive supramolecular architecture.

Self-Reported Sexual Behavioral Interests and Polymorphisms in the Dopamine Receptor D4 (DRD4) Exon III VNTR in Heterosexual Young Adults.

PubMed

Halley, Andrew C; Boretsky, Melanie; Puts, David A; Shriver, Mark

2016-11-01

Polymorphisms in the dopamine D4 receptor (DRD4) have previously been shown to associate with a variety of human behavioral phenotypes, including ADHD pathology, alcohol and tobacco craving, financial risk-taking in males, and broader personality traits such as novelty seeking. Recent research has linked the presence of a 7-repeat (7R) allele in a 48-bp variable number of tandem repeats (VNTR) along exon III of DRD4 to age at first sexual intercourse, sexual desire, arousal and function, and infidelity and promiscuity. We hypothesized that carriers of longer DRD4 alleles may report interest in a wider variety of sexual behaviors and experiences than noncarriers. Participants completed a 37-item questionnaire measuring sexual interests as well as Cloninger's Temperament and Character Inventory, and were genotyped for the 48-bp VNTR on exon III of DRD4. Based on our final genotyped sample of female (n = 139) and male (n = 115) participants, we found that 7R carriers reported interest in a wider variety of sexual behaviors (r = 0.16) within a young adult heterosexual sample of European descent. To our knowledge, this is the first reported association between DRD4 exon III VNTR genotype and interest in a variety of sexual behaviors. We discuss these findings within the context of DRD4 research and broader trends in human evolutionary history.

Melanocortin-4 receptor pathway dysfunction in obesity: Patient stratification aimed at MC4R agonist treatment.

PubMed

Ayers, Kristin L; Glicksberg, Benjamin S; Garfield, Alastair S; Longerich, Simonne; White, Joseph A; Yang, Pengwei; Du, Lei; Chittenden, Thomas W; Gulcher, Jeffery R; Roy, Sophie; Fiedorek, Fred; Gottesdiener, Keith; Cohen, Sarah; North, Kari E; Schadt, Eric E; Li, Shuyu D; Chen, Rong; Van der Ploeg, Lex H T

2018-05-02

The hypothalamic melanocortin 4 receptor (MC4R)-pathway serves a critical role in regulating bodyweight. Loss of function (LoF) mutations in the MC4R pathway including mutations in the POMC (1), PCSK1, LEPR (2) or the MC4R genes (3) have been shown to be causative of early-onset severe obesity. Through a comprehensive epidemiological analysis of known and predicted LoF variants in the POMC, PCSK1 and LEPR genes, we sought to estimate the number of US individuals with bi-allelic MC4R pathway LoF variants. We predict approximately 650 α-MSH/POMC, 8,500 PCSK1 and 3,600 LEPR homozygous and compound heterozygous individuals in the US, cumulatively enumerating over 12,800 MC4R pathway deficient obese patients. Very few of these have been genetically diagnosed to date. These estimates increase when we include a small subset of less rare variants: β-MSH/POMC, PCSK1 N221D, and a novel PCSK1 LoF variant (T640A). To further define the MC4R pathway and its potential impact on obesity we tested associations between body-mass index (BMI) and LoF mutation-burden in the POMC, PCSK1 and LEPR genes in various populations. We show that the cumulative allele burden in individuals with two or more LoF alleles in one or more genes in the MC4R pathway predisposes to a higher BMI than non-carriers or heterozygous LoF carriers with a defect in only one gene. Our analysis represents a genetically-rationalized study of the hypothalamic MC4R pathway aimed at genetic patient stratification to determine which obese sub-populations should be studied to understand MC4R agonist (e.g., setmelanotide) treatment responsiveness.

FY2016 Advanced Batteries R&D Annual Progress Report

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

None, None

The Advanced Batteries research and development (R&D) subprogram within the DOE Vehicle Technologies Office (VTO) provides support and guidance for projects focusing on batteries for plug-in electric vehicles. Program targets focus on overcoming technical barriers to enable market success including: (1) significantly reducing battery cost, (2) increasing battery performance (power, energy, durability), (3) reducing battery weight & volume, and (4) increasing battery tolerance to abusive conditions such as short circuit, overcharge, and crush. This report describes the progress made on the research and development projects funded by the Battery subprogram in 2016. This section covers the Vehicle Technologies Office overview;more » the Battery subprogram R&D overview; Advanced Battery Development project summaries; and Battery Testing, Analysis, and Design project summaries. It also includes the cover and table of contents.« less

R&D Opportunities for Membranes and Separation Technologies in Building Applications

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

Goetzler, William; Guernsey, Matt; Bargach, Youssef

This report recommends innovative membrane and separation technologies that can assist the Building Technologies Office in achieving its 2030 goal. This report identifies research and development (R&D) initiatives across several building applications where further investigations could result in impactful savings.

U.S. Federal Investments in Energy R&D: 1961-2008

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

Dooley, James J.

2008-10-10

This paper documents nearly a half century of U.S. federal government support for energy research and development (R&D). Data on energy R&D expenditures disaggregated by major program area are presented here for the first time for the period 1961-2008. This paper also documents U.S. federal government spending on key large scale energy R&D programs that were initiated in response to the oil crisis of the 1970s. Since 1961, the U.S. government has invested nearly $172 billion (in inflation adjusted 2005 US dollars) for the development of advanced energy technologies and for the necessary underlying basic science. Over this period, nearlymore » 24% of the total federal investment in energy R&D occurred during the short seven-year span of 1974-1980. From 1977-1981, energy R&D investments briefly rose above 10% of all federal R&D; however, since the mid-1990s energy R&D has accounted for only about 1% of all federal R&D investments.« less

The D1 family dopamine receptor, DopR, potentiates hind leg grooming behavior in Drosophila

PubMed Central

Pitmon, E.; Stephens, G.; Parkhurst, S. J.; Wolf, F. W.; Kehne, G.; Taylor, M.

2016-01-01

Drosophila groom away debris and pathogens from the body using their legs in a stereotyped sequence of innate motor behaviors. Here, we investigated one aspect of the grooming repertoire by characterizing the D1 family dopamine receptor, DopR. Removal of DopR results in decreased hind leg grooming, as substantiated by quantitation of dye remaining on mutant and RNAi animals vs. controls and direct scoring of behavioral events. These data are also supported by pharmacological results that D1 receptor agonists fail to potentiate grooming behaviors in headless DopR flies. DopR protein is broadly expressed in the neuropil of the thoracic ganglion and overlaps with TH‐positive dopaminergic neurons. Broad neuronal expression of dopamine receptor in mutant animals restored normal grooming behaviors. These data provide evidence for the role of DopR in potentiating hind leg grooming behaviors in the thoracic ganglion of adult Drosophila. This is a remarkable juxtaposition to the considerable role of D1 family dopamine receptors in rodent grooming, and future investigations of evolutionary relationships of circuitry may be warranted. PMID:26749475

AdS and stabilized extra dimensions in multi-dimensional gravitational models with nonlinear scalar curvature terms R-1 and R4

NASA Astrophysics Data System (ADS)

Günther, Uwe; Zhuk, Alexander; Bezerra, Valdir B.; Romero, Carlos

2005-08-01

We study multi-dimensional gravitational models with scalar curvature nonlinearities of types R-1 and R4. It is assumed that the corresponding higher dimensional spacetime manifolds undergo a spontaneous compactification to manifolds with a warped product structure. Special attention has been paid to the stability of the extra-dimensional factor spaces. It is shown that for certain parameter regions the systems allow for a freezing stabilization of these spaces. In particular, we find for the R-1 model that configurations with stabilized extra dimensions do not provide a late-time acceleration (they are AdS), whereas the solution branch which allows for accelerated expansion (the dS branch) is incompatible with stabilized factor spaces. In the case of the R4 model, we obtain that the stability region in parameter space depends on the total dimension D = dim(M) of the higher dimensional spacetime M. For D > 8 the stability region consists of a single (absolutely stable) sector which is shielded from a conformal singularity (and an antigravity sector beyond it) by a potential barrier of infinite height and width. This sector is smoothly connected with the stability region of a curvature-linear model. For D < 8 an additional (metastable) sector exists which is separated from the conformal singularity by a potential barrier of finite height and width so that systems in this sector are prone to collapse into the conformal singularity. This second sector is not smoothly connected with the first (absolutely stable) one. Several limiting cases and the possibility of inflation are discussed for the R4 model.

‘The world is full of big bad wolves’: investigating the experimental therapeutic spaces of R.D. Laing and Aaron Esterson

PubMed Central

2014-01-01

In conjunction with the recent critical assessments of the life and work of R.D. Laing, this paper seeks to demonstrate what is revealed when Laing’s work on families and created spaces of mental health care are examined through a geographical lens. The paper begins with an exploration of Laing’s time at the Tavistock Clinic in London during the 1960s, and of the co-authored text with Aaron Esterson entitled, Sanity, Madness and the Family (1964). The study then seeks to demonstrate the importance Laing and his colleague placed on the time-space situatedness of patients and their worlds. Finally, an account is provided of Laing’s and Esterson’s spatial thinking in relation to their creation of both real and imagined spaces of therapeutic care. PMID:25114145

76 FR 19724 - Airworthiness Directives; Airbus Model A300 B4-600, B4-600R, and F4-600R Series Airplanes, and...

Federal Register 2010, 2011, 2012, 2013, 2014

2011-04-08

... B4-600, B4-600R, and F4-600R Series Airplanes, and Model C4-605R Variant F Airplanes (Collectively... F4-605R and F4-622R airplanes, and Model A300 C4-605R Variant F airplanes; and Model A310-203, -204...

Alanine and glycine conjugates of (2S,4R)-4-[18F]fluoroglutamine for tumor imaging.

PubMed

Zha, Zhihao; Ploessl, Karl; Lieberman, Brian P; Wang, Limin; Kung, Hank F

2018-05-01

Glutamine is an essential source of energy, metabolic substrates, and building block for supporting tumor proliferation. Previously, (2S,4R)-4-[ 18 F]fluoroglutamine (4F-Gln) was reported as a glutamine-related metabolic imaging agent. To improve the in vivo kinetics of this radiotracer, two new dipeptides, [ 18 F]Gly-(2S,4R)4-fluoroglutamine (Gly-4F-Gln) and [ 18 F]Ala-(2S,4R)4-fluoroglutamine (Ala-4F-Gln) were investigated. Radiolabeling was performed via 2-steps 18 F-fluorination. Cell uptake studies of Gly-4F-Gln and Ala-4F-Gln were investigated in 9 L cell lines. In vitro and in vivo metabolism studies were carried out in Fisher 344 rats. Biodistribution and microPET imaging studies were performed in 9 L tumor-bearing rats. In vitro incubation of these [ 18 F]dipeptides in rat and human blood showed a rapid conversion to (2S,4R)-4-[ 18 F]fluoroglutamine (t 1/2  = 2.3 and 0.2 min for [ 18 F]Gly-4F-Gln and [ 18 F]Ala-4F-Gln, respectively for human blood). Biodistribution and PET imaging in Fisher 344 rats bearing 9 L tumor xenografts showed that these dipeptides rapidly localized in the tumors, comparable to that of (2S,4R)-4-[ 18 F]fluoroglutamine (4F-Gln). The results support that these dipeptides, [ 18 F]Gly-4F-Gln and [ 18 F]Ala-4F-Gln, are prodrugs, which hydrolyze in the blood after an iv injection. They appear to be selectively taken up and trapped by tumor tissue in vivo. The dipeptide, [ 18 F]Ala-4F-Gln, may be suitable as a PET tracer for imaging glutaminolysis in tumors. Copyright © 2018 Elsevier Inc. All rights reserved.

Investigation of undersampling and reconstruction algorithm dependence on respiratory correlated 4D-MRI for online MR-guided radiation therapy

NASA Astrophysics Data System (ADS)

Mickevicius, Nikolai J.; Paulson, Eric S.

2017-04-01

The purpose of this work is to investigate the effects of undersampling and reconstruction algorithm on the total processing time and image quality of respiratory phase-resolved 4D MRI data. Specifically, the goal is to obtain quality 4D-MRI data with a combined acquisition and reconstruction time of five minutes or less, which we reasoned would be satisfactory for pre-treatment 4D-MRI in online MRI-gRT. A 3D stack-of-stars, self-navigated, 4D-MRI acquisition was used to scan three healthy volunteers at three image resolutions and two scan durations. The NUFFT, CG-SENSE, SPIRiT, and XD-GRASP reconstruction algorithms were used to reconstruct each dataset on a high performance reconstruction computer. The overall image quality, reconstruction time, artifact prevalence, and motion estimates were compared. The CG-SENSE and XD-GRASP reconstructions provided superior image quality over the other algorithms. The combination of a 3D SoS sequence and parallelized reconstruction algorithms using computing hardware more advanced than those typically seen on product MRI scanners, can result in acquisition and reconstruction of high quality respiratory correlated 4D-MRI images in less than five minutes.

Modulation of physiological responses with TiO2 nano-particle in Azolla pinnata R.Br. under 2,4-D toxicity.

PubMed

De, Arnab Kumar; Ghosh, Arijit; Debnath, Subhas Chandra; Sarkar, Bipul; Saha, Indraneel; Adak, Malay Kumar

2018-06-05

The present work is emphasised with the herbicidal tolerance of Azolla pinnata R.Br. and its modulation with TiO 2 nano-particle. Both carbohydrate and nitrogen metabolism were effected with 2,4-D as herbicide and in few cases TiO 2 -NP had recovered few detrimental effects. From the nutrient status in Azolla it recorded the recovery of nitrogen as well as potassium by TiO 2 -NP but not in case of phosphorus. However, a conversion of nitrate to ammonium was more induced by TiO 2 -NP under herbicidal toxicity. Similar results were obtained for inter-conversion of amino acid-nitrate pool, but no changes with glutamine synthase activity with TiO 2 -NP. Initially, the effects of 2,4-D was monitored with changes of chlorophyll content but had not been recovered with nanoparticle. Photosynthetic reserves expressed as both total and reducing sugar were insensitive to TiO 2 -NP interference but activity of soluble and wall bound invertase was in reverse trend as compared to control. The 2,4-D mediated changes of redox and its oxidative stress was ameliorated in plants with over expressed ADH activity. As a whole the Azolla bio system with TiO 2 supplementation may be useful in sustenance against 2,4-D toxicity through recovery of nitrogen metabolism. Thus, Azolla-TiO 2 -NP bio system would be realised to monitor the herbicidal toxicity in soil and its possible bioremediation.

Minimal Unified Resolution to R_{K^{(*)}} and R(D^{(*)}) Anomalies with Lepton Mixing.

PubMed

Choudhury, Debajyoti; Kundu, Anirban; Mandal, Rusa; Sinha, Rahul

2017-10-13

It is a challenging task to explain, in terms of a simple and compelling new physics scenario, the intriguing discrepancies between the standard model expectations and the data for the neutral-current observables R_{K} and R_{K^{*}}, as well as the charged-current observables R(D) and R(D^{*}). We show that this can be achieved in an effective theory with only two unknown parameters. In addition, this class of models predicts some interesting signatures in the context of both B decays as well as high-energy collisions.

Federal R&D Funding by Budget Function. Fiscal Years 1983-85.

ERIC Educational Resources Information Center

National Science Foundation, Washington, DC. Div. of Science Resources Studies.

This report provides a distribution of research and development (R&D) programs by the functions of the federal budget. It includes only federal conduct of R&D programs, with R&D plant and all non-R&D activities excluded. The sections of the report are presented in descending order of R&D budget authority for the various…

Office of Operations R&D

DOT National Transportation Integrated Search

2013-04-30

The Office of Operations Research and Development (R&D) produces technology and tools to improve transportation system productivity, efficiency, and performance by proactively anticipating congestion and managing traffic.

The mGlu(2/3) agonist 2R,4R-4-aminopyrrolidine-2,4-dicarboxylate, is anti- and proconvulsant in DBA/2 mice.

PubMed

Moldrich, R X; Talebi, A; Beart, P M; Chapman, A G; Meldrum, B S

2001-02-16

The anticonvulsant activity of the selective group II metabotropic glutamate receptor (mGlu) agonist 2R,4R-4-aminopyrrolidine-2,4-dicarboxylate (2R,4R-APDC) has been evaluated in chemoconvulsant and sound-induced models of epileptic seizures in DBA/2 mice. 2R,4R-APDC (> or =10 nmol, intracerebroventricularly (i.c.v.), -15 min) transiently reduced sound-induced seizure activity including clonic seizures to 40% of vehicle at 20 nmol (i.c.v.) and 30% of vehicle at 100 mg/kg (intraperitoneally (i.p.), -15 min). 2R,4R-APDC inhibited clonic seizures induced by the group III mGlu antagonist (R,S)-alpha-methylserine-O-phosphate (2.5 micromol, i.c.v.) when co-injected at 20-40 nmol and inhibited limbic seizure activity induced by the mGlu(1/5) agonist (R,S)-3,5-dihydroxyphenylglycine (1.5 micromol, i.c.v.) when co-injected at 10-40 nmol. A reversal of the anticonvulsant activity of 2R,4R-APDC was observed at (>20 nmol) in each of the chemoconvulsant and sound-induced models of epileptic seizures. 2R,4R-APDC (0.1-1 micromol, i.c.v.) induced stimulus-independent, rapid and dose-dependent clonic seizures. Selective mGlu(2/3) agonists represent a novel class of potential anti-epileptic drugs, however due to the proconvulsant activity observed here, 2R,4R-APDC is obviously limited in this regard.

CERN openlab: Engaging industry for innovation in the LHC Run 3-4 R&D programme

NASA Astrophysics Data System (ADS)

Girone, M.; Purcell, A.; Di Meglio, A.; Rademakers, F.; Gunne, K.; Pachou, M.; Pavlou, S.

2017-10-01

LHC Run3 and Run4 represent an unprecedented challenge for HEP computing in terms of both data volume and complexity. New approaches are needed for how data is collected and filtered, processed, moved, stored and analysed if these challenges are to be met with a realistic budget. To develop innovative techniques we are fostering relationships with industry leaders. CERN openlab is a unique resource for public-private partnership between CERN and leading Information Communication and Technology (ICT) companies. Its mission is to accelerate the development of cutting-edge solutions to be used by the worldwide HEP community. In 2015, CERN openlab started its phase V with a strong focus on tackling the upcoming LHC challenges. Several R&D programs are ongoing in the areas of data acquisition, networks and connectivity, data storage architectures, computing provisioning, computing platforms and code optimisation and data analytics. This paper gives an overview of the various innovative technologies that are currently being explored by CERN openlab V and discusses the long-term strategies that are pursued by the LHC communities with the help of industry in closing the technological gap in processing and storage needs expected in Run3 and Run4.

Synthesis and biological characterization of (3R,4R)-4-(2-(benzhydryloxy)ethyl)-1-((R)-2-hydroxy-2-phenylethyl)-piperidin-3-ol and its stereoisomers for activity toward monoamine transporters.

PubMed

Kharkar, Prashant S; Batman, Angela M; Zhen, Juan; Beardsley, Patrick M; Reith, Maarten E A; Dutta, Aloke K

2009-07-01

A novel series of optically active molecules based on a 4-(2-(benzhydryloxy)ethyl)-1-((R)-2-hydroxy-2-phenylethyl)-piperidin-3-ol template were developed. Depending on stereochemistry, the compounds exhibit various degrees of affinity for three dopamine, serotonin, and norepinephrine transporters. These molecules have the potential for treating several neurological disorders such as drug abuse, depression, and attention deficit hyperactivity disorder.Herein we describe the synthesis and biological evaluation of a series of asymmetric 4-(2-(benzhydryloxy)ethyl)-1-((R)-2-hydroxy-2-phenylethyl)-piperidin-3-ol-based dihydroxy compounds in which the hydroxy groups are located on both the piperidine ring and the N-phenylethyl side chain. In vitro uptake inhibition data of these molecules indicate high affinity for the dopamine transporter (DAT) in addition to moderate to high affinity for the norepinephrine transporter (NET). Interestingly, compounds 9 b and 9 d exhibit affinities for all three monoamine transporters, with highest potency at DAT and NET, and moderate potency at the serotonin transporter (SERT) (K(i): 2.29, 78.4, and 155 nM for 9 b and 1.55, 14.1, and 259 nM for 9 d, respectively). Selected compounds 9 a, 9 d, and 9 d' were tested for their locomotor activity effects in mice and for their ability to occasion the cocaine-discriminative stimulus in rats. These test compounds generally exhibit a much longer duration of action than cocaine for elevating locomotor activity, and completely generalize the cocaine-discriminative stimulus in a dose-dependent manner.

Distorting general relativity: gravity's rainbow and f(R) theories at work

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

Garattini, Remo, E-mail: Remo.Garattini@unibg.it

2013-06-01

We compute the Zero Point Energy in a spherically symmetric background combining the high energy distortion of Gravity's Rainbow with the modification induced by a f(R) theory. Here f(R) is a generic analytic function of the Ricci curvature scalar R in 4D and in 3D. The explicit calculation is performed for a Schwarzschild metric. Due to the spherically symmetric property of the Schwarzschild metric we can compare the effects of the modification induced by a f(R) theory in 4D and in 3D. We find that the final effect of the combined theory is to have finite quantities that shift themore » Zero Point Energy. In this context we setup a Sturm-Liouville problem with the cosmological constant considered as the associated eigenvalue. The eigenvalue equation is a reformulation of the Wheeler-DeWitt equation which is analyzed by means of a variational approach based on gaussian trial functionals. With the help of a canonical decomposition, we find that the relevant contribution to one loop is given by the graviton quantum fluctuations around the given background. A final discussion on the connection of our result with the observed cosmological constant is also reported.« less

FY2013 Energy Storage R&D Progress Report

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

none,

2014-02-01

The FY 2013 Progress Report for Energy Storage R&D focuses on advancing the development of batteries to enable a large market penetration of hybrid and electric vehicles. Program targets focus on overcoming technical barriers to enable market success including: (1) significantly reducing battery cost, (2) increasing battery performance (power, energy, durability), (3) reducing battery weight & volume, and (4) increasing battery tolerance to abusive conditions such as short circuit, overcharge, and crush.

Occlusion veineuse rétinienne et syndrome d'hyperviscosité

PubMed Central

Younes, Samar; Abdellaoui, Meriem; Zahir, Fadoua; Benatiya, Idriss A; Tahri, Hicham

2015-01-01

Les occlusions veineuses rétiniennes secondaires aux syndromes d'hyperviscosité sont rares. Plusieurs cas d'occlusion de la veine centrale de la rétine [OVCR] compliquant une hémopathie ont été décrits, principalement au cours des polycythémies primitives ou secondaires, des lymphomes ou des leucémies. A travers cette observation, nous rapportons le cas d'un patient qui présente une OVCR de l’œil droit survenant dans le cadre d'un myélome multiple. La rétinopathie du syndrome d'hyperviscosité est liée au ralentissement circulatoire qui affecte de manière prépondérante le secteur veineux et donne un aspect de rétinopathie de stase bilatérale, avec dilatation et tortuosité de l'ensemble des veines rétiniennes. A un certain degré d'hyperviscosité, une occlusion veineuse véritable peut survenir. Le traitement comprend la réhydratation, phlébotomie, et plasmaphérèse. PMID:25995806

Design of a Personnel and Training Information System for Educational R&D Personnel. The Domain of R&D Training Resources.

ERIC Educational Resources Information Center

Hood, Paul D.

This document reports an attempt to examine the content and structure of the domain of research and development (R&D) training resources. The project began by locating instructional materials within a larger matrix that classified R&D resources by structure (primary/secondary, oral/written, documentary/non-document) and level of formalization…

NREL Research Teams Win Three R&D 100 Awards

Science.gov Websites

Research Teams Win Three R&D 100 Awards Golden, Colo., Oct. 4, 2001 - Since 1982, the U.S research teams have brought that total number of awards to 31. The 2001 awards are for a solar cell that method involves applying a current to the battery for five seconds to overcharge the battery slightly

Technological Innovation, Corporate R&D Alliances and Organizational Learning

DTIC Science & Technology

1995-01-01

public corporations . On the other hand, the questionnaire response bias was a potential problem. As explained in Section 4, the size and innovativeness...DISSERTATION RAND. " " .,’ Technological Innovation, Corporate R&D Alliances and Organizational Learning Wayne G. Walker RAND Graduate School... response , including the time for reviewing instructions, searching existing data sources, gathering and maintaining the data needed, and completing

Absolute structure and structure-function relationships of 4R,2‧R and 4S,2‧S Pidotimod®

NASA Astrophysics Data System (ADS)

Sarno, Simone; Manzo, Angelo M.; Ferraris, Davide M.; Miggiano, Riccardo; Rizzi, Menico; Palin, Luca; Boccaleri, Enrico; Milanesio, Marco

2017-11-01

Pidotimod® is a dipeptide with widely recognized immunomodulatory properties and with particularly beneficial effects for the treatment of acute respiratory and urinary tract infections. Pidotimod® presents two chiral centres which originate four stereoisomers. (4R,2‧S, 4S,2‧R, 4R,2‧R and 4S,2‧S). To date, only the 4R,2‧S and 4S,2‧R stereoisomers are reported in the literature. We report here the absolute crystal structure of the 4R,2‧R and 4S,2‧S diastereoisomers of Pidotimod®, obtained by crystals grown by slow evaporation of a mixture of water and ethanol. The analysis of the crystal structures revealed the key role of a solvent water molecule in the crystal packing engaged in an extended hydrogen bonds network. This water-assisted H-bond network explained the recalcitrance of 4R,2‧R and 4S,2‧S Pidotimod® to crystallize in pure ethanol, despite their high solubility, and the growth of well-diffracting crystals only in presence of water. Hence, Pidotimod®4R,2‧R and 4S,2‧S stereoisomers markedly differ from the 4R,2‧S and 4S,2‧R ones, which crystallize in absence of water. The molecular and crystal structures of the 4R,2‧R and 4S,2‧S Pidotimod® stereoisomers here presented gave some hints on the differences in bioactivity with respect to the 4R,2‧S stereoisomer. In fact, beyond an expected different dispositions of hydrophilic ligands, 4R,2‧R and 4S,2‧S showed an incremented tendency to intermolecular H-bonds with water.

The D1 family dopamine receptor, DopR, potentiates hind leg grooming behavior in Drosophila.

PubMed

Pitmon, E; Stephens, G; Parkhurst, S J; Wolf, F W; Kehne, G; Taylor, M; Lebestky, T

2016-03-01

Drosophila groom away debris and pathogens from the body using their legs in a stereotyped sequence of innate motor behaviors. Here, we investigated one aspect of the grooming repertoire by characterizing the D1 family dopamine receptor, DopR. Removal of DopR results in decreased hind leg grooming, as substantiated by quantitation of dye remaining on mutant and RNAi animals vs. controls and direct scoring of behavioral events. These data are also supported by pharmacological results that D1 receptor agonists fail to potentiate grooming behaviors in headless DopR flies. DopR protein is broadly expressed in the neuropil of the thoracic ganglion and overlaps with TH-positive dopaminergic neurons. Broad neuronal expression of dopamine receptor in mutant animals restored normal grooming behaviors. These data provide evidence for the role of DopR in potentiating hind leg grooming behaviors in the thoracic ganglion of adult Drosophila. This is a remarkable juxtaposition to the considerable role of D1 family dopamine receptors in rodent grooming, and future investigations of evolutionary relationships of circuitry may be warranted. © 2016 The Authors. Genes, Brain and Behavior published by International Behavioural and Neural Genetics Society and John Wiley & Sons Ltd.

Identification of rice Os4BGlu13 as a β-glucosidase which hydrolyzes gibberellin A4 1-O-β-d-glucosyl ester, in addition to tuberonic acid glucoside and salicylic acid derivative glucosides.

PubMed

Hua, Yanling; Ekkhara, Watsamon; Sansenya, Sompong; Srisomsap, Chantragan; Roytrakul, Sittiruk; Saburi, Wataru; Takeda, Ryosuke; Matsuura, Hideyuki; Mori, Haruhide; Ketudat Cairns, James R

2015-10-01

Gibberellin 1-O-β-d-glucose ester hydrolysis activity has been detected in rice seedling extracts, but no enzyme responsible for this activity has ever been purified and identified. Therefore, gibberellin A4 glucosyl ester (GA4-GE) β-d-glucosidase activity was purified from ten-day rice seedling stems and leaves. The family 1 glycoside hydrolase Os4BGlu13 was identified in the final purification fraction. The Os4BGlu13 cDNA was amplified from rice seedlings and expressed as an N-terminal thioredoxin-tagged fusion protein in Escherichia coli. The purified recombinant Os4BGlu13 protein (rOs4BGlu13) had an optimum pH of 4.5, for hydrolysis of p-nitrophenyl β-d-glucopyranoside (pNPGlc), which was the best substrate identified, with a kcat/Km of 637 mM(-1) s(-1). rOs4BGlu13 hydrolyzed helicin best among natural glycosides tested (kcat/Km of 74.4 mM(-1) s(-1)). Os4BGlu13 was previously designated tuberonic acid glucoside (TAG) β-glucosidase (TAGG), and here the kcat/Km of rOsBGlu13 for TAG was 6.68 mM(-1) s(-1), while that for GA4-GE was 3.63 mM(-1) s(-1) and for salicylic acid glucoside (SAG) is 0.88 mM(-1) s(-1). rOs4BGlu13 also hydrolyzed oligosaccharides, with preference for short β-(1 → 3)-linked over β-(1 → 4)-linked glucooligosaccharides. The enzymatic data suggests that Os4BGlu13 may contribute to TAG, SAG, oligosaccharide and GA4-GE hydrolysis in the rice plant, although helicin or a similar compound may be its primary target. Copyright © 2015 Elsevier Inc. All rights reserved.

Summary of findings of the R&D committee

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

Kenley, C.R.; Kokenge, B.R.

1996-05-01

In March 1995, the Department of Energy`s (DOE) Nuclear Materials Stabilization Task Group (NMST) chartered a committee to formulate a research and development (R&D) plan in response to Sub-recommendation (2) of Defense Nuclear Facilities Safety Board (DNFSB) Recommendation 94-1. The NMSTG was established as an organizational unit operating under the auspices of the DOE Office of the Environmental Management. As a result of its efforts, the Research Committee concluded that, in general, the technology needs for stabilizing 94-1 nuclear materials are being adequately met by existing or planned DOE programs. At the same time, the committee, in the form ofmore » recommendations, noted specific R&D program areas that should be addressed by the NMSTG. These recommendations are documented in the R&D plan and formulated based on: (1) existing {open_quotes}gaps{close_quotes} in DOE`s R&D stabilization program, (2) the relative maturity of various technologies, and (3) other important R&D program issues that, in the judgement of the committee, should be addressed by the NMSTG. A systems engineering approach, derived form the aerospace industry, was applied to the various stabilization technologies to assess their relative maturity and availability for use in treating 94-1 nuclear materials.« less

MiR-144 Increases Intestinal Permeability in IBS-D Rats by Targeting OCLN and ZO1.

PubMed

Hou, Qiuke; Huang, Yongquan; Zhu, Shuilian; Li, Peiwu; Chen, Xinlin; Hou, Zhengkun; Liu, Fengbin

2017-01-01

Irritable bowel syndrome with diarrhoea (IBS-D) is a chronic, functional bowel disorder characterized by abdominal pain or diarrhoea and altered bowel habits, which correlate with intestinal hyperpermeability. MicroRNAs (miRNAs) are involved in regulating intestinal permeability in IBS-D. However, the role of miRNAs in regulating intestinal permeability and protecting the epithelial barrier remains unclear. Our goals were to (i) identify differential expression of miRNAs and their targets in the distal colon of IBS-D rats; (ii) verify in vitro whether occludin (OCLN) and zonula occludens 1 (ZO1/TJP1) were direct targets of miR-144 and were down-regulated in IBS-D rats; and (iii) determine whether down-regulation of miR-144 in vitro could reverse the pathological hallmarks of intestinal hyperpermeability via targeting OCLN and ZO1. The IBS-D rat model was established using 4% acetic acid and evaluated by haematoxylin-eosin (HE) staining. The distal colon was obtained in order to perform miRNA microarray analysis and to isolate and culture colonic epithelial cells. When differential expression of miRNA was found, the results were verified by qRT-PCR, and the target genes were further explored by bioinformatics analysis. Correlation analyses were carried out to compare the expression of miRNA and target genes. Then, mutants, miRNA mimics and inhibitors of the target genes were constructed and transfected to colonic epithelial cells. qRT-PCR, western blotting, enzyme-linked immunosorbent assays (ELISAs) and dual-luciferase assays were used to investigate the expression of miR-144 and OCLN, ZO1 in IBS-D rats. There were 8 up-regulated and 18 down-regulated miRNAs identified in the IBS-D rat model. Of these, miR-144 was markedly up-regulated and resulted in the down-regulation of OCLN and ZO1 expression. Overexpression of miR-144 by transfection of miR-144 precursor markedly inhibited the expression of OCLN and ZO1. Further studies confirmed that OCLN and ZO1 were direct

4D flow mri post-processing strategies for neuropathologies

NASA Astrophysics Data System (ADS)

Schrauben, Eric Mathew

4D flow MRI allows for the measurement of a dynamic 3D velocity vector field. Blood flow velocities in large vascular territories can be qualitatively visualized with the added benefit of quantitative probing. Within cranial pathologies theorized to have vascular-based contributions or effects, 4D flow MRI provides a unique platform for comprehensive assessment of hemodynamic parameters. Targeted blood flow derived measurements, such as flow rate, pulsatility, retrograde flow, or wall shear stress may provide insight into the onset or characterization of more complex neuropathologies. Therefore, the thorough assessment of each parameter within the context of a given disease has important medical implications. Not surprisingly, the last decade has seen rapid growth in the use of 4D flow MRI. Data acquisition sequences are available to researchers on all major scanner platforms. However, the use has been limited mostly to small research trials. One major reason that has hindered the more widespread use and application in larger clinical trials is the complexity of the post-processing tasks and the lack of adequate tools for these tasks. Post-processing of 4D flow MRI must be semi-automated, fast, user-independent, robust, and reliably consistent for use in a clinical setting, within large patient studies, or across a multicenter trial. Development of proper post-processing methods coupled with systematic investigation in normal and patient populations pushes 4D flow MRI closer to clinical realization while elucidating potential underlying neuropathological origins. Within this framework, the work in this thesis assesses venous flow reproducibility and internal consistency in a healthy population. A preliminary analysis of venous flow parameters in healthy controls and multiple sclerosis patients is performed in a large study employing 4D flow MRI. These studies are performed in the context of the chronic cerebrospinal venous insufficiency hypothesis. Additionally, a

Developing R&D portfolio business validity simulation model and system.

PubMed

Yeo, Hyun Jin; Im, Kwang Hyuk

2015-01-01

The R&D has been recognized as critical method to take competitiveness by not only companies but also nations with its value creation such as patent value and new product. Therefore, R&D has been a decision maker's burden in that it is hard to decide how much money to invest, how long time one should spend, and what technology to develop which means it accompanies resources such as budget, time, and manpower. Although there are diverse researches about R&D evaluation, business factors are not concerned enough because almost all previous studies are technology oriented evaluation with one R&D technology based. In that, we early proposed R&D business aspect evaluation model which consists of nine business model components. In this research, we develop a simulation model and system evaluating a company or industry's R&D portfolio with business model point of view and clarify default and control parameters to facilitate evaluator's business validity work in each evaluation module by integrate to one screen.

Integrative knowledge management to enhance pharmaceutical R&D.

PubMed

Marti-Solano, Maria; Birney, Ewan; Bril, Antoine; Della Pasqua, Oscar; Kitano, Hiroaki; Mons, Barend; Xenarios, Ioannis; Sanz, Ferran

2014-04-01

Information technologies already have a key role in pharmaceutical research and development (R&D), but achieving substantial advances in their use and effectiveness will depend on overcoming current challenges in sharing, integrating and jointly analysing the range of data generated at different stages of the R&D process.

Search for r-parity violating supersymmetry in multilepton final states with the D0 detector

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

Kaefer, Daniela

Results obtained from a search for the trilepton signature μμℓ (with ℓ = e, or μ) are combined with two complementary searches for the trilepton signatures eeℓ and eer and interpreted in the framework of R-parity violating Supersymmetry. Pairwise, R-parity conserving production of the supersymmetric particles is assumed, followed by R-parity violating decays via an LLmore » $$\\bar{E}$$-operator with one dominant coupling λ 122. An LL$$\\bar{E}$$-operator couples two weak isospin doublet and one singlet (s)lepton fields and thus violates lepton number conservation. The data, collected with the D0 detector at the Fermilab proton-antiproton collider Tevatron, corresponds to an integrated luminosity of ∫ L dt = 360 ± 23 pb -1. No evident is observed, while 0.41 ± 0.11(stat) ± 0.07(sys) events are expected from Standard Model processes. The resulting 95% confidence level cross section limits on new physics producing a μμℓ signature in the detector are of the order of 0.020 to 0.136 pb. They are interpreted in two different supersymmetry scenarios: the mSUGRA and the MSSM model. The corresponding lower limits on the masses of the lightest neutralino ($$\\tilde{X}$$$0\\atop{1}$$) and the lightest chargino ($$\\tilde{X}$$$±\\atop{1}$$ in case of the mSUGRA model are found to be in the range of: mSUGRA, μ > 0: M($$\\tilde{X}$$$0\\atop{1}$$) ~> 115-128 GeV and M($$\\tilde{X}$$$±\\atop{1}$$) ~> 215-241 GeV; mSUGRA, μ < 0: ($$\\tilde{X}$$$0\\atop{1}$$) ~> 101-114 GeV and M($$\\tilde{X}$$$±\\atop{1}$$) ~> 194-230 GeV, depending on the actual values of the model parameters: m 0, m 1/2, A 0, tanβ, and μ. The first and second parameters provide the boundary conditions for the masses of the supersymmetric spin-0 and spin-1/2 particles, respectively, while A 0 gives the universal value for the trilinear couplings at the GUT scale. The parameter tan β denotes the ratio of the vacuum expectation values of the two Higgs fields and μ, finally, represents

Inhibition of AMP Kinase by the Protein Phosphatase 2A Heterotrimer, PP2APpp2r2d*

PubMed Central

Joseph, Biny K.; Liu, Hsing-Yin; Francisco, Jamie; Pandya, Devanshi; Donigan, Melissa; Gallo-Ebert, Christina; Giordano, Caroline; Bata, Adam; Nickels, Joseph T.

2015-01-01

AMP kinase is a heterotrimeric serine/threonine protein kinase that regulates a number of metabolic processes, including lipid biosynthesis and metabolism. AMP kinase activity is regulated by phosphorylation, and the kinases involved have been uncovered. The particular phosphatases counteracting these kinases remain elusive. Here we discovered that the protein phosphatase 2A heterotrimer, PP2APpp2r2d, regulates the phosphorylation state of AMP kinase by dephosphorylating Thr-172, a residue that activates kinase activity when phosphorylated. Co-immunoprecipitation and co-localization studies indicated that PP2APpp2r2d directly interacted with AMP kinase. PP2APpp2r2d dephosphorylated Thr-172 in rat aortic and human vascular smooth muscle cells. A positive correlation existed between decreased phosphorylation, decreased acetyl-CoA carboxylase Acc1 phosphorylation, and sterol response element-binding protein 1c-dependent gene expression. PP2APpp2r2d protein expression was up-regulated in the aortas of mice fed a high fat diet, and the increased expression correlated with increased blood lipid levels. Finally, we found that the aortas of mice fed a high fat diet had decreased AMP kinase Thr-172 phosphorylation, and contained an Ampk-PP2APpp2r2d complex. Thus, PP2APpp2r2d may antagonize the aortic AMP kinase activity necessary for maintaining normal aortic lipid metabolism. Inhibiting PP2APpp2r2d or activating AMP kinase represents a potential pharmacological treatment for many lipid-related diseases. PMID:25694423

High-Resolution FTIR Spectrum of the ν 9 Band of Ethylene- D4 (C 2D 4)

NASA Astrophysics Data System (ADS)

Tan, T. L.; Goh, K. L.; Ong, P. P.; Teo, H. H.

2000-08-01

The spectrum of the ν9 fundamental band of ethylene-d4 (C2D4) has been measured with an unapodized resolution of 0.004 cm-1 in the frequency range of 2300-2400 cm-1 using a Fourier transform infrared spectrometer. A total of 549 transitions have been assigned and fitted using a Watson's A-reduced Hamiltonian in the Ir representation to derive rovibrational constants for the upper state (v9 = 1) up to five quartic terms with a standard deviation of 0.00087 cm-1. They represent the most accurate rovibrational constants for the ν9 band so far. About 30 transitions of Ka‧ = 0, one transition of ν9 which were identified to be perturbed possibly by the nearby ν11 and ν2 + ν12 transitions, were not included in the final fit. The ν9 band of C2D4 was found to be basically B-type with an unperturbed band center at 2341.836 94 ± 0.000 13 cm-1.

Risk taking and effective R&D management.

PubMed

Banholzer, William F; Vosejpka, Laura J

2011-01-01

Several key strategies can be used to manage the risk associated with innovation to create maximum value. These include balancing the timing of investments versus cash flows, management of fads, prioritization across the company, savvy portfolio management, and a system of metrics that measure real success. Successful R&D managers will do whatever is necessary to manage the risks associated with an R&D program and stick to their long-term strategy.

A Gene Cluster for Biosynthesis of Mannosylerythritol Lipids Consisted of 4-O-β-D-Mannopyranosyl-(2R,3S)-Erythritol as the Sugar Moiety in a Basidiomycetous Yeast Pseudozyma tsukubaensis

PubMed Central

Saika, Azusa; Koike, Hideaki; Fukuoka, Tokuma; Yamamoto, Shuhei; Kishimoto, Takahide; Morita, Tomotake

2016-01-01

Mannosylerythritol lipids (MELs) belong to the glycolipid biosurfactants and are produced by various fungi. The basidiomycetous yeast Pseudozyma tsukubaensis produces diastereomer type of MEL-B, which contains 4-O-β-D-mannopyranosyl-(2R,3S)-erythritol (R-form) as the sugar moiety. In this respect it differs from conventional type of MELs, which contain 4-O-β-D-mannopyranosyl-(2S,3R)-erythritol (S-form) as the sugar moiety. While the biosynthetic gene cluster for conventional type of MELs has been previously identified in Ustilago maydis and Pseudozyma antarctica, the genetic basis for MEL biosynthesis in P. tsukubaensis is unknown. Here, we identified a gene cluster involved in MEL biosynthesis in P. tsukubaensis. Among these genes, PtEMT1, which encodes erythritol/mannose transferase, had greater than 69% identity with homologs from strains in the genera Ustilago, Melanopsichium, Sporisorium and Pseudozyma. However, phylogenetic analysis placed PtEMT1p in a separate clade from the other proteins. To investigate the function of PtEMT1, we introduced the gene into a P. antarctica mutant strain, ΔPaEMT1, which lacks MEL biosynthesis ability owing to the deletion of PaEMT1. Using NMR spectroscopy, we identified the biosynthetic product as MEL-A with altered sugar conformation. These results indicate that PtEMT1p catalyzes the sugar conformation of MELs. This is the first report of a gene cluster for the biosynthesis of diastereomer type of MEL. PMID:27327162

Searches for R -parity-violating supersymmetry in p p collisions at √{s }=8 TeV in final states with 0-4 leptons

NASA Astrophysics Data System (ADS)

Khachatryan, V.; Sirunyan, A. M.; Tumasyan, A.; Adam, W.; Asilar, E.; Bergauer, T.; Brandstetter, J.; Brondolin, E.; Dragicevic, M.; Erö, J.; Flechl, M.; Friedl, M.; Frühwirth, R.; Ghete, V. M.; Hartl, C.; Hörmann, N.; Hrubec, J.; Jeitler, M.; König, A.; Krammer, M.; Krätschmer, I.; Liko, D.; Matsushita, T.; Mikulec, I.; Rabady, D.; Rad, N.; Rahbaran, B.; Rohringer, H.; Schieck, J.; Strauss, J.; Treberer-Treberspurg, W.; Waltenberger, W.; Wulz, C.-E.; Mossolov, V.; Shumeiko, N.; Suarez Gonzalez, J.; Alderweireldt, S.; Cornelis, T.; De Wolf, E. A.; Janssen, X.; Knutsson, A.; Lauwers, J.; Luyckx, S.; Van De Klundert, M.; Van Haevermaet, H.; Van Mechelen, P.; Van Remortel, N.; Van Spilbeeck, A.; Abu Zeid, S.; Blekman, F.; D'Hondt, J.; Daci, N.; De Bruyn, I.; Deroover, K.; Heracleous, N.; Keaveney, J.; Lowette, S.; Moortgat, S.; Moreels, L.; Olbrechts, A.; Python, Q.; Strom, D.; Tavernier, S.; Van Doninck, W.; Van Mulders, P.; Van Parijs, I.; Brun, H.; Caillol, C.; Clerbaux, B.; De Lentdecker, G.; Fasanella, G.; Favart, L.; Goldouzian, R.; Grebenyuk, A.; Karapostoli, G.; Lenzi, T.; Léonard, A.; Maerschalk, T.; Marinov, A.; Randle-conde, A.; Seva, T.; Vander Velde, C.; Vanlaer, P.; Yonamine, R.; Zenoni, F.; Zhang, F.; Benucci, L.; Cimmino, A.; Crucy, S.; Dobur, D.; Fagot, A.; Garcia, G.; Gul, M.; Mccartin, J.; Ocampo Rios, A. A.; Poyraz, D.; Ryckbosch, D.; Salva, S.; Schöfbeck, R.; Sigamani, M.; Tytgat, M.; Van Driessche, W.; Yazgan, E.; Zaganidis, N.; Beluffi, C.; Bondu, O.; Brochet, S.; Bruno, G.; Caudron, A.; Ceard, L.; De Visscher, S.; Delaere, C.; Delcourt, M.; Forthomme, L.; Francois, B.; Giammanco, A.; Jafari, A.; Jez, P.; Komm, M.; Lemaitre, V.; Magitteri, A.; Mertens, A.; Musich, M.; Nuttens, C.; Piotrzkowski, K.; Quertenmont, L.; Selvaggi, M.; Vidal Marono, M.; Wertz, S.; Beliy, N.; Hammad, G. H.; Aldá Júnior, W. L.; Alves, F. L.; Alves, G. A.; Brito, L.; Correa Martins Junior, M.; Hamer, M.; Hensel, C.; Moraes, A.; Pol, M. E.; Rebello Teles, P.; Belchior Batista Das Chagas, E.; Carvalho, W.; Chinellato, J.; Custódio, A.; Da Costa, E. M.; De Jesus Damiao, D.; De Oliveira Martins, C.; Fonseca De Souza, S.; Huertas Guativa, L. M.; Malbouisson, H.; Matos Figueiredo, D.; Mora Herrera, C.; Mundim, L.; Nogima, H.; Prado Da Silva, W. L.; Santoro, A.; Sznajder, A.; Tonelli Manganote, E. J.; Vilela Pereira, A.; Ahuja, S.; Bernardes, C. A.; De Souza Santos, A.; Dogra, S.; Fernandez Perez Tomei, T. R.; Gregores, E. M.; Mercadante, P. G.; Moon, C. S.; Novaes, S. F.; Fernandez Perez Padula, Sandra S.; Romero Abad, D.; Ruiz Vargas, J. C.; Aleksandrov, A.; Hadjiiska, R.; Iaydjiev, P.; Rodozov, M.; Stoykova, S.; Sultanov, G.; Vutova, M.; Dimitrov, A.; Glushkov, I.; Litov, L.; Pavlov, B.; Petkov, P.; Fang, W.; Ahmad, M.; Bian, J. G.; Chen, G. M.; Chen, H. S.; Chen, M.; Cheng, T.; Du, R.; Jiang, C. H.; Leggat, D.; Plestina, R.; Romeo, F.; Shaheen, S. M.; Spiezia, A.; Tao, J.; Wang, C.; Wang, Z.; Zhang, H.; Asawatangtrakuldee, C.; Ban, Y.; Li, Q.; Liu, S.; Mao, Y.; Qian, S. J.; Wang, D.; Xu, Z.; Avila, C.; Cabrera, A.; Chaparro Sierra, L. F.; Florez, C.; Gomez, J. P.; Gomez Moreno, B.; Sanabria, J. C.; Godinovic, N.; Lelas, D.; Puljak, I.; Ribeiro Cipriano, P. M.; Antunovic, Z.; Kovac, M.; Brigljevic, V.; Ferencek, D.; Kadija, K.; Luetic, J.; Micanovic, S.; Sudic, L.; Attikis, A.; Mavromanolakis, G.; Mousa, J.; Nicolaou, C.; Ptochos, F.; Razis, P. A.; Rykaczewski, H.; Finger, M.; Finger, M.; Carrera Jarrin, E.; Abdelalim, A. A.; El-khateeb, E.; Elkafrawy, T.; Mahmoud, M. A.; Calpas, B.; Kadastik, M.; Murumaa, M.; Perrini, L.; Raidal, M.; Tiko, A.; Veelken, C.; Eerola, P.; Pekkanen, J.; Voutilainen, M.; Härkönen, J.; Karimäki, V.; Kinnunen, R.; Lampén, T.; Lassila-Perini, K.; Lehti, S.; Lindén, T.; Luukka, P.; Peltola, T.; Tuominiemi, J.; Tuovinen, E.; Wendland, L.; Talvitie, J.; Tuuva, T.; Besancon, M.; Couderc, F.; Dejardin, M.; Denegri, D.; Fabbro, B.; Faure, J. L.; Favaro, C.; Ferri, F.; Ganjour, S.; Givernaud, A.; Gras, P.; Hamel de Monchenault, G.; Jarry, P.; Locci, E.; Machet, M.; Malcles, J.; Rander, J.; Rosowsky, A.; Titov, M.; Zghiche, A.; Abdulsalam, A.; Antropov, I.; Baffioni, S.; Beaudette, F.; Busson, P.; Cadamuro, L.; Chapon, E.; Charlot, C.; Davignon, O.; Dobrzynski, L.; Granier de Cassagnac, R.; Jo, M.; Lisniak, S.; Miné, P.; Naranjo, I. N.; Nguyen, M.; Ochando, C.; Ortona, G.; Paganini, P.; Pigard, P.; Regnard, S.; Salerno, R.; Sirois, Y.; Strebler, T.; Yilmaz, Y.; Zabi, A.; Agram, J.-L.; Andrea, J.; Aubin, A.; Bloch, D.; Brom, J.-M.; Buttignol, M.; Chabert, E. C.; Chanon, N.; Collard, C.; Conte, E.; Coubez, X.; Fontaine, J.-C.; Gelé, D.; Goerlach, U.; Goetzmann, C.; Le Bihan, A.-C.; Merlin, J. A.; Skovpen, K.; Van Hove, P.; Gadrat, S.; Beauceron, S.; Bernet, C.; Boudoul, G.; Bouvier, E.; Carrillo Montoya, C. A.; Chierici, R.; Contardo, D.; Courbon, B.; Depasse, P.; El Mamouni, H.; Fan, J.; Fay, J.; Gascon, S.; Gouzevitch, M.; Ille, B.; Lagarde, F.; Laktineh, I. B.; Lethuillier, M.; Mirabito, L.; Pequegnot, A. L.; Perries, S.; Popov, A.; Ruiz Alvarez, J. D.; Sabes, D.; Sordini, V.; Vander Donckt, M.; Verdier, P.; Viret, S.; Toriashvili, T.; Tsamalaidze, Z.; Autermann, C.; Beranek, S.; Feld, L.; Heister, A.; Kiesel, M. K.; Klein, K.; Lipinski, M.; Ostapchuk, A.; Preuten, M.; Raupach, F.; Schael, S.; Schomakers, C.; Schulte, J. F.; Schulz, J.; Verlage, T.; Weber, H.; Zhukov, V.; Ata, M.; Brodski, M.; Dietz-Laursonn, E.; Duchardt, D.; Endres, M.; Erdmann, M.; Erdweg, S.; Esch, T.; Fischer, R.; Güth, A.; Hebbeker, T.; Heidemann, C.; Hoepfner, K.; Knutzen, S.; Merschmeyer, M.; Meyer, A.; Millet, P.; Mukherjee, S.; Olschewski, M.; Padeken, K.; Papacz, P.; Pook, T.; Radziej, M.; Reithler, H.; Rieger, M.; Scheuch, F.; Sonnenschein, L.; Teyssier, D.; Thüer, S.; Cherepanov, V.; Erdogan, Y.; Flügge, G.; Geenen, H.; Geisler, M.; Hoehle, F.; Kargoll, B.; Kress, T.; Künsken, A.; Lingemann, J.; Nehrkorn, A.; Nowack, A.; Nugent, I. M.; Pistone, C.; Pooth, O.; Stahl, A.; Aldaya Martin, M.; Asin, I.; Beernaert, K.; Behnke, O.; Behrens, U.; Borras, K.; Campbell, A.; Connor, P.; Contreras-Campana, C.; Costanza, F.; Diez Pardos, C.; Dolinska, G.; Dooling, S.; Eckerlin, G.; Eckstein, D.; Eichhorn, T.; Gallo, E.; Garay Garcia, J.; Geiser, A.; Gizhko, A.; Grados Luyando, J. M.; Gunnellini, P.; Harb, A.; Hauk, J.; Hempel, M.; Jung, H.; Kalogeropoulos, A.; Karacheban, O.; Kasemann, M.; Kieseler, J.; Kleinwort, C.; Korol, I.; Lange, W.; Lelek, A.; Leonard, J.; Lipka, K.; Lobanov, A.; Lohmann, W.; Mankel, R.; Melzer-Pellmann, I.-A.; Meyer, A. B.; Mittag, G.; Mnich, J.; Mussgiller, A.; Ntomari, E.; Pitzl, D.; Placakyte, R.; Raspereza, A.; Roland, B.; Sahin, M. Ö.; Saxena, P.; Schoerner-Sadenius, T.; Seitz, C.; Spannagel, S.; Stefaniuk, N.; Trippkewitz, K. D.; Van Onsem, G. P.; Walsh, R.; Wissing, C.; Blobel, V.; Centis Vignali, M.; Draeger, A. R.; Dreyer, T.; Erfle, J.; Garutti, E.; Goebel, K.; Gonzalez, D.; Görner, M.; Haller, J.; Hoffmann, M.; Höing, R. S.; Junkes, A.; Klanner, R.; Kogler, R.; Kovalchuk, N.; Lapsien, T.; Lenz, T.; Marchesini, I.; Marconi, D.; Meyer, M.; Niedziela, M.; Nowatschin, D.; Ott, J.; Pantaleo, F.; Peiffer, T.; Perieanu, A.; Pietsch, N.; Poehlsen, J.; Sander, C.; Scharf, C.; Schleper, P.; Schlieckau, E.; Schmidt, A.; Schumann, S.; Schwandt, J.; Stadie, H.; Steinbrück, G.; Stober, F. M.; Tholen, H.; Troendle, D.; Usai, E.; Vanelderen, L.; Vanhoefer, A.; Vormwald, B.; Barth, C.; Baus, C.; Berger, J.; Böser, C.; Butz, E.; Chwalek, T.; Colombo, F.; De Boer, W.; Descroix, A.; Dierlamm, A.; Fink, S.; Frensch, F.; Friese, R.; Giffels, M.; Gilbert, A.; Haitz, D.; Hartmann, F.; Heindl, S. M.; Husemann, U.; Katkov, I.; Kornmayer, A.; Lobelle Pardo, P.; Maier, B.; Mildner, H.; Mozer, M. U.; Müller, T.; Müller, Th.; Plagge, M.; Quast, G.; Rabbertz, K.; Röcker, S.; Roscher, F.; Schröder, M.; Sieber, G.; Simonis, H. J.; Ulrich, R.; Wagner-Kuhr, J.; Wayand, S.; Weber, M.; Weiler, T.; Williamson, S.; Wöhrmann, C.; Wolf, R.; Anagnostou, G.; Daskalakis, G.; Geralis, T.; Giakoumopoulou, V. A.; Kyriakis, A.; Loukas, D.; Psallidas, A.; Topsis-Giotis, I.; Agapitos, A.; Kesisoglou, S.; Panagiotou, A.; Saoulidou, N.; Tziaferi, E.; Evangelou, I.; Flouris, G.; Foudas, C.; Kokkas, P.; Loukas, N.; Manthos, N.; Papadopoulos, I.; Paradas, E.; Strologas, J.; Filipovic, N.; Bencze, G.; Hajdu, C.; Hidas, P.; Horvath, D.; Sikler, F.; Veszpremi, V.; Vesztergombi, G.; Zsigmond, A. J.; Beni, N.; Czellar, S.; Karancsi, J.; Molnar, J.; Szillasi, Z.; Bartók, M.; Makovec, A.; Raics, P.; Trocsanyi, Z. L.; Ujvari, B.; Choudhury, S.; Mal, P.; Mandal, K.; Nayak, A.; Sahoo, D. K.; Sahoo, N.; Swain, S. K.; Bansal, S.; Beri, S. B.; Bhatnagar, V.; Chawla, R.; Gupta, R.; Bhawandeep, U.; Kalsi, A. K.; Kaur, A.; Kaur, M.; Kumar, R.; Mehta, A.; Mittal, M.; Singh, J. B.; Walia, G.; Kumar, Ashok; Bhardwaj, A.; Choudhary, B. C.; Garg, R. B.; Keshri, S.; Kumar, A.; Malhotra, S.; Naimuddin, M.; Nishu, N.; Ranjan, K.; Sharma, R.; Sharma, V.; Bhattacharya, R.; Bhattacharya, S.; Chatterjee, K.; Dey, S.; Dutta, S.; Ghosh, S.; Majumdar, N.; Modak, A.; Mondal, K.; Mukhopadhyay, S.; Nandan, S.; Purohit, A.; Roy, A.; Roy, D.; Roy Chowdhury, S.; Sarkar, S.; Sharan, M.; Chudasama, R.; Dutta, D.; Jha, V.; Kumar, V.; Mohanty, A. K.; Pant, L. M.; Shukla, P.; Topkar, A.; Aziz, T.; Banerjee, S.; Bhowmik, S.; Chatterjee, R. M.; Dewanjee, R. K.; Dugad, S.; Ganguly, S.; Ghosh, S.; Guchait, M.; Gurtu, A.; Jain, Sa.; Kole, G.; Kumar, S.; Mahakud, B.; Maity, M.; Majumder, G.; Mazumdar, K.; Mitra, S.; Mohanty, G. B.; Parida, B.; Sarkar, T.; Sur, N.; Sutar, B.; Wickramage, N.; Chauhan, S.; Dube, S.; Kapoor, A.; Kothekar, K.; Rane, A.; Sharma, S.; Bakhshiansohi, H.; Behnamian, H.; Etesami, S. 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M.; Maruyama, S.; Mason, D.; McBride, P.; Merkel, P.; Mrenna, S.; Nahn, S.; Newman-Holmes, C.; O'Dell, V.; Pedro, K.; Prokofyev, O.; Rakness, G.; Sexton-Kennedy, E.; Soha, A.; Spalding, W. J.; Spiegel, L.; Stoynev, S.; Strobbe, N.; Taylor, L.; Tkaczyk, S.; Tran, N. V.; Uplegger, L.; Vaandering, E. W.; Vernieri, C.; Verzocchi, M.; Vidal, R.; Wang, M.; Weber, H. A.; Whitbeck, A.; Acosta, D.; Avery, P.; Bortignon, P.; Bourilkov, D.; Brinkerhoff, A.; Carnes, A.; Carver, M.; Curry, D.; Das, S.; Field, R. D.; Furic, I. K.; Konigsberg, J.; Korytov, A.; Kotov, K.; Ma, P.; Matchev, K.; Mei, H.; Milenovic, P.; Mitselmakher, G.; Rank, D.; Rossin, R.; Shchutska, L.; Sperka, D.; Terentyev, N.; Thomas, L.; Wang, J.; Wang, S.; Yelton, J.; Linn, S.; Markowitz, P.; Martinez, G.; Rodriguez, J. L.; Ackert, A.; Adams, J. R.; Adams, T.; Askew, A.; Bein, S.; Bochenek, J.; Diamond, B.; Haas, J.; Hagopian, S.; Hagopian, V.; Johnson, K. F.; Khatiwada, A.; Prosper, H.; Santra, A.; Weinberg, M.; Baarmand, M. M.; Bhopatkar, V.; Colafranceschi, S.; Hohlmann, M.; Kalakhety, H.; Noonan, D.; Roy, T.; Yumiceva, F.; Adams, M. R.; Apanasevich, L.; Berry, D.; Betts, R. R.; Bucinskaite, I.; Cavanaugh, R.; Evdokimov, O.; Gauthier, L.; Gerber, C. E.; Hofman, D. J.; Kurt, P.; O'Brien, C.; Sandoval Gonzalez, I. D.; Turner, P.; Varelas, N.; Wu, Z.; Zakaria, M.; Zhang, J.; Bilki, B.; Clarida, W.; Dilsiz, K.; Durgut, S.; Gandrajula, R. P.; Haytmyradov, M.; Khristenko, V.; Merlo, J.-P.; Mermerkaya, H.; Mestvirishvili, A.; Moeller, A.; Nachtman, J.; Ogul, H.; Onel, Y.; Ozok, F.; Penzo, A.; Snyder, C.; Tiras, E.; Wetzel, J.; Yi, K.; Anderson, I.; Blumenfeld, B.; Cocoros, A.; Eminizer, N.; Fehling, D.; Feng, L.; Gritsan, A. V.; Maksimovic, P.; Osherson, M.; Roskes, J.; Sarica, U.; Swartz, M.; Xiao, M.; Xin, Y.; You, C.; Baringer, P.; Bean, A.; Bruner, C.; Castle, J.; Kenny, R. P.; Kropivnitskaya, A.; Majumder, D.; Malek, M.; Mcbrayer, W.; Murray, M.; Sanders, S.; Stringer, R.; Wang, Q.; Ivanov, A.; Kaadze, K.; Khalil, S.; Makouski, M.; Maravin, Y.; Mohammadi, A.; Saini, L. K.; Skhirtladze, N.; Toda, S.; Lange, D.; Rebassoo, F.; Wright, D.; Anelli, C.; Baden, A.; Baron, O.; Belloni, A.; Calvert, B.; Eno, S. C.; Ferraioli, C.; Gomez, J. A.; Hadley, N. J.; Jabeen, S.; Kellogg, R. G.; Kolberg, T.; Kunkle, J.; Lu, Y.; Mignerey, A. C.; Shin, Y. H.; Skuja, A.; Tonjes, M. B.; Tonwar, S. C.; Apyan, A.; Barbieri, R.; Baty, A.; Bi, R.; Bierwagen, K.; Brandt, S.; Busza, W.; Cali, I. A.; Demiragli, Z.; Di Matteo, L.; Gomez Ceballos, G.; Goncharov, M.; Gulhan, D.; Hsu, D.; Iiyama, Y.; Innocenti, G. M.; Klute, M.; Kovalskyi, D.; Krajczar, K.; Lai, Y. S.; Lee, Y.-J.; Levin, A.; Luckey, P. D.; Marini, A. C.; Mcginn, C.; Mironov, C.; Narayanan, S.; Niu, X.; Paus, C.; Roland, C.; Roland, G.; Salfeld-Nebgen, J.; Stephans, G. S. F.; Sumorok, K.; Tatar, K.; Varma, M.; Velicanu, D.; Veverka, J.; Wang, J.; Wang, T. W.; Wyslouch, B.; Yang, M.; Zhukova, V.; Benvenuti, A. C.; Dahmes, B.; Evans, A.; Finkel, A.; Gude, A.; Hansen, P.; Kalafut, S.; Kao, S. C.; Klapoetke, K.; Kubota, Y.; Lesko, Z.; Mans, J.; Nourbakhsh, S.; Ruckstuhl, N.; Rusack, R.; Tambe, N.; Turkewitz, J.; Acosta, J. G.; Oliveros, S.; Avdeeva, E.; Bartek, R.; Bloom, K.; Bose, S.; Claes, D. R.; Dominguez, A.; Fangmeier, C.; Gonzalez Suarez, R.; Kamalieddin, R.; Knowlton, D.; Kravchenko, I.; Meier, F.; Monroy, J.; Ratnikov, F.; Siado, J. E.; Snow, G. R.; Stieger, B.; Alyari, M.; Dolen, J.; George, J.; Godshalk, A.; Harrington, C.; Iashvili, I.; Kaisen, J.; Kharchilava, A.; Kumar, A.; Parker, A.; Rappoccio, S.; Roozbahani, B.; Alverson, G.; Barberis, E.; Baumgartel, D.; Chasco, M.; Hortiangtham, A.; Massironi, A.; Morse, D. M.; Nash, D.; Orimoto, T.; Teixeira De Lima, R.; Trocino, D.; Wang, R.-J.; Wood, D.; Zhang, J.; Bhattacharya, S.; Hahn, K. A.; Kubik, A.; Low, J. F.; Mucia, N.; Odell, N.; Pollack, B.; Schmitt, M. H.; Sung, K.; Trovato, M.; Velasco, M.; Dev, N.; Hildreth, M.; Jessop, C.; Karmgard, D. J.; Kellams, N.; Lannon, K.; Marinelli, N.; Meng, F.; Mueller, C.; Musienko, Y.; Planer, M.; Reinsvold, A.; Ruchti, R.; Rupprecht, N.; Smith, G.; Taroni, S.; Valls, N.; Wayne, M.; Wolf, M.; Woodard, A.; Antonelli, L.; Brinson, J.; Bylsma, B.; Durkin, L. S.; Flowers, S.; Hart, A.; Hill, C.; Hughes, R.; Ji, W.; Liu, B.; Luo, W.; Puigh, D.; Rodenburg, M.; Winer, B. L.; Wulsin, H. W.; Driga, O.; Elmer, P.; Hardenbrook, J.; Hebda, P.; Koay, S. A.; Lujan, P.; Marlow, D.; Medvedeva, T.; Mooney, M.; Olsen, J.; Palmer, C.; Piroué, P.; Stickland, D.; Tully, C.; Zuranski, A.; Malik, S.; Barker, A.; Barnes, V. E.; Benedetti, D.; Gutay, L.; Jha, M. K.; Jones, M.; Jung, A. W.; Jung, K.; Miller, D. H.; Neumeister, N.; Radburn-Smith, B. C.; Shi, X.; Sun, J.; Svyatkovskiy, A.; Wang, F.; Xie, W.; Xu, L.; Parashar, N.; Stupak, J.; Adair, A.; Akgun, B.; Chen, Z.; Ecklund, K. M.; Geurts, F. J. M.; Guilbaud, M.; Li, W.; Michlin, B.; Northup, M.; Padley, B. P.; Redjimi, R.; Roberts, J.; Rorie, J.; Tu, Z.; Zabel, J.; Betchart, B.; Bodek, A.; de Barbaro, P.; Demina, R.; Duh, Y.-T.; Eshaq, Y.; Ferbel, T.; Galanti, M.; Garcia-Bellido, A.; Han, J.; Hindrichs, O.; Khukhunaishvili, A.; Lo, K. H.; Tan, P.; Verzetti, M.; Chou, J. P.; Contreras-Campana, E.; Gershtein, Y.; Gómez Espinosa, T. A.; Halkiadakis, E.; Heindl, M.; Hidas, D.; Hughes, E.; Kaplan, S.; Kunnawalkam Elayavalli, R.; Kyriacou, S.; Lath, A.; Nash, K.; Randall, S.; Saka, H.; Salur, S.; Schnetzer, S.; Sheffield, D.; Somalwar, S.; Stone, R.; Thomas, S.; Thomassen, P.; Walker, M.; Foerster, M.; Heideman, J.; Riley, G.; Rose, K.; Spanier, S.; Thapa, K.; Bouhali, O.; Castaneda Hernandez, A.; Celik, A.; Dalchenko, M.; De Mattia, M.; Delgado, A.; Dildick, S.; Eusebi, R.; Gilmore, J.; Huang, T.; Kamon, T.; Krutelyov, V.; Mueller, R.; Osipenkov, I.; Pakhotin, Y.; Patel, R.; Perloff, A.; Perniè, L.; Rathjens, D.; Rose, A.; Safonov, A.; Tatarinov, A.; Ulmer, K. A.; Akchurin, N.; Cowden, C.; Damgov, J.; Dragoiu, C.; Dudero, P. R.; Faulkner, J.; Kunori, S.; Lamichhane, K.; Lee, S. W.; Libeiro, T.; Undleeb, S.; Volobouev, I.; Wang, Z.; Appelt, E.; Delannoy, A. G.; Greene, S.; Gurrola, A.; Janjam, R.; Johns, W.; Maguire, C.; Mao, Y.; Melo, A.; Ni, H.; Sheldon, P.; Tuo, S.; Velkovska, J.; Xu, Q.; Arenton, M. W.; Barria, P.; Cox, B.; Francis, B.; Goodell, J.; Hirosky, R.; Ledovskoy, A.; Li, H.; Neu, C.; Sinthuprasith, T.; Sun, X.; Wang, Y.; Wolfe, E.; Xia, F.; Clarke, C.; Harr, R.; Karchin, P. E.; Kottachchi Kankanamge Don, C.; Lamichhane, P.; Sturdy, J.; Belknap, D. A.; Carlsmith, D.; Dasu, S.; Dodd, L.; Duric, S.; Gomber, B.; Grothe, M.; Herndon, M.; Hervé, A.; Klabbers, P.; Lanaro, A.; Levine, A.; Long, K.; Loveless, R.; Mohapatra, A.; Ojalvo, I.; Perry, T.; Pierro, G. A.; Polese, G.; Ruggles, T.; Sarangi, T.; Savin, A.; Sharma, A.; Smith, N.; Smith, W. H.; Taylor, D.; Verwilligen, P.; Woods, N.; CMS Collaboration

2016-12-01

Results are presented from searches for R -parity-violating supersymmetry in events produced in p p collisions at √{s }=8 TeV at the LHC. Final states with 0, 1, 2, or multiple leptons are considered independently. The analysis is performed on data collected by the CMS experiment corresponding to an integrated luminosity of 19.5 fb-1 . No excesses of events above the standard model expectations are observed, and 95% confidence level limits are set on supersymmetric particle masses and production cross sections. The results are interpreted in models featuring R -parity-violating decays of the lightest supersymmetric particle, which in the studied scenarios can be either the gluino, a bottom squark, or a neutralino. In a gluino pair production model with baryon number violation, gluinos with a mass less than 0.98 and 1.03 TeV are excluded, by analyses in a fully hadronic and one-lepton final state, respectively. An analysis in a dilepton final state is used to exclude bottom squarks with masses less than 307 GeV in a model considering bottom squark pair production. Multilepton final states are considered in the context of either strong or electroweak production of superpartners and are used to set limits on the masses of the lightest supersymmetric particles. These limits range from 300 to 900 GeV in models with leptonic and up to approximately 700 GeV in models with semileptonic R -parity-violating couplings.

CYP2R1 mutations causing vitamin D-deficiency rickets.

PubMed

Thacher, Tom D; Levine, Michael A

2017-10-01

CYP2R1 is the principal hepatic 25-hydroxylase responsible for the hydroxylation of parent vitamin D to 25-hydroxyvitamin D [25(OH)D]. Serum concentrations of 25(OH)D reflect vitamin D status, because 25(OH)D is the major circulating metabolite of vitamin D. The 1α-hydroxylation of 25(OH)D in the kidney by CYP27B1 generates the fully active vitamin D metabolite, 1,25-dihydroxyvitamin D (1,25(OH) 2 D). The human CYP2R1 gene, located at 11p15.2, has five exons, coding for an enzyme with 501 amino acids. In Cyp2r1-/- knockout mice, serum 25(OH)D levels were reduced by more than 50% compared wild-type mice. Genetic polymorphisms of CYP2R1 account for some of the individual variability of circulating 25(OH)D values in the population. We review the evidence that inactivating mutations in CYP2R1 can lead to a novel form of vitamin D-deficiency rickets resulting from impaired 25-hydroxylation of vitamin D. We sequenced the promoter, exons and intron-exon flanking regions of the CYP2R1 gene in members of 12 Nigerian families with rickets in more than one family member. We found missense mutations (L99P and K242N) in affected members of 2 of 12 families. The L99P mutation had previously been reported as a homozygous defect in an unrelated child of Nigerian origin with rickets. In silico analyses predicted impaired CYP2R1 folding or reduced interaction with substrate vitamin D by L99P and K242N mutations, respectively. In vitro studies of the mutant CYP2R1 proteins in HEK293 cells confirmed normal expression levels but completely absent or markedly reduced 25-hydroxylase activity by the L99P and K242N mutations, respectively. Heterozygous subjects had more moderate biochemical and clinical features of vitamin D deficiency than homozygous subjects. After an oral bolus dose of 50,000 IU of vitamin D 2 or vitamin D 3 , heterozygous subjects had lower increases in serum 25(OH)D than control subjects, and homozygous subjects had minimal increases, supporting a semidominant

Public funding and private investment for R&D: a survey in China's pharmaceutical industry.

PubMed

Qiu, Lan; Chen, Zi-Ya; Lu, Deng-Yu; Hu, Hao; Wang, Yi-Tao

2014-06-13

In recent years, China has experienced tremendous growth in its pharmaceutical industry. Both the Chinese government and private investors are motivated to invest into pharmaceutical research and development (R&D). However, studies regarding the different behaviors of public and private investment in pharmaceutical R&D are scarce. Therefore, this paper aims to investigate the current situation of public funding and private investment into Chinese pharmaceutical R&D. The primary data used in the research were obtained from the China High-tech Industry Statistics Yearbook (2002-2012) and China Statistical Yearbook of Science and Technology (2002-2012). We analyzed public funding and private investment in five aspects: total investment in the industry, funding sources of the whole industry, differences between provinces, difference in subsectors, and private equity/venture capital investment. The vast majority of R&D investment was from private sources. There is a significantly positive correlation between public funding and private investment in different provinces of China. However, public funding was likely to be invested into less developed provinces with abundant natural herbal resources. Compared with the chemical medicine subsector, traditional Chinese medicine and biopharmaceutical subsectors obtained more public funding. Further, the effect of the government was focused on private equity and venture capital investment although private fund is the mainstream of this type of investment. Public funding and private investment play different but complementary roles in pharmaceutical R&D in China. While being less than private investment, public funding shows its significance in R&D investment. With rapid growth of the industry, the pharmaceutical R&D investment in China is expected to increase steadily from both public and private sources.

Multinucleon pion absorption on {sup 4}He into the pppn final state

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

Lehmann, A.; Backenstoss, G.; Koehler, J.

1997-10-01

Results from a 4{pi} solid angle measurement of the reaction {pi}{sup +4}He{r_arrow}pppn at incident pion energies of T{sub {pi}{sup +}}= 70, 118, 162, 239, and 330 MeV are presented. Integrated cross sections are given for the reactions where three nucleons participate, leading to energetic (ppp) or (ppn) final states, and for states where four nucleons are involved (pppn). The two three-nucleon absorption modes were investigated in particular, and an energy dependent isospin ratio of the cross sections of {sigma}{sub ppn}/ {sigma}{sub ppp}=3.6{plus_minus}1.3, 2.6 {plus_minus}0.5, 1.8{plus_minus}0.3, 1.4{plus_minus} 0.2, and 1.8{plus_minus}0.6 was determined from 70 to 330 MeV. The differential cross sectionsmore » were described by a complete set of eight independent variables and compared to simple cascade and phase space models. From this analysis the contributions from initial state interactions to the multinucleon absorption cross sections were found to be more important at higher pion energies, while those from final state interactions are stronger at lower energies. However, both mechanisms combined were found to account for not more than one-third of the total pppn multinucleon yield. The remaining strength is reasonably well reproduced by phase space models, but shows a dependence on the incident pion{close_quote}s orbital angular momentum. The isospin structure of the (ppp) and (ppn) final states is not understood, nor are some structures in their distributions. The four-nucleon yield (pppn) was found to be weak (1{endash}8{percent} of the total absorption cross section) and shows no evidence for a {open_quotes}double- {Delta}{close_quotes} excitation. {copyright} {ital 1997} {ital The American Physical Society}« less

R&D Alert. Volume 7, Number 2, 2005

ERIC Educational Resources Information Center

White, Noel, Ed.

2005-01-01

"R&D Alert" covers issues affecting schools in the Western Regional Educational Laboratory's four-state region--Arizona, California, Nevada, and Utah--and throughout the United States. This issue of "R&D Alert" shares what WestEd is learning from a sample of their latest work, focusing on three points in the process:…

4. Photocopy of measured drawing (from Robert R. Harvey's 'Historic ...

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

4. Photocopy of measured drawing (from Robert R. Harvey's 'Historic Stone Architecture of Winterset, Iowa, Prior To and During the Civil War Period,' Unpublished Report, Iowa State University, (Ames, IA), 1960.) FLOOR PLAN, THIRD ADDITION ('Fig. 5-D') - J. G. Vawter House, First Avenue & South Street, Winterset, Madison County, IA

Solar Research Earns Three Prestigious R&D 100 Awards | News | NREL

Science.gov Websites

1 » Solar Research Earns Three Prestigious R&D 100 Awards News Release: Solar Research Earns Three Prestigious R&D 100 Awards June 22, 2011 A technique to turn silicon into ink, a faster way to significant innovations by R&D Magazine. The three prestigious awards bring to 50 the number of R&D

Digit Ratio (2D:4D) Predicts Self-Reported Measures of General Competitiveness, but Not Behavior in Economic Experiments

PubMed Central

Bönte, Werner; Procher, Vivien D.; Urbig, Diemo; Voracek, Martin

2017-01-01

The ratio of index finger length to ring finger length (2D:4D) is considered to be a putative biomarker of prenatal androgen exposure (PAE), with previous research suggesting that 2D:4D is associated with human behaviors, especially sex-typical behaviors. This study empirically examines the relationship between 2D:4D and individual competitiveness, a behavioral trait that is found to be sexually dimorphic. We employ two related, but distinct, measures of competitiveness, namely behavioral measures obtained from economic experiments and psychometric self-reported measures. Our analyses are based on two independent data sets obtained from surveys and economic experiments with 461 visitors of a shopping mall (Study I) and 617 university students (Study II). The correlation between behavior in the economic experiment and digit ratios of both hands is not statistically significant in either study. In contrast, we find a negative and statistically significant relationship between psychometric self-reported measures of competitiveness and right hand digit ratios (R2D:4D) in both studies. This relationship is especially strong for younger people. Hence, this study provides some robust empirical evidence for a negative association between R2D:4D and self-reported competitiveness. We discuss potential reasons why digit ratio may relate differently to behaviors in specific economics experiments and to self-reported general competitiveness. PMID:29276479

Digit Ratio (2D:4D) Predicts Self-Reported Measures of General Competitiveness, but Not Behavior in Economic Experiments.

PubMed

Bönte, Werner; Procher, Vivien D; Urbig, Diemo; Voracek, Martin

2017-01-01

The ratio of index finger length to ring finger length (2D:4D) is considered to be a putative biomarker of prenatal androgen exposure (PAE), with previous research suggesting that 2D:4D is associated with human behaviors, especially sex-typical behaviors. This study empirically examines the relationship between 2D:4D and individual competitiveness, a behavioral trait that is found to be sexually dimorphic. We employ two related, but distinct, measures of competitiveness, namely behavioral measures obtained from economic experiments and psychometric self-reported measures. Our analyses are based on two independent data sets obtained from surveys and economic experiments with 461 visitors of a shopping mall (Study I) and 617 university students (Study II). The correlation between behavior in the economic experiment and digit ratios of both hands is not statistically significant in either study. In contrast, we find a negative and statistically significant relationship between psychometric self-reported measures of competitiveness and right hand digit ratios (R2D:4D) in both studies. This relationship is especially strong for younger people. Hence, this study provides some robust empirical evidence for a negative association between R2D:4D and self-reported competitiveness. We discuss potential reasons why digit ratio may relate differently to behaviors in specific economics experiments and to self-reported general competitiveness.

Investigation of cyano-bridged coordination nanoparticles Gd3+/[Fe(CN)6]3-/d-mannitol as T1-weighted MRI contrast agents

NASA Astrophysics Data System (ADS)

Perrier, M.; Gallud, A.; Ayadi, A.; Kennouche, S.; Porredon, C.; Gary-Bobo, M.; Larionova, J.; Goze-Bac, Ch.; Zanca, M.; Garcia, M.; Basile, I.; Long, J.; de Lapuente, J.; Borras, M.; Guari, Y.

2015-07-01

Cyano-bridged Gd3+/[Fe(CN)6]3- coordination polymer nanoparticles of 3-4 nm stabilized with d-mannitol presenting a high r1 relaxivity value of 11.4 mM-1 s-1 were investigated in vivo as contrast agents (CA) for Magnetic Resonance Imaging (MRI). They allow an increase of the MR image contrast and can act as an efficient intravascular T1 CA with a relatively long blood-circulation lifetime (60 min) without specific toxicity.Cyano-bridged Gd3+/[Fe(CN)6]3- coordination polymer nanoparticles of 3-4 nm stabilized with d-mannitol presenting a high r1 relaxivity value of 11.4 mM-1 s-1 were investigated in vivo as contrast agents (CA) for Magnetic Resonance Imaging (MRI). They allow an increase of the MR image contrast and can act as an efficient intravascular T1 CA with a relatively long blood-circulation lifetime (60 min) without specific toxicity. Electronic supplementary information (ESI) available: Experimental details and procedures, toxicological data, physical characterization. See DOI: 10.1039/c5nr01557j

Pharmacokinetics and Metabolism of 4R-Cembranoid.

PubMed

Vélez-Carrasco, Wanda; Green, Carol E; Catz, Paul; Furimsky, Anna; O'Loughlin, Kathleen; Eterović, Vesna A; Ferchmin, P A

2015-01-01

4R-cembranoid (4R) is a natural cyclic diterpenoid found in tobacco leaves that displays neuroprotective activity. 4R protects against NMDA, paraoxon (POX), and diisopropylfluorophosphate (DFP) damage in rat hippocampal slices and against DFP in rats in vivo. The purpose of this study was to examine the metabolism and pharmacokinetics of 4R as part of its preclinical development as a neuroprotective drug. 10 µM 4R was found to be very stable in plasma for up to 1 hr incubation. 4R metabolism in human microsomes was faster than in the rat. Ten metabolites of 4R were detected in the microsomal samples; 6 dihydroxy and 4 monohydroxy forms of 4R. Male rats received a single dose of 4R at 6 mg/kg i.v., i.m., or s.c. The i.v. group had the highest plasma concentration of 1017 ng/mL. The t1/2 was 36 min and reached the brain within 10 min. The brain peak concentration was 6516 ng/g. The peak plasma concentration in the i.m. group was 163 ng/mL compared to 138 ng/mL in the s.c. group. The t1/2 of 4R after i.m. and s.c. administration was approximately 1.5 hr. The brain peak concentration was 329 ng/g in the i.m. group and 323 ng/g for the s.c. group. The brain to plasma ratio in the i.v. group was 6.4, reached 10 min after dose, whereas in the i.m. and s.c. groups was 2.49 and 2.48, respectively, at 90 min after dose. Our data show that 4R crosses the BBB and concentrates in the brain where it exerts its neuroprotective effect.

Pharmacokinetics and Metabolism of 4R-Cembranoid

PubMed Central

Vélez-Carrasco, Wanda; Green, Carol E.; Catz, Paul; Furimsky, Anna; O’Loughlin, Kathleen; Eterović, Vesna A.; Ferchmin, P. A.

2015-01-01

4R-cembranoid (4R) is a natural cyclic diterpenoid found in tobacco leaves that displays neuroprotective activity. 4R protects against NMDA, paraoxon (POX), and diisopropylfluorophosphate (DFP) damage in rat hippocampal slices and against DFP in rats in vivo. The purpose of this study was to examine the metabolism and pharmacokinetics of 4R as part of its preclinical development as a neuroprotective drug. 10 µM 4R was found to be very stable in plasma for up to 1 hr incubation. 4R metabolism in human microsomes was faster than in the rat. Ten metabolites of 4R were detected in the microsomal samples; 6 dihydroxy and 4 monohydroxy forms of 4R. Male rats received a single dose of 4R at 6 mg/kg i.v., i.m., or s.c. The i.v. group had the highest plasma concentration of 1017 ng/mL. The t1/2 was 36 min and reached the brain within 10 min. The brain peak concentration was 6516 ng/g. The peak plasma concentration in the i.m. group was 163 ng/mL compared to 138 ng/mL in the s.c. group. The t1/2 of 4R after i.m. and s.c. administration was approximately 1.5 hr. The brain peak concentration was 329 ng/g in the i.m. group and 323 ng/g for the s.c. group. The brain to plasma ratio in the i.v. group was 6.4, reached 10 min after dose, whereas in the i.m. and s.c. groups was 2.49 and 2.48, respectively, at 90 min after dose. Our data show that 4R crosses the BBB and concentrates in the brain where it exerts its neuroprotective effect. PMID:25811857

Developing R&D Portfolio Business Validity Simulation Model and System

PubMed Central

2015-01-01

The R&D has been recognized as critical method to take competitiveness by not only companies but also nations with its value creation such as patent value and new product. Therefore, R&D has been a decision maker's burden in that it is hard to decide how much money to invest, how long time one should spend, and what technology to develop which means it accompanies resources such as budget, time, and manpower. Although there are diverse researches about R&D evaluation, business factors are not concerned enough because almost all previous studies are technology oriented evaluation with one R&D technology based. In that, we early proposed R&D business aspect evaluation model which consists of nine business model components. In this research, we develop a simulation model and system evaluating a company or industry's R&D portfolio with business model point of view and clarify default and control parameters to facilitate evaluator's business validity work in each evaluation module by integrate to one screen. PMID:25893209

How much is energy R and D worth?

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

Schock, R. N., LLNL

1997-05-06

The value of energy technology R and D as an insurance investment to reduce the cost of climate change stabilization, oil price shocks, urban air pollution, and energy disruptions is estimated to be $5-8 billion/year in sum total. However, the total that is justified is actually less than this sum because some R and D is applicable to more than one risk. nevertheless, the total DOE investment in energy technology R and D (about $1.3 billion/year in FY97) seems easily justified by its insurance value alone; and, in fact, more might be warranted, particularly in the areas related to climatemore » change and urban air pollution. This conclusion appears robust even if the private sector is assumed to be investing a comparable amount. Not counted is the value to the economy and to US competitiveness of better energy technologies that may result from the R and D; only the insurance value for reducing the cost of these four risks to society was estimated.« less

Photonic network R and D activities in Japan

NASA Astrophysics Data System (ADS)

Kitayama, Ken-ichi; Miki, Tetsuya; Morioka, Toshio; Tsushima, Hideaki; Koga, Masafumi; Mori, Kazuyuki; Araki, Soichiro; Sato, Ken-ichi; Onaka, Hiroshi; Namiki, Shu; Aovama, Tomonori

2005-11-01

R and D activities on photonic networks in Japan are presented. First, milestones in current, ongoing R and D programs supported by Japanese government agencies are introduced, including long-distance and WDM fiber transmission, wavelength routing, optical burst switching, and control plane technology for IP backbone networks. Their goal was set to evolve a legacy telecommunications network to IP over WDM networks by introducing technologies for WDM and wavelength routing. We then discuss the perspectives of so-called PHASE II R and D programs for photonic networks over the next five years until 2010, by focusing on the report which has been recently issued by the Photonic Internet Forum (PIF), a consortium that has major carriers, telecom vendors, and Japanese academics as members. The PHASE II R and D programs should serve to establish a photonic platform to provide abundant bandwidth on demand, at any time on a real-time basis through the customer's initiative, to promote bandwidth-rich applications, such as grid computing, real-time digital-cinema streaming, medical and educational applications, and network storage in e-commerce.

R3D Align web server for global nucleotide to nucleotide alignments of RNA 3D structures.

PubMed

Rahrig, Ryan R; Petrov, Anton I; Leontis, Neocles B; Zirbel, Craig L

2013-07-01

The R3D Align web server provides online access to 'RNA 3D Align' (R3D Align), a method for producing accurate nucleotide-level structural alignments of RNA 3D structures. The web server provides a streamlined and intuitive interface, input data validation and output that is more extensive and easier to read and interpret than related servers. The R3D Align web server offers a unique Gallery of Featured Alignments, providing immediate access to pre-computed alignments of large RNA 3D structures, including all ribosomal RNAs, as well as guidance on effective use of the server and interpretation of the output. By accessing the non-redundant lists of RNA 3D structures provided by the Bowling Green State University RNA group, R3D Align connects users to structure files in the same equivalence class and the best-modeled representative structure from each group. The R3D Align web server is freely accessible at http://rna.bgsu.edu/r3dalign/.

Developing Our Future: American R&D in International Perspective.

ERIC Educational Resources Information Center

El-Khawas, Elaine; Anderson, Charles J.

1993-01-01

This report offers a profile of the financial and human resources devoted to research and development (R&D) in the United States and other nations, focusing on the role of universities in carrying out R&D and in supporting the development of scientific and technical personnel needed for a competitive economy. It found that R&D…

Scientific R&D: time to revise the rules?

PubMed

Crump, Andy

2004-11-01

For several decades scientific R&D has been failing communities around the world, especially in developing countries, by not producing an adequate level of benefits (for example, improved health and living standards) and essential public goods (for example, the provision of safe water, sanitation and energy). It is time for a complete overhaul of the R&D process, with a comprehensive review of the mechanisms by which R&D is financed, how and where the work and results are published and disseminated, how the results and knowledge are exploited, and how ownership is decided. This is particularly important for public goods, for which there is often no market or prospect of commercial return or profit.

Investigation of Presage 3D Dosimetry as a Method of Clinically Intuitive Quality Assurance and Comparison to a Semi-3D Delta4 System

NASA Astrophysics Data System (ADS)

Crockett, Ethan Van

The need for clinically intuitive metrics for patient-specific quality assurance in radiation therapy has been well-documented (Zhen, Nelms et al. 2011). A novel transform method has shown to be effective at converting full-density 3D dose measurements made in a phantom to dose values in the patient geometry, enabling comparisons using clinically intuitive metrics such as dose-volume histograms (Oldham et al. 2011). This work investigates the transform method and compares its calculated dose-volume histograms (DVHs) to DVH values calculated by a Delta4 QA device (Scandidos), marking the first comparison of a true 3D system to a semi-3D device using clinical metrics. Measurements were made using Presage 3D dosimeters, which were readout by an in-house optical-CT scanner. Three patient cases were chosen for the study: one head-and-neck VMAT treatment and two spine IMRT treatments. The transform method showed good agreement with the planned dose values for all three cases. Furthermore, the transformed DVHs adhered to the planned dose with more accuracy than the Delta4 DVHs. The similarity between the Delta4 DVHs and the transformed DVHs, however, was greater for one of the spine cases than it was for the head-and-neck case, implying that the accuracy of the Delta4 Anatomy software may vary from one treatment site to another. Overall, the transform method, which incorporates data from full-density 3D dose measurements, provides clinically intuitive results that are more accurate and consistent than the corresponding results from a semi-3D Delta 4 system.

1-[3-(4-Butylpiperidin-1-yl)propyl]-1,2,3,4-tetrahydroquinolin-2-one (77-LH-28-1) as a Model for the Rational Design of a Novel Class of Brain Penetrant Ligands with High Affinity and Selectivity for Dopamine D4 Receptor.

PubMed

Del Bello, Fabio; Bonifazi, Alessandro; Giorgioni, Gianfabio; Cifani, Carlo; Micioni Di Bonaventura, Maria Vittoria; Petrelli, Riccardo; Piergentili, Alessandro; Fontana, Stefano; Mammoli, Valerio; Yano, Hideaki; Matucci, Rosanna; Vistoli, Giulio; Quaglia, Wilma

2018-04-26

In the present article, the M 1 mAChR bitopic agonist 1-[3-(4-butylpiperidin-1-yl)propyl]-1,2,3,4-tetrahydroquinolin-2-one (77-LH-28-1, 1) has been demonstrated to show unexpected D 4 R selectivity over D 2 R and D 3 R and to behave as a D 4 R antagonist. To better understand the structural features required for the selective interaction with the D 4 R and to obtain compounds unable to activate mAChRs, the aliphatic butyl chain and the piperidine nucleus of 1 were modified, affording compounds 2-14. The 4-benzylpiperidine 9 and the 4-phenylpiperazine 12 showed high D 4 R affinity and selectivity not only over the other D 2 -like subtypes, but also over M 1 -M 5 mAChRs. Derivative 12 was also highly selective over some selected off-targets. This compound showed biased behavior, potently and partially activating G i protein and inhibiting β-arrestin2 recruitment in functional studies. Pharmacokinetic studies demonstrated that it was characterized by a relevant brain penetration. Therefore, 12 might be a useful tool to better clarify the role played by D 4 R in disorders in which this subtype is involved.

HUMAN GRK4γ142V VARIANT PROMOTES AT1R-MEDIATED HYPERTENSION VIA RENAL HDAC1 INHIBITION

PubMed Central

Wang, Zheng; Zeng, Chunyu; Villar, Van Anthony M.; Chen, Shi-You; Konkalmatt, Prasad; Wang, Xiaoyan; Asico, Laureano D.; Jones, John E.; Yang, Yu; Sanada, Hironobu; Felder, Robin A.; Eisner, Gilbert M.; Weir, Matthew R.; Armando, Ines; Jose, Pedro A.

2015-01-01

The influence of a single gene on the etiology of essential hypertension may be difficult to ascertain, unless the gene interacts with other genes that are germane to blood pressure regulation. G protein-coupled receptor kinase type 4 (GRK4) is one such gene. We have reported that the expression of its variant hGRK4γ142V in mice results in hypertension due to impaired dopamine D1 receptor (D1R). Signaling through D1R and angiotensin II type I receptor (AT1R) reciprocally modulates renal sodium excretion and blood pressure. Here, we demonstrate the ability of the hGRK4γ142V to increase the expression and activity of the AT1R. We show that hGRK4γ142V phosphorylates histone deacetylase type 1 and promotes its nuclear export to the cytoplasm, resulting in increased AT1R expression and greater pressor response to angiotensin II. AT1R blockade and the deletion of the Agtr1a gene normalize the hypertension in hGRK4γ142V mice. These findings illustrate the unique role of GRK4 by targeting receptors with opposite physiological activity for the same goal of maintaining blood pressure homeostasis, and thus making the GRK4 a relevant therapeutic target to control blood pressure. PMID:26667412

Investigation of Performance of Concrete and Concreting Materials Exposed to Natural Weathering. Volume 1. Active Investigations. Revision

DTIC Science & Technology

1980-08-01

Ms. K. Mather, Messrs. B. Mather, J. M. Scanlon, B. R. Sullivan, R. V. Tye, Jr., E. E. McCoy, E. C. Roshore, H. T. Thornton, R. E. Black, D. Glass , D...Investigations, Phases D (CW R&D) Section 9: Passamaquoddy Tidal Power Project Section 10: Missouri River Division Program Section 1: Portland Blast-Furnace Slag ...Missouri River Division Props.m 3- by 4-1/2- by 16-in. beam 3 2 No? 1965 10 pack 5 Portland lst-Puiiace Slag 3-1/2- by 1-1/2- by 16-in. beam 108 66 May

Federal R&D Funding: Trends and Projections

NASA Astrophysics Data System (ADS)

White, K. S.

2014-12-01

Between sequestration, shutdowns, and budget "cliffs," the federal budget process has experienced many challenges in recent years. Budgets for research and development (R&D) have mirrored these larger fiscal constraints. Over the past decade, many agencies and programs have seen flat or declining budgets, particularly when inflation is considered. This talk will examine recent geoscience R&D funding in the historical context and examine projections of future science funding in the framework of the Budget Control Act and other initiatives.

Bidirectional signaling between TM4SF5 and IGF1R promotes resistance to EGFR kinase inhibitors.

PubMed

Choi, Jungeun; Kang, Minkyung; Nam, Seo Hee; Lee, Gyu-Ho; Kim, Hye-Jin; Ryu, Jihye; Cheong, Jin Gyu; Jung, Jae Woo; Kim, Tai Young; Lee, Ho-Young; Lee, Jung Weon

2015-10-01

The membrane glycoprotein TM4SF5 (transmembrane 4 L6 family member 5), which is similar to the tetraspanins, is highly expressed in different cancers and causes epithelial-mesenchymal transition (EMT). TM4SF5 interacts with other membrane proteins during its pro-tumorigenic roles, presumably at tetraspanin-enriched microdomains (TEMs/TERMs). Here, we explored TM4SF5-mediated resistance against the clinically important EGFR kinase inhibitors, with regards to cooperation with other membrane proteins, particularly the insulin-like growth factor 1 receptor (IGF1R). Using cancer cells including NSCLC with TM4SF5 overexpression or IGF1R suppression in either normal 2 dimensional (2D), 3D aqueous spheroids, or 3D collagen I gels systems, the sensitivity to tyrosine kinase inhibitors (TKIs) were evaluated. We found that TM4SF5 and IGF1R transcriptionally modulated one another, with each protein promoting the expressions of the other. Expression of TM4SF5 in gefitinib-sensitive HCC827 cells caused resistance to erlotinib and gefitinib, but not to sorafenib [a platelet derived growth factor receptor (PDGFR) inhibitor]; whereas suppression of IGF1R from gefitinib-resistant NCI-H1299 cells caused enhanced sensitization to the inhibitors. Expression of TM4SF5 and IGF1R in the drug-sensitive cells promoted signaling activities of extracellular signal-regulated kinases (ERKs), protein kinase B (Akt), and S6 kinase (S6K), and resulted in a higher residual EGFR activity, even after EGFR kinase inhibitor treatment. Complex formation between TM4SF5 and IGF1R was observed, and also included EGFR, dependent on TM4SF5 expression. The TM4SF5-mediated drug resistance was further confirmed in an aqueous 3D spheroid system or upon being embedded in 3D extracellular matrix (ECM)-surrounded gel systems. Collectively, these data suggest that anti-TM4SF5 reagents may be combined with the EGFR kinase inhibitors to enhance the efficacy of chemotherapies against NSCLC. Copyright © 2015 Elsevier

Helical 4D CT and Comparison with Cine 4D CT

NASA Astrophysics Data System (ADS)

Pan, Tinsu

4D CT was one of the most important developments in radiation oncology in the last decade. Its early development in single slice CT and commercialization in multi-slice CT has radically changed our practice in radiation treatment of lung cancer, and has enabled the stereotactic radiosurgery of early stage lung cancer. In this chapter, we will document the history of 4D CT development, detail the data sufficiency condition governing the 4D CT data collection; present the design of the commercial helical 4D CTs from Philips and Siemens; compare the differences between the helical 4D CT and the GE cine 4D CT in data acquisition, slice thickness, acquisition time and work flow; review the respiratory monitoring devices; and understand the causes of image artifacts in 4D CT.

NREL Research Honored With R&D 100 Awards | News | NREL

Science.gov Websites

Research Honored With R&D 100 Awards NREL Research Honored With R&D 100 Awards November 16 research into using a strain of cyanobacteria to produce bioethylene won both awards in the category of innovation - in five categories. Only one Editor's Choice Award was given in each of the five R&D 100

Baicalein induces G1 arrest in oral cancer cells by enhancing the degradation of cyclin D1 and activating AhR to decrease Rb phosphorylation

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

Cheng, Ya-Hsin, E-mail: yhcheng@mail.cmu.edu.tw; Li, Lih-Ann; Lin, Pinpin

Baicalein is a flavonoid, known to have anti-inflammatory and anti-cancer effects. As an aryl hydrocarbon receptor (AhR) ligand, baicalein at high concentrations blocks AhR-mediated dioxin toxicity. Because AhR had been reported to play a role in regulating the cell cycle, we suspected that the anti-cancer effect of baicalein is associated with AhR. This study investigated the molecular mechanism involved in the anti-cancer effect of baicalein in oral cancer cells HSC-3, including whether such effect would be AhR-mediated. Results revealed that baicalein inhibited cell proliferation and increased AhR activity in a dose-dependent manner. Cell cycle was arrested at the G1 phasemore » and the expression of CDK4, cyclin D1, and phosphorylated retinoblastoma (pRb) was decreased. When the AhR was suppressed by siRNA, the reduction of pRb was partially reversed, accompanied by a decrease of cell population at G1 phase and an increase at S phase, while the reduction of cyclin D1 and CDK4 did not change. This finding suggests that the baicalein activation of AhR is indeed associated with the reduction of pRb, but is independent of the reduction of cyclin D1 and CDK4. When cells were pre-treated with LiCl, the inhibitor of GSK-3β, the decrease of cyclin D1 was blocked and the reduction of pRb was recovered. The data indicates that in HSC-3 the reduction of pRb is both mediated by baicalein through activation of AhR and facilitation of cyclin D1 degradation, which causes cell cycle arrest at the G1 phase, and results in the inhibition of cell proliferation. -- Highlights: ► Baicalein causes the G1 phase arrest by decreasing Rb phosphorylation. ► Baicalein modulates AhR-mediated cell proliferation. ► Both AhR activation and cyclin D1 degradation results in hypophosphorylation of Rb. ► Baicalein facilitates cyclin D1 degradation by signalling the GSK-3β pathway.« less

Leptonic decays of charged D and Ds mesons

NASA Astrophysics Data System (ADS)

Menaa, Nabil

Using 281 pb--1 of data taken on the psi(3770) resonance and 314 pb--1 of data near or at 4170 MeV collected with the CLEO-c detector, we present two analyses to study the purely leptonic decays of charmed and charmed strange charged mesons. In the first analysis, we extract a relatively precise value for the decay constant of the D+ meson by measuring B (D+ → mu+nu) = (4.40 +/- 0.66+0.09-0.12 ) x 10-4. We find fD + = (222.6 +/- 16.7+2.8-3.4 ) MeV, and compare with current theoretical calculations. We also set a 90% confidence upper limit on B (D+ → e +nu) < 2.4 x 10-5 which constrains new physics models. Finally with this data sample, we test whether or not the tau lepton manifests the same couplings as the mu lepton by investigating the relative decay rates in purely leptonic D+ meson decays. We limit B (D+ → tau+nu) < 2.1 x 10--3 at 90% confidence level (C. L.), thus allowing us to place the first upper limit on the ratio R = Gamma (D+ → tau+nu)/Gamma( D+ → mu+nu). The ratio of R to the Standard Model expectation of 2.65 then is <1.8 at 90% C. L., consistent with the prediction of lepton universality. In the second analysis, we examine e+ e-- → D-sD*+s and D-*sD+s interactions at 4170 MeV using the CLEO-c detector in order to measure the decay constant fD+s . We use the D+s → ℓ+nu channel, where the ℓ+ designates either a mu+ or a tau+, when the tau+ → pi+nu. Analyzing both modes independently, we determine B ( D+s → mu+nu) = (0.594 +/- 0.066 +/- 0.031)%, B ( D+s → tau+nu) = (8.0 +/- 1.3 +/- 0.4)%. We also analyze them simultaneously to find an effective value of B ( D+s → mu+nu) = (0.621 +/- 0.058 +/- 0.032)% and extract fD+s = 270 +/- 13 +/- 7 MeV. Combining with our previous determination of B (D+ → mu+nu), we also find the ratio fD+s/fD+ = 1.21 +/- 0.11 +/- 0.04. We compare with current theoretical estimates. Finally, we limit B ( D+s → e+nu) < 1.3 x 10 --4 at 90% confidence level.

20 CFR 349.4 - Late completion of timely investigation.

Code of Federal Regulations, 2010 CFR

2010-04-01

... 20 Employees' Benefits 1 2010-04-01 2010-04-01 false Late completion of timely investigation. 349.4 Section 349.4 Employees' Benefits RAILROAD RETIREMENT BOARD REGULATIONS UNDER THE RAILROAD UNEMPLOYMENT INSURANCE ACT FINALITY OF DECISIONS REGARDING UNEMPLOYMENT AND SICKNESS INSURANCE BENEFITS § 349.4...

20 CFR 349.4 - Late completion of timely investigation.

Code of Federal Regulations, 2011 CFR

2011-04-01

... 20 Employees' Benefits 1 2011-04-01 2011-04-01 false Late completion of timely investigation. 349.4 Section 349.4 Employees' Benefits RAILROAD RETIREMENT BOARD REGULATIONS UNDER THE RAILROAD UNEMPLOYMENT INSURANCE ACT FINALITY OF DECISIONS REGARDING UNEMPLOYMENT AND SICKNESS INSURANCE BENEFITS § 349.4...

20 CFR 349.4 - Late completion of timely investigation.

Code of Federal Regulations, 2012 CFR

2012-04-01

... 20 Employees' Benefits 1 2012-04-01 2012-04-01 false Late completion of timely investigation. 349.4 Section 349.4 Employees' Benefits RAILROAD RETIREMENT BOARD REGULATIONS UNDER THE RAILROAD UNEMPLOYMENT INSURANCE ACT FINALITY OF DECISIONS REGARDING UNEMPLOYMENT AND SICKNESS INSURANCE BENEFITS § 349.4...

Design, synthesis, characterisation, conformation and biological investigation of N-acyl r-2,c-6-bis (4-methoxyphenyl)-c-3,t-3-dimethylpiperidin-4-ones

NASA Astrophysics Data System (ADS)

Mohanraj, V.; Ponnuswamy, S.

2017-09-01

In a wide research programme towards the study of piperidin-4-ones with efficient pharmacological effect, a new series of N-acyl r-2,c-6-bis(4-methoxyphenyl)-c-3,t-3-dimethylpiperidin-4-ones 2-5 are synthesized and characterized by IR spectra, 1H, 13C, DEPT - 135 and 2D (COSY and HSQC) NMR and mass spectra. The parent compound 1 prefers to exist in a chair conformation whereas the extracted coupling constant, chemical shifts and estimated dihedral angles show that the N-acyl piperdine-4-ones 2-5 prefer to exist in a distorted boat conformation B1 (with C2 and C5 in prow and stern positions) with coplanar orientation of Nsbnd Cdbnd O moiety. The existence of a fast Nsbnd CO rotational equilibrium between the boat conformations B (I) and B (II) has also been observed. Anti bacterial activity of the above test compounds 1-5 is determined against pseudomonas sp. and salmonella sp. The antioxidant activities are determined by the ABTS, DPPH and superoxide assays. Furthermore, molecular docking studies have been carried out for the compounds 1-5 with target protein CHK1.

Synthesis, characterization, structural and biological aspects of copper(II) dithiocarbamate complexes - Part II, [Cu{S2CN(Me)(R1)}2], [Cu{S2CN(Me)(R2)}2] and [Cu{S2CN(R3)(R4)}2] {R1 = CH2CH(OMe)2, R2 = 2-methyl-1,3-dioxolane, R3 = CH2(CH2)2NCHPhOCH2Ph and R4 = CH2CH2OH}

NASA Astrophysics Data System (ADS)

Ferreira, Isabella P.; de Lima, Geraldo M.; Paniago, Eucler B.; Takahashi, Jacqueline A.; Krambrock, Klaus; Pinheiro, Carlos B.; Wardell, James L.; Visentin, Lorenzo C.

2013-09-01

Three new copper(II) dithiocarbamates (DTC), [Cu{S2CN(Me)(R1)}2] (1), [Cu{S2CN(Me)(R2)}2] (2) and [Cu{S2CN(R3)(R4)}2] (3) with R1 = CH2CH(OMe)2, R2 = 2-methyl-1,3-dioxolane, R3 = CH2(CH2)2NCHPhOCH2Ph and R4 = CH2CH2OH, have been synthesized and characterized by different spectroscopic techniques. Complexes (1) and (2) display typical EPR spectra for separated Cu(II) centers, and the spectrum of (3) is characteristic of two magnetically coupled Cu(II) ions with S = 1. The X-ray crystallographic determination has shown that complexes (1) and (2) crystallise in the triclinic and monoclinic systems. In addition both complexes are monomers in which the geometry at each Cu(II) is square planar. The in vitro antimicrobial activity of the sodium salts of ligands, and of the Cu(II)-DTC complexes have been screened against Aspergillus flavus, Aspergillus niger, Aspergillus parasiticus, Penicillium citrinum and Curvularia senegalensis, as well as Gram positive and Gram negative bacteria. Finally, the toxic effects of complexes (1)-(3) were performed using Chlorella vulgaris.

R34D1NG W0RD5 W1TH NUMB3R5.

PubMed

Perea, Manuel; Duñabeitia, Jon Andoni; Carreiras, Manuel

2008-02-01

Letter identities and number identities are usually thought to imply different cortical mechanisms. Specifically, the left fusiform gyrus responds more to letters than to digits (T. A. Polk et al., 2002). However, a widely circulated statement on the internet illustrates that it is possible to use numbers (leet digits) as parts of words, 4ND TH3 R35ULT1NG S3NT3NC3 C4N B3 R34D W1TH0UT GR34T 3FF0RT. Two masked priming lexical decision experiments were conducted to determine whether leet digits produce (automatic) lexical activation. Results showed that words are identified substantially faster when they are preceded by a masked leet word (M4T3R14L-MATERIAL) than when they are preceded by a control condition with other letters or digits. In addition, there was only a negligible advantage of the identity condition over the related leet condition. This leet-priming effect is not specific to numbers: A prime in which leet digits are replaced by letter-like symbols (M(Delta symbol)T(euro symbol)R!(Delta symbol)L - MATERIAL) facilitates word processing to the same degree as an identity prime. Therefore, the cognitive system regularizes the shape of the leet digits and letter-like symbols embedded in words with very little cost.

On international cost-sharing of pharmaceutical R&D.

PubMed

Barros, Pedro Pita; Martinez-Giralt, Xavier

2008-12-01

Ramsey pricing has been proposed in the pharmaceutical industry as a principle to price discriminate among markets while allowing to recover the (fixed) R&D cost. However, such analyses neglect the presence of insurance or the fund raising costs for most of drug reimbursement. By incorporating these new elements, we aim at providing some building blocks towards an economic theory incorporating Ramsey pricing and insurance coverage. We show how coinsurance affects the optimal prices to pay for the R&D investment. We also show that under certain conditions, there is no strategic incentive by governments to set coinsurance rates in order to shift the financial burden of R&D. This will have important implications to the application of Ramsey pricing principles to pharmaceutical products across countries.

D4 dopamine-receptor (DRD4) alleles and novelty seeking in substance-dependent, personality-disorder, and control subjects.

PubMed Central

Gelernter, J; Kranzler, H; Coccaro, E; Siever, L; New, A; Mulgrew, C L

1997-01-01

Two reports have been published suggesting an association between the personality trait of novelty seeking and the DRD4*7R allele at the D4 dopamine-receptor locus (with heterozygotes or homozygotes for DRD4*7R having higher novelty seeking). We studied novelty seeking and four coding-sequence polymorphisms affecting protein structure in the D4 dopamine-receptor gene (DRD4) in a sample of 341 American subjects, of whom 224 are of primarily European ancestry and 117 are of primarily African ancestry. These subjects had diagnoses of substance dependence or personality disorder (PD) or were screened to exclude major psychiatric diagnosis. We found that, although the substance-dependent subjects had significantly higher novelty seeking than the control and PD subjects, they did not differ in DRD4*7R allele frequency. There was no association between any DRD4 polymorphism and novelty seeking in any population or diagnostic group, except for a significant association between the DRD4*7R allele and lower novelty seeking among European American females and African American substance abusers. The novelty seeking of subjects heterozygous for a null mutation did not differ from that of subjects with two functional alleles. We conclude that the most likely explanation of these results is that the DRD4 VNTR does not influence directly the trait of novelty seeking, in these samples. PMID:9345090

Reduced translocation in 2,4-D-resistant oriental mustard populations (Sisymbrium orientale L.) from Australia.

PubMed

Dang, Hue Thi; Malone, Jenna M; Boutsalis, Peter; Krishnan, Mahima; Gill, Gurjeet; Preston, Christopher

2018-06-01

Two oriental mustard populations (P2 and P13) collected from Port Broughton, South Australia were identified as resistant to 2,4-D. The level of resistance, mechanism and the mode of inheritance for 2,4-D resistance in these populations were investigated. Populations P2 and P13 were confirmed to be resistant to 2,4-D at the field rate (600 g a.e. ha -1 ). P2 and P13 were 81- and 67-fold more resistant than the susceptible populations (S1 and S2) at the dose required for 50% mortality (LD 50 ), respectively. No predicted amino acid modification was detected in sequences of potential target-site genes (ABP, TIR1 and AFB5). Resistant populations had reduced 2,4-D translocation compared with the susceptible populations, with 77% of [ 14 C]2,4-D retained in the treated leaf versus 32% at 72 h after treatment. Resistance to 2,4-D is encoded on the nuclear genome and is dominant, as the response to 2,4-D of all F 2 individuals were similar to the resistant biotypes. The segregation of F 2 phenotypes fitted a 3: 1 (R: S) inheritance model. Resistance to 2,4-D in oriental mustard is likely due to reduced translocation of 2,4-D out of the treated leaf. Inheritance of 2,4-D resistance is conferred by a single gene with a high level of dominance. © 2017 Society of Chemical Industry. © 2017 Society of Chemical Industry.

miR-146a facilitates osteoarthritis by regulating cartilage homeostasis via targeting Camk2d and Ppp3r2.

PubMed

Zhang, Xudong; Wang, Chuandong; Zhao, Jingyu; Xu, Jiajia; Geng, Yiyun; Dai, Liming; Huang, Yan; Fu, Sai-Chuen; Dai, Kerong; Zhang, Xiaoling

2017-04-06

Osteoarthritis (OA), characterized by insufficient extracellular matrix synthesis and cartilage degeneration, is known as an incurable disease because its pathogenesis is poorly elucidated. Thus far, limited information is available regarding the pathophysiological role of microRNAs (miRNAs) in OA. In this study, we investigated the specific function of miR-146a in OA pathophysiology using mouse OA models. We found that the articular cartilage degeneration of miR-146a knockout (KO) mice was alleviated compared with that of the wild-type (WT) mice in spontaneous and instability-induced OA models. We demonstrate that miR-146a aggravated pro-inflammatory cytokines induced suppressing the expression of cartilage matrix-associated genes. We further identified calcium/calmodulin-dependent protein kinase II delta (Camk2d) and protein phosphatase 3, regulatory subunit B, beta isoform (Ppp3r2, also known as calcineurin B, type II) were essential targets of miR-146a in regulating cartilage homeostasis. Moreover, we found that surgical-induced OA mice treated with a miR-146a inhibitor significantly alleviated the destruction of articular cartilage via targeting Camk2d and Ppp3r2. These results suggested that miR-146a has a crucial role in maintaining cartilage homeostasis. MiR-146a inhibition in chondrocytes can be a potential therapeutic strategy to ameliorate OA.

R and D Resource Allocations by Selected Foreign Countries,

DTIC Science & Technology

1974-01-01

sustain themselves by innovations which have their source in theory . "’ Prior to the second half of the nine- j teenth century it was rare to find...Tabie r:5,"d 0 D, Chm~lgin Prioritios for Go... ugt R&D, AN BIG SCEC /EENN SR Eorscm AS, A PECNTG OFGPI-9116,AD16 115 The OECD has used one other

FY2015 Energy Storage R&D Annual Progress Report

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

None, None

The Energy Storage research and development (R&D) subprogram within the DOE Vehicle Technologies Office (VTO) provides support and guidance for projects focusing on batteries for plug-in electric vehicles. Program targets focus on overcoming technical barriers to enable market success including: (1) significantly reducing battery cost, (2) increasing battery performance (power, energy, durability), (3) reducing battery weight & volume, and (4) increasing battery tolerance to abusive conditions such as short circuit, overcharge, and crush.

K-t GRAPPA-accelerated 4D flow MRI of liver hemodynamics: influence of different acceleration factors on qualitative and quantitative assessment of blood flow.

PubMed

Stankovic, Zoran; Fink, Jury; Collins, Jeremy D; Semaan, Edouard; Russe, Maximilian F; Carr, James C; Markl, Michael; Langer, Mathias; Jung, Bernd

2015-04-01

We sought to evaluate the feasibility of k-t parallel imaging for accelerated 4D flow MRI in the hepatic vascular system by investigating the impact of different acceleration factors. k-t GRAPPA accelerated 4D flow MRI of the liver vasculature was evaluated in 16 healthy volunteers at 3T with acceleration factors R = 3, R = 5, and R = 8 (2.0 × 2.5 × 2.4 mm(3), TR = 82 ms), and R = 5 (TR = 41 ms); GRAPPA R = 2 was used as the reference standard. Qualitative flow analysis included grading of 3D streamlines and time-resolved particle traces. Quantitative evaluation assessed velocities, net flow, and wall shear stress (WSS). Significant scan time savings were realized for all acceleration factors compared to standard GRAPPA R = 2 (21-71 %) (p < 0.001). Quantification of velocities and net flow offered similar results between k-t GRAPPA R = 3 and R = 5 compared to standard GRAPPA R = 2. Significantly increased leakage artifacts and noise were seen between standard GRAPPA R = 2 and k-t GRAPPA R = 8 (p < 0.001) with significant underestimation of peak velocities and WSS of up to 31 % in the hepatic arterial system (p <0.05). WSS was significantly underestimated up to 13 % in all vessels of the portal venous system for k-t GRAPPA R = 5, while significantly higher values were observed for the same acceleration with higher temporal resolution in two veins (p < 0.05). k-t acceleration of 4D flow MRI is feasible for liver hemodynamic assessment with acceleration factors R = 3 and R = 5 resulting in a scan time reduction of at least 40 % with similar quantitation of liver hemodynamics compared with GRAPPA R = 2.

20 CFR 349.4 - Late completion of timely investigation.

Code of Federal Regulations, 2014 CFR

2014-04-01

... 20 Employees' Benefits 1 2014-04-01 2012-04-01 true Late completion of timely investigation. 349.4 Section 349.4 Employees' Benefits RAILROAD RETIREMENT BOARD REGULATIONS UNDER THE RAILROAD UNEMPLOYMENT INSURANCE ACT FINALITY OF DECISIONS REGARDING UNEMPLOYMENT AND SICKNESS INSURANCE BENEFITS § 349.4 Late...

20 CFR 349.4 - Late completion of timely investigation.

Code of Federal Regulations, 2013 CFR

2013-04-01

... 20 Employees' Benefits 1 2013-04-01 2012-04-01 true Late completion of timely investigation. 349.4 Section 349.4 Employees' Benefits RAILROAD RETIREMENT BOARD REGULATIONS UNDER THE RAILROAD UNEMPLOYMENT INSURANCE ACT FINALITY OF DECISIONS REGARDING UNEMPLOYMENT AND SICKNESS INSURANCE BENEFITS § 349.4 Late...

Potential usefulness of D2R reporter gene imaging by IBF as gene therapy monitoring for cerebellar neurodegenerative diseases.

PubMed

Shiba, Kazuhiro; Torashima, Takashi; Hirai, Hirokazu; Ogawa, Kazuma; Akhter, Nasima; Nakajima, Kenichi; Kinuya, Seigo; Mori, Hirofumi

2009-02-01

We investigated a gene expression imaging method to examine the level of therapeutic gene expression in the cerebellum. Using a human immunodeficiency virus derived lentivial vector, we expressed the dopamine D(2) receptor (D(2)R) as a reporter protein to mouse cerebellar Purkinje cells. Biodistribution and ex vivo autoradiography studies were performed by giving [(125)I]5-iodo-7-N-[(1-ethyl-2-pyrrolidinyl)methyl]carboxamide-2,3-dihydrobenzofuran ([(125)I]IBF) (1.85 MBq), as a radioactive D(2)R ligand, to model mice expressing the D(2)R with an HA tag (HA-D(2)R) in the cerebellum. In this study, [(125)I]IBF was bound to the D(2)R expressed in the cerebellum of the model mice selectively. Immunostaining was performed to confirm the HA-D(2)R expression in the cerebellum of the model mice. A significant correlation (r=0.900, P<0.001) between areas that expressed HA-D(2)R by immunostaining and areas in which [(125)I]IBF accumulated by the ex vivo autoradiograms was found. These results indicated that radioiodinated IBF is useful as a reporter probe to detect D(2)R reporter gene expression, which can be used for monitoring therapeutic gene expression in the cerebellum.

Functional Fast Scan Cyclic Voltammetry Assay to Characterize Dopamine D2 and D3 Autoreceptors in the Mouse Striatum

PubMed Central

2010-01-01

Dopamine D2 and D3 autoreceptors are located on presynaptic terminals and are known to control the release and synthesis of dopamine. Dopamine D3 receptors have a fairly restricted pattern of expression in the mammalian brain. Their localization in the nucleus accumbens core and shell is of particular interest because of their association with the rewarding properties of drugs of abuse. Using background subtracted fast scan cyclic voltammetry, we investigated the effects of dopamine D2 and D3 agonists on electrically stimulated dopamine release and uptake rates in the mouse caudate putamen and nucleus accumbens core and shell. The dopamine D2 agonists (−)-quinpirole hydrochloride and 5,6,7,8-tetrahydro-6-(2-propen-1-yl)-4H-thiazolo[4,5-d]azepin-2-amine dihydrochloride (B-HT 920) had the same dopamine release inhibition effects on caudate putamen and nucleus accumbens (core and shell) on the basis of their EC50 values and efficacies. This suggests that the dopamine D2 autoreceptor functionality is comparable in all three striatal regions investigated. The dopamine D3 agonists (4aR,10bR)-3,4a,4,10b-tetrahydro-4-propyl-2H,5H-[1]benzopyrano-[4,3-b]-1,4-oxazin-9-ol hydrochloride ((+)-PD 128907) and (±)-7-Hydroxy-2-dipropylaminotetralin hydrobromide (7-OH-DPAT) had a significantly greater effect on dopamine release inhibition in the nucleus accumbens shell than in the caudate putamen. This study confirms that, the dopamine D3 autoreceptor functionality is greater in the nucleus accumbens shell followed by the nucleus accumbens core, with the caudate putamen having the least. Neither dopamine D2 nor D3 agonists affected the uptake rates in nucleus accumbens but concentrations greater than 0.1 μM lowered the uptake rate in caudate putamen. To validate our method of evaluating dopamine D2 and D3 autoreceptors, sulpiride (D2 antagonist) and nafadotride (D3 antagonist) were used to reverse the effects of the dopamine agonists to approximately 100% of the preagonist

Trans-tail regulation of MLL4-catalyzed H3K4 methylation by H4R3 symmetric dimethylation is mediated by a tandem PHD of MLL4

PubMed Central

Dhar, Shilpa S.; Lee, Sung-Hun; Kan, Pu-Yeh; Voigt, Philipp; Ma, Li; Shi, Xiaobing; Reinberg, Danny; Lee, Min Gyu

2012-01-01

Mixed-lineage leukemia 4 (MLL4; also called MLL2 and ALR) enzymatically generates trimethylated histone H3 Lys 4 (H3K4me3), a hallmark of gene activation. However, how MLL4-deposited H3K4me3 interplays with other histone marks in epigenetic processes remains largely unknown. Here, we show that MLL4 plays an essential role in differentiating NT2/D1 stem cells by activating differentiation-specific genes. A tandem plant homeodomain (PHD4–6) of MLL4 recognizes unmethylated or asymmetrically dimethylated histone H4 Arg 3 (H4R3me0 or H4R3me2a) and is required for MLL4's nucleosomal methyltransferase activity and MLL4-mediated differentiation. Kabuki syndrome mutations in PHD4–6 reduce PHD4–6's binding ability and MLL4's catalytic activity. PHD4–6's binding strength is inhibited by H4R3 symmetric dimethylation (H4R3me2s), a gene-repressive mark. The protein arginine methyltransferase 7 (PRMT7), but not PRMT5, represses MLL4 target genes by up-regulating H4R3me2s levels and antagonizes MLL4-mediated differentiation. Consistently, PRMT7 knockdown increases MLL4-catalyzed H3K4me3 levels. During differentiation, decreased H4R3me2s levels are associated with increased H3K4me3 levels at a cohort of genes, including many HOXA and HOXB genes. These findings indicate that the trans-tail inhibition of MLL4-generated H3K4me3 by PRMT7-regulated H4R3me2s may result from H4R3me2s's interference with PHD4–6's binding activity and is a novel epigenetic mechanism that underlies opposing effects of MLL4 and PRMT7 on cellular differentiation. PMID:23249737

Trans-tail regulation of MLL4-catalyzed H3K4 methylation by H4R3 symmetric dimethylation is mediated by a tandem PHD of MLL4.

PubMed

Dhar, Shilpa S; Lee, Sung-Hun; Kan, Pu-Yeh; Voigt, Philipp; Ma, Li; Shi, Xiaobing; Reinberg, Danny; Lee, Min Gyu

2012-12-15

Mixed-lineage leukemia 4 (MLL4; also called MLL2 and ALR) enzymatically generates trimethylated histone H3 Lys 4 (H3K4me3), a hallmark of gene activation. However, how MLL4-deposited H3K4me3 interplays with other histone marks in epigenetic processes remains largely unknown. Here, we show that MLL4 plays an essential role in differentiating NT2/D1 stem cells by activating differentiation-specific genes. A tandem plant homeodomain (PHD(4-6)) of MLL4 recognizes unmethylated or asymmetrically dimethylated histone H4 Arg 3 (H4R3me0 or H4R3me2a) and is required for MLL4's nucleosomal methyltransferase activity and MLL4-mediated differentiation. Kabuki syndrome mutations in PHD(4-6) reduce PHD(4-6)'s binding ability and MLL4's catalytic activity. PHD(4-6)'s binding strength is inhibited by H4R3 symmetric dimethylation (H4R3me2s), a gene-repressive mark. The protein arginine methyltransferase 7 (PRMT7), but not PRMT5, represses MLL4 target genes by up-regulating H4R3me2s levels and antagonizes MLL4-mediated differentiation. Consistently, PRMT7 knockdown increases MLL4-catalyzed H3K4me3 levels. During differentiation, decreased H4R3me2s levels are associated with increased H3K4me3 levels at a cohort of genes, including many HOXA and HOXB genes. These findings indicate that the trans-tail inhibition of MLL4-generated H3K4me3 by PRMT7-regulated H4R3me2s may result from H4R3me2s's interference with PHD(4-6)'s binding activity and is a novel epigenetic mechanism that underlies opposing effects of MLL4 and PRMT7 on cellular differentiation.

3. Photocopy of Sheet 1 of Building Plan R495D, (USDA, ...

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

3. Photocopy of Sheet 1 of Building Plan R4-95D, (USDA, Forest Service, Intermountain Region, Ogden. File 7300, 'Buildings'.) ELEVATION, FRAMING AND CONSTRUCTION DETAILS - Buffalo Guard Station, Pumphouse, U.S. Highway 20/191 at Buffalo River, Island Park, Fremont County, ID

Candidate R&D Thrusts for the Software Technology Initiative.

DTIC Science & Technology

1981-05-01

computer-aided design and manufacturing efforts provide examples of multiple representations and multiple manipulation modes. R&D difficulties exist in...farfetched, but the potential payoffs are enormous. References Birk, J., and R. Kelley. Research Needed to Advance the State of Knowledge in Robotics . In...and specifica- tion languages would be benefical . This R&D effort may also result in fusion with management tools with which an acquisition manager

R&D Toward a Neutrino Factory and Muon Collider

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

Zisman, Michael S

2011-03-20

Significant progress has been made in recent years in R&D towards a neutrino factory and muon collider. The U.S. Muon Accelerator Program (MAP) has been formed recently to expedite the R&D efforts. This paper will review the U.S. MAP R&D programs for a neutrino factory and muon collider. Muon ionization cooling research is the key element of the program. The first muon ionization cooling demonstration experiment, MICE (Muon Ionization Cooling Experiment), is under construction now at RAL (Rutherford Appleton Laboratory) in the UK. The current status of MICE will be described.

First scintillating bolometer tests of a CLYMENE R&D on Li2MoO4 scintillators towards a large-scale double-beta decay experiment

NASA Astrophysics Data System (ADS)

Buşe, G.; Giuliani, A.; de Marcillac, P.; Marnieros, S.; Nones, C.; Novati, V.; Olivieri, E.; Poda, D. V.; Redon, T.; Sand, J.-B.; Veber, P.; Velázquez, M.; Zolotarova, A. S.

2018-05-01

A new R&D on lithium molybdate scintillators has begun within a project CLYMENE (Czochralski growth of Li2MoO4 crYstals for the scintillating boloMeters used in the rare EveNts sEarches). One of the main goals of the CLYMENE is a realization of a Li2MoO4 crystal growth line to be complementary to the one recently developed by LUMINEU in view of a mass production capacity for CUPID, a next-generation tonne-scale bolometric experiment to search for neutrinoless double-beta decay. In the present paper we report the investigation of performance and radiopurity of 158-g and 13.5-g scintillating bolometers based on a first large-mass (230 g) Li2MoO4 crystal scintillator developed within the CLYMENE project. In particular, a good energy resolution (2-7 keV FWHM in the energy range of 0.2-5 MeV), one of the highest light yield (0.97 keV/MeV) amongst Li2MoO4 scintillating bolometers, an efficient alpha particles discrimination (10 σ) and potentially low internal radioactive contamination (below 0.2-0.3 mBq/kg of U/Th, but 1.4 mBq/kg of 210Po) demonstrate prospects of the CLYMENE in the development of high quality and radiopure Li2MoO4 scintillators for CUPID.

Open the `black box' creativity and innovation: a study of activities in R&D departments. Some prospects for engineering education

NASA Astrophysics Data System (ADS)

Millet, Charlyne; Oget, David; Cavallucci, Denis

2017-11-01

Innovation is a key component to the success and longevity of companies. Our research opens the 'black box' of creativity and innovation in R&D teams. We argue that understanding the nature of R&D projects in terms of creativity/innovation, efficiency/inefficiency, is important for designing education policies and improving engineering curriculum. Our research addresses the inventive design process, a lesser known aspect of the innovation process, in 197 R&D departments of industrial sector companies in France. One fundamental issue facing companies is to evaluate processes and results of innovation. Results show that the evaluation of innovation is confined by a lack of methodology of inventive projects. We will be establishing the foundations of a formal ontology for inventive design projects and finally some recommendations for engineering education.

Public funding and private investment for R&D: a survey in China’s pharmaceutical industry

PubMed Central

2014-01-01

Background In recent years, China has experienced tremendous growth in its pharmaceutical industry. Both the Chinese government and private investors are motivated to invest into pharmaceutical research and development (R&D). However, studies regarding the different behaviors of public and private investment in pharmaceutical R&D are scarce. Therefore, this paper aims to investigate the current situation of public funding and private investment into Chinese pharmaceutical R&D. Methods The primary data used in the research were obtained from the China High-tech Industry Statistics Yearbook (2002–2012) and China Statistical Yearbook of Science and Technology (2002–2012). We analyzed public funding and private investment in five aspects: total investment in the industry, funding sources of the whole industry, differences between provinces, difference in subsectors, and private equity/venture capital investment. Results The vast majority of R&D investment was from private sources. There is a significantly positive correlation between public funding and private investment in different provinces of China. However, public funding was likely to be invested into less developed provinces with abundant natural herbal resources. Compared with the chemical medicine subsector, traditional Chinese medicine and biopharmaceutical subsectors obtained more public funding. Further, the effect of the government was focused on private equity and venture capital investment although private fund is the mainstream of this type of investment. Conclusions Public funding and private investment play different but complementary roles in pharmaceutical R&D in China. While being less than private investment, public funding shows its significance in R&D investment. With rapid growth of the industry, the pharmaceutical R&D investment in China is expected to increase steadily from both public and private sources. PMID:24925505

Neutron scattering studies of K3H(SO4)2 and K3D(SO4)2: the particle-in-a-box model for the quantum phase transition.

PubMed

Fillaux, François; Cousson, Alain

2012-08-21

In the crystal of K(3)H(SO(4))(2) or K(3)D(SO(4))(2), dimers SO(4)···H···SO(4) or SO(4)···D···SO(4) are linked by strong centrosymmetric hydrogen or deuterium bonds whose O···O length is ≈2.50 Å. We address two open questions. (i) Are H or D sites split or not? (ii) Is there any structural counterpart to the phase transition observed for K(3)D(SO(4))(2) at T(c) ≈ 85.5 K, which does not exist for K(3)H(SO(4))(2)? Neutron diffraction by single-crystals at cryogenic or room temperature reveals no structural transition and no resolvable splitting of H or D sites. However, the width of the probability densities suggest unresolved splitting of the wavefunctions suggesting rigid entities H(L1/2)-H(R1/2) or D(L1/2)-D(R1/2) whose separation lengths are l(H) ≈ 0.16 Å or l(D) ≈ 0.25 Å. The vibrational eigenstates for the center of mass of H(L1/2)-H(R1/2) revealed by inelastic neutron scattering are amenable to a square-well and we suppose the same potential holds for D(L1/2)-D(R1/2). In order to explain dielectric and calorimetric measurements of mixed crystals K(3)D((1-ρ))H(ρ)(SO(4))(2) (0 ≤ ρ ≤ 1), we replace the classical notion of order-disorder by the quantum notion of discernible (e.g., D(L1/2)-D(R1/2)) or indiscernible (e.g., H(L1/2)-H(R1/2)) components depending on the separation length of the split wavefunction. The discernible-indiscernible isostructural transition at finite temperatures is induced by a thermal pure quantum state or at 0 K by ρ.

Directional sinogram interpolation for motion weighted 4D cone-beam CT reconstruction

NASA Astrophysics Data System (ADS)

Zhang, Hua; Kruis, Matthijs; Sonke, Jan-Jakob

2017-03-01

The image quality of respiratory sorted four-dimensional (4D) cone-beam (CB) computed tomography (CT) is often limited by streak artifacts due to insufficient projections. A motion weighted reconstruction (MWR) method is proposed to decrease streak artifacts and improve image quality. Firstly, respiratory correlated CBCT projections were interpolated by directional sinogram interpolation (DSI) to generate additional CB projections for each phase and subsequently reconstructed. Secondly, local motion was estimated by deformable image registration of the interpolated 4D CBCT. Thirdly, a regular 3D FDK CBCT was reconstructed from the non-interpolated projections. Finally, weights were assigned to each voxel, based on the local motion, and then were used to combine the 3D FDK CBCT and interpolated 4D CBCT to generate the final 4D image. MWR method was compared with regular 4D CBCT scans as well as McKinnon and Bates (MKB) based reconstructions. Comparisons were made in terms of (1) comparing the steepness of an extracted profile from the boundary of the region-of-interest (ROI), (2) contrast-to-noise ratio (CNR) inside certain ROIs, and (3) the root-mean-square-error (RMSE) between the planning CT and CBCT inside a homogeneous moving region. Comparisons were made for both a phantom and four patient scans. In a 4D phantom, RMSE were reduced by 24.7% and 38.7% for MKB and MWR respectively, compared to conventional 4D CBCT. Meanwhile, interpolation induced blur was minimal in static regions for MWR based reconstructions. In regions with considerable respiratory motion, image blur using MWR is less than the MKB and 3D Feldkamp (FDK) methods. In the lung cancer patients, average CNRs of MKB, DSI and MWR improved by a factor 1.7, 2.8 and 3.5 respectively relative to 4D FDK. MWR effectively reduces RMSE in 4D cone-beam CT and improves the image quality in both the static and respiratory moving regions compared to 4D FDK and MKB methods.

Directional sinogram interpolation for motion weighted 4D cone-beam CT reconstruction.

PubMed

Zhang, Hua; Kruis, Matthijs; Sonke, Jan-Jakob

2017-03-21

The image quality of respiratory sorted four-dimensional (4D) cone-beam (CB) computed tomography (CT) is often limited by streak artifacts due to insufficient projections. A motion weighted reconstruction (MWR) method is proposed to decrease streak artifacts and improve image quality. Firstly, respiratory correlated CBCT projections were interpolated by directional sinogram interpolation (DSI) to generate additional CB projections for each phase and subsequently reconstructed. Secondly, local motion was estimated by deformable image registration of the interpolated 4D CBCT. Thirdly, a regular 3D FDK CBCT was reconstructed from the non-interpolated projections. Finally, weights were assigned to each voxel, based on the local motion, and then were used to combine the 3D FDK CBCT and interpolated 4D CBCT to generate the final 4D image. MWR method was compared with regular 4D CBCT scans as well as McKinnon and Bates (MKB) based reconstructions. Comparisons were made in terms of (1) comparing the steepness of an extracted profile from the boundary of the region-of-interest (ROI), (2) contrast-to-noise ratio (CNR) inside certain ROIs, and (3) the root-mean-square-error (RMSE) between the planning CT and CBCT inside a homogeneous moving region. Comparisons were made for both a phantom and four patient scans. In a 4D phantom, RMSE were reduced by 24.7% and 38.7% for MKB and MWR respectively, compared to conventional 4D CBCT. Meanwhile, interpolation induced blur was minimal in static regions for MWR based reconstructions. In regions with considerable respiratory motion, image blur using MWR is less than the MKB and 3D Feldkamp (FDK) methods. In the lung cancer patients, average CNRs of MKB, DSI and MWR improved by a factor 1.7, 2.8 and 3.5 respectively relative to 4D FDK. MWR effectively reduces RMSE in 4D cone-beam CT and improves the image quality in both the static and respiratory moving regions compared to 4D FDK and MKB methods.

Company Partners in Photovoltaic Manufacturing R&D | Photovoltaic Research

Science.gov Websites

| NREL Company Partners in Photovoltaic Manufacturing R&D Company Partners in Photovoltaic Manufacturing R&D More than 40 private-sector companies partnered with NREL on successful Global Photovoltaic Specialists Global Solar Energy Golden Photon Iowa Thin Film Technologies ITN Energy

"D.L.&W. R.R. Profile for New Tunnel Through Bergen Hill" Plan ...

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

"D.L.&W. R.R. Profile for New Tunnel Through Bergen Hill" Plan Sheet. December 1, 1905. On file at New Jersey Transit Corporation Headquarters, Newark, New Jersey - Delaware, Lackawanna & Western Railroad, South Bergen Tunnel, Jersey City, Hudson County, NJ

R&D incentives for neglected diseases.

PubMed

Dimitri, Nicola

2012-01-01

Neglected diseases are typically characterized as those for which adequate drug treatment is lacking, and the potential return on effort in research and development (R&D), to produce new therapies, is too small for companies to invest significant resources in the field. In recent years various incentives schemes to stimulate R&D by pharmaceutical firms have been considered. Broadly speaking, these can be classified either as 'push' or 'pull' programs. Hybrid options, that include push and pull incentives, have also become increasingly popular. Supporters and critics of these various incentive schemes have argued in favor of their relative merits and limitations, although the view that no mechanism is a perfect fit for all situations appears to be widely held. For this reason, the debate on the advantages and disadvantages of different approaches has been important for policy decisions, but is dispersed in a variety of sources. With this in mind, the aim of this paper is to contribute to the understanding of the economic determinants behind R&D investments for neglected diseases by comparing the relative strength of different incentive schemes within a simple economic model, based on the assumption of profit maximizing firms. The analysis suggests that co-funded push programs are generally more efficient than pure pull programs. However, by setting appropriate intermediate goals hybrid incentive schemes could further improve efficiency.

R&D Incentives for Neglected Diseases

PubMed Central

Dimitri, Nicola

2012-01-01

Neglected diseases are typically characterized as those for which adequate drug treatment is lacking, and the potential return on effort in research and development (R&D), to produce new therapies, is too small for companies to invest significant resources in the field. In recent years various incentives schemes to stimulate R&D by pharmaceutical firms have been considered. Broadly speaking, these can be classified either as ‘push’ or ‘pull’ programs. Hybrid options, that include push and pull incentives, have also become increasingly popular. Supporters and critics of these various incentive schemes have argued in favor of their relative merits and limitations, although the view that no mechanism is a perfect fit for all situations appears to be widely held. For this reason, the debate on the advantages and disadvantages of different approaches has been important for policy decisions, but is dispersed in a variety of sources. With this in mind, the aim of this paper is to contribute to the understanding of the economic determinants behind R&D investments for neglected diseases by comparing the relative strength of different incentive schemes within a simple economic model, based on the assumption of profit maximizing firms. The analysis suggests that co-funded push programs are generally more efficient than pure pull programs. However, by setting appropriate intermediate goals hybrid incentive schemes could further improve efficiency. PMID:23284648

Bidirectional modulation of hippocampal synaptic plasticity by Dopaminergic D4-receptors in the CA1 area of hippocampus.

PubMed

Navakkode, Sheeja; Chew, Katherine C M; Tay, Sabrina Jia Ning; Lin, Qingshu; Behnisch, Thomas; Soong, Tuck Wah

2017-11-14

Long-term potentiation (LTP) is the persistent increase in the strength of the synapses. However, the neural networks would become saturated if there is only synaptic strenghthening. Synaptic weakening could be facilitated by active processes like long-term depression (LTD). Molecular mechanisms that facilitate the weakening of synapses and thereby stabilize the synapses are also important in learning and memory. Here we show that blockade of dopaminergic D4 receptors (D4R) promoted the formation of late-LTP and transformed early-LTP into late-LTP. This effect was dependent on protein synthesis, activation of NMDA-receptors and CaMKII. We also show that GABA A -receptor mediated mechanisms are involved in the enhancement of late-LTP. We could show that short-term plasticity and baseline synaptic transmission were unaffected by D4R inhibition. On the other hand, antagonizing D4R prevented both early and late forms of LTD, showing that activation of D4Rs triggered a dual function. Synaptic tagging experiments on LTD showed that D4Rs act as plasticity related proteins rather than the setting of synaptic tags. D4R activation by PD 168077 induced a slow-onset depression that was protein synthesis, NMDAR and CaMKII dependent. The D4 receptors, thus exert a bidirectional modulation of CA1 pyramidal neurons by restricting synaptic strengthening and facilitating synaptic weakening.

Knowledge Integration in Global R&D Networks

NASA Astrophysics Data System (ADS)

Erkelens, Rose; van den Hooff, Bart; Vlaar, Paul; Huysman, Marleen

This paper reports a qualitative study conducted at multinational organizations' R&D departments about their process of knowledge integration. Taking into account the knowledge based view (KBV) of the firm and the practice-based view of knowledge, and building on the literatures concerning specialization and integration of knowledge in organizations, we explore which factors may have a significant influence on the integration process of knowledge between R&D units. The findings indicated (1) the contribution of relevant factors influencing knowledge integration processes and (2) a thoughtful balance between engineering and emergent approaches to be helpful in understanding and overcoming knowledge integration issues.

76 FR 6581 - Airworthiness Directives; Airbus Model A300 B4-600, B4-600R, and F4-600R Series Airplanes, and...

Federal Register 2010, 2011, 2012, 2013, 2014

2011-02-07

... B4-600, B4-600R, and F4-600R Series Airplanes, and Model C4-605R Variant F Airplanes (Collectively Called A300-600 Series Airplanes) AGENCY: Federal Aviation Administration (FAA), DOT. ACTION: Notice of... design review against explosion risks. During improvement of the protection of fuel pump wiring against...

76 FR 27242 - Airworthiness Directives; Airbus Model A300 B4-600, B4-600R, and F4-600R Series Airplanes, and...

Federal Register 2010, 2011, 2012, 2013, 2014

2011-05-11

... Airworthiness Directives; Airbus Model A300 B4-600, B4-600R, and F4-600R Series Airplanes, and Model C4-605R Variant F Airplanes (Collectively Called A300-600 Series Airplanes) AGENCY: Federal Aviation... required to conduct a design review against explosion risks. During improvement of the protection of fuel...

What does leaf wax δD from a mixed C3/C4 vegetation region tell us?

NASA Astrophysics Data System (ADS)

Wang, Yiming V.; Larsen, Thomas; Leduc, Guillaume; Andersen, Nils; Blanz, Thomas; Schneider, Ralph R.

2013-06-01

Hydrogen isotope values (δD) of sedimentary terrestrial leaf wax such as n-alkanes or n-acids have been used to map and understand past changes in rainfall amount in the tropics because δD of precipitation is commonly assumed as the first order controlling factor of leaf wax δD. Plant functional types and their photosynthetic pathways can also affect leaf wax δD but these biological effects are rarely taken into account in paleo studies relying on this rainfall proxy. To investigate how biological effects may influence δD values we here present a 37,000-year old record of δD and stable carbon isotopes (δ13C) measured on four n-alkanes (n-C27, n-C29, n-C31, n-C33) from a marine sediment core collected off the Zambezi River mouth. Our paleo δ13C records suggest that each individual n-alkanes had different C3/C4 proportional contributions. n-C29 was mostly derived from a C3 dicots (trees, shrubs and forbs) dominant vegetation throughout the entire record. In contrast, the longer chain n-C33 and n-C31 were mostly contributed by C4 grasses during the Glacial period but shifted to a mixture of C4 grasses and C3 dicots during the Holocene. Strong correlations between δD and δ13C values of n-C33 (correlation coefficient R2 = 0.75, n = 58) and n-C31 (R2 = 0.48, n = 58) suggest that their δD values were strongly influenced by changes in the relative contributions of C3/C4 plant types in contrast to n-C29 (R2 = 0.07, n = 58). Within regions with variable C3/C4 input, we conclude that δD values of n-C29 are the most reliable and unbiased indicator for past changes in rainfall, and that δD and δ13C values of n-C31 and n-C33 are sensitive to C3/C4 vegetation changes. Our results demonstrate that a robust interpretation of palaeohydrological data using n-alkane δD requires additional knowledge of regional vegetation changes from which n-alkanes are synthesized, and that the combination of δD and δ13C values of multiple n-alkanes can help to differentiate

Final Remedial Investigation Report Area of Contamination (AOC) 57. Volume II. Appendices A through D

DTIC Science & Technology

2000-06-01

completed over AOC 57 at the former Fort Devens in Ayer, MA. Geophysical work was conducted in two...data generated from chemical analyses performed on soil samples collected during the 1995 AOC 57 , 63AX, and 69W Remedial Investigations at Fort Devens ...pg/g W0059621.T80/1 9144-03 continued TABLE D-1 SUMMARY OF ANALYTICAL PARAMETERS AOC 57 , 63AX, AND 69W REMEDIAL INVESTIGATION FORT DEVENS

76 FR 28914 - Airworthiness Directives; Airbus Model A300 B4-600, B4-600R, and F4-600R Series Airplanes, and...

Federal Register 2010, 2011, 2012, 2013, 2014

2011-05-19

... of the rudder system design. Rudder pedal sensitivity on Model A300-600 and A310 series airplanes is... B4-600, B4-600R, and F4-600R Series Airplanes, and Model C4-605R Variant F Airplanes (Collectively Called A300-600 Series Airplanes); and Model A310 Series Airplanes AGENCY: Federal Aviation...

Immunocytochemical localization of metabotropic (mGluR2/3 and mGluR4a) and ionotropic (GluR2/3) glutamate receptors in adrenal medullary ganglion cells.

PubMed

Sarría, R; Díez, J; Losada, J; Doñate-Oliver, F; Kuhn, R; Grandes, P

2006-02-01

The localization of metabotropic glutamate receptors of groups II (mGluR2/3) and III (mGluR4a) and the subunits 2 and 3 of alfa-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid (AMPA) ionotropic glutamate receptors (GluR2/3) was investigated with immunocytochemical methods in the rat adrenal gland. MGluR2/3, mGluR4a and GluR2/3 immunoreactivities were observed in large-sized, centrally located type I adrenal medullary ganglion neurons. Furthermore, the small-sized type II adrenal ganglion neurons identified by their immunoreactivity to brain nitric oxide synthase (bNOS), also expressed mGluR2/3, mGluR4a and GluR2/3. These cells were disposed in the peripheral portion of the adrenal medulla. None of the type I neurons were positively labeled for bNOS. These morphological observations suggest that activation of glutamate receptors in ganglion neurons may be instrumental in the control of adrenal endocrine systems as well as blood regulation.

Relationships between digit ratio (2D:4D) and basketball performance in Australian men.

PubMed

Frick, Nathan A; Hull, Melissa J; Manning, John T; Tomkinson, Grant R

2017-05-06

To investigate relationships between the digit ratio (2D:4D) and competitive basketball performance in Australian men. Using an observational cross-sectional design a total of 221 Australian basketball players who competed in the Olympic Games, International Basketball Federation World Championships/Cup, Australian National Basketball League, Central Australian Basketball League or socially had their 2D:4Ds measured. Analysis of variance was used to assess differences in mean 2D:4Ds between men playing at different competitive standards, with relationships between 2D:4Ds and basketball game-related statistics assessed using Pearson's product moment correlations in men playing at a single competitive standard. There were significant differences between competitive standards for the left 2D:4D following Bonferroni correction, but not for the right 2D:4D, with basketballers who achieved higher competitive standards tending to have lower left 2D:4Ds. No important correlations between 2D:4D and basketball game-related statistics were found, with correlations typically negligible. This study indicated that the 2D:4D can discriminate between basketballers competing at different standards, but not between basketballers within a single competitive standard using objective game-related statistics. © 2016 Wiley Periodicals, Inc.

78 FR 5498 - Importer of Controlled Substances; Notice of Registration; R & D Systems, Inc.

Federal Register 2010, 2011, 2012, 2013, 2014

2013-01-25

...) II Cocaine (9041) II Oxycodone (9143) II Thebaine (9333) II Fentanyl (9801) II The company plans to..., conventions, or protocols in effect on May 1, 1971, at this time. DEA has investigated R & D Systems, Inc., to...

6R-tetrahydrobiopterin treated PKU patients below 4 years of age: Physical outcomes, nutrition and genotype.

PubMed

Aldámiz-Echevarría, Luis; Bueno, María A; Couce, María L; Lage, Sergio; Dalmau, Jaime; Vitoria, Isidro; Llarena, Marta; Andrade, Fernando; Blasco, Javier; Alcalde, Carlos; Gil, David; García, María C; González-Lamuño, Domingo; Ruiz, Mónica; Ruiz, María A; Peña-Quintana, Luis; González, David; Sánchez-Valverde, Felix

2015-05-01

Phenylalanine-restricted diets have proven effective in treating phenylketonuria. However, such diets have occasionally been reported to hinder normal development. Our study aimed to assess whether treating 0-4-year-old phenylketonuric patients with 6R-tetrahydrobiopterin might prevent growth retardation later in life. We conducted a longitudinal retrospective study which examined anthropometric characteristics of phenylketonuric patients on 6R-tetrahydrobiopterin therapy (22 subjects), and compared them with a group of phenylketonuric patients on protein-restricted diets (44 subjects). Nutritional issues were also considered. We further explored possible relationships between mutations in the PAH gene, BH4 responsiveness and growth outcome. No significant growth improvements were observed in either the group on 6R-tetrahydrobiopterin treatment (height Z-score: initial= -0.57 ± 1.54; final=-0.52 ± 1.29; BMI Z-score: initial=0.17 ± 1.05; final=0.18 ± 1.00) or the diet-only group (height Z-score: initial=-0.92 ± 0.96; final= -0.78 ± 1.08; BMI Z-score: initial=0.17 ± 0.97; final=-0.07 ± 1.03) over the 1-year observation period. Furthermore, we found no significant differences (p>0.05) between the two groups at any of the time points considered (0, 6 and 12 months). Patients on 6R-tetrahydrobiopterin increased their phenylalanine intake (from 49.1 [25.6-60.3] to 56.5 [39.8-68.3] mgkg(-1)day(-1)) and natural protein intake (from 1.0 [0.8-1.7] to 1.5 [1.0-1.8] g kg(-1)day(-1)), and some patients managed to adopt normal diets. Higher phenylalanine and natural protein intakes were positively correlated with better physical outcomes in the diet-only group (p<0.05). No correlation was found between patient genotype and physical outcomes, results being similar regardless of the nutritional approach used. We did not detect any side effects due to 6R-tetrahydrobiopterin administration. Our study indicates that treating 0-4-year-old phenylketonuric patients with 6R

43 CFR 4.845 - Final review by Secretary.

Code of Federal Regulations, 2010 CFR

2010-10-01

... 43 Public Lands: Interior 1 2010-10-01 2010-10-01 false Final review by Secretary. 4.845 Section 4.845 Public Lands: Interior Office of the Secretary of the Interior DEPARTMENT HEARINGS AND APPEALS... § 4.845 Final review by Secretary. Paragraph (f) of § 17.9 of this title requires that any final...

JPRS Report, Science & Technology, Japan, MITI’s Large-Scale R&D Projects Reviewed

DTIC Science & Technology

1990-02-08

pollutions, red tide, Active enzymes etc. for cleaners and detergents -- .... .... Intermediates aw materials for r rcosmetics and and medicines moisturizers...PN 00 1H carq 1 0 HZc4 IO -l~ to u .ci~’ *H 0 w 1 Q 0 r - 0 0J w H 04P 04- c0 a) 00 bD O44 0 w w 0 -p 00 021.J4 COQ )a > u0𔃺-0 T1 CL Cfp p P H -H14 OL

NsrR from Streptomyces coelicolor Is a Nitric Oxide-sensing [4Fe-4S] Cluster Protein with a Specialized Regulatory Function*

PubMed Central

Crack, Jason C.; Munnoch, John; Dodd, Erin L.; Knowles, Felicity; Al Bassam, Mahmoud M.; Kamali, Saeed; Holland, Ashley A.; Cramer, Stephen P.; Hamilton, Chris J.; Johnson, Michael K.; Thomson, Andrew J.; Hutchings, Matthew I.; Le Brun, Nick E.

2015-01-01

The Rrf2 family transcription factor NsrR controls expression of genes in a wide range of bacteria in response to nitric oxide (NO). The precise form of the NO-sensing module of NsrR is the subject of controversy because NsrR proteins containing either [2Fe-2S] or [4Fe-4S] clusters have been observed previously. Optical, Mössbauer, resonance Raman spectroscopies and native mass spectrometry demonstrate that Streptomyces coelicolor NsrR (ScNsrR), previously reported to contain a [2Fe-2S] cluster, can be isolated containing a [4Fe-4S] cluster. ChIP-seq experiments indicated that the ScNsrR regulon is small, consisting of only hmpA1, hmpA2, and nsrR itself. The hmpA genes encode NO-detoxifying flavohemoglobins, indicating that ScNsrR has a specialized regulatory function focused on NO detoxification and is not a global regulator like some NsrR orthologues. EMSAs and DNase I footprinting showed that the [4Fe-4S] form of ScNsrR binds specifically and tightly to an 11-bp inverted repeat sequence in the promoter regions of the identified target genes and that DNA binding is abolished following reaction with NO. Resonance Raman data were consistent with cluster coordination by three Cys residues and one oxygen-containing residue, and analysis of ScNsrR variants suggested that highly conserved Glu-85 may be the fourth ligand. Finally, we demonstrate that some low molecular weight thiols, but importantly not physiologically relevant thiols, such as cysteine and an analogue of mycothiol, bind weakly to the [4Fe-4S] cluster, and exposure of this bound form to O2 results in cluster conversion to the [2Fe-2S] form, which does not bind to DNA. These data help to account for the observation of [2Fe-2S] forms of NsrR. PMID:25771538

Neuroprotective Activity of (1S,2E,4R,6R,-7E,11E)-2,7,11-cembratriene-4,6-diol (4R) in vitro and in vivo in Rodent Models of Brain Ischemia

PubMed Central

Xu, Zhenfeng; Mu, Chaofeng; Alvarez, Paloma; Ford, Byron D.; El Sayed, Khalid; Eterovic, Vesna A.; Ferchmin, Pedro A.; Hao, Jiukuan

2015-01-01

(1S,2E,4R,6R,-7E,11E)-2,7,11-cembratriene-4,6-diol (4R) is a precursor to key flavor ingredients in leaves of Nicotiana species. The present study shows 4R decreased brain damage in rodent ischemic stroke models. The 4R-pretreated mice had lower infarct volume (26.2±9.7 mm3) than those in control groups (untreated: 63.4±4.2 mm3, DMSO: 60.2±14.2 mm3). The 4R-posttreated rats also had less infarct volume (120±65 mm3) than those in the rats of DMSO group (291±95 mm3). The results from in vitro experiments indicate that 4R decreased neuro2a cells (neuroblastoma cells) apoptosis induced by oxygen glucose deprivation (OGD), and improved the population spikes (PSs) recovery in rat acute hippocampal slices under OGD; a phosphatidylinositol 3-kinase (PI3K) inhibitor, wortmannin, abolished the effect of 4R on PSs recovery. Furthermore, 4R also inhibited monocyte adhesion to bEND5 cells (murine brain-derived endothelial cells) and upregulation of intercellular adhesion molecule-1(ICAM-1) induced by OGD/reoxygenation (OGD/R), and restored the p-Akt level to pre-OGD/R values in bEND5 cells. In conclusion, the present study indicates that 4R has a protective effect in rodent ischemic stroke models. Inhibition of ICAM-1 expression and restoration of Akt phosphorylation are the possible mechanisms involved in cellular protection by 4R. PMID:25677097

Synthesis and biological characterization of (3R,4R)-4-(2-(benzhydryloxy)ethyl)-1-((R)-2-hydroxy-2-phenylethyl)-piperidin-3-ol and its stereoisomers for monoamine transporters

PubMed Central

Kharkar, Prashant S.; Batman, Angela M.; Zhen, Juan; Beardsley, Patrick M.; Reith, Maarten E. A.

2012-01-01

In this report we describe synthesis and biological evaluation of a series of asymmetric 4-(2-(benzhydryloxy)ethyl)-1-((R)-2-hydroxy-2-phenylethyl)-piperidin-3-ol based dihydroxy compounds where the hydroxy groups are located both on the piperidine ring and also on the N-phenylethyl side chain exo-cyclically. In vitro uptake inhibition data indicates high affinity of these molecules for the dopamine transporter (DAT) in addition to their moderate to high affinity for the norepinephrine transporter (NET). Interestingly, compounds 9b and 9d exhibited affinities for all three monoamine transporters with highest potency at DAT and NET and moderate potency at the serotonin transporter (SERT) (Ki 2.29, 78.4 and 155 nM for 9b and 1.55, 14.1 and 259 nM for 9d, respectively). Selected compounds, 9a, 9d and 9d’ were tested for their locomotor activity effects in mice, and for their ability to occasion the cocaine discriminative stimulus in rats. These test compounds generally exhibited a much longer duration of action than cocaine for elevating locomotor activity, and dose-dependently completely generalized the cocaine discriminative stimulus. PMID:19449323

Insight into a conformation of the PNA-PNA duplex with (2‧R,4‧R)- and (2‧R,4‧S)-prolyl-(1S,2S)-2-aminocyclopentanecarboxylic acid backbones

NASA Astrophysics Data System (ADS)

Maitarad, Amphawan; Poomsuk, Nattawee; Vilaivan, Chotima; Vilaivan, Tirayut; Siriwong, Khatcharin

2018-04-01

Suitable conformations for peptide nucleic acid (PNA) self-hybrids with (2‧R,4‧R)- and (2‧R,4‧S)-prolyl-(1S,2S)-2-aminocyclopentanecarboxylic acid backbones (namely, acpcPNA and epi-acpcPNA, respectively) were investigated based on molecular dynamics simulations. The results revealed that hybridization of the acpcPNA was observed only in the parallel direction, with a conformation close to the P-type structure. In contrast, self-hybrids of the epi-acpcPNA were formed in the antiparallel and parallel directions; the antiparallel duplex adopted the B-form conformation, and the parallel duplex was between B- and P-forms. The calculated binding energies and the experimental data indicate that the antiparallel epi-acpcPNA self-hybrid was more stable than the parallel duplex.

NASA Ames Research Center R and D Services Directorate Biomedical Systems Development

NASA Technical Reports Server (NTRS)

Pollitt, J.; Flynn, K.

1999-01-01

The Ames Research Center R&D Services Directorate teams with NASA, other government agencies and/or industry investigators for the development, design, fabrication, manufacturing and qualification testing of space-flight and ground-based experiment hardware for biomedical and general aerospace applications. In recent years, biomedical research hardware and software has been developed to support space-flight and ground-based experiment needs including the E 132 Biotelemetry system for the Research Animal Holding Facility (RAHF), E 100 Neurolab neuro-vestibular investigation systems, the Autogenic Feedback Systems, and the Standard Interface Glove Box (SIGB) experiment workstation module. Centrifuges, motion simulators, habitat design, environmental control systems, and other unique experiment modules and fixtures have also been developed. A discussion of engineered systems and capabilities will be provided to promote understanding of possibilities for future system designs in biomedical applications. In addition, an overview of existing engineered products will be shown. Examples of hardware and literature that demonstrate the organization's capabilities will be displayed. The Ames Research Center R&D Services Directorate is available to support the development of new hardware and software systems or adaptation of existing systems to meet the needs of academic, commercial/industrial, and government research requirements. The Ames R&D Services Directorate can provide specialized support for: System concept definition and feasibility Mathematical modeling and simulation of system performance Prototype hardware development Hardware and software design Data acquisition systems Graphical user interface development Motion control design Hardware fabrication and high-fidelity machining Composite materials development and application design Electronic/electrical system design and fabrication System performance verification testing and qualification.

The pure rotational spectrum of TiF (X 4Φr): 3d transition metal fluorides revisited

NASA Astrophysics Data System (ADS)

Sheridan, P. M.; McLamarrah, S. K.; Ziurys, L. M.

2003-11-01

The pure rotational spectrum of TiF in its X 4Φr (v=0) ground state has been measured using millimeter/sub-millimeter wave direct absorption techniques in the range 140-530 GHz. In ten out of the twelve rotational transitions recorded, all four spin-orbit components were observed, confirming the 4Φr ground state assignment. Additional small splittings were resolved in several of the spin components in lower J transitions, which appear to arise from magnetic hyperfine interactions of the 19F nucleus. In contrast, no evidence for Λ-doubling was seen in the data. The rotational transitions of TiF were analyzed using a case (a) Hamiltonian, resulting in the determination of rotational and fine structure constants, as well as hyperfine parameters for the fluorine nucleus. The data were readily fit in a case (a) basis, indicating strong first order spin-orbit coupling and minimal second-order effects, as also evidenced by the small value of λ, the spin-spin parameter. Moreover, only one higher order term, η, the spin-orbit/spin-spin interaction term, was needed in the analysis, again suggesting limited perturbations in the ground state. The relative values of the a, b, and c hyperfine constants indicate that the three unpaired electrons in this radical lie in orbitals primarily located on the titanium atom and support the molecular orbital picture of TiF with a σ1δ1π1 single electron configuration. The bond length of TiF (1.8342 Å) is significantly longer than that of TiO, suggesting that there are differences in the bonding between 3d transition metal fluorides and oxides.

ITER-FEAT vacuum vessel and blanket design features and implications for the R&D programme

NASA Astrophysics Data System (ADS)

Ioki, K.; Dänner, W.; Koizumi, K.; Krylov, V. A.; Cardella, A.; Elio, F.; Onozuka, M.; ITER Joint Central Team; ITER Home Teams

2001-03-01

A configuration in which the vacuum vessel (VV) fits tightly to the plasma aids the passive plasma vertical stability, and ferromagnetic material in the VV reduces the toroidal field ripple. The blanket modules are supported directly by the VV. A full scale VV sector model has provided critical information related to fabrication technology and for testing the magnitude of welding distortions and achievable tolerances. This R&D validated the fundamental feasibility of the double wall VV design. The blanket module configuration consists of a shield body to which a separate first wall is mounted. The separate first wall has a facet geometry consisting of multiple flat panels, where 3-D machining will not be required. A configuration with deep slits minimizes the induced eddy currents and loads. The feasibility and robustness of solid hot isostatic pressing joining were demonstrated in the R&D by manufacturing and testing several small and medium scale mock-ups and finally two prototypes. Remote handling tests and assembly tests of a blanket module have demonstrated the basic feasibility of its installation and removal.

Gene encoding the group B streptococcal protein R4, its presence in clinical reference laboratory isolates & R4 protein pepsin sensitivity.

PubMed

Smith, B L; Flores, A; Dechaine, J; Krepela, J; Bergdall, A; Ferrieri, P

2004-05-01

R proteins were first identified by Lancefield in group B Streptococcus (GBS) as resistant to trypsin at pH8 and sensitive to pepsin at pH2. The R4 protein found predominantly in type III and some type II and V invasive isolates conforms to these criteria. The Rib protein, although structurally and epidemiologically similar to R4, was reported as resistant to both proteases. We report here the gene encoding the R4 protein from a type III group B streptococcal isolate (76-043) well characterized in our laboratory. Trypsin extracted GBS proteins were assayed for protease sensitivities by double-diffusion Ouchterlony using varying conditions for the enzyme pepsin. Standard haemoglobin assay was used to examine pepsin enzymatic activity. Thirty clinical isolates of varying protein profiles identified by double-diffusion from our reference strain laboratory were screened by PCR and Southern technique. SDS-PAGE gel purified R4 amino acid sequences were determined and used to design oligonucleotide primers for screening a 76-043 genomic library. R4 was sensitive to pepsin at pH2 but appeared resistant at pH4, the reported pH used for Rib. By standard haemoglobin assay and trypsin extract studies of R4 protein, pepsin was shown to be active at pH2, yet easily inactivated; assays of GBS surface proteins are critical at pH2. Of the amino acids initially sequenced from R4, 88 per cent (61/69) showed identity to Rib; the r4 nucleotide sequence was identical to that of rib. All isolates with strong positive protein reactions for R4 were positive in both PCR and Southern technique, whereas isolates expressing alpha, beta, R1/R4, and R5 (BPS) protein profiles were not. Sequenced PCR products aligned with identity to the R4 and Rib nucleotide sequences and confirmed the identity of these proteins and their molecular sequences.

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

PubMed

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

2014-08-01

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

Patoka Lake Foundation Report. Book 4. Appendix D. Contractor Drill Logs.

DTIC Science & Technology

1983-04-01

IJK1 f°- ..... . .0 e". a I’e ~ .1 , 34.. 411 go-- t.__ 4p//, /, -.z fr FNC PORN 1836 PREVIOUS EDITIONS ARE OBSOLETE PROJECT HOLE NO. MAR71 t...AE OSOLTS. PROECT 4OL NO BEEI 71 /A*I .. ~ ~ ISO LOCATIONIO (C.U4.i. N, TII~ .3____________________________ 1. -ROJET IA. siOTAND NTMPER orE BOi E S...IN ~ .. d N.1 K. SGAUEOINPO. R I.*.R. f.4~k . T Od OF HOLELVTO LEGEN ", UIIC , CL •% COE ,p JNP LIt ./" /yIf/ -z- 8MNG PORN # 18 36 PREVIOUS EDI

Neuroprotective activity of (1S,2E,4R,6R,-7E,11E)-2,7,11-cembratriene-4,6-diol (4R) in vitro and in vivo in rodent models of brain ischemia.

PubMed

Martins, Antonio H; Hu, Jing; Xu, Zhenfeng; Mu, Chaofeng; Alvarez, Paloma; Ford, Byron D; El Sayed, Khalid; Eterovic, Vesna A; Ferchmin, Pedro A; Hao, Jiukuan

2015-04-16

(1S,2E,4R,6R,-7E,11E)-2,7,11-cembratriene-4,6-diol (4R) is a precursor to key flavor ingredients in leaves of Nicotiana species. The present study shows 4R decreased brain damage in rodent ischemic stroke models. The 4R-pretreated mice had lower infarct volumes (26.2±9.7 mm3) than those in control groups (untreated: 63.4±4.2 mm3, DMSO: 60.2±14.2 mm3). The 4R-posttreated rats also had less infarct volumes (120±65 mm3) than those in the rats of the DMSO group (291±95 mm3). The results from in vitro experiments indicate that 4R decreased neuro2a cell (neuroblastoma cells) apoptosis induced by oxygen-glucose deprivation (OGD), and improved the population spikes' (PSs) recovery in rat acute hippocampal slices under OGD; a phosphatidylinositol 3-kinase (PI3K) inhibitor, wortmannin, abolished the effect of 4R on PSs recovery. Furthermore, 4R also inhibited monocyte adhesion to murine brain-derived endothelial (bEND5) cells and upregulation of intercellular adhesion molecule-1(ICAM-1) induced by OGD/reoxygenation (OGD/R), and restored the p-Akt level to pre-OGD/R values in bEND5 cells. In conclusion, the present study indicates that 4R has a protective effect in rodent ischemic stroke models. Inhibition of ICAM-1 expression and restoration of Akt phosphorylation are the possible mechanisms involved in cellular protection by 4R. Copyright © 2015 IBRO. Published by Elsevier Ltd. All rights reserved.

Comparison of International Transportation R&D Expenditures and Priorities. (Second clearance edition)

DOT National Transportation Integrated Search

1999-07-01

This report provides a summary of total expenditures on research and development (R&D) in general, and of transportation R&D in particular, by the major performers of transportation R&D within the international community. It also compares these level...

The 4d8-(4d74f + 4d76p + 4p54d9) transitions in the spectrum of five times ionized indium (In VI)

NASA Astrophysics Data System (ADS)

Ryabtsev, A. N.; Tauheed, A.; Swapnil; Kildiyarova, R. R.; Kononov, E. Ya

2018-06-01

The spectrum of five times ionized indium excited in a vacuum spark has been studied in the wavelength region 180-250 Å using a 3 m grazing incidence spectrograph. Transitions from highly excited interacting configurations 4d74f + 4d76p + 4p54d9 to the ground state 4d8 configuration were studied. 165 spectral lines were identified and 81 levels of the excited configurations were found.

The Plasmodium falciparum exported protein PF3D7_0402000 binds to erythrocyte ankyrin and band 4.1

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

Shakya, Bikash; Penn, Wesley D.; Nakayasu, Ernesto S.

Plasmodium falciparum extensively modifies the infected red blood cell (RBC), resulting in changes in deformability, shape and surface properties. These alterations suggest that the RBC cytoskeleton is a major target for modification during infection. However, the molecular mechanisms leading to these changes are largely unknown. To begin to address this question, we screened for exported P. falciparum proteins that bound to the erythrocyte cytoskeleton proteins ankyrin 1 (ANK1) and band 4.1 (4.1R), which form critical interactions with other cytoskeletal proteins that contribute to the deformability and stability of RBCs. Yeast two-hybrid screens with ANK1 and 4.1R identified eight interactions withmore » P. falciparum exported proteins, including an interaction between 4.1R and PF3D7_0402000 (PFD0090c). This interaction was first identified in a large-scale screen (Vignali et al., Malaria J, 7:211, 2008), which also reported an interaction between PF3D7_0402000 and ANK1. We confirmed the interactions of PF3D7_0402000 with 4.1R and ANK1 in pair-wise yeast two-hybrid and co-precipitation assays. In both cases, an intact PHIST domain in PF3D7_0402000 was required for binding. Complex purification followed by mass spectrometry analysis provided additional support for the interaction of PF3D7_0402000 with ANK1 and 4.1R. RBC ghost cells loaded with maltose-binding protein (MBP)-PF3D7_0402000 passed through a metal microsphere column less efficiently than mock- or MBP-loaded controls, consistent with an effect of PF3D7_0402000 on RBC rigidity or membrane stability. This study confirmed the interaction of PF3D7_0402000 with 4.1R in multiple independent assays, provided the first evidence that PF3D7_0402000 also binds to ANK1, and suggested that PF3D7_0402000 affects deformability or membrane stability of uninfected RBC ghosts.« less

Digit ratio (2D:4D) in individuals with intellectual disability: investigating the role of testosterone in the establishment of cerebral lateralisation.

PubMed

Ypsilanti, Antonia; Ganou, Maria; Koidou, Irene; Grouios, George

2008-11-01

It has been proposed that the ratio of the second to fourth digits (2D:4D) may be a proxy of prenatal androgen exposure, such that low 2D:4D ratio is associated with high prenatal androgen exposure. The aim of the present study was to measure the 2D:4D ratio in 100 right- and non-right-handed individuals with intellectual disability of unknown idiopathic origin and compare them to a control group of 85 typically developing individuals. We also sought to determine whether sexually dimorphic traits, such as 2D:4D ratio, tend to be more pronounced on the right hand of these groups than on the left. Our results indicated that males had lower 2D:4D ratios than females in both groups, and individuals with intellectual disability had higher ratios only in their right hand compared to typically developing individuals. Further, right-handed individuals had lower ratios in both hands compared to non-right-handed individuals. Our results are discussed in relation to the "Geschwind-Behan-Galaburda theory of cerebral lateralisation" and Witelson's callosal hypothesis that differential levels of prenatal testosterone exposure will cause atypical cerebral laterality in individuals with intellectual disability, and the suggestion that this atypicality will become evident in the 2D:4D ratio (Manning, Scutt, Wilson, & Lewis-Jones, 1998).

4D superfield reduction of 5D orbifold SUGRA and heterotic M-theory

NASA Astrophysics Data System (ADS)

Paccetti Correia, Filipe; Schmidt, Michael G.; Tavartkiladze, Zurab

2006-09-01

We present a detailed study of the reduction to 4D of 5D supergravity compactified on the S/Z orbifold. For this purpose we develop and employ a recently proposed N=1 conformal superfield description of the 5D supergravity couplings to Abelian vector and hypermultiplets. In particular, we obtain a unique relation of the "radion" to chiral superfields as in global 5D SUSY and we can embed the universal hypermultiplet into this formalism. In our approach, it is transparent how the superconformal structure of the effective 4D actions is inherited from the one of the original 5D supergravity. We consider both ungauged and gauged 5D supergravities. This includes compactifications in unwarped geometries, generalizations of the supersymmetric Randall-Sundrum (RS) model as well as 5D heterotic M-theory. In the unwarped case, after obtaining the effective Kähler potentials and superpotentials, we demonstrate that the tree-level 4D potentials have flat and/or tachyonic directions. One-loop corrections to the Kähler potential and gaugino condensation are presented as suitable tools for moduli stabilization to be discussed in subsequent work. Turning to the RS-like models, we obtain a master formula for the Kähler potential for an arbitrary number of vector and hyper moduli, which we evaluate exactly for special cases. Finally, we formulate the superfield description of 5D heterotic M-theory and obtain its effective 4D description for the universal ( h=1) case, in the presence of an arbitrary number of bulk 5-branes. We present, as a check of our expressions, time-dependent solutions of 4D heterotic M-theory, which uplift to 5D solutions generalizing the ones recently found in [W. Chen, Z.-W. Chong, G.W. Gibbons, H. Lü, C.N. Pope, Hořava-Witten stability: Eppur si muove, Nucl. Phys. B 732 (2006) 118, hep-th/0502077].

Dopamine D3/D2 Receptor Antagonist PF-4363467 Attenuates Opioid Drug-Seeking Behavior without Concomitant D2 Side Effects.

PubMed

Wager, Travis T; Chappie, Thomas; Horton, David; Chandrasekaran, Ramalakshmi Y; Samas, Brian; Dunn-Sims, Elizabeth R; Hsu, Cathleen; Nawreen, Nawshaba; Vanase-Frawley, Michelle A; O'Connor, Rebecca E; Schmidt, Christopher J; Dlugolenski, Keith; Stratman, Nancy C; Majchrzak, Mark J; Kormos, Bethany L; Nguyen, David P; Sawant-Basak, Aarti; Mead, Andy N

2017-01-18

Dopamine receptor antagonism is a compelling molecular target for the treatment of a range of psychiatric disorders, including substance use disorders. From our corporate compound file, we identified a structurally unique D3 receptor (D3R) antagonist scaffold, 1. Through a hybrid approach, we merged key pharmacophore elements from 1 and D3 agonist 2 to yield the novel D3R/D2R antagonist PF-4363467 (3). Compound 3 was designed to possess CNS drug-like properties as defined by its CNS MPO desirability score (≥4/6). In addition to good physicochemical properties, 3 exhibited low nanomolar affinity for the D3R (D3 K i = 3.1 nM), good subtype selectivity over D2R (D2 K i = 692 nM), and high selectivity for D3R versus other biogenic amine receptors. In vivo, 3 dose-dependently attenuated opioid self-administration and opioid drug-seeking behavior in a rat operant reinstatement model using animals trained to self-administer fentanyl. Further, traditional extrapyramidal symptoms (EPS), adverse side effects arising from D2R antagonism, were not observed despite high D2 receptor occupancy (RO) in rodents, suggesting that compound 3 has a unique in vivo profile. Collectively, our data support further investigation of dual D3R and D2R antagonists for the treatment of drug addiction.

Do large mergers increase or decrease the productivity of pharmaceutical R&D?

PubMed

Ringel, Michael S; Choy, Michael K

2017-12-01

There is current uncertainty regarding the effects of mergers on pharmaceutical R&D productivity, with various mechanisms reported by which mergers could either help or harm R&D, and mixed empirical findings in prior analyses. Here, we present an analysis that is novel in several ways: we use downstream measures of R&D productivity, account for both inputs and outputs in our calculations, and use a self-controlled design. We find that recent large pharmaceutical mergers are associated with statistically significant increases in R&D productivity. These results are perhaps not surprising in light of the broader literature on R&D productivity that points to two factors as instrumental in driving higher R&D productivity (depth of scientific information, and objectivity of decision-making based on that information), both of which could be expected to increase because of a merger. Copyright © 2017 Elsevier Ltd. All rights reserved.

Fear Memory Recall Potentiates Opiate Reward Sensitivity through Dissociable Dopamine D1 versus D4 Receptor-Dependent Memory Mechanisms in the Prefrontal Cortex.