Dynamics, integrability and topology for some classes of Kolmogorov Hamiltonian systems in R+4
NASA Astrophysics Data System (ADS)
Llibre, Jaume; Xiao, Dongmei
2017-02-01
In this paper we first give the sufficient and necessary conditions in order that two classes of polynomial Kolmogorov systems in R+4 are Hamiltonian systems. Then we study the integrability of these Hamiltonian systems in the Liouville sense. Finally, we investigate the global dynamics of the completely integrable Lotka-Volterra Hamiltonian systems in R+4. As an application of the invariant subsets of these systems, we obtain topological classifications of the 3-submanifolds in R+4 defined by the hypersurfaces axy + bzw + cx2 y + dxy2 + ez2 w + fzw2 = h, where a , b , c , d , e , f , w and h are real constants.
The perspectives, information and conclusions conveyed in research project abstracts, progress reports, final reports, journal abstracts and journal publications convey the viewpoints of the principal investigator and may not represent the views and policies of ORD and EPA. Concl...
The perspectives, information and conclusions conveyed in research project abstracts, progress reports, final reports, journal abstracts and journal publications convey the viewpoints of the principal investigator and may not represent the views and policies of ORD and EPA. Concl...
1983-05-31
ANALYSIS OF SEABED STABILITY AT THE NORFOLK OCEAN DISPOSAL SITE PART 1: GEOLOGICAL ANALYSIS U LU D George F. Oertel, Principal Investigator i- Final Report...eC.it ,ie _. _ r. .. .... All e d !t-o i’~$ ~- - - • ° . .. • : " . o . . . , . . ... - . • , .. . . . . . kkN 4. 18. parameters, diver reconnaissance of...For the period ending September 30, 1982 Prepared for the Department of the Army Norfolk District, Corps of Engineers 803 Front Street D I *Norfolk
Customized Blueprints to Enhance the Participation of HBCU/MIs in DoD-Related R&D Programs
1991-12-15
I AD-A245 212 FINAL REPORT FOR PROJECT ENTILED CUSTOMIZED BLUEPRINTS TO ENHANCE THE [ PARTICIPATION OF tIBCU/MIs IN DoD-RELATED R& D PROGRAMS I U...ELECTE. December 15, 1991 JAN 2 3 1992 I Submitted to: D Ms. Tracy Pinson Dennis Office of the Secretary of Defense Office of Small and Disadvantaged...fox Public rlocise and sale; its - "" " - , d ’ tribution is unlimited.U! FOREWORD 4 This Final Report by TRACTELL, Incorporated summarizes its
Instrumentation for Detecting Hazardous Materials.
1980-06-01
CATALOG NUMBER 1940-4)_ _ _ _ _ _ 4. TITLE (,.d Subtitle) _ JVE OF r , AL*3O.[OYE_ D .- / Final ; , .. P - 4^NSTRUtENTAT ION FOR DETECTING HAZARDOUS...CL a D- 4- a ... E - 0US m -i M r i US U Ci 0 Ui . Ci C) Ci. 4.. 9* Ci0 44. 4-S i C U i 5U - . ’- -) 0 C- c -CiOZ E 0 04 CiC C’ - E-.0 m N 4- 10 m E4...1 z 0 - C)4 -4 54-1 C)) 04Q). 0U $4i 4I - 40. U a) 0)U r -H 0) -a 0r- u 1-- 1% 4J ( C.) 4 0 0 4~J >1) C) r ’ (0 4 T - -4 U) C C) 0 *- C)0 - 4 f 04 C) C
R&D Progress of HTS Magnet Project for Ultrahigh-field MRI
NASA Astrophysics Data System (ADS)
Tosaka, Taizo; Miyazaki, Hiroshi; Iwai, Sadanori; Otani, Yasumi; Takahashi, Masahiko; Tasaki, Kenji; Nomura, Shunji; Kurusu, Tsutomu; Ueda, Hiroshi; Noguchi, So; Ishiyama, Atsushi; Urayama, Shinichi; Fukuyama, Hidenao
An R&D project on high-temperature superconducting (HTS) magnets using rare-earth Ba2Cu3O7 (REBCO) wires was started in 2013. The project objective is to investigate the feasibility of adapting REBCO magnets to ultrahigh field (UHF) magnetic resonance imaging (MRI) systems. REBCO wires are promising components for UHF-MRI magnets because of their superior superconducting and mechanical properties, which make them smaller and lighter than conventional ones. Moreover, REBCO magnets can be cooled by the conduction-cooling method, making liquid helium unnecessary. In the past two years, some test coils and model magnets have been fabricated and tested. This year is the final year of the project. The goals of the project are: (1) to generate a 9.4 T magnetic field with a small test coil, (2) to generate a homogeneous magnetic field in a 200 mm diameter spherical volume with a 1.5 T model magnet, and (3) to perform imaging with the 1.5 T model magnet. In this paper, the progress of this R&D is described. The knowledge gained through these R&D results will be reflected in the design of 9.4 T MRI magnets for brain and whole body imaging.
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.
Quantum deformations of conformal algebras with mass-like deformation parameters
DOE Office of Scientific and Technical Information (OSTI.GOV)
Frydryszak, Andrzej; Lukierski, Jerzy; Mozrzymas, Marek
1998-12-15
We recall the mathematical apparatus necessary for the quantum deformation of Lie algebras, namely the notions of coboundary Lie algebras, classical r-matrices, classical Yang-Baxter equations (CYBE), Froebenius algebras and parabolic subalgebras. Then we construct the quantum deformation of D=1, D=2 and D=3 conformal algebras, showing that this quantization introduce fundamental mass parameters. Finally we consider with more details the quantization of D=4 conformal algebra. We build three classes of sl(4,C) classical r-matrices, satisfying CYBE and depending respectively on 8, 10 and 12 generators of parabolic subalgebras. We show that only the 8-dimensional r-matrices allow to impose the D=4 conformal o(4,2){approx_equal}su(2,2)more » reality conditions. Weyl reflections and Dynkin diagram automorphisms for o(4,2) define the class of admissible bases for given classical r-matrices.« less
Small Unix data acquisition system
NASA Astrophysics Data System (ADS)
Engberg, D.; Glanzman, T.
1994-02-01
A R&D program has been established to investigate the use of Unix in the various aspects of experimental computation. Earlier R&D work investigated the basic real-time aspects of the IBMRS/6000 workstation running AIX, which claims to be a real-time operating system. The next step in this R&D is the construction of prototype data acquisition system which attempts to exercise many of the features needed in the final on-line system in a realistic situation. For this project, we have combined efforts with a team studying the use of novel cell designs and gas mixtures in a new prototype drift chamber.
Liang, Wei -Hong; Molina, R.; Xie, Ju -Jun; ...
2015-05-22
We investigate the decay ofmore » $$\\bar B^0 \\to \\bar K^{*0} R$$ and $$\\bar B^0_s \\to \\phi R$$ with $R$ being the $X(4160)$, $Y(3940)$, $Z(3930)$ resonances. Under the assumption that these states are dynamically generated from the vector-vector interaction, as has been concluded from several theoretical studies, we use a reaction mechanism of quark production at the elementary level, followed by hadronization of one final $$q \\bar q$$ pair into two vectors and posterior final state interaction of this pair of vector mesons to produce the resonances. With this procedure we are able to predict five ratios for these decays, which are closely linked to the dynamical nature of these states, and also predict the order of magnitude of the branching ratios which we find of the order of $$10^{-4}$$, well within the present measurable range. In order to further test the dynamical nature of these resonances we study the $$\\bar B^0_s \\to \\phi D^* \\bar D^*$$ and $$\\bar B^0_s \\to \\phi D_s^* \\bar D_s^*$$ decays close to the $$D^* \\bar D^*$$ and $$D_s^* \\bar D_s^*$$ thresholds and make predictions for the ratio of the mass distributions in these decays and the $$\\bar B^0_s \\to \\phi R$$ decay widths. In conclusion, the measurement of these decays rates can help unravel the nature of these resonances.« less
R&D status of linear collider technology at KEK
NASA Astrophysics Data System (ADS)
Urakawa, Junji
1992-02-01
This paper gives an outline of the Japan Linear Collider (JLC) project, especially JLC-I. The status of the various R&D works is particularly presented for the following topics: (1) electron and positron sources, (2) S-band injector linacs, (3) damping rings, (4) high power klystrons and accelerating structures, (5) the final focus system. Finally, the status of the construction and design studies for the Accelerator Test Facility (ATF) is summarized.
Laboratory for Computer Science Progress Report 24, July 1986-June 1987
1987-06-01
Szolovits, Group Leader R. Patil Collaborating Investigators M. Criscitiello, M.D., Tufts-New England Medical Center Hospital M. Eckman, M.D., Tufts-New...solutiolls from previously seen patients to aid in the treatment of subsequent patients. Finally, some knowledge (e.g., strategic and treatment, but...Academic Staff Arvind, Group Leader J.B. Dennis R.S. Nikhil Research Staff G.A. Boughton Graduate Students P.S. Barth G.K. Maa S.A. Brobst D.R. Morals
SU-D-18C-01: A Novel 4D-MRI Technology Based On K-Space Retrospective Sorting
DOE Office of Scientific and Technical Information (OSTI.GOV)
Liu, Y; Yin, F; Cai, J
2014-06-01
Purpose: Current 4D-MRI techniques lack sufficient temporal/spatial resolution and consistent tumor contrast. To overcome these limitations, this study presents the development and initial evaluation of an entirely new framework of 4D-MRI based on k-space retrospective sorting. Methods: An important challenge of the proposed technique is to determine the number of repeated scans(NR) required to obtain sufficient k-space data for 4D-MRI. To do that, simulations using 29 cancer patients' respiratory profiles were performed to derive the relationship between data acquisition completeness(Cp) and NR, also relationship between NR(Cp=95%) and the following factors: total slice(NS), respiratory phase bin length(Lb), frame rate(fr), resolution(R) andmore » image acquisition starting-phase(P0). To evaluate our technique, a computer simulation study on a 4D digital human phantom (XCAT) were conducted with regular breathing (fr=0.5Hz; R=256×256). A 2D echo planer imaging(EPI) MRI sequence were assumed to acquire raw k-space data, with respiratory signal and acquisition time for each k-space data line recorded simultaneously. K-space data was re-sorted based on respiratory phases. To evaluate 4D-MRI image quality, tumor trajectories were measured and compared with the input signal. Mean relative amplitude difference(D) and cross-correlation coefficient(CC) are calculated. Finally, phase-sharing sliding window technique was applied to investigate the feasibility of generating ultra-fast 4D-MRI. Result: Cp increased with NR(Cp=100*[1-exp(-0.19*NR)], when NS=30, Lb=100%/6). NR(Cp=95%) was inversely-proportional to Lb (r=0.97), but independent of other factors. 4D-MRI on XCAT demonstrated highly accurate motion information (D=0.67%, CC=0.996) with much less artifacts than those on image-based sorting 4D-MRI. Ultra-fast 4D-MRI with an apparent temporal resolution of 10 frames/second was reconstructed using the phase-sharing sliding window technique. Conclusions: A novel 4D-MRI technology based on k-space sorting has been successfully developed and evaluated on the digital phantom. Framework established can be applied to a variety of MR sequences, showing great promises to develop the optimal 4D-MRI technique for many radiation therapy applications. NIH (1R21CA165384-01A1)« less
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
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
2012-04-22
... j. J i \\ | 1 BCI Hi-Volume Air Si:. plrr Cnl !*>r.it !» r. It.-.' i Sh(-v Hl-Vol S/N J'ro), ,L ::.-. ... I T" 187 ; - '' of /« n r ! BCI I'i-V >hirt- All '..n p 1 • ii ) il iti hi-Xol S/N ...
Biomarkers of Risk for Post-Traumatic Stress Disorder (PTSD)
2008-05-01
post - traumatic stress disorder ( PTSD ),” Principal Investigator, 4/07-4/10, $276,422. 12. R01 MH0687670-01 “DEX/CRH Response... Stress Disorder ( PTSD ) PRINCIPAL INVESTIGATOR: Audrey R. Tyrka, M.D., Ph.D. CONTRACTING ORGANIZATION: Butler Hospital... Stress Disorder ( PTSD ) 5a. CONTRACT NUMBER 5b. GRANT NUMBER W81XWH-07-1-0269 5c. PROGRAM ELEMENT NUMBER 6. AUTHOR(S) Audrey R.
Remedial Investigation Badger Army Ammunition Plant, Baraboo, Wisconsin. Volume 5. Appendix K.5
1991-01-01
4 -4 -4 -4 -4.4 -4r44 4 4-4 -4 ~ 4 .010 -4 000000000000000000000000 000000000000000000000000000 *d -4 8 (a *~ SI * 4JI j -OZ2~404 ZtM0G. .P4000I 4bd ...000000000000000 4.3 tD ~-O-.4- 4-%iCiIO f ~~a to -: u t A w 00000000000000000000000000 )1 310000000000000000000000000000 m o >.,V 0i. 01 00 01 r4rle4r e4
Paul, Noel M.; Taylor, Michelle; Kumar, Rakesh; Deschamps, Jeffrey R.; Luedtke, Robert R.; Newman, Amy Hauck
2011-01-01
Discovering dopamine D2-like receptor subtype-selective ligands has been a focus of significant investigation. The D2R-selective antagonist 3-[4-(4-chlorophenyl)-4-hydroxypiperidinyl]methylindole (1, L741,626; Ki(D2R/D3R) = 11.2:163 nM) has previously provided a lead template for chemical modification. Herein, analogues have been synthesized where the piperidine was replaced by a tropane ring that reversed the selectivity seen in the parent compound, in human hD2LR- or hD3R-transfected HEK 293 cells (31, Ki(D2R/D3R) = 33.4: 15.5 nM). Further exploration of both N-substituted and aryl ring-substituted analogues resulted in the discovery of several high affinity D2R/D3R ligands with 3-benzofurylmethyl-substituents (e.g., 45, Ki(D2R/D3R) = 1.7:0.34 nM) that induced high affinity not achieved in similarly N-substituted piperidine analogues and significantly (470-fold) improved D3R binding affinity compared to the parent ligand 1. X-ray crystallographic data revealed a distinctive spatial arrangement of pharmacophoric elements in the piperidinol vs tropine analogues, providing clues for the diversity in SAR at the D2 and D3 receptor subtypes. PMID:18774793
NASA Astrophysics Data System (ADS)
Liang, Wen; Yin, Yuan; Li, Zeming; Li, Rui; Li, Lin; He, Yu; Dong, Haini; Li, Zengsheng; Yan, Shuai; Zhai, Shuangmeng; Li, Heping
2018-03-01
Single crystals of impurity-free siderite were grown successfully using high-temperature-pressure annealing. The size of crystals ranged up to 100 µm, and they exhibited a rhomboid shape upon cleavage along the (101) plane. The composition of Fe0.9988±0.0011CO3 was quantified using electron probe analysis. Accurate crystalline structural data were investigated by means of single crystal X-ray diffraction (XRD) and the unit cell dimensions obtained in the rhombohedral symmetry of the R\\bar {3}c space group were a = 4.6861(3) and c = 15.362(2), and the final R = 0.0499. Using in situ synchrotron XRD, the high-pressure behavior of impurity-free siderite was investigated up to 20 GPa at ambient temperature. The pressure-volume (P-V) EoS was fitted by a third-order Birch-Murnaghan equation, and the isothermal bulk modulus was K 0 = 97.5(11) GPa for K 0' = 4. High-pressure Raman spectroscopy was performed at up to 30 GPa at ambient temperature, and the Raman bands shifted as the increase of pressure ({{d/ν _i}}{{{d}P}} ) was determined. In combination with the high-pressure Raman results and the bulk modulus K 0, the mode Grüneisen parameters of each vibration were calculated. Meanwhile, high-temperature Raman spectroscopy was carried out at up to 300 °C and the Raman band shift ({{d/ν _i}}{{{d}t}} ) was also quantified.
Korb, Alexander S.; Hunter, Aimee M.; Cook, Ian A.; Leuchter, Andrew F.
2011-01-01
In treatment trials for Major Depressive Disorder (MDD), early symptom improvement is predictive of eventual clinical response. Clinical response may also be predicted by elevated pretreatment theta (4-7 Hz) current density in the rostral anterior cingulate (rACC) and medial orbitofrontal cortex (mOFC). We investigated the relationship between pretreatment EEG and early improvement in predicting clinical outcome in 72 MDD subjects across three placebo-controlled treatment trials. Subjects were randomized to receive fluoxetine, venlafaxine, or placebo. Theta current density in the rACC and mOFC was computed with Low-Resolution Brain Electromagnetic Tomography (LORETA). An ANCOVA, examining week 8 Hamilton Depression Rating Scale (HamD) percent change, showed a significant effect of week-2-HamD-percent-change, and a significant three-way interaction of week-2-HamD-percent-change × Treatment × rACC. Medication subjects with robust early improvement showed almost no relationship between rACC theta current density and final clinical outcome. However, in subjects with little early improvement, rACC activity showed a strong relationship with clinical outcome. The model examining mOFC showed a trend in the three-way interaction. A combination of pretreatment rACC activity and early symptom improvement may be useful for predicting treatment response. PMID:21546222
Pathogenesis of Dengue Vaccine Viruses in Mosquitoes.
1982-07-01
r AD Af29 019 PA I4OGENESIS OF DENGUE VACCINE VIRUSES IN MOSQITOES U) YALE UNIV NEW YIAVEN CONN SCHOOL OF MEDICINE B JBEAT ET AL 01 JUL 82 DAMD1779...1963-A ’UNCLASS IFIET) .AD.- PATHOGENESIS OF DENGUE VACCINE VIRUSES IN MOSQUITOES FINAL REPORT Barry J. Beaty, Ph.D. Thomas H. G. Aitken, Ph.D. July 1...NUMBER 4. TITLE (mid Subdl.) S. KVPE OF REPORT & PERIOD COVERED PATHOGENESIS OF DENGUE VACCINE VIRUSES Final Scientific Report IN MOSQUITOES 6/1/79 to 6
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 dopamine release concentration. Finally, these results demonstrate a functional voltammetric assay that characterizes dopamine D2-like agonists as either D2- or D3-preferring agonists by taking advantage of the unique receptor density within the striatum. PMID:20567609
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 secretion, strongly suggesting their involvement in the rPmp18.1-induced IL-1β cytokine secretion. Taken together, these results indicate that C. abortus Pmp18.1 induces IL-1β secretion by TLR4 activation through the MyD88, NF-κB as well as the Caspase-1 signaling pathways and may be a potential C. abortus vaccine candidate. The vaccine potential of Pmp18.1 will subsequently be evaluated in an appropriate animal model, using VCG as an immunomodulator, following immunization and challenge. PMID:29326885
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
Investigation of the Effect of Low Level Maritime Haze on DMSP VHR and LF Imagery.
1980-09-09
LA S LO i-4 CNJ 0) r m~X LA3 crj (N > Co -i s- - -I CN r -~ 4J. 4-4 C) 4-) >1 Cl) 0H 9 -r-( Nl NV C 0 MN (1)0 r4 s-4 L 4-)4 Uv) Cu...be approximated as : 5-12 o 0 LA r40 oD (n rn N .4 .-4 0 C14.. LA Ln LA N- 0N 0C) LA 4 . l4-) r-. LA en C4 N . 049 0 1 E-4~ . (1 0 .t 0 ’p .r LA LA LA ...w CN C1 04 .00 C4.) r -4 O N~ ’. r - CA a ’.0 LA w m~ N1 Q4-1 Ř .4.4 Q) I- Q) in - r-4 O 4 1d -4 0 0 4J *-0 0~
Modeling of Flowing Plasmas and Pulse Power Schemes for O2(1Delta) Production for Chemical Lasers
2008-01-19
Project (0704-0188) Washington, DC 20503. PLEASE DO NOT RETURN YOUR FORM TO THE ABOVE ADDRESS. 1. R E P O R T D A T E (D D -M M Y Y M 2 . R E P O R T T Y P... E . U mI 2 00AJL r- r - u g u s 2 0 0 7 Final Technical Report 1i September 2005- 31 August 2007 4. TITLE AND SUBTITLE Sa. CONTRACT NUMBER Modeling...should be near 1.2 eV, which corresponds to an E /N of t10 Townsend [ 1 Townsend (Td) = 101 7 V-cm 2]. Self-sustained discharges in He/0 2 mixtures
Two-point correlation function in systems with van der Waals type interaction
NASA Astrophysics Data System (ADS)
Dantchev, D.
2001-09-01
The behavior of the bulk two-point correlation function G( r; T| d ) in d-dimensional system with van der Waals type interactions is investigated and its consequences on the finite-size scaling properties of the susceptibility in such finite systems with periodic boundary conditions is discussed within mean-spherical model which is an example of Ornstein and Zernike type theory. The interaction is supposed to decay at large distances r as r - (d + σ), with 2 < d < 4, 2 < σ < 4 and d + σ≤6. It is shown that G( r; T| d ) decays as r - (d - 2) for 1 ≪ r≪ξ, exponentially for ξ≪ r≪ r *, where r * = (σ - 2)ξlnξ, and again in a power law as r - (d + σ) for r≫ r *. The analytical form of the leading-order scaling function of G( r; T| d ) in any of these regimes is derived.
Tooele Army Depot Revised Final Site-Wide Ecological Risk Assessment. Volume IV.
1998-02-01
SS!5!55 "^ **i "i *n Q ti ti d ci *»S «S «n *n «n 6 Ö Ö «*$ «ri «r> *r) Wj «1 «rj o c> o <a fr^ «•! *rj f) rrj «*j fry ...Venugopal and Luckey 1978. Arsenic 0.94 (mouse, AsIII and AsV) 0.95 (dog, AsV) 60 - 90 (rat) 2.5 ( chicken ) 2.4 (dog) 0.0077-0.012 0.277 0.288...reservation. A pan of that investigation involves a search for rare plant species, those that might be included under stipulations of the Endangered
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.
A small Unix-based data acquisition system
DOE Office of Scientific and Technical Information (OSTI.GOV)
Engberg, D.; Glanzman, T.
1994-02-01
The proposed SLAC B Factory detector plans to use Unix-based machines for all aspects of computing, including real-time data acquisition and experimental control. A R and D program has been established to investigate the use of Unix in the various aspects of experimental computation. Earlier R and D work investigated the basic real-time aspects of the IBM RS/6000 workstation running AIX, which claims to be a real-time operating system. The next step in this R and D is the construction of a prototype data acquisition system which attempts to exercise many of the features needed in the final on-line systemmore » in a realistic situation. For this project, the authors have combined efforts with a team studying the use of novel cell designs and gas mixtures in a new prototype drift chamber.« less
1976-05-01
film airflow anemometry used for vortex measurements in the series of tests is described in reference 6. However, there were two major differences in...LOCKHEED 11011 TRAILING VORTEX SYSTEM USING TOWER FLY-BY TECHNIQUE Leo J. fiarodz ,OtTt4V MAY 1976 FINAL REPORT D k ■?tp r~ "ft UElaibu u...THE LOCKHEED L1011 TRAILING VORTEX SYSTEM USING TOWER FLY-BY TECHNIQUE 7. Authc Leo J. Garodz 9. Performing Orgoni lotion Nome ond Address
1993-09-22
SURVEY OF THREE IBERVILLE PARISH LEVEE ENLARGEMENT AND REVETMENT CONSTRUCTION ITEMS September 1993 Sam .4 D2 FINAL REPORT E R. Christopher Goodwin...LEVEE ENLARGEMENT ANj REVETMENT CONSTRUCTION ITEMS 12. PERSONAL AUTHOR(S) R. Christopher Goodwin, Ph.d., Rebecca E. Bruce, Lawrence L Hewitt, and E... block number) FIELD GROUP SUB-GROUP Acadian Coast Historic Arche6cogy Rice Antebellum Iberville Parish Saw Mill Plantation Carville Leprosarium Ophelia
Investigation of the Phase Stabilizing Effect of Potassium Fluoride on Ammonium Nitrate
1989-07-01
fit? FE CP R+bD S&1:,C)4-0i Investigation of the Phase Stabilizing Effect of Potassium Fluoride on Ammonium Nitrate Re-f.-: R& D # 5955-CH-OX...Distribution I Series KF 220988 Humide Amonium Nitrate AvaIldbII~ty Codes Avail arid i or Dist Special 3. DISCUSSION 4. SUMMARY 5. APPENDIX Io. . 1...the participating phases. The system was used to investigate the phase properties of amonium nitrate samples, which were melted with 2 weight % of
An Investigation of Long Term Orbits About the Planet Mars Using a Dynamic Atmosphere Model
1989-12-01
O ( c IT1 I,5")) Figure 1.2: Ionosphere...20.1272 2TC - Met*t210 | ’K 40 - Ix cl o ~ /2-. o 6 230 220Z- \\AW - Ii Z10 - A €, c , , , , zoo- ’, I ,, O - %%" ISIO- %% 170- U Figure 1.4: Atmospheric...sini +’I-e2 R n ’ C ’. dk -_ -e2 R + h coti R - k P’yI-e 2 R (.1.1.4d) dt na- h na2it-e2 i haS O r)LN d121 IR (. .1. 4e) dt na2 sini il-e2 i dLN
Yoo, Su Jeong; Kim, Hea Ok; Lim, Yoongho; Kim, Jeongmin; Jeong, Lak Shin
2002-01-01
Novel (2R,4R)- and (2S,4S)-iso dideoxynucleosides with exocyclic methylene have been designed and synthesized, based on the lead BMS-200475 (3) which exhibited potent anti-HBV activity. For the synthesis of D types of (2R,4R)-nucleosides, L-xylose was converted to the key intermediate 14. The intermediate 14 was converted to the uracil derivative 4a and the cytosine derivative 4b. Compound 14 was also converted to the purine derivatives such as adenine derivative 4c, hypoxanthine derivative 4d, and guanine derivative 4e. The corresponding L types of (2S,4S)-enantiomers were more efficiently synthesized from the commercially available 1,2-isopropylidene-D-xylose (20) than the synthetic method used in the synthesis of (2R,4R)-nucleosides. The key intermediate 25 was converted to the pyrimidine analogues 5a and 5b and the purine derivatives 5c, 5d, and 5e using the similar method used in the preparation of 4c, 4d, and 4e. The synthesized final (2R,4R)- and (2S,4S)-nucleosides were tested against several viruses such as HIV-1, HSV-1, HSV-2, HCMV and HBV. (2R,4R)-Adenine analogue 4c exhibited potent anti-HBV activity (EC(50)=1.5 microM in 2.2.15 cells) among compounds tested, while (2R,4R)-uracil derivative 4a was the most active against HCMV among compounds tested and (2R,4R)-adenine derivative 4c was found to be moderately active against the same virus. However, the corresponding (2S,4S)-isomers were found to be totally inactive against all tested viruses. Both (2R,4R)-adenine derivative 4c and (2S,4S)-adenine analogue 5c were totally resistant to the adenosine deaminase like iso-ddA (1). From the molecular modeling study the hydroxymethyl side chains of BMS-200475 (3) and 4c were almost overlapped, indicating that 4c may be suitable for phosphorylation by cellular kinases like the lead 3, but some discrepancy between two bases was observed, indicating why 4c is less potent against HBV than 3. It is concluded that discovery of (2R,4R)-adenine analogue 4c as potent anti-HBV agent suggested that the sugar moiety of this series can be regarded as a novel template for the development of new anti-HBV agent and oxygen atom can be acted as a bioisostere of C-OH.
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.
Current drug treatments targeting dopamine D3 receptor.
Leggio, Gian Marco; Bucolo, Claudio; Platania, Chiara Bianca Maria; Salomone, Salvatore; Drago, Filippo
2016-09-01
Dopamine receptors (DR) have been extensively studied, but only in recent years they became object of investigation to elucidate the specific role of different subtypes (D1R, D2R, D3R, D4R, D5R) in neural transmission and circuitry. D1-like receptors (D1R and D5R) and D2-like receptors (D2R, D2R and D4R) differ in signal transduction, binding profile, localization in the central nervous system and physiological effects. D3R is involved in a number of pathological conditions, including schizophrenia, Parkinson's disease, addiction, anxiety, depression and glaucoma. Development of selective D3R ligands has been so far challenging, due to the high sequence identity and homology shared by D2R and D3R. As a consequence, despite a rational design of selective DR ligands has been carried out, none of currently available medicines selectively target a given D2-like receptor subtype. The availability of the D3R ligand [(11)C]-(+)-PHNO for positron emission tomography studies in animal models as well as in humans, allows researchers to estimate the expression of D3R in vivo; displacement of [(11)C]-(+)-PHNO binding by concurrent drug treatments is used to estimate the in vivo occupancy of D3R. Here we provide an overview of studies indicating D3R as a target for pharmacological therapy, and a review of market approved drugs endowed with significant affinity at D3R that are used to treat disorders where D3R plays a relevant role. Copyright © 2016 Elsevier Inc. All rights reserved.
Xue, Li; Geng, Yan; Li, Ming; Jin, Yao-Feng; Ren, Hui-Xun; Li, Xia; Wu, Feng; Wang, Biao; Cheng, Wei-Ying; Chen, Teng; Chen, Yan-Jiong
2016-07-01
Accumulating studies have revealed that the dopamine D3 receptor (D3R) plays an important role in methamphetamine (METH) addiction. However, the action of D3R on METH-mediated immune response and the underlying mechanism remain unclear. Mast cells (MCs) are currently identified as effector cells in many processes of immune responses, and MC activation is induced by various stimuli such as lipopolysaccharide (LPS). Moreover, CD117 and FcεRI are known as MC markers due to their specific expression in MCs. To investigate the effects of D3R on METH-mediated alteration of LPS-induced MCs activation and the underlying mechanism, in this study, we examined the expression of CD117 and FcεRI in the intestines of wild-type (D3R(+/+)) and D3R-deficient (D3R(-/-)) mice. We also measured the production of MC-derived cytokines, including TNF-α, IL-6, IL-4, IL-13 and CCL-5, in the bone marrow-derived mast cells (BMMCs) of WT and D3R(-/-) mice. Furthermore, we explored the effects of D3R on METH-mediated TLR4 and downstream MAPK and NF-κB signaling induced by LPS in mouse BMMCs. We found that METH suppressed MC activation induced by LPS in the intestines of D3R(+/)mice. In contrast, LPS-induced MC activation was less affected by METH in D3R(-/-) mice. Furthermore, METH altered LPS-induced cytokine production in BMMCs of D3R(+/+) mice but not D3R(-/-) mice. D3R was also involved in METH-mediated modulation of LPS-induced expression of TLR4 and downstream MAPK and NF-κB signaling molecules in mouse BMMCs. Taken together, our findings demonstrate that the effect of D3R on TLR4 signaling may be implicated in the regulation of METH-mediated MCs activation induced by LPS. Copyright © 2016 Elsevier B.V. All rights reserved.
Three New Sesquiterpene Glycosides from the Rhizomes of Trillium tschonoskii.
Yang, Jie; Yang, Yin-Jun; Sun, Xin-Guang; Zhang, Jie; Zhao, Yang; Wang, Bei; Ding, Qian-Zhi; Guo, Bao-Lin; Ma, Bai-Ping
2017-08-02
Three new sesquiterpene glycosides, possessing a rare aglycone with a sulfonyl between C-1 and C-15 positions, named 3-(3' E -7' R ,8'-dihydroxy-4',8'-dimethyl-3'-nonenyl)-2,5-dihydro-1,1-dioxo-thiophen 7'- O -β-d-glucopyranosyl-(1→4)- O -β-d-glucopyranosyl-(1→4)- O -β-d-glucopyranoside ( 1 ), 3-(3' E -7' R ,8'-dihydroxy-4',8'-dimethyl-3'-nonenyl)-2,5-dihydro-1,1-dioxo-thiophen 7'- O -β-d-glucopyranosyl-(1→4)- O -β-d-glucopyranoside ( 2 ), and 3-(3' E -7' R ,8'-dihydroxy-4',8'-dimethyl-3'-nonenyl)-2,5-dihydro-1,1-dioxo-thiophen 7'- O -β-d-glucopyranosyl-6'- O -acetyl-(1→4)- O -β-d-glucopyranosyl-(1→4)- O -β-d-glucopyranoside ( 3 ), respectively, were isolated from the rhizomes of Trillium tschonoskii . Their structures were established on the basis of spectroscopic data, including HR-ESI-MS, IR, 1D and 2D NMR. The cytotoxic properties of the three compounds were investigated using human hepatic L02 cells.
An Investigation of Fitness and Health Parameters in a U.S. Navy Population.
1980-11-30
body weight by percent fat, i-4 0- -1-4 r_4 0% 0 0 14 0% r- r’- 0 co 0 0 0o 01 07 0 0 0 0 0o 0 0 0 0D 0 w 0 0% N r4 r 0 0 0 0W1 - % 0 0 a 00 cn n UI m ...4 - H- r, .*r m 4% IT GoJ en 1-4 %0 %0 0% C14 4% H 00 w ~ r ci 1 -4 C C14 Go -T IT .t~Z -4 _.? %%~ 0 C 0 en U, .- 1 c1 en M ~ u, P W q 0% ...T 0 0~4 co ON 0% 4% cli enJ _.T 4- U 0 L, -.t 00 o en 00 %0 0 C l *q r 0% 14 r_ %0 a% 0 m - %D 0% r, U, 0 0, r1 % 0I %a~~ ~ ~ Ln .-4 0%1 0%W % 1 V 0
ISOTROPIC CORRELATION FUNCTIONS ON D-DIMENSIONAL BALLS. (R825173)
The perspectives, information and conclusions conveyed in research project abstracts, progress reports, final reports, journal abstracts and journal publications convey the viewpoints of the principal investigator and may not represent the views and policies of ORD and EPA. Concl...
Red River of the North Reconnaissance Report: Pembina River.
1980-12-01
the mallard, blue -winged teal, pintail, gadwall, northern shoveler, green -winged teal, American wigeon, and redhead. [ Rush Lake receives heavy use...r.D-Ri4. 787 RED RIVER OF THE NORTH RECONNAISSANCE REPORT: PEMBINA 1/2 RIVER(IJ) GULF SOUTH RESEAPRCH INST BATON ROUGE LA DEC 9 DACU77-8@-C-e8i7B...ii% ---. :w: U ;r u --- ’w AD-A140 787 RED RIVER OF THE NORTH RECONNAISSANCE , %h,%! iREPORT , _ PEMBINA ; RIVER CD j- - D FINAL RMPORT ’ December
Investigation of Continuously Variable Slope Delta Modulator/Demodulator Compatability.
1980-12-01
20 d,"mO Test Signal) 4 stp Ize Pratio -J-l Li] c4 u FnoR~e mx -,cli - td 32k/ I’.’: (2 .Bm’ et i~ l z s tep g ize Ratio MJismatc(_h Bd FREQUENCY (HZJ...Ste~p Size it-tio flisriatch ’ F] - ,a tc he d 0 - 2 dB [: L’\\- 4 dB 4Bd B 0’ 0 0 b l - FREQUENCY (HZ) Figure 49a. CVSD Encoder/Decoder Back-to-Back...APPENDIX rl Total t’,ar-onic i tor’i w’. -r -,,,t ,ntl Po’..’r PROGRAM DTHD(I PUT,OUTPUT,TAPES-INPUT.TAPE6-OUTPUT,PLOT) CT_---- -- - TD US. INPUT POER
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.
Non-analytic terms from nested divergences in maximal supergravity
NASA Astrophysics Data System (ADS)
Basu, Anirban
2016-07-01
The {D}4{{ R }}4 and {D}6{{ R }}4 coefficient functions in the effective action of type II string theory compactified on T d contain terms of the form {{ E }}1{{ln}}{g}d and {{ E }}2{({{ln}}{g}d)}2 in specific dimensions, where g d is the T-duality invariant string coupling, and {{ E }}1 and {{ E }}2 are U-duality invariant coefficient functions. We derive these non-analytic terms from nested ultraviolet divergences in two and three loop maximal supergravity. For the {D}4{{ R }}4 coupling, the contribution involves {{ E }}{{ R }4}{{ln}}{g}d, while for the {D}6{{ R }}4 coupling, it involves {{ E }}{{ R }4}{{ln}}{g}d, {{ E }}{D2{{ R }}4}{({{ln}}{g}d)}2 and {{ E }}{D4{{ R }}4}{{ln}}{g}d; where {{ E }}{{ R }4}, {{ E }}{D2{{ R }}4} and {{ E }}{D4{{ R }}4} are the {{ R }}4, {D}2{{ R }}4 and {D}4{{ R }}4 coefficient functions respectively. The contribution from {{ E }}{D2{{ R }}4}, the coefficient function of an amplitude that vanishes onshell, arises from a two loop nested subdivergence of the three loop amplitude.
EFFECTS OF ZINC ON D-GLUCOSE TRANSPORT IN FISH AND CRUSTACEAN GUT. (R823068)
The perspectives, information and conclusions conveyed in research project abstracts, progress reports, final reports, journal abstracts and journal publications convey the viewpoints of the principal investigator and may not represent the views and policies of ORD and EPA. Concl...
NASA Astrophysics Data System (ADS)
Cartier, Camille; Hammouda, Tahar; Doucelance, Régis; Boyet, Maud; Devidal, Jean-Luc; Moine, Bertrand
2014-04-01
In order to investigate the influence of very reducing conditions, we report enstatite-melt trace element partition coefficients (D) obtained on enstatite chondrite material at 5 GPa and under oxygen fugacities (fO2) ranging between 0.8 and 8.2 log units below the iron-wustite (IW) buffer. Experiments were conducted in a multianvil apparatus between 1580 and 1850 °C, using doped (Sc, V, REE, HFSE, U, Th) starting materials. We used a two-site lattice strain model and a Monte-Carlo-type approach to model experimentally determined partition coefficient data. The model can fit our partitioning data, i.e. trace elements repartition in enstatite, which provides evidence for the attainment of equilibrium in our experiments. The precision on the lattice strain model parameters obtained from modelling does not enable determination of the influence of intensive parameters on crystal chemical partitioning, within our range of conditions (fO2, P, T, composition). We document the effect of variable oxygen fugacity on the partitioning of multivalent elements. Cr and V, which are trivalent in the pyroxene at around IW - 1 are reduced to 2+ state with increasingly reducing conditions, thus affecting their partition coefficients. In our range of redox conditions Ti is always present as a mixture between 4+ and 3+ states. However the Ti3+-Ti4+ ratio increases strongly with increasingly reducing conditions. Moreover in highly reducing conditions, Nb and Ta, that usually are pentavalent in magmatic systems, appear to be reduced to lower valence species, which may be Nb2+ and Ta3+. We propose a new proxy for fO2 based on D(Cr)/D(V). Our new data extend the redox range covered by previous studies and allows this proxy to be used in the whole range of redox conditions of the solar system objects. We selected trace-element literature data of six chondrules on the criterion of their equilibrium. Applying the proxy to opx-matrix systems, we estimated that three type I chondrules have equilibrated at IW - 7 ± 1, one type I chondrule at IW - 4 ± 1, and two type II chondrules at IW + 3 ± 1. This first accurate estimation of enstatite-melt fO2 for type I chondrules is very close to CAI values. Find the best-fit for trivalent elements. We set the r0M1 (3+) range to 0.55-0.75 Å, based on visual observations of the datapoints. For the other variables we have set boundary values beyond which the solutions would be unacceptable. For example, r0M2 (3+) has to be larger than r0M1 (3+). Finally we restricted the D0 range as follow: 0.2
1984-11-01
R &D investigations. 1.3 PHASE IV SITE DESCRIPTIONS I Three primary sites are included in this Phase IV...34C z I L . ...- I I E I I i -\\ = _ _ _ . .. .....,. . .. .. I x FIGURE 1.7 a qq"-.. .. .. .. .. .. "- _ r JI I g I I1 ,n I , I I I " I - I Br-.,,-%~l...0 0 4J 4) 44 4) V ) -H 0 4 6: 144 d 0 4 14 404)-4 -4 4 .4 N ) 4 0 4) 4 40 4) 4) 0.0
ERIC Educational Resources Information Center
National Science Foundation, Washington, DC.
This report analyzes data on research and development (R&D) performed by industry during 1979, examines historical trends for key R&D funding variables, and presents information on industry-employed R&D scientists and engineers. Areas addressed in the first section on R&D funds include: major R&D industries (aircraft/missiles,…
An Investigation of a Design for a Finite-Difference Time Domain (FDTD) Hardware Accelerator
1991-12-01
D PTR), accumulators A and B ( ACCA & ACCB), and the third fixed incrementer (IN3). The stack file in the floating-point unit is untouched. The first...of data. REGISTERS: R1, R2, R4, R5, R7, R8, R9, R11, R12, R13, ACCA , ACCB, MBR. MAR, STAT POINTERS: APT, BPT, CPT, DPT, AIN, BIN, CIN, DIN, IN3 LINES...BBUS MARh-2 READ BACTL, 12 R2 =En(lj) R2=D MAR+2 READ BAACT; 13 MBR = En+I(1j) ACCA = En(0,j-1) + En(lj-1) BU=R2 BL=R2 CD C=R1 MBR=D FP++ a=CBUS b=BBUS
Military Children’s Perceptions of Parents’ Frequent Missile Base Deployments
2017-04-26
investigations, 502 ISG/JAC ( Ethics Review) and Public Affairs (59 MOW/PA) for review and then forward you a final letter of approval or disapproval. 9. Once...Medical and Technical Papers, for additional information. 11 . The Joint Ethics Regulation (JER) DoD 5500.07-R, Standards of Conduct, provides...standards of ethical conduct for all DoD personnel and their interactions with other non-DoD entities, organizations, societies, conferences, etc. Part of
Plasma Exchange for Refractory MDA5 Myositis and ILD
2017-04-26
investigations. S02 ISG/JAC ( Ethics Review) and Public Affa irs (S9 MOW/PA) for review and then forward you a final letter of approval or disapproval. 9...Medical and Technical Papers, for additional information. 11 . The Joint Ethics Regulation (JER) DoD SS00.07 -R, Standards of Conduct. provides...standards of ethical conduct for all DoD personnel and their interactions with other non-DoD entities. organizations, societies. conferences, etc. Part of
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.
Yang, Jiue-in; Benecke, Scott; Jeske, Daniel R.; Rocha, Fernando S.; Smith Becker, Jennifer; Timper, Patricia; Ole Becker, J.
2012-01-01
A series of experiments were performed to examine the population dynamics of the sugarbeet cyst nematode, Heterodera schachtii, and the nematophagus fungus Dactylella oviparasitica. After two nematode generations, the population densities of H. schachtii were measured in relation to various initial infestation densities of both D. oviparasitica and H. schachtii. In general, higher initial population densities of D. oviparasitica were associated with lower final population densities of H. schachtii. Regression models showed that the initial densities of D. oviparasitica were only significant when predicting the final densities of H. schachtii J2 and eggs as well as fungal egg parasitism, while the initial densities of J2 were significant for all final H. schachtii population density measurements. We also showed that the densities of H. schachtii-associated D. oviparasitica fluctuate greatly, with rRNA gene numbers going from zero in most field-soil-collected cysts to an average of 4.24 x 108 in mature females isolated directly from root surfaces. Finally, phylogenetic analysis of rRNA genes suggested that D. oviparasitica belongs to a clade of nematophagous fungi that includes Arkansas Fungus strain L (ARF-L) and that these fungi are widely distributed. We anticipate that these findings will provide foundational data facilitating the development of more effective decision models for sugar beet planting. PMID:23481664
Growth hormone therapy in a girl with Turner syndrome and diabetes type 1 - case report.
Obara-Moszynska, Monika; Banaszak, Magdalena; Niedziela, Marek
2015-01-01
The studies indicate the complex etiology of abnormal glucose metabolism in the Turner syndrome (TS). In the light of these carbohydrate disorders a therapy with recombinant growth hormone (rGH) in TS may be associated with complications, as growth hormone has a diabetogenic potential. Perinatal history is unknown since the patient was adopted at the age of 4 years. At 11 years old, due to typical phenotype, TS was diagnosed. The karyotype was 45,X[43]/46,X,i(X)(q10)[7]. At the same age, basing on laboratory results, insulin dependent diabetes was diagnosed and the conventional insulin therapy was initiated. During the hospitalization, at the age of 12 years, the patient was 123.5cm (-4.4SD). At the same age rGH tre-atment was initiated, with the dose 0.045 mg/kg/d. After 3 months of therapy the height velocity rose to 8.2 cm/ year. At the age of 13 years, substitution with 17β-estradiol was started. After 3 years and 4 months the growth hormone treatment was stopped because of poor height velocity. The final height of the patient was 140 cm (-4,OSD). Two years after the end of rGH treatment the height was 141.2 cm. After termination of rGH treatment the need for daily insulin dose decreased from 50-60U/d to 38-44U/d. The decision of rGH therapy in TS with diabetes is certainly difficult. While starting the growth hormone treatment the clinician must keep in mind the risk of metabolic complications, but also the awareness that gives the patient a chance to improve the final height. In terms of the proper psycho-emotional development the reduction of growth deficit is very important. © Polish Society for Pediatric Endocrinology and Diabetology.
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 timely and unique insight into the importance of ongoing efforts to develop a new global framework for biomedical R&D. As we progress to phase 2, an evaluation tool for initiatives focused on identifying which approaches have truly achieved increased innovation and access for patients, we aim to demonstrate that there are a handful of initiatives which represent some, but not all, of the building blocks for a new approach to R&D.Through this mapping and our forthcoming evaluation, UAEM aims to initiate an evidence-based conversation around a truly alternative biomedical R&D model that serves people rather than profits.
The perspectives, information and conclusions conveyed in research project abstracts, progress reports, final reports, journal abstracts and journal publications convey the viewpoints of the principal investigator and may not represent the views and policies of ORD and EPA. Concl...
The perspectives, information and conclusions conveyed in research project abstracts, progress reports, final reports, journal abstracts and journal publications convey the viewpoints of the principal investigator and may not represent the views and policies of ORD and EPA. Concl...
The perspectives, information and conclusions conveyed in research project abstracts, progress reports, final reports, journal abstracts and journal publications convey the viewpoints of the principal investigator and may not represent the views and policies of ORD and EPA. Concl...
The perspectives, information and conclusions conveyed in research project abstracts, progress reports, final reports, journal abstracts and journal publications convey the viewpoints of the principal investigator and may not represent the views and policies of ORD and EPA. Concl...
The perspectives, information and conclusions conveyed in research project abstracts, progress reports, final reports, journal abstracts and journal publications convey the viewpoints of the principal investigator and may not represent the views and policies of ORD and EPA. Concl...
Xu, Rui; Huang, Huaping; Han, Zhong; Li, Minchao; Zhou, Xiangdong
2016-01-01
To investigate the role of miR-21 in airway immunologic dysfunction induced by cold air irritation. Immortalized human airway epithelial cell lines BEAS-2B and 16HBE cells were cultured in air-liquid phases. The differential expressions of endogenous miR-21, miR-164, and miR-155 in the cells induced by cold air exposure for different time were detected by real-time PCR. The reporter plasmid containing wild-type or mutated 3'UTR of TLR-4 were constructed and co-transfected into BEAS-2B cells or 16HBE cells together with miR-21 mimic, miR-21 mimic control, miR-21 inhibitor, or miR-21 inhibitor control. Following the transfection, dual luciferase reporter assay was performed to verify the action of miR-21 on TLR-4. miR-21 mimic, miR-21 mimic control, miR-21 inhibitor, and miR-21 inhibitor control were transfected via lipofectamine 2000 in BEAS-2B or 16HBE cells that were subsequently exposed to a temperature at 37 degrees celsius; or cold irritation (30 degrees celsius;), and the protein levels of TLR-4/MyD88 were detected by Western blotting. Cold irritation caused a time- dependent up-regulation of miR-21 in both BEAS-2B and 16HBE cells (P<0.05) without obviously affecting the expressions of miR-164 and miR-155. Dual luciferase reporter assay demonstrated a direct combination of miR-21 and its target protein TLR-4. The synthesis levels of TLR-4/MyD88 protein were decreased in miR-21 mimic group even at a routine culture temperature (P<0.05), as also seen in cells with cold irritation (P<0.05). Treatment with the miR-21 inhibitor partially attenuated cold irritation-induced down-regulation of TLR-4/MyD88 protein (P<0.05). Cold air irritation-induced airway immunologic dysfunction is probably associated with TLR-4/MyD88 down-regulation by an increased endogenic miR-21.
Search for b→u transitions in B±→[K∓π±π0]DK± decays
NASA Astrophysics Data System (ADS)
Lees, J. P.; Poireau, V.; Tisserand, V.; Garra Tico, J.; Grauges, E.; Martinelli, M.; Milanes, D. A.; Palano, A.; Pappagallo, M.; Eigen, G.; Stugu, B.; Sun, L.; Brown, D. N.; Kerth, L. T.; Kolomensky, Yu. G.; Lynch, G.; Koch, H.; Schroeder, T.; Asgeirsson, D. J.; Hearty, C.; Mattison, T. S.; McKenna, J. A.; Khan, A.; Blinov, V. E.; Buzykaev, A. R.; Druzhinin, V. P.; Golubev, V. B.; Kravchenko, E. A.; Onuchin, A. P.; Serednyakov, S. I.; Skovpen, Yu. I.; Solodov, E. P.; Todyshev, K. Yu.; Yushkov, A. N.; Bondioli, M.; Curry, S.; Kirkby, D.; Lankford, A. J.; Mandelkern, M.; Stoker, D. P.; Atmacan, H.; Gary, J. W.; Liu, F.; Long, O.; Vitug, G. M.; Campagnari, C.; Hong, T. M.; Kovalskyi, D.; Richman, J. D.; West, C. A.; Eisner, A. M.; Kroseberg, J.; Lockman, W. S.; Martinez, A. J.; Schalk, T.; Schumm, B. A.; Seiden, A.; Cheng, C. H.; Doll, D. A.; Echenard, B.; Flood, K. T.; Hitlin, D. G.; Ongmongkolkul, P.; Porter, F. C.; Rakitin, A. Y.; Andreassen, R.; Dubrovin, M. S.; Meadows, B. T.; Sokoloff, M. D.; Bloom, P. C.; Ford, W. T.; Gaz, A.; Nagel, M.; Nauenberg, U.; Smith, J. G.; Wagner, S. R.; Ayad, R.; Toki, W. H.; Spaan, B.; Kobel, M. J.; Schubert, K. R.; Schwierz, R.; Bernard, D.; Verderi, M.; Clark, P. J.; Playfer, S.; Watson, J. E.; Bettoni, D.; Bozzi, C.; Calabrese, R.; Cibinetto, G.; Fioravanti, E.; Garzia, I.; Luppi, E.; Munerato, M.; Negrini, M.; Piemontese, L.; Baldini-Ferroli, R.; Calcaterra, A.; de Sangro, R.; Finocchiaro, G.; Nicolaci, M.; Pacetti, S.; Patteri, P.; Peruzzi, I. M.; Piccolo, M.; Rama, M.; Zallo, A.; Contri, R.; Guido, E.; Lo Vetere, M.; Monge, M. R.; Passaggio, S.; Patrignani, C.; Robutti, E.; Bhuyan, B.; Prasad, V.; Lee, C. L.; Morii, M.; Edwards, A. J.; Adametz, A.; Marks, J.; Uwer, U.; Bernlochner, F. U.; Ebert, M.; Lacker, H. M.; Lueck, T.; Dauncey, P. D.; Tibbetts, M.; Behera, P. K.; Mallik, U.; Chen, C.; Cochran, J.; Crawley, H. B.; Meyer, W. T.; Prell, S.; Rosenberg, E. I.; Rubin, A. E.; Gritsan, A. V.; Guo, Z. J.; Arnaud, N.; Davier, M.; Derkach, D.; Grosdidier, G.; Le Diberder, F.; Lutz, A. M.; Malaescu, B.; Roudeau, P.; Schune, M. H.; Stocchi, A.; Wormser, G.; Lange, D. J.; Wright, D. M.; Bingham, I.; Chavez, C. A.; Coleman, J. P.; Fry, J. R.; Gabathuler, E.; Hutchcroft, D. E.; Payne, D. J.; Touramanis, C.; Bevan, A. J.; di Lodovico, F.; Sacco, R.; Sigamani, M.; Cowan, G.; Paramesvaran, S.; Brown, D. N.; Davis, C. L.; Denig, A. G.; Fritsch, M.; Gradl, W.; Hafner, A.; Prencipe, E.; Alwyn, K. E.; Bailey, D.; Barlow, R. J.; Jackson, G.; Lafferty, G. D.; Cenci, R.; Hamilton, B.; Jawahery, A.; Roberts, D. A.; Simi, G.; Dallapiccola, C.; Cowan, R.; Dujmic, D.; Sciolla, G.; Lindemann, D.; Patel, P. M.; Robertson, S. H.; Schram, M.; Biassoni, P.; Lazzaro, A.; Lombardo, V.; Palombo, F.; Stracka, S.; Cremaldi, L.; Godang, R.; Kroeger, R.; Sonnek, P.; Summers, D. J.; Nguyen, X.; Taras, P.; de Nardo, G.; Monorchio, D.; Onorato, G.; Sciacca, C.; Raven, G.; Snoek, H. L.; Jessop, C. P.; Knoepfel, K. J.; Losecco, J. M.; Wang, W. F.; Honscheid, K.; Kass, R.; Brau, J.; Frey, R.; Sinev, N. B.; Strom, D.; Torrence, E.; Feltresi, E.; Gagliardi, N.; Margoni, M.; Morandin, M.; Posocco, M.; Rotondo, M.; Simonetto, F.; Stroili, R.; Ben-Haim, E.; Bomben, M.; Bonneaud, G. R.; Briand, H.; Calderini, G.; Chauveau, J.; Hamon, O.; Leruste, Ph.; Marchiori, G.; Ocariz, J.; Sitt, S.; Biasini, M.; Manoni, E.; Rossi, A.; Angelini, C.; Batignani, G.; Bettarini, S.; Carpinelli, M.; Casarosa, G.; Cervelli, A.; Forti, F.; Giorgi, M. A.; Lusiani, A.; Neri, N.; Oberhof, B.; Paoloni, E.; Perez, A.; Rizzo, G.; Walsh, J. J.; Lopes Pegna, D.; Lu, C.; Olsen, J.; Smith, A. J. S.; Telnov, A. V.; Anulli, F.; Cavoto, G.; Faccini, R.; Ferrarotto, F.; Ferroni, F.; Gaspero, M.; Li Gioi, L.; Mazzoni, M. A.; Piredda, G.; Buenger, C.; Hartmann, T.; Leddig, T.; Schröder, H.; Waldi, R.; Adye, T.; Olaiya, E. O.; Wilson, F. F.; Emery, S.; Hamel de Monchenault, G.; Vasseur, G.; Yèche, Ch.; Aston, D.; Bard, D. J.; Bartoldus, R.; Benitez, J. F.; Cartaro, C.; Convery, M. R.; Dorfan, J.; Dubois-Felsmann, G. P.; Dunwoodie, W.; Field, R. C.; Franco Sevilla, M.; Fulsom, B. G.; Gabareen, A. M.; Graham, M. T.; Grenier, P.; Hast, C.; Innes, W. R.; Kelsey, M. H.; Kim, H.; Kim, P.; Kocian, M. L.; Leith, D. W. G. S.; Lewis, P.; Li, S.; Lindquist, B.; Luitz, S.; Luth, V.; Lynch, H. L.; Macfarlane, D. B.; Muller, D. R.; Neal, H.; Nelson, S.; Ofte, I.; Perl, M.; Pulliam, T.; Ratcliff, B. N.; Roodman, A.; Salnikov, A. A.; Santoro, V.; Schindler, R. H.; Snyder, A.; Su, D.; Sullivan, M. K.; Va'Vra, J.; Wagner, A. P.; Weaver, M.; Wisniewski, W. J.; Wittgen, M.; Wright, D. H.; Wulsin, H. W.; Yarritu, A. K.; Young, C. C.; Ziegler, V.; Park, W.; Purohit, M. V.; White, R. M.; Wilson, J. R.; Randle-Conde, A.; Sekula, S. J.; Bellis, M.; Burchat, P. R.; Miyashita, T. S.; Alam, M. S.; Ernst, J. A.; Gorodeisky, R.; Guttman, N.; Peimer, D. R.; Soffer, A.; Lund, P.; Spanier, S. M.; Eckmann, R.; Ritchie, J. L.; Ruland, A. M.; Schilling, C. J.; Schwitters, R. F.; Wray, B. C.; Izen, J. M.; Lou, X. C.; Bianchi, F.; Gamba, D.; Lanceri, L.; Vitale, L.; Lopez-March, N.; Martinez-Vidal, F.; Oyanguren, A.; Ahmed, H.; Albert, J.; Banerjee, Sw.; Choi, H. H. F.; King, G. J.; Kowalewski, R.; Lewczuk, M. J.; Lindsay, C.; Nugent, I. M.; Roney, J. M.; Sobie, R. J.; Gershon, T. J.; Harrison, P. F.; Latham, T. E.; Puccio, E. M. T.; Band, H. R.; Dasu, S.; Pan, Y.; Prepost, R.; Vuosalo, C. O.; Wu, S. L.
2011-07-01
We present a study of the decays B±→DK± with D mesons reconstructed in the K+π-π0 or K-π+π0 final states, where D indicates a D0 or a D¯0 meson. Using a sample of 474×106 BB¯ pairs collected with the BABAR detector at the PEP-II asymmetric-energy e+e- collider at SLAC, we measure the ratios R±≡(Γ(B±→[K∓π±π0]DK±))/(Γ(B±→[K±π∓π0]DK±)). We obtain R+=(5-10+12(stat)-4+2(syst))×10-3 and R-=(12-10+12(stat)-5+3(syst))×10-3, from which we extract the upper limits at 90% probability: R+<23×10-3 and R-<29×10-3. Using these measurements, we obtain an upper limit for the ratio rB of the magnitudes of the b→u and b→c amplitudes rB<0.13 at 90% probability.
An Analysis of Competencies for Managing Science and Technology Programs
2008-03-19
competency modeling through a two-year task force commissioned by the Society for Industrial and Organizational Psychology (Shippmann and others, 2000:704...positions—specifically within Research and Development (R&D) programs. If so, the final investigative question tests whether those differences are...statistics are used to analyze the comparisons through hypothesis testing and t- tests relevant to the research investigative questions. These
Federal Register 2010, 2011, 2012, 2013, 2014
2011-11-08
... to section 14(d) of the CPSA to section 14(i) of the CPSA due to renumbering arising out of H.R. 2715... CPSA to cite section 14(i) of the CPSA, as a result of renumbering arising out of H.R. 2715. 4... INFORMATION: I. Introduction A. What is the purpose of the final rule? Elsewhere in this issue of the Federal...
A novel MC4R deletion coexisting with FTO and MC1R gene variants, causes severe early onset obesity.
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.
NASA Astrophysics Data System (ADS)
Schübler, Moritz; Sadek, Bassem; Kottke, Tim; Weizel, Lilia; Stark, Holger
2017-09-01
Neurleptic drugs, e.g. aripiprazole, targeting the dopamine D2s and D3 receptors (D2sR and D3R) in the central nervous system are widely used in the treatment of several psychotic and neurodegenerative diseases. Therefore, a new series of benz[d]thiazole-based ligands (1-18) was synthesized by applying the bioisosteric approach derived from the selective D3Rs ligand BP-897 and its structurally related benz[d]imidazole derivatives. Herein, introduction of the benz[d]thiazole moiety was well tolerated by D2sR and D3R binding sites leading to antagonist affinities in the low nanomolar concentration range at both receptor subtypes. Further exploration of different substitution patterns at the benz[d]thiazole heterocycle and the basic 4-phenylpiperazine resulted in the discovery of high dually acting D2sR and D3R ligands. Moreover, the methoxy substitution at 2-position of 4-phenylpiperazine resulted in significantly (22-fold) increased D2sR binding affinity as compared to the parent ligand BP-897, and improved physicochemical and drug-likeness properties of ligands 1-9. However, the latter structural modifications failed to improve the drug-able properties in ligands having un-substituted 4-phenylpiperazine analogues (10-18). Accordingly, compound 7 showed in addition to high dual affinity at the D2sR and D3R (Ki (hD2SR) = 2.8 ± 0.8 nM; Ki (hD3R) = 3.0 ± 1.6 nM), promising clogS, clogP, LE (hD2sR, hD3R), LipE (hD2sR, hD3R), and drug-likeness score values of -4.7, 4.2, (0.4, 0.4), (4.4, 4.3), and 0.7, respectively. Also, the deaminated analogue 8 (Ki (hD2SR) = 3.2 ± 0.4 nM; Ki (hD3R) = 8.5 ± 2.2 nM) revealed clogS, clogP, LE (hD2sR, hD3R), LipE (hD2sR, hD3R) and drug-likeness score values of -4.7, 4.2, (0.4, 0.4), (3.9, 3.5), and 0.4, respectively. The results observed for the newly developed benz[d]thiazole-based ligands 1-18 provide clues for the diversity in structure activity relationships (SARs) at the D2sR and D3R subtypes.
Digit ratio (2D:4D) in primary brain tumor patients: A case-control study.
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.
Review of the Fire Control System.
1980-11-18
TIE FIRE CONTROL SYSTEM Final Report;, CDRL #A005 a weaa . 1 VItdbu!i A UaR11.d Gy 8.Ic.80 12 05 028 W Unclassified. Uf e C’ L V A’ N ON -A iAC’ , 14 n...ta FI..Ie d) REPORT DOCUMENTATON PAREAD INSTRU-TION. PR--PAGE FRE COMPLETING FORM W 4E,’ 1 - " r ’ i:!VBE i 2 GOVT ACESSION NO. 3 RECIPIENT’S...enhancements of old applications. (continued on next page) DD 1 FAM , 1473 E ITON OF I NOV 65IS OBSOLETES.IN 0102-LF.014-6601 Unclassified SECUAITY
Big Gains for R&D in Carter's Final Budget.
ERIC Educational Resources Information Center
Long, Janice R.; And Others
1981-01-01
Summarizes President Carter's 1982 budget proposal for research and development (R and D) in science, technology, and related areas, with largest increases going to defense, and NASA. Indicates that R and D money could be affected by the Reagan Administration budget cuts. (SK)
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.
Allergic Bronchopulmonary Mycosis Caused by Cladosporidium
2017-05-23
request form to clinical investigations, S02 ISG/JAC ( Ethics Review) and Public Affairs (S9 MOW/PA) for review and then forward you a final letter of...Presentation and Publication of Medical and Technical Papers. for additional information. 11 . The Joint Ethics Regulation (JER) DoD SS00.07-R...Standards of Conduct, provides standards of ethical conduct for all OoO personnel and their interactions with other non-DoD entities, organizations
Istyastono, Enade P; Nijmeijer, Saskia; Lim, Herman D; van de Stolpe, Andrea; Roumen, Luc; Kooistra, Albert J; Vischer, Henry F; de Esch, Iwan J P; Leurs, Rob; de Graaf, Chris
2011-12-08
The histamine H(4) receptor (H(4)R) is a G protein-coupled receptor (GPCR) that plays an important role in inflammation. Similar to the homologous histamine H(3) receptor (H(3)R), two acidic residues in the H(4)R binding pocket, D(3.32) and E(5.46), act as essential hydrogen bond acceptors of positively ionizable hydrogen bond donors in H(4)R ligands. Given the symmetric distribution of these complementary pharmacophore features in H(4)R and its ligands, different alternative ligand binding mode hypotheses have been proposed. The current study focuses on the elucidation of the molecular determinants of H(4)R-ligand binding modes by combining (3D) quantitative structure-activity relationship (QSAR), protein homology modeling, molecular dynamics simulations, and site-directed mutagenesis studies. We have designed and synthesized a series of clobenpropit (N-(4-chlorobenzyl)-S-[3-(4(5)-imidazolyl)propyl]isothiourea) derivatives to investigate H(4)R-ligand interactions and ligand binding orientations. Interestingly, our studies indicate that clobenpropit (2) itself can bind to H(4)R in two distinct binding modes, while the addition of a cyclohexyl group to the clobenpropit isothiourea moiety allows VUF5228 (5) to adopt only one specific binding mode in the H(4)R binding pocket. Our ligand-steered, experimentally supported protein modeling method gives new insights into ligand recognition by H(4)R and can be used as a general approach to elucidate the structure of protein-ligand complexes.
DOE-EPSCoR Final Report Period: September 1, 2008- August 31, 2016
DOE Office of Scientific and Technical Information (OSTI.GOV)
Katiyar, Ram; Gomez, M.; Morell, G.
In this project, multifunctional nanostructured spintronic and magnetoelectric materials were investigated by experimental and computational efforts for applications in energy efficient electronic systems that integrate functionalities and thus have the potential to enable a new generation of faster responding devices and increased integration densities. The team systematically investigated transition metal (TM)-doped ZnO nanostructures, silicide nanorods, magnetoelectric oxides, and ferroelectric/ferromagnetic heterostructures. In what follows, we report the progress made by researchers during the above period in developing and understanding of 1) Spintronics nanostructures; 2) Resistive switching phenomenon in oxides for memory devices; 3) Magnetoelectric multiferroics; 4) Novel high-k gate oxides formore » logic devices; 5) Two dimensional (2D) materials; and 6) Theoretical studies in the above fields.« less
TLR4 MUTATION IS ASSOCIATED WITH ENDOTOXIN HYPORESPONSIVENESS IN HUMANS. (R826711C001,R826711C002)
The perspectives, information and conclusions conveyed in research project abstracts, progress reports, final reports, journal abstracts and journal publications convey the viewpoints of the principal investigator and may not represent the views and policies of ORD and EPA. Concl...
Dopamine D4 receptor (D4R) deletion in mice does not affect operant responding for food or cocaine
DOE Office of Scientific and Technical Information (OSTI.GOV)
Thanos, P.K.
In this study we examined the genetic contribution of the D4R in food and cocaine self-administration using D4R mice. Mice were examined for operant responding to food pellets or intravenous cocaine. Compared to wild-type mice (D4R{sup +/+}), both heterozygous (D4R{sup +/-}) and knockout (D4R{sup -/-}) mice showed no difference in responding for food or cocaine. Our findings suggest that the D4R is not directly involved in mediating operant response behaviors for food or cocaine.
The perspectives, information and conclusions conveyed in research project abstracts, progress reports, final reports, journal abstracts and journal publications convey the viewpoints of the principal investigator and may not represent the views and policies of ORD and EPA. Concl...
The perspectives, information and conclusions conveyed in research project abstracts, progress reports, final reports, journal abstracts and journal publications convey the viewpoints of the principal investigator and may not represent the views and policies of ORD and EPA. Concl...
The perspectives, information and conclusions conveyed in research project abstracts, progress reports, final reports, journal abstracts and journal publications convey the viewpoints of the principal investigator and may not represent the views and policies of ORD and EPA. Concl...
2007-09-01
IO B LV D G S T AR KA N S AS R D FIRST ST AT LA N TA A... IO A VE C S T O A K ST SALEM RD K N ER R D R M AD IS O N D R STARKEY AVE TENNESSEE AVE PATRICK RD S. D AK O TA A VE TOPE KA ST VANDE NBERG...DR CHIC AGO DR TY LE R R D CELME R LN HALL CT WACO LN BUNKER HILL ST O P ER AT IO N S D R MAPL E CT SEATTLE AVE RE NO DR O R E G O N C IR AL
NASA Astrophysics Data System (ADS)
Maroulis, George
1998-04-01
The electric multipole moments, dipole and quadrupole polarizability and hyperpolarizability of hydrogen chloride have been determined from an extensive and systematic study based on finite-field fourth-order many-body perturbation theory and coupled-cluster calculations. Our best values for the dipole, quadrupole, octopole and hexadecapole moment at the experimental internuclear separation of Re=2.408645a0 are μ=0.4238ea0, Θ=2.67ea02, Ω=3.94ea03, and Φ=13.37ea04, respectively. For the mean and the anisotropy of the dipole polarizability ααβ we recommend ᾱ=17.41±0.02 and Δα=1.60±0.03e2a02Eh-1. For the mean value of the first dipole hyperpolarizability βαβγ we advance β¯=-6.8±0.3e3a03Eh-2. Extensive calculations with a [8s6p6d3f/5s4p2d1f] basis set at the CCSD(T) level of theory yield the R-dependence of the Cartesian components and the mean of the second dipole hyperpolarizability γαβγδ(R)/e4a04Eh-3 around Re as γzzzz(R)=1907+1326(R-Re)+570(R-Re)2+10(R-Re)3-40(R-Re)4, γxxxx(R)=3900+747(R-Re)-65(R-Re)2-38(R-Re)3-7(R-Re)4, γxxzz(R)=962+222(R-Re)+88(R-Re)2+49(R-Re)3+5(R-Re)4, γ¯(R)=3230+841(R-Re)+151(R-Re)2+21(R-Re)3-9(R-Re)4, with z as the molecular axis. The present investigation suggests an estimate of (26.7±0.3)×102e4a04Eh-3 for the Hartree-Fock limit of the mean value γ¯ at Re. CCSD(T) calculations with basis sets of [8s6p6d3f/5s4p2d1f] and [9s7p5d4f/6s5p4d1f] size and MP4 calculations with the even larger [15s12p7d3f/12s7p2d1f] give (7.0±0.3)×102e4a04Eh-3 for the electron correlation effects for this property, thus leading to a recommended value of γ¯=(33.7±0.6)×102e4a04Eh-3. For the quadrupole polarizability Cαβ,γδ/e2a04Eh-1 at Re our best values are Czz,zz=41.68, Cxz,xz=26.11, and Cxx,xx=35.38, calculated with the [9s7p5d4f/6s5p4d1f] basis set at the CCSD(T) level of theory. The following CCSD(T) values were obtained with [8s6p6d3f/5s4p2d1f] at Re: dipole-quadrupole polarizability Aα,βγ/e2a03Eh-1, Az,zz=14.0, and Ax,zx=3.75, dipole-octopole polarizability Eα,βγδ/e2a04Eh-1, Ez,zzz=20.0, and Ex,xxx=3.0, and dipole-dipole-quadrupole hyperpolarizability Bαβ,γδ/e3a04Eh-2, Bzz,zz=-277, Bxz,xz=-261, Bxx,zz=246, and Bxx,xx=-416. A comparison of the mean polarizability and hyperpolarizability of some 18-electron systems shows that ᾱ(H2S)>ᾱ(HCl)>ᾱ(HOOH)>ᾱ(HOF)>ᾱ(Ar)>ᾱ(F2), and γ¯(H2S)>γ¯(HCl)>γ¯(HOOH)>γ¯(HOF)≈γ¯(Ar)>γ¯(F2).
Inhibition of rat prostate tumor growth by an octapeptide analog of somatostatin.
Murphy, W A; Lance, V A; Moreau, S; Moreau, J P; Coy, D H
1987-06-29
Analogs of a potent octapeptide analog of somatostatin (SRIF) H-(D)Phe-Cys-Tyr-(D)Trp-Lys-Val-Cys-Thr(NH2) were synthesized. Aromatic substitutions for Tyr resulted in little change in inhibitory potency on growth hormone (GH) secretion in the rat. Substitutions for Val or (D)Trp resulted in analogs with diminished activity. Substitution of (D)Nal for (D)Phe increased duration of GH inhibition. Final weights of subcutaneously implanted prostate tumors (R3327) were 41% lower in rats treated with an N-terminal 4-chloro-(D)phenylalanyl analog as compared to vehicle treated controls. The analog had no effect on testicular weight or final plasma testosterone levels. SRIF analogs may represent an alternative treatment for prostate cancer that would be free of the untoward reproductive effects of other treatments (e.g. LH-RH or castration).
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, these data indicate the bitterness of RebA and RebD cannot be predicted by AceK bitterness, reinforcing our view that bitterness is not a simple monolithic trait that is high or low in an individual. This also implies consumers who reject AceK may not find RebA and RebD aversive, and vice versa. Finally, RebD may be a superior natural non-nutritive sweetener to RebA, as it elicits significantly less bitterness at similar levels of sweetness. PMID:24187601
Aldolase as a Chirality Intersection of L-Amino Acids and D-Sugars
NASA Astrophysics Data System (ADS)
Munegumi, Toratane
2015-06-01
Aldolase plays an important role in glycolysis and gluconeogenesis to produce D-fructose-1,6-bisphosphate (D-FBP) from dihydroxyacetone phosphate (DHP) and D-glyceraldehyde-3-phosphate (D-GAP). This reaction is stereoselective and retains the D-GAP 2R configuration and yields D-FBP (with the configuration: 3S, 4S, 5R). The 3- and 4-position carbons are the newly formed chiral carbons because the 5-position carbon of D-FBP comes from the 2-position of D-GAP. Although four diastereomeric products, ( 3S, 4R, 5R), ( 3R, 4R, 5R), ( 3R, 4S, 5R), ( 3S, 4S, 5R), are expected in the nonenzymatic reaction, only the ( 3S, 4S, 5R) diastereomer (D-FBP) is obtained. Therefore, the chirality in the 3- and 4-positions is induced by the chirality of the enzyme composed of L-amino acid residues. D-Glucose-6-phosphate (D-G6P), which is generated from D-FBP in the gluconeogenesis pathway, produces D-ribose-5-phosphate (D-R5P) in the pentose phosphate pathway. D-R5P is converted to PRPP (5-phosphoribosyl-α-pyrophosphate), which is used for the de novo synthesis of nucleotides. Ribonucleic acid (RNA) uses the nucleotides as building blocks. The configurations of the 4R-carbon and of the 3S-carbon are retained. The stereochemical structure of RNA is based on 3S as well as 4R (D). The consideration above suggests that aldolase is a key enzyme that determines the 3S configuration in D-R5P. It is thus a chirality intersection between amino acids and sugars, because the sugar chirality is determined by the chiral environment of an L-amino acid protein, aldolase, to produce D-FBP.
Federal Register 2010, 2011, 2012, 2013, 2014
2012-10-22
....D. and 0.165 inch wall thickness (gage 8) 4.000 inch O.D. and 0.148 inch wall thickness (gage 9) 4.000 inch O.D. and 0.165 inch wall thickness (gage 8) 4.500 inch O.D. and 0.203 inch wall thickness... investigation is Zenith Birla (India) Limited (previously known as Zenith Steel Pipes and Industries Ltd...
Investigation of Behaviorally Modified Rats for Use in Explosives Detection Systems
1981-12-01
c. 4o t W iet s mi4w dltr’elm-jueiealolf- ltii*liti . .t.wnu sit - ass e-nz Iati ifovit l iutr in jIrrf-rt-F1wr to. thr lkillin aitinal. il if" O.W.tf...8217joizzle iwo% ill .,rdtr . d1a44, tit" alsa Ilsr"’I (olf..~ .4144 if i Ow .1fi4j4.Iiumi.4-l4p sit Iii- t.’ l m~I14r.414r1 d4 atiim l-. leo *.rt1.-r is...urvisisi-. I Ifi- -1its 1%a- 1.11, -esi f, rf a 1 -Illijvvt. li-es ill [ies 1 irtlit- wyit eirmr ilist-- sit . ii- IsrpIllssLitinitijl 1Imi-iid
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.
Shams Eldin, Safa M; Radwan, Mohamed M; Wanas, Amira S; Habib, Abdel-Azim M; Kassem, Fahima F; Hammoda, Hala M; Khan, Shabana I; Klein, Michael L; Elokely, Khaled M; ElSohly, Mahmoud A
2018-05-25
The in vitro antidiabetic and antihyperlipidemic activities of an alcoholic extract of Trigonella stellata were evaluated in terms of the activation of PPAR α and PPAR γ in human hepatoma (HepG2) cells. The extract was investigated phytochemically, aiming at the isolation of the most active compounds to be used as a platform for drug discovery. Three new isoflavans, (3 S,4 R)-4,2',4'-trihydroxy)-7-methoxyisoflavan (1), (3 R,4 S)-4,2',4'-trihydroxy-7-methoxy-4'- O-β-d-glucopyranosylisoflavan (2), and (2 S,3 R,4 R)-4,2',4'-trihydroxy-2,7-dimethoxyisoflavan (3), were isolated and characterized along with the five known compounds p-hydroxybenzoic acid (4), 7,4'-dihydroxyflavone (5), dihydromelilotoside (6), quercetin-3,7- O-α-l-dirhamnoside (7), and soyasaponin I (8). The structures of 1-3 were elucidated using various spectroscopic techniques including HRESIMS and 1D and 2D NMR. The absolute stereochemistry of the new isoflavans (1-3) was determined using both experimental and calculated electronic circular dichroism as well as DP4 calculations. The isolated compounds were tested for their PPAR α and PPAR γ activation effects in HepG2 cells.
Glass Fibre/Epoxy Resin Interface Life-Time Prediction.
1983-04-01
RD-Ai32 26 GLASS FIBRE /POXY RESIN INTERFACE LIFE-TIME PREDICTION 1/1 (U) BRISTOL UNIV (ENGLAND) H H WILLS PHYSICS LAB K H RSHBEE ET AL. APR 83...D 3005-MS GLASS FIBRE /EPOXY RESIN INTERFACE LIFE-TIME PREDICTION - Final Report by K H G Ashbee, Principal Investigator R Ho~l J P Sargent Elizabeth...REPORT h PERIOD COVERED. Glass Fibre /Epoxy Resin Interface Life-time F-inal Technical 11’ port PreictonApril 1981 - A:’ril 1983 6. PERFORMING ORG. REPORT
2017-10-01
Amplification of Neuropathic Pain from Traumatic Injury PRINCIPAL INVESTIGATOR: Linda R. Watkins , Ph.D. CONTRACTING ORGANIZATION: Regents of the...0161 5c. PROGRAM ELEMENT NUMBER 6. AUTHOR(S) Linda R Watkins , Ph.D. Peter M Grace, Ph.D. Suzanne M Fulgham, M.S. 5d. PROJECT NUMBER 5e. TASK...but from their action on glia cells by binding to the TLR4 receptor ( Watkins , Hutchinson, Rice, Maier, Trends Pharmacol Sci., 2009). Opioid
Federal Register 2010, 2011, 2012, 2013, 2014
2012-12-26
... determines that material injury, or threat of material injury, does not exist, this proceeding will be... R&D Program/Information Display R&D Center Program [squf] Support for SME ``Green Partnerships... R&D'' Program Comment 15: Whether the Department Erred in Finding That the ``SME Green Partnerships...
1990-01-01
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Sánchez-Soto, Marta; Bonifazi, Alessandro; Cai, Ning Sheng; Ellenberger, Michael P.; Newman, Amy Hauck
2016-01-01
The Gαi/o-coupled dopamine D2-like receptor family comprises three subtypes: the D2 receptor (D2R), with short and long isoform variants (D2SR and D2LR), D3 receptor (D3R), and D4 receptor (D4R), with several polymorphic variants. The common overlap of norepinephrine innervation and D2-like receptor expression patterns prompts the question of a possible noncanonical action by norepinephrine. In fact, previous studies have suggested that norepinephrine can functionally interact with D4R. To our knowledge, significant interactions between norepinephrine and D2R or D3R receptors have not been demonstrated. By using radioligand binding and bioluminescent resonance energy transfer (BRET) assays in transfected cells, the present study attempted a careful comparison between dopamine and norepinephrine in their possible activation of all D2-like receptors, including the two D2R isoforms and the most common D4R polymorphic variants. Functional BRET assays included activation of G proteins with all Gαi/o subunits, adenylyl cyclase inhibition, and β arrestin recruitment. Norepinephrine acted as a potent agonist for all D2-like receptor subtypes, with the general rank order of potency of D3R > D4R ≥ D2SR ≥ D2L. However, for both dopamine and norepinephrine, differences depended on the Gαi/o protein subunit involved. The most striking differences were observed with Gαi2, where the rank order of potencies for both dopamine and norepinephrine were D4R > D2SR = D2LR >> D3R. Furthermore the results do not support the existence of differences in the ability of dopamine and norepinephrine to activate different human D4R variants. The potency of norepinephrine for adrenergic α2A receptor was only about 20-fold higher compared with D3R and D4R across the three functional assays. PMID:26843180
Jiang, Yushi; Bachner-Melman, Rachel; Chew, Soo Hong; Ebstein, Richard P
2015-01-01
On a large sample of 2288 Han Chinese undergraduates, we investigated how religion and DRD4 are related to human altruistic giving behavior as measured with the Andreoni-Miller Dictator Game. This game enables us to clearly specify (non-)selfishness, efficiency, and fairness motives for sharing. Participants were further classified into religious categories (Christian, Buddhist-Tao, and No Religion) based on self-reports, and genotyped for the dopamine D4 receptor (DRD4) gene exon III VNTR. Our analysis revealed a significant interaction between religion and DRD4 correlated with giving behavior solely among males: Whereas no significant association between religion and sharing decisions was observed in the majority 4R/4R genotype group, a significant difference in giving behavior between Christian and non-Christian males was seen in the non-4R/4R group, with Christian men being overall more altruistic (less selfish and fairer) than non-Christian men. These results support the vantage sensitivity hypothesis regarding DRD4 that the non-4R/4R "susceptibility" genotype is more responsive to a positive environment provided by some religions.
Jiang, Yushi; Bachner-Melman, Rachel; Chew, Soo Hong; Ebstein, Richard P.
2015-01-01
On a large sample of 2288 Han Chinese undergraduates, we investigated how religion and DRD4 are related to human altruistic giving behavior as measured with the Andreoni-Miller Dictator Game. This game enables us to clearly specify (non-)selfishness, efficiency, and fairness motives for sharing. Participants were further classified into religious categories (Christian, Buddhist-Tao, and No Religion) based on self-reports, and genotyped for the dopamine D4 receptor (DRD4) gene exon III VNTR. Our analysis revealed a significant interaction between religion and DRD4 correlated with giving behavior solely among males: Whereas no significant association between religion and sharing decisions was observed in the majority 4R/4R genotype group, a significant difference in giving behavior between Christian and non-Christian males was seen in the non-4R/4R group, with Christian men being overall more altruistic (less selfish and fairer) than non-Christian men. These results support the vantage sensitivity hypothesis regarding DRD4 that the non-4R/4R “susceptibility” genotype is more responsive to a positive environment provided by some religions. PMID:26441510
Wong, Kuan Yee; Esguerra, Roxanna Jean; Chia, Vanessa Ai Ping; Tan, Ying Han; Tan, Keson Beng Choon
2018-02-01
Prior studies have defined the accuracy of intraoral scanner (IOS) systems but the accuracy of the digital static interocclusal registration function of these systems has not been reported. This study compared the three-dimensional (3D) accuracy of the digital static interocclusal registration of 3 IOS systems using the buccal bite scan function. Three IOS systems compared were 3M TM True Definition Scanner (TDS), TRIOS Color (TRC), and CEREC AC with CEREC Omnicam (CER). Using each scanner, 7 scans (n = 7) of the mounted and articulated SLA master models were obtained. The measurement targets (SiN reference spheres and implant abutment analogs) were in the opposing models at the right (R), central (C), and left (L) regions; abutments #26 and #36, respectively. A coordinate measuring machine with metrology software compared the physical and virtual targets to derive the global 3D linear distortion between the centroids of the respective target reference spheres and abutment analogs (dR R , dR C , dR L , and dR M ) and 2D distances between the pierce points of the abutment analogs (dX M , dY M , dZ M ), with 3 measurement repetitions for each scan. Mean 3D distortion ranged from -471.9 to 31.7 μm for dR R , -579.0 to -87.0 μm for dR C , -381.5 to 69.4 μm for dR L , and -184.9 to -23.1 μm for dR M . Mean 2D distortion ranged from -225.9 to 0.8 μm for dX M , -130.6 to -126.1 μm for dY M , and -34.3 to 26.3 μm for dZ M . Significant differences were found for interarch distortions across the three systems. For dR R and dR L , all three test groups were significantly different, whereas for dR C , the TDS was significantly different from the TRC and CER. For 2D distortion, significant differences were found for dX M only. Interarch and global interocclusal distortions for the three IOS systems were significantly different. TRC performed overall the best and TDS was the worst. The interarch (dR R , dR C , dR L ) and interocclusal (dX M ) distortions observed will affect the magnitude of occlusal contacts of restorations clinically. The final restoration may be either hyperoccluded or infraoccluded, requiring compensations during the CAD design stage or clinical adjustments at issue. © 2017 by the American College of Prosthodontists.
miRNA-216 and miRNA-499 target cyb561d2 in zebrafish in response to fipronil exposure.
Zhou, Yongyong; Huang, Hannian; Zhang, Kai; Ding, Xianfeng; Jia, Longlue; Yu, Liang; Zhu, Guonian; Guo, Jiangfeng
2016-07-01
MicroRNA (miRNA) can regulate the expression of its target gene by mediating mRNA cleavage or by translational repression at a post-transcriptional level. Usually, one miRNA may regulate many genes as its targets, while one gene may also be targeted by many miRNAs. We previously demonstrated that cyb561d2, whose protein product is involved in cell defense, and chemical stress, is targeted by miR-155 in adult zebrafish (Danio rerio) when exposed to fipronil (5-amino-1-[2,6-dichloro-4-(trifluoromethyl) phenyl]-4-[(trifluoromethyl) sulphinyl]-1H-pyrazole-3-carbonitrile). Microcosm Targets prediction showed that the cyb561d2 gene is also highly possibly targeted by miR-194a, miR-216b, miR-429, and miR-499. These interactions need to be further validated experimentally. In this study, we evaluated the effects of fipronil on miR-194a, miR-216b, miR-429, miR-499 and cyb561d2 in zebrafish and investigated whether these four miRNAs could regulate the expression of cyb561d2 in both mRNA and protein levels. The expression of cyb561d2 was upregulated in both mRNA and protein level in a dose-dependent manner upon stimulation of fipronil, and miR-216b and miR-499 were downregulated concurrently, whereas there was no significant changes were observed in the expression level of miR-194a and miR-429. The dual luciferase report assay demonstrated that miR-216b and miR-499 interacted with cyb561d2 3'-untranslated regions (3'-UTR), miR-194a and miR-429 did not stimulate degradation of cyb561d2 mRNA. The expression of cyb561d2 was reduced in both mRNA and protein level when ZF4 cells were transfected with miR-499 mimic, whereas expression level of both mRNA and protein was increased when endogenous miR-499 was inhibited by transfection with miR-499 inhibitor. Likewise, the mRNA and protein level of cyb561d2 was affected by treatment with the mimics and the inhibitor of miR-216b. In contrast, when ZF4 cells were transfected with a mimic of miR-194a or miR-429, the expression of cyb561d2 mRNA was not significantly changed. As a result, cyb561d2 is targeted by miR-155, miR-216b and miR-499 upon fipronil exposure, and miR-194a and miR-429 can not target cyb561d2. The expression pattern of these 3 miRNAs presents novel fipronil responses that could be used as a toxicological biomarker. Copyright © 2016 Elsevier B.V. All rights reserved.
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.
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.
Higher-order gravity in higher dimensions: geometrical origins of four-dimensional cosmology?
NASA Astrophysics Data System (ADS)
Troisi, Antonio
2017-03-01
Determining the cosmological field equations is still very much debated and led to a wide discussion around different theoretical proposals. A suitable conceptual scheme could be represented by gravity models that naturally generalize Einstein theory like higher-order gravity theories and higher-dimensional ones. Both of these two different approaches allow one to define, at the effective level, Einstein field equations equipped with source-like energy-momentum tensors of geometrical origin. In this paper, the possibility is discussed to develop a five-dimensional fourth-order gravity model whose lower-dimensional reduction could provide an interpretation of cosmological four-dimensional matter-energy components. We describe the basic concepts of the model, the complete field equations formalism and the 5-D to 4-D reduction procedure. Five-dimensional f( R) field equations turn out to be equivalent, on the four-dimensional hypersurfaces orthogonal to the extra coordinate, to an Einstein-like cosmological model with three matter-energy tensors related with higher derivative and higher-dimensional counter-terms. By considering the gravity model with f(R)=f_0R^n the possibility is investigated to obtain five-dimensional power law solutions. The effective four-dimensional picture and the behaviour of the geometrically induced sources are finally outlined in correspondence to simple cases of such higher-dimensional solutions.
Exploring cosmic homogeneity with the BOSS DR12 galaxy sample
DOE Office of Scientific and Technical Information (OSTI.GOV)
Ntelis, Pierros; Hamilton, Jean-Christophe; Busca, Nicolas Guillermo
2017-06-01
In this study, we probe the transition to cosmic homogeneity in the Large Scale Structure (LSS) of the Universe using the CMASS galaxy sample of BOSS spectroscopic survey which covers the largest effective volume to date, 3 h {sup −3} Gpc{sup 3} at 0.43 ≤ z ≤ 0.7. We study the scaled counts-in-spheres, N(< r ), and the fractal correlation dimension, D{sub 2}( r ), to assess the homogeneity scale of the universe using a Landy and Szalay inspired estimator. Defining the scale of transition to homogeneity as the scale at which D{sub 2}( r ) reaches 3 within 1%,more » i.e. D{sub 2}( r )>2.97 for r >R {sub H} , we find R {sub H} = (63.3±0.7) h {sup −1} Mpc, in agreement at the percentage level with the predictions of the ΛCDM model R {sub H} =62.0 h {sup −1} Mpc. Thanks to the large cosmic depth of the survey, we investigate the redshift evolution of the transition to homogeneity scale and find agreement with the ΛCDM prediction. Finally, we find that D{sub 2} is compatible with 3 at scales larger than 300 h {sup −1} Mpc in all redshift bins. These results consolidate the Cosmological Principle and represent a precise consistency test of the ΛCDM model.« less
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.
DOE Office of Scientific and Technical Information (OSTI.GOV)
Yip, S; Aerts, H; Berbeco, R
2014-06-15
Purpose: PET-based texture features are used to quantify tumor heterogeneity due to their predictive power in treatment outcome. We investigated the sensitivity of texture features to tumor motion by comparing whole body (3D) and respiratory-gated (4D) PET imaging. Methods: Twenty-six patients (34 lesions) received 3D and 4D [F-18]FDG-PET scans before chemo-radiotherapy. The acquired 4D data were retrospectively binned into five breathing phases to create the 4D image sequence. Four texture features (Coarseness, Contrast, Busyness, and Complexity) were computed within the the physician-defined tumor volume. The relative difference (δ) in each measure between the 3D- and 4D-PET imaging was calculated. Wilcoxonmore » signed-rank test (p<0.01) was used to determine if δ was significantly different from zero. Coefficient of variation (CV) was used to determine the variability in the texture features between all 4D-PET phases. Pearson correlation coefficient was used to investigate the impact of tumor size and motion amplitude on δ. Results: Significant differences (p<<0.01) between 3D and 4D imaging were found for Coarseness, Busyness, and Complexity. The difference for Contrast was not significant (p>0.24). 4D-PET increased Busyness (∼20%) and Complexity (∼20%), and decreased Coarseness (∼10%) and Contrast (∼5%) compared to 3D-PET. Nearly negligible variability (CV=3.9%) was found between the 4D phase bins for Coarseness and Complexity. Moderate variability was found for Contrast and Busyness (CV∼10%). Poor correlation was found between the tumor volume and δ for the texture features (R=−0.34−0.34). Motion amplitude had moderate impact on δ for Contrast and Busyness (R=−0.64− 0.54) and no impact for Coarseness and Complexity (R=−0.29−0.17). Conclusion: Substantial differences in textures were found between 3D and 4D-PET imaging. Moreover, the variability between phase bins for Coarseness and Complexity was negligible, suggesting that similar quantification can be obtained from all phases. Texture features, blurred out by respiratory motion during 3D-PET acquisition, can be better resolved by 4D-PET imaging with any phase.« less
Collisional and Dynamical Evolution of Planetary Systems
NASA Technical Reports Server (NTRS)
Weidenschilling, Stuart J.
2004-01-01
Senior Scientst S. J. Weidenschilling presents his final administrative report in the research program entitled "Collisional and Dynamical Evolution of Planetary Systems," on which he was the Principal Investigator. This research program produced the following publications: 1) "Jumping Jupiters" in binary star systems. F. Marzari, S. J. Weidenschilling, M. Barbieri and V. Granata. Astrophys. J., in press, 2005; 2) Formation of the cores of the outer planets. To appear in "The Outer Planets" (R. Kallenbach, ED), ISSI Conference Proceedings (Space Sci. Rev.), in press, 2005; 3) Accretion dynamics and timescales: Relation to chondrites. S. J. Weidenschilling and J. Cuzzi. In Meteorites and the Early Solar System LI (D. Lauretta et al., Eds.), Univ. of Arizona Press, 2005; 4) Asteroidal heating and thermal stratification of the asteroid belt. A. Ghosh, S. J.Weidenschilling, H. Y. McSween, Jr. and A. Rubin. In Meteorites and the Early Solar System I1 (D. Lauretta et al., Eds.), Univ. of Arizona Press, 2005.
Gastro esophageal reflux: an over investigated entity in neonates and infants.
Khan, Zahid Anwar; Ahmad, Sarfraz; Sheikh, Muhammad Younus
2010-12-01
To determine the outcome of clinically suspected gastro esophageal reflux in neonates and infants. To find a protocol for evaluation of these patients in order to reduce unnecessary radiation to neonates and infants. Fifty three neonates and infants of up to 1 year of age with clinical suspicion of gastro esophageal reflux (GER) were referred for Upper gastro intestinal barium studies. This retrospective descriptive case study was carried out over a period of one year starting from October, 2006 to September, 2007. Positive cases were followed for another one year to see the final outcome. The neonate and infants of upto one year of age, referred from Neonatal intensive care unit (NICU), Paediatric ward and Out Patient Department (OPD) were included in this study. Out of 53 cases 32 were positive for G.E.R and no reflux could be identified in rest of the patients. Out of these positive cases only 4 had massive or severe G.E.R. These patients were prescribed conservative and medical treatment and were advised to follow up in the O.P.D where on subsequent follow ups the medical treatment was stopped as there were no further complaints .These patients showed normal weight gain on subsequent O.P.D visits. Other positive cases only had mild to moderate G.E.R and they were managed conservatively. These patients showed normal weight gain on subsequent O.P.D visits with complete resolution of symptoms. Regurgitation or gastro esophageal reflux is a common finding in the first 3 months of life (especially in preterm infants) and usually resolves by 6-12 months of age and should not be over investigated.
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
Federal Register 2010, 2011, 2012, 2013, 2014
2010-03-24
...; Airspace Docket No. 10-ASO-19] RIN 2120-AA66 Amendment of Using Agency for Restricted Areas R-3005A, R-3305B, R-3005C, R-3005D and R-3005E; Fort Stewart, GA AGENCY: Federal Aviation Administration (FAA), DOT. ACTION: Final rule. SUMMARY: This action changes the using agency of restricted areas R- 3005A, R-3005B...
The perspectives, information and conclusions conveyed in research project abstracts, progress reports, final reports, journal abstracts and journal publications convey the viewpoints of the principal investigator and may not represent the views and policies of ORD and EPA. Concl...
Synthesis of methyl 2-O- and 3-O-alpha-D-talopyranosyl-alpha-D-mannopyranoside.
Rana, S S; Matta, K L
1986-09-01
Methyl 3,4,6-tri-O-benzyl-2-O-[6-O-(tert-butyldiphenylsilyl)-alpha-D- mannopyranosyl]-alpha-D-mannopyranoside (2) was synthesized by treatment of methyl 3,4,6-tri-O-benzyl-2-O-alpha-D-mannopyranosyl-alpha-D-mannopyranoside with tert-butylchlorodiphenylsilane in the presence of imidazole. Isopropylidenation, followed by oxidation with pyridinium chlorochromate, and stereoselective reduction with sodium borohydride, converted 2 into methyl 3,4,6-tri-O-benzyl-2-O-[6-O-(tert-butyldiphenylsilyl)-2,3-O-isopro pylidene- alpha-D-talopyranosyl]-alpha-D-mannopyranoside (5). Treatment of 5 with a molar solution of tetrabutylammonium fluoride in dry oxolane produced a diol which, on O-de-isopropylidenation followed by catalytic hydrogenolysis, afforded the disaccharide glycoside methyl 2-O-alpha-D-talopyranosyl-alpha-D-mannopyranoside. Synthesis of methyl 3-O-alpha-D-talopyranosyl-alpha-D-mannopyranoside was accomplished by a similar reaction-sequence. The structures of the final disaccharides, and of various other intermediates, were established by 1H- and 13C-n.m.r. spectroscopy.
Balsalobre-Fernández, Carlos; Cordón, Ángel; Unquiles, Nazaret; Muñoz-García, Daniel
2018-01-01
The purpose of this study was to analyze the relationships between muscular performance consisting of a single repetition on the chair squat exercise (CSQ) and different measures of functional capacity, balance, quality of life and cognitive status in older adults. A total of 40 participants (22 women, 18 men; age = 72.2 ± 4.9 years) joined the investigation. Muscular performance was assessed by measuring movement velocity in the CSQ with no external load using a validated smartphone application ( PowerLift for iOS). Functional capacity, balance, quality of life and cognitive status were evaluated using the hand-grip strength (HGS) test, the Berg-scale, the EuroQol 5D (EQ-5D) and the Mini mental state examination questionnaire (MMSE). Finally, participants were divided into two subgroups ( N = 20) according to their velocity in the CSQ exercise. Positive correlations were obtained between movement velocity in the CSQ and HGS ( r = 0.76, p < 0.001), the Berg-scale ( r = 0.65, p < 0.001), the EQ-5D ( r = 0.34, p = 0.03) and the MMSE ( r = 0.36, p = 0.02). Participants in the fastest subgroup showed very likely higher scores in the Berg-scale (ES = 1.15) and the HGS (ES = 1.79), as well as likely higher scores in the MMSE scale (ES = 0.69). These results could have potential clinical relevance as they support the use of a time-efficient, non-fatiguing test of muscular performance (i.e., the CSQ) to evaluate functional capacity and mental cognition in older adults.
The perspectives, information and conclusions conveyed in research project abstracts, progress reports, final reports, journal abstracts and journal publications convey the viewpoints of the principal investigator and may not represent the views and policies of ORD and EPA. Concl...
IMPACTS OF (NH4)2SO4 TREATMENT ON FOLIAR CHEMISTRY AT BBWM. (R825762)
The perspectives, information and conclusions conveyed in research project abstracts, progress reports, final reports, journal abstracts and journal publications convey the viewpoints of the principal investigator and may not represent the views and policies of ORD and EPA. Concl...
Real, Joana I; Simões, Ana Patrícia; Cunha, Rodrigo A; Ferreira, Samira G; Rial, Daniel
2018-05-01
Prefrontal cortex (PFC) circuits are modulated by dopamine acting on D 1 - and D 2 -like receptors, which are pharmacologically exploited to manage neuropsychiatric conditions. Adenosine A 2A receptors (A 2 A R) also control PFC-related responses and A 2 A R antagonists are potential anti-psychotic drugs. As tight antagonistic A 2 A R-D 2 R and synergistic A 2 A R-D 1 R interactions occur in other brain regions, we now investigated the crosstalk between A 2 A R and D 1 /D 2 R controlling synaptic transmission between layers II/III and V in mouse PFC coronal slices. Dopamine decreased synaptic transmission, a presynaptic effect based on the parallel increase in paired-pulse responses. Dopamine inhibition was prevented by the D 2 R-like antagonist sulpiride but not by the D 1 R antagonist SCH23390 and was mimicked by the D 2 R agonist sumanirole, but not by the agonists of either D 4 R (A-412997) or D 3 R (PD128907). Dopamine inhibition was prevented by the A 2 A R antagonist, SCH58261, and attenuated in A 2 A R knockout mice. Accordingly, triple-labelling immunocytochemistry experiments revealed the co-localization of A 2 A R and D 2 R immunoreactivity in glutamatergic (vGluT1-positive) nerve terminals of the PFC. This reported positive A 2 A R-D 2 R interaction controlling PFC synaptic transmission provides a mechanistic justification for the anti-psychotic potential of A 2 A R antagonists. © 2018 Federation of European Neuroscience Societies and John Wiley & Sons Ltd.
Dwarf Galaxies in the Coma Cluster. II. Photometry and Analysis
NASA Astrophysics Data System (ADS)
Secker, J.; Harris, W. E.; Plummer, J. D.
1997-12-01
We use the data set derived in our previous paper (Secker & Harris 1997) to study the dwarf galaxy population in the central =~ 700 arcmin(2) of the Coma cluster, the majority of which are early-type dwarf elliptical (dE) galaxies. Analysis of the statistically-decontaminated dE galaxy sequence in the color-magnitude diagram reveals that the mean dE color at R = 18.0 mag is (B-R) =~ 1.4 mag, but that a highly significant trend of color with magnitude exists (Delta (B-R)/Delta R = -0.056+/-0.002 mag) in the sense that fainter dEs are bluer and thus presumably more metal-poor. The mean color of the faintest dEs in our sample is (B-R) =~ 1.15 mag, consistent with a color measurement of the diffuse intracluster light in the Coma core. This intracluster light could then have originated from the tidal disruption of faint dEs in the cluster core. The total galaxy luminosity function (LF) is well modeled as the sum of a log-normal distribution for the giant galaxies, and a Schechter function for the dE galaxies with a faint-end slope alpha = -1.41+/-0.05. This value of alpha is consistent with those measured for the Virgo and Fornax clusters. The spatial distribution of the faint dE galaxies (19.0 < R <= 22.5 mag) is well fit by a standard King model with a central surface density of Sigma_0 = 1.17 dEs arcmin(-2) and a core radius R_c = 22.15 arcmin ( =~ 0.46h(-1) Mpc). This core is significantly larger than the R_c = 13.71 arcmin ( =~ 0.29h(-1) Mpc) found for the cluster giants and the brighter dEs (R <= 19.0 mag), again consistent with the idea that faint dEs in the dense core have been disrupted. Finally, we find that most dEs belong to the general Coma cluster potential rather than as satellites of individual giant galaxies: An analysis of the number counts around 10 cluster giants reveals that they each have on average 4+/- 1 dE companions within a projected radius of 13.9h(-1) kpc. (SECTION: Galaxies)
Federal Register 2010, 2011, 2012, 2013, 2014
2013-02-27
..., sugars, minerals, and salts. Xanthan gum is a polysaccharide produced by aerobic fermentation of... backbone of two P-1,4-D- Glucose monosaccharide units, the second with a trisaccharide side chain consisting of P-D-Mannose-(1,4)-P-DGlucuronic acid-(1,2)-a-D- Mannose monosaccharide units. The terminal...
Eisenstein Series and String Thresholds
NASA Astrophysics Data System (ADS)
Obers, N. A.; Pioline, B.
We investigate the relevance of Eisenstein series for representing certain G()-invariant string theory amplitudes which receive corrections from BPS states only. G() may stand for any of the mapping class, T-duality and U-duality groups Sl(d,(), SO(d,d,() or Ed+1(d+1)(() respectively. Using G()-invariant mass formulae, we construct invariant modular functions on the symmetric space K\\G() of non-compact type, with K the maximal compact subgroup of G(), that generalize the standard non-holomorphic Eisenstein series arising in harmonic analysis on the fundamental domain of the Poincaré upper half-plane. Comparing the asymptotics and eigenvalues of the Eisenstein series under second order differential operators with quantities arising in one- and g-loop string amplitudes, we obtain a manifestly T-duality invariant representation of the latter, conjecture their non-perturbative U-duality invariant extension, and analyze the resulting non-perturbative effects. This includes the R4 and R4H4g-4 couplings in toroidal compactifications of M-theory to any dimension D>= 4 and D>= 6 respectively.
Kilian, Yvonne; Wehmeier, Udo F; Wahl, Patrick; Mester, Joachim; Hilberg, Thomas; Sperlich, Billy
2016-01-01
The aim of the present study was to analyze the response of vascular circulating microRNAs (miRNAs; miR-16, miR-21, miR-126) and the VEGF mRNA following an acute bout of HIIT and HVT in children. Twelve healthy competitive young male cyclists (14.4 ± 0.8 years; 57.9 ± 9.4 ml·min(-1)·kg(-1) peak oxygen uptake) performed one session of high intensity 4 × 4 min intervals (HIIT) at 90-95% peak power output (PPO), each interval separated by 3 min of active recovery, and one high volume session (HVT) consisting of a constant load exercise for 90 min at 60% PPO. Capillary blood from the earlobe was collected under resting conditions, during exercise (d1 = 20 min, d2 = 30 min, d3 = 60 min), and 0, 30, 60, 180 min after the exercise to determine miR-16, -21, -126, and VEGF mRNA. HVT significantly increased miR-16 and miR-126 during and after the exercise compared to pre-values, whereas HIIT showed no significant influence on the miRNAs compared to pre-values. VEGF mRNA significantly increased during and after HIIT (d1, 30', 60', 180') and HVT (d3, 0', 60'). RESULTS of the present investigation suggest a volume dependent exercise regulation of vascular regulating miRNAs (miR-16, miR-21, miR-126) in children. In line with previous data, our data show that acute exercise can alter circulating miRNAs profiles that might be used as novel biomarkers to monitor acute and chronic changes due to exercise in various tissues.
Laser Raman Spectroscopy of Ultraviolet-Induced Cataracts in Rabbits and Monkeys.
1979-12-01
ILTRAVIOLETINHUCED CATARACTS SIN RABBITS AND MONKEYS Dwaine M. Thomas, Ph.D. ,KennethL. Schepler, Captain, USAF December 1979 Final Report for Period...3AMAN VECTROSCOPY OF .JLTRAV IOLET;NDUCED) POR U77 -FbR7 WATARACTS IN RABBITS AND MONKEYS .0 R. O,;4MIE V 111___ 2= _ 7. AUTHOR(*) S. CONTRACT OR GRANT...cataracts ABSTRACT (Continue on rev’erse side if necessary art# identify hV block numb~er) he Raman spectrl .of aormal rabbit’ana monkey lenses have been
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.
Dynamics analysis of epidemic and information spreading in overlay networks.
Liu, Guirong; Liu, Zhimei; Jin, Zhen
2018-05-07
We establish an SIS-UAU model to present the dynamics of epidemic and information spreading in overlay networks. The overlay network is represented by two layers: one where the dynamics of the epidemic evolves and another where the information spreads. We theoretically derive the explicit formulas for the basic reproduction number of awareness R 0 a by analyzing the self-consistent equation and the basic reproduction number of disease R 0 d by using the next generation matrix. The formula of R 0 d shows that the effect of awareness can reduce the basic reproduction number of disease. In particular, when awareness does not affect epidemic spreading, R 0 d is shown to match the existing theoretical results. Furthermore, we demonstrate that the disease-free equilibrium is globally asymptotically stable if R 0 d <1; and the endemic equilibrium is globally asymptotically stable if R 0 d >1. Finally, numerical simulations show that information plays a vital role in preventing and controlling disease and effectively reduces the final disease scale. Copyright © 2018 Elsevier Ltd. All rights reserved.
The perspectives, information and conclusions conveyed in research project abstracts, progress reports, final reports, journal abstracts and journal publications convey the viewpoints of the principal investigator and may not represent the views and policies of ORD and EPA. Concl...
The cat lipocalin Fel d 7 and its cross-reactivity with the dog lipocalin Can f 1.
Apostolovic, D; Sánchez-Vidaurre, S; Waden, K; Curin, M; Grundström, J; Gafvelin, G; Cirkovic Velickovic, T; Grönlund, H; Thomas, W R; Valenta, R; Hamsten, C; van Hage, M
2016-10-01
We investigated the prevalence of sensitization to the cat lipocalin Fel d 7 among 140 cat-sensitized Swedish patients and elucidated its allergenic activity and cross-reactivity with the dog lipocalin Can f 1. Sixty-five of 140 patients had IgE to rFel d 7 whereof 60 also had IgE to rCan f 1. A moderate correlation between IgE levels to rFel d 7 and rCan f 1 was found. rFel d 7 activated basophils in vitro and inhibited IgE binding to rCan f 1 in 4 of 13 patients, whereas rCan f 1 inhibited IgE binding to rFel d 7 in 7 of 13 patients. Fel d 7 and Can f 1 showed high similarities in protein structure and epitopes in common were found using cross-reactive antisera. Fel d 7 is a common allergen in a Swedish cat-sensitized population that cross-reacts with Can f 1, and may contribute to symptoms in cat- but also in dog-allergic patients. © 2016 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.
View of Mission Control Center during the Apollo 13 emergency return
1970-04-16
S70-35369 (16 April 1970) --- Discussion in the Mission Operations Control Room (MOCR) dealing with the Apollo 13 crewmen during their final day in space. From left to right are Glynn S. Lunney, Shift 4 flight director; Gerald D. Griffin, Shift 2 flight director; astronaut James A. McDivitt, manager, Apollo Spacecraft Program, MSC; Dr. Donald K. Slayton, director of Flight Crew Operations, MSC; and Dr. Willard R. Hawkins, M.D., Shift 1 flight surgeon.
Clinical Investigation Program, Reports Control Symbol MED-300(R1), Fiscal Year 1988
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
NASA Astrophysics Data System (ADS)
Alturki, Uthman T.
The goal of this research was to research, design, and develop a hypertext program for students who study biology. The Ecology Hypertext Program was developed using Research and Development (R&D) methodology. The purpose of this study was to place the final "product", a CD-ROM for learning biology concepts, in the hands of teachers and students to help them in learning and teaching process. The product was created through a cycle of literature review, needs assessment, development, and a cycle of field tests and revisions. I applied the ten steps of R&D process suggested by Borg and Gall (1989) which, consisted of: (1) Literature review, (2) Needs assessment, (3) Planning, (4) Develop preliminary product, (5) Preliminary field-testing, (6) Preliminary revision, (7) Main field-testing, (8) Main revision, (9) Final field-testing, and (10) Final product revision. The literature review and needs assessment provided a support and foundation for designing the preliminary product---the Ecology Hypertext Program. Participants in the needs assessment joined a focus group discussion. They were a group of graduate students in education who suggested the importance for designing this product. For the preliminary field test, the participants were a group of high school students studying biology. They were the potential user of the product. They reviewed the preliminary product and then filled out a questionnaire. Their feedback and suggestions were used to develop and improve the product in a step called preliminary revision. The second round of field tasting was the main field test in which the participants joined a focus group discussion. They were the same group who participated in needs assessment task. They reviewed the revised product and then provided ideas and suggestions to improve the product. Their feedback were categorized and implemented to develop the product as in the main revision task. Finally, a group of science teachers participated in this study by reviewing the product and then filling out the questionnaire. Their suggestions were used to conduct the final step in R&D methodology, the final product revision. The primary result of this study was the Ecology Hypertext Program. It considered a small attempt to give students an opportunity to learn through an interactive hypertext program. In addition, using the R&D methodology was an ideal procedure for designing and developing new educational products and material.
The perspectives, information and conclusions conveyed in research project abstracts, progress reports, final reports, journal abstracts and journal publications convey the viewpoints of the principal investigator and may not represent the views and policies of ORD and EPA. Concl...
Investigation of YAG:Ce Scintillating Fiber Properties Using Silicon Photomultipliers
2011-03-01
Maj Benjamin R. Kowash (Chairman) Date ____________________________________ ________________ Lt Col Michael R. Hawks...Member) Date ____________________________________ ________________ Abigail Bickley, PhD (Member) Date iv AFIT/GNE/ENP/11-M11 Abstract...Properties of Rare Earth Garnet Crystals ...........................................................36 Page vii 4. 2. Properties of the
DOE Office of Scientific and Technical Information (OSTI.GOV)
Guiseppe, Vince
2013-10-01
The USD Majorana group focused all of its effort in support of the MAJORANA DEMONSTRATOR (MJD) experiment. Final designs of the shielding subsystems are complete. Construction of the MJD shielding systems at SURF has begun and the proposed activities directly support the completion of the shield systems. The PI and the group contribute heavily to the onsite construction activities of the MJD experiment. The group led investigations into neutron and neutron-induced backgrounds, shielding effectiveness and design, and radon backgrounds.
Valence and L-shell photoionization of Cl-like argon using R-matrix techniques
NASA Astrophysics Data System (ADS)
Tyndall, N. B.; Ramsbottom, C. A.; Ballance, C. P.; Hibbert, A.
2016-02-01
Photoionization cross-sections are obtained using the relativistic Dirac Atomic R-matrix Codes (DARC) for all valence and L-shell energy ranges between 27 and 270 eV. A total of 557 levels arising from the dominant configurations 3s23p4, 3s3p5, 3p6, 3s23p3[3d, 4s, 4p], 3p53d, 3s23p23d2, 3s3p43d, 3s3p33d2 and 2s22p53s23p5 have been included in the target wavefunction representation of the Ar III ion, including up to 4p in the orbital basis. We also performed a smaller Breit-Pauli (BP) calculation containing the lowest 124 levels. Direct comparisons are made with previous theoretical and experimental work for both valence shell and L-shell photoionization. Excellent agreement was found for transitions involving the 2Po initial state to all allowed final states for both calculations across a range of photon energies. A number of resonant states have been identified to help analyse and explain the nature of the spectra at photon energies between 250 and 270 eV.
Low Cost 2-D Heatshield Materials
1982-03-05
1 -4 - -,--. WE: 190 LUU LU w 4A (A IC a -’ I- 0 3c z L U LLJ u0 ud Lad 10 .- qVa . IC -Ab In this test, a...REPOR.’ Dn _1,EHTA’ 1 .;ij PAGE DRSCMLý%IGF" ____ __4 1 33 813C M~J.~~ŽOP Ř. ’rT.19ddsmto S. Type F1@60pNIaOPobw~, aOcovItNK Final Technical Report May...IYD13NUBROPAE Redstone ArseralL.AL 35ý1 __20 1 -MONO’. CRING AG.:hiY HAM41 & AVOR&;S(11 dill. il I.,. Can-r..INA, OflICS) IS- SECUWI *Y CLASS. (@ 1
NASA Technical Reports Server (NTRS)
1975-01-01
Preliminary development plans, analysis of required R and D and production resources, the costs of such resources, and, finally, the potential profitability of a commercial space processing opportunity for the production of very high frequency surface acoustic wave devices are presented.
Remedial Investigation Badger Army Ammunition Plant, Baraboo, Wisconsin. Volume 6. Appendix L
1991-01-01
N - - aM o o 00 aW~ w .oori -5 o-itw ,121LZ stst s a 1" 0 4 4, d 1!i 1 it& a o vvi P.w .d = 9- o ww II 4c - AL A- 4v r, 17 . f Q 4c 4A 0L C...Ud4 &fXXXl:C1 >4v 0 41 0 1 Pý0 1 1ma 0 07 P1 Pl ŕ 01 P34P.P3 .4.4.4.40.at4t.04aW4A.b4.9 00 -.4M 0100 toI 0000 0000 0000 0000 0000 0 000 0000 0000...r~’n’oaom1010o0810010881wo wo w ~f41 ,c000001 010100 000 01 s00.01 8810101c WI W w Wl c 40 04 in x n ODI0a 00Xrac0(l1r a GOV MV 0 MOOO 04Uf MMAor=AQM
DOE Office of Scientific and Technical Information (OSTI.GOV)
Capelle, Lisa; Warkentin, Heather; MacKenzie, Marc
Purpose: We investigated whether treatment-planning system (TPS)-calculated dose accurately reflects skin dose received for patients receiving adjuvant breast radiotherapy (RT) with standard three-dimensional conformal RT (3D-CRT) or skin-sparing helical tomotherapy (HT). Methods and Materials: Fifty patients enrolled in a randomized controlled trial investigating acute skin toxicity from adjuvant breast RT with 3D-CRT compared to skin-sparing HT, where a 5-mm strip of ipsilateral breast skin was spared. Thermoluminescent dosimetry or optically stimulated luminescence measurements were made in multiple locations and were compared to TPS-calculated doses. Skin dosimetric parameters and acute skin toxicity were recorded in these patients. Results: With HT theremore » was a significant correlation between calculated and measured dose in the medial and lateral ipsilateral breast (r = 0.67, P<.001; r = 0.44, P=.03, respectively) and the medial and central contralateral breast (r = 0.73, P<.001; r = 0.88, P<.001, respectively). With 3D-CRT there was a significant correlation in the medial and lateral ipsilateral breast (r = 0.45, P=.03; r = 0.68, P<.001, respectively); the medial and central contralateral breast (r = 0.62, P=.001; r = 0.86, P<.001, respectively); and the mid neck (r = 0.42, P=.04, respectively). On average, HT-calculated dose overestimated the measured dose by 14%; 3D-CRT underestimated the dose by 0.4%. There was a borderline association between highest measured skin dose and moist desquamation (P=.05). Skin-sparing HT had greater skin homogeneity (homogeneity index of 1.39 vs 1.65, respectively; P=.005) than 3D-CRT plans. HT plans had a lower skin{sub V50} (1.4% vs 5.9%, respectively; P=.001) but higher skin{sub V40} and skin{sub V30} (71.7% vs 64.0%, P=.02; and 99.0% vs 93.8%, P=.001, respectively) than 3D-CRT plans. Conclusion: The 3D-CRT TPS more accurately reflected skin dose than the HT TPS, which tended to overestimate dose received by 14% in patients receiving adjuvant breast RT.« less
Exploring cosmic homogeneity with the BOSS DR12 galaxy sample
NASA Astrophysics Data System (ADS)
Ntelis, Pierros; Hamilton, Jean-Christophe; Le Goff, Jean-Marc; Burtin, Etienne; Laurent, Pierre; Rich, James; Guillermo Busca, Nicolas; Tinker, Jeremy; Aubourg, Eric; du Mas des Bourboux, Hélion; Bautista, Julian; Palanque Delabrouille, Nathalie; Delubac, Timothée; Eftekharzadeh, Sarah; Hogg, David W.; Myers, Adam; Vargas-Magaña, Mariana; Pâris, Isabelle; Petitjean, Partick; Rossi, Graziano; Schneider, Donald P.; Tojeiro, Rita; Yeche, Christophe
2017-06-01
In this study, we probe the transition to cosmic homogeneity in the Large Scale Structure (LSS) of the Universe using the CMASS galaxy sample of BOSS spectroscopic survey which covers the largest effective volume to date, 3 h-3 Gpc3 at 0.43 <= z <= 0.7. We study the scaled counts-in-spheres, N(
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
Tang, Weizhi; Dong, Mingsheng; Wang, Weilu; Han, Shuo; Rui, Xin; Chen, Xiaohong; Jiang, Mei; Zhang, Qiuqin; Wu, Junjun; Li, Wei
2017-10-01
Three released exopolysaccharide fractions (r-EPS1, r-EPS2 and r-EPS3) were isolated from the fermented milk of Lactobacillus delbrueckii ssp. bulgaricus SRFM-1 and purified by anion exchange chromatography, and characterizations of the structures were conducted. The r-EPS1 and r-EPS2 were homogenous with the average molecular weights of 3.97×10 5 Da and 3.86×10 5 Da, respectively. Three r-EPS fractions were composed of galactose and glucose with a molar ratio of 1.23: 1.00, 1.33: 1.00 and 1.00: 1.34, respectively. Structural characterization indicated that the r-EPS1 contained a backbone of →6-β-d-Galp-(1→4)-β-d-Glcp-(1→4)-α-d-Galp-(1→4)-β-d-Galp-(1→6)-β-d-Galp-(1→4)-β-d-Glcp-(1→4)-α-d-Galp-(1→4)-β-d-Galp-(1→4)-α-d-Glcp-(1→, and had three branching points which existed in terminal with D-Glcp residues with α/β-d-(1→6) linkages. The r-EPS2 was composed of →6-β-d-Galp-(1→4)-β-d-Glcp-(1→6)-α-d-Galp-(1→ as the backbone chain with a branching point which also existed in terminal D-Glcp residue with β-(1→6) linkage. In addition, three r-EPS fractions exhibited strong scavenging activities on superoxide radical, hydroxyl radical, DPPH radical and chelating activity on ferrous ion, and their antioxidant activities decreased in the order of r-EPS1>r-EPS2>r-EPS3. Copyright © 2017 Elsevier Ltd. All rights reserved.
DOE Office of Scientific and Technical Information (OSTI.GOV)
Dowe, N.
2014-05-01
This research program will convert acid pretreated corn stover to sugars at the National Renewable Energy Laboratory (NREL) and then transfer these sugars to Honda R&D and its partner the Green Earth Institute (GEI) for conversion to ethanol via a novel fermentation organism. In phase one, NREL will adapt its pretreatment and saccharification process to the unique attributes of this organism, and Honda R&D/GEI will increase the sugar conversion rate as well as the yield and titer of the resulting ethanol. In later phases, NREL, Honda R&D, and GEI will work together at NREL to optimize and scale-up to pilot-scalemore » the Honda R&D/GEI bioethanol production process. The final stage will be to undertake a pilot-scale test at NREL of the optimized bioethanol conversion process.« less
1995-12-01
Geotechnical Data D Geophysical Surveys E Analysis of QA/QC Program F Aquifer Hydraulic Characterization (Slug Testing) G Groundwater Model Report H...M " f ; Soil/Rock ~ Dataii~ 2!Desc~lpliOn ccl - -GR OUND SURFACE- -~~ MMJrb OMOE U)IF ’G gm~ * t -iG O p& 11 i 1 ’ w //* I M E - F .51"’/j H5As o4 2-e...o fS A D 11tL IN SNE,7f ’(;v ,* , F * It~ .-. 4 1I4O WLD ~*’h4,Ft , T6.r,17,L ’DIULLe8ING NOTa 4 14.6@AO 0w- IUL W 33s - reyce pae A-, 7 1= amd n 01r0r
1980-11-01
Systems: A Raytheon Project History", RADC-TR-77-188, Final Technical Report, June 1977. 4. IBM Federal Systems Division, "Statistical Prediction of...147, June 1979. 4. W. D. Brooks, R. W. Motley, "Analysis of Discrete Software Reliability Models", IBM Corp., RADC-TR-80-84, RADC, New York, April 1980...J. C. King of IBM (Reference 9) and Lori A. Clark (Reference 10) of the University of Massachusetts. Programs, so exercised must be augmented so they
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.
32 CFR 105.5 - Responsibilities.
Code of Federal Regulations, 2013 CFR
2013-07-01
... consulted on any changes in DoD policy or the UCMJ relating to sexual assault. (4) With the Director, SAPRO... SAPRO. (2) Inform the USD(P&R) of any sexual assault related changes to the UCMJ. (e) IG DoD. The IG DoD... changes relating to sexual assault investigation policy or guidance. (3) DoD IG shall collaborate with...
32 CFR 105.5 - Responsibilities.
Code of Federal Regulations, 2014 CFR
2014-07-01
... consulted on any changes in DoD policy or the UCMJ relating to sexual assault. (4) With the Director, SAPRO... SAPRO. (2) Inform the USD(P&R) of any sexual assault related changes to the UCMJ. (e) IG DoD. The IG DoD... changes relating to sexual assault investigation policy or guidance. (3) DoD IG shall collaborate with...
Approximate Reasoning and the REVEAL Software System. Users Guide.
1985-03-01
Oi O O Sko mwr-r . . U~ -n APPENDIX B TACTICAL MODEL REVEAL CONTEXT *-4 u)63U .0 W -4 - 0-oLL 0 LA,- X -4 .- q 0 S... 0 03 Q C4U u r= <c El) ty E:, Ui...u .jI - k0 jC~ q ( 0t’ COr *o (0 C) V)0 r C C-r’ ko o A Ul -)- - ’ r) -UIUrU 0<D( . .* . . . . . . . . . . . (S 0< )(D< ()%D(D ( - Z C D IDC ()tD...i.N 0 0t0-400 U Uo 03 V4’U ko 0 o.... L) 4 40.). .4.4’ 403p03 L) -4 - --4 .- 4v V4 4 U)- U) 0 0U)U I u )uU) u ) - P tn V -C ) V~U)~) E -4 R -- 4
Final Report for Contract N00014-86-C-0598 (Thermo Electron Technologies Corporation)
1989-12-28
At least 20 A/cm2 were observed at 193 nm. 248 nm (KrF) and 308 (XeCl). Beam brightness appears to be a minimum of 4 x 105 A/cm 2 -rad 2 at 248 nm...governed by the envelope equation3, d2r K b 0 dz (4) For a weakly relativistic beam. e J o r0 2 2 Co 0Mo (yac) 3 (5) where Jo is the beam current...correspond to laser wavotengths of the present study, preliminary measurement for ArF given by x .1 pattern ot spots on the phosphor screen for 248 nm
Fate of MgSiO3 Post-Perovskite at Terapascal Pressures
NASA Astrophysics Data System (ADS)
Wentzcovitch, R. M.; Umemoto, K.; Wu, S.; Ho, K. M.; Ji, M.; Wang, C. Z.
2016-12-01
Understanding the fate of MgSiO3 post-perovskite (ppv) under TPa pressures should provide insights into the nature of the interiors of Super-Earths-type exoplanets. The prediction that ppv should dissociate into the elementary oxides MgO and SiO2 at TPa pressures [1] has been confirmed by all ab initio computational studies so far [2-4]. The most recent high pressure and high temperature (PT) studies agree that at 2.2 TPa the dissociation process should be completed [2,3]. These studies also agree that the final dissociation phase boundary has a negative Clapeyron slope [1-3], irrespective of the dissociation paths, suggesting a barrier to whole mantle convection possibly leading to chemical stratification in the deep mantle of these planets. The dissociation paths identified more recently [2-4] involve partial dissociation into MgO, SiO2, and Mg- and Si-rich intermediate compounds whose compositions are temperature dependent. Here we re-investigate the high PT phase diagram of the MgO-SiO2 system and identify novel phase fields and dissociation paths that push the final dissociation boundary to 3 TPa. 1) K. Umemoto, R. M. Wentzcovitch, & P. B. Allen, Dissociation of MgSiO3 in the cores of Gas Giants and Terrestrial Exoplanets, Science 311, 983 (2006). 2) K. Umemoto & R. M. Wentzcovitch, Two-stage dissociation of MgSiO3 post- perovskite, Earth & Planet. Sc. Lett. 311, 225 (2011). 3) H. Niu, A. R. Oganov, X.-C. Chen, & D. Li, Prediction of novel stable compounds in the Mg-Si-O system under exoplanet pressures, Sc. Rep. 5, 18347 (2015). 4) S. Q. Wu, M. Ji, C. Z. Wang, M. C. Nguye, X. Zhao, K. Umemoto, R. M. Wentzcovitch, & K. M. Ho, Adaptive genetic algorithm for crystal structure prediction, J. Phys.: Condens. Matter 26, 035402 (2014).
Qi, Mengwen; Wu, Chunfeng; Wang, Zhouqing; Zhou, Li; Men, Chen; Du, Yimei; Huang, Songming; Chen, Lei; Chen, Ling
2018-01-01
Glycine plays an important role in regulating hippocampal inhibitory/ excitatory neurotransmission through activating glycine receptors (GlyRs) and acting as a co-agonist of N-methyl-d-aspartate-type glutamate receptors. Activation of transient receptor potential vanilloid 4 (TRPV4) is reported to inhibit hippocampal A-type γ-aminobutyric acid receptor, a ligand-gated chloride ion channel. GlyRs are also ligand-gated chloride ion channels and this paper aimed to explore whether activation of TRPV4 could modulate GlyRs. Whole-cell patch clamp recording was employed to record glycine-activated current (IGly) and Western blot was conducted to assess GlyRs subunits protein expression. Application of TRPV4 agonist (GSK1016790A or 5,6-EET) increased IGly in mouse hippocampal CA1 pyramidal neurons. This action was blocked by specific antagonists of TRPV4 (RN-1734 or HC-067047) and GlyR (strychnine), indicating that activation of TRPV4 increases strychnine-sensitive GlyR function in mouse hippocampal pyramidal neurons. GSK1016790A-induced increase in IGly was significantly attenuated by protein kinase C (PKC) (BIM II or D-sphingosine) or calcium/calmodulin-dependent protein kinase II (CaMKII) (KN-62 or KN-93) antagonists but was unaffected by protein kinase A or protein tyrosine kinase antagonists. Finally, hippocampal protein levels of GlyR α1 α2, α3 and β subunits were not changed by treatment with GSK1016790A for 30 min or 1 h, but GlyR α2, α3 and β subunits protein levels increased in mice that were intracerebroventricularly (icv.) injected with GSK1016790A for 5 d. Activation of TRPV4 increases GlyR function and expression, and PKC and CaMKII signaling pathways are involved in TRPV4 activation-induced increase in IGly. This study indicates that GlyRs may be effective targets for TRPV4-induced modulation of hippocampal inhibitory neurotransmission. © 2018 The Author(s). Published by S. Karger AG, Basel.
Raman Investigation of the Effects on Fused Silica Fibers
1983-01-12
Howard University NR-051-733 Washington, D.C. 20059v=4 1- CO-NTROLLING OFFICE NAME AND ADDRESS 12. RIEPORT DATE Office of Naval Research January 12, 1983...0.. Chemistry Department Howard University Washington, D.C. 20059 r P" -2- The application of... Howard University , 1981. (4) Scrambled laser polarization was used prior to Raman excitation, Figs. l(c) and l(d), to counteract effects of
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 perspectives, information and conclusions conveyed in research project abstracts, progress reports, final reports, journal abstracts and journal publications convey the viewpoints of the principal investigator and may not represent the views and policies of ORD and EPA. Concl...
The perspectives, information and conclusions conveyed in research project abstracts, progress reports, final reports, journal abstracts and journal publications convey the viewpoints of the principal investigator and may not represent the views and policies of ORD and EPA. Concl...
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.
Terminal Area Forecasts, FY 1993-2005
1993-07-01
0 td U) ~ 4-) 4.J.4 0 J~ :s 0- -"C4 4o U ).4CO ) 0 u *Wý44 o 41C kdQ(n v 00 UrC~ 4) -4 0 M 0~ 4j > (D M kca 41 Ř b bO CA -A~ ..O 0 .0 Cd~ bl ~ - k...o tD ~ Hr- Nr,- `4v oH f n% oM 0( ON %D ~H w H LnODH (1 O O D DO ODG OD 00 OhOh(T ma % m %0 HC4.Ch h %Ch( i % )d% HN 4J H 1-0 %D- O M (NWN DU VO D...I ~ J)I C1 F "H OD ,- V 1 D ( -r r -4 Ch’. ON 00 -4 c,4 mu) n( (n A;1 m tD b r-4 rJ’q~~ I Nr-W L o 0 ( O HM N~ - I- IV N- M M O ’ rI % NN . OD U NCh0
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
Evaluating the Environmental Impact, Cost, and Performance of Biobased Alternatives
2007-05-01
r r r. r ASTM D 445: At 40°C: 38.5 • 45.5 cStDAt 100°C: min 4.8 est MIL -H- 81019 I r r r. r r r. ASTM D 445: At 100°(: 2.5 x 10-6 m’l/s, minD...r. r r mm>/s(cSt)DGrade 2 btw 41.4 and 50.6 mm 2 /sDGrade 3 btw 6 1.2 and 74.8 mm 2 /sDGrade 4 r. r r btw 135 and 165 mm’/s MIL -H- 19457 I r r...At 40°C: 7.0 x 10-6 m>/s, minD At -54°C: 800 x 10-6 m 2 /s, max D At ·70°C: 0.008 m 2 /s, m~x MIL -PRF-32073 I r. r r r. r r ASTM D 445: At 40°C
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.
Low serum vitamin D is associated with higher cortical porosity in elderly men.
Sundh, D; Mellström, D; Ljunggren, Ö; Karlsson, M K; Ohlsson, C; Nilsson, M; Nilsson, A G; Lorentzon, M
2016-11-01
Bone loss at peripheral sites in the elderly is mainly cortical and involves increased cortical porosity. However, an association between bone loss at these sites and 25-hydroxyvitamin D has not been reported. To investigate the association between serum levels of 25-hydroxyvitamin D, bone microstructure and areal bone mineral density (BMD) in elderly men. A population-based cohort of 444 elderly men (mean ± SD age 80.2 ± 3.5 years) was investigated. Bone microstructure was measured by high-resolution peripheral quantitative computed tomography, areal BMD by dual-energy X-ray absorptiometry and serum 25-hydroxyvitamin D and parathyroid hormone levels by immunoassay. Mean cortical porosity at the distal tibia was 14.7% higher (12.5 ± 4.3% vs. 10.9 ± 4.1%, P < 0.05) whilst cortical volumetric BMD, area, trabecular bone volume fraction and femoral neck areal BMD were lower in men in the lowest quartile of vitamin D levels compared to the highest. In men with vitamin D deficiency (<25 nmol L -1 ) or insufficiency [25-49 nmol L -1 , in combination with an elevated serum level of parathyroid hormone (>6.8 pmol L -1 )], cortical porosity was 17.2% higher than in vitamin D-sufficient men (P < 0.01). A linear regression model including age, weight, height, daily calcium intake, physical activity, smoking vitamin D supplementation and parathyroid hormone showed that 25-hydroxyvitamin D independently predicted cortical porosity (standardized β = -0.110, R 2 = 1.1%, P = 0.024), area (β = 0.123, R 2 = 1.4%, P = 0.007) and cortical volumetric BMD (β = 0.125, R 2 = 1.4%, P = 0.007) of the tibia as well as areal BMD of the femoral neck (β = 0.102, R 2 = 0.9%, P = 0.04). Serum vitamin D is associated with cortical porosity, area and density, indicating that bone fragility as a result of low vitamin D could be due to changes in cortical bone microstructure and geometry. © 2016 The Authors. Journal of Internal Medicine published by John Wiley & Sons Ltd on behalf of Association for Publication of The Journal of Internal Medicine.
Investigation of Cadmium Selenide Photoelectrochemical Cells.
1980-01-01
80-4 _INVESTIGATION OF C ADMIUM ,ELENIDE .PHOTOELECTROCHEMICAL CELLS by R.A. Sawchuk and D.R. Snelling Energy Systems Section AccsseionPar Energy ...cadmium selenide photo- anodes, a polysulphide redox’electrolyte and an in situ energy storage com- partment were evaluated at DREO. The...electron-hole recombination.- centers, and shorting to the nickel substrate. The concept of in situ energy storage was not successfully demonstrated. It is
The perspectives, information and conclusions conveyed in research project abstracts, progress reports, final reports, journal abstracts and journal publications convey the viewpoints of the principal investigator and may not represent the views and policies of ORD and EPA. Concl...
The perspectives, information and conclusions conveyed in research project abstracts, progress reports, final reports, journal abstracts and journal publications convey the viewpoints of the principal investigator and may not represent the views and policies of ORD and EPA. Concl...
The perspectives, information and conclusions conveyed in research project abstracts, progress reports, final reports, journal abstracts and journal publications convey the viewpoints of the principal investigator and may not represent the views and policies of ORD and EPA. Concl...
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...
Denham, Susanne A; Bassett, Hideko Hamada; Thayer, Sara K; Mincic, Melissa S; Sirotkin, Yana S; Zinsser, Katherine
2012-01-01
Social-emotional behavior of 352 3- and 4-year-olds attending private child-care and Head Start programs was observed using the Minnesota Preschool Affect Checklist, Revised (MPAC-R). Goals of the investigation included (a) using MPAC-R data to extract a shortened version, MPAC-R/S, comparing structure, internal consistency, test-retest reliability, and stability of both versions; and, using the shortened measure, to examine (b) age, gender, and risk status differences in social-emotional behaviors; (c) contributions of emotion knowledge and executive function to social-emotional behaviors; and (d) contributions of social-emotional behaviors to early school adjustment and kindergarten academic success. Results show that reliability of MPAC-R/S was as good, or better, than the MPAC-R. MPAC-R/S structure, at both times of observation, included emotionally negative/aggressive, emotionally regulated/prosocial, and emotionally positive/productive behaviors; MPAC-R structure was similar but less replicable over time. Age, gender, and risk differences were found. Children's emotion knowledge contributed to later emotionally regulated/prosocial behavior. Finally, preschool emotionally negative/aggressive behaviors were associated with concurrent and kindergarten school success, and there was evidence of social-emotional behavior mediating relations between emotion knowledge or executive function, and school outcomes. The importance of portable, empirically supported observation measures of social-emotional behaviors is discussed along with possible applications, teacher utilization, and implementation barriers.
Gatell, José M; Assoumou, Lambert; Moyle, Graeme; Waters, Laura; Johnson, Margaret; Domingo, Pere; Fox, Julie; Martinez, Esteban; Stellbrink, Hans-Jürgen; Guaraldi, Giovanni; Masia, Mar; Gompels, Mark; De Wit, Stephane; Florence, Eric; Esser, Stefan; Raffi, François; Stephan, Christoph; Rockstroh, Juergen; Giacomelli, Andrea; Vera, Jaime; Bernardino, José Ignacio; Winston, Alan; Saumoy, Maria; Gras, Julien; Katlama, Christine; Pozniak, Anton L
2018-06-14
Both immediate or deferred switching from a PI/r to DTG may improve lipid profile. NEAT022 is a European, open label, randomized, trial. HIV-infected adults ≥ 50 years or with a Framingham score ≥10% were eligible if HIV RNA < 50 copies/mL. Patients were randomized to switch the PI/r to DTG immediately (DTG-I) or to deferred switch at week 48 (DTG-D) . Week 96 end-points were: proportion of patients with HIV RNA < 50 copies/ml, percentage change of lipid fractions and adverse events. 415 patients were randomized: 205 to DTG-I and 210 to continue PI/r plus a deferred switch (DTG-D) at week 48 . The primary objective of non-inferiority at week 48 was met. At week 96, treatment success rate was 92.2 % in DTG-I arm and 87% in DTG-D arm (difference 5.2%, 95% CI -0.6 to 11). There were 5 virological failures in the DTG-I arm and 5 (1 while on PI/r and 4 after switching to DTG) in the DTG-D arm without selection of resistance mutations. There was no significant difference in terms of grade 3 or 4 AE´s or treatment modifying AE´s. Total cholesterol and other lipid fractions (except HDL) significantly (p<0.001) improved both after immediate and deferred switching to DTG overall and regardless of baseline PI/r strata. Both immediate and deferred switching from a PI/r to a DTG regimen in virologically suppressed HIV patients ≥ 50 years old or with a Framingham score ≥10% was highly efficacious, well tolerated and improved lipid profile.
Isherwood, Sarah N; Robbins, Trevor W; Nicholson, Janet R; Dalley, Jeffrey W; Pekcec, Anton
2017-09-01
Metabotropic glutamate receptor 4 (mGluR4) and dopamine D 2 receptors are specifically expressed within the indirect pathway neurons of the striato-pallidal-subthalamic pathway. This unique expression profile suggests that mGluR4 and D 2 receptors may play a cooperative role in the regulation and inhibitory control of behaviour. We investigated this possibility by testing the effects of a functionally-characterised positive allosteric mGluR4 modulator, 4-((E)-styryl)-pyrimidin-2-ylamine (Cpd11), both alone and in combination with the D 2 receptor antagonist eticlopride, on two distinct forms of impulsivity. Rats were trained on the five-choice serial reaction time task (5-CSRTT) of sustained visual attention and segregated according to low, mid, and high levels of motor impulsivity (LI, MI and HI, respectively), with unscreened rats used as an additional control group. A separate group of rats was trained on a delay discounting task (DDT) to assess choice impulsivity. Systemic administration of Cpd11 dose-dependently increased motor impulsivity and impaired attentional accuracy on the 5-CSRTT in all groups tested. Eticlopride selectively attenuated the increase in impulsivity induced by Cpd11, but not the accompanying attentional impairment, at doses that had no significant effect on behavioural performance when administered alone. Cpd11 also decreased choice impulsivity on the DDT (i.e. increased preference for the large, delayed reward) and decreased locomotor activity. These findings demonstrate that mGluR4s, in conjunction with D 2 receptors, affect motor- and choice-based measures of impulsivity, and therefore may be novel targets to modulate impulsive behaviour associated with a number of neuropsychiatric syndromes. Copyright © 2017 The Authors. Published by Elsevier Ltd.. All rights reserved.
N, Nagasundaram; Zhu, Hailong; Liu, Jiming; V, Karthick; C, George Priya Doss; Chakraborty, Chiranjib; Chen, Luonan
2015-01-01
The cyclin-dependent kinase 4 (CDK4)-cyclin D1 complex plays a crucial role in the transition from the G1 phase to S phase of the cell cycle. Among the CDKs, CDK4 is one of the genes most frequently affected by somatic genetic variations that are associated with various forms of cancer. Thus, because the abnormal function of the CDK4-cyclin D1 protein complex might play a vital role in causing cancer, CDK4 can be considered a genetically validated therapeutic target. In this study, we used a systematic, integrated computational approach to identify deleterious nsSNPs and predict their effects on protein-protein (CDK4-cyclin D1) and protein-ligand (CDK4-flavopiridol) interactions. This analysis resulted in the identification of possible inhibitors of mutant CDK4 proteins that bind the conformations induced by deleterious nsSNPs. Using computational prediction methods, we identified five nsSNPs as highly deleterious: R24C, Y180H, A205T, R210P, and R246C. From molecular docking and molecular dynamic studies, we observed that these deleterious nsSNPs affected CDK4-cyclin D1 and CDK4-flavopiridol interactions. Furthermore, in a virtual screening approach, the drug 5_7_DIHYDROXY_ 2_ (3_4_5_TRI HYDROXYPHENYL) _4H_CHROMEN_ 4_ONE displayed good binding affinity for proteins with the mutations R24C or R246C, the drug diosmin displayed good binding affinity for the protein with the mutation Y180H, and the drug rutin displayed good binding affinity for proteins with the mutations A205T and R210P. Overall, this computational investigation of the CDK4 gene highlights the link between genetic variation and biological phenomena in human cancer and aids in the discovery of molecularly targeted therapies for personalized treatment. PMID:26252490
Federal Register 2010, 2011, 2012, 2013, 2014
2010-09-08
... in 48 CFR Part 217 Government procurement. Ynette R. Shelkin, Editor, Defense Acquisition Regulations...). ACTION: Final rule. SUMMARY: DoD is adopting as final, without change, an interim rule amending the... interim rule. Therefore, DoD is finalizing the interim rule without change. This rule was not subject to...
Accurate electric multipole moment, static polarizability and hyperpolarizability derivatives for N2
NASA Astrophysics Data System (ADS)
Maroulis, George
2003-02-01
We report accurate values of the electric moments, static polarizabilities, hyperpolarizabilities and their respective derivatives for N2. Our values have been extracted from finite-field Møller-Pleset perturbation theory and coupled cluster calculations performed with carefully designed basis sets. A large [15s12p9d7f] basis set consisting of 290 CGTF is expected to provide reference self-consistent-field values of near-Hartree-Fock quality for all properties. The Hartree-Fock limit for the mean hyperpolarizability is estimated at γ¯=715±4e4a04Eh-3 at the experimental bond length Re=2.074 32a0. Accurate estimates of the electron correlation effects were obtained with a [10s7p6d4f] basis set. Our best values are Θ=-1.1258ea02 for the quadrupole and Φ=-6.75ea04 for the hexadecapole moment, ᾱ=11.7709 and Δα=4.6074e2a02Eh-1 for the mean and the anisotropy of the dipole polarizability, C¯=41.63e2a04Eh-1 for the mean quadrupole polarizability and γ¯=927e4a04Eh-3 for the dipole hyperpolarizability. The latter value is quite close to Shelton's experimental estimate of 917±5e4a04Eh-3 [D. P. Shelton, Phys. Rev. A 42, 2578 (1990)]. The R dependence of all properties has been calculated with a [7s5p4d2f] basis set. At the CCSD(T) level of theory the dipole polarizability varies around Re as ᾱ(R)/e2a02Eh-1=11.8483+6.1758(R-Re)+0.9191(R-Re)2-0.8212(R-Re)3-0.0006(R-Re)4, Δα(R)/e2a02Eh-1=4.6032+7.0301(R-Re)+1.9340(R-Re)2-0.5708(R-Re)3+0.1949(R-Re)4. For the Cartesian components and the mean of γαβγδ, (dγzzzz/dR)e=1398, (dγxxxx/dR)e=867, (dγxxzz/dR)e=317, and (dγ¯/dR)e=994e4a03Eh-3. For the quadrupole polarizability Cαβ,γδ, we report (dCzz,zz/dR)e=19.20, (dCxz,xz/dR)e=16.55, (dCxx,xx/dR)e=10.20, and (dC¯/dR)e=23.31e2a03Eh-1. At the MP2 level of theory the components of the dipole-octopole polarizability (Eα,βγδ) and the mean dipole-dipole-octopole hyperpolarizability B¯ we have obtained (dEz,zzz/dR)e=36.71, (dEx,xxx/dR)e=-12.94e2a03Eh-1, and (dB¯/dR)e=-108e3a03Eh-2. In comparison with some other 14-electron systems, N2 appears to be less (hyper)polarizable than most, as near the Hartree-Fock limit we observe ᾱ(N2)<ᾱ(CO)<ᾱ(HCN)<ᾱ(BF)<ᾱ(HCCH) and γ¯(N2)<γ¯(CO)<γ¯(HCN)<γ¯(HCCH)<γ¯(BF).
Cultivation of aerobic granules in a novel configuration of sequencing batch airlift reactor.
Rezaei, Laya Siroos; Ayati, Bita; Ganjidoust, Hossein
2012-01-01
Aerobic granules can be formed in sequencing batch airlift reactors (SBAR) and sequencing batch reactors (SBR). Comparing these two systems, the SBAR has excellent mixing condition, but due to a high height-to-diameter ratio (H/D), there is no performance capability at full scale at the present time. This research examined a novel configuration of SBAR at laboratory scale (with a box structure) for industrial wastewater treatment. To evaluate chemical oxygen demand (COD) removal efficiency and granule formation of the novel reactor (R1), in comparison a conventional SBAR (R2) was operated under similar conditions during the experimental period. R1 and R2 with working volumes of 3.6 L and 4.5 L, respectively, were used to cultivate aerobic granules. Both reactors were operated for 4 h per cycle. Experiments were done at different organic loading rates (OLRs) ranging from 0.6-4.5 kg COD/m3.d for R1 and from 0.72-5.4 kg COD/m3.d for R2. After 150 days of operation, large-sized black filamentous granules with diameters of 0.5-2 mm and 2-11 mm were formed in R1 and R2, respectively. In the second part of the experiment, the efficiency of removal of a toxic substance by aerobic granules was investigated using aniline as a carbon source with a concentration in the range 1.2-6.6 kg COD/m3.d and 1.44-7.92 kg COD/m3.d in R1 and R2, respectively. It was found that COD removal efficiency of the novel airlift reactor was over 97% and 94.5% using glucose and aniline as carbon sources, respectively. Sludge volume index (SVI) was also decreased to 30 mL/g by granulation in the novel airlift reactor.
Endo, J; Watanabe, A; Sasho, T; Yamaguchi, S; Saito, M; Akagi, R; Muramatsu, Y; Mukoyama, S; Katsuragi, J; Akatsu, Y; Fukawa, T; Okubo, T; Osone, F; Takahashi, K
2015-02-01
To investigate the effectiveness of quantitative Magnetic resonance imaging (MRI) for evaluating the quality of cartilage repair over time following allograft chondrocyte implantation using a three-dimensional scaffold for osteochondral lesions. Thirty knees from 15 rabbits were analyzed. An osteochondral defect (diameter, 4 mm; depth, 1 mm) was created on the patellar groove of the femur in both legs. The defects were filled with a chondrocyte-seeded scaffold in the right knee and an empty scaffold in the left knee. Five rabbits each were euthanized at 4, 8, and 12 weeks and their knees were examined via macroscopic inspection, histological and biochemical analysis, and quantitative MRI (T2 mapping and dGEMRIC) to assess the state of tissue repair following allograft chondrocyte implantation with a three-dimensional scaffold for osteochondral lesions. Comparatively good regenerative cartilage was observed both macroscopically and histologically. In both chondrocyte-seeded and control knees, the T2 values of repair tissues were highest at 4 weeks and showed a tendency to decrease with time. ΔR1 values of dGEMRIC also tended to decrease with time in both groups, and the mean ΔR1 was significantly lower in the CS-scaffold group than in the control group at all time points. ΔR1 = 1/r (R1post - R1pre), where r is the relaxivity of Gd-DTPA(2-), R1 = 1/T1 (longitudinal relaxation time). T2 mapping and dGEMRIC were both effective for evaluating tissue repair after allograft chondrocyte implantation. ΔR1 values of dGEMRIC represented good correlation with histologically and biochemically even at early stages after the implantation. Copyright © 2014 Osteoarthritis Research Society International. Published by Elsevier Ltd. All rights reserved.
General Aviation Activity and Avionics Survey
1988-01-01
tD to U) C’) m’ %0 V al Cm r. %0 H1 2:) ) C’) H 1; 1; U) 0 0) a; 0 N H; U; ) C) 0 H 0 0 Cl) CD M’ tD U) H1 r- U) U) A N N wD 0m w H...8217 r- w N - - H H N O z fz 4 OO O CO CO N 0 O fU D (A w’ r- tD 0 1 r4 (n 0 (0D CO t- m Hl -0 r D CO H4 N) N1 D C N it) N o 0A P4 E-4 H Hl ’r - ol u COC...l) ChH U) ’’ ’ 0H W) ) U) H- H N ON r o 1 tp Ne’ WW ( 00 Oo U ChL ’I](N tD ca N C% O U)U 0(1 M~’ OW U) 1W N CIN40N H 020 L 00l’ C,, ’I 4 01IH’
ERIC Educational Resources Information Center
Hadromi; Rachman, Maman; Soesanto; Kartana, Tri Jaka
2015-01-01
The purpose of this research is to develop automotive Mechanical Technology Skill Program (TMO) in Vocational School. The Research and Development (R&D) object was done in SMK 1, 4 and 7 Semarang, Indonesia. The result was achieved productivity Practical Management Final Model at TMO skill Program in Vocational school named momanticproter.…
Lumped Nonlinear System Analysis with Volterra Series.
1980-04-01
f h2 (t-=,t-r )x(r)x(t2)dl d 2 (4- 1 )O0 0 Consider the input signal comprising two unit sinusoidal signals at fre- quencies wa and wb. The input x... 1 - 2 . Nonlinear System Analysis Methods. .............. 2 1 -3. Objectives of the Investigation ....... ............... 6 1 -4. Organization of...the Report ..... ... ................. 9 CHAPTER 2 - VOLTERRA FUNCTIONAL SERIES ...... ............... 12 2 - 1 . Introduction
Measurement of B(D+-->K(*0)l(+)nu(l)).
Brandenburg, G; Ershov, A; Kim, D Y-J; Wilson, R; Benslama, K; Eisenstein, B I; Ernst, J; Gollin, G D; Hans, R M; Karliner, I; Lowrey, N; Marsh, M A; Plager, C; Sedlack, C; Selen, M; Thaler, J J; Williams, J; Edwards, K W; Ammar, R; Besson, D; Zhao, X; Anderson, S; Frolov, V V; Kubota, Y; Lee, S J; Li, S Z; Poling, R; Smith, A; Stepaniak, C J; Urheim, J; Ahmed, S; Alam, M S; Jian, L; Saleem, M; Wappler, F; Eckhart, E; Gan, K K; Gwon, C; Hart, T; Honscheid, K; Hufnagel, D; Kagan, H; Kass, R; Pedlar, T K; Thayer, J B; Von Toerne, E; Wilksen, T; Zoeller, M M; Richichi, S J; Severini, H; Skubic, P; Dytman, S A; Nam, S; Savinov, V; Chen, S; Hinson, J W; Lee, J; Miller, D H; Pavlunin, V; Shibata, E I; Shipsey, I P J; Cronin-Hennessy, D; Lyon, A L; Park, C S; Park, W; Thorndike, E H; Coan, T E; Gao, Y S; Liu, F; Maravin, Y; Narsky, I; Stroynowski, R; Ye, J; Artuso, M; Boulahouache, C; Bukin, K; Dambasuren, E; Mountain, R; Skwarnicki, T; Stone, S; Wang, J C; Mahmood, A H; Csorna, S E; Danko, I; Xu, Z; Bonvicini, G; Cinabro, D; Dubrovin, M; McGee, S; Bornheim, A; Lipeles, E; Pappas, S P; Shapiro, A; Sun, W M; Weinstein, A J; Masek, G; Paar, H P; Mahapatra, R; Briere, R A; Chen, G P; Ferguson, T; Tatishvili, G; Vogel, H; Adam, N E; Alexander, J P; Bebek, C; Berkelman, K; Blanc, F; Boisvert, V; Cassel, D G; Drell, P S; Duboscq, J E; Ecklund, K M; Ehrlich, R; Gibbons, L; Gittelman, B; Gray, S W; Hartill, D L; Heltsley, B K; Hsu, L; Jones, C D; Kandaswamy, J; Kreinick, D L; Magerkurth, A; Mahlke-Krüger, H; Meyer, T O; Mistry, N B; Nordberg, E; Palmer, M; Patterson, J R; Peterson, D; Pivarski, J; Riley, D; Sadoff, A J; Schwarthoff, H; Shepherd, M R; Thayer, J G; Urner, D; Valant-Spaight, B; Viehhauser, G; Warburton, A; Weinberger, M; Athar, S B; Avery, P; Stoeck, H; Yelton, J
2002-11-25
Using 13.53 fb(-1) of CLEO data, we have measured the ratios of the branching fractions R(+)(e),R(+)(mu) and the combined branching fraction ratio R(+)(l), defined by R(+)(l)=[B(D+-->K(*0)l(+)nu(l))]/[B(D+-->K-pi(+)pi(+))]. We find R(+)(e)=0.74+/-0.04+/-0.05, R(+)(mu)=0.72+/-0.10+/-0.05, and R(+)(l)=0.74+/-0.04+/-0.05, where the first and second errors are statistical and systematic, respectively. The known branching fraction B(D+-->K-pi(+)pi(+)) leads to B(D+-->K(*0)e(+)nu(e))=(6.7+/-0.4+/-0.5+/-0.4)%, B(D+-->K(*0)mu(+)nu(mu))=(6.5+/-0.9+/-0.5+/-0.4)%, and B(D+-->K(*0)l(+)nu(l))=(6.7+/-0.4+/-0.5+/-0.4)%, where the third error is due to the uncertainty in B(D+-->K-pi(+)pi(+)).
1978-12-01
4 L-7 hiI<±b fd .rvc~ a .3",d,! i:; ba ’-ii~ y :nztructl~n :).L a -- flattctod r~-%3 i Pazo u-3 and r.). 1yzj. f r 3n- the road-rmy, S11eet 13...Program " Final Report Bowling Green Reservoir Dam (MO 10262) 6. PERFORMING-ORG. REPORT NUMBER Pike County, Missouri 7. AUTHOR( a ) S. CONTRACT OR GRANT...if possible. If a classification is required, identify the classified items on the page by the appropriate symbol. CC; -ETION GUIDE General. Make
Begmanova, Mamura; Mit, Nata; Amirgaliyeva, Anara; Tolebayeva, A.; Djansugurova, Leyla
2014-01-01
Introduction Aging and longevity control are among the greatest problems in biology and medicine. The fruit fly Drosophila melanogaster is a nice model organism for longevity investigations because of its biological features. Many D. melanogaster genes have their orthologs, similar in other eukaryotes, including human. The role of nitric oxide (NO) in the D. melanogaster lifespan has been analyzed. Methods Virgin flies of dNOS4 transgenic strain were used for the experiment. This strain contains non-functional additional copies of nitric oxide synthase (NOS) gene under heat shock promoter. For promoter activation, transgenic flies on their second day of life were exposed to heat shock (37°C) for an hour. After heat shock, flies were maintained on standard medium temperatures at 25°C, with females separate from males. Two types of control were used: Oregon R wild-type strain and Oregon R strain exposed to heat shock. The average lifespan was evaluated. Results It was revealed that the longevity of females was significantly higher than males in each series of experiments (p < 0.05). The survival rate of females and males was similar in the first month of their life, but in the second month the mortality among males was much higher than among females in all series of experiments. The average lifespan of dNOS4 imago was 31 days (34 days for females and 28 days for males), maximum lifespan was 63 days. In controls, the average lifespan of Oregon R flies was 54 days (58 days for females and 50 days for males), and the maximum lifespan was 94 days. The average lifespan of Oregon R flies exposed to heat shock was 45 days (48 days for females and 41 days for males), and the maximum lifespan was 72 days. The difference between average lifespan in all studied groups is statistically significant (p < 0.05). Conclusion Thus, NOS-transgene activation results in formation of non-functional dNOS4-transcripts and NO deficiency. In turn, NO deficiency decreases dNOS4 imago lifespan. PMID:29805886
Tayeb, Wafa; Nakbi, Amel; Cheraief, Imed; Miled, Abdelhedi; Hammami, Mohamed
2013-07-01
This study aims to investigate the effects of the 2,4-dichlorophenoxyacetic herbicide (2,4-D) on plasma lipids, lipoproteins concentrations, hepatic lipid peroxidation, fatty acid composition and antioxidant enzyme activities in rats. Animals were randomly divided into four groups of 10 each: control group and three 2,4-D-treated groups G1, G2 and G3 were administered 15, 75 and 150 mg/kg/BW/d 2,4-D by gavage for 28 d, respectively. Results showed that 2,4-D caused significant negative changes in the biochemical parameters investigated. The malondialdehyde level was significantly increased in 2,4-D-treated groups. Fatty acid composition of the liver was also significantly changed with 2,4-D exposure. Furthermore, the hepatic antioxidant enzyme activities were significantly affected. Finally, 2,4-D at the studied doses modifies lipidic status, disrupt lipid metabolism and induce hepatic oxidative stress. In conclusion, at higher doses, 2,4-D may play an important role in the development of vascular disease via metabolic disorder of lipoproteins, lipid peroxidation and oxidative stress.
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
T2-weighted four dimensional magnetic resonance imaging with result-driven phase sorting
DOE Office of Scientific and Technical Information (OSTI.GOV)
Liu, Yilin; Yin, Fang-Fang; Cai, Jing, E-mail: jing.cai@duke.edu
2015-08-15
Purpose: T2-weighted MRI provides excellent tumor-to-tissue contrast for target volume delineation in radiation therapy treatment planning. This study aims at developing a novel T2-weighted retrospective four dimensional magnetic resonance imaging (4D-MRI) phase sorting technique for imaging organ/tumor respiratory motion. Methods: A 2D fast T2-weighted half-Fourier acquisition single-shot turbo spin-echo MR sequence was used for image acquisition of 4D-MRI, with a frame rate of 2–3 frames/s. Respiratory motion was measured using an external breathing monitoring device. A phase sorting method was developed to sort the images by their corresponding respiratory phases. Besides, a result-driven strategy was applied to effectively utilize redundantmore » images in the case when multiple images were allocated to a bin. This strategy, selecting the image with minimal amplitude error, will generate the most representative 4D-MRI. Since we are using a different image acquisition mode for 4D imaging (the sequential image acquisition scheme) with the conventionally used cine or helical image acquisition scheme, the 4D dataset sufficient condition was not obviously and directly predictable. An important challenge of the proposed technique was to determine the number of repeated scans (N{sub R}) required to obtain sufficient phase information at each slice position. To tackle this challenge, the authors first conducted computer simulations using real-time position management respiratory signals of the 29 cancer patients under an IRB-approved retrospective study to derive the relationships between N{sub R} and the following factors: number of slices (N{sub S}), number of 4D-MRI respiratory bins (N{sub B}), and starting phase at image acquisition (P{sub 0}). To validate the authors’ technique, 4D-MRI acquisition and reconstruction were simulated on a 4D digital extended cardiac-torso (XCAT) human phantom using simulation derived parameters. Twelve healthy volunteers were involved in an IRB-approved study to investigate the feasibility of this technique. Results: 4D data acquisition completeness (C{sub p}) increases as NR increases in an inverse-exponential fashion (C{sub p} = 100 − 99 × exp(−0.18 × N{sub R}), when N{sub B} = 6, fitted using 29 patients’ data). The N{sub R} required for 4D-MRI reconstruction (defined as achieving 95% completeness, C{sub p} = 95%, N{sub R} = N{sub R,95}) is proportional to N{sub B} (N{sub R,95} ∼ 2.86 × N{sub B}, r = 1.0), but independent of N{sub S} and P{sub 0}. Simulated XCAT 4D-MRI showed a clear pattern of respiratory motion. Tumor motion trajectories measured on 4D-MRI were comparable to the average input signal, with a mean relative amplitude error of 2.7% ± 2.9%. Reconstructed 4D-MRI for healthy volunteers illustrated clear respiratory motion on three orthogonal planes, with minimal image artifacts. The artifacts were presumably caused by breathing irregularity and incompleteness of data acquisition (95% acquired only). The mean relative amplitude error between critical structure trajectory and average breathing curve for 12 healthy volunteers is 2.5 ± 0.3 mm in superior–inferior direction. Conclusions: A novel T2-weighted retrospective phase sorting 4D-MRI technique has been developed and successfully applied on digital phantom and healthy volunteers.« less
Neiens, Patrick; De Simone, Angela; Ramershoven, Anna; Höfner, Georg; Allmendinger, Lars; Wanner, Klaus T
2018-03-03
MS Binding Assays represent a label-free alternative to radioligand binding assays. In this study, we present an LC-ESI-MS/MS method for the quantification of (R,R)-4-(2-benzhydryloxyethyl)-1-(4-fluorobenzyl)piperidin-3-ol [(R,R)-D-84, (R,R)-1], (S,S)-reboxetine [(S,S)-2], and (S)-citalopram [(S)-3] employed as highly selective nonlabeled reporter ligands in MS Binding Assays addressing the dopamine [DAT, (R,R)-D-84], norepinephrine [NET, (S,S)-reboxetine] and serotonin transporter [SERT, (S)-citalopram], respectively. The developed LC-ESI-MS/MS method uses a pentafluorphenyl stationary phase in combination with a mobile phase composed of acetonitrile and ammonium formate buffer for chromatography and a triple quadrupole mass spectrometer in the multiple reaction monitoring mode for mass spectrometric detection. Quantification is based on deuterated derivatives of all three analytes serving as internal standards. The established LC-ESI-MS/MS method enables fast, robust, selective and highly sensitive quantification of all three reporter ligands in a single chromatographic run. The method was validated according to the Center for Drug Evaluation and Research (CDER) guideline for bioanalytical method validation regarding selectivity, accuracy, precision, calibration curve and sensitivity. Finally, filtration-based MS Binding Assays were performed for all three monoamine transporters based on this LC-ESI-MS/MS quantification method as read out. The affinities determined in saturation experiments for (R,R)-D-84 toward hDAT, for (S,S)-reboxetine toward hNET, and for (S)-citalopram toward hSERT, respectively, were in good accordance with results from literature, clearly demonstrating that the established MS Binding Assays have the potential to be an efficient alternative to radioligand binding assays widely used for this purpose so far. Copyright © 2018 John Wiley & Sons, Ltd.
1977-03-10
rKanqaQoo P4OSe 7-T -PALLID KANGAROO MOLUS IM p rVf ,CtojI8. - PALLID KANGAROO MOUSE WM 1)Pu * -of the Fali~ Kaniaaroo Mice FISH (Figures D-13, D-14...and sudden noises. Conclusive data on effects of booms on production are not available, but no change in milk production by one dairy herd was noted...press). Parker, J. B. and N. D. Bayley. 1960. Investigations on effects of aircraft sound on milk production of dairy cattle, 1957-1958. U.S. Dept. of
Clinical Investigation Program Annual Progress Report
1989-10-01
Investigators: Linda K. Kullama, Ph.D., Dr. Kenneth T. Nakamura,MD; Dr. Venkataraman Balaraman, MD, Wayne M. Ichimura, Biomedical Engineer. Department/Section...Investigators: John R. Claybaugh, Ph.D.; Kenneth T. Nakamura, MD; Dr. Venkataraman Balaraman, M.D. Department/Section: Clinical Investigation/Physiology Key...Pigs and Rats Principal ’Investigator: Linda K. Kullama, Ph.D.; John R. Claybaugh, Ph.D. Associate Investigators: Dr. Venkataraman Balaraman, M.D.; Dr
Observation of B→D(*) π^(+)π^(-)ℓ^(-)ν Decays in e^(+)e^(-) Collisions at the Υ(4S) Resonance.
Lees, J P; Poireau, V; Tisserand, V; Grauges, E; Palano, A; Eigen, G; Stugu, B; Brown, D N; Kerth, L T; Kolomensky, Yu G; Lee, M J; Lynch, G; Koch, H; Schroeder, T; Hearty, C; Mattison, T S; McKenna, J A; So, R Y; Khan, A; Blinov, V E; Buzykaev, A R; Druzhinin, V P; Golubev, V B; Kravchenko, E A; Onuchin, A P; Serednyakov, S I; Skovpen, Yu I; Solodov, E P; Todyshev, K Yu; Lankford, A J; Gary, J W; Long, O; Franco Sevilla, M; Hong, T M; Kovalskyi, D; Richman, J D; West, C A; Eisner, A M; Lockman, W S; Panduro Vazquez, W; Schumm, B A; Seiden, A; Chao, D S; Cheng, C H; Echenard, B; Flood, K T; Hitlin, D G; Kim, J; Miyashita, T S; Ongmongkolkul, P; Porter, F C; Röhrken, M; Andreassen, R; Huard, Z; Meadows, B T; Pushpawela, B G; Sokoloff, M D; Sun, L; Ford, W T; Smith, J G; Wagner, S R; Ayad, R; Toki, W H; Spaan, B; Bernard, D; Verderi, M; Playfer, S; Bettoni, D; Bozzi, C; Calabrese, R; Cibinetto, G; Fioravanti, E; Garzia, I; Luppi, E; Santoro, V; Calcaterra, A; de Sangro, R; Finocchiaro, G; Martellotti, S; Patteri, P; Peruzzi, I M; Piccolo, M; Zallo, A; Contri, R; Monge, M R; Passaggio, S; Patrignani, C; Bhuyan, B; Prasad, V; Adametz, A; Uwer, U; Lacker, H M; Mallik, U; Chen, C; Cochran, J; Prell, S; Ahmed, H; Gritsan, A V; Arnaud, N; Davier, M; Derkach, D; Grosdidier, G; Le Diberder, F; Lutz, A M; Malaescu, B; Roudeau, P; Stocchi, A; Wormser, G; Lange, D J; Wright, D M; Coleman, J P; Fry, J R; Gabathuler, E; Hutchcroft, D E; Payne, D J; Touramanis, C; Bevan, A J; Di Lodovico, F; Sacco, R; Cowan, G; Brown, D N; Davis, C L; Denig, A G; Fritsch, M; Gradl, W; Griessinger, K; Hafner, A; Schubert, K R; Barlow, R J; Lafferty, G D; Cenci, R; Hamilton, B; Jawahery, A; Roberts, D A; Cowan, R; Cheaib, R; Patel, P M; Robertson, S H; Dey, B; Neri, N; Palombo, F; Cremaldi, L; Godang, R; Summers, D J; Simard, M; Taras, P; De Nardo, G; Onorato, G; Sciacca, C; Raven, G; Jessop, C P; LoSecco, J M; Honscheid, K; Kass, R; Margoni, M; Morandin, M; Posocco, M; Rotondo, M; Simi, G; Simonetto, F; Stroili, R; Akar, S; Ben-Haim, E; Bomben, M; Bonneaud, G R; Briand, H; Calderini, G; Chauveau, J; Leruste, Ph; Marchiori, G; Ocariz, J; Biasini, M; Manoni, E; Rossi, A; Angelini, C; Batignani, G; Bettarini, S; Carpinelli, M; Casarosa, G; Chrzaszcz, M; Forti, F; Giorgi, M A; Lusiani, A; Oberhof, B; Paoloni, E; Rama, M; Rizzo, G; Walsh, J J; Lopes Pegna, D; Olsen, J; Smith, A J S; Anulli, F; Faccini, R; Ferrarotto, F; Ferroni, F; Gaspero, M; Pilloni, A; Piredda, G; Bünger, C; Dittrich, S; Grünberg, O; Hess, M; Leddig, T; Voß, C; Waldi, R; Adye, T; Olaiya, E O; Wilson, F F; Emery, S; Vasseur, G; Aston, D; Bard, D J; Cartaro, C; Convery, M R; Dorfan, J; Dubois-Felsmann, G P; Dunwoodie, W; Ebert, M; Field, R C; Fulsom, B G; Graham, M T; Hast, C; Innes, W R; Kim, P; Leith, D W G S; Luitz, S; Luth, V; MacFarlane, D B; Muller, D R; Neal, H; Pulliam, T; Ratcliff, B N; Roodman, A; Schindler, R H; Snyder, A; Su, D; Sullivan, M K; Va'vra, J; Wisniewski, W J; Wulsin, H W; Purohit, M V; Wilson, J R; Randle-Conde, A; Sekula, S J; Bellis, M; Burchat, P R; Puccio, E M T; Alam, M S; Ernst, J A; Gorodeisky, R; Guttman, N; Peimer, D R; Soffer, A; Spanier, S M; Ritchie, J L; Schwitters, R F; Izen, J M; Lou, X C; Bianchi, F; De Mori, F; Filippi, A; Gamba, D; Lanceri, L; Vitale, L; Martinez-Vidal, F; Oyanguren, A; Albert, J; Banerjee, Sw; Beaulieu, A; Bernlochner, F U; Choi, H H F; King, G J; Kowalewski, R; Lewczuk, M J; Lueck, T; Nugent, I M; Roney, J M; Sobie, R J; Tasneem, N; Gershon, T J; Harrison, P F; Latham, T E; Band, H R; Dasu, S; Pan, Y; Prepost, R; Wu, S L
2016-01-29
We report on measurements of the decays of B¯ mesons into the semileptonic final states B¯→D^(*)π^(+)π^(-)ℓ^(-)ν¯, where D^(*) represents a D or D^(*) meson and ℓ^(-) is an electron or a muon. These measurements are based on 471×10^(6) BB ¯ pairs recorded with the BABAR detector at the SLAC asymmetric B factory PEP-II. We determine the branching fraction ratios R_{π^{+}π^{-}}^{(*)}=B(B[over ¯]→D^{(*)}π^{+}π^{-}ℓ^{-}ν[over ¯])/B(B[over ¯]→D^{(*)}ℓ^{-}ν[over ¯]) using events in which the second B meson is fully reconstructed. We find R_{π^{+}π^{-}}=0.067±0.010±0.008 and R_{π^{+}π^{-}}^{*}=0.019±0.005±0.004, where the first uncertainty is statistical and the second is systematic. Based on these results and assuming isospin invariance, we estimate that B[over ¯]→D^{(*)}ππℓ^{-}ν[over ¯] decays, where π denotes either a π^{±} and π^{0} meson, account for up to half the difference between the measured inclusive semileptonic branching fraction to charm hadrons and the corresponding sum of previously measured exclusive branching fractions.
The Orbit of 1972-05B in its Final Phase, with Geophysical Inferences.
1980-09-01
0- C4 -0- -0- I- -0-t " r,- N , c o C, 0 ’ C Z .2 to U- 0 - (ar 0-- -G- ( La - c/ m in o a in in in . I" m m as m, a; .0 w D Go4D 0 Fig 2 6660 6640 a...decrease in-orbital inclination a1A..40- .. Iv/"IY- t" east sal Wind 2020./a, at & MaM height of Sb~i 14# ., was 01-M2 he soja activity vat high-, and thelttd o eMl from I to 64S~ N -W I
The perspectives, information and conclusions conveyed in research project abstracts, progress reports, final reports, journal abstracts and journal publications convey the viewpoints of the principal investigator and may not represent the views and policies of ORD and EPA. Concl...
A peptide disrupting the D2R-DAT interaction protects against dopamine neurotoxicity.
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.
CYTOTOXICITY ASSOCIATED WITH TRICHLOROETHYLENE OXIDATION IN BURKHOLDERIA CEPACIA G4. (R828772)
The perspectives, information and conclusions conveyed in research project abstracts, progress reports, final reports, journal abstracts and journal publications convey the viewpoints of the principal investigator and may not represent the views and policies of ORD and EPA. Concl...
Final Report for Research in High Energy Physics (University of Hawaii)
DOE Office of Scientific and Technical Information (OSTI.GOV)
Browder, Thomas E.
2013-08-31
Here we present a final report for the DOE award for the University of Hawaii High Energy Physics Group (UHHEPG) for the period from December 1, 2009 to May 31, 2013 (including a period of no-cost extension). The high energy physics (HEP) group at the University of Hawaii (UH) has been engaged in experiments at the intensity frontier studying flavor physics (Task A: Belle, Belle-II and Task B: BES) and neutrinos (Task C: SuperK, LBNE, Double Chooz, DarkSide, and neutrino R\\&D). On the energy frontier, new types of pixel detectors were developed for upgrades of the ATLAS experiment at themore » LHC (Task D). On the cosmic frontier, there were investigations of ultra high-energy neutrino astrophysics and the highest energy cosmic rays using special radio detection techniques (Task E: AMBER, ANITA R\\&D) and results of the analysis of ANITA data. In addition, we have developed new types of sophisticated and cutting edge instrumentation based on novel ``oscilloscope on a chip'' electronics (Task F). Theoretical physics research (Task G) is phenomenologically oriented and has studied experimental consequences of existing and proposed new theories relevant to the energy, cosmic and intensity frontiers. The senior investigators for proposal were T. E. Browder (Task A), F. A. Harris (Task B), P. Gorham (Task E), J. Kumar (Task G), J. Maricic (Task C), J. G. Learned (Task C), S. Pakvasa (Task G), S. Parker (Task D), S. Matsuno (Task C), X. Tata (Task G) and G. S. Varner (Tasks F, A, E).« less
Miller, Michelle C; Klyosov, Anatole; Platt, David; Mayo, Kevin H
2009-07-06
Glycans comprise perhaps the largest biomass in nature, and more and more glycans are used in a number of applications, including those as pharmaceutical agents in the clinic. However, defining glycan molecular weight distributions during and after their preparation is not always straightforward. Here, we use pulse field gradient (PFG) (1)H NMR self-diffusion measurements to assess molecular weight distributions in various glycan preparations. Initially, we derived diffusion coefficients, D, on a series of dextrans with reported weight-average molecular weights from about 5 kDa to 150 kDa. For each dextran sample, we analyzed 15 diffusion decay curves, one from each of the 15 major (1)H resonance envelopes, to provide diffusion coefficients. By measuring D as a function of dextran concentration, we determined D at infinite dilution, D(inf), which allowed estimation of the hydrodynamic radius, R(h), using the Stokes-Einstein relationship. A plot of log D(inf) versus log R(h) was linear and provided a standard calibration curve from which R(h) is estimated for other glycans. We then applied this methodology to investigate two other glycans, an alpha-(1-->2)-L-rhamnosyl-alpha-(1-->4)-D-galacturonosyl with quasi-randomly distributed, mostly terminal beta(1-->4)-linked galactose side-chains (GRG) and an alpha(1-->6)-D-galacto-beta(1-->4)-D-mannan (Davanat), which is presently being tested against cancer in the clinic. Using the dextran-derived calibration curve, we find that average R(h) values for GRG and Davanat are 76+/-6 x 10(-10) m and 56+/-3 x 10(-10) m, with GRG being more polydispersed than Davanat. Results from this study will be useful to investigators requiring knowledge of polysaccharide dispersity, needing to study polysaccharides under various solution conditions, or wanting to follow degradation of polysaccharides during production.
1982-05-01
Raiffa (831, LaValle [891, and other books on decision analysis. 4.2 Risk Attitudes Much recent research has focused on the investigation of various risk...Issacs, G.L., Hamer, R., Chen, J., Chuang, D., Woodworth, G., Molenaar , I., Lewis C., and Libby, D., Manual for the Computer-Assisted Data Analysis (CADA
The perspectives, information and conclusions conveyed in research project abstracts, progress reports, final reports, journal abstracts and journal publications convey the viewpoints of the principal investigator and may not represent the views and policies of ORD and EPA. Concl...
Effect of tumor amplitude and frequency on 4D modeling of Vero4DRT system.
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.
NASA Astrophysics Data System (ADS)
Tegafaw, Tirusew; Xu, Wenlong; Wasi Ahmad, Md; Baeck, Jong Su; Chang, Yongmin; Bae, Ji Eun; Chae, Kwon Seok; Kim, Tae Jeong; Lee, Gang Ho
2015-09-01
A new type of dual-mode T1 and T2 magnetic resonance imaging (MRI) contrast agent based on mixed lanthanide oxide nanoparticles was synthesized. Gd3+ (8S7/2) plays an important role in T1 MRI contrast agents because of its large electron spin magnetic moment resulting from its seven unpaired 4f-electrons, and Dy3+ (6H15/2) has the potential to be used in T2 MRI contrast agents because of its very large total electron magnetic moment: among lanthanide oxide nanoparticles, Dy2O3 nanoparticles have the largest magnetic moments at room temperature. Using these properties of Gd3+ and Dy3+ and their oxide nanoparticles, ultrasmall mixed gadolinium-dysprosium oxide (GDO) nanoparticles were synthesized and their potential to act as a dual-mode T1 and T2 MRI contrast agent was investigated in vitro and in vivo. The D-glucuronic acid coated GDO nanoparticles (davg = 1.0 nm) showed large r1 and r2 values (r2/r1 ≈ 6.6) and as a result clear dose-dependent contrast enhancements in R1 and R2 map images. Finally, the dual-mode imaging capability of the nanoparticles was confirmed by obtaining in vivo T1 and T2 MR images.
Chain, Amina; Koury, Josely C; Bezerra, Flávia Fioruci
2012-09-01
Severe bone loss is a recognized complication of chronic spinal cord injury (SCI). Physical exercise contributes to bone health; however, its influence on bone mass of cervical SCI individuals has not been investigated. The aim of this study was to investigate the influence of physical activity on bone mass, bone metabolism, and vitamin D status in quadriplegics. Total, lumbar spine (L1-L4), femur and radius bone mineral density (BMD) were assessed in active (n = 15) and sedentary (n = 10) quadriplegic men by dual energy X-ray absorptiometry. Concentrations of 25-hydroxyvitamin D [25(OH)D], PTH, IGF1, osteocalcin and NTx were measured in serum. After adjustments for duration of injury, total body mass, and habitual calcium intake, bone indices were similar between groups, except for L1-L4 BMD Z score that was higher in the sedentary group (P < 0.05). Hours of physical exercise per week correlated positively with 25(OH)D (r = 0.59; P < 0.05) and negatively with PTH (r = -0.50; P < 0.05). Femur BMD was negatively associated with the number of months elapsed between the injury and the onset of physical activity (r = -0.60; P < 0.05). Moreover, in the active subjects, both L1-L4 BMD Z score (r = 0.72; P < 0.01) and radius BMD (r = 0.59; P < 0.05) were positively associated with calcium intake. In this cross-sectional study, both the onset of physical activity after injury and the number of hours dedicated to exercise were able to influence bone density and bone-related hormones in quadriplegic men. Our results also suggest a positive combined effect of exercise and calcium intake on bone health of quadriplegic individuals.
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.
1998-04-13
f73o* ^V^^- l^-J&4-g>- «Ajjv»^*^Y gvrg-ft^i Q^r-^vj-eJl -^TVYN ffa 3c 4*> lඑ^=> -£=r~. cgyjv-p f...fvvo H’fefat. l°3> A 13,o — £.3’ fW=> {vfi- ffa ^ os-iC 6 lza/1 *2- r^5^ to/»e(%L C83’ ISTR/METHOD: 8 jPS-g- |17^ I a«, IT N^T K... BBP -Beplieatt MST-bsmmeat
1992-07-15
Modeling SENIOR PRINCIPAL INVESTIGATOR: R. M. Mersereau, Regents’ Professor SCIENTIFIC PERSONNEL: F. J. Malassenet, (Ph.D. received, Dec. 1991) T. R. Gardos ...multiprocessor environment. RESEARCH ACCOMPLISHMENTS: Students Gardos , Martucci, Rao, and Truong were partially supported using funds supplied by Georgia...pp. 21- 56, 1991. [4] T. R. Gardos and R. M. Mersereau, "FIR Filtering on a Lattice with Periodically Deleted Samples," Proc. 1991 IEEE Int. Conf
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.
Tran, Q L; Adnyana, I K; Tezuka, Y; Nagaoka, T; Tran, Q K; Kadota, S
2001-04-01
The methanol extract of Vietnamese ginseng (Panax vietnamensis) was found to possess hepatocytoprotective effects on D-galactosamine (D-GalN)/tumor necrosis factor-alpha (TNF-alpha)-induced cell death in primary cultured mouse hepatocytes. Further chemical investigation of the extract afforded two new dammarane-type triterpene saponins, ginsenoside Rh(5) (1) and vina-ginsenoside R(25) (2), as well as eight known dammarane-type triterpene saponins, majonoside R(2) (3), pseudo-ginsenoside RT(4) (4), vina-ginsenosides R(1) (5), R(2) (6), and R(10) (7), ginsenosides Rg(1) (8), Rh(1) (9), and Rh(4) (10), and a known sapogenin protopanaxatriol oxide II (11). Their structures were elucidated on the basis of spectral analysis. In addition, by the using LC-electrospray ionization (ESI)-MS method, five known saponins, ginsenosides Rb(1), Rb(2), Rc, Rd, and Re (12--16), were also identified in the extract. Among the compounds isolated, majonoside R(2) (3), the main saponin in Vietnamese ginseng, showed strong protective activity against D-GalN/TNF-alpha-induced cell death in primary cultured mouse hepatocytes. This demonstrates that the hepatocytoprotective effect of Vietnamese ginseng is due to dammarane-type triterpene saponins that have an ocotillol-type side chain, a characteristic constituent of Vietnamese ginseng.
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
2012-01-01
The incidence of malignant melanoma is rising faster than that of any other cancer in the United States. Due to 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 over-express MC1R, MC4R or MC5R. Of these, compound 1 (4-phenylbutyryl-His-Dphe-Arg-Trp-NH2) exhibited high (0.2 nM) binding affinity for MC1R, and low (high nM) affinities for MC4R and MC5R. Subsequently 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 nM binding affinity. PMID:22011200
On the Sensitivity of Solutions of Parametrized Equations
1991-03-22
that the mapping 0 Sd -+ R’, ~()=y is of class C’ on Sd. Evidently, we have I b(0) =0 and (2.10) 4bD : Sd C Rd +R’, (D(r) =xo±+V-r +Vm(-r), V7 CSd, j...ran~k td d there exists some A C Isomn Rd Such that, I I d LA whence 3n VLd(VdT L’d)’ V~dAA1 d Ud) d(rndd d) 4. Some Geometrical Aspects As, lbefore
The Autonomous Sciencecraft and applications to future science missions
NASA Astrophysics Data System (ADS)
Chien, S.
2006-05-01
The Autonomous Sciencecraft Software has operated the Earth Observing One (EO-1) Mission for over 5000 science observations [Chien et al. 2005a]. This software enables onboard analysis of data to drive: 1. production of rapid alerts summary products, 2. data editing, and 3. to inform subsequent observations. This methodology has been applied to more effectively study Volcano, Flooding, and Cryosphere processes on Earth. In this talk we discuss how this software enables new paradigms for science missions and discuss the types of science phenomena that can now be more readily studied (e.g. dynamic investigations, large scale searches for specific events). We also describe a range of Earth, Solar, and Space science applications under concept study for onboard autonomy. Finally, we describe ongoing work to link EO-1 with other spacecraft and in-situ sensor networks to enable a sensorweb for monitoring dynamic science events [Chien et al. 2005b]. S. Chien, R. Sherwood, D. Tran, B. Cichy, G. Rabideau, R. Castano, A. Davies, D. Mandl, S. Frye, B. Trout, S. Shulman, D. Boyer, "Using Autonomy Flight Software to Improve Science Return on Earth Observing One, Journal of Aerospace Computing, Information, & Communication, April 2005, AIAA. S. Chien, B. Cichy, A. Davies, D. Tran, G. Rabideau, R. Castano, R. Sherwood, D. Mandl, S. Frye, S. Shulman, J. Jones, S. Grosvenor, "An Autonomous Earth Observing Sensorweb," IEEE Intelligent Systems, May-June 2005, pp. 16- 24.
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.
NFκB-mediated cyclin D1 expression by microRNA-21 influences renal cancer cell proliferation.
Bera, Amit; Ghosh-Choudhury, Nandini; Dey, Nirmalya; Das, Falguni; Kasinath, Balakuntalam S; Abboud, Hanna E; Choudhury, Goutam Ghosh
2013-12-01
MicroRNAs regulate post-transcriptomic landscape in many tumors including renal cell carcinoma. We have recently shown significantly increased expression of miR-21 in renal tumors and that this miRNA contributes to the proliferation of renal cancer cells in culture. However, the mechanism by which miR-21 regulates renal cancer cell proliferation is poorly understood. Addiction to constitutive NFκB activity is hallmark of many cancers including renal cancer. Using miR-21 Sponge in renal cancer cells to block endogenous function of miR-21, we show inhibition of phosphorylation of p65 subunit of NFκB, IKKβ and IκB, which results in attenuation of NFκB transcriptional activity. Subtle reduction in the tumor suppressor PTEN has been linked to various malignancies. We showed previously that miR-21 targeted PTEN in renal cancer cells. Inhibition of PTEN by siRNAs restored miR-21 Sponge-induced suppression of phosphorylation of p65, IKKβ, IκB and NFκB transcriptional activity along with reversal of miR-21 Sponge-reduced phosphorylation of Akt. Expression of constitutively active Akt protected against miR-21 Sponge- and PTEN-mediated decrease in p65/IKKβ/IκB phosphorylation and NFκB transcriptional activity. Furthermore, IKKβ and p65 were required for miR-21-induced renal cancer cell proliferation. Interestingly, miR-21 controlled the expression of cyclin D1 through NFκB-dependent transcription. Finally, we demonstrate that miR-21-regulated renal cancer cell proliferation is mediated by cyclin D1 and CDK4. Together, our results establish a molecular order of a phosphatase-kinase couple involving PTEN/Akt/IKKβ and NFκB-dependent cyclin D1 expression for renal carcinoma cell proliferation by increased miR-21 levels. © 2013.
NFκB-mediated cyclin D1 expression by microRNA-21 influences renal cancer cell proliferation
Bera, Amit; Ghosh-Choudhury, Nandini; Dey, Nirmalya; Das, Falguni; Kasinath, Balakuntalam S.; Abboud, Hanna E.; Choudhury, Goutam Ghosh
2013-01-01
MicroRNAs regulate post-transcriptomic landscape in many tumors including renal cell carcinoma. We have recently shown significantly increased expression of miR-21 in renal tumors and that this miRNA contributes to the proliferation of renal cancer cells in culture. However, the mechanism by which miR-21 regulates renal cancer cells proliferation is poorly understood. Addiction to constitutive NFκB activity is hallmark of many cancers including renal cancer. Using miR-21 Sponge in renal cancer cells to block endogenous function of miR-21, we show inhibition of phosphorylation of p65 subunit of NFκB, IKKβ and IκB, which results in attenuation of NFκB transcriptional activity. Subtle reduction in the tumor suppressor PTEN has been linked to various malignancies. We showed previously that miR-21 targeted PTEN in renal cancer cells. Inhibition of PTEN by siRNAs restored miR-21 Sponge-induced suppression of phosphorylation of p65, IKKβ, IκB and NFκB transcriptional activity along with reversal of miR-21 Sponge-reduced phosphorylation of Akt. Expression of constitutively active Akt protected against miR-21 Sponge- and PTEN-mediated decrease in p65/IKKβ/IκB phosphorylation and NFκB transcriptional activity. Furthermore, IKKβ and p65 were required for miR-21-induced renal cancer cell proliferation. Interestingly, miR-21 controlled the expression of cyclin D1 through NFκB-dependent transcription. Finally, we demonstrate that miR-21-regulated renal cancer cell proliferation is mediated by cyclin D1 and CDK4. Together, our results establish a molecular order of a phosphatase-kinase couple involving PTEN/Akt/IKKβ and NFκB-dependent cyclin D1 expression for renal carcinoma cell proliferation by increased miR-21 levels. PMID:23981302
BACTERIOPHAGE T4 MULTIPLICATION IN A GLUCOSE-LIMITED ESCHERICHIA COLI BIOFILM. (R825503)
The perspectives, information and conclusions conveyed in research project abstracts, progress reports, final reports, journal abstracts and journal publications convey the viewpoints of the principal investigator and may not represent the views and policies of ORD and EPA. Concl...
TRICHLOROETHYLENE ACTIVATES CD4+ T CELLS: POTENTIAL ROLE IN AN AUTOIMMUNE RESPONSE. (R826409)
The perspectives, information and conclusions conveyed in research project abstracts, progress reports, final reports, journal abstracts and journal publications convey the viewpoints of the principal investigator and may not represent the views and policies of ORD and EPA. Concl...
DESTRUCTION OF 2,4,6-TRINITROTOLUENE (TNT) BY FENTON OXIDATION. (R825549C043)
The perspectives, information and conclusions conveyed in research project abstracts, progress reports, final reports, journal abstracts and journal publications convey the viewpoints of the principal investigator and may not represent the views and policies of ORD and EPA. Concl...
DISSOCIATIVE ADSORPTION AND HYDRODECHLORINATION OF CCL4 ON IR(110). (R828598C802)
The perspectives, information and conclusions conveyed in research project abstracts, progress reports, final reports, journal abstracts and journal publications convey the viewpoints of the principal investigator and may not represent the views and policies of ORD and EPA. Concl...
LANDSCAPE PATTERNS OF CH4 FLUXES IN AN ALPINE TUNDRA ECOSYSTEM. (R823442)
The perspectives, information and conclusions conveyed in research project abstracts, progress reports, final reports, journal abstracts and journal publications convey the viewpoints of the principal investigator and may not represent the views and policies of ORD and EPA. Concl...
CYTOTOXICITY ASSOCIATED WITH TRICHLOROETHYLENE OXIDATION IN BURKHOLDERIA CEPACIA G4. (R825689C027)
The perspectives, information and conclusions conveyed in research project abstracts, progress reports, final reports, journal abstracts and journal publications convey the viewpoints of the principal investigator and may not represent the views and policies of ORD and EPA. Concl...
1-CHLORO-(2S, 3S)-DIHYDROXYCYCLO-HEXA-4, 6-DIENE. (R826113)
The perspectives, information and conclusions conveyed in research project abstracts, progress reports, final reports, journal abstracts and journal publications convey the viewpoints of the principal investigator and may not represent the views and policies of ORD and EPA. Concl...
2012-10-14
of high-gradient cobalt -tipped cantilevers, NanoMRI Conference 2012; Ascona, Switzerland; July 22 – 27, 2012, [url]. 4. R. Picone, J. Garbini, and J...url]. 5. J. G. Longenecker, H. J. Mamin, A. W. Senko, L. Chen, C. T. Rettner, D. Rugar, and J. A. Marohn, High gradient cobalt nanomagnets...Longenecker, H. J. Mamin, A. W. Senko, L. Chen, C. T. Rettner, D. Rugar, and J. A. Marohn, Development and characterization of high-gradient cobalt -tipped
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.
Wu, Che-Wei; Hao, Min; Tian, Mengzi; Dionigi, Gianlorenzo; Tufano, Ralph P; Kim, Hoon Yub; Jung, Kwang Yoon; Liu, Xiaoli; Sun, Hui; Lu, I-Cheng; Chang, Pi-Ying; Chiang, Feng-Yu
2017-06-01
During monitored thyroidectomy, a partially or completely disrupted point of nerve conduction on the exposed recurrent laryngeal nerve (RLN) indicates true electrophysiologic nerve injury. Complete loss of signal (LOS; absolute threshold value <100 μV) at the end of operation often indicates a postoperative vocal cord (VC) palsy. However, the evaluation for the injured RLN with incomplete LOS and its functional outcome has not been well described. Three hundred twenty-three patients with 522 RLNs at risk who underwent standardized monitored thyroidectomy were enrolled. The RLN was routinely stimulated at the most proximal (R 2p signal) and distal (R 2d signal) ends of exposure after thyroid resection to determine if there was an injured point on the RLN. Pre- and postoperative VC function was routinely examined. Twenty-nine RLNs (5.6 %) were detected with an injury point. Five nerves had complete LOS and other 24 nerves had incomplete LOS where the R 2p /R 2d reduction (% of amplitude reduction compared with proximal to distal RLN stimulation) ranged from 22 to 79 %. Postoperative temporary VC palsy was noted in those five RLNs with complete LOS (final vagal signal, V 2 < 100 μV) and four RLNs with incomplete LOS (R 2p /R 2d reduction 62-79 %; V 2 181-490 μV). In the remaining 20 nerves with R 2p /R 2d reduction ≤53 % (V 2 373-1623 μV), all showed normal VC mobility. Overall, false negative results were found in two RLNs (0.4 %) featuring unchanged V 2 and R 2p /R 2d but developed VC palsy. Testing and comparing the R 2p /R 2d signal is a simple and useful procedure to evaluate RLN injury after its dissection and predict functional outcome. When the relative threshold value R 2p /R 2d reduction reaches over 60 %, surgeon should consider the possibility of postoperative VC palsy.
NASA Astrophysics Data System (ADS)
Oruc, Gizem; Varnali, Tereza; Bekiroglu, Somer
2018-05-01
The solution properties of ethylene glycol (ethane-1,2-diol), glycerol (propane-1,2,3-triol), erythritol ((2R,3S)-butane-1,2,3,4-tetraol), D-xylitol ((2R,3r,4S)-pentane-1,2,3,4,5-pentaol), D-mannitol ((2R,3R,4R,5R)-hexane-1,2,3,4,5,6-hexaol), and D-sorbitol ((2S,3R,4R,5R)-hexane-1,2,3,4,5,6-hexaol), constituting a subgroup of polyalcohols/polyols of maximum six carbon atoms have been investigated using 1H NMR chemical shifts, coupling constants, temperature coefficients, and chemical exchange rates of hydroxy protons in aqueous medium. Relative within a molecule, minimum two-fold difference in rate of exchange values and higher temperature dependence of chemical shifts of the hydroxy protons on terminal carbon atoms confirm that sustainable hydrogen bonding interactions is accentuated for the hydroxyl groups on secondary carbons. Compared to the primary carbons i.e. terminal ones, the hydroxy protons on second and third carbon atoms exhibit much lower rate of exchange and smaller temperature coefficients, indicating that they are further involved in transient hydrogen bonding interactions. Scalar 3JOH,CH-couplings ranging between 3.9 and 7.2 Hz imply that the hydroxyl groups are practically in free rotation regime. Examination of the chemical shift differences with respect to the shift of glycol hydroxy proton reveals that the disparity between terminal and inner hydroxyl groups disclosed by the exchange rates and temperature coefficients is sustained with the exception of 0.003 and 0.053 ppm for O(3)H of mannitol and O(5)H of sorbitol respectively. The experimental findings have been augmented by quantum chemical calculations targeting theoretical NMR chemical shifts, as well as the conformational analysis of the structures.
The Impact of Selective Dopamine D2, D3 and D4 Ligands on the Rat Gambling Task.
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.
Spectral Analysis of Breast Cancer on Tissue Microarrays: Seeing Beyond Morphology
2005-04-01
Harvey N., Szymanski J.J., Bloch J.J., Mitchell M. investigation of image feature extraction by a genetic algorithm. Proc. SPIE 1999;3812:24-31. 11...automated feature extraction using multiple data sources. Proc. SPIE 2003;5099:190-200. 15 4 Spectral-Spatial Analysis of Urine Cytology Angeletti et al...Appendix Contents: 1. Harvey, N.R., Levenson, R.M., Rimm, D.L. (2003) Investigation of Automated Feature Extraction Techniques for Applications in
Qian, Andan; Wang, Xin; Liu, Huiru; Tao, Jiejie; Zhou, Jiejie; Ye, Qiong; Li, Jiance; Yang, Chuang; Cheng, Jingliang; Zhao, Ke; Wang, Meihao
2018-06-01
Attention deficit hyperactivity disorder (ADHD) is a common childhood neuropsychiatric disorder that has been linked to the dopaminergic system. This study aimed to investigate the effects of regulation of the dopamine D4 receptor (DRD4) on functional brain activity during the resting state in ADHD children using the methods of regional homogeneity (ReHo) and functional connectivity (FC). Resting-state functional magnetic resonance imaging data were analyzed in 49 children with ADHD. All participants were classified as either carriers of the DRD4 4-repeat/4-repeat (4R/4R) allele (n = 30) or the DRD4 2-repeat (2R) allele (n = 19). The results showed that participants with the DRD4 2R allele had decreased ReHo bilaterally in the posterior lobes of the cerebellum, while ReHo was increased in the left angular gyrus. Compared with participants carrying the DRD4 4R/4R allele, those with the DRD4 2R allele showed decreased FC to the left angular gyrus in the left striatum, right inferior frontal gyrus, and bilateral lobes of the cerebellum. The increased FC regions included the left superior frontal gyrus, medial frontal gyrus, and rectus gyrus. These data suggest that the DRD4 polymorphisms are associated with localized brain activity and specific functional connections, including abnormality in the frontal-striatal-cerebellar loop. Our study not only enhances the understanding of the correlation between the cerebellar lobes and ADHD, but also provides an imaging basis for explaining the neural mechanisms underlying ADHD in children.
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.
Ballet, Steven; Mayorov, Alexander V.; Cai, Minying; Tymecka, Dagmara; Chandler, Kevin B.; Palmer, Erin S.; Van Rompaey, Karolien; Misicka, Aleksandra; Tourwé, Dirk; Hruby, Victor J.
2008-01-01
In search of new selective antagonists and/or agonists for the human melanocortin receptor subtypes hMC1R to hMC5R to elucidate the specific biological roles of each GPCR, we modified the structures of the superagonist MT-II (Ac-Nle-c[Asp-His-D-Phe-Arg-Trp-Lys]-NH2) and the hMC3R/hMC4R antagonist SHU9119 (Ac-Nle-c[Asp-His-D-Nal(2′)-Arg-Trp-Lys]-NH2) by replacing the His-D-Phe and His-D-Nal(2′) fragments in MT-II and SHU9119, respectively, with Aba-Xxx (4-amino-1,2,4,5-tetrahydro-2-benzazepin-3-one-Xxx) dipeptidomimetics (Xxx = D-Phe/pCl-D-Phe/D-Nal(2′)). Employment of the Aba mimetic yielded novel selective high affinity hMC3R and hMC3R/hMC5R antagonists. PMID:17314042
Zhou, You; Hao, Yinghua; Li, Yuxia; Li, Ruizhen; Wu, Ruifang; Wang, Shubin; Fang, Zhengyu
2017-03-29
Cervical squamous cell carcinoma (CSCC) is the most frequent type among cervical cancers. Although the altered miRNA miR-30d expression and the amplified chromosome locus of MIR30D, 8q24, have been reported in somatic cancers, the definitive functional impact of such region especially in CSCC remains under-investigated. One hundred thirty-six cases of CSCC tissues and matched adjacent normal ovarian epithelial tissues were assessed in this study. FISH and qPCR were performed to detect the copy number and microRNA expression of MIR30D gene in the collected samples. In in-vitro study, proliferation of CSCC cells were analyzed using WST-1 assay and invasion abilities of CSCC cells were evaluated by transwell assay. In-vivo study using a model of nude mice bearing tumor was also performed. Copy number gains of MIR30D were detected in 22.8% (31 out of 136) of CSCC samples. Copy number of MIR30D was positively correlated with tumor progression. CSCCs with lymph node metastases (LNM) also showed more frequencies (36.4%) of MIR30D amplification than those without LNM (18.4%, p < 0.05). CSCCs with increased copy number of MIR30D also showed a positive correlation with miR-30d up-regulation. Inhibition of miR-30d in CSCC cells led to impaired tumor growth and migration. Copy number amplifications of MIR30D gene and enhanced expression of miR-30d were positively correlated with tumor progression in CSCCs, indicating miR-30d might play an oncomiric role in the progression of CSCC.
DOE Office of Scientific and Technical Information (OSTI.GOV)
Belloni, Alberto
This document is the final report for the U.S. D.O.E. Grant No. DE-SC0014088, which covers the period from May 15, 2015 to March 31, 2016. The funded research covered the study of multi-boson final states, culminated in the measurement of the W ±γγ and, for the first time at an hadronic collider, of the Zγγ production cross sections. These processes, among the rarest multi-boson final states measurable by LHC experiments, allow us to investigate the possibility of new physics in a model-independent way, by looking for anomalies in the standard model couplings among electroweak bosons. In particular, these 3-boson finalmore » states access quartic gauge couplings; the W ±γγ analysis performed as a part of this proposal sets limits on anomalies in the WWγγ quartic gauge coupling. The award also covered R&D activities to define a radiation-tolerant material to be used in the incoming upgrade of the CMS hadronic endcap calorimeter. In particular, the usage of a liquid-scintillator-based detector was investigated. The research work performed in this direction has been collected in a paper recently submitted for publication in the Journal of Instrumentation (JINST).« less
Singh, Anamika; Tala, Srinivasa R; Flores, Viktor; Freeman, Katie; Haskell-Luevano, Carrie
2015-05-14
The melanocortin-3 and -4 receptors are expressed in the brain and play key roles in regulating feeding behavior, metabolism, and energy homeostasis. In the present study, incorporation of β(3)-amino acids into a melanocortin tetrapeptide template was investigated. Four linear α/β(3)-hybrid tetrapeptides were designed with the modifications at the Phe, Arg, and Trp residues in the agonist sequence Ac-His-dPhe-Arg-Trp-NH2. The most potent mouse melanocortin-4 receptor (mMC4R) agonist, Ac-His-dPhe-Arg-β(3)hTrp-NH2 (8) showed 35-fold selectivity versus the mMC3R. The study presented here has identified a new template with heterogeneous backbone for designing potent and selective melanocortin receptor ligands.
2015-01-01
The melanocortin-3 and -4 receptors are expressed in the brain and play key roles in regulating feeding behavior, metabolism, and energy homeostasis. In the present study, incorporation of β3-amino acids into a melanocortin tetrapeptide template was investigated. Four linear α/β3-hybrid tetrapeptides were designed with the modifications at the Phe, Arg, and Trp residues in the agonist sequence Ac-His-dPhe-Arg-Trp-NH2. The most potent mouse melanocortin-4 receptor (mMC4R) agonist, Ac-His-dPhe-Arg-β3hTrp-NH2 (8) showed 35-fold selectivity versus the mMC3R. The study presented here has identified a new template with heterogeneous backbone for designing potent and selective melanocortin receptor ligands. PMID:26005535
Biotransformation and metabolism of three mulberry anthocyanin monomers by rat gut microflora.
Chen, Yao; Li, Qian; Zhao, Ting; Zhang, Zhen; Mao, Guanghua; Feng, Weiwei; Wu, Xiangyang; Yang, Liuqing
2017-12-15
Anthocyanins (ACNs) are naturally occurring components of human diet. Evidence has accumulated regarding the positive association of their intake with chronic disease. Because microbiota has been considered as a metabolic organ, the bacterial-dependent metabolisms of three types of ACNs from mulberry fruits (cyanidin-3-glucoside (C3G), cyanidin-3-rutinoside (C3R), delphinidin-3-rutinoside (D3R)) during a simulation of large intestine conditions were investigated. ACNs and metabolites were analysed and characterized by high performance liquid chromatography-electrospray ionization-mass spectrum (HPLC-ESI-MS/MS). C3G disappeared after 6h of metabolism, while C3R and D3R were no longer detected after 8h. The metabolism of C3G and C3R mainly resulted in the formation of protocatechuic, vanillic, and p-coumaric acids, as well as 2,4,6-trihydroxybenzaldehyde, while the main metabolites of D3R were gallic acid, syringic acid and 2,4,6-trihydroxybenzaldehyde. This research indicated that the intake of ACNs may result in the appearance of specific metabolites that exert a protective effect in the host physiology. Copyright © 2017 Elsevier Ltd. All rights reserved.
1981-06-01
which affect the corrosion of steel in concrete. The effects of moisture content [21, 22] of the concrete and the use of inhibitors in concrete mixes...use of inhibitors to reduce or eliminate corrosion. 3. The use of different alloys as rebar. 4. The use of cathodic protection in new and...8217- qq q or-wwr- - 4 m ON unlw Nr H E4E-4 0 vv o ~ o wq O % UU%D www AI L % z H Z 00 %ocnrj %o w o w (% N or csq r- qr IM c4 n NLn r- r -w 00 ’ 04
The perspectives, information and conclusions conveyed in research project abstracts, progress reports, final reports, journal abstracts and journal publications convey the viewpoints of the principal investigator and may not represent the views and policies of ORD and EPA. Concl...
The perspectives, information and conclusions conveyed in research project abstracts, progress reports, final reports, journal abstracts and journal publications convey the viewpoints of the principal investigator and may not represent the views and policies of ORD and EPA. Concl...
Evolution of magnetism in single-crystal C a 2 R u 1 - x I r x O 4 ( 0 ≤ x ≤ 0.65 )
Yuan, S. J.; Terzic, J.; Wang, J. C.; ...
2015-07-24
In this paper, we report structural, magnetic, transport, and thermal properties of single-crystal Ca 2Ru 1-xIr xO 4(0≤x≤0.65). Ca 2RuO 4 is a structurally driven Mott insulator with a metal-insulator transition at T MI=357K, which is well separated from antiferromagnetic order at T N=110K. Substitution of a 5d element, Ir, for Ru enhances spin-orbit coupling and locking between the structural distortions and magnetic moment canting. Ir doping intensifies the distortion or rotation of Ru/IrO 6 octahedra and induces weak ferromagnetic behavior along the c axis. In particular, Ir doping suppresses T N but concurrently causes an additional magnetic ordering Tmore » N2 at a higher temperature up to 210 K for x=0.65. The effect of Ir doping sharply contrasts with that of 3d-element doping such as Cr, Mn, and Fe, which suppresses T N and induces unusual negative volume thermal expansion. Finally, the stark difference between 3d- and 5d-element doping underlines a strong magnetoelastic coupling inherent in the Ir-rich oxides.« less
High-pressure synthesis and characterizations of the R2Pt2O7 pyrochlores.
NASA Astrophysics Data System (ADS)
Cai, Yunqi; Cui, Qi; Cheng, Jinguang; Dun, Zhiling; Zhou, Haidong; Ma, Jie; Cruz, C. Dela; Yan, Jiaqiang; Li, Xiang; Zhou, Jianshi
Pyrochlore R2B2O7 where R3 + stands for rear-earth ion and B4 + for a nonmagnetic cation such as Sn4 +or Ti4 +consist of an important family of geometrically frustrated magnets, which have been the focus of extensive investigations over last decades. To further enlarge the R2B2O7, we have chosen to stabilize the Pt-based cubic pyrochlores under HPHT conditions for two reasons: (1) Pt4 + is in a low-spin state which ionic radius is located in between Ti4 + (0.605\\x85) and Sn4 + (0.69\\x85), and (2) Pt4 + has a spatially much more extended 5d orbitals and thus enhanced Pt 5d-O 2p hybridizations that might modify the local anisotropic exchange interactions. Such an effect has never been taken into account in the previous studies. In this work, we will present the detailed characterizations on the pyrochlores R2Pt2O7 obtained under HPHT conditions. This work is supported by the National Science Foundation of China (Grant Nos.11304371, 11574377), part of the work was supported by the CEM, and NSF MRSEC, under Grant DMR-1420451, and Grant No. NSF-DMR-1350002.
BIOTRANSFORMATION OF 2,4,6-TRINITROTOLUENE (TNT) IN ANABAENA SP. CULTURES. (R825513C013)
The perspectives, information and conclusions conveyed in research project abstracts, progress reports, final reports, journal abstracts and journal publications convey the viewpoints of the principal investigator and may not represent the views and policies of ORD and EPA. Concl...
SYNTHESIS OF ALLENE ARYL DELTA-LACTONES VIA INDIUM-MEDIATED [4+2] CYCLIZATION IN WATER. (R822668)
The perspectives, information and conclusions conveyed in research project abstracts, progress reports, final reports, journal abstracts and journal publications convey the viewpoints of the principal investigator and may not represent the views and policies of ORD and EPA. Concl...
The perspectives, information and conclusions conveyed in research project abstracts, progress reports, final reports, journal abstracts and journal publications convey the viewpoints of the principal investigator and may not represent the views and policies of ORD and EPA. Concl...
The perspectives, information and conclusions conveyed in research project abstracts, progress reports, final reports, journal abstracts and journal publications convey the viewpoints of the principal investigator and may not represent the views and policies of ORD and EPA. Concl...
Recharge Data for Hawaii Island
Nicole Lautze
2015-01-01
Recharge data for Hawaii Island in shapefile format. The data are from the following sources: Whittier, R.B and A.I. El-Kadi. 2014. Human Health and Environmental Risk Ranking of On-Site Sewage Disposal systems for the Hawaiian Islands of Kauai, Molokai, Maui, and Hawaii – Final, Prepared for Hawaii Dept. of Health, Safe Drinking Water Branch by the University of Hawaii, Dept. of Geology and Geophysics. Oki, D. S. 1999. Geohydrology and Numerical Simulation of the Ground-Water Flow System of Kona, Island of Hawaii. U.S. Water-Resources Investigation Report: 99-4073. Oki, D. S. 2002. Reassessment of Ground-water Recharge and Simulated Ground-Water Availability for the Hawi Area of North Kohala, Hawaii. U.S. Geological Survey Water-Resources Investigation report 02-4006.
Begemann, Petra; Boysen, Gunnar; Georgieva, Nadia I.; Sangaiah, Ramiah; Koshlap, Karl M.; Koc, Hasan; Zhang, Daping; Golding, Bernard T.; Gold, Avram; Swenberg, James A.
2011-01-01
Isoprene, the 2-methyl analog of 1,3-butadiene, is ubiquitous in the environment, with major contributions to total isoprene emissions stemming from natural processes despite the compound being a bulk industrial chemical. Additionally, isoprene is a combustion product and a major component in cigarette smoke. Isoprene has been classified as possibly carcinogenic to humans (group 2B) by IARC and as reasonably anticipated to be a human carcinogen by the National Toxicology Program. Isoprene, like butadiene, requires metabolic activation to reactive epoxides to exhibit its carcinogenic properties. The mode of action has been postulated to be that of a genotoxic carcinogen, with formation of promutagenic DNA adducts being essential for mutagenesis and carcinogenesis. In rodents, isoprene-induced tumors show unique point mutations (A→T transversions) in the K-ras protooncogene at codon 61. Therefore, we investigated adducts formed after reaction of 2′-deoxyadenosine (dAdo1) with the two monoepoxides of isoprene, 2-ethenyl-2-methyloxirane (IP-1,2-O) and propen-2-yloxirane (IP-3,4-O), under physiological conditions. The formation of N1–2′-deoxyinosine (N1-dIno) due to deamination of N1-dAdo adducts was of particular interest, since N1-dIno adducts are suspected to have high mutagenic potential based on in vitro experiments. Major stable adducts were identified by HPLC, UV-Spectrometry and LC-MS/MS and characterized by 1H and 1H,13C HSQC and NMR experiments. Adducts of IP-1,2-O that were fully identified are: R,S-C1-N6-dAdo, R-C2-N6-dAdo, and S-C2-N6-dAdo; adducts of IP-3,4-O are: S-C3-N6-dAdo, R-C3-N6-dAdo, R,S-C4-N6-dAdo, S-C4-N1-dIno, R-C4-N1-dIno, R-C3-N1-dIno, S-C3-N1-dIno, and C3-N7-Ade. Both monoepoxides formed adducts on the external and internal oxirane carbons. This is the first study to describe adducts of isoprene monoepoxides with dAdo. Characterization of adducts formed by isoprene monoepoxides with deoxynucleosides and subsequently with DNA represent the first step toward evaluating their potential for being converted into a mutation, or as biomarkers of isoprene metabolism and exposure. PMID:21548641
Realization and characterization of a beam of titanium atoms
NASA Astrophysics Data System (ADS)
Azaroual, E. M.; Luc, P.; Vetter, R.
1992-06-01
A dense thermal beam of titanium atoms has been realized using a tungsten crucible inside a high temperature oven (leqslant 2 300 K). Its flux (≈ 10^{14} atom/cm^2/s) and its long term stability have been measured by means of a quartz balance, its angular divergence has been evaluated from the size of a metallic spot deposited on a glass plate. A spectroscopic investigation performed via the laser-induced fluorescence technique has led to the measurement of the isotope shifts between ^{46}Ti, ^{48}Ti and ^{50}Ti, for six visible 3d^2 4s^2 a ^3FJ''to 3d^2 4s4p z ^5DJ' transitions. This beam offers the characteristics required to apply high resolution laser techniques to reaction dynamics crossed-beam experiments. Un jet intense de titane atomique a été réalisé à partir d'un creuset de tungstène porté à haute température (leqslant 2 300 K). Le flux (≈ 10^{14} atomes/cm^2/s) et la stabilité à long terme du jet ont été mesurés avec une balance à quartz ; la divergence angulaire a été évaluée à partir de la dimension de dépôts métalliques sur des lames-témoin. Le jet a également été caractérisé par spectroscopie : la technique de fluorescence induite par laser a permis de mesurer le déplacement spectral dû aux isotopes 46, 48 et 50 de Ti, pour six transitions visibles du type 3d^2 4s^2 a ^3FJ''to 3d^2 4s4p z ^5DJ'. Le jet réalisé offre les caractéristiques requises pour l'application des techniques laser à haute résolution aux expériences de dynamique réactionnelle en faisceaux croisés.
Structural energetics of the adenine tract from an intrinsic transcription terminator.
Huang, Yuegao; Weng, Xiaoli; Russu, Irina M
2010-04-02
Intrinsic transcription termination sites generally contain a tract of adenines in the DNA template that yields a tract of uracils at the 3' end of the nascent RNA. To understand how this base sequence contributes to termination of transcription, we have investigated two nucleic acid structures. The first is the RNA-DNA hybrid that contains the uracil tract 5'-rUUUUUAU-3' from the tR2 intrinsic terminator of bacteriophage lambda. The second is the homologous DNA-DNA duplex that contains the adenine tract 5'-dATAAAAA-3'. This duplex is present at the tR2 site when the DNA is not transcribed. The opening and the stability of each rU-dA/dT-dA base pair in the two structures are characterized by imino proton exchange and nuclear magnetic resonance spectroscopy. The results reveal concerted opening of the central rU-dA base pairs in the RNA-DNA hybrid. Furthermore, the stability profile of the adenine tract in the RNA-DNA hybrid is very different from that of the tract in the template DNA-DNA duplex. In the RNA-DNA hybrid, the stabilities of rU-dA base pairs range from 4.3 to 6.5 kcal/mol (at 10 degrees C). The sites of lowest stability are identified at the central positions of the tract. In the template DNA-DNA duplex, the dT-dA base pairs are more stable than the corresponding rU-dA base pairs in the hybrid by 0.9 to 4.6 kcal/mol and, in contrast to the RNA-DNA hybrid, the central base pairs have the highest stability. These results suggest that the central rU-dA/dT-dA base pairs in the adenine tract make the largest energetic contributions to transcription termination by promoting both the dissociation of the RNA transcript and the closing of the transcription bubble. The results also suggest that the high stability of dT-dA base pairs in the DNA provides a signal for the pausing of RNA polymerase at the termination site. Copyright 2010 Elsevier Ltd. All rights reserved.
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.
Workshop on Robotics Materials
2017-12-28
TELEPHONE NUMBER Nicolaus Correll 611102 c. THIS PAGE The public reporting burden for this collection of information is estimated to average 1 hour per...Period: 12-Sep-2017 Submitted By: Ph.D Nicolaus Correll Phone: (303) 492-2233 STEM Degrees: 4 STEM Participants: 1 RPPR Final Report as of 15-Feb...Transfer: Nothing to Report Report Date: 12-Dec-2017 INVESTIGATOR(S): Phone Number: 3034922233 Principal: Y Name: Ph.D Nicolaus Correll Email
Four new neolignan glucosides from the fruits of Arctium lappa.
Huang, Xiao-Ying; Feng, Zi-Ming; Yang, Ya-Nan; Jiang, Jian-Shuang; Zhang, Pei-Cheng
2015-05-01
Four new neolignan glucosides named (7S, 8R)-4,7,9,9'-tetrahydroxy-3,3'-dimethoxy-8-O-4'-neolignan-9'-O-β-d-apiofuranosyl-(1 → 6)-O-β-d-glucopyranoside (1), (8R)-4,9,9'-trihydroxy-3,3'-dimethoxy-7-oxo-8-O-4'-neolignan-4-O-β-d-glucopyranoside (2), (7R, 8S)-dihydrodehydrodiconiferyl alcohol-7'-oxo-4-O-β-d-glucopyranoside (3), and (7'S, 8'R, 8S)-4,4',9'-trihydroxy-3,3'-dimethoxy-7',9-epoxylignan-7-oxo-4-O-β-d-glucopyranoside (4) were isolated from the fruits of Arctium lappa L. Their structures and absolute configurations were elucidated on the basis of comprehensive spectroscopic analyses (UV, IR, HR-ESI-MS, 1D and 2D NMR, CD), as well as by comparison with known analogues in the literature.
Ekhteiari Salmas, Ramin; Seeman, Philip; Aksoydan, Busecan; Stein, Matthias; Yurtsever, Mine; Durdagi, Serdar
2017-04-19
The dopamine D2 receptor (D2R) plays an important part in the human central nervous system and it is considered to be a focal target of antipsychotic agents. It is structurally modeled in active and inactive states, in which homodimerization reaction of the D2R monomers is also applied. The ASP2314 (also known as ACR16) ligand, a D2R stabilizer, is used in tests to evaluate how dimerization and conformational changes may alter the ligand binding space and to provide information on alterations in inhibitory mechanisms upon activation. The administration of the D2R agonist ligand ACR16 [ 3 H](+)-4-propyl-3,4,4a,5,6,10b-hexahydro-2H-naphtho[1,2-b][1,4]oxazin-9-ol ((+)PHNO) revealed K i values of 32 nM for the D2 high R and 52 μM for the D2 low R. The calculated binding affinities of ACR16 with post processing molecular dynamics (MD) simulations analyses using MM/PBSA for the monomeric and homodimeric forms of the D2 high R were -9.46 and -8.39 kcal/mol, respectively. The data suggests that the dimerization of the D2R leads negative cooperativity for ACR16 binding. The dimerization reaction of the D2 high R is energetically favorable by -22.95 kcal/mol. The dimerization reaction structurally and thermodynamically stabilizes the D2 high R conformation, which may be due to the intermolecular forces formed between the TM4 of each monomer, and the result strongly demonstrates dimerization essential for activation of the D2R.
77 FR 15939 - Airworthiness Directives; Pratt & Whitney Turbofan Engines
Federal Register 2010, 2011, 2012, 2013, 2014
2012-03-19
... Airworthiness Directives; Pratt & Whitney Turbofan Engines AGENCY: Federal Aviation Administration (FAA), DOT... & Whitney (PW) JT9D series turbofan engines. That AD currently requires revisions to the Airworthiness..., -7R4E, - 7R4E1, -7R4E4, -7R4G2, and -7R4H1 series turbofan engines. (d) Unsafe Condition This AD results...
Immunology Research in Israel.
1985-11-14
sonCLSIIDFG6S 1 .01 56 *3 2 . 1.8. 11111.2 1111 . MICROCOPY RESOLU TION TEST CHART W NAIN L 8UE OSTNA1936 - Ilile I.. - t"t 4-. r; I...pursued by Israel.i scientists include investigation of irmuno- globulin genes, structure-f unction analysis of antibodies and regulation of antibody...investigation of immuno- that had been first formulated by M. globulin genes, structure-function anal- Sela and R. Arnon. D. Givol pioneered in ysis of
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.
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.
Durdagi, Serdar; Salmas, Ramin Ekhteiari; Stein, Matthias; Yurtsever, Mine; Seeman, Philip
2016-02-17
We have recently reported G-protein coupled receptor (GPCR) model structures for the active and inactive states of the human dopamine D2 receptor (D2R) using adrenergic crystal structures as templates. Since the therapeutic concentrations of dopamine agonists that suppress the release of prolactin are the same as those that act at the high-affinity state of the D2 receptor (D2High), D2High in the anterior pituitary gland is considered to be the functional state of the receptor. In addition, the therapeutic concentrations of anti-Parkinson drugs are also related to the dissociation constants in the D2High form of the receptor. The discrimination between the high- and low-affinity (D2Low) components of the D2R is not obvious and requires advanced computer-assisted structural biology investigations. Therefore, in this work, the derived D2High and D2Low receptor models (GPCR monomer and dimer three-dimensional structures) are used as drug-binding targets to investigate binding interactions of dopamine and apomorphine. The study reveals a match between the experimental dissociation constants of dopamine and apomorphine at their high- and low-affinity sites of the D2 receptor in monomer and dimer and their calculated dissociation constants. The allosteric receptor-receptor interaction for dopamine D2R dimer is associated with the accessibility of adjacent residues of transmembrane region 4. The measured negative cooperativity between agonist ligand at dopamine D2 receptor is also correctly predicted using the D2R homodimerization model.
The Double R Theory of Language Comprehension
2004-02-01
AFRL-HE-AZ-TR- 2003 - 0110 Approved for public release; distribution is unlimited. AIR FORCE MATERIEL COMMAND AIR FORCE RESEARCH LABORATORY Human...REPORT TYPE Final 3. DATES COVERED (From - To) March 2003 to February 2004 5a. CONTRACT NUMBER F41624-97-D-5000 5b. GRANT NUMBER 4. TITLE...Laboratory Human Effectiveness Directorate Warfighter Training Research Division 6030 South Kent Street Mesa AZ 85212-6061 AFRL-HE-AZ-TR- 2003
C2 Approaches: Looking for the Sweet Spot
2013-06-01
more information) IMAGE (see Lizotte et al., 2008; Lizotte, Bernier, Mokhtari , & Boivin, 2013) was developed as a suite of generic representation...439–446). Fukuoka, Japan. Lizotte, M., Bernier, F., Mokhtari , M., & Boivin, E. (2013). IMAGE Final Report: An Interactive Computer-aided Cognition...Capability for C4ISR Complexity Discovery (No. TR 2013-397). Québec, Canada: Defence R&D Canada - Valcartier. Lizotte, M., Bernier, F., Mokhtari , M
Detectors for Linear Colliders: Tracking and Vertexing (2/4)
Battaglia, Marco
2018-04-16
Efficient and precise determination of the flavour of partons in multi-hadron final states is essential to the anticipated LC physics program. This makes tracking in the vicinity of the interaction region of great importance. Tracking extrapolation and momentum resolution are specified by precise physics requirements. The R&D; towards detectors able to meet these specifications will be discussed, together with some of their application beyond particle physics.
NASA Technical Reports Server (NTRS)
Pinelli, Thomas E.; Barclay, Rebecca O.; Kennedy, John M.
1994-01-01
The U.S. government technical report is a primary means by which the results of federally funded research and development (R&D) are transferred to the U.S. aerospace industry. However, little is known about this information product in terms of its actual use, importance, and value in the transfer of federally funded R&D. To help establish a body of knowledge, the U.S. government technical report is being investigated as part of the NASA/DOD Aerospace Knowledge Diffusion Research Project. In this report, we summarize the literature on technical reports and provide a model that depicts the transfer of federally funded aerospace R&D via the U.S. government technical report. We present results from our investigation of aerospace knowledge diffusion vis-a-vis the U.S. government technical report, and present the results of research that investigated aerospace knowledge diffusion vis-a-vis the technical communications practices of British aerospace engineers and scientists.
Exemption of certain systems of records under the Privacy Act. Final rule.
2008-09-26
This final rule exempts four systems of records (SORs) from subsections (c)(3), (d)(1) through (d)(4), (e)(4)(G) and (H), and (f) of the Privacy Act pursuant to 5 U.S.C. 552a(k)(2): The Automated Survey Processing Environment (ASPEN) Complaint/ Incidents Tracking System (ACTS), HHS/CMS, System No. 09-70-0565; the Health Insurance Portability and Accountability Act (HIPAA) Information Tracking System (HITS), HHS/CMS, System No. 09-70-0544; the Organ Procurement Organizations System (OPOS), HHS/CMS, System No. 09-70- 0575; and the Fraud Investigation Database (FID), HHS/CMS, System No. 09-70-0527.
Al-Gheethi, A A; Mohamed, R M; Jais, N M; Efaq, A N; Abd Halid, Abdullah; Wurochekke, A A; Amir-Hashim, M K
2017-10-01
The present study aims to investigate the influence of Staphylococcus aureus, Escherichia coli and Enterococcus faecalis in public market wastewater on the removal of nutrients in terms of ammonium (NH 4 - ) and orthophosphate (PO 4 3 ) using Scenedesmus sp. The removal rates of NH 4 - and orthophosphate PO 4 3- and batch kinetic coefficient of Scenedesmus sp. were investigated. The phycoremediation process was carried out at ambient temperature for 6 days. The results revealed that the pathogenic bacteria exhibited survival potential in the presence of microalgae but they were reduced by 3-4 log at the end of the treatment process. The specific removal rates of NH 4 - and PO 4 3- have a strong relationship with initial concentration in the public market wastewater (R 2 = 0.86 and 0.80, respectively). The kinetic coefficient of NH 4 - removal by Scenedesmus sp. was determined as k = 4.28 mg NH 4 - 1 log 10 cell mL -1 d -1 and k m = 52.01 mg L -1 (R 2 = 0.94) while the coefficient of PO 4 3- removal was noted as k = 1.09 mg NH 4 - 1 log 10 cell mL -1 d -1 and k m = 85.56 mg L -1 (R 2 = 0.92). It can be concluded that Scenedesmus sp. has high competition from indigenous bacteria in the public market wastewater to remove nutrients, with a higher coefficient of removal of NH 4 - than PO 4 3 .
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.
2010-03-29
IR FO R C E\\ 32 99 91 AI R SP A C E EA \\G IS \\M X D \\F IG U R E- A LT ER N AT IV E A. M X D M KO U BE K...basis. BO I \\\\O W L\\ PR O J\\ M O U N TA IN H O M EA IR FO R C E\\ 32 99 91 AI R SP A C E EA \\G IS \\M X D \\F IG U R E- A LT ER N AT IV E B. M X D M KO...MTR. MTR segments are identified and charted as either IR routes (IFR) or VR routes
The perspectives, information and conclusions conveyed in research project abstracts, progress reports, final reports, journal abstracts and journal publications convey the viewpoints of the principal investigator and may not represent the views and policies of ORD and EPA. Concl...
The perspectives, information and conclusions conveyed in research project abstracts, progress reports, final reports, journal abstracts and journal publications convey the viewpoints of the principal investigator and may not represent the views and policies of ORD and EPA. Concl...
The perspectives, information and conclusions conveyed in research project abstracts, progress reports, final reports, journal abstracts and journal publications convey the viewpoints of the principal investigator and may not represent the views and policies of ORD and EPA. Concl...
DIFFUSIVE TRANSPORT OF 2,4,6-TNT FROM A CONTAMINATED SOIL TO OVERLYING WATER. (R825513C013)
The perspectives, information and conclusions conveyed in research project abstracts, progress reports, final reports, journal abstracts and journal publications convey the viewpoints of the principal investigator and may not represent the views and policies of ORD and EPA. Concl...
The perspectives, information and conclusions conveyed in research project abstracts, progress reports, final reports, journal abstracts and journal publications convey the viewpoints of the principal investigator and may not represent the views and policies of ORD and EPA. Concl...
The perspectives, information and conclusions conveyed in research project abstracts, progress reports, final reports, journal abstracts and journal publications convey the viewpoints of the principal investigator and may not represent the views and policies of ORD and EPA. Concl...
The perspectives, information and conclusions conveyed in research project abstracts, progress reports, final reports, journal abstracts and journal publications convey the viewpoints of the principal investigator and may not represent the views and policies of ORD and EPA. Concl...
The perspectives, information and conclusions conveyed in research project abstracts, progress reports, final reports, journal abstracts and journal publications convey the viewpoints of the principal investigator and may not represent the views and policies of ORD and EPA. Concl...
The perspectives, information and conclusions conveyed in research project abstracts, progress reports, final reports, journal abstracts and journal publications convey the viewpoints of the principal investigator and may not represent the views and policies of ORD and EPA. Concl...
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.
LETTER: Test of Te profile invariance by sensitivity studies
NASA Astrophysics Data System (ADS)
Becker, G.
1992-06-01
The response of the electron temperature profile shape to variations of the electron heating and density profiles is investigated in different confinement regimes. It is shown that the changes in rTe = -Te/(dTe/dr) exceed the measurement error if the shape of the electron heat diffusivity χe(r) is kept fixed. The observed constancy of rTe(r) in the outer half of the plasma is incompatible with such a fixed χe(r) shape, i.e., a Te profile constraining mechanism must be present. Local transport laws of the form χe varies as rTe-α with α gtrsim 4 and χe propto (dTe/dr)α with α >= 2 yield the experimental stiffness of the Te(r) shape but conflict with empirical χe scalings. These results support the model of a self-organizing and adjusting χe(r) causing Te profile invariance
2D Hybrid Nanomaterials for Selective Detection of NO2 and SO2 Using "Light On and Off" Strategy.
Chen, Aimin; Liu, Rui; Peng, Xiao; Chen, Qiaofen; Wu, Jianmin
2017-10-25
In order to distinguish NO 2 and SO 2 gas with one sensor, we designed a paper chip assembled with a 2D g-C 3 N 4 /rGO stacking hybrid fabricated via a layer-by-layer self-assembly approach. The g-C 3 N 4 /rGO hybrid exhibited a remarkable photoelectric property due to the construction of a van der Waals heterostructure. For the first time, we have been able to selectively detect NO 2 and SO 2 gas using a "light on and off" strategy. Under the "light off" condition, the g-C 3 N 4 /rGO sensor exhibited a p-type semiconducting behavior with a low detection limit of 100 ppb of NO 2 , but with no response toward SO 2 . In contrast, the sensor showed n-type semiconducting behavior which could detect SO 2 at concentration as low as 2 ppm under UV light irradiation. The effective electron transfer among the 2D structure of g-C 3 N 4 and rGO nanosheets as well as highly porous structures could play an important role in gas sensing. The different sensing mechanisms at "light on and off" circumstances were also investigated in detail.
The Development of Laminated Armor
1948-09-27
U.S. Army Ramie Sea Island Mills, Inc. Ramie-Rayon Sea Island Mills, Ilc. Inconel Fabric (006R260R13) Metal Tex Co. -4- Inconel Fabric (00R21OMl6...Plies .02 U.D. Glass Mat 3111-44 4 Plies .02 IT.D. Glass Mat f 110 90 100 1 Ply Nylon Dusk(13 Oz.) I Ply 00R260R13 2-l/4# Inconel 2 Puiem Nylon Duck(13 Oz...13 Oz.) 1 Ply O07R210M16 2-1/4# Inconel 2 Pl•es Nylon Duck(13 Oz.) I Ply 007R210MI( ?-1/4# Inconel 1 Ply Nylon Duck(13 Oz.) 4 Plies .02 U.D. Mlass Mat
3D T2-weighted imaging to shorten multiparametric prostate MRI protocols.
Polanec, Stephan H; Lazar, Mathias; Wengert, Georg J; Bickel, Hubert; Spick, Claudio; Susani, Martin; Shariat, Shahrokh; Clauser, Paola; Baltzer, Pascal A T
2018-04-01
To determine whether 3D acquisitions provide equivalent image quality, lesion delineation quality and PI-RADS v2 performance compared to 2D acquisitions in T2-weighted imaging of the prostate at 3 T. This IRB-approved, prospective study included 150 consecutive patients (mean age 63.7 years, 35-84 years; mean PSA 7.2 ng/ml, 0.4-31.1 ng/ml). Two uroradiologists (R1, R2) independently rated image quality and lesion delineation quality using a five-point ordinal scale and assigned a PI-RADS score for 2D and 3D T2-weighted image data sets. Data were compared using visual grading characteristics (VGC) and receiver operating characteristics (ROC)/area under the curve (AUC) analysis. Image quality was similarly good to excellent for 2D T2w (mean score R1, 4.3 ± 0.81; R2, 4.7 ± 0.83) and 3D T2w (mean score R1, 4.3 ± 0.82; R2, 4.7 ± 0.69), p = 0.269. Lesion delineation was rated good to excellent for 2D (mean score R1, 4.16 ± 0.81; R2, 4.19 ± 0.92) and 3D T2w (R1, 4.19 ± 0.94; R2, 4.27 ± 0.94) without significant differences (p = 0.785). ROC analysis showed an equivalent performance for 2D (AUC 0.580-0.623) and 3D (AUC 0.576-0.629) T2w (p > 0.05, respectively). Three-dimensional acquisitions demonstrated equivalent image and lesion delineation quality, and PI-RADS v2 performance, compared to 2D in T2-weighted imaging of the prostate. Three-dimensional T2-weighted imaging could be used to considerably shorten prostate MRI protocols in clinical practice. • 3D shows equivalent image quality and lesion delineation compared to 2D T2w. • 3D T2w and 2D T2w image acquisition demonstrated comparable diagnostic performance. • Using a single 3D T2w acquisition may shorten the protocol by 40%. • Combined with short DCE, multiparametric protocols of 10 min are feasible.
Dependence of acoustic levitation capabilities on geometric parameters.
Xie, W J; Wei, B
2002-08-01
A two-cylinder model incorporating boundary element method simulations is developed, which builds up the relationship between the levitation capabilities and the geometric parameters of a single-axis acoustic levitator with reference to wavelength. This model proves to be successful in predicting resonant modes of the acoustic field and explaining axial symmetry deviation of the levitated samples near the reflector and emitter. Concave reflecting surfaces of a spherical cap, a paraboloid, and a hyperboloid of revolution are investigated systematically with regard to the dependence of the levitation force on the section radius R(b) and curvature radius R (or depth D) of the reflector. It is found that the levitation force can be remarkably enhanced by choosing an optimum value of R or D, and the possible degree of this enhancement for spherically curved reflectors is the largest. The degree of levitation force enhancement by this means can also be facilitated by enlarging R(b) and employing a lower resonant mode. The deviation of the sample near the reflector is found likely to occur in case of smaller R(b), larger D, and a higher resonant mode. The calculated dependence of levitation force on R, R(b), and the resonant mode is also verified by experiment and finally demonstrated to be in good agreement with experimental results, in which considerably a strong levitation force is achieved to levitate an iridium sphere which has the largest density of 22.6 g/cm(3).
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.
Sabatino, Laura; Lubrano, Valter; Balzan, Silvana; Kusmic, Claudia; Del Turco, Serena; Iervasi, Giorgio
2015-01-01
Endothelial system acts as a large endocrine organ in the human body; however, little is still known about the regulative role of THs on endothelial cells. Aim of the present study was to investigate the expression of the TH deiodinases (D1, D2, and D3) and TH receptors (TRα1, TRα2, and TRβ1) in an endothelial microvascular cultured cell model (HMEC-1), after stimulation with triiodothyronine (T3, 10-100 nM), thyroxine (T4, 10-100 nM), and reverse T3 (rT3, 1-10 nM). DIO1 was significantly inhibited by T4 at 10 and 100 nM (p < 0.001). rT3 significantly inhibited DIO1 at 1 nM concentration (p < 0.01) and stimulated DIO1 at 10 nM dosage (p < 0.001). T4 and rT3 significantly inhibited DIO2 at all concentrations. DIO3 was induced at 100 nM T3 (p < 0.05) and 100 nM rT3 (p < 0.01), and TRα1 and TRα2 mRNAs were significantly increased after 100 nM T3 treatment (p < 0.05) and decreased after 1 and 10 nM rT3 (p < 0.05). TRβ1 was significantly increased by all THs at different concentrations: 10 nM T3 and 100 nM T3 (p < 0.05), 1 nM rT3 (p < 0.001), and 100 nM T4 (p < 0.01). D1 and D2 protein levels were evaluated, but no significant difference was observed for any hormonal treatment. For the first time, we found that the TH deiodinases and receptors are expressed in endothelial HMEC-1 cells. These findings might be of significant clinical relevance, given the important regulatory role of the endothelium as first barrier to the bloodstream.
High Reynolds Number Wave Force Investigation in a Wave Flume.
1985-03-01
RESULTS 43 6.0 CONCLUSIONS 45 7.0 REFERENCES 49 8.0 ACKNOWLEDGEMENTS 51 9.0 TABLES 53 10.0 FIGURES 93 11.0 APPENDIX A" 11.1 Druck Pressure Transducer...adjoining test cylinder by 0.7 mm, which had a negligible influence on the resulting measurements. After the Druck pressure transducers were installed and...dC C 3d 4 ;88dC 38dC CI8 cninfl"nV0to .t" o ,t in cv d-. ,0 en w . nC M..r nin - -0 - I!- I!- V! - -i !V L4JN C; .0 d C0000000 40000008 o .6 C
NASA Astrophysics Data System (ADS)
Galvez, Óscar; Gomez, Pedro C.; Gomez-Martin, Juan C.; Saiz-Lopez, Alfonso; Pacios, Luis F.
2013-04-01
Atmospheric iodine has received considerable attention in the past two decades due to both its potential role in the catalytic destruction of ozone (1) and its contribution to the formation of ultrafine particles (2). Seaweeds, marine phytoplankton, and abiotic processes release iodocarbons and I2 to the atmosphere, which are photo-oxidized giving iodine oxides that polymerize to finally form iodine oxide particles (IOPs). In the last years, some laboratory studies have been carried out to investigate this process (see e.g. (3)), however the complete mechanism of formation of such particles and the role of water, and other condensable vapors, in this process have not yet been elucidated. In this context, quantum calculations could help to unravel essential steps of these processes and to evaluate relevant physicochemical properties that can be incorporated into atmospheric models. In this contribution, we show results of a theoretical study on different reactions that iodine oxides, in the presence of water, can undergo to form IOPs. Thermodynamic and kinetic properties of these reactions have been obtained at high level ab initio correlated calculations that included relativistic corrections. In these calculations, we have used a relativistic effective potential (REP) and REP-optimized basis sets for iodine atom developed in our group, which have previously been employed in a theoretical study about several iodinated species (4). (1) Saiz-Lopez, A.; Mahajan, A.S.; Salmon, R.A.; Bauguitte, J.B.; Jones, A.E.; Roscoe, H.K.; Plane, J.M.C. Science 2007, 317, 348-351 (2) O'Dowd, C.D.; Jimenez, J.L.; Bahreini, R.; Flagan, R.C.; Seinfeld, J.H.; Hämeri, K.; Pirjola, L.; Kulmala, M.; Jennings, S.G.; Hoffmann, T. Nature, 2002, 417, 632-636. (3) Saunders, R.W.; Kumar, R.; Gómez Martin, J.C.; Mahajan, A.S.; Murray, B.J.; Plane, J.M.C. Z. Phys. Chem. 2010, 224, 1095-1117. (4) Pacios, L.F.; Gálvez, O. J. Chem. Theory Comput., 2010, 6, 1738-1752.
Vijayaraj, Ramadoss; Devi, Mekapothula Lakshmi Vasavi; Subramanian, Venkatesan; Chattaraj, Pratim Kumar
2012-06-01
Three-dimensional quantitative structure activity relationship (3D-QSAR) study has been carried out on the Escherichia coli DHFR inhibitors 2,4-diamino-5-(substituted-benzyl)pyrimidine derivatives to understand the structural features responsible for the improved potency. To construct highly predictive 3D-QSAR models, comparative molecular field analysis (CoMFA) and comparative molecular similarity indices analysis (CoMSIA) methods were used. The predicted models show statistically significant cross-validated and non-cross-validated correlation coefficient of r2 CV and r2 nCV, respectively. The final 3D-QSAR models were validated using structurally diverse test set compounds. Analysis of the contour maps generated from CoMFA and CoMSIA methods reveals that the substitution of electronegative groups at the first and second position along with electropositive group at the third position of R2 substitution significantly increases the potency of the derivatives. The results obtained from the CoMFA and CoMSIA study delineate the substituents on the trimethoprim analogues responsible for the enhanced potency and also provide valuable directions for the design of new trimethoprim analogues with improved affinity. © 2012 John Wiley & Sons A/S.
Elbaz, Mohammed S M; Calkoen, Emmeline E; Westenberg, Jos J M; Lelieveldt, Boudewijn P F; Roest, Arno A W; van der Geest, Rob J
2014-09-27
LV diastolic vortex formation has been suggested to critically contribute to efficient blood pumping function, while altered vortex formation has been associated with LV pathologies. Therefore, quantitative characterization of vortex flow might provide a novel objective tool for evaluating LV function. The objectives of this study were 1) assess feasibility of vortex flow analysis during both early and late diastolic filling in vivo in normal subjects using 4D Flow cardiovascular magnetic resonance (CMR) with retrospective cardiac gating and 3D vortex core analysis 2) establish normal quantitative parameters characterizing 3D LV vortex flow during both early and late ventricular filling in normal subjects. With full ethical approval, twenty-four healthy volunteers (mean age: 20±10 years) underwent whole-heart 4D Flow CMR. The Lambda2-method was used to extract 3D LV vortex ring cores from the blood flow velocity field during early (E) and late (A) diastolic filling. The 3D location of the center of vortex ring core was characterized using cylindrical cardiac coordinates (Circumferential, Longitudinal (L), Radial (R)). Comparison between E and A filling was done with a paired T-test. The orientation of the vortex ring core was measured and the ring shape was quantified by the circularity index (CI). Finally, the Spearman's correlation between the shapes of mitral inflow pattern and formed vortex ring cores was tested. Distinct E- and A-vortex ring cores were observed with centers of A-vortex rings significantly closer to the mitral valve annulus (E-vortex L=0.19±0.04 versus A-vortex L=0.15±0.05; p=0.0001), closer to the ventricle's long-axis (E-vortex: R=0.27±0.07, A-vortex: R=0.20±0.09, p=0.048) and more elliptical in shape (E-vortex: CI=0.79±0.09, A-vortex: CI=0.57±0.06; <0.001) compared to E-vortex. The circumferential location and orientation relative to LV long-axis for both E- and A-vortex ring cores were similar. Good to strong correlation was found between vortex shape and mitral inflow shape through both the annulus (r=0.66) and leaflet tips (r=0.83). Quantitative characterization and comparison of 3D vortex rings in LV inflow during both early and late diastolic phases is feasible in normal subjects using retrospectively-gated 4D Flow CMR, with distinct differences between early and late diastolic vortex rings.
1991-01-01
CN 040 cOm 0 1- 00 ɘ 5.00 X0 w 1- Imn w* a 0 6 004 x -.400 N - ery 4N 0t I-NC .7-4 540 0. -m 0 C a0 n is CA IS I (0(04 If so* AO .flmfl -3115 EC) 4...0 0 0 0 0, 0 0D 0 o 0 W CU .- 00 Cm, .0m .0m .0m GoaM com caM c0m 00am cam Mcam ccaM S4W I -1 .4c P.4 l 1-4 ’ .4 <.. r.4x r -C4 r.4c r. 4 r_< . < I...x X NNX XNxX X XN X N NN W * )4.O I 0~ C7 D c aCD 200 0CDCD (9 00 10 5 5 ( 0(9 (90 D 0CDCD 9 (D(5(D D C90 ) 0C90 ( C * 0 qo U 4 4 44 4 4 4 44 4 4 4
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 molecular behavior in A{sub 2A}R/D{sub 2L}R dimer. Thus, these results indicate that the various designed types of functional A{sub 2A}R/D{sub 2}R exist even in living cells and that this fusion expression system would be useful to analyze as a model of the interaction between class A GPCRs.« less
DOE Office of Scientific and Technical Information (OSTI.GOV)
Shin, D; Kang, S; Kim, D
Purpose: The dose difference between three-dimensional dose (3D dose) and 4D dose which considers motion due to respiratory can be varied according to geometrical relationship between planning target volume (PTV) and organ at risk (OAR). The purpose of the study is to investigate the dose difference between 3D and 4D dose using overlap volume histogram (OVH) which is an indicator that quantify geometrical relationship between a PTV and an OAR. Methods: Five liver cancer patients who previously treated stereotactic body radiotherapy (SBRT) were investigated. Four-dimensional computed tomography (4DCT) images were acquired for all patients. ITV-based treatment planning was performed. 3Dmore » dose was calculated on the end-exhale phase image as a reference phase image. 4D dose accumulation was implemented from all phase images using dose warping technique used deformable image registration (DIR) algorithm (Horn and Schunck optical flow) in DIRART. In this study OVH was used to quantify geometrical relationship between a PTV and an OAR. OVH between a PTV and a selected OAR was generated for each patient case and compared for all cases. The dose difference between 3D and 4D dose for normal organ was calculated and compared for all cases according to OVH. Results: The 3D and 4D dose difference for OAR was analyzed using dose-volume histogram (DVH). On the basis of a specific point which corresponds to 10% of OAR volume overlapped with expanded PTV, mean dose difference was 34.56% in minimum OVH distance case and 13.36% in maximum OVH distance case. As the OVH distance increased, mean dose difference between 4D and 3D dose was decreased. Conclusion: The tendency of dose difference variation was verified according to OVH. OVH is seems to be indicator that has a potential to predict the dose difference between 4D and 3D dose. This work was supported by the Radiation Technology R&D program (No. 2013M2A2A7043498) and the Mid-career Researcher Program (2014R1A2A1A10050270) through the National Research Foundation of Korea funded by the Ministry of Science, ICT&Future Planning.« less
Military Dimensions of Communist Systems
1988-06-01
DI 0)~ I -c-i -q -o C ) 1 1 ! c 1 1 -- l d--. - co 0d, 17’~ H N ~ C) ,4; 10 N 0 I Q 0 0o olf 0 ’D ILO W NO co - 1n. -4 - 0... L C--4 n O c r- co(’ LO %DJ - ) ON- - C-4 ’ 0~ -1D 1-1 . W 0 1L -1 C-’- _;A L C- (IN 1 m I C- (I a% 0!. 0 !’ 0 11 AJ a’( cl DI LON r-14 0 0LD -4 (1...D 4 (n 1) to,- C-jLU) Vf) - C> Ir)U) 17 0 - C1 4 - L 4 0 C ( Di 10r 0 0 0 0 ’A-~ 0 ID a, U) 0 In r- 0 l -- CD 0 r- c C . C C . C C -,A C-a . (0 m1-
Global Well-Posedness and Temporal Decay Estimates for the 3D Nematic Liquid Crystal Flows
NASA Astrophysics Data System (ADS)
Liu, Qiao
2018-03-01
In this paper, we investigate global well-posedness and large time behavior of the Cauchy problem for the 3D incompressible nematic liquid crystal flows. By using the advantage of suitable weighted function, we show that for any initial data (u0,d0-\\overline{d}0) in critical Besov spaces \\dot{B}^{3/p-1}_{p,1}(R3)× \\dot{B}^{3/q}_{q,1}(R3) with 1< p, q<∞ and -\\inf {1/3,1/2p}≤1/q-1/p≤1/3 , if the initial orientation d0-\\overline{d}0 and a certain nonlinear function of initial velocity u0 are small enough, then there exists a global-in-time solution to the nematic liquid crystal flows. We also give an example of initial velocity satisfying that nonlinear smallness condition, but each component of its norm may be arbitrarily large. Moreover, if we further assume that (u0,d0-\\overline{d}0)\\in \\dot{B}^{-s}_{r,∞}(R3)× \\dot{B}^{-s+1}_{r,∞}(R3) with 1
Aircraft Fatigue - with Particular Emphasis on Australian Operations and Research.
1983-04-01
its research on the fatigue behaviour of full-scale alluminium -alloy structures by undertaking a major investigation using surplus wings from North...on the corrosion fatigue of Taper-Lok bolted joints in D6AC steel. In March 1973 the RAAF finally took delivery of its first F-IliC, and among the...development of multiple defects, corrosion /stress corrosion , detvrirrat- ion of bonded joints, undetected cracks or damage, inadquate repairs 2r untested
Nonlinear Real-Time Optical Signal Processing.
1984-10-01
I 1.8 IIII III1 1 / U , 0 7 USCIPI Report 1130 E ~C~,OUTfitA N Ivj) UNIVERSITY OF SOUTHERN CALIFORNIA - I FINAL TECHNICAL REPORT April 15, 1981 - June...30, 1984 N NONLINEAR REAL-TIME OPTICAL SIGNAL PROCESSING i E ~ A.A. Sawchuk, Principal Investigator T.C. Strand and A.R. Tanguay. Jr. October 1, 1984...Erter.d) logic system. A computer generated hologram fabricated on an e -beam system serves as a beamsteering interconnection element. A completely
Dron, Julien; Dodi, Alain
2011-06-15
The removal of chloride, nitrate and sulfate ions from aqueous solutions by a macroporous resin is studied through the ion exchange systems OH(-)/Cl(-), OH(-)/NO(3)(-), OH(-)/SO(4)(2-), and HCO(3)(-)/Cl(-), Cl(-)/NO(3)(-), Cl(-)/SO(4)(2-). They are investigated by means of Langmuir, Freundlich, Dubinin-Radushkevitch (D-R) and Dubinin-Astakhov (D-A) single-component adsorption isotherms. The sorption parameters and the fitting of the models are determined by nonlinear regression and discussed. The Langmuir model provides a fair estimation of the sorption capacity whatever the system under study, on the contrary to Freundlich and D-R models. The adsorption energies deduced from Dubinin and Langmuir isotherms are in good agreement, and the surface parameter of the D-A isotherm appears consistent. All models agree on the order of affinity OH(-)
The perspectives, information and conclusions conveyed in research project abstracts, progress reports, final reports, journal abstracts and journal publications convey the viewpoints of the principal investigator and may not represent the views and policies of ORD and EPA. Concl...
A novel glycoside from Acanthus hirsutus (Acanthaceae).
Capanlar, Seval; Böke, Nazli; Yaşa, Ihsan; Kirmizigül, Süheyla
2010-04-01
A novel glycoside, hirsutusoide (1), characterized as 2-(o-hydroxyphenyl)-2-hydroxyethenyl-O-beta-glucopyranoside, was isolated from the endemic Acanthus hirsutus Boiss. In addition to compound 1, three known glycosides, luteolin-7-O-beta-D-glucuronide (2), beta-sitosterol-3-O-beta-D-glucopyranoside (3) and (2R)-2-O-beta-D-glucopyranosyl-2H-1,4-benzoxazin-3(4H)-one (4), were also isolated. Compound 2 was the first report from this genus. Antimicrobial and antioxidant activity of the extracts and the novel compound were investigated by determining MIC (microg/mL) and IC50 (microg/mL) values, respectively.
UP2 400 High Activity Oxide Legacy Waste Retrieval Project Scope and Progress-13048
DOE Office of Scientific and Technical Information (OSTI.GOV)
Chabeuf, Jean-Michel; Varet, Thierry
The High Activity Oxide facility (HAO) reprocessed sheared and dissolved 4500 metric tons of light water reactor fuel the fuel of the emerging light water reactor spent fuel between 1976 and 1998. Over the period, approximately 2200 tons of process waste, composed primarily of sheared hulls, was produced and stored in a vast silo in the first place, and in canisters stored in pools in subsequent years. Upon shutdown of the facility, AREVA D and D Division in La Hague launched a thorough investigation and characterization of the silos and pools content, which then served as input data for themore » definition of a legacy waste retrieval and reconditioning program. Basic design was conducted between 2005 and 2007, and was followed by an optimization phase which lead to the definition of a final scenario and budget, 12% under the initial estimates. The scenario planned for the construction of a retrieval and reconditioning cell to be built on top of the storage silo. The retrieved waste would then be rinsed and sorted, so that hulls could subsequently be sent to La Hague high activity compacting facility, while resins and sludge would be cemented within the retrieval cell. Detailed design was conducted successfully from 2008 until 2011, while a thorough research and development program was conducted in order to qualify each stage of the retrieval and reconditioning process, and assist in the elaboration of the final waste package specification. This R and D program was defined and conducted as a response and mitigation of the major project risks identified during the basic design process. Procurement and site preparatory works were then launched in 2011. By the end of 2012, R and D is nearly completed, the retrieval and reconditioning process have been secured, the final waste package specification is being completed, the first equipment for the retrieval cell is being delivered on site, while preparation works are allowing to free up space above and around the silo, to allow for construction which is scheduled to being during the first semester of 2013. The elaboration of the final waste package is still undergoing and expected to be completed by then end of 2013, following some final elements of R and D required to demonstrate the full compatibility of the package with deep geological repository. The HAO legacy waste retrieval project is so far the largest such project entering operational phase on the site of La Hague. It is on schedule, under budget, and in conformity with the delivery requirements set by the French Safety Authority, as well as other stakeholders. This project paves the way for the successful completion of AREVA La Hague other legacy waste retrieval projects, which are currently being drafted or already in active R and D phase. (authors)« less
DOE Office of Scientific and Technical Information (OSTI.GOV)
Xu, Zhong-Xuan, E-mail: xuzhongxuan1974@163.com; State Key Laboratory of Structural Chemistry, Fujian Institute of Research on the Structure of Matter, the Chinese Academy of Sciences, Fuzhou, Fujian 350002; Ao, Ke-Hou
A pair of novel 3D homochiral metal−organic frameworks (HMOFs), namely [Cd{sub 2.5}((R)-CIA){sub 6}(1,4-DIB)(H{sub 2}O){sub 2}]·((CH{sub 3}){sub 2}NH{sub 2})·H{sub 2}O (1-D), [Cd{sub 2.5}((S)-CIA){sub 6}(1,4-DIB)(H{sub 2}O){sub 2}]·((CH{sub 3}){sub 2}NH{sub 2})·H{sub 2}O (1-L), have been synthesized using lactic acid derivative ligands ((R)-H{sub 3}CIA and (S)-H{sub 3}CIA) and 1,4-DIB. Crystallographic analyses indicate that the complexes 1-D and 1-L are packed by cage substructures. Some physical characteristics, such as solid-state circular dichroism (CD), thermal stabilities and photoluminescent properties are also investigated. Our results highlight the effective method to apply lactic acid derivative ligands to form interesting HMOFs. - Graphical abstract: Using lactic acid derivative ligandsmore » ((R)-H{sub 3}CIA and (S)-H{sub 3}CIA) and 1,4-DIB to assemble with Cd{sup 2+} ions, a pair of novel 3D homochiral metal-organic frameworks (HMOFs) with cage substructures have been synthesized. Display Omitted - Highlights: • Lactic acid derivative ligands • Cage substructure • Enantiomers.« less
NASA Astrophysics Data System (ADS)
Lefebvre, Eric
Cette thèse propose de tester la Chromodynamique Quantique (QCD) en effectuant une mesure précise d'une des trois constantes fondamentales du groupe de symétrie SU(3) utilisé pour décrire la physique des interactions fortes. Cette constante fondamentale, appelée TF, est reliée à certains états finaux spécifiques des désintégrations du Z0. Ces états apparaissent sous forme de perturbations du deuxième ordre en as et sont illustrés par des diagrammes de Feynman. À cet ordre, la chromodynamique prévoit deux types de diagrammes de Feynman distincts; le premier contient, un quark, un antiquark et deux gluons, et le second, deux quarks et deux antiquarks. La constante TF est directement proportionnelle à la fraction d'événements à deux quarks et deux antiquarks qui est l'objet de notre mesure. Notre mesure est fondée sur l'étude des événements à quatre partons dans l'état final. Ces quatre partons, en s'hadronisant, produisent quatre jets de particules qui peuvent être détectés expérimentalement et identifiés à l'aide d'algorithmes de reconstruction des jets. Des observables angulaires nous permettent de faire une discrimination parmi les états finaux de la désintégration du Z0, et ainsi déterminer la valeur de la fraction d'événements à deux quarks et deux antiquarks fq. Cette fraction peut s'exprimer par le rapport de la fraction observée expérimentalement fexq sur la fraction théorique fthq , R4q=
Enlisted MOS Suitable for the Physically Handicapped
1958-12-01
highly motivated in a mobili- zation situation. The pr.mary reason for using this approach was the need for a standardized classification system which...the classification process. The solution was to consider all disabili- ties as "severe" and motivation to perform "good." Thus any individual disabled...MC+e0)H 4E-4)OOHe~~~ A A A P44 O0O)HCeHl H’d e (d *Hc.3d,4-4 HO) HQ .r4 to’- L 4 Xe - H r4 Ps4 p) HO -i -i--I<-) rdr r d 90 P 4-- >< d0I - d a)0SoSS
The hobbit - an unexpected deficiency.
Hopkinson, Joseph A; Hopkinson, Nicholas S
2013-12-16
Vitamin D has been proposed to have beneficial effects in a wide range of contexts. We investigate the hypothesis that vitamin D deficiency, caused by both aversion to sunlight and unwholesome diet, could also be a significant contributor to the triumph of good over evil in fantasy literature. Data on the dietary habits, moral attributes and martial prowess of various inhabitants of Middle Earth were systematically extracted from J R R Tolkien's novel The hobbit. Goodness and victoriousness of characters were scored with binary scales, and dietary intake and habitual sun exposure were used to calculate a vitamin D score (range, 0-4). The vitamin D score was significantly higher among the good and victorious characters (mean, 3.4; SD, 0.5) than the evil and defeated ones (mean, 0.2; SD, 0.4; P < 0.001). Further work is needed to see if these pilot results can be extrapolated to other fantastic situations and whether randomised intervention trials need to be imagined.
1985-04-01
Ratino, R.K.H. Geber , A.A. Karl, D.R. Nelson, "OPTO Electronic Methodology Suitable for Electroretinographic Investigations During Environmental Stess...R.K.H. Geber , A.A. Karl, D.R. Nelson, "OPTO Electronic Methodology Suitable for Electroretinographic Investigations During Environmental Stess...6 Section M -Page 167 Author Index Gaudio, R. L-62, 67 Gawain,G.C.V. A-12 Geber ,R.K.H. G-42,H-22 Geer,R.L. F-92 Gehrich,J.L. A-273 Gell,C.F. D-33,F-97
South Atlantic Omega Validation. Volume 1. Summary, Analysis, Appendices A-E.
1983-01-01
JAN 63 UNLASSIFIED DTC O23-0 -C-4-23 F/O 17?3 L Wi 1j.1 Vll 11.2 MICOCPV ESLUIO TETC6 R NATINAL U~ i L 4.& STNAO .0 64:4 1ILE ()PY < SPAGE MILL RD. I ...NCO. I 10C .PALO M.O, CAUPOIUi CCII) 1ir,- SOUTH ATLANTIC OMEGA VALIDATION Final Report VOLUME I : SUMMARY, ANALYSIS, APPENDICES A-E January 1983...OPERATIONS DETAIL Washington, D.C. 20590 e.lS~ i ..lz... CEU I . ASSIFICATION OF THIS PAGE’ REPORT DOCUMENTATION PAGE Ia. REPORT SECURITY CLASSIFICATION lb
What Role Does Sleep Play in Weight Gain in the First Semester of University?
Roane, BM; Seifer, R; Sharkey, KM; Van Reen, E; Bond, TLY; Raffray, T; Carskadon, MA
2016-01-01
Objectives We hypothesized that shorter sleep durations and greater variability in sleep patterns are associated with weight gain in the first semester of university. Methods Students (N=132) completed daily sleep diaries for 9-weeks, completed the MEQ (chronotype) and CES-D (depressed mood) at week9, and self-reported weight/height (weeks 1&9). Mean and variability scores were calculated for sleep duration (TST,TSTv), bedtime (BT,BTv), and wake time (WT,WTv). Results An initial hierarchical regression evaluated (block1) sex, ethnicity; (block2) depressed mood, chronotype; (block3) TST; (block4) BT, WT; and (block5; R2change=0.09, p=0.005) TSTv, BTv, WTv with weight change. A sex-by-TSTv interaction was found. A final model showed that ethnicity, TST, TSTv, and BTv accounted for 31% of the variance in weight change for males; TSTv was the most significant contributor (R2 change=0.21, p<0.001). Conclusions Daily variability in sleep duration contributes to males’ weight gain. Further investigation needs to examine sex-specific outcomes for sleep and weight. PMID:25115969
Strategic Offensive Airpower: The Role of the Long Range Bomber.
1988-04-01
Joint Flag Office-s’ Warfighting Corse. AvtiLi1ity fodes it- j Avail ana/or Dist Speial. 4,- 5 I - - - - - - -. F~’ .~ r d’-~rP .- -. % -’TABLE OF...philosophy. I . PROBLEM: The creation of a purely ccnventioral ong , which has significant combat power provide s an r .. r ........ !-T...tha. conflict places their homeland in Iimed1 tR convent_:n l danger. TI 0 u r -7N *4 LU F: . ’ dWk- r 4v A V 77No (Sedo)- I ’:00 Kastan. No d
Gannagé-Yared, Marie-Hélène; Chemali, Rana; Sfeir, Cynthia; Maalouf, Ghassan; Halaby, Georges
2005-07-01
Little is known about calcium and vitamin D intakes in Middle Eastern countries, where the prevalence of hypovitaminosis D is high. This study identifies major sources of calcium and vitamin D in the Lebanese diet, examines lifestyle factors that may influence intake of these nutrients and investigates the relationship between nutritional or lifestyle factors and parathyroid hormone (PTH). Three hundred sixteen young healthy volunteers aged 30 to 50 (men, non-veiled and veiled women) were recruited from different rural and urban Lebanese community centers. Food frequency questionnaire was used to evaluate the consumption of vitamin D and calcium-rich foods. We also measured serum PTH levels. Mean daily calcium and vitamin D intake were respectively 683.8 +/- 281.2 mg and 100.6 +/- 71.0 IU. Daily vitamin D sources were divided as follows: 30.4 +/- 46.4 IU from milk and dairy products, 28.2 +/- 26.3 IU from meat and poultry, 25.8 +/- 25 IU from fish, 8.5 +/- 8.6 IU from eggs, and 7.8 +/- 14.3 IU from sweets (respectively 30.2%, 28%, 25.6%, 8.4% and 7.7% of the total vitamin D intake). Mean daily calcium from animal and vegetable sources were respectively 376.3 +/- 233.6 mg and 307.9 +/- 118.5 mg. Animal/total calcium intake ratio was 52% and was only statistically significantly higher in urban people compared to rural ones. Multivariate analysis showed that male sex and urban residence were independent predictors of both vitamin D and calcium intakes (p < 0.01 and p < 0.01 respectively). In addition, veiling was an independent predictor of low vitamin D intake (p < 0.05) and a high body mass index (BMI) was an independent predictor of low calcium intake (p < 0.05). Finally, PTH was inversely correlated with vitamin D intake and the animal/total calcium intake ratio (r = -0.18 and r = -0.22, p < 0.01), while no significant results were achieved for the vegetable calcium. In a multivariate model, urban living, female gender, low vitamin D and calcium intakes, low animal/total calcium intake ratio, and high BMI, are independent predictors of hyperparathyroidism. The deficient nutritional status of vitamin D and calcium in Lebanon justify the implementation of dietary public health measures. People at most risk for secondary hyperparathyroidism should be advised to increase their dietary calcium (mostly animal calcium) and vitamin D, to take supplements, or to increase their sun exposure.
Torrisi, Sebastiano Alfio; Salomone, Salvatore; Geraci, Federica; Caraci, Filippo; Bucolo, Claudio; Drago, Filippo; Leggio, Gian Marco
2017-01-01
Background: Several efforts have been made to develop effective antipsychotic drugs. Currently, available antipsychotics are effective on positive symptoms, less on negative symptoms, but not on cognitive impairment, a clinically relevant dimension of schizophrenia. Drug repurposing offers great advantages over the long-lasting, risky and expensive, de novo drug discovery strategy. To our knowledge, the possible antipsychotic properties of buspirone, an azapirone anxiolytic drug marketed in 1986 as serotonin 5-HT1A receptor (5-HT1AR) partial agonist, have not been extensively investigated despite its intriguing pharmacodynamic profile, which includes dopamine D3 (D3R) and D4 receptor (D4R) antagonist activity. Multiple lines of evidence point to D3R as a valid therapeutic target for the treatment of several neuropsychiatric disorders including schizophrenia. In the present study, we tested the hypothesis that buspirone, behaving as dopamine D3R antagonist, may have antipsychotic-like activity. Materials and Methods: Effects of acute administration of buspirone was assessed on a wide-range of schizophrenia-relevant abnormalities induced by a single administration of the non-competitive NMDAR antagonist MK-801, in both wild-type mice (WT) and D3R-null mutant mice (D3R-/-). Results: Buspirone (3 mg⋅kg-1, i.p.) was devoid of cataleptogenic activity in itself, but resulted effective in counteracting disruption of prepulse inhibition (PPI), hyperlocomotion and deficit of temporal order recognition memory (TOR) induced by MK-801 (0.1 mg⋅kg-1, i.p.) in WT mice. Conversely, in D3R-/- mice, buspirone was ineffective in preventing MK-801-induced TOR deficit and it was only partially effective in blocking MK-801-stimulated hyperlocomotion. Conclusion: Taken together, these results indicate, for the first time, that buspirone, might be a potential therapeutic medication for the treatment of schizophrenia. In particular, buspirone, through its D3R antagonist activity, may be a useful tool for improving the treatment of cognitive deficits in schizophrenia that still represents an unmet need of this disease. PMID:29046641
Uehara, Shotaro; Ishii, Sakura; Uno, Yasuhiro; Inoue, Takashi; Sasaki, Erika; Yamazaki, Hiroshi
2017-08-01
A β -blocker, metoprolol, is one of the in vivo probes for human cytochrome P450 (P450) 2D6. Investigation of nonhuman primate P450 enzymes helps to improve the accuracy of the extrapolation of pharmacokinetic data from animals into humans. Common marmosets ( Callithrix jacchus ) are a potential primate model for preclinical research, but the detailed roles of marmoset P450 enzymes in metoprolol oxidation remain unknown. In this study, regio- and stereo-selectivity of metoprolol oxidations by a variety of P450 enzymes in marmoset and human livers were investigated in vitro. Although liver microsomes from cynomolgus monkeys and rats preferentially mediated S -metoprolol O -demethylation and R -metoprolol α -hydroxylation, respectively, those from humans, marmosets, minipigs, and dogs preferentially mediated R -metoprolol O -demethylation, in contrast to the slow rates of R - and S -metoprolol oxidation in mouse liver microsomes. R - and S -metoprolol O -demethylation activities in marmoset livers were strongly inhibited by quinidine and ketoconazole, and were significantly correlated with bufuralol 1'-hydroxylation and midazolam 1'-hydroxylation activities and also with P450 2D and 3A4 contents, which is different from the case in human livers that did not have any correlations with P450 3A-mediated midazolam 1'-hydroxylation. Recombinant human P450 2D6 enzyme and marmoset P450 2D6/3A4 enzymes effectively catalyzed R -metoprolol O -demethylation, comparable to the activities of human and marmoset liver microsomes, respectively. These results indicated that the major roles of P450 2D enzymes for the regio- and stereo-selectivity of metoprolol oxidation were similar between human and marmoset livers, but the minor roles of P450 3A enzymes were unique to marmosets. Copyright © 2017 by The American Society for Pharmacology and Experimental Therapeutics.
Test Results MM Stage 1, S/N 0012199
1988-10-01
D k LUULIJ " - en) L C -q -L LN - 0 2 LU O)iLf)0 L)U-LiU C) C: )u C r- ~ N 0 - ) $ CY)z zZ D O : lz bo1 LL J d ) C:, U (Do~ LL~o LL v L.O... D 4c b. 0 0 a 0 0 00 Q. 9 00e O , .4 Ok ;. -u - -q f- . P .4 t- j . P -W) c. U. .0 0 0 0 00 ’ O~ . ..... LL 0 0 0 00 0 0 0 0 9 ul . J .. . .++++ l z P...00I t0,00r4 0 0 0, 000 a % C " r C 4 0 ULLJ LAj It 0) 0 r-~uu 0’ o _C CV) .0cn L 0 - z~a u IS a: *I - D r Goraa -r b-LLL ZL - j uj w _L
Separation of Protactinium Employing Sulfur-Based Extraction Chromatographic Resins
Mastren, Tara; Stein, Benjamin W.; Parker, T. Gannon; ...
2018-05-14
Protactinium-230 (t 1/2 = 17.4 d) is the parent isotope of 230U (t 1/2 = 20.8 d), a radionuclide of interest for targeted alpha therapy (TAT). Column chromatographic methods have been developed to separate no-carrier-added 230Pa from proton irradiated thorium targets and accompanying fission products. Results reported within this paper demonstrate the use of novel sulfur bearing chromatographic extraction resins for the selective separation of protactinium. The recovery yield of 230Pa was 93 ± 4% employing a R 3P=S type commercially available resin and 88 ± 4% employing a DGTA (diglycothioamide) containing custom synthesized extraction chromatographic resin. The radiochemical puritymore » of the recovered 230Pa was measured via high purity germanium γ-ray spectroscopy to be >99.5% with the remaining radioactive contaminant being 95Nb due to its similar chemistry to protactinium. Finally, measured equilibrium distribution coefficients for protactinium, thorium, uranium, niobium, radium, and actinium on both the R 3P=S type and the DGTA resin in hydrochloric acid media are reported, to the best of our knowledge, for the first time.« less
Separation of Protactinium Employing Sulfur-Based Extraction Chromatographic Resins
DOE Office of Scientific and Technical Information (OSTI.GOV)
Mastren, Tara; Stein, Benjamin W.; Parker, T. Gannon
Protactinium-230 (t 1/2 = 17.4 d) is the parent isotope of 230U (t 1/2 = 20.8 d), a radionuclide of interest for targeted alpha therapy (TAT). Column chromatographic methods have been developed to separate no-carrier-added 230Pa from proton irradiated thorium targets and accompanying fission products. Results reported within this paper demonstrate the use of novel sulfur bearing chromatographic extraction resins for the selective separation of protactinium. The recovery yield of 230Pa was 93 ± 4% employing a R 3P=S type commercially available resin and 88 ± 4% employing a DGTA (diglycothioamide) containing custom synthesized extraction chromatographic resin. The radiochemical puritymore » of the recovered 230Pa was measured via high purity germanium γ-ray spectroscopy to be >99.5% with the remaining radioactive contaminant being 95Nb due to its similar chemistry to protactinium. Finally, measured equilibrium distribution coefficients for protactinium, thorium, uranium, niobium, radium, and actinium on both the R 3P=S type and the DGTA resin in hydrochloric acid media are reported, to the best of our knowledge, for the first time.« less
TacSat-4 COMMx, Advanced SATCOM Experiment
2009-01-01
Schein, M. T. Marley, C. T. Apland, R. E. Lee, B. D . Williams, E. D . Schaefer, S. R. Vernon, P . D . Schwartz , B. L. Kantsiper, E. J. Finnegan;The...Lee, B. D . Williams, E. D . Schaefer, P . D . Schwartz, R. Denissen, B. Kantsiper, E. J. Finnegan; The Johns Hopkins University Applied Physics...Mission Ops Lead, NRL Code 8233 Bob Kuzma, TacSat-4 Payload Controller, NRL Code 8242 Bob Skalitzky, TacSat-4 Power Systems, NRL Code 8244 Doug Bentz
Advanced GaAs Process Modeling. Volume 1
1988-05-01
c4p 0 nm cap r( l* . On u i- + t .] ONrci i Fag. I "a.t sirci trbtos 0 ke S SirecolI. S134 ap L4b N reo d ~trb. 10 ke SI oon$0 n3 ca "S lrancap 1... CA 94305 May 1989 Final Report For Period December 1985 - October 1988 Approved for public release; distribution is unlimited E 80 MATERIALS LABORATORY...llm nmE nmn A UNCLASSIFIED SECURITY CLASSIFICATION OF THIS PAGE Form Approved REPORT DOCUMENTATION PAGE OMB No. 0704018 10 . REPORT SECURITY
Shumay, E; Fowler, J S; Wang, G-J; Logan, J; Alia-Klein, N; Goldstein, R Z; Maloney, T; Wong, C; Volkow, N D
2012-01-01
Low dopamine D2 receptor (D2R) levels in the striatum are consistently reported in cocaine abusers; inter-individual variations in the degree of the decrease suggest a modulating effect of genetic makeup on vulnerability to addiction. The PER2 (Period 2) gene belongs to the clock genes family of circadian regulators; circadian oscillations of PER2 expression in the striatum was modulated by dopamine through D2Rs. Aberrant periodicity of PER2 contributes to the incidence and severity of various brain disorders, including drug addiction. Here we report a newly identified variable number tandem repeat (VNTR) polymorphism in the human PER2 gene (VNTR in the third intron). We found significant differences in the VNTR alleles prevalence across ethnic groups so that the major allele (4 repeats (4R)) is over-represented in non-African population (4R homozygosity is 88%), but not in African Americans (homozygosity 51%). We also detected a biased PER2 genotype distribution among healthy controls and cocaine-addicted individuals. In African Americans, the proportion of 4R/three repeat (3R) carriers in healthy controls is much lower than that in cocaine abusers (23% vs 39%, P=0.004), whereas among non-Africans most 3R/4R heterozygotes are healthy controls (10.5% vs 2.5%, P=0.04). Analysis of striatal D2R availability measured with positron emission tomography and [11C]raclopride revealed higher levels of D2R in carriers of 4R/4R genotype (P<0.01). Taken together, these results provide preliminary evidence for the role of the PER2 gene in regulating striatal D2R availability in the human brain and in vulnerability for cocaine addiction. PMID:22832851
Pati-Salam version of subcritical hybrid inflation
NASA Astrophysics Data System (ADS)
Bryant, B. Charles; Raby, Stuart
2016-05-01
In this paper we present a model of subcritical hybrid inflation with a Pati-Salam (PS) symmetry group. Both the inflaton and waterfall fields contribute to the necessary e -foldings of inflation, while only the waterfall field spontaneously breaks PS hence monopoles produced during inflation are diluted during the inflationary epoch. The model is able to produce a tensor-to-scalar ratio, r <0.09 consistent with the latest BICEP2/Keck and Planck data, as well as scalar density perturbations and spectral index, ns, consistent with Planck data. For particular values of the parameters, we find r =0.084 and ns=0.0963 . The energy density during inflation is directly related to the PS breaking scale, vPS. The model also incorporates a Z4R symmetry which can resolve the μ problem and suppress dimension 5 operators for proton decay, leaving over an exact R parity. Finally the model allows for a complete three-family extension with a D4 family symmetry which reproduces low energy precision electroweak and LHC data.
Enterprise Systems Value-Based R&D Portfolio Analytics: Methods, Processes, and Tools
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
Fire Safety Aspects of Polymeric Materials. Volume 1. Materials. State of the Art
1977-01-01
polymers (e.g. silk, collagen) has not been investigated ( Crawshaw et a!., 1973). 4.3 Synthetic Fibers The production of man-made fibers and natural...Thornton, A. M., Modern Plastics 43(2), 154 (1964). Coskren, R. J., SAMPE Quart., 4, No. 4, July (1973). Crawshaw , G. H., Delman, A. D., and Mehta, P
Redefining the properties of an osmotic agent in an intestinal-specific preservation solution
Schlachter, Kimberly; Kokotilo, Matthew S; Carter, Jodi; Thiesen, Aducio; Ochs, Angela; Khadaroo, Rachel G; Churchill, Thomas A
2010-01-01
AIM: To investigate the effects of dextrans of various molecular weights (Mw) during a 12 h cold storage time-course on energetics, histology and mucosal infiltration of fluorescein isothiocyanate (FITC)-dextran. METHODS: Rodent intestines were isolated and received a standard University of Wisconsin vascular flush followed by intraluminal administration of a nutrient-rich preservation solution containing dextrans of varying Mw: Group D1, 73 kdal; Group D2, 276 kdal; Group D3, 534 kdal; Group D4, 1185 kdal; Group D5, 2400 kdal. RESULTS: Using FITC-labeled dextrans, fluorescent micrographs demonstrated varying degrees of mucosal infiltration; lower Mw (groups D1-D3: 73-534 kdal) dextrans penetrated the mucosa as early as 2 h, whereas the largest dextran (D5: 2400 kdal) remained captive within the lumen and exhibited no permeability even after 12 h. After 12 h, median injury grades ranged from 6.5 to 7.5 in groups D1-D4 (73-1185 kdal) representing injury of the regenerative cryptal regions and submucosa; this was in contrast to group D5 (2400 kdal) which exhibited villus denudation (with intact crypts) corresponding to a median injury grade of 4 (P < 0.05). Analysis of tissue energetics reflected a strong positive correlation between Mw and adenosine triphosphate (r2 = 0.809), total adenylates (r2 = 0.865) and energy charge (r2 = 0.667). CONCLUSION: Our data indicate that dextrans of Mw > 2400 kdal act as true impermeant agents during 12 h ischemic storage when incorporated into an intraluminal preservation solution. PMID:21128319
1979-01-01
web " AL ***atfa IL X a 42 U 4j ft ut C IC a % % alms j we__w Z A CA 00- ’co 49 a. j -D Lbl ŘV (qw IA. .4L i ) ’IV Lhw . 94 U CD1 ca C. 1 1 .4 I~l...4C E: qw C Zw (1 - - 1U -7 -: - *t -r z~ -: do’.’.. ~ V.(O (11U * III ,~ * SS~ ŗ filU. * zu lc )0( Lid 014- CA__ G -4 0 I ~ IA L4,A t WIx W U V4 soft
Digit ratio (2D:4D) and male facial attractiveness: new data and a meta-analysis.
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.
2004-11-01
s s a c h u s e t t s i n s t ...i t u t e o f t e c h n o l o g y, c a m b r i d g e , m a 0 2 1 3 9 u s a — w w w . c s a i l . m i t . e d u m a ss a c h u se t t s i n...st i t u t e o f t e c h n o l o g y — co m p u t e r sc i e n ce a n d a r t i f ic ia l i n t e l l ig e n ce l a b o ra t o r y
Consequences of ChemR23 Heteromerization with the Chemokine Receptors CXCR4 and CCR7
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.
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.
MicroRNA-214 Suppresses Gluconeogenesis by Targeting Activating Transcriptional Factor 4*
Li, Kai; Zhang, Jin; Yu, Junjie; Liu, Bin; Guo, Yajie; Deng, Jiali; Chen, Shanghai; Wang, Chunxia; Guo, Feifan
2015-01-01
Although the gluconeogenesis pathway is already a target for the treatment of type 2 diabetes, the potential role of microRNAs (miRNAs) in gluconeogenesis remains unclear. Here, we investigated the physiological functions of miR-214 in gluconeogenesis. The expression of miR-214 was suppressed by glucagon via protein kinase A signaling in primary hepatocytes, and miR-214 was down-regulated in the livers of fasted, high fat diet-induced diabetic and leptin receptor-mutated (db/db) mice. The overexpression of miR-214 in primary hepatocytes suppressed glucose production, and silencing miR-214 reversed this effect. Gluconeogenesis was suppressed in the livers of mice injected with an adenovirus expressing miR-214 (Ad-miR-214). Additionally, Ad-miR-214 alleviated high fat diet-induced elevation of gluconeogenesis and hyperglycemia. Furthermore, we found that activating transcription factor 4 (ATF4), a reported target of miR-214, can reverse the suppressive effect of miR-214 on gluconeogenesis in primary hepatocytes, and this suppressive effect was blocked in liver-specific ATF4 knock-out mice. ATF4 regulated gluconeogenesis via affecting forkhead box protein O1 (FOXO1) transcriptional activity. Finally, liver-specific miR-214 transgenic mice exhibited suppressed gluconeogenesis and reduced expression of ATF4, phosphoenolpyruvate carboxykinase, and glucose-6-phosphatase in liver. Taken together, our results suggest that the miR-214-ATF4 axis is a novel pathway for the regulation of hepatic gluconeogenesis. PMID:25657009
Steroidal saponins from Tribulus terrestris.
Kang, Li-Ping; Wu, Ke-Lei; Yu, He-Shui; Pang, Xu; Liu, Jie; Han, Li-Feng; Zhang, Jie; Zhao, Yang; Xiong, Cheng-Qi; Song, Xin-Bo; Liu, Chao; Cong, Yu-Wen; Ma, Bai-Ping
2014-11-01
Sixteen steroidal saponins, including seven previously unreported compounds, were isolated from Tribulus terrestris. The structures of the saponins were established using 1D and 2D NMR spectroscopy, mass spectrometry, and chemical methods. They were identified as: 26-O-β-d-glucopyranosyl-(25R)-furost-4-en-2α,3β,22α,26-tetrol-12-one (terrestrinin C), 26-O-β-d-glucopyranosyl-(25R)-furost-4-en-22α,26-diol-3,12-dione (terrestrinin D), 26-O-β-d-glucopyranosyl-(25S)-furost-4-en-22α,26-diol-3,6,12-trione (terrestrinin E), 26-O-β-d-glucopyranosyl-(25R)-5α-furostan-3β,22α,26-triol-12-one (terrestrinin F), 26-O-β-d-glucopyranosyl-(25R)-furost-4-en-12β,22α,26-triol-3-one (terrestrinin G), 26-O-β-d-glucopyranosyl-(1→6)-β-d-glucopyranosyl-(25R)-furost-4-en-22α,26-diol-3,12-dione (terrestrinin H), and 24-O-β-d-glucopyranosyl-(25S)-5α-spirostan-3β,24β-diol-12-one-3-O-β-d-glucopyranosyl-(1→4)-β-d-galactopyranoside (terrestrinin I). The isolated compounds were evaluated for their platelet aggregation activities. Three of the known saponins exhibited strong effects on the induction of platelet aggregation. Copyright © 2014 Elsevier Ltd. All rights reserved.
Wang, Shuangshuang; Ren, Huanhuan; Jiang, Wenbo; Chen, Honglin; Hu, Hongxing; Chen, Zhiwei
2017-01-01
ABSTRACT Recent studies have shown that Fc-Fcγ receptor (FcγR) interactions are required for in vivo protection against influenza viruses by broadly reactive anti-hemagglutinin (HA) stem, but not virus strain-specific, anti-receptor binding site (RBS), antibodies (Abs). Since only a few Abs recognizing epitopes in the head region but outside the RBS have been tested against single-challenge virus strains, it remains unknown whether Fc-FcγR interactions are required for in vivo protection by Abs recognizing epitopes outside the RBS and whether the requirement is virus strain specific or epitope specific. In the present study, we therefore investigated the requirements for in vivo protection using two pan-H5 Abs, 65C6 and 100F4. We generated chimeric Abs, 65C6/IgG2a and 100F4/IgG2a, which preferentially engage activating FcγRs, and isogenic forms, 65C6/D265A and 100F4/D265A, which do not bind FcγR. Virus neutralizing activity, binding, antibody-dependent cellular cytotoxicity (ADCC), and in vivo protection of these Abs were compared using three H5 strains, A/Shenzhen/406H/2006 (SZ06), A/chicken/Shanxi/2/2006 (SX06), and A/chicken/Netherlands/14015526/2014 (NE14). We found that all four chimeric Abs bound and neutralized the SZ06 and NE14 strains but poorly inhibited the SX06 strain. 65C6/IgG2a and 100F4/IgG2a, but not 65C6/D265A and 100F4/D265A, mediated ADCC against target cells expressing HA derived from all three virus strains. Interestingly, both 65C6/IgG2a and 65C6/D265A demonstrated comparable protection against all three virus strains in vivo; however, 100F4/IgG2a, but not 100F4/D265A, showed in vivo protection. Thus, we conclude that Fc-FcγR interactions are required for in vivo protection by 100F4, but not by 65C6, and therefore, protection is not virus strain specific but epitope specific. IMPORTANCE Abs play an important role in immune protection against influenza virus infection. Fc-FcγR interactions are required for in vivo protection by broadly neutralizing antistem, but not by virus strain-specific, anti-receptor binding site (RBS), Abs. Whether such interactions are necessary for protection by Abs that recognize epitopes outside RBS is not fully understood. In the present study, we investigated in vivo protection mechanisms against three H5 strains by two pan-H5 Abs, 65C6 and 100F4. We show that although these two Abs have similar neutralizing, binding, and ADCC activities against all three H5 strains in vitro, they have divergent requirements for Fc-FcγR interactions to protect against the three H5 strains in vivo. The Fc-FcγR interactions are required for in vivo protection by 100F4, but not by 65C6. Thus, we conclude that Fc-FcγR interactions for in vivo protection by pan-H5 Abs is not strain specific, but epitope specific. PMID:28331095
Wang, Shuangshuang; Ren, Huanhuan; Jiang, Wenbo; Chen, Honglin; Hu, Hongxing; Chen, Zhiwei; Zhou, Paul
2017-06-01
Recent studies have shown that Fc-Fcγ receptor (FcγR) interactions are required for in vivo protection against influenza viruses by broadly reactive anti-hemagglutinin (HA) stem, but not virus strain-specific, anti-receptor binding site (RBS), antibodies (Abs). Since only a few Abs recognizing epitopes in the head region but outside the RBS have been tested against single-challenge virus strains, it remains unknown whether Fc-FcγR interactions are required for in vivo protection by Abs recognizing epitopes outside the RBS and whether the requirement is virus strain specific or epitope specific. In the present study, we therefore investigated the requirements for in vivo protection using two pan-H5 Abs, 65C6 and 100F4. We generated chimeric Abs, 65C6/IgG2a and 100F4/IgG2a, which preferentially engage activating FcγRs, and isogenic forms, 65C6/D265A and 100F4/D265A, which do not bind FcγR. Virus neutralizing activity, binding, antibody-dependent cellular cytotoxicity (ADCC), and in vivo protection of these Abs were compared using three H5 strains, A/Shenzhen/406H/2006 (SZ06), A/chicken/Shanxi/2/2006 (SX06), and A/chicken/Netherlands/14015526/2014 (NE14). We found that all four chimeric Abs bound and neutralized the SZ06 and NE14 strains but poorly inhibited the SX06 strain. 65C6/IgG2a and 100F4/IgG2a, but not 65C6/D265A and 100F4/D265A, mediated ADCC against target cells expressing HA derived from all three virus strains. Interestingly, both 65C6/IgG2a and 65C6/D265A demonstrated comparable protection against all three virus strains in vivo ; however, 100F4/IgG2a, but not 100F4/D265A, showed in vivo protection. Thus, we conclude that Fc-FcγR interactions are required for in vivo protection by 100F4, but not by 65C6, and therefore, protection is not virus strain specific but epitope specific. IMPORTANCE Abs play an important role in immune protection against influenza virus infection. Fc-FcγR interactions are required for in vivo protection by broadly neutralizing antistem, but not by virus strain-specific, anti-receptor binding site (RBS), Abs. Whether such interactions are necessary for protection by Abs that recognize epitopes outside RBS is not fully understood. In the present study, we investigated in vivo protection mechanisms against three H5 strains by two pan-H5 Abs, 65C6 and 100F4. We show that although these two Abs have similar neutralizing, binding, and ADCC activities against all three H5 strains in vitro , they have divergent requirements for Fc-FcγR interactions to protect against the three H5 strains in vivo The Fc-FcγR interactions are required for in vivo protection by 100F4, but not by 65C6. Thus, we conclude that Fc-FcγR interactions for in vivo protection by pan-H5 Abs is not strain specific, but epitope specific. Copyright © 2017 American Society for Microbiology.
1987-01-01
0-4 .4n~(D r-4.4.4.--00-4N -4O4N4N Q 103 (n 0 l 0 I I toN (n oC 00 0 000000c000 o 0000 00 4i 0000000000000000000000000 00000000 -0 1I00007mo 00...Ij 0 0 00 0000 0 o 7Ŕ CA 00O Io L) ’- I- 4n (oWI W rh - 4 -4 - "oi Io DO Io .- D 01 4NCA 00 01 n0) 0) 0) z0 NI -4 coo N I3 OO I y)W( -4 -0 -4 4 4 0 0...4 00 00 C’) C) 0D 0-4 000 In 0 0 0- 00030 00000 蓐 M40) 1 Co W- Inco COW(D’ CO I CIDr CO r-Cr--- 0 pC-- pD (-pW r--r.-ow0 -4) ow ow 0000 COCOCO
MiR-137 inhibited inflammatory response and apoptosis after spinal cord injury via targeting of MK2.
Gao, Lin; Dai, Chenfei; Feng, Zhiping; Zhang, Lixin; Zhang, Zhiqiang
2018-04-01
Spinal cord injuries are common and troublesome disorder, which is mediated by various signal pathways and mechanisms. MK2 is also involved in numerous inflammatory diseases including spinal cord injury. The role of microRNA-137 (miR-137) and its detailed working mechanism in spinal cord injuries remain unclear. In the present study, we found that an elevated MK2 but a decreased miR-137 was expressed in serum specimens of patients with spinal cord injury and in hydrogen peroxide-treated C8-D1A and C8-B4 cells. Meanwhile, we suggested that upregulation of miR-137 could inhibit the expression of TNF-α and IL-6, two markers of inflammatory response after SCI, and apoptosis in hydrogen peroxide-treated C8-D1A and C8-B4 cells. Furthermore, we verified that MK2 was a direct target of miR-137 thorough a constructed luciferase assay. Even further, we elucidated that miR-137 could suppress the inflammatory response and apoptosis via negative regulation of MK2. Finally, through an animal model trial performed using mice, we demonstrated the protective effect of how miR-137 works on inflammatory response and apoptosis after spinal cord injury. Considering all the forementioned, our findings revealed that miR-137 inhibited inflammatory response and apoptosis after spinal cord injury via the targeting of MK2. The outcomes of the present study might indicate a new target in molecular treatment of SCI. © 2017 Wiley Periodicals, Inc.
Recharge Data for the Islands of Kauai, Lanai and Molokai, Hawaii
Nicole Lautze
2015-01-01
Recharge data for the islands of Kauai, Lanai and Molokai in shapefile format. These data are from the following sources: Whittier, R.B and A.I. El-Kadi. 2014. Human Health and Environmental Risk Ranking of On-Site Sewage Disposal systems for the Hawaiian Islands of Kauai, Molokai, Maui, and Hawaii – Final, Prepared for Hawaii Dept. of Health, Safe Drinking Water Branch by the University of Hawaii, Dept. of Geology and Geophysics. (for Kauai, Lanai, Molokai). Shade, P.J., 1995, Water Budget for the Island of Kauai, Hawaii, USGS Water-Resources Investigations Report 95-4128, 25 p. (for Kauai). Izuka, S.K. and D.S. Oki, 2002 Numerical simulation of ground-water withdrawals in the Southern Lihue Basin, Kauai, Hawaii, U.S. Geologic Survey Water-Resources Investigations Report 01-4200, 52 pgs. (for Kauai). Hardy, W.R., 1996, A Numerical Groundwater Model for the Island of Lanai, Hawaii - CWRM Report No., CWRM-1, Commission on Water Resources Management, Department of Natural Resources, State of Hawaii, Honolulu, HI. (for Lanai). Oki, D.S., 1997, Geohydrology and numerical Simulation of the Ground-Water Flow System of Molokai, Hawaii, USGS Water-Resources Investigations Report 97-4176, 62 p. (for Molokai).
Demura, S; Sato, S; Kitabayashi, T
2006-06-01
This study examined a method of predicting body density based on hydrostatic weighing without head submersion (HWwithoutHS). Donnelly and Sintek (1984) developed a method to predict body density based on hydrostatic weight without head submersion. This method predicts the difference (D) between HWwithoutHS and hydrostatic weight with head submersion (HWwithHS) from anthropometric variables (head length and head width), and then calculates body density using D as a correction factor. We developed several prediction equations to estimate D based on head anthropometry and differences between the sexes, and compared their prediction accuracy with Donnelly and Sintek's equation. Thirty-two males and 32 females aged 17-26 years participated in the study. Multiple linear regression analysis was performed to obtain the prediction equations, and the systematic errors of their predictions were assessed by Bland-Altman plots. The best prediction equations obtained were: Males: D(g) = -164.12X1 - 125.81X2 - 111.03X3 + 100.66X4 + 6488.63, where X1 = head length (cm), X2 = head circumference (cm), X3 = head breadth (cm), X4 = head thickness (cm) (R = 0.858, R2 = 0.737, adjusted R2 = 0.687, standard error of the estimate = 224.1); Females: D(g) = -156.03X1 - 14.03X2 - 38.45X3 - 8.87X4 + 7852.45, where X1 = head circumference (cm), X2 = body mass (g), X3 = head length (cm), X4 = height (cm) (R = 0.913, R2 = 0.833, adjusted R2 = 0.808, standard error of the estimate = 137.7). The effective predictors in these prediction equations differed from those of Donnelly and Sintek's equation, and head circumference and head length were included in both equations. The prediction accuracy was improved by statistically selecting effective predictors. Since we did not assess cross-validity, the equations cannot be used to generalize to other populations, and further investigation is required.
Neves, Patrícia C C; Rudersdorf, Richard A; Galler, Ricardo; Bonaldo, Myrna C; de Santana, Marlon Gilsepp Veloso; Mudd, Philip A; Martins, Maurício A; Rakasz, Eva G; Wilson, Nancy A; Watkins, David I
2010-11-29
The yellow fever 17D (YF-17D) vaccine is one of the most efficacious vaccines developed to date. Interestingly, vaccination with YF-17D induces IFN-γ production early after vaccination (days 5-7) before the development of classical antigen-specific CD8(+) and CD4(+) T cell responses. Here we investigated the cellular source of this early IFN-γ production. At days 5 and 7 post-vaccination activated CD8(+) gamma-delta TCR T cells produced IFN-γ and TNF-α. Activated CD4(+) T cells produced IFN-γ and TNF-α at day 7 post-vaccination. This early IFN-γ production was also induced after vaccination with recombinant YF-17D (rYF-17D), but was not observed after recombinant Adenovirus type 5 (rAd5) vaccination. Early IFN-γ production, therefore, might be an important aspect of yellow fever vaccination. Copyright © 2010 Elsevier Ltd. All rights reserved.
Nava, Phillip; Cecchini, Matt; Chirico, Sara; Gordon, Heather; Morley, Samantha; Manor, Danny; Atkinson, Jeffrey
2006-06-01
Sixteen fluorescent analogues of the lipid-soluble antioxidant vitamin alpha-tocopherol were prepared incorporating fluorophores at the terminus of omega-functionalized 2-n-alkyl-substituted chromanols (1a-d and 4a-d) that match the methylation pattern of alpha-tocopherol, the most biologically active form of vitamin E. The fluorophores used include 9-anthroyloxy (AO), 7-nitrobenz-2-oxa-1,3-diazole (NBD), N-methyl anthranilamide (NMA), and dansyl (DAN). The compounds were designed to function as fluorescent reporter ligands for protein-binding and lipid transfer assays. The fluorophores were chosen to maximize the fluorescence changes observed upon moving from an aqueous environment (low fluorescence intensity) to an hydrophobic environment such as a protein's binding site (high fluorescence intensity). Compounds 9d (anthroyloxy) and 10d (nitrobenzoxadiazole), having a C9-carbon chain between the chromanol and the fluorophore, were shown to bind specifically and reversibly to recombinant human tocopherol transfer protein (alpha-TTP) with dissociation constants of approximately 280 and 60 nM, respectively, as compared to 25 nM for the natural ligand 2R,4'R,8'R-alpha-tocopherol. Thus, compounds have been prepared that allow the investigation of the rate of alpha-TTP-mediated inter-membrane transfer of alpha-tocopherol and to investigate the mechanism of alpha-TTP function at membranes of different composition.
CH4 AND N2O FLUXES IN THE COLORADO SHORTGRASS STEPPE: LONG-TERM IMPACT OF LAND USE CHANGE. (R824993)
The perspectives, information and conclusions conveyed in research project abstracts, progress reports, final reports, journal abstracts and journal publications convey the viewpoints of the principal investigator and may not represent the views and policies of ORD and EPA. Concl...
The perspectives, information and conclusions conveyed in research project abstracts, progress reports, final reports, journal abstracts and journal publications convey the viewpoints of the principal investigator and may not represent the views and policies of ORD and EPA. Concl...
THE PUTATIVE HIGH ACTIVITY VARIANT CYP3A4*1B PREDICTS THE ONSET OF PUBERTY IN YOUNG GIRLS. (R825816)
The perspectives, information and conclusions conveyed in research project abstracts, progress reports, final reports, journal abstracts and journal publications convey the viewpoints of the principal investigator and may not represent the views and policies of ORD and EPA. Concl...
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
3 d printing of 2 d N=(0,2) gauge theories
NASA Astrophysics Data System (ADS)
Franco, Sebastián; Hasan, Azeem
2018-05-01
We introduce 3 d printing, a new algorithm for generating 2 d N=(0,2) gauge theories on D1-branes probing singular toric Calabi-Yau 4-folds using 4 d N=1 gauge theories on D3-branes probing toric Calabi-Yau 3-folds as starting points. Equivalently, this method produces brane brick models starting from brane tilings. 3 d printing represents a significant improvement with respect to previously available tools, allowing a straightforward determination of gauge theories for geometries that until now could only be tackled using partial resolution. We investigate the interplay between triality, an IR equivalence between different 2 d N=(0,2) gauge theories, and the freedom in 3 d printing given an underlying Calabi-Yau 4-fold. Finally, we present the first discussion of the consistency and reduction of brane brick models.
NASA Astrophysics Data System (ADS)
Aoyama, Shigeyoshi
2013-04-01
The study of the 4He nucleus is important because it is the most basic sub-unit (cluster) in nuclei. We have investigated the structures and the reaction mechanisms in 4He by using the correlated Gaussian basis function with the global vector representation. In order to treat the boundary condition for the ab-initio calculation of the four nucleons, we employ the Microscopic R-matrix Method (MRM) and the Complex Scaling Method (CSM) . Elastic-scattering phase shifts for four-nucleon systems are studied in an ab-initio type cluster model with MRM in order to clarify the role of the tensor force and to investigate cluster distortions in low energy d+d and t+p scattering. For 1S0, the calculated phase shifts show that the t+p and h+n channels are strongly coupled to the d+d channel for the case of the realistic interaction.
Lin, Kuo-Shyan; Ding, Yu-Shin; Kim, Sung-Won; Kil, Kun-Eek
2005-05-01
Racemic and enantiomerically pure ((S,S) and (R,R)) 2-[alpha-(2-(2-[(18)F]fluoroethoxy)phenoxy)benzyl]morpholine ([(18)F]FRB) and its tetradeuterated form [(18)F]FRB-D(4), analogs of the highly selective norepinephrine reuptake inhibitor reboxetine (2-[alpha-(2-ethoxyphenoxy)benzyl]morpholine, RB), have been synthesized for studies of norepinephrine transporter (NET) system with positron emission tomography (PET). The [(18)F]fluorinated precursor, (S,S)/(R,R)-N-tert-butyloxycarbonyl-2-[alpha-(2-hydroxyphenoxy)benzyl]morpholine ((S,S)/(R,R)-N-Boc-desethylRB), was prepared by the N-protection of (S,S)/(R,R)-2-[alpha-(2-hydroxyphenoxy)benzyl]morpholine ((S,S)/(R,R)-desethylRB) with a tert-butyloxycarbonyl (Boc) group followed by enantiomeric resolution with chiral HPLC to provide both (S,S) and (R,R) enantiomers with >99% enantiomeric purity. These compounds were then used for radiosynthesis to prepare enantiomerically pure [(18)F]FRB and [(18)F]FRB-D(4) via the following three-step procedure: (1) formation of 1-bromo-2-[(18)F]fluoroethane ([(18)F]BFE or [(18)F]BFE-D(4)) by nucleophilic displacement of 2-bromoethyl triflate (or D(4) analog) with no-carrier added [(18)F]F(-) in THF; (2) reaction of [(18)F]BFE (or [(18)F]BFE-D(4)) with N-Boc-desethylRB in DMF in the presence of excess base; and (3) deprotection with trifluoroacetic acid. The racemates, (S,S) and (R,R) enantiomers of [(18)F]FRB and [(18)F]FRB-D(4) were obtained in 11-27% (decay corrected to the end of bombardment, EOB) in 120-min synthesis time with a radiochemical purity of >98% and specific activities of 21-48 GBq/micromol (EOB). The results of the whole-body biodistribution studies with (S,S)-[(18)F]FRB-D(4) were similar to those with (S,S)-[(18)F]FRB but showed relatively faster blood clearance and no significant in vivo defluorination. Positron emission tomography studies in baboon brain also showed that (S,S)-[(18)F]FRB-D(4) may be a potentially useful ligand for imaging NET with PET.
Celver, Jeremy; Sharma, Meenakshi; Thanawala, Vaidehi; Octeau, J. Christopher; Kovoor, Abraham
2016-01-01
We reconstituted D2 like dopamine receptor (D2R) and the delta opioid receptor (DOR) coupling to G-protein gated inwardly rectifying potassium channels (Kir3) and directly compared the effects of co-expression of G-protein coupled receptor kinase (GRK) and arrestin on agonist-dependent desensitization of the receptor response. We found, as described previously, that co-expression of a GRK and an arrestin synergistically increased the rate of agonist-dependent desensitization of DOR. In contrast, only arrestin expression was required to produce desensitization of D2R responses. Furthermore, arrestin-dependent GRK-independent desensitization of D2R-Kir3 coupling could be transferred to DOR by substituting the third cytoplasmic loop of DOR with that of D2R. The arrestin-dependent GRK-independent desensitization of D2R desensitization was inhibited by staurosporine treatment, and blocked by alanine substitution of putative protein kinase C phosphorylation sites in the third cytoplasmic loop of D2R. Finally, the D2R construct in which putative protein kinase C phosphorylation sites were mutated did not undergo significant agonist-dependent desensitization even after GRK co-expression, suggesting that GRK phosphorylation of D2R does not play an important role in uncoupling of the receptor. PMID:23815307
Celver, Jeremy; Sharma, Meenakshi; Thanawala, Vaidehi; Christopher Octeau, J; Kovoor, Abraham
2013-10-01
We reconstituted D2 like dopamine receptor (D2R) and the delta opioid receptor (DOR) coupling to G-protein gated inwardly rectifying potassium channels (K(ir)3) and directly compared the effects of co-expression of G-protein coupled receptor kinase (GRK) and arrestin on agonist-dependent desensitization of the receptor response. We found, as described previously, that co-expression of a GRK and an arrestin synergistically increased the rate of agonist-dependent desensitization of DOR. In contrast, only arrestin expression was required to produce desensitization of D2R responses. Furthermore, arrestin-dependent GRK-independent desensitization of D2R-K(ir)3 coupling could be transferred to DOR by substituting the third cytoplasmic loop of DOR with that of D2R. The arrestin-dependent GRK-independent desensitization of D2R desensitization was inhibited by staurosporine treatment, and blocked by alanine substitution of putative protein kinase C phosphorylation sites in the third cytoplasmic loop of D2R. Finally, the D2R construct in which putative protein kinase C phosphorylation sites were mutated did not undergo significant agonist-dependent desensitization even after GRK co-expression, suggesting that GRK phosphorylation of D2R does not play an important role in uncoupling of the receptor. © 2013 International Society for Neurochemistry.
Ololade, Isaac A; Alomaja, Folasade; Oladoja, Nurudeen A; Ololade, Oluwaranti O; Oloye, Femi F
2015-01-01
2,4-dichlorophenoxyl acetic acid (2,4-D, pKa = 2.8) is used extensively as a herbicide in agricultural practices. Its sorption behavior on both untreated and soils treated to significantly remove specific components (organic and iron and manganese [Fe-Mn] oxides and hydroxides phases) was investigated under oxic and anoxic conditions. The chemical and structural heterogeneity of the soil components were characterized by elemental analysis and X-ray diffraction (XRD). The coexistence of the various components seems to either mask sorption sites on the untreated soil surfaces or inhibit interlayer diffusion of 2,4-D. All sorption data conform to the Freundlich description and a pseudo-second-order kinetic model. There was a strong positive correlation between sorption capacity K(d), and surface area (r(2) ≤ 0.704), but a negative correlation was uncovered with both pH and organic carbon (r(2) ≤ -0.860). The results indicate that 2,4-D is preferably sorbed under oxic rather than anoxic conditions and it is greater on soils containing a high Fe content. There was incomplete 2,4-D sorption reversibility, with desorption occurring more rapidly under anoxic conditions. The study suggests that stimulation of Fe III reduction could be used for the bioremediation of a 2,4-D-contaminated site.
Carniglia, Lila; Durand, Daniela; Caruso, Carla; Lasaga, Mercedes
2013-01-01
Brain inflammation plays a central role in numerous brain pathologies. Microglia and astrocytes are the main effector cells that become activated when an inflammatory process takes place within the central nervous system. α-melanocyte-stimulating hormone (α-MSH) is a neuropeptide with proven anti-inflammatory properties. It binds with highest affinity to the melanocortin receptor 4 (MC4R), which is present in astrocytes and upon activation triggers anti-inflammatory pathways. The aim of this research was to identify anti-inflammatory mediators that may participate in the immunomodulatory effects of melanocortins in glial cells. Since peroxisome proliferator-activated receptors (PPARs) have recently been implicated in the modulation of inflammation, we investigated the effect of an α-MSH analog, [Nle4, D-Phe7]-α-MSH (NDP-α-MSH), on PPAR-β and PPAR-γ gene and protein expression in rat primary astrocytes and microglia. We initially demonstrated that rat primary microglia express MC4R and showed that treatment with NDP-α-MSH increases PPAR-γ protein levels and strongly decreases PPAR-β levels in both astrocytes and microglia. We also showed that extracellular signal-regulated kinase 1/2 (ERK1/2)–mediated signaling is partially involved in these effects in a cell-specific fashion. Finally, we showed that NDP-α-MSH stimulates the release of the anti-inflammatory cytokines IL-10 and TGF-β from microglia and astrocytes, respectively. The presented data suggest a role for IL-10 and TGF-β in the protective action of melanocortins and a connection between MC4R pathway and that of the nuclear receptor PPAR-γ. This is the first report providing evidence that MC4R is expressed in rat primary microglia and that melanocortins modulate PPAR levels in glial cells. Our findings provide new insights into the mechanisms underlying the activation of glial MC4R and open perspectives for new therapeutic strategies for the treatment of inflammation-mediated brain diseases. PMID:23468969
Disposal and Reuse of England Air Force Base, Louisiana, Final Environmental Impact Statement.
1992-11-01
norvegicus), house mouse ( Mus musculus ), and raccoon (Procyon lotor). Raptors observed foraging in the grassy areas include the red-tailed hawk...m CC cZ 2jCL W u~.0 U)< ( 0 C) (n CD 0.. Cc < .C - OEr-L C o_ p 0Cc 0 m r0 C C0 D- ~ 0 0000 E c r c< MU Lw -Z0W0 6i0( .0~ 00 CO cCV 0 2 < N...Proposed Action, By Phase ....................... 2-11 2.2-4 Projected Flight Operations - Proposed Action .......................... 2-12 2.2-5 Reuse
Dopamine D2-Like Receptors and Behavioral Economics of Food Reinforcement
Soto, Paul L; Hiranita, Takato; Xu, Ming; Hursh, Steven R; Grandy, David K; Katz, Jonathan L
2016-01-01
Previous studies suggest dopamine (DA) D2-like receptor involvement in the reinforcing effects of food. To determine contributions of the three D2-like receptor subtypes, knockout (KO) mice completely lacking DA D2, D3, or D4 receptors (D2R, D3R, or D4R KO mice) and their wild-type (WT) littermates were exposed to a series of fixed-ratio (FR) food-reinforcement schedules in two contexts: an open economy with additional food provided outside the experimental setting and a closed economy with all food earned within the experimental setting. A behavioral economic model was used to quantify reinforcer effectiveness with food pellets obtained as a function of price (FR schedule value) plotted to assess elasticity of demand. Under both economies, as price increased, food pellets obtained decreased more rapidly (ie, food demand was more elastic) in DA D2R KO mice compared with WT littermates. Extinction of responding was studied in two contexts: by eliminating food deliveries and by delivering food independently of responding. A hyperbolic model quantified rates of extinction. Extinction in DA D2R KO mice occurred less rapidly compared with WT mice in both contexts. Elasticity of food demand was higher in DA D4R KO than WT mice in the open, but not closed, economy. Extinction of responding in DA D4R KO mice was not different from that in WT littermates in either context. No differences in elasticity of food demand or extinction rate were obtained in D3R KO mice and WT littermates. These results indicate that the D2R is the primary DA D2-like receptor subtype mediating the reinforcing effectiveness of food. PMID:26205210
Search for b\\to u Transitions in \\Bz \\to \\Dz \\Kstarz Decays
DOE Office of Scientific and Technical Information (OSTI.GOV)
Aubert, B.; Bona, M.; Karyotakis, Y.
We present a study of the decays B{sup 0} {yields} D{sup 0} K*{sup 0} and B{sup 0} {yields} {bar D}{sup 0} K*{sup 0} with K*{sup 0} {yields} K{sup +}{pi}{sup -}. The D{sup 0} and the {bar D}{sup 0} mesons are reconstructed in the final states f = K{sup +} {pi}{sup -}, K{sup +}{pi}{sup -}{pi}{sup 0}, K{sup +}{pi}{sup -}{pi}{sup +}{pi}{sup -} and their charge conjugates. Using a sample of 465 million B{bar B} pairs collected with the BABAR detector at PEP-II asymmetric-energy e{sup +}e{sup -} collider at SLAC, we measure the ratio R{sub ADS} {triple_bond} [{Lambda}({bar B}{sup 0} {yields} [f]{sub D}{barmore » K}*{sup 0}) + {Lambda}(B{sup 0} {yields} [{bar f}]{sub D}K*{sup 0})]/[{Lambda}({bar B}{sup 0} {yields} [{bar f}]{sub D}{bar K}*{sup 0}) + {Lambda}(B{sup 0} {yields} [f]{sub D}K*{sup 0})] for the three final states. We do not find significant evidence for a signal and set the following limits at 95% probability: R{sub ADS}(K{pi}) < 0.244, R{sub ADS}(K{pi}{pi}{sup 0}) < 0.181 and R{sub ADS}(K{pi}{pi}{pi}) < 0.391. From the combination of these three results, we find that the ratio r{sub S} between the b {yields} u and the b {yields} c amplitudes lies in the range [0.07; 0.41] at 95% probability.« less
2011-04-01
1-9. R esources N ot C arried Forw ard for D etailed A nalysis Legend Environmental Justice Concerns c:::J Proposed Project Area No Concerns...11 FEF/FIF C onstruction Environm ental A ssessm ent Page 3-6 Eglin A ir Force B ase, FL Final Figure 3-1. W ater R esources A t or N...Ecological A ssociations and Biological R esources A t or N ear the Proposed A ction Location Ecological Association Flatwoods Landscaped!Urban c:J
NASA Astrophysics Data System (ADS)
Andonov, Zdravko
This R&D represent innovative multidimensional 6D-N(6n)D Space-Time (S-T) Methodology, 6D-6nD Coordinate Systems, 6D Equations, new 6D strategy and technology for development of Planetary Space Sciences, S-T Data Management and S-T Computational To-mography. . . The Methodology is actual for brain new RS Microwaves' Satellites and Compu-tational Tomography Systems development, aimed to defense sustainable Earth, Moon, & Sun System evolution. Especially, extremely important are innovations for monitoring and protec-tion of strategic threelateral system H-OH-H2O Hydrogen, Hydroxyl and Water), correspond-ing to RS VHRS (Very High Resolution Systems) of 1.420-1.657-22.089GHz microwaves. . . One of the Greatest Paradox and Challenge of World Science is the "transformation" of J. L. Lagrange 4D Space-Time (S-T) System to H. Minkovski 4D S-T System (O-X,Y,Z,icT) for Einstein's "Theory of Relativity". As a global result: -In contemporary Advanced Space Sciences there is not real adequate 4D-6D Space-Time Coordinate System and 6D Advanced Cosmos Strategy & Methodology for Multidimensional and Multitemporal Space-Time Data Management and Tomography. . . That's one of the top actual S-T Problems. Simple and optimal nD S-T Methodology discovery is extremely important for all Universities' Space Sci-ences' Education Programs, for advances in space research and especially -for all young Space Scientists R&D!... The top ten 21-Century Challenges ahead of Planetary and Space Sciences, Space Data Management and Computational Space Tomography, important for successfully de-velopment of Young Scientist Generations, are following: 1. R&D of W. R. Hamilton General Idea for transformation all Space Sciences to Time Sciences, beginning with 6D Eukonal for 6D anisotropic mediums & velocities. Development of IERS Earth & Space Systems (VLBI; LLR; GPS; SLR; DORIS Etc.) for Planetary-Space Data Management & Computational Planetary & Space Tomography. 2. R&D of S. W. Hawking Paradigm for 2D Complex Time and Quan-tum Wave Cosmology Paradigm for Decision of the Main Problem of Contemporary Physics. 3. R&D of Einstein-Minkowski Geodesies' Paradigm in the 4D-Space-Time Continuum to 6D-6nD Space-Time Continuum Paradigms and 6D S-T Equations. . . 4. R&D of Erwin Schrüdinger 4D S-T Universe' Evolutional Equation; It's David Bohm 4D generalization for anisotropic mediums and innovative 6D -for instantaneously quantum measurement -Bohm-Schrüdinger 6D S-T Universe' Evolutional Equation. 5. R&D of brain new 6D Planning of S-T Experi-ments, brain new 6D Space Technicks and Space Technology Generalizations, especially for 6D RS VHRS Research, Monitoring and 6D Computational Tomography. 6. R&D of "6D Euler-Poisson Equations" and "6D Kolmogorov Turbulence Theory" for GeoDynamics and for Space Dynamics as evolution of Gauss-Riemann Paradigms. 7. R&D of N. Boneff NASA RD for Asteroid "Eros" & Space Science' Laws Evolution. 8. R&D of H. Poincare Paradigm for Nature and Cosmos as 6D Group of Transferences. 9. R&D of K. Popoff N-Body General Problem & General Thermodynamic S-T Theory as Einstein-Prigogine-Landau' Paradigms Development. ü 10. R&D of 1st GUT since 1958 by N. S. Kalitzin (Kalitzin N. S., 1958: Uber eine einheitliche Feldtheorie. ZAHeidelberg-ARI, WZHUmnR-B., 7 (2), 207-215) and "Multitemporal Theory of Relativity" -With special applications to Photon Rockets and all Space-Time R&D. GENERAL CONCLUSION: Multidimensional Space-Time Methodology is advance in space research, corresponding to the IAF-IAA-COSPAR Innovative Strategy and R&D Programs -UNEP, UNDP, GEOSS, GMES, Etc.
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
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.
Hrapchak, Matt; Latli, Bachir; Wang, Xiao-Jun; Lee, Heewon; Campbell, Scot; Song, Jinhua J; Senanayake, Chris H
2014-10-01
Empagliflozin, (2S,3R,4R,5S,6R)-2-[4-chloro-3-[[4-[(3S)-oxolan-3-yl]oxyphenyl]methyl]phenyl]-6-(hydroxymethyl)oxane-3,4,5-triol was recently approved by the FDA for the treatment of chronic type 2 diabetes mellitus. Herein, we report the synthesis of carbon-13 and carbon-14 labeled empagliflozin. Carbon-13 labeled empagliflozin was prepared in five steps and in 34% overall chemical yield starting from the commercially available α-D-glucose-[(13)C6]. For the radiosynthesis, the carbon-14 atom was introduced in three different positions of the molecule. In the first synthesis, Carbon-14 D-(+)-gluconic acid δ-lactone was used to prepare specifically labeled empagliflozin in carbon-1 of the sugar moiety in four steps and in 19% overall radiochemical yield. Carbon-14 labeled empagliflozin with the radioactive atom in the benzylic position was obtained in eight steps and in 7% overall radiochemical yield. In the last synthesis carbon-14 uniformly labeled phenol was used to give [(14)C]empagliflozin in eight steps and in 18% overall radiochemical yield. In all these radiosyntheses, the specific activities of the final compounds were higher than 53 mCi/mmol, and the radiochemical purities were above 98.5%. Copyright © 2014 John Wiley & Sons, Ltd.
1991-07-23
8217 I ,R . -, Thir cnc-:-. a-:. On *: - ’y -e ir~d is Dle-: £ .. _... . . STINFO P No ’ &Cz" Final Report for Period I July 1987 - 30 April 1991...OF RESEARCH PAPERS AND ABSTRACTS Appendix K I. OVERALL OBJECTIVE AND STATEMENT OF WORK The overall objective of the proposed project is to investigate...determine what adjustments in administered dose are necessary to achieve equal brain levels of test compounds in each species. An inhalation and oral
d-Leucine: Evaluation in an epilepsy model.
Holden, Kylie; Hartman, Adam L
2018-01-01
Current medicines do not provide sufficient seizure control for nearly one-third of patients with epilepsy. New options are needed to address this treatment gap. We recently found that the atypical amino acid d-leucine protected against acutely-induced seizures in mice, but its effect in chronic seizures has not been explored. We hypothesized that d-leucine would protect against spontaneous recurrent seizures. We also investigated whether mice lacking a previously-described d-leucine receptor (Tas1R2/R3) would be protected against acutely-induced seizures. Male FVB/NJ mice were subjected to kainic acid-induced status epilepticus and monitored by video-electroencephalography (EEG) (surgically implanted electrodes) for 4weeks before, during, and after treatment with d-leucine. Tas1R2/R3 knockout mice and controls underwent the maximal electroshock threshold (MES-T) and 6-Hz tests. There was no difference in number of calendar days with seizures or seizure frequency with d-leucine treatment. In an exploratory analysis, mice treated with d-leucine had a lower number of dark cycles with seizures. Tas1R2/R3 knockout mice had elevated seizure thresholds in the MES-T test but not the 6-Hz test. d-Leucine treatment was ineffective against chronic seizures after kainic acid-induced status epilepticus, but there was some efficacy during the dark cycle. Because d-leucine is highly concentrated in the pineal gland, these data suggest that d-leucine may be useful as a tool for studying circadian patterns in epilepsy. Deletion of the Tas1R2/R3 receptor protected against seizures in the MES-T test and, therefore, may be a novel target for treating seizures. Published by Elsevier Inc.
Sulkowski, Grzegorz; Dąbrowska-Bouta, Beata; Strużyńska, Lidia
2013-01-01
The aim of our investigation was to characterize the role of group I mGluRs and NMDA receptors in pathomechanisms of experimental autoimmune encephalomyelitis (EAE), the rodent model of MS. We tested the effects of LY 367385 (S-2-methyl-4-carboxyphenylglycine, a competitive antagonist of mGluR1), MPEP (2-methyl-6-(phenylethynyl)-pyridine, an antagonist of mGluR5), and the uncompetitive NMDA receptor antagonists amantadine and memantine on modulation of neurological deficits observed in rats with EAE. The neurological symptoms of EAE started at 10-11 days post-injection (d.p.i.) and peaked after 12-13 d.p.i. The protein levels of mGluRs and NMDA did not increase in early phases of EAE (4 d.p.i.), but starting from 8 d.p.i. to 25 d.p.i., we observed a significant elevation of mGluR1 and mGluR5 protein expression by about 20% and NMDA protein expression by about 10% over the control at 25 d.p.i. The changes in protein levels were accompanied by changes in mRNA expression of group I mGluRs and NMDARs. During the late disease phase (20-25 d.p.i.), the mRNA expression levels reached 300% of control values. In contrast, treatment with individual receptor antagonists resulted in a reduction of mRNA levels relative to untreated animals.
1987-01-01
44 44 0 ( 4 0 I 14 4 n bJ4 11) - 0 0 0 0 4 o c40N C,) a ima) -t.4 n c00000.co 03- 4 4 )- 0 00 C(,I0)0 0) r c)00 W0 0 enC Go6 ,r 00 c 0 w P00(IW0...cI enC en (0) m) r-- 0 00G L 0 enO -’ M0 U-100 U 00 L) 0( m 1 0 0 -40 0 00 0C - 0-4 00 0 00 0 *44( C II M 4-- I-. (D04- r- P4r- r., (D r- to r-- - r- r...q 14 Z LJOOO LaDO W-7)hI0~ 0.OXX OOON-400000 0( 00 0. LAO LOCDM - XLALA)Oao L)0~ o mO U00 ~ 0 ": 0 0 V-40 ’-’CC10 M ICC 0000D04
Analysis of the Pilot Conversion Process for the Air Force T-46A Jet Trainer Aircraft.
1983-09-01
both the T-37 and T-46. Therefore, when an IP begins transition training into the T-46, he can no longer fly the T-37. One exception to this policy may...4 4 ’- - C14 -4 r-4 1-4 o 0. 1 >% 0 r I- r-0 C4co =- r.=. D 03 40 cnCD 0.M nC4r. % - - -,P , D-4 M ’r % > a. m0 >r 0 *1*** Ln S-.~ U- 10 .. a 4...Equipment Maintenance Policies , Objectives and Responsibilities. Accomplish for the implementing command depot level maintenance source repair
77 FR 24137 - Airworthiness Directives; Airbus Airplanes
Federal Register 2010, 2011, 2012, 2013, 2014
2012-04-23
... Directives; Airbus Airplanes AGENCY: Federal Aviation Administration (FAA), DOT. ACTION: Final rule... Register. That AD applies to all Airbus Model A300 B4-600, B4-600R, and F4-600R series airplanes, Model... Airbus Model A300 B4-600, B4- 600R, and F4-600R series airplanes, Model A300 C4-605R Variant F airplanes...
77 FR 16916 - Airworthiness Directives; Pratt & Whitney (PW)Turbofan Engines
Federal Register 2010, 2011, 2012, 2013, 2014
2012-03-23
... Airworthiness Directives; Pratt & Whitney (PW)Turbofan Engines AGENCY: Federal Aviation Administration (FAA... and -7R4H1 turbofan engines. This AD was prompted by the determination that a new lower life limit for... PW JT9D-7R4G2 and -7R4H1 turbofan engine models. We agree. In addition to the JT9D-7R4G2 and -7R4H1...
Jacobi, H; Leier, G; Witte, I
1996-04-01
The binary combination effects of DNA synthesis of human fibroblasts were investigated using 2,4-D with 15 xenobiotics of different chemical substance classes. Results were compared with previous investigations on cell growth. Each of the 15 chemicals tested at their no effect concentrations (NOEC's) increased the effects of 2,4-D on DNA synthesis. Thereby, the EC20 value of 2,4-D was reduced by approximately 40% in the combinations. The NOEC's of the xenobiotics used in the combinations varied by a factor of 1,600 and depended strongly on the lipophilicity of the agents combined with 2,4-D. A significant statistical correlation of r = 0.90 was found between the NOEC's of the 15 combined xenobiotics and their lipophilicity. The combination effects on DNA synthesis were similar to those on cell growth. The regression lines of the relationship between the NOEC's and lipophilicity in both assays showed only slight differences in the slopes. This is an additional confirmation of our hypothesis on a facilitated uptake of 2,4-D in the binary combinations.
Dopamine D₂-Like Receptors and Behavioral Economics of Food Reinforcement.
Soto, Paul L; Hiranita, Takato; Xu, Ming; Hursh, Steven R; Grandy, David K; Katz, Jonathan L
2016-03-01
Previous studies suggest dopamine (DA) D2-like receptor involvement in the reinforcing effects of food. To determine contributions of the three D2-like receptor subtypes, knockout (KO) mice completely lacking DA D2, D3, or D4 receptors (D2R, D3R, or D4R KO mice) and their wild-type (WT) littermates were exposed to a series of fixed-ratio (FR) food-reinforcement schedules in two contexts: an open economy with additional food provided outside the experimental setting and a closed economy with all food earned within the experimental setting. A behavioral economic model was used to quantify reinforcer effectiveness with food pellets obtained as a function of price (FR schedule value) plotted to assess elasticity of demand. Under both economies, as price increased, food pellets obtained decreased more rapidly (ie, food demand was more elastic) in DA D2R KO mice compared with WT littermates. Extinction of responding was studied in two contexts: by eliminating food deliveries and by delivering food independently of responding. A hyperbolic model quantified rates of extinction. Extinction in DA D2R KO mice occurred less rapidly compared with WT mice in both contexts. Elasticity of food demand was higher in DA D4R KO than WT mice in the open, but not closed, economy. Extinction of responding in DA D4R KO mice was not different from that in WT littermates in either context. No differences in elasticity of food demand or extinction rate were obtained in D3R KO mice and WT littermates. These results indicate that the D2R is the primary DA D2-like receptor subtype mediating the reinforcing effectiveness of food.
1994-09-30
DE LME NDO G E R A R D O MAR I GZA A I R F O R C E D E LMUNDO L I LY F E D E R I S NAVY D E LOACH B O B B Y D E A N A I R F ORCE D E LOGE B...YAN LAMON EAR LE JAME S ARTHUR EAR LEY KEN W EAR LEY R OB E R T WI L L IAM J R EAR LS M I CHAE L G EAR LS OMAR DALE EAR LY BE N JAMIN J R...8 9 B R OOK LYN E 0 4 2 2 F e b 8 2 KEN TON E 0 7 14 D e c 9 1 R OCKH I L L 0 0 2 1 4 J u l 8 1 T E XAS C I T Y E 0 6 24 Oc t 7 9
NASA Astrophysics Data System (ADS)
He, Huijuan; Huang, Langhuan; Zhong, Zijun; Tan, Shaozao
2018-05-01
Photocatalysis has been widely considered to be an effective way for solving the worldwide environmental pollution issues. Herein, a new type of three-dimensional (3D) ternary graphene-carbon quantum dots/g-C3N4 nanosheet (GA-CQDs/CNN) aerogel visible-light-driven photocatalyst was synthesized via a two-step hydrothermal method. In this unique ternary photocatalyst, both carbon quantum dots (CQDs) and reduced graphene oxide (rGO) could improve the visible light absorption and promote the charge separation. Furthermore, reduced graphene oxide (rGO) could act as a supportor for the 3D framework. Such a ternary system overcame the drawbacks of bulk g-C3N4 (BCN) and achieved the enhanced photocatalytic activity and long-term stability. As a result, the methyl orange (MO) removal ratio of GA-CQDs/CNN-24% was up to 91.1%, which was about 7.6 times higher than that of bulk g-C3N4 (BCN) under the identical conditions. Moreover that GA-CQDs/CNN-24% exhibited inappreciable loss of photocatalytic activity after four-cycle degradation processes. Finally, the photocatalytic mechanism of GA-CQDs/CNN-24% was interpreted both theoretically and experimentally.
Optimization of Fenton's oxidation of herbicide dicamba in water using response surface methodology
NASA Astrophysics Data System (ADS)
Sangami, Sanjeev; Manu, Basavaraju
2017-12-01
In this study Fenton's oxidation of dicamba in aqueous medium was investigated by using the response surface methodology. The influence of H2O2/COD ( A), H2O2/Fe2+ ( B), pH ( C) and reaction time ( D) as independent variables were studied on two responses (COD and dicamba removal efficiency). The dosage of H2O2 (5.35-17.4 mM) and Fe2+ (0.09-2.13 mM) were varied and optimum percentage removal of dicamba of 84.01% with H2O2 and Fe2+ dosage of 11.38 and 0.33 mM respectively. The whole oxidation process was monitored by high performance liquid chromatography (HPLC) along with liquid chromatography/mass spectrometry (LC/MS). It was found that 82% of dicamba was mineralized to oxalic acid, chloride ion, CO2 and H2O, which was confirmed with COD removal of 81.53%. The regression analysis was performed, in which standard deviation (<4%), coefficient of variation (<8), F value (Fisher's Test) (>2.74), coefficient of correlation ( R 2 = R_{adj}2) and adequate precision (>12) were in good agreement with model values. Finally, the treatment process was validated by performing the additional experiments.
An Experimental and Analytical Investigation of a Radial Face Seal
1976-01-01
c \\]f’ n" •’ * TIMOTHY W. SWAFFORD h ; January 1976 Cjl...Vi 4J to c H Ö o Ö Ü (D M s Ö • H tfl 1-1 U a) :r^J. y^^^^^l 32 From NA iransparent tubing To seal ^xH— Globe valves Supply... c . 3 n) cNi a o cu <• C8 rH CC 1 A > o. U T-: 1 ^O J ^ ’ k 3 o a c ^ ^O TI —< r- -i! O 0) H - H rH H
The Use of Ion Implantation for Materials Processing.
1983-09-28
SPUTTERING ANALYSIS WITH PIXE.......................... 31 J.M. Lambert, P.A. Treado, D . Trbojevic ,2 R.G. Alias, A.R. Knudson, G.W. Reynolds and F.R...Lambert and P. . Treado I D . Trbojevic R. G. Allas and A. R. Knudson 3 G. W. Reynolds and F. R. Vozzo 4 IGeorgetown University Washington, D . C. and...D.C. 20057 and 20375 D . Trbojevic Georgetown University, Washington, D.C. 20057 R.G. Alias and A.R. Knudson Naval Research Laboratory, Washington, D.C
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
Dual-Modality Prostate Imaging with PET and Transrectal Ultrasound
2009-04-01
TD (e<@?<K(a4S6(<B8R<%R(#M(A$#@Ŝ"&(*8%*&$(Q@<%R(*8$=#%0>>0 *?#:<%&Kb(!"#$%&"’()K(F#:D(JIK(AAD...1( BBD (\\=](O#N<M<&N(;SO!(^a4&$M#$B8%*&(O&8@Q$&B&%"@(#M(4#@<"$#%(SB<@@<#%( 6#B#R$8A?@Kb(;8"<#%8:(S:&*"$<*8:(O8%QM8*"Q$&$@(!@@#*ɠ"<#%(\\;SO!](V&A...34<#%(<%("?&(=8*+R$#Q%N(A&:F<@($&R<#%D(.B8R&( $&A$&@&%"@(GJG(O(*#Q%"@(\\+-(-=(13(B<%Q"&@(#M(N8Ŝ]D(6?&(F#Z&:(@<j&(<@(>D2W(BB(Z(>D2W(BB(Z(JD>J( BBD
da Cunha-Bang, Caspar; Sørensen, Søren S; Iversen, Martin; Sengeløv, Henrik; Hillingsø, Jens G; Rasmussen, Allan; Mortensen, Svend A; Fox, Zoe V; Kirkby, Nikolai S; Christiansen, Claus B; Lundgren, Jens D
2011-05-01
Infection with cytomegalovirus (CMV) remains a potentially serious complication in transplant patients. In this study we explored the risk factors for CMV infection in the 12 months following a solid organ transplantation (n = 242) in patients monitored for CMV infection from 2004 to 2007. CMV infection was defined as 2 consecutive quantifiable CMV-polymerase chain reaction (PCR) values or 1 measurement of >3000 copies/ml. Data describing pre- and post-transplantation variables were extracted from electronic health records. Time to CMV infection was investigated using Cox proportional hazards analysis. Overall, 31% (75/242) of solid organ transplant patients developed CMV infection: 4/8 (50.0%) heart, 15/43 (34.9%) liver, 30/89 (33.7%) lung and 26/102 (25.5%) kidney transplant patients. The risk of CMV infection according to donor (D)/recipient (R) CMV serostatus (positive + or negative-) was highest for D+/R-(adjusted hazard ratio 2.6, 95% confidence interval 1.6-4.2) vs D+/R+, and was reduced for D-/R+(adjusted hazard ratio 0.2, 95% confidence interval 0.2-0.8) vs D+/R+. Positive donor CMV-serostatus is a major risk factor for CMV-infection in CMV-na ve recipients, but also in recipients with positive CMV-serostatus. Conversely, if donor is CMV serostatus is negative, the risk of CMV infection is low, irrespective of recipients CMV-serostatus. These findings suggest poorer immune function towards donor-induced strains of CMV versus recipient own latent strains.
ACE DD genotype: a predisposing factor for abdominal aortic aneurysm.
Fatini, C; Pratesi, G; Sofi, F; Gensini, F; Sticchi, E; Lari, B; Pulli, R; Dorigo, W; Azas, L; Pratesi, C; Gensini, G F; Abbate, R
2005-03-01
To examine the role of polymorphisms in angiotensin converting enzyme (ACE, I/D) and angiotensin II receptor (AT1R, A1166C) in the development of abdominal aortic aneurysm (AAA). We investigated 250 consecutive patients, 217 males and 33 females (median age 72, range 50-83), undergone AAA elective repair and 250 healthy controls, comparable for sex and age. ACE and AT1R polymorphisms were studied by PCR-RFLP analysis. The genotype distribution was in Hardy-Weinberg equilibrium for all polymorphisms. The genotype distribution and allele frequency of ACE I/D, but not AT1R A1166C polymorphism were significantly different between patients and controls (ACE I/D: p=0.0002 and p<0.0001, respectively, and AT1R A1166C: p=0.6 and p=0.4, respectively). An association between the ACE DD genotype and the predisposition to AAA was found (OR DD vs. ID+II=1.9 95% CI 1.3-2.9, p<0.0001). Multivariate analysis adjusted for age, sex, traditional vascular risk factors and other atherosclerotic localizations, showed ACE DD genotype to be independently related to the disease (OR DD vs. ID+II=2.4, 95% CI 1.3-4.2 p=0.003). Our findings document that ACE DD genotype represents a susceptibility factor for AAA.
Gago, Belén; Suárez-Boomgaard, Diana; Fuxe, Kjell; Brené, Stefan; Reina-Sánchez, María Dolores; Rodríguez-Pérez, Luis M; Agnati, Luigi F; de la Calle, Adelaida; Rivera, Alicia
2011-08-17
Acute administration of the dopamine D(4) receptor (D(4)R) agonist PD168,077 induces a down-regulation of the μ opioid receptor (MOR) in the striosomal compartment of the rat caudate putamen (CPu), suggesting a striosomal D(4)R/MOR receptor interaction in line with their high co-distribution in this brain subregion. The present work was designed to explore if a D(4)R/MOR receptor interaction also occurs in the modulation of the expression pattern of several transcription factors in striatal subregions that play a central role in drug addiction. Thus, c-Fos, FosB/ΔFosB and P-CREB immunoreactive profiles were quantified in the rat CPu after either acute or continuous (6-day) administration of morphine and/or PD168,077. Acute and continuous administration of morphine induced different patterns of expression of these transcription factors, effects that were time-course and region dependent and fully blocked by PD168,077 co-administration. Moreover, this effect of the D(4)R agonist was counteracted by the D(4)R antagonist L745,870. Interestingly, at some time-points, combined treatment with morphine and PD168,077 substantially increased c-Fos, FosB/ΔFosB and P-CREB expression. The results of this study give indications for a general antagonistic D(4)R/MOR receptor interaction at the level of transcription factors. The change in the transcription factor expression by D(4)R/MOR interactions in turn suggests a modulation of neuronal activity in the CPu that could be of relevance for drug addiction. Copyright © 2011 Elsevier B.V. All rights reserved.
Mora, Claudia; Medina-Rosas, Jorge; Santos, Ana Maria; Jaimes, Diego A; Arbeláez, Ana M; Romero, Consuelo; Cortes, Annie; Londono, John
2016-09-01
There are no laboratory tools that detect early flares in systemic lupus erythematosus (SLE). Our aim was to validate in our population the previous findings of the association of C4d-bearing reticulocytes (R-C4d) compared to anti-dsDNA antibodies, with disease activity assessed by the Safety of Estrogens in Lupus Erythematosus National Assessment-Systemic Lupus Erythematosus Disease Activity Index (SELENA-SLEDAI) and the British Isles Lupus Assessment Group (BILAG) 2004 scales. All patients who met the 1987 American College of Rheumatology classification criteria and were seen consecutively in 2013 at a specialized SLE care clinic were included. Disease activity was established by the SELENA-SLEDAI and BILAG 2004. Anti-dsDNA and R-C4d were quantified in peripheral blood. Comparisons were made between values of active and inactive patients, and the correlations between the SELENA-SLEDAI and serum levels of anti-dsDNA and R-C4d were measured. Sixty-two patients (83.9% women) were included. A total of 32.3% had active disease according to the SELENA-SLEDAI. There was a significant statistical difference (p = 0.0001) in the distribution of R-C4d between disease activity groups. The correlation coefficient between R-C4d and the SELENA-SLEDAI score was rs = 0.738 (p = 0.0001). R-C4d differed between patients with and without activity in the BILAG 2004 constitutional, mucocutaneous, gastrointestinal, renal, and hematological domains. R-C4d showed a higher correlation with SLE activity measured by the SELENA-SLEDAI and BILAG 2004 than anti-dsDNA did, suggesting a possible involvement in diagnosing disease activity. Prospective studies that confirm these findings and evaluate its involvement in followup are needed.
MiR-205 and MiR-373 Are Associated with Aggressive Human Mucinous Colorectal Cancer.
Eyking, Annette; Reis, Henning; Frank, Magdalena; Gerken, Guido; Schmid, Kurt W; Cario, Elke
2016-01-01
Mucinous adenocarcinoma (MAC) represents a distinct histopathological entity of colorectal cancer (CRC), which is associated with disease progression and poor prognosis. Here, we found that expression levels of miR-205 and miR-373 were specifically upregulated only in patients with mucinous colon cancers, but not in CRC that lack mucinous components. To investigate the effects of miR-205 and miR-373 on intestinal epithelial cell (IEC) biology by gain- and loss-of-function experiments in a proof-of-concept approach, we chose previously established in-vitro human Caco-2-based models of differentiated, non-invasive (expressing TLR4 wild-type; termed Caco-2[WT]) versus undifferentiated, invasive (expressing TLR4 mutant D299G; termed Caco-2[D299G]) IEC. Enterocyte-like Caco-2[WT] showed low levels of miR-205 and miR-373 expression, while both miRNAs were significantly upregulated in colorectal carcinoma-like Caco-2[D299G], thus resembling the miRNA expression pattern of paired normal versus tumor samples from MAC patients. Using stable transfection, we generated miR-205- or miR-373-expressing and miR-205- or miR-373-inhibiting subclones of these IEC lines. We found that introduction of miR-205 into Caco-2[WT] led to expansion of mucus-secreting goblet cell-like cells, which was associated with induction of KLF4, MUC2 and TGFβ1 expression. Activation of miR-205 in Caco-2[WT] induced chemoresistance, while inhibition of miR-205 in Caco-2[D299G] promoted chemosensitivity. Caco-2[WT] overexpressing miR-373 showed mitotic abnormalities and underwent morphologic changes (loss of epithelial polarity, cytoskeletal reorganization, and junctional disruption) associated with epithelial-mesenchymal transition and progression to inflammation-associated colonic carcinoma, which correlated with induction of phosphorylated STAT3 and N-CADHERIN expression. Functionally, introduction of miR-373 into Caco-2[WT] mediated loss of cell-cell adhesion and increased proliferation and invasion. Reversely, inhibition of miR-373 allowed mesenchymal IEC to regain epithelial properties, which correlated with absence of neoplastic progression. Using xenografts in mice demonstrated miR-373-mediated acceleration of malignant intestinal tumor growth. In conclusion, our results provide first evidence that miR-205 and miR-373 may differentially contribute to the aggressive phenotype of MAC in CRC.
Anthropometric Survey of the Imperial Iranian Armed Forces. Volume 2. Statistical Data
1971-03-01
nI JIni D D 0c41 1. 4n Lk MN ~ LAMO NOO’O-0’r4 -4 ’t 4 ~ ý N-*I4Lr- -44 o.L .4 - o N"-4 0 4lA in0. coN -4. -4 . 41 Go N- -4 0 - 0 0LINA .4 4 P.4LA...m -4 0r o40 r4 C4 N 0 - -n 0 ’-40 t . . 41 .-. 4, d O - .0tiI-P .- A -n 0 N m a,4( 0 gao Mr .’m00 < OD r- mo N~ m,- (314- 0 0.0C l i O ~ j - 000 04 m
Séchage d'un enduit pigmenté avec application à l'étude d'une couche papetière
NASA Astrophysics Data System (ADS)
Bernada, P.; Bruneau, D.
1996-07-01
Paper color coating drying is investigated from several experimental view points which include drying kinetics and time evolution of moisture content profiles, pore size distribution in the dried coating, and natural binder (starch) distribution in the dried coating. A study of the effects of drying conditions on those experimental parameters is carried out. Furthermore, gelification and consolidation characteristic moisture contents of the coating are determined using a graphical approach. Le séchage d'un enduit pigmenté à l'usage d'une couche papetière est absorbé sous diverts aspects : cinétiques de séchage et évolution temporelle des profils de teneur en eau, profils de répartition de la taille des pores dans la couche séchée, et répartition finale d'un liant hydrophile de la sauce de couchage (amidon). Les conséquences des conditions de séchage sur ces paramètres expérimentaux sont mises en évidence. De plus, les teneurs en eau caractéristiques de gélification et consolidation de la sauce de couchage sont obtenues par une approche graphique.
Nguyen, X Cuong; Chang, S Woong; Nguyen, Thi Loan; Ngo, H Hao; Kumar, Gopalakrishnan; Banu, J Rajesh; Vu, M Cuong; Le, H Sinh; Nguyen, D Duc
2018-09-15
A pilot-scale hybrid constructed wetland with vertical flow and horizontal flow in series was constructed and used to investigate organic material and nutrient removal rate constants for wastewater treatment and establish a practical predictive model for use. For this purpose, the performance of multiple parameters was statistically evaluated during the process and predictive models were suggested. The measurement of the kinetic rate constant was based on the use of the first-order derivation and Monod kinetic derivation (Monod) paired with a plug flow reactor (PFR) and a continuously stirred tank reactor (CSTR). Both the Lindeman, Merenda, and Gold (LMG) analysis and Bayesian model averaging (BMA) method were employed for identifying the relative importance of variables and their optimal multiple regression (MR). The results showed that the first-order-PFR (M 2 ) model did not fit the data (P > 0.05, and R 2 < 0.5), whereas the first-order-CSTR (M 1 ) model for the chemical oxygen demand (COD Cr ) and Monod-CSTR (M 3 ) model for the COD Cr and ammonium nitrogen (NH 4 -N) showed a high correlation with the experimental data (R 2 > 0.5). The pollutant removal rates in the case of M 1 were 0.19 m/d (COD Cr ) and those for M 3 were 25.2 g/m 2 ∙d for COD Cr and 2.63 g/m 2 ∙d for NH 4 -N. By applying a multi-variable linear regression method, the optimal empirical models were established for predicting the final effluent concentration of five days' biochemical oxygen demand (BOD 5 ) and NH 4 -N. In general, the hydraulic loading rate was considered an important variable having a high value of relative importance, which appeared in all the optimal predictive models. Copyright © 2018 Elsevier Ltd. All rights reserved.
Reduced Anxiety in Forensic Inpatients after a Long-Term Intervention with Atlantic Salmon
Hansen, Anita L.; Olson, Gina; Dahl, Lisbeth; Thornton, David; Grung, Bjørn; Graff, Ingvild E.; Frøyland, Livar; Thayer, Julian F.
2014-01-01
The aim of the present study was to investigate the effects of Atlantic salmon consumption on underlying biological mechanisms associated with anxiety such as heart rate variability (HRV) and heart rate (HR) as well as a measure of self-reported anxiety. Moreover, these biological and self-reported outcome measures were investigated in relation to specific nutrients; vitamin D status, eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA). Ninety-five male forensic inpatients were randomly assigned into a Fish (Atlantic salmon three times per week from September to February) or a Control group (alternative meal, e.g., chicken, pork, or beef three times per week during the same period). HRV measured as the root mean square of successive differences (rMSSD), HR, state- and trait-anxiety (STAI), were assessed before (pre-test) and at the end of the 23 weeks dietary intervention period (post-test). The Fish group showed significant improvements in both rMSSD and HR. The Fish group also showed significant decreases in state-anxiety. Finally, there was a positive relationship between rMSSD and vitamin D status. The findings suggest that Atlantic salmon consumption may have an impact on mental health related variables such as underlying mechanisms playing a key role in emotion-regulation and state-anxiety. PMID:25431880
Reduced anxiety in forensic inpatients after a long-term intervention with Atlantic salmon.
Hansen, Anita L; Olson, Gina; Dahl, Lisbeth; Thornton, David; Grung, Bjørn; Graff, Ingvild E; Frøyland, Livar; Thayer, Julian F
2014-11-26
The aim of the present study was to investigate the effects of Atlantic salmon consumption on underlying biological mechanisms associated with anxiety such as heart rate variability (HRV) and heart rate (HR) as well as a measure of self-reported anxiety. Moreover, these biological and self-reported outcome measures were investigated in relation to specific nutrients; vitamin D status, eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA). Ninety-five male forensic inpatients were randomly assigned into a Fish (Atlantic salmon three times per week from September to February) or a Control group (alternative meal, e.g., chicken, pork, or beef three times per week during the same period). HRV measured as the root mean square of successive differences (rMSSD), HR, state- and trait-anxiety (STAI), were assessed before (pre-test) and at the end of the 23 weeks dietary intervention period (post-test). The Fish group showed significant improvements in both rMSSD and HR. The Fish group also showed significant decreases in state-anxiety. Finally, there was a positive relationship between rMSSD and vitamin D status. The findings suggest that Atlantic salmon consumption may have an impact on mental health related variables such as underlying mechanisms playing a key role in emotion-regulation and state-anxiety.
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 compared to the corresponding unmodified duplex. The reduced base stacking at the adduct sites may also contribute to the thermal instability.
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 adduct sites may also contribute to the thermal instability. PMID:24741991
Wang, Zhi-Qiang; Wang, Wei; Shi, Lin; Chai, Ji-Tian; Zhang, Xin-Jun; Tao, Ya-Xiong
2016-04-01
The melanocortin-4 receptor (MC4R) is critical in regulating mammalian food intake and energy expenditure. Giant panda (Ailuropoda melanoleuca), famous as the living fossil, is an endangered species endemic to China. We are interested in exploring the functions of the giant panda MC4R (amMC4R) in regulating energy homeostasis and report herein the molecular cloning and pharmacology of the amMC4R. Sequence analysis revealed that amMC4R was highly homologous (>88%) at nucleotide and amino acid sequences to several mammalian MC4Rs. Western blot revealed that the expression construct myc-amMC4R in pcDNA3.1 was successfully constructed and expressed in HEK293T cells. With human MC4R (hMC4R) as a control, pharmacological characteristics of amMC4R were analyzed with binding and signaling assays. Four agonists, including [Nle(4), D-Phe(7)]-α-melanocyte stimulating hormone (NDP-MSH), α- and β-MSH, and a small molecule agonist, THIQ, were used in binding and signaling assays. We showed that amMC4R bound NDP-MSH with the highest affinity followed by THIQ, α-MSH, and β-MSH, with the same ranking order as hMC4R. Treatment of HEK293T cells expressing amMC4R with different concentrations of agonists resulted in dose-dependent increase of intracellular cAMP levels, with similar EC50s for the four agonists. The results suggested that the cloned amMC4R encoded a functional MC4R. The availability of amMC4R and its binding and signaling properties will facilitate the investigation of amMC4R in regulating food intake and energy homeostasis. Copyright © 2016 Elsevier Inc. All rights reserved.
3D-QSAR studies on 1,2,4-triazolyl 5-azaspiro [2.4]-heptanes as D3R antagonists
NASA Astrophysics Data System (ADS)
Zhang, Xin; Zhang, Hui
2018-07-01
Dopamine D3 receptor has become an attractive target in the treatment of abused drugs. 3D-QSAR studies were performed on a novel series of D3 receptor antagonists, 1,2,4-triazolyl 5-azaspiro [2.4]-heptanes, using CoMFA and CoMSIA methods. Two predictive 3D-QSAR models have been generated for the modified design of D3R antagonists. Based on the steric, electrostatic, hydrophobic and hydrogen-bond acceptor information of contour maps, key structural factors affecting the bioactivity were explored. This work gives helpful suggestions on the design of novel D3R antagonists with increased activities.
Baseline Noise Measurements at Vandenberg AFB, California.
1988-01-01
8217w.h . ’.0 n r,,’a in nr’.Iwqpknn n. %a..a *k ae @ d - ’a %e q0 - .am0" o P miP ’ r m h~ in hi# mOffi r4hinP w I @ 4r" ha.maw .mha.A-v ’w, aa a...system, and therefore, are available for future analysis if required. D . Observations: A review of the data charts indicates there is no seasonal...qp)l3Ar- 3SION 13 I (4 C4O7r4 CocqV-4r- Ln ~0 ’ (Ŕwr4qw,.c I q wm V % "( 0 n q* (" ul *n *1 *n *n *n 00 tnL .L n% D % i % lu nU n cc ( tflf0 f" %a C4
MRAP and MRAP2 are bidirectional regulators of the melanocortin receptor family
Chan, Li F.; Webb, Tom R.; Chung, Teng-Teng; Meimaridou, Eirini; Cooray, Sadani N.; Guasti, Leonardo; Chapple, J. Paul; Egertová, Michaela; Elphick, Maurice R.; Cheetham, Michael E.; Metherell, Louise A.; Clark, Adrian J. L.
2009-01-01
The melanocortin receptor (MCR) family consists of 5 G protein-coupled receptors (MC1R–MC5R) with diverse physiologic roles. MC2R is a critical component of the hypothalamic–pituitary–adrenal axis, whereas MC3R and MC4R have an essential role in energy homeostasis. Mutations in MC4R are the single most common cause of monogenic obesity. Investigating the way in which these receptors signal and traffic to the cell membrane is vital in understanding disease processes related to MCR dysfunction. MRAP is an MC2R accessory protein, responsible for adrenal MC2R trafficking and function. Here we identify MRAP2 as a unique homologue of MRAP, expressed in brain and the adrenal gland. We report that MRAP and MRAP2 can interact with all 5 MCRs. This interaction results in MC2R surface expression and signaling. In contrast, MRAP and MRAP2 can reduce MC1R, MC3R, MC4R, and MC5R responsiveness to [Nle4,D-Phe7]alpha-melanocyte-stimulating hormone (NDP-MSH). Collectively, our data identify MRAP and MRAP2 as unique bidirectional regulators of the MCR family. PMID:19329486
Turbine Engine Flowpath Averaging Techniques
1980-10-01
u~%x AEDC- TMR- 8 I-G 1 • R. P TURBINE ENGINE FLOWPATH AVERAGING TECHNIQUES T. W. Skiles ARO, Inc. October 1980 Final Report for Period...COVERED 00-01-1980 to 00-10-1980 4. TITLE AND SUBTITLE Turbine Engine Flowpath Averaging Techniques 5a. CONTRACT NUMBER 5b. GRANT NUMBER 5c...property for gas turbine engines were investigated. The investigation consisted of a literature review and review of turbine engine current flowpath
Oceanographic Analyses and Forecasts for Fleet Support (Services and Codes). Revised.
1967-08-01
unit of thousands is omitted.) 11I SOUND VELOCITY PROFILE The SVP message form will normally follow the TD profile to which it pertains in the following...i ra 0 0 a 3’: VE C//3 000Q F- A E-4 =) 4-4 0.. 0- P4 C4 L) r. ~ N C)(D~ > a) CO C4 IHQ N E- .,1 0 r 4 4-4 V L 04 04 0 0 = rz - r- i r- 4(0 Ow ( (D
Wang, Dexin; Ma, Wencheng; Han, Hongjun; Li, Kun; Xu, Hao; Fang, Fang; Hou, Baolin; Jia, Shengyong
2016-12-01
Coupling of the Fe-C micro-electrolysis (IC-ME) into the up-flow anaerobic sludge blanket (UASB) was developed for enhanced Fischer-Tropsch wastewater treatment. The COD removal efficiency and methane production in R 3 with IC-ME assisted both reached up to 80.6 ± 1.7% and 1.38 ± 0.11 L/L·d that higher than those values in R 1 with GAC addition (63.0 ± 3.4% and 0.95 ± 0.09 L/L·d) and R 2 with ZVI addition (74.5 ± 2.8% and 1.21 ± 0.09 L/L·d) under the optimum HRT (5 d). The Fe corrosion as electron donor reduced the ORP values and stimulated the activities of hydrogenotrophic methanogens to lower H 2 partial pressure in R 2 and R 3 . Additionally, Fe 2+ as by-product of iron corrosion, its presence could effectively increase the percentage of protein content in tightly bound extracellular polymeric substances (TB-EPS) to promote better bioflocculation, increasing to 90.5 mg protein/g·VSS (R 2 ) and 106.3 mg protein/g·VSS (R 3 ) while this value in R1 was simply 56.6 mg protein/g·VSS. More importantly, compared with R 1 , the excess accumulation of propionic acid and butyric acid in system was avoided. The macroscopic galvanic cells around Fe-C micro-electrolysis carriers in R 3 , that larger than microscopic galvanic cells in R 2 , further accelerate to transfer the electrons from anodic Fe to cathodic carbon that enhance interspecies hydrogen transfer, making the decomposition of propionic acid and butyric acid more thermodynamically feasible, finally facilitate more methane production. Copyright © 2016 Elsevier Ltd. All rights reserved.
Development of a Hazard Classification Procedure for Inprocess Propellant and Explosive Materials
1980-11-01
Manual of Sensitiveness Tests," Canadian Armament Research and Development Establishment, February 1966. 8-4 Dorough, G. D., et al ., "The SUSAN Test...Materials," RAD 100.10, Final Engineering Report on Production Engineering Project PE-489 (Preliminary), AMCMS Code 4932.05.4289. 8-10 Avramic, L., et al ...Performance Tests for Energetic Materials. 8-14 Leining, R. B.. et al , "Air Launched Missile Motor Behavior," AFRPL-TR-78-54, Technical
Expression of Bacillus anthracis Protective Antigen in Bacillus megaterium
2004-03-01
was easily purified to homogeneity in a single step by ion exchange chromatography. N-terminal amino acid sequencing of the final product confirmed...and this material was purified in a single step by ion-exchange chromatography. N-terminal amino acid sequencing definitively proved that the rPA was...production of a poly-D-glutamic acid capsule, encoded by pXO2, is essential for immune evasion and cellular survival in the host [3,4]. The lethal effects
Preventing Depression in Final Year Secondary Students: School-Based Randomized Controlled Trial
Perry, Yael; Werner-Seidler, Aliza; Calear, Alison; Mackinnon, Andrew; King, Catherine; Scott, Jan; Merry, Sally; Fleming, Theresa; Stasiak, Karolina; Batterham, Philip J
2017-01-01
Background Depression often emerges for the first time during adolescence. There is accumulating evidence that universal depression prevention programs may have the capacity to reduce the impact of depression when delivered in the school environment. Objective This trial investigated the effectiveness of SPARX-R, a gamified online cognitive behavior therapy intervention for the prevention of depression relative to an attention-matched control intervention delivered to students prior to facing a significant stressor—final secondary school exams. It was hypothesized that delivering a prevention intervention in advance of a stressor would reduce depressive symptoms relative to the control group. Methods A cluster randomized controlled trial was conducted in 10 government schools in Sydney, Australia. Participants were 540 final year secondary students (mean 16.7 [SD 0.51] years), and clusters at the school level were randomly allocated to SPARX-R or the control intervention. Interventions were delivered weekly in 7 modules, each taking approximately 20 to 30 minutes to complete. The primary outcome was symptoms of depression as measured by the Major Depression Inventory. Intention-to-treat analyses were performed. Results Compared to controls, participants in the SPARX-R condition (n=242) showed significantly reduced depression symptoms relative to the control (n=298) at post-intervention (Cohen d=0.29) and 6 months post-baseline (d=0.21) but not at 18 months post-baseline (d=0.33). Conclusions This is the first trial to demonstrate a preventive effect on depressive symptoms prior to a significant and universal stressor in adolescents. It demonstrates that an online intervention delivered in advance of a stressful experience can reduce the impact of such an event on the potential development or exacerbation of depression. Trial Registration Australian New Zealand Clinical Trials Registry ACTRN12614000316606; https://www.anzctr.org.au/Trial/Registration/TrialReview.aspx?id=365986 (Archived by WebCite at http://www.webcitation.org/ 6u7ou1aI9) PMID:29097357
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 high affinity, 1 is a potent, dual inhibitor of both of the isostates of PDE 4. Kinetic and thermodynamic models describing the interactions between the nonexchangeable isostates of PDE 4 and its ligands are discussed.
Zanella, Gloria; Pullini, Serena; Como, Giuseppe; Bazzocchi, Massimo
2014-01-01
Purpose. To quantify the impact of diagnostic confidence on radiological diagnosis with a fuzzy logic-based method. Materials and Methods. Twenty-two oncologic patients with 20 cysts and 30 metastases ≤1 cm in size found at 64-row computed tomography were included. Two readers (R1/R2) expressed diagnoses as a subjective level of confidence P(d) in malignancy within the interval [0,1] rather than on a “crisp” basis (malignant/benign); confidence in benignancy was 1 − p(d). When cross-tabulating data according to the standard of reference, 2 × 2 table cells resulted from the aggregation between p(d)/1 − p(d) and final diagnosis. We then assessed (i) readers diagnostic performance on a fuzzy and crisp basis; (ii) the “divergence” δ(F, C) (%) as a measure of how confidence impacted on crisp diagnosis. Results. Diagnoses expressed with lower confidence increased fuzzy false positives compared to crisp ones (from 0 to 0.2 for R1; from 1 to 2.4 for R2). Crisp/fuzzy accuracy was 94.0%/93.6% (R1) and 94.0/91.6% (R2). δ(F, C) (%) was larger in the case of the less experienced reader (R2) (up to +7.95% for specificity). According to simulations, δ(F, C) (%) was negative/positive depending on the level of confidence in incorrect diagnoses. Conclusion. Fuzzy evaluation shows a measurable effect of uncertainty on radiological diagnoses. PMID:24587815
When chocolate seeking becomes compulsion: gene-environment interplay.
Patrono, Enrico; Di Segni, Matteo; Patella, Loris; Andolina, Diego; Valzania, Alessandro; Latagliata, Emanuele Claudio; Felsani, Armando; Pompili, Assunta; Gasbarri, Antonella; Puglisi-Allegra, Stefano; Ventura, Rossella
2015-01-01
Eating disorders appear to be caused by a complex interaction between environmental and genetic factors, and compulsive eating in response to adverse circumstances characterizes many eating disorders. We compared compulsion-like eating in the form of conditioned suppression of palatable food-seeking in adverse situations in stressed C57BL/6J and DBA/2J mice, two well-characterized inbred strains, to determine the influence of gene-environment interplay on this behavioral phenotype. Moreover, we tested the hypothesis that low accumbal D2 receptor (R) availability is a genetic risk factor of food compulsion-like behavior and that environmental conditions that induce compulsive eating alter D2R expression in the striatum. To this end, we measured D1R and D2R expression in the striatum and D1R, D2R and α1R levels in the medial prefrontal cortex, respectively, by western blot. Exposure to environmental conditions induces compulsion-like eating behavior, depending on genetic background. This behavioral pattern is linked to decreased availability of accumbal D2R. Moreover, exposure to certain environmental conditions upregulates D2R and downregulates α1R in the striatum and medial prefrontal cortex, respectively, of compulsive animals. These findings confirm the function of gene-environment interplay in the manifestation of compulsive eating and support the hypothesis that low accumbal D2R availability is a "constitutive" genetic risk factor for compulsion-like eating behavior. Finally, D2R upregulation and α1R downregulation in the striatum and medial prefrontal cortex, respectively, are potential neuroadaptive responses that parallel the shift from motivated to compulsive eating.
Wang, Liang-Jen; Chou, Miao-Chun; Chou, Wen-Jiun; Lee, Min-Jing; Lee, Sheng-Yu; Lin, Pao-Yen; Lee, Yi-Hsuan; Yang, Yi-Hsin; Yen, Cheng-Fang
2017-01-01
Both prenatal testosterone (T) exposure and postnatal T levels have been associated with developing neural circuitry and behavioral systems. This study examined the potential correlation between pre- and postnatal T levels and behavioral and neurocognitive profiles of children with attention-deficit/hyperactivity disorder (ADHD). Two hundred ADHD patients with a mean age of 8.7±2.0 years (158 boys and 42 girls) were recruited. The ratio of the length of the right index finger (2D) to that of the right ring finger (4D) (2D/4D ratio) served as a surrogate of prenatal T exposure, and postnatal T was determined using salivary T concentration. Behavioral symptoms were evaluated using the Swanson, Nolan, and Pelham - Version IV Scale for ADHD (SNAP-IV). Neurocognitive function was assessed using the Wechsler Intelligence Scale for Children - Fourth Edition (WISC-IV) and Conners' Continuous Performance Test (CPT). Lower 2D/4D ratios were associated with comorbid disruptive behavior disorders ( t =2.15, P =0.033) in all participants. Among the boys with ADHD, neither 2D/4D ratios nor salivary T levels were associated with behavioral symptoms or neurocognitive function. Among the girls with ADHD, the salivary T level was positively correlated with the Perceptual Reasoning Index of the WISC-IV ( r =0.48, P =0.001) and the Confidence Index ( r =0.37, P =0.017) and Omission Errors of the CPT ( r =0.62, P <0.001). Findings suggest that a higher prenatal T exposure is associated with a greater risk of developing disruptive behavior disorders, and T may exert differential neurocognitive effects between boys and girls with ADHD. However, the neurobiological mechanisms of T involved in the pathogenesis of ADHD warrant further investigation.
1997-09-01
91-D-0012 Task Order No. 0007 2.4.7 Milan Army Ammunition Plant, Phytoremediation Pilot Study, USAEC, 1996 .. .............................. 2-28 2.5...indicated that heavy metal contamination (lead, chromium, and mercury ) was present at relatively low levels, and explosive contamination was limited to...and MI172 where lead was found at 22.9 j.g/1 and 18.4 Ig/l, respectively. 2.4.7 Milan Army Ammunition Plant, Phytoremediation Pilot Study, USAEC, 1996
Klawonn, Anna M; Wilhelms, Daniel B; Lindström, Sarah H; Singh, Anand Kumar; Jaarola, Maarit; Wess, Jürgen; Fritz, Michael; Engblom, David
2018-01-01
The neurotransmitter acetylcholine has been implicated in reward learning and drug addiction. However, the roles of the various cholinergic receptor subtypes on different neuron populations remain elusive. Here we study the function of muscarinic M4 receptors (M4Rs) in dopamine D1 receptor (D1R) expressing neurons and cholinergic neurons (expressing choline acetyltransferase; ChAT), during various reward-enforced behaviors and in a "waiting"-impulsivity test. We applied cell-type-specific gene deletions targeting M4Rs in D1RCre or ChATCre mice. Mice lacking M4Rs in D1R-neurons displayed greater cocaine seeking and drug-primed reinstatement than their littermate controls in a Pavlovian conditioned place preference (CPP) paradigm. Furthermore, the M4R-D1RCre mice initiated significantly more premature responses (PRs) in the 5-choice-serial-reaction-time-task (5CSRTT) than their littermate controls, indicating impaired waiting impulse control. In contrast, mice lacking M4Rs in cholinergic neurons did not acquire cocaine Pavlovian conditioning. The M4R-ChATCre mice were also unable to learn positive reinforcement to either natural reward or cocaine in an operant runway paradigm. Immediate early gene (IEG) expression ( cFos and FosB ) induced by repeated cocaine injections was significantly increased in the forebrain of M4R-D1RCre mice, whereas it remained normal in the M4R-ChATCre mice. Our study illustrates that muscarinic M4Rs on specific neural populations, either cholinergic or D1R-expressing, are pivotal for learning processes related to both natural reward and drugs of abuse, with opposing functionality. Furthermore, we found that neurons expressing both M4Rs and D1Rs are important for signaling impulse control.
Potent and selective oxytocin receptor agonists without disulfide bridges.
Adachi, Yusuke; Sakimura, Katsuya; Shimizu, Yuji; Nakayama, Masaharu; Terao, Yasuko; Yano, Takahiko; Asami, Taiji
2017-06-01
Oxytocin (OT) is a neuropeptide involved in a wide variety of physiological actions, both peripherally and centrally. Many human studies have revealed the potential of OT to treat autism spectrum disorders and schizophrenia. OT interacts with the OT receptor (OTR) as well as vasopressin 1a and 1b receptors (V 1a R, V 1b R) as an agonist, and agonistic activity for V 1a R and V 1b R may have a negative impact on the therapeutic effects of OTR agonism in the CNS. An OTR-selective agonistic peptide, FE 202767, in which the structural differences from OT are a sulfide bond instead of a disulfide bond, and N-alkylglycine replacement for Pro at position 7, was reported. However, the effects of amino acid substitutions in OT have not been comprehensively investigated to compare OTR, V 1a R, and V 1b R activities. This led us to obtain a new OTR-selective analog by comprehensive amino acid substitutions of OT and replacement of the disulfide bond. A systematic amino acid scanning (Ala, Leu, Phe, Ser, Glu, or Arg) of desamino OT (dOT) at positions 2, 3, 4, 5, 7, and 8 revealed the tolerability for the substitution at positions 7 and 8. Further detailed study showed that trans-4-hydroxyproline (trans-Hyp) at position 7 and γ-methylleucine [Leu(Me)] at position 8 were markedly effective for improving receptor selectivity without decreasing the potency at the OTR. Subsequently, a combination of these amino acid substitutions with the replacement of the disulfide bond of dOT analogs with a sulfide bond (carba analog) or an amide bond (lactam analog) yielded several promising analogs, including carba-1-[trans-Hyp 7 ,Leu(Me) 8 ]dOT (14) with a higher potency (7.2pM) at OTR than that of OT and marked selectivity (>10,000-fold) over V 1a R and V 1b R. Hence, we investigated comprehensive modification of OT and obtained new OT analogs that exhibited high potency at OTR with marked selectivity. These OTR-selective agonists could be useful to investigate OTR-mediated effects on psychiatric disorders. Copyright © 2017 Elsevier Ltd. All rights reserved.
Polarizability of Rydberg atoms and the dominant long-range interactions
NASA Astrophysics Data System (ADS)
Hahn, Yukap
2000-10-01
The dominant long-range interaction of an alkali-metal atom with charged particles at low energies is given for large separation R by the dispersive potential W~=-αd/R4 in terms of the dipole polarizability αd. For atoms prepared initially in Rydberg states of quantum numbers (n, l), the potential assumes a more complicated form due to the complete or near degeneracy of the n manifold. Contributions to the polarizability are treated in two parts, (a) one for the nondegenerate states and (b) the other for the degenerate or near degenerate cases. It is shown that α~(b)d for case (b) is in general R dependent, and in the limit of complete degeneracy, diverges as R2. That is, for a small energy gap Δ between a pair of nearly degenerate states which are dipole coupled, the dispersion potential W(b)~=D/R2 for R
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.
1984-01-01
Regulus calendula ) 104. American Robin (Turdus migratorius) 105. Varied Thrush (Ixoreus naevius) 106. Water Pipit (Anthus spinoletta) 107. Northern...Sparrow (Passer domesticus) 67 Cq n n Ln4 in 0n IV~ Oil xoi CDw q f) D"j4 ( O N r-IN" HI-4 r-1 N O% OD 0% 14 % 4 E4-40 "- Z r4 0D C 00 P-4 CD" NN C4 r4
DOE Office of Scientific and Technical Information (OSTI.GOV)
Minesaki, Yukitaka
2015-01-01
We propose the discrete-time restricted four-body problem (d-R4BP), which approximates the orbits of the restricted four-body problem (R4BP). The d-R4BP is given as a special case of the discrete-time chain regularization of the general N-body problem published in Minesaki. Moreover, we analytically prove that the d-R4BP yields the correct orbits corresponding to the elliptic relative equilibrium solutions of the R4BP when the three primaries form an equilateral triangle at any time. Such orbits include the orbit of a relative equilibrium solution already discovered by Baltagiannis and Papadakis. Until the proof in this work, there has been no discrete analog thatmore » preserves the orbits of elliptic relative equilibrium solutions in the R4BP. For a long time interval, the d-R4BP can precisely compute some stable periodic orbits in the Sun–Jupiter–Trojan asteroid–spacecraft system that cannot necessarily be reproduced by other generic integrators.« less
Analyses of direct and indirect impacts of a positive list system on pharmaceutical R&D investments.
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. Copyright © 2013 Elsevier HS Journals, Inc. All rights reserved.
1994-03-01
W) CV) Ln C4 ý qr v 0 V m tD Ln mw qw co en CY) m Pý- CD CA CL 0 E x 0 ui 0 (D tO lD r,. rý. ej 0 Cn 0 Cj CY) (D (n Go L) W L) 0 LO CY) (Y) Cl rý m w...C " L~ 0 - -L C. L. L. s- ol U=~ M0C0 o.-0eý= G CO C- Co*-I’U rC ’U td 06 0 060 0 m 0 f’>-J (n 4- (d )O00 ŕ 0 4- ed - 4- 1’-O 0 0 0 - 05 4dS- 4...Mcc CL L) 41 CL 0 cc U) = cn u 0 c 4n td (D (n u u z w go to 0 LID = a. - I u L) U - < 0 w (D CL 0 w cn u I-- u 0 ww < I-- z 1-- 0 (n cy 4 = (D Cn L
The perspectives, information and conclusions conveyed in research project abstracts, progress reports, final reports, journal abstracts and journal publications convey the viewpoints of the principal investigator and may not represent the views and policies of ORD and EPA. Concl...
The perspectives, information and conclusions conveyed in research project abstracts, progress reports, final reports, journal abstracts and journal publications convey the viewpoints of the principal investigator and may not represent the views and policies of ORD and EPA. Concl...
The perspectives, information and conclusions conveyed in research project abstracts, progress reports, final reports, journal abstracts and journal publications convey the viewpoints of the principal investigator and may not represent the views and policies of ORD and EPA. Concl...
The perspectives, information and conclusions conveyed in research project abstracts, progress reports, final reports, journal abstracts and journal publications convey the viewpoints of the principal investigator and may not represent the views and policies of ORD and EPA. Concl...
The perspectives, information and conclusions conveyed in research project abstracts, progress reports, final reports, journal abstracts and journal publications convey the viewpoints of the principal investigator and may not represent the views and policies of ORD and EPA. Concl...
Theoretical study of local structure for Ni2+ ions at tetragonal sites in K2ZnF4:Ni2+ system.
Wang, Su-Juan; Kuang, Xiao-Yu; Lu, Cheng
2008-12-15
A theoretical method for studying the local lattice structure of Ni2+ ions in (NiF6)(4-) coordination complex is presented. Using the ligand-field model, the formulas relating the microscopic spin Hamiltonian parameters with the crystal structure parameters are derived. Based on the theoretical formulas, the 45 x 45 complete energy matrices for d8 (d2) configuration ions in a tetragonal ligand-field are constructed. By diagonalizing the complete energy matrices, the local distortion structure parameters (R perpendicular and R || ) of Ni2+ ions in K2ZnF4:Ni2+ system have been investigated. The theoretical results are accorded well with the experimental values. Moreover, to understand the detailed physical and chemical properties of the fluoroperovskite crystals, the theoretical values of the g factor of K2ZnF4:Ni2+ system at 78 and 290 K are reported first.
MicroRNA-214 suppresses gluconeogenesis by targeting activating transcriptional factor 4.
Li, Kai; Zhang, Jin; Yu, Junjie; Liu, Bin; Guo, Yajie; Deng, Jiali; Chen, Shanghai; Wang, Chunxia; Guo, Feifan
2015-03-27
Although the gluconeogenesis pathway is already a target for the treatment of type 2 diabetes, the potential role of microRNAs (miRNAs) in gluconeogenesis remains unclear. Here, we investigated the physiological functions of miR-214 in gluconeogenesis. The expression of miR-214 was suppressed by glucagon via protein kinase A signaling in primary hepatocytes, and miR-214 was down-regulated in the livers of fasted, high fat diet-induced diabetic and leptin receptor-mutated (db/db) mice. The overexpression of miR-214 in primary hepatocytes suppressed glucose production, and silencing miR-214 reversed this effect. Gluconeogenesis was suppressed in the livers of mice injected with an adenovirus expressing miR-214 (Ad-miR-214). Additionally, Ad-miR-214 alleviated high fat diet-induced elevation of gluconeogenesis and hyperglycemia. Furthermore, we found that activating transcription factor 4 (ATF4), a reported target of miR-214, can reverse the suppressive effect of miR-214 on gluconeogenesis in primary hepatocytes, and this suppressive effect was blocked in liver-specific ATF4 knock-out mice. ATF4 regulated gluconeogenesis via affecting forkhead box protein O1 (FOXO1) transcriptional activity. Finally, liver-specific miR-214 transgenic mice exhibited suppressed gluconeogenesis and reduced expression of ATF4, phosphoenolpyruvate carboxykinase, and glucose-6-phosphatase in liver. Taken together, our results suggest that the miR-214-ATF4 axis is a novel pathway for the regulation of hepatic gluconeogenesis. © 2015 by The American Society for Biochemistry and Molecular Biology, Inc.
The Human Operator and System Effectiveness.
1984-06-01
required in some decision process (e. g., component selection). 14 le NWC TP 6541 3. Be clearly stated in the final study report, with the rationale...BICYC LES t 5 - : BUSRSTO %* -.-’. ... % .% % . . J . % ... ~ ,4~ V’ .- *’ .-.-. , -LOADER T 1 = 1 + t 2 + LARGEST OF (t 3, t 4, t5) ,’ .t 2 t 3...34’,"t OPEN I UNLOAD " "I t DOORS PASSENGERSHI H" "" I PARK" "B. I AT t 5 t 4 BU SO OPERATE UNLOAD • . _ P LO A D ER BICYC LES -’, ",T 1 t I + L A R G
An in Vivo Investigation of Brain Inflammation in Gulf War Illness with Integrated PET/MR Imaging
2015-10-01
Research Assistant Researcher Identifier (ORCID ID): N /A Nearest Person Month Worked: 3 Contribution to...Izquierdo-Garcia,1 Ru-Rong Ji,2,6 Misha Riley,1 Ajay D. Wasan,2,4,7 Nicole R. Zürcher,1 Daniel S. Albrecht,1 Mark G. Vangel,1 Bruce R. Rosen,1,8 Vitaly ...12 | 5 by guest on January 12, 2015 D ow nloaded from 18 Figure 2 Whole-brain voxel-wise analyses. (A) Median SUVR map from healthy controls ( n = 9
Civilian Manpower Statistics, December 31, 1992.
1992-12-31
CC CA C~Ch4 u, 004 - C C/) s 4 C) clIi a), fuQ 6 ’V -, -- 0C) 00’ 4 ) 4J ~C 0 a)Q)O 00 0 4 -4 aj a) 4-) 00b -. 4-2.rS 0 E rs o w 0 ,a +) td 0 0 0G P4...4) 4-; W. 4 -. 2C ( > 4) 0 :$r v +- b h"-I Q) 1 o 0 < 44 4) (n (d n 4) >. 0) , U ) U 4bD " -)414 0d 4-) 4j 0 V) M (. -) 4)f -. 0) -A 10) -ZU4 r=U 4ý
1980-04-01
r G 2 W to* L- .0 -- >0m0 L tox >- td . U74o m Et -t C V).--01- MU a#CO Cmto (D 3- 4h - ’- ; %14 4 , c o ’ow ft 000 -- -t4ME’toL0S:Oj- D- C - L 1: 0) d...I- C M-D w 0A--DC C 0 c c 0 :3 -DmC tD 4)Oft- (A OU .l C). 4A LDQC4--U-- M*; U.;O 0 fu ,0 4 a> U W, GD >. 0 D GDI GDO; )D Co C U ODDDL MG (n 4 In 41...r4C4 u 41 C, a, -300c’- 41.. : WC WA 140U Zm L: 1 >. O X424.a 0 L E -0 0) z’ a- W - 3uV ’oC o w mc C-1 (000 40 02 .D Ga cr > -4 II -, 0r0 OC L
Mechanical Determinants of Faster Change of Direction Speed Performance in Male Athletes.
DosʼSantos, Thomas; Thomas, Christopher; Jones, Paul A; Comfort, Paul
2017-03-01
Dos'Santos, T, Thomas, C, Jones, PA, and Comfort, P. Mechanical determinants of faster change of direction speed performance in male athletes. J Strength Cond Res 31(3): 696-705, 2017-Mechanical variables during change of directions, for example, braking and propulsive forces, impulses, and ground contact times (GCT) have been identified as determinants of faster change of direction speed (CODS) performance. The purpose of this study was to investigate the mechanical determinants of 180° CODS performance with mechanical characteristic comparisons between faster and slower performers; while exploring the role of the penultimate foot contact (PEN) during the change of direction. Forty multidirectional male athletes performed 6 modified 505 (mod505) trials (3 left and right), and ground reaction forces were collected across the PEN and final foot contact (FINAL) during the change of direction. Pearson's correlation coefficients and coefficients of determination were used to explore the relationship between mechanical variables and mod505 completion time. Independent T-tests and Cohen's d effect sizes (ES) were conducted between faster (n = 10) and slower (n = 10) mod505 performers to explore differences in mechanical variables. Faster CODS performance was associated (p ≤ 0.05) with shorter GCTs (r = 0.701-0.757), greater horizontal propulsive forces (HPF) (r = -0.572 to -0.611), greater horizontal braking forces (HBF) in the PEN (r = -0.337), lower HBF ratios (r = -0.429), and lower FINAL vertical impact forces (VIF) (r = 0.449-0.559). Faster athletes demonstrated significantly (p ≤ 0.05, ES = 1.08-2.54) shorter FINAL GCTs, produced lower VIF, lower HBF ratios, and greater HPF in comparison to slower athletes. These findings suggest that different mechanical properties are required to produce faster CODS performance, with differences in mechanical properties observed between fast and slower performers. Furthermore, applying a greater proportion of braking force during the PEN relative to the FINAL may be advantageous for turning performance.
The Onsala Twin Telescope Project
NASA Astrophysics Data System (ADS)
Haas, R.
2013-08-01
This paper described the Onsala Twin Telescope project. The project aims at the construction of two new radio telescopes at the Onsala Space Observatory, following the VLBI2010 concept. The project starts in 2013 and is expected to be finalized within 4 years. Z% O. Rydbeck. Chalmers Tekniska Högskola, Göteborg, ISBN 91-7032-621-5, 407-823, 1991. B. Petrachenko, A. Niell, D. Behrend, B. Corey, J. Böhm, P. Charlot, A. Collioud, J. Gipson, R. Haas, Th. Hobiger, Y. Koyama, D. MacMillan, Z. Malkin, T. Nilsson, A. Pany, G. Tuccari, A. Whitney, and J. Wresnik. Design Aspects of the VLBI2010 System. NASA/TM-2009-214180, 58 pp., 2009. R. Haas, G. Elgered, J. Löfgren, T. Ning, and H.-G. Scherneck. Onsala Space Observatory - IVS Network Station. In K. D. Baver and D. Behrend, editors, International VLBI Service for Geodesy and Astrometry 2011 Annual Report, NASA/TP-2012-217505, 88-91, 2012. H.-G. Scherneck, G. Elgered, J. M. Johansson, and B. O. Rönnäng. Phys. Chem. Earth, Vol. 23, No. 7-8, 811-823, 1998. A. R. Whitney. Ph.D. thesis, Dept. of Electrical engineering, MIT Cambridge, MA., 1974. B. A. Harper, J. D. Kepert, and J. D. Ginger. Guidelines for converting between various wind averaging periods in tropical cyclone conditions. WMO/TD-No. 1555, 64 pp., 2010 (available at \\url{http://www.wmo.int/pages/prog/www/tcp/documents/WMO_TD_1555_en.pdf})
Vergara, Macarena D; Keller, Victor N; Fuentealba, José A; Gysling, Katia
2017-05-01
The prelimbic area (PL) of the medial Prefrontal cortex (mPFC) is involved in the acquisition and expression of conditioned and innate fear. Both types of fear share several neuronal pathways. It has been documented that dopamine (DA) plays an important role in the regulation of aversive memories in the mPFC. The exposure to an aversive stimulus, such as the smell of a predator odor or the exposure to footshock stress is accompanied by an increase in mPFC DA release. Evidence suggests that the type 4 dopaminergic receptor (D4R) is the molecular target through which DA modulates fear expression. In fact, the mPFC is the brain region with the highest expression of D4R; however, the role of D4R in the expression of innate fear has not been fully elucidated. Therefore, the principal objective of this work was to evaluate the participation of mPFC D4R in the expression of innate fear. Rats were exposed to the elevated plus-maze (EPM) and to the cat odor paradigm after the intra PL injection of L-745,870, selective D4R antagonist, to measure the expression of fear-related behaviors. Intra PL injection of L-745,870 increased the time spent in the EPM open arms and decreased freezing behavior in the cat odor paradigm. Our results also showed that D4R is expressed in GABAergic and pyramidal neurons in the PL region of PFC. Thus, D4R antagonism in the PL decreases the expression of innate fear-behavior indicating that the activation of D4R in the PL is necessary for the expression of innate fear-behavior. Copyright © 2017 Elsevier B.V. All rights reserved.
1986-12-01
Y CLS$1F-.AT N OF THIS...1 MN cD jO 0 -O Ocn00 ~ c" W) 400’ rno n + a9 .9 .i , vi 4 -W cm C44. y c 000 CD %D 1% CD-. U 4 CnN C! - N ON N N TV o 00 e~. r, ML 4r WL ne 0...to N D N4 ’aN N " Nf Y N Nm 00 1C’ bq D Wc iG f". rC W C4 No N N D On ’-0 0 0 f" .4l cc W.4 LoP doE N 04 In Ins. +. V. 0 0 fn 10 C Go 0D C 00’ 4o
Ultrastructure Processing and Characterization of Polymers
1988-01-01
Eur. Polym. J . 24, 123-127 (1988) (with R. Vukovic , G. Bogdanic, V. Kuresevic, and W.J. MacKnight) "Miscibility and Phase Behavior in Poly (2,6...Month, Day) |I5 fAGE U d FINAL FROM TO j -"_ 16. SUPPLEMENTARY NOTATION 17. COSATI CODES 18. SUBJECT TERMS (Continue on reverse if necessary and...Lee Dr. J . Obrzut Dr. D. Rice Dr. J . Schlenoff Dr. J . Shim V. JUNIOR RESEARCH PERSONNEL: M. Bishop R. Gregorius M. Lux J . Machado M. Masse R
Loss of TLR2 Worsens Spontaneous Colitis in MDR1A Deficiency through Commensally Induced Pyroptosis
Ey, Birgit; Eyking, Annette; Klepak, Magdalena; Salzman, Nita H.; Göthert, Joachim R.; Rünzi, Michael; Schmid, Kurt W.; Gerken, Guido; Podolsky, Daniel K.
2013-01-01
Variants of the multidrug resistance gene (MDR1/ABCB1) have been associated with increased susceptibility to severe ulcerative colitis (UC). In this study, we investigated the role of TLR/IL-1R signaling pathways including the common adaptor MyD88 in the pathogenesis of chronic colonic inflammation in MDR1A deficiency. Double- or triple-null mice lacking TLR2, MD-2, MyD88, and MDR1A were generated in the FVB/N background. Deletion of TLR2 in MDR1A deficiency resulted in fulminant pancolitis with early expansion of CD11b+ myeloid cells and rapid shift toward TH1-dominant immune responses in the lamina propria. Colitis exacerbation in TLR2/MDR1A double-knockout mice required the unaltered commensal microbiota and the LPS coreceptor MD-2. Blockade of IL-1β activity by treatment with IL-1R antagonist (IL-1Ra; Anakinra) inhibited colitis acceleration in TLR2/MDR1A double deficiency; intestinal CD11b+Ly6C+-derived IL-1β production and inflammation entirely depended on MyD88. TLR2/MDR1A double-knockout CD11b+ myeloid cells expressed MD-2/TLR4 and hyperresponded to nonpathogenic Escherichia coli or LPS with reactive oxygen species production and caspase-1 activation, leading to excessive cell death and release of proinflammatory IL-1β, consistent with pyroptosis. Inhibition of reactive oxygen species–mediated lysosome degradation suppressed LPS hyperresponsiveness. Finally, active UC in patients carrying the TLR2-R753Q and MDR1-C3435T polymorphisms was associated with increased nuclear expression of caspase-1 protein and cell death in areas of acute inflammation, compared with active UC patients without these variants. In conclusion, we show that the combined defect of two UC susceptibility genes, MDR1A and TLR2, sets the stage for spontaneous and uncontrolled colitis progression through MD-2 and IL-1R signaling via MyD88, and we identify commensally induced pyroptosis as a potential innate immune effector in severe UC pathogenesis. PMID:23636052
Loss of TLR2 worsens spontaneous colitis in MDR1A deficiency through commensally induced pyroptosis.
Ey, Birgit; Eyking, Annette; Klepak, Magdalena; Salzman, Nita H; Göthert, Joachim R; Rünzi, Michael; Schmid, Kurt W; Gerken, Guido; Podolsky, Daniel K; Cario, Elke
2013-06-01
Variants of the multidrug resistance gene (MDR1/ABCB1) have been associated with increased susceptibility to severe ulcerative colitis (UC). In this study, we investigated the role of TLR/IL-1R signaling pathways including the common adaptor MyD88 in the pathogenesis of chronic colonic inflammation in MDR1A deficiency. Double- or triple-null mice lacking TLR2, MD-2, MyD88, and MDR1A were generated in the FVB/N background. Deletion of TLR2 in MDR1A deficiency resulted in fulminant pancolitis with early expansion of CD11b(+) myeloid cells and rapid shift toward TH1-dominant immune responses in the lamina propria. Colitis exacerbation in TLR2/MDR1A double-knockout mice required the unaltered commensal microbiota and the LPS coreceptor MD-2. Blockade of IL-1β activity by treatment with IL-1R antagonist (IL-1Ra; Anakinra) inhibited colitis acceleration in TLR2/MDR1A double deficiency; intestinal CD11b(+)Ly6C(+)-derived IL-1β production and inflammation entirely depended on MyD88. TLR2/MDR1A double-knockout CD11b(+) myeloid cells expressed MD-2/TLR4 and hyperresponded to nonpathogenic Escherichia coli or LPS with reactive oxygen species production and caspase-1 activation, leading to excessive cell death and release of proinflammatory IL-1β, consistent with pyroptosis. Inhibition of reactive oxygen species-mediated lysosome degradation suppressed LPS hyperresponsiveness. Finally, active UC in patients carrying the TLR2-R753Q and MDR1-C3435T polymorphisms was associated with increased nuclear expression of caspase-1 protein and cell death in areas of acute inflammation, compared with active UC patients without these variants. In conclusion, we show that the combined defect of two UC susceptibility genes, MDR1A and TLR2, sets the stage for spontaneous and uncontrolled colitis progression through MD-2 and IL-1R signaling via MyD88, and we identify commensally induced pyroptosis as a potential innate immune effector in severe UC pathogenesis.
The D 2 k R 4 invariants of mathcal{N} = 8 supergravity
NASA Astrophysics Data System (ADS)
Freedman, Daniel Z.; Tonni, Erik
2011-04-01
The existence of a linearized SUSY invariant for mathcal{N} = 8 supergravity whose gravitational components are usually called R 4 was established long ago by on-shell super-space arguments. Superspace and string theory methods have also established analogous higher dimensional D 2 k R 4 invariants. However, very little is known about the SUSY completions of these operators which involve other fields of the theory. In this paper we find the detailed component expansion of the linearized R 4 invariant starting from the corresponding superamplitude which generates all component matrix elements of the operator. It is then quite straightforward to extend results to the entire set of D 2 k R 4 operators.
Handheld Frequency Domain Vector EMI Sensing for UXO Discrimination
2010-07-01
the metric coefficient hξ = d 2 √ ξ 20 −η2 ξ 20 −1 . (4.1.18) The orthogonality of the Legendre and trigonometric functions [29] yields bpmn =− ∫ 1 −1...m Nr ∑ l=1 ρl,mnΓ µ l,mn(r j), (4.1.20) where Γµl,mn(r j) = 1 ∑ p=0 bpmn (r j) ∫ Rµ(r j) dsRµ n̂µ · ∫ 2π 0 Tpm(φ ′) 3(ξ̂′ ·Rl)Rl/R2l − ξ̂′ 4πR3l χl dφ...j) = 1 ∑ p=0 bpmn (r j) ∮ Rµ(r j) dlRµ · ∫ 2π 0 Tpm(φ ′) ξ̂′×Rl 4πR3l χl dφ ′. (4.1.23) Equation (4.1.20) can be turned into a linear system by finding
Efficient Training Methods for Conditional Random Fields
2008-02-01
Artificial Intelli - gence (UAI), 2002. [129] Ben Taskar, Carlos Guestrin, and Daphne Koller. Max...new, old) R es id ua l( ne w , c vg ) − R es id ua l( ol d, c vg ) −2 0 2 4 6 − 4 − 2 0 2 4 Error dynamic range (new, old) R es id ua l( ne w , c vg...R es id ua l( ol d, c vg ) −2 0 2 4 6 − 4 − 2 0 2 4 KL (old, new) R es id ua l( ne w , c vg ) − R es id ua
Enriori, Pablo J.; Jensen, Thomas Elbenhardt; Garcia-Rudaz, Cecilia; Litwak, Sara A.; Raun, Kirsten; Wojtaszewski, Jørgen; Wulff, Birgitte Schjellerup; Cowley, Michael A.
2016-01-01
The melanocortin system includes five G-protein coupled receptors (family A) defined as MC1R-MC5R, which are stimulated by endogenous agonists derived from proopiomelanocortin (POMC). The melanocortin system has been intensely studied for its central actions in body weight and energy expenditure regulation, which are mainly mediated by MC4R. The pituitary gland is the source of various POMC-derived hormones released to the circulation, which raises the possibility that there may be actions of the melanocortins on peripheral energy homeostasis. In this study, we examined the molecular signaling pathway involved in α-MSH-stimulated glucose uptake in differentiated L6 myotubes and mouse muscle explants. In order to examine the involvement of AMPK, we investigate α-MSH stimulation in both wild type and AMPK deficient mice. We found that α-MSH significantly induces phosphorylation of TBC1 domain (TBC1D) family member 1 (S237 and T596), which is independent of upstream PKA and AMPK. We find no evidence to support that α-MSH-stimulated glucose uptake involves TBC1D4 phosphorylation (T642 and S704) or GLUT4 translocation. PMID:27467141
NASA Astrophysics Data System (ADS)
Pini, Maria Gloria; Rettori, Angelo
1993-08-01
The thermodynamical properties of an alternating spin (S,s) one-dimensional (1D) Ising model with competing nearest- and next-nearest-neighbor interactions are exactly calculated using a transfer-matrix technique. In contrast to the case S=s=1/2, previously investigated by Harada, the alternation of different spins (S≠s) along the chain is found to give rise to two-peaked static structure factors, signaling the coexistence of different short-range-order configurations. The relevance of our calculations with regard to recent experimental data by Gatteschi et al. in quasi-1D molecular magnetic materials, R (hfac)3 NITEt (R=Gd, Tb, Dy, Ho, Er, . . .), is discussed; hfac is hexafluoro-acetylacetonate and NlTEt is 2-Ethyl-4,4,5,5-tetramethyl-4,5-dihydro-1H-imidazolyl-1-oxyl-3-oxide.
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, such as those of the B horizon. PMID:10919784
Cluzeau, Jérôme; Lubell, William D
2004-03-05
Four methyl 9-oxo-8-(N-(Boc)-amino)-4-phenyl-1-azabicyclo[4.3.0]nonane carboxylates (11, 4-Ph-I(9)aa-OMe) were synthesized from (2S,8S,5E)-di-tert-butyl-4-oxo-5-ene-2,8-bis[N-(PhF)amino]azelate [(5E)-7, PhF = 9-(9-phenylfluorenyl)] via a seven-step process featuring a conjugate addition/reductive amination/lactam cyclization sequence. Various nucleophiles were used in the conjugate addition reactions on enone (5E)-7 as a general route for making alpha,omega-diaminoazelates possessing different substituents in good yield albeit low diastereoselectivity except in the case of aryl Grignard reagents (9/1 to 15/1 drs). 6-Phenylazelates (6S)-8d and (6R)-8d were separated by chromatography and diastereoselective precipitation and independently transformed into 4-Ph-I(9)aa-OMe. From (6S)-8d, (2S,4R,6R,8S)-4-Ph-I(9)aa-OMe 11 was prepared selectively in 51% yield. Reductive amination of (6R)-8d provided the desired pipecolates 9 along with desamino compound 10, which was minimized by performing the hydrogenation in the presence of ammonium acetate. Subsequent ester exchange, lactam cyclization, and amine protection provided three products (2R,4S,6S,8R)-, (2R,4S,6S,8S)-, and (2S,4S,6R,8S)-4-Ph-I(9)aa-OMe 11 in 10, 6, and 6% yields, respectively, from (6R)-8d. Ester hydrolysis of (2S,4R,6R,8S)-11 furnished 4-phenyl indolizidin-9-one N-(Boc)amino acid 3 as a novel constrained Ala-Phe dipeptide surrogate for studying conformation-activity relationships of biologically active peptides.
D4 receptor deficiency in mice has limited effects on impulsivity and novelty seeking.
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.
An EUDET/AIDA Pixel Beam Telescope for Detector Development
NASA Astrophysics Data System (ADS)
Rubinskiy, I.; EUDET Consortium; AIDA Consortium
Ahigh resolution(σ< 2 μm) beam telescope based on monolithic active pixel sensors (MAPS) was developed within the EUDET collaboration. EUDET was a coordinated detector R&D programme for the future International Linear Collider providing test beam infrastructure to detector R&D groups. The telescope consists of six sensor planes with a pixel pitch of either 18.4 μm or 10 μmand canbe operated insidea solenoidal magnetic fieldofupto1.2T.Ageneral purpose cooling, positioning, data acquisition (DAQ) and offine data analysis tools are available for the users. The excellent resolution, readout rate andDAQintegration capabilities made the telescopea primary beam tests tool also for several CERN based experiments. In this report the performance of the final telescope is presented. The plans for an even more flexible telescope with three differentpixel technologies(ATLASPixel, Mimosa,Timepix) withinthenew European detector infrastructure project AIDA are presented.
Field Quality from Tolerance Stack-up In R&D Quadrupoles for the Advanced Photon Source Upgrade
DOE Office of Scientific and Technical Information (OSTI.GOV)
Liu, J.; Jaski, M.; Dejus, R.
2016-10-01
The Advanced Photon Source (APS) at Argonne National Laboratory (ANL) is considering upgrading the current double-bend, 7-GeV, 3rd generation storage ring to a 6-GeV, 4th generation storage ring with a Multibend Achromat (MBA) lattice. In this study, a novel method is proposed to determine fabrication and assembly tolerances through a combination of magnetic and mechanical tolerance analyses. Mechanical tolerance stackup analyses using Teamcenter Variation Analysis are carried out to determine the part and assembly level fabrication tolerances. Finite element analyses using OPERA are conducted to estimate the effect of fabrication and assembly errors on the magnetic field of a quadrupolemore » magnet and to determine the allowable tolerances to achieve the desired magnetic performance. Finally, results of measurements in R&D quadrupole prototypes are compared with the analysis results.« less
Clinical anthropometrics and body composition from 3D whole-body surface scans.
Ng, B K; Hinton, B J; Fan, B; Kanaya, A M; Shepherd, J A
2016-11-01
Obesity is a significant worldwide epidemic that necessitates accessible tools for robust body composition analysis. We investigated whether widely available 3D body surface scanners can provide clinically relevant direct anthropometrics (circumferences, areas and volumes) and body composition estimates (regional fat/lean masses). Thirty-nine healthy adults stratified by age, sex and body mass index (BMI) underwent whole-body 3D scans, dual energy X-ray absorptiometry (DXA), air displacement plethysmography and tape measurements. Linear regressions were performed to assess agreement between 3D measurements and criterion methods. Linear models were derived to predict DXA body composition from 3D scan measurements. Thirty-seven external fitness center users underwent 3D scans and bioelectrical impedance analysis for model validation. 3D body scan measurements correlated strongly to criterion methods: waist circumference R 2 =0.95, hip circumference R 2 =0.92, surface area R 2 =0.97 and volume R 2 =0.99. However, systematic differences were observed for each measure due to discrepancies in landmark positioning. Predictive body composition equations showed strong agreement for whole body (fat mass R 2 =0.95, root mean square error (RMSE)=2.4 kg; fat-free mass R 2 =0.96, RMSE=2.2 kg) and arms, legs and trunk (R 2 =0.79-0.94, RMSE=0.5-1.7 kg). Visceral fat prediction showed moderate agreement (R 2 =0.75, RMSE=0.11 kg). 3D surface scanners offer precise and stable automated measurements of body shape and composition. Software updates may be needed to resolve measurement biases resulting from landmark positioning discrepancies. Further studies are justified to elucidate relationships between body shape, composition and metabolic health across sex, age, BMI and ethnicity groups, as well as in those with metabolic disorders.
2015-01-01
Antagonist and partial agonist modulators of the dopamine D3 receptor (D3R) have emerged as promising therapeutics for the treatment of substance abuse and neuropsychiatric disorders. However, development of druglike lead compounds with selectivity for the D3 receptor has been challenging because of the high sequence homology between the D3R and the dopamine D2 receptor (D2R). In this effort, we synthesized a series of acylaminobutylpiperazines incorporating aza-aromatic units and evaluated their binding and functional activities at the D3 and D2 receptors. Docking studies and results from evaluations against a set of chimeric and mutant receptors suggest that interactions at the extracellular end of TM7 contribute to the D3R versus D2R selectivity of these ligands. Molecular insights from this study could potentially enable rational design of potent and selective D3R ligands. PMID:25126833
1974-08-31
AO-AO185 902 TECI4NOMICS INC OAKTON VA F/* 5/9 SYSTEM APPROACH TO NAVY MEDICAL EDUCATION AND TRAINING. APPEN--ETC(U) AUG 74 N0001A69-C-024A...CURRICULUM FOR DERMATOLOGY ASSISTANT APPLICATION OF A SYSTEM APPROACH U.*S. NAVY MEDICAL DEPARTMENT EDUCATION AND TRAINING PROGRAMS FINAL REPORT Di b j c, L...Education and Training R&D Bureau of Medicine and Surgery (Code 71G) o docau’wn’t has bcvn appmved n k its UNCLASSIFIED sEcuptiry CLASSIFICArIoN OF TH4IS PAGE
1975-09-29
no D AD-AO16 837 OPTIMIZATION OF EQUIPMENT AND TECHNIQUES FOR WELDING ALUMINUM IN THE THICKNESS RANGE OF ABOUT 1/16 TO 1/4 INCH Richard K. Sager, et...TECHNIQUES FOR WELDING ALUMINUM IN THE THICKNESS RANGE OF ABOUT 6~ TO ’i INCH by Richard K Sager Paul B Dickerson James E Grant Walter R Reichelt Maurice C...SharpMByron Shurnaker 0 Contract No N0024-74-C 5502 *,j Issued by NAVAL SEA SYSTEM COMMAND Project Serial No SF 541-702 Task 17016 FINAL REPORT Richard
Cocker, P J; Lin, M Y; Barrus, M M; Le Foll, B; Winstanley, C A
2016-09-01
Rats, like humans, are susceptible to the reinforcing effects of reward-related stimuli presented within a compound stimulus array, putatively analogous to the so-called near-miss effect. We have previously demonstrated using a rodent slot machine task (rSMT) that the reward expectancy these stimuli elicit is critically mediated by the dopamine D4 receptor. D4 receptors are principally located in prefrontal regions activated during slot machine play in humans, such as the insular cortex. The insula has recently attracted considerable interest as it appears to play a crucial role in substance and behavioral addictions. However, the insula is a heterogeneous area, and the relative contributions of subregions to addictive behaviors are unclear. Male Long Evans rats were trained to perform the rSMT, and then bilateral cannula targeting either the granular or agranular insula were implanted. The effects of inactivation and local administration of a D4 agonist were investigated. Temporary inactivation of the agranular, but not the granular insula impaired performance on the rSMT. In contrast, local infusion of the D4 agonist PD168077 into the agranular insula had no effect on task performance, but when administered into the granular insula, it improved animals' ability to differentiate winning from non-winning trials. The agranular insula may therefore modulate decision making when conflicting stimuli are present, potentially due to its role in generating a cohesive emotional percept based on both externally and internally generated signals, whereas the granular insular is not critical for this process. Nevertheless, D4 receptors within the granular insula may amplify the incentive salience of aversive environmental stimuli. These data provide insight into the neurobiological mechanism underpinning maladaptive reward expectancy during gambling and provide further evidence that D4 receptors represent a potential target for developing pharmacotherapies for problem gambling.
The Effects of Blast Trauma (Impulse Noise) on Hearing: A Parametric Study
1988-07-22
8217 q 2~~L m AALLA LAN LALALA v O 0- N( N N r4OD r: el LAr:r: v) 0n n LALALAL LAn LA vLnLA LAL LO 55 0 w * . . * 0 * * * * 0 w4 I n 4)L nL nr n nL nL nr...0ý LnLn LLLA r-in toN fLn Ln oA LA(n C.* * . . . * 10 C0 -. ~~0, NN m- AULA v *- r4~~~ ~- -1 H~i-r -4C (’eN r4* ntni L Len LAo mS- rLAn f m 04 0D LAAALL...C r-: 4 ýr- r- r-o8*i c oG o - G D% vooi %Vr- r- -4 ’-4 ( DE 0n u) tn A tn r- gn Ln .An inLn .n c4 0) 91 * . . ** Nn * LAn’Ln~ Ln to~ uiL . n nL n 040
An in Vivo Investigation of Brain Inflammation in Gulf War Illness with Integrated PET/MR Imaging
2017-10-01
personnel, collected data Funding Support: Name: Courtney Bergan Project Role: Research Assistant Researcher Identifier (ORCID ID): N /A Nearest...2015). 6. Owen, D. R. et al. Clin and Transl Imaging, 1-6 (2015). 7. Turkheimer, et al., Biochem Soc Trans 43(4), 586-592 (2015). 8. Zurcher, N . R. et...Oluwaseun Akeju4, George Cohen5, J. M. Hooker1, Vitaly Napadow1, M. L. Loggia1 1A. A. Martinos Center for Biomedical Imaging, Department of Radiology
NASA Astrophysics Data System (ADS)
Laslo, A.; Dudric, R.; Neumann, M.; Isnard, O.; Coldea, M.; Pop, V.
2014-12-01
The electronic properties of RCo5-xMx (R=Er, Sm, Tm; M=Si, Ga, Al; x=0 and 1) compounds were investigated by X-ray photoelectron spectroscopy (XPS). The study was focused on the Co 3s exchange splitting, the valence bands and chemical shifts of the elements from the analyzed compounds. The Co 2p3/2 core-level chemical shifts were described by means of the Auger parameters and Wagner plot. The hybridization between the R 5d6s and M 3sp and 4sp states and Co 3d states leads to a partial filling of the Co 3d band and to a decrease of the Co magnetic moments in comparison with the value in pure Co metal, in good agreement with the magnetic measurements.
Bidasee, Keshore R; Nallani, Karuna; Besch, Henry R; Dincer, U Deniz
2003-06-01
In a previous study, we showed that after 6 weeks of streptozotocin-induced diabetes (6D), expression of type 2 ryanodine receptor calcium-release channels (RyR2) did not change significantly in rat hearts. However, the ability of this protein to bind [3H]ryanodine was compromised. Loss in activity therefore resulted from diabetes-induced increases in post-translational modifications on RyR2. In the present study, the effects of diabetes on one type of modification, namely, changes in oxidative state of reactive sulfhydryls was investigated. RyR2 protein from 6D bound 42.3 +/- 7.6 less [3H]ryanodine than RyR2 from controls (6C). The loss in binding was minimized with 2 weeks of insulin treatment initiated after 4 weeks of diabetes (77.8 +/- 5.5% of 6C). Pretreating RyR2 from 6D with 2 mM dithiothreitol in vitro increases [3H]ryanodine binding by 60.8 +/- 5.3%. Dithiothreitol pretreatment of RyR2 from 6C increased [3H]ryanodine binding by 16.8 +/- 4.3%. The reagent pyrocoll interacts with distinct classes of free sulfhydryl groups on 6C RyR2 to induce two major effects. At concentrations < or = 10 microM, it deactivates RyR2 (decreases [3H]ryanodine binding), whereas at higher concentrations it activates them (increases [3H]ryanodine binding). This reagent was unable to activate RyR2 from 6D. Although RyR2 from insulin-treated animals was deactivated by low concentrations of pyrocoll, it was only partially activated at higher concentrations. These data suggest that the dysfunction of RyR2 induced by diabetes may be due in part to formation of disulfide bonds between adjacent sulfhydryl groups and that these changes were attenuated with insulin treatment.
Kołaczkowski, Marcin; Marcinkowska, Monika; Bucki, Adam; Śniecikowska, Joanna; Pawłowski, Maciej; Kazek, Grzegorz; Siwek, Agata; Jastrzębska-Więsek, Magdalena; Partyka, Anna; Wasik, Anna; Wesołowska, Anna; Mierzejewski, Paweł; Bienkowski, Przemyslaw
2015-03-06
We describe a novel class of designed multiple ligands (DMLs) combining serotonin 5-HT6 receptor (5-HT6R) antagonism with dopamine D2 receptor (D2R) partial agonism. Prototype hybrid molecules were designed using docking to receptor homology models. Diverse pharmacophore moieties yielded 3 series of hybrids with varying in vitro properties at 5-HT6R and D2R, and at M1 receptor and hERG channel antitargets. 4-(piperazin-1-yl)-1H-indole derivatives showed highest antagonist potency at 5-HT6R, with 7-butoxy-3,4-dihydroquinolin-2(1H)-one and 2-propoxybenzamide derivatives having promising D2R partial agonism. 2-(3-(4-(1-(phenylsulfonyl)-1H-indol-4-yl)piperazin-1-yl)propoxy)benzamide (47) exhibited nanomolar affinity at both 5-HT6R and D2R and was evaluated in rat models. It displayed potent antidepressant-like and anxiolytic-like activity in the Porsolt and Vogel tests, respectively, more pronounced than that of a reference selective 5-HT6R antagonist or D2R partial agonist. In addition, 47 also showed antidepressant-like activity (Porsolt's test) and anxiolytic-like activity (open field test) in aged (>18-month old) rats. In operant conditioning tests, 47 enhanced responding for sweet reward in the saccharin self-administration test, consistent with anti-anhedonic properties. Further, 47 facilitated extinction of non-reinforced responding for sweet reward, suggesting potential procognitive activity. Taken together, these studies suggest that DMLs combining 5-HT6R antagonism and D2R partial agonism may successfully target affective disorders in patients from different age groups without a risk of cognitive deficits. Copyright © 2014 Elsevier Masson SAS. All rights reserved.
1972-09-19
Dextrinated Lead Azide. ŕ.4.2 Reports. Applied Mathematic Panel of the National Defense Research Committee (AMP Report No. t01.1R, SRG-P No. 40). 1-2 0D 44811... dextrinated lead azide. (A normal ranae for these compounds shall have been obtained at the time of testing the explosive to be qualified.) 4.3...normal lead styphnate and dextrinated lead azide obtained using the same apparatus and procedure and run at the same time. 4.3.5 Special Requirements
Three essays on research and development
NASA Astrophysics Data System (ADS)
Sanyal, Paroma
The impact of institutional changes and market structure on research and development (R&D) and technical progress is controversial. My dissertation investigates the determinants of R&D in the context of institutional change. The first two papers address the impact of deregulation in the US electric utility industry on R&D. The third paper investigates the linkage between patenting and different funding sources and patent office attributes. The first paper, "Deregulation, Restructuring and Changing R&D Paradigms in the US Electric Utility Industry", investigates the linkage between market structures and the conduct of R&D in the US electric utility industry. The primary finding of this paper is that institutional and competition factors interact in a way that suggest that the occurrence of full deregulation, coupled with effective retail competition in the market may mitigate the problem of declining R&D expenditures in the face of deregulation. The second paper, "Powering a Green Progress: Environmental Research in the Absence of Regulatory Oversight" analyzes the impact of changing market structure on environmental R&D expenditures by IOUs in the electric utility industry. Conventional wisdom holds that increased competition would lead firms to cut back on R&D funds directed towards social goals, such as the environment. But these arguments fail to take account the threat of future environmental regulations and its influence on disciplining firms. Theory and empirical results from this paper suggest that under certain conditions, even with high monitoring costs, an environmental regulatory agency's threat of stricter future regulations will successfully stem the decrease in environmental R&D expenditures. My third paper, "Birth of a Patent: the Role of Parents, Nursemaids and Constraints", presents an integrated theoretical and empirical approach that models the effects of different sources of R&D funding and patent office attributes on the patenting process. The primary results are: First, the source of R&D funding as well as performer (academic, federal and industry) has a differential effect on patenting. Second, federal R&D has positive spillovers for company R&D. Third, in the short run patenting is heavily influenced by patent office attributes.
2011-08-01
9 4 INTRODUCTION Substance use disorders (SUD) and Posttraumatic stress disorder ( PTSD ) are some of the most prominent...Fee, F. (in press). Substance use disorder , PTSD , and traumatic brain injury. In J. Vasterling, R. Bryant, T. Keane (Eds). PTSD and Mild Traumatic ...another DoD investigator, on a paper on dissociation, PTSD , and substance use disorder , using DoD Naval Health research data. Dr. Najavits presented at
Molecular Identification of the Schwannomatosis Locus
2008-07-01
Schwannomatosis Locus PRINCIPAL INVESTIGATOR: Mia MacCollin Scott R. Plotkin, M.D., Ph.D...DATES COVERED 1 July 2003 – 30 June 2008 4. TITLE AND SUBTITLE 5a. CONTRACT NUMBER Molecular Identification of the Schwannomatosis Locus 5b...In 2007, mutations in the SMARCB1 tumor suppressor (also known as INI1 and hSNF5), which lies in the familial schwannomatosis candidate region, were
Projects in Computer Aided Climatology.
1981-07-01
LA 00 rn 0, LI) IT MA m ’N LA ) LA ) 4 ~’’ r~ M 6 LA ) 1.0 qT m o C: r- N r a 0 cc -4z ~~~ LA - 0 - 0 7n LA %D LALn’ m ’IT 0’ n’ LI co ID...8217. ’T co ff 41 N~ .C, r’ LAO 4o cr co Ln m m .i -IT 0’r-, Cm C.’Z ’.D 0 Q - LA LMA v’’ LnL NO - ’ LA N’ D ’..0 0’, 0 N1 N- D LA n LA 0 Ni L A A 4 ~ L...and Class B data. The set of Class A observacions are characterized by
1947-07-01
specimen melting through. Neither metallic nor refrac- tory strips were used to hack up the weld groove. The single-head weld was used, rather than a...fr>J NACA TN No. 1361 co m > m d O •P CM CO s o In «3 § • rH 8 g 8 "S| « a> rH ^ j5 r— "-1 rH +» » • • • rH d VX> vo o in i-i J- K...01 5 o d 4> 01 4> J5 oi g 4> 4> 4» C -Ö P Q, O 5- 5 o g. o 8> II 2 - u d •do *» a, d 2
Rose, Stuart; Minagawa, Jun; Seufferheld, Manfredo; Padden, Sean; Svensson, Bengt; Kolling, Derrick R. J.; Crofts, Antony R.; Govindjee
2009-01-01
Arginine257 (R257), in the de-helix that caps the QB site of the D1 protein, has been shown by mutational studies to play a key role in the sensitivity of Photosystem II (PS II) to bicarbonate-reversible binding of the formate anion. In this article, the role of this residue has been further investigated through D1 mutations (R257E, R257Q, and R257K) in Chlamydomonas reinhardtii. We have investigated the activity of the QB site by studying differences from wild type on the steady-state turnover of PS II, as assayed through chlorophyll (Chl) a fluorescence yield decay after flash excitation. The effects of p-benzoquinone (BQ, which oxidizes reduced QB, QB−) and 3-(3,4-dichlorophenyl)-1,1-dimethylurea (DCMU, which blocks electron flow from QA− to QB) were measured. The equilibrium constants of the two-electron gate were obtained through thermoluminescence measurements. The thermoluminescence properties were changed in the mutants, especially when observed after pretreatment with 100 μM BQ. A theoretical analysis of the thermoluminescence data, based mainly on the recombination pathways model of Rappaport et al. (2005), led to the conclusion that the free-energy difference for the recombination of QB− with S2 was reduced by 20–40 mV in the three mutants (D1-R257K, D1-R257Q, and D1-R257E); this was interpreted to be due to a lowering of the redox potential of QB/QB−. Further, since the recombination of QA− with S2 was unaffected, we suggest that no significant change in redox potential of QA/QA− occurred in these three mutants. The maximum variable Chl a fluorescence yield is lowered in the mutants, in the order R257K > R257Q > R257E, compared to wild type. Our analysis of the binary oscillations in Chl a fluorescence following pretreatment of cells with BQ showed that turnover of the QB site was relatively unaffected in the three mutants. The mutant D1-R257E had the lowest growth rate and steady-state activity and showed the weakest binary oscillations. We conclude that the size and the charge of the amino acid at the position D1-257 play a role in PS II function by modulating the effective redox potential of the QB/QB− pair. We discuss an indirect mechanism mediated through electrostatic and/or surface charge effects and the possibility of more pleiotropic effects arising from decreased stability of the D1/D2 and D1/CP47 interfaces. PMID:18777103
A Practicality Study of Air Force Depot Maintenance Cost Allocation.
1987-09-01
of Master of Science in Systems Management Bruce M. Kalish, B.S. Captain, USAF September 1987 Approved for public release; distribution unlimited...8217u foW’J.4D r-4 W) 0 r-- -% i -w vD 4 -W " V0%L : -40 r4c4c j nJ o Jm0 (n-)W 1W q 0 - m m O V 0 1oar-0co.o C.J, InaV -4 Io Dr- co %o %oc4 f5 0) r-’iD...Bibliography 1. AFSC Cost Estimating Handbook. Prepared for Air Force Systems Command by the Analytical Sciences Corporation, undated. 2. Air Force
Stereoselective and regiospecific hydroxylation of ketamine and norketamine.
Desta, Zeruesenay; Moaddel, Ruin; Ogburn, Evan T; Xu, Cong; Ramamoorthy, Anuradha; Venkata, Swarajya Lakshmi Vattem; Sanghvi, Mitesh; Goldberg, Michael E; Torjman, Marc C; Wainer, Irving W
2012-11-01
The objective was to determine the cytochrome P450s (CYPs) responsible for the stereoselective and regiospecific hydroxylation of ketamine [(R,S)-Ket] to diastereomeric hydroxyketamines, (2S,6S;2R,6R)-HK (5a) and (2S,6R;2R,6S)-HK (5b) and norketamine [(R,S)-norKet] to hydroxynorketamines, (2S,6S;2R,6R)-HNK (4a), (2S,6R;2R,6S)-HNK (4b), (2S,5S;2R,5R)-HNK (4c), (2S,4S;2R,4R)-HNK (4d), (2S,4R;2R,4S)-HNK (4e), (2S,5R;2R,5S)-HNK (4f). The enantiomers of Ket and norKet were incubated with characterized human liver microsomes (HLMs) and expressed CYPs. Metabolites were identified and quantified using LC/MS/MS and apparent kinetic constants estimated using single-site Michaelis-Menten, Hill or substrate inhibition equation. 5a was predominantly formed from (S)-Ket by CYP2A6 and N-demethylated to 4a by CYP2B6. 5b was formed from (R)- and (S)-Ket by CYP3A4/3A5 and N-demethylated to 4b by multiple enzymes. norKet incubation produced 4a, 4c and 4f and minor amounts of 4d and 4e. CYP2A6 and CYP2B6 were the major enzymes responsible for the formation of 4a, 4d and 4f, and CYP3A4/3A5 for the formation of 4e. The 4b metabolite was not detected in the norKet incubates. 5a and 4b were detected in plasma samples from patients receiving (R,S)-Ket, indicating that 5a and 5b are significant Ket metabolites. Large variations in HNK concentrations were observed suggesting that pharmacogenetics and/or metabolic drug interactions may play a role in therapeutic response.
Magnetochromic effect in multiferroic R In 1 ₋ x Mn x O 3 ( R = Tb , Dy)
Chen, P.; Holinsworth, B. S.; O'Neal, K. R.; ...
2015-05-26
We combined high field magnetization and magneto-optical spectroscopy to investigate spin-charge coupling in Mn-substituted rare-earth indium oxides of chemical formula RIn₁₋ xMn xO₃ (R=Tb, Dy). The edge states, on-site Mn³⁺d to d excitations, and rare-earth f-manifold excitations all track the magnetization energy due to dominant Zeeman interactions. The field-induced modifications to the rare-earth excitations are quite large because spin-orbit coupling naturally mixes spin and charge, suggesting that the next logical step in the design strategy should be to bring spin-orbit coupling onto the trigonal bipyramidal chromophore site with a 4 or 5d center.
Flight investigation of a four-dimensional terminal area guidance system for STOL aircraft
NASA Technical Reports Server (NTRS)
Neuman, F.; Hardy, G. H.
1981-01-01
A series of flight tests and fast-time simulations were conducted, using the augmentor wing jet STOL research aircraft and the STOLAND 4D-RNAV system to add to the growing data base of 4D-RNAV system performance capabilities. To obtain statistically meaningful data a limited amount of flight data were supplemented by a statistically significant amount of data obtained from fast-time simulation. The results of these tests are reported. Included are comparisons of the 4D-RNAV estimated winds with actual winds encountered in flight, as well as data on along-track navigation and guidance errors, and time-of-arrival errors at the final approach waypoint. In addition, a slight improvement of the STOLAND 4D-RNAV system is proposed and demonstrated, using the fast-time simulation.
Li, Qun; Sun, Jie; Ren, Tianhao; Guo, Lin; Yang, Zhilin; Yang, Qi; Chen, Hai
2018-04-01
Adsorption by carbon materials is one of the relatively fast methods in present research, which is widely used in emergency events. Activated carbon fiber (ACF) modified by nitric acid (N-ACF) was studied in this research to determine the adsorption performance for 2,4-dichlorophenoxyacetic acid (2,4-D). Subsequently, influence factors, adsorption isotherm models, kinetics and thermodynamic were investigated in a batch system to realize this adsorption. Experimental results showed that ACF modified by 0.1M nitric acid had a better removal ability than 2,4-D. Removal rate of 2,4-D by N-ACF was greatly influenced by pH with the optimum pH at 2. The superiority of the Langmuir isotherm model in describing the adsorption equilibrium was revealed by correlation coefficients R2 (R 2 ≥ 0.997). Furthermore, adsorption kinetics was well described by pseudo-second-order model. The results of thermodynamic showed that adsorption was a spontaneous, endothermic process with randomness increasing. Additionally, surface structure properties of adsorbent were characterized by Scanning electron microscopy, Fourier transform infrared spectroscopy, Specific surface area analysis of Brunauer, Emmett and Teller and Boehm's titration. It turned out that the micropore structure and functional groups on N-ACF all can contribute to the removal of 2,4-D.
Structural determination of the acidic exopolysaccharide produced by a Pseudomonas sp. strain 1.15.
Cescutti, P; Toffanin, R; Pollesello, P; Sutherland, I W
1999-01-31
Pseudomonas strain 1.15 was isolated from a freshwater biofilm and shown to produce considerable amounts of an acidic polysaccharide which was investigated by methylation analysis, NMR spectroscopy and ionspray mass spectrometry (ISMS). The polysaccharide was depolymerised by a bacteriophage-associated endoglucosidase and by autohydrolysis, and the resulting oligosaccharides were investigated by NMR spectroscopy and mass spectrometry. The resulting data showed that the parent repeating unit of the 1.15 exopolysaccharide (EPS) is a branched hexasaccharide. The main chain is constituted of the trisaccharide -->4)-alpha-L-Fucp-(1-->4)-alpha-L-Fucp-(1-->3)-beta-D-Glcp- (1--> and the side chain alpha-D-Galp-(1-->4)-beta-D-GlcAp-(1-->3)-alpha-D-Galp-(1-->is linked to O-3 of the first Fuc residue. The terminal non-reducing Gal carries a 1-carboxyethylidene acetal in the R configuration at the positions 4 and 6. Of the four different O-acetyl groups present in non-stoichiometric amounts, two were established to be on O-2 of the 3-linked Gal and on O-2 of the 4-linked Fuc.
Advanced Metallic Air Vehicle Structure Program
1976-08-01
r-Ř Z- cq rXH H ý-q P7 PI-I .rý17 > r4 %. I~tf Ifr )~ 1 m L cc -I O’t %D-Z r- 0~ c-4) 0ff f ~ ~ L ~ L~f a’oY C ca \\D oIt 01\\ mc I’DJ c-o ’-4<tD -zt...FIGURE~COV 2..111 HET O FASTNERHOLEIDETIFIATIN - PPE UCOER 87;B 7- 276 C-1 UPPER 5URFACE Tyl so L2 2.O-t- y ESP AT APPLED O AVSUR \\L1 Lt OF02O~ X72
Radiation Protection by the Antioxidant Alpha-Tocopherol Succinate
2005-01-01
agents, which are non- toxic and moderately radioprotective. These antioxidants include tocols (tocopherols and tocotrienols ), soy- isoflavones, vitamin...family of 8 tocols—4 each of α, β, γ, and δ tocopherols and tocotrienols (Figure 1). O CH3 R1 R2 HO CH3 CH3 CH3 CH3 CH3 R1 = R2 = CH3 d-alpha...CH3 CH3 R1 = R2 = CH3 R1 = R2 = H R1 = H, R2 = CH3 R1 = CH3, R2 = H d-alpha- tocotrienol d-beta- tocotrienol d-gamma- tocotrienol d-delta- tocotrienol
When Chocolate Seeking Becomes Compulsion: Gene-Environment Interplay
Patella, Loris; Andolina, Diego; Valzania, Alessandro; Latagliata, Emanuele Claudio; Felsani, Armando; Pompili, Assunta; Gasbarri, Antonella; Puglisi-Allegra, Stefano; Ventura, Rossella
2015-01-01
Background Eating disorders appear to be caused by a complex interaction between environmental and genetic factors, and compulsive eating in response to adverse circumstances characterizes many eating disorders. Materials and Methods We compared compulsion-like eating in the form of conditioned suppression of palatable food-seeking in adverse situations in stressed C57BL/6J and DBA/2J mice, two well-characterized inbred strains, to determine the influence of gene-environment interplay on this behavioral phenotype. Moreover, we tested the hypothesis that low accumbal D2 receptor (R) availability is a genetic risk factor of food compulsion-like behavior and that environmental conditions that induce compulsive eating alter D2R expression in the striatum. To this end, we measured D1R and D2R expression in the striatum and D1R, D2R and α1R levels in the medial prefrontal cortex, respectively, by western blot. Results Exposure to environmental conditions induces compulsion-like eating behavior, depending on genetic background. This behavioral pattern is linked to decreased availability of accumbal D2R. Moreover, exposure to certain environmental conditions upregulates D2R and downregulates α1R in the striatum and medial prefrontal cortex, respectively, of compulsive animals. These findings confirm the function of gene-environment interplay in the manifestation of compulsive eating and support the hypothesis that low accumbal D2R availability is a “constitutive” genetic risk factor for compulsion-like eating behavior. Finally, D2R upregulation and α1R downregulation in the striatum and medial prefrontal cortex, respectively, are potential neuroadaptive responses that parallel the shift from motivated to compulsive eating. PMID:25781028
1994-03-01
CyC)444 11_ n (0m m m ~ V c0 ( 40 00-4.- 4 -0 -4 -42 z O CAO1000Z de ON I~si CON1 02 0000000000 00 >-0000000000000 Cl!0 X0000 C toON Iiz Cci OOOOOOO 0...C0OV N 4 v de . d 00-49I 0~Ia I r*U- 4 4444 4 4 00ON 0 0 cThII1 600000 N 0004 ULg4 4(< . Co :: en UU4 4 P44 4r,0CUU0 0 0 0 If 1 U 4cqu 0 NIUJ-MG00 0 0 0...m CO) 0 Cq ’D rý 100111OLn mo If I Ca 0 Go 11 om 000 00 . 0 V 0-4 0Ln(DN - 0 M 0040 - 0 m 0OV(D - 0 (D if I cacao 11 z It Z Ln Z Ln-i C r4% z to
A Search for New Fuel Components in Explosive Mixtures with Ammonium Nitrate
1981-04-30
i AP-PENIMY A. rol~our Tnd#Ix entrl-s for dyes tested for euatecticmixture form7ation with wnmoniua.i nitrate 12010 C.!. Snivent tR.. d 3...lirainhto. %k ith sodium hydroide itnd sodium ýhlnrate l1r6nner, BP 739 182 o d )r nitrate (GP I1S52q) lh-lftier, Gi’ 3628P 9 (1’. 1, 308) (it) Iaat...K -__ __ __ __ _ R___ __ _ __ LEVEL... 0 Final Report A SEARCH FOR NEW FUEL COMPONENTS IN EXPLOSIVE MIXTURES WITH AMMONIUM NITRATE -m i Dr. Maurice C
Zhou, B; E, C Q; Bu, Y Y; Meng, L; Yan, X H; Wang, X F
2017-03-01
Eu 3 + -doped transparent glass ceramics containing MF 2 (M = Ba, Ca, Sr) nanocrystals were fabricated using a melt-quenching method, and the resulting structures were studied using X-ray diffraction. Levels 5 D 1 and 5 D 0 of Eu 3 + ions were verified as thermally coupled levels using the fluorescence intensity ratio method. The fluorescence intensity ratios, optical temperature sensitivity and thermal quenching ratios of the transparent glass ceramics were studied as a function of temperature. With an increase in temperature, the relative sensitivity (S R ) decreased sharply at first, then slowly increased, before finally decreasing. The minimum S R values of GCBaF 2 (GCB), GCCaF 2 (GCC) and GCSrF 2 (GCS) were 2.8 × 10 -4 , 0.8 × 10 -4 and 1.9 × 10 - 4 K -1 at 360, 269 and 319 K, respectively. Glass ceramics with an intense emission intensity can be used to convert the measured spectrum into temperature and may have an important role in temperature detectors. Copyright © 2016 John Wiley & Sons, Ltd.
Quan, Xiangchun; Ma, Jingyun; Xiong, Weicong; Wang, Xinrui
2015-06-01
Aerobic granular sludge degrading recalcitrant compounds are generally hard to be cultivated. This study investigated the feasibility of cultivating 2,4-dichlorophenoxyacetic acid (2,4-D) degrading aerobic granules using half-matured sludge granules pre-grown on glucose as the seeds and bioaugmentation with a 2,4-D degrading strain Achromobacter sp. QXH. Results showed that bioaugmentation promoted the steady transformation of glucose-grown granules to 2,4-D degrading sludge granules and fast establishment of 2,4-D degradation ability. The 2,4-D degradation rate of the bioaugmented granules was enhanced by 36-62 % compared to the control at 2,4-D concentrations of 144-565 mg/L on Day 18. The inoculated strain was incorporated into the half-matured granules successfully and survived till the end of operation (220 days). Sludge granules at a mean size of 420 µm and capable of utilizing 500 mg/L 2,4-D as the sole carbon source were finally obtained. Sludge microbial community shifted slightly during the whole operation and the dominant bacteria species belonged to Proteobacteria.
General/Flag Officer Worldwide Roster
1990-09-01
1 in 1 .mm ~o to00 c~J *L: to’ LLI0C Lu coz .- 01 No .jk - 1 , Id 0 - r-I...V)4) w4rI ) H -rl4 V) cd0 A)U 43) CH 0 0 1 $ 0 W 0 0) *’ 00 .4a 4) UP >, ’o 0 q U) r. ( 1 P 4’ 4)+ PC 4’ ,0~ P~ C)0O 41 4) P 4- -r4 W 4- P, 03 P4...8217) 0 vi 4l 0 rO 4-4’ ~ ) . 0 9 4)> d 04- 0.k 4 0, 0 L r4- -P +H (’I P 4. 4- 4U)W aQ ) 4C) Hd4 0 N N N ) P 4 4 I D 4-’ H 4 ( 1 a) 0 W) 0Y) L %
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...
Evaluation of 3-D Laser Scanning Equipment : 2018 Final Report
DOT National Transportation Integrated Search
2018-05-01
As a follow-up to ICT Project R27-030, Evaluation of 3-D Laser Scanning, this report provides findings of an evaluation of 3-D laser scanning equipment to determine the tangible costs versus benefits and the manpower savings realized by using the equ...
NASA Astrophysics Data System (ADS)
Fan, Weiqiang; Zhu, Lin; Shi, Weidong; Chen, Fuxiao; Bai, Hongye; Song, Shuyan; Yan, Yongsheng
2013-04-01
A novel metal-organic coordination polymer [Cu(phen)(L)0.5(H2O)]n (H4L = (N,N‧-5,5‧-bis(isophthalic acid)-p-xylylenediamine, and phen = 1,10-phenanthroline) has been hydrothermally synthesized and characterized by elemental analysis, IR, TGA, and single-crystal X-ray diffraction. The crystallographic data show that the title compound crystallizes in monoclinic space group P21/n with a = 10.682(2), b = 15.682(3), c = 11.909(2) Å, β = 91.39(3)°, V = 1994.3(7) Å3, C24H17CuN3O5, Mr = 490.95, Dc = 1.635 g/cm3, F(000) = 1004, Z = 4, μ(MoKα) = 1.141 mm-1, the final R = 0.0418 and wR = 0.0983 for 3578 observed reflections (I > 2σ(I)). The structural analyses reveal that the title compound exhibits shows a 2D layer structure, which are further linked by hydrogen bonding interactions to form a three-dimensional supramolecular network. In addition, the thermal stability and electrochemical behavior of title compound has been studied. CCDC: 900413.
Guide to Canadian Aerospace-Related Industries
1990-08-01
Quebec PLANT SIZE: 28,700 sq ft Canada H4L 4X8 EXPERIENCE: Barringer experience is worldwide. Recent R &D clients Plan t include Transport Canada, Revenue...Products, Ampheno Canada, ard J R Longts!affe"tel: (604) 530-2324 Fax: (604) 530-6242 CAPABILITY: Bruce D Vallillee Electronics Ltd, Marketing Consultants...Helicopters) BRISTOL AEROSPACE Ltd Instrumentation R &O (Helicopters) CANADIAN HELICOPTERS Ltd Quality Assurance Programs BRUCE D VALLILLEE R &O
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.
DOE Office of Scientific and Technical Information (OSTI.GOV)
Walsh, Jr., Richard M.; Polizzi, Samuel J.; Kadirvelraj, Renuka
The man o’ war (mow) phenotype in zebrafish is characterized by severe craniofacial defects due to a missense mutation in UDP-α-D-xylose synthase (UXS), an essential enzyme in proteoglycan biosynthesis. The mow mutation is located in the UXS dimer interface ~16 Å away from the active site, suggesting an indirect effect on the enzyme mechanism. We have examined the structural and catalytic consequences of the mow mutation (R236H) in the soluble fragment of human UXS (hUXS), which shares 93% sequence identity with the zebrafish enzyme. In solution, hUXS dimers undergo a concentration-dependent association to form a tetramer. Sedimentation velocity studies showmore » that the R236H substitution induces the formation of a new hexameric species. Using two new crystal structures of the hexamer, we show that R236H and R236A substitutions cause a local unfolding of the active site that allows for a rotation of the dimer interface necessary to form the hexamer. The disordered active sites in the R236H and R236A mutant constructs displace Y231, the essential acid/base catalyst in the UXS reaction mechanism. The loss of Y231 favors an abortive catalytic cycle in which the reaction intermediate, UDP-α-D-4-keto-xylose, is not reduced to the final product, UDP-α-D-xylose. Surprisingly, the mow-induced hexamer is almost identical to the hexamers formed by the deeply divergent UXS homologues from Staphylococcus aureus and Helicobacter pylori (21% and 16% sequence identity, respectively). The persistence of a latent hexamer-building interface in the human enzyme suggests that the ancestral UXS may have been a hexamer.« less
DOE Office of Scientific and Technical Information (OSTI.GOV)
Kafafi, S.A.
1998-12-10
A novel general purpose density functional methodology for the computation of accurate electronic and thermodynamic properties of molecules and improved long-range behavior is reported. Assuming the separability of the exchange (E{sub x}) and correlation (E{sub c}) contributions to the total exchange-correlation energy functional (E{sub xc}), the E{sub x} term consists of a hybrid mixture of 37.5% Hartree-Fock exchange and the appropriate local spin density exchange using the adiabatic connection formula. He demonstrated that E{sub x} and its corresponding potential V{sub x} [=dE{sub x}/d{rho}(r)] have the proper asymptotic limits at r = 0 and r {r_arrow} {infinity}, E{sub c} consists ofmore » the Vosko, Wilk, and Nusair formula for the free-electron gas correlation energy and a generalized gradient approximation term with one adjustable parameter. V{sub c} [=dE{sub c}/d{rho}(r)] was shown to obey the r {r_arrow} {infinity} limit of the corresponding potential derived from exact atomic exchange-correlation computations; namely, V{sub c} is proportional to r{sup {minus}4}. Most importantly, he demonstrated that, at r values where dispersion forces are operating, V{sub c} is proportional to 1/r{sup n} (n = 4, 6, 8, {hor_ellipsis}). The reported method was denoted by K2-BVWN because it used two adjustable parameters in its formulation. The K2-BVWN scheme scales as N{sup 3}, where N is the number of basis functions, compared to {approximately}N{sup 7} for Gaussian-2 (G2) ab initio theory and related methods, {approximately}N{sup 5} for Barone`s mPW1,3PW, and {approximately}N{sup 4} for Becke`s three-parameter density functional approaches. The G2 data set complemented by the reported molecular systems investigated in this work was recommended as a critical test for evaluating novel ab initio and density functional methodologies. The K2-BVWN method has been implemented in the Gaussian series of programs.« less
The Disulfide Bonding System Suppresses CsgD-Independent Cellulose Production in Escherichia coli
Hufnagel, David A.; DePas, William H.
2014-01-01
The bacterial extracellular matrix encases cells and protects them from host-related and environmental insults. The Escherichia coli master biofilm regulator CsgD is required for the production of the matrix components curli and cellulose. CsgD activates the diguanylate cyclase AdrA, which in turn stimulates cellulose production through cyclic di-GMP (c-di-GMP). Here, we identified and characterized a CsgD- and AdrA-independent cellulose production pathway that was maximally active when cultures were grown under reducing conditions or when the disulfide bonding system (DSB) was compromised. The CsgD-independent cellulose activation pathway was dependent on a second diguanylate cyclase, called YfiN. c-di-GMP production by YfiN was repressed by the periplasmic protein YfiR, and deletion of yfiR promoted CsgD-independent cellulose production. Conversely, when YfiR was overexpressed, cellulose production was decreased. Finally, we found that YfiR was oxidized by DsbA and that intraprotein YfiR disulfide bonds stabilized YfiR in the periplasm. Altogether, we showed that reducing conditions and mutations in the DSB system caused hyperactivation of YfiN and subsequent CsgD-independent cellulose production. PMID:25112475
The disulfide bonding system suppresses CsgD-independent cellulose production in Escherichia coli.
Hufnagel, David A; DePas, William H; Chapman, Matthew R
2014-11-01
The bacterial extracellular matrix encases cells and protects them from host-related and environmental insults. The Escherichia coli master biofilm regulator CsgD is required for the production of the matrix components curli and cellulose. CsgD activates the diguanylate cyclase AdrA, which in turn stimulates cellulose production through cyclic di-GMP (c-di-GMP). Here, we identified and characterized a CsgD- and AdrA-independent cellulose production pathway that was maximally active when cultures were grown under reducing conditions or when the disulfide bonding system (DSB) was compromised. The CsgD-independent cellulose activation pathway was dependent on a second diguanylate cyclase, called YfiN. c-di-GMP production by YfiN was repressed by the periplasmic protein YfiR, and deletion of yfiR promoted CsgD-independent cellulose production. Conversely, when YfiR was overexpressed, cellulose production was decreased. Finally, we found that YfiR was oxidized by DsbA and that intraprotein YfiR disulfide bonds stabilized YfiR in the periplasm. Altogether, we showed that reducing conditions and mutations in the DSB system caused hyperactivation of YfiN and subsequent CsgD-independent cellulose production. Copyright © 2014, American Society for Microbiology. All Rights Reserved.
Building bridges from process R&D: from a customer-supplier relationship to full partnership.
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.
Physical properties and scaling relations of molecular clouds: the effect of stellar feedback
NASA Astrophysics Data System (ADS)
Grisdale, Kearn; Agertz, Oscar; Renaud, Florent; Romeo, Alessandro B.
2018-06-01
Using hydrodynamical simulations of entire galactic discs similar to the Milky Way, reaching 4.6{ pc} resolution, we study the origins of observed physical properties of giant molecular clouds (GMCs). We find that efficient stellar feedback is a necessary ingredient in order to develop a realistic interstellar medium (ISM), leading to molecular cloud masses, sizes, velocity dispersions and virial parameters in excellent agreement with Milky Way observations. GMC scaling relations observed in the Milky Way, such as the mass-size (M-R), velocity dispersion-size (σ-R), and the σ-RΣ relations, are reproduced in a feedback driven ISM when observed in projection, with M∝R2.3 and σ∝R0.56. When analysed in 3D, GMC scaling relations steepen significantly, indicating potential limitations of our understanding of molecular cloud 3D structure from observations. Furthermore, we demonstrate how a GMC population's underlying distribution of virial parameters can strongly influence the scatter in derived scaling relations. Finally, we show that GMCs with nearly identical global properties exist in different evolutionary stages, where a majority of clouds being either gravitationally bound or expanding, but with a significant fraction being compressed by external ISM pressure, at all times.
A Global Optimization Algorithm Using Stochastic Differential Equations.
1985-02-01
Bari (Italy).2Istituto di Fisica, 2 UniversitA di Roma "Tor Vergata", Via Orazio Raimondo, 00173 ( La Romanina) Roma (Italy). 3Istituto di Matematica ...4T N C -- 4 z L -4 Ln o n C en r-4 C14 fl r- " u-4~ - t*, - r- te - ~ ~ I vt ON 00 c tA R3 ’r LA tL 32 Cl C) CDC Q 0 C 0 C D 0000000000"CDOA0 00 c...LD ’l O V 0 to -4 -4 N n tA . L Vt -4) 0) IA\\o ., D = t) 4-r 1-4 Cf) -44 0 V-4 N n \\0 N- 00 m~ 0l N- " A r4 LA N-N N N~~r n NtA el ~At t~A t .. 0) 33
Effects of high-voltage electrostatic fields on the quality of tilapia meat during refrigeration.
Hsieh, Chang-Wei; Lai, Cheng-Hung; Lee, Chia-Hsin; Ko, Wen-Ching
2011-08-01
Fresh fish is typically brought to market refrigerated at approximately 4 °C, R-storage. A storage method has been devised that combines refrigeration with a high-voltage electrostatic field (100 kV/m; E-storage). It was developed to improve the quality and prolong the shelf life of foods. This study investigated changes in the freshness of tilapia meat under E-storage conditions. The total viable count of tilapia reached 10⁷ CFU/g on the 7th d of refrigeration in R-storage. By the 6th d, K-value had increased from 20% to 61.7% for E-storage and to 94.7% for R-storage. Volatile basic nitrogen had increased from 12.54 mg/100 g to about 24.34 and 25.03 mg/100 g for R- and E-storage (on the 7th and 10th d), respectively. The sensory assessment also indicated that E-storage yielded an improvement in quality over that of R-storage. Practical application of the study model has the potential to prolong the freshness of fish. © 2011 Institute of Food Technologists®
The perspectives, information and conclusions conveyed in research project abstracts, progress reports, final reports, journal abstracts and journal publications convey the viewpoints of the principal investigator and may not represent the views and policies of ORD and EPA. Concl...
Tejas-Juárez, Juan Gabriel; Cruz-Martínez, Ana María; López-Alonso, Verónica Elsa; García-Iglesias, Brenda; Mancilla-Díaz, Juan Manuel; Florán-Garduño, Benjamín; Escartín-Pérez, Rodrigo Erick
2014-06-22
Obesity is a serious worldwide health problem, affecting 20-40% of the population in several countries. According to animal models, obesity is related to changes in the expression of proteins that control energy homeostasis and in neurotransmission associated to regulation of food intake. For example, it has been reported that diet-induced obesity produces overexpression of dopamine D4 receptor (D4R) mRNA in the ventromedial hypothalamic nucleus (VMH) of mice. Neurons in the VMH send dense glutamatergic projections to other hypothalamic regions as the paraventricular nucleus (PVN), where multiple signals are integrated to finely regulate energy homeostasis and food intake. Although it is well established that dopaminergic transmission in the hypothalamus plays a key role in modulating feeding, the specific mechanisms involved in the activation of D4R in the PVN and its modulatory action on glutamate release and feeding behavior have remained unexplored. To fill this gap, we characterize the behavioral and neurochemical role of D4R in the PVN. In behavioral experiments, we examined the effects of activation of dopamine D4 receptors in the PVN on food intake and on the behavioral satiety sequence in rats exposed to a food-restricted feeding program. In vitro experiments were conducted to study the effects of activation of dopamine D4 receptors on [(3)H]glutamate release and on plasma corticosterone in explants of the PVN. We found that activation of D4R in the PVN induced inhibition of glutamate release and stimulated food intake by inhibiting satiety. Furthermore, activation of D4R in the PVN decreased plasma levels of corticosterone, and this effect was reverted by NMDA. According to our findings, D4R in the PVN may be a target for the pharmacotherapy for obesity as well as eating disorder patients who show restrictive patterns and overweight. Copyright © 2014 Elsevier Inc. All rights reserved.
Ross, Breyan H; Lin, Yimo; Corales, Esteban A; Burgos, Patricia V; Mardones, Gonzalo A
2014-01-01
Adaptor protein (AP) complexes facilitate protein trafficking by playing key roles in the selection of cargo molecules to be sorted in post-Golgi compartments. Four AP complexes (AP-1 to AP-4) contain a medium-sized subunit (μ1-μ4) that recognizes YXXØ-sequences (Ø is a bulky hydrophobic residue), which are sorting signals in transmembrane proteins. A conserved, canonical region in μ subunits mediates recognition of YXXØ-signals by means of a critical aspartic acid. Recently we found that a non-canonical YXXØ-signal on the cytosolic tail of the Alzheimer's disease amyloid precursor protein (APP) binds to a distinct region of the μ4 subunit of the AP-4 complex. In this study we aimed to determine the functionality of both binding sites of μ4 on the recognition of the non-canonical YXXØ-signal of APP. We found that substitutions in either binding site abrogated the interaction with the APP-tail in yeast-two hybrid experiments. Further characterization by isothermal titration calorimetry showed instead loss of binding to the APP signal with only the substitution R283D at the non-canonical site, in contrast to a decrease in binding affinity with the substitution D190A at the canonical site. We solved the crystal structure of the C-terminal domain of the D190A mutant bound to this non-canonical YXXØ-signal. This structure showed no significant difference compared to that of wild-type μ4. Both differential scanning fluorimetry and limited proteolysis analyses demonstrated that the D190A substitution rendered μ4 less stable, suggesting an explanation for its lower binding affinity to the APP signal. Finally, in contrast to overexpression of the D190A mutant, and acting in a dominant-negative manner, overexpression of μ4 with either a F255A or a R283D substitution at the non-canonical site halted APP transport at the Golgi apparatus. Together, our analyses support that the functional recognition of the non-canonical YXXØ-signal of APP is limited to the non-canonical site of μ4.
Ross, Breyan H.; Lin, Yimo; Corales, Esteban A.; Burgos, Patricia V.; Mardones, Gonzalo A.
2014-01-01
Adaptor protein (AP) complexes facilitate protein trafficking by playing key roles in the selection of cargo molecules to be sorted in post-Golgi compartments. Four AP complexes (AP-1 to AP-4) contain a medium-sized subunit (μ1-μ4) that recognizes YXXØ-sequences (Ø is a bulky hydrophobic residue), which are sorting signals in transmembrane proteins. A conserved, canonical region in μ subunits mediates recognition of YXXØ-signals by means of a critical aspartic acid. Recently we found that a non-canonical YXXØ-signal on the cytosolic tail of the Alzheimer's disease amyloid precursor protein (APP) binds to a distinct region of the μ4 subunit of the AP-4 complex. In this study we aimed to determine the functionality of both binding sites of μ4 on the recognition of the non-canonical YXXØ-signal of APP. We found that substitutions in either binding site abrogated the interaction with the APP-tail in yeast-two hybrid experiments. Further characterization by isothermal titration calorimetry showed instead loss of binding to the APP signal with only the substitution R283D at the non-canonical site, in contrast to a decrease in binding affinity with the substitution D190A at the canonical site. We solved the crystal structure of the C-terminal domain of the D190A mutant bound to this non-canonical YXXØ-signal. This structure showed no significant difference compared to that of wild-type μ4. Both differential scanning fluorimetry and limited proteolysis analyses demonstrated that the D190A substitution rendered μ4 less stable, suggesting an explanation for its lower binding affinity to the APP signal. Finally, in contrast to overexpression of the D190A mutant, and acting in a dominant-negative manner, overexpression of μ4 with either a F255A or a R283D substitution at the non-canonical site halted APP transport at the Golgi apparatus. Together, our analyses support that the functional recognition of the non-canonical YXXØ-signal of APP is limited to the non-canonical site of μ4. PMID:24498434
Loppini, Mattia; Longo, Umile Giuseppe; Ragucci, Pasquala; Trenti, Nicoletta; Balzarini, Luca; Grappiolo, Guido
2017-03-01
We investigated the relationship between pelvic incidence (PI) with anterior pelvic plane angle (APPA), pelvic tilt (PT) angle, and sacral slope (SS) in standing and sitting positions to identify the best parameter expressing the pelvic functional orientation in the sagittal plane. We enrolled 109 consecutive patients (M:F = 43:66) eligible for a primary total hip arthroplasty (THA) with an average age of 63.4 years (15-85). EOS 2D/3D radiography was performed in standing and sitting positions before THA to evaluate the functional pelvic orientation. 3D images took into account the patient-specific sagittal balance measuring APPA, PT, SS, and PI. In standing position, functional parameters measured 5° ± 7.1 for APPA, 11° ± 8.3 for PT, 43° ± 8.5 for SS, and 53° ± 10.9 for PI. In sitting position, they were -18° ± 10.4 for APPA, 34° ± 11.8 for PT, 20° ± 12.6 for SS, and 54° ± 10.9 for PI. There was no significant difference between men and women in terms of the functional parameters in both positions. No relationship was found between APPA and PI in both positions. SS correlated with PI in standing (r = 0.66; P < .0001; R 2 = 0.44) and sitting (r = 0.51; P < .0001; R 2 = 0.26). PT correlated with PI in standing (r = 0.65; P < .0001; R 2 = 0.42) and sitting (r = 0.38; P < .0001; R 2 = 0.14). SS shows the highest correlation with functional pelvic tilt. The study suggests that adjustments in acetabular anteversion during primary THA should be based on SS. Copyright © 2016 Elsevier Inc. All rights reserved.
Multisource Localization from Delay and Doppler Measurements.
1986-07-01
evaluated using the chain rule : 4a ,. .w aR sd aRs ad fT ()s -’s R d -au = d - (2n) where R _x sa and xs /R s of have been used to evaluate .3R/axs...I as the tth row/column entry. The derivative, .3(R.d)/cz., isa evaluated ,tsing the product rule : 3(R.d) R d 3R. R d =3z 3. : _ i = ._L -in(5 i...mean square error is shown to be in the range of two to ten times the corresponding Crammer -Rao bounds when these techniques - are applied to 2-sensor
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.
Rate-distortion optimized tree-structured compression algorithms for piecewise polynomial images.
Shukla, Rahul; Dragotti, Pier Luigi; Do, Minh N; Vetterli, Martin
2005-03-01
This paper presents novel coding algorithms based on tree-structured segmentation, which achieve the correct asymptotic rate-distortion (R-D) behavior for a simple class of signals, known as piecewise polynomials, by using an R-D based prune and join scheme. For the one-dimensional case, our scheme is based on binary-tree segmentation of the signal. This scheme approximates the signal segments using polynomial models and utilizes an R-D optimal bit allocation strategy among the different signal segments. The scheme further encodes similar neighbors jointly to achieve the correct exponentially decaying R-D behavior (D(R) - c(o)2(-c1R)), thus improving over classic wavelet schemes. We also prove that the computational complexity of the scheme is of O(N log N). We then show the extension of this scheme to the two-dimensional case using a quadtree. This quadtree-coding scheme also achieves an exponentially decaying R-D behavior, for the polygonal image model composed of a white polygon-shaped object against a uniform black background, with low computational cost of O(N log N). Again, the key is an R-D optimized prune and join strategy. Finally, we conclude with numerical results, which show that the proposed quadtree-coding scheme outperforms JPEG2000 by about 1 dB for real images, like cameraman, at low rates of around 0.15 bpp.
Effects of the FITKids randomized controlled trial on executive control and brain function.
Hillman, Charles H; Pontifex, Matthew B; Castelli, Darla M; Khan, Naiman A; Raine, Lauren B; Scudder, Mark R; Drollette, Eric S; Moore, Robert D; Wu, Chien-Ting; Kamijo, Keita
2014-10-01
To assess the effect of a physical activity (PA) intervention on brain and behavioral indices of executive control in preadolescent children. Two hundred twenty-one children (7-9 years) were randomly assigned to a 9-month afterschool PA program or a wait-list control. In addition to changes in fitness (maximal oxygen consumption), electrical activity in the brain (P3-ERP) and behavioral measures (accuracy, reaction time) of executive control were collected by using tasks that modulated attentional inhibition and cognitive flexibility. Fitness improved more among intervention participants from pretest to posttest compared with the wait-list control (1.3 mL/kg per minute, 95% confidence interval [CI]: 0.3 to 2.4; d = 0.34 for group difference in pre-to-post change score). Intervention participants exhibited greater improvements from pretest to posttest in inhibition (3.2%, 95% CI: 0.0 to 6.5; d = 0.27) and cognitive flexibility (4.8%, 95% CI: 1.1 to 8.4; d = 0.35 for group difference in pre-to-post change score) compared with control. Only the intervention group increased attentional resources from pretest to posttest during tasks requiring increased inhibition (1.4 µV, 95% CI: 0.3 to 2.6; d = 0.34) and cognitive flexibility (1.5 µV, 95% CI: 0.6 to 2.5; d = 0.43). Finally, improvements in brain function on the inhibition task (r = 0.22) and performance on the flexibility task correlated with intervention attendance (r = 0.24). The intervention enhanced cognitive performance and brain function during tasks requiring greater executive control. These findings demonstrate a causal effect of a PA program on executive control, and provide support for PA for improving childhood cognition and brain health. Copyright © 2014 by the American Academy of Pediatrics.
Wurtzel, Jeremy G.T.; Kumar, Puneet; Goldfinger, Lawrence E.
2012-01-01
In this study we investigated the dynamics of R-Ras intracellular trafficking and its contributions to the unique roles of R-Ras in membrane ruffling and cell spreading. Wild type and constitutively active R-Ras localized to membranes of both Rab11- and transferrin-positive and -negative vesicles, which trafficked anterograde to the leading edge in migrating cells. H-Ras also co-localized with R-Ras in many of these vesicles in the vicinity of the Golgi, but R-Ras and H-Ras vesicles segregated proximal to the leading edge, in a manner dictated by the C-terminal membrane-targeting sequences. These segregated vesicle trafficking patterns corresponded to distinct modes of targeting to membrane ruffles at the leading edge. Geranylgeranylation was required for membrane anchorage of R-Ras, whereas palmitoylation was required for exit from the Golgi in post-Golgi vesicle membranes and trafficking to the plasma membrane. R-Ras vesicle membranes did not contain phosphatidylinositol (3,4,5)-trisphosphate (PtdIns(3,4,5)P3), whereas R-Ras co-localized with PtdIns(3,4,5)P3 in membrane ruffles. Finally, palmitoylation-deficient R-Ras blocked membrane ruffling, R-Ras/PI3-kinase interaction, enrichment of PtdIns(3,4,5)P3 at the plasma membrane, and R-Ras-dependent cell spreading. Thus, lipid modification of R-Ras dictates its vesicle trafficking, targeting to membrane ruffles, and its unique roles in localizing PtdIns(3,4,5)P3 to ruffles and promoting cell spreading. PMID:22751447
MiR-205 and MiR-373 Are Associated with Aggressive Human Mucinous Colorectal Cancer
Eyking, Annette; Reis, Henning; Frank, Magdalena; Gerken, Guido; Schmid, Kurt W.; Cario, Elke
2016-01-01
Mucinous adenocarcinoma (MAC) represents a distinct histopathological entity of colorectal cancer (CRC), which is associated with disease progression and poor prognosis. Here, we found that expression levels of miR-205 and miR-373 were specifically upregulated only in patients with mucinous colon cancers, but not in CRC that lack mucinous components. To investigate the effects of miR-205 and miR-373 on intestinal epithelial cell (IEC) biology by gain- and loss-of-function experiments in a proof-of-concept approach, we chose previously established in-vitro human Caco-2-based models of differentiated, non-invasive (expressing TLR4 wild-type; termed Caco-2[WT]) versus undifferentiated, invasive (expressing TLR4 mutant D299G; termed Caco-2[D299G]) IEC. Enterocyte-like Caco-2[WT] showed low levels of miR-205 and miR-373 expression, while both miRNAs were significantly upregulated in colorectal carcinoma-like Caco-2[D299G], thus resembling the miRNA expression pattern of paired normal versus tumor samples from MAC patients. Using stable transfection, we generated miR-205- or miR-373-expressing and miR-205- or miR-373-inhibiting subclones of these IEC lines. We found that introduction of miR-205 into Caco-2[WT] led to expansion of mucus-secreting goblet cell-like cells, which was associated with induction of KLF4, MUC2 and TGFβ1 expression. Activation of miR-205 in Caco-2[WT] induced chemoresistance, while inhibition of miR-205 in Caco-2[D299G] promoted chemosensitivity. Caco-2[WT] overexpressing miR-373 showed mitotic abnormalities and underwent morphologic changes (loss of epithelial polarity, cytoskeletal reorganization, and junctional disruption) associated with epithelial-mesenchymal transition and progression to inflammation-associated colonic carcinoma, which correlated with induction of phosphorylated STAT3 and N-CADHERIN expression. Functionally, introduction of miR-373 into Caco-2[WT] mediated loss of cell-cell adhesion and increased proliferation and invasion. Reversely, inhibition of miR-373 allowed mesenchymal IEC to regain epithelial properties, which correlated with absence of neoplastic progression. Using xenografts in mice demonstrated miR-373-mediated acceleration of malignant intestinal tumor growth. In conclusion, our results provide first evidence that miR-205 and miR-373 may differentially contribute to the aggressive phenotype of MAC in CRC. PMID:27271572
DOE Office of Scientific and Technical Information (OSTI.GOV)
Jiu-Fu, Lu, E-mail: jiufulu@163.com; Hong-Guang, Ge; Juan, Shi
2015-12-15
Reaction of 2-(1-methyl-1,2-dihydroimidazol-3-yl)acetonitrile tetrafluoroborate with silver oxide in dichloromethane readily yields [Ag(DIM){sub 2}]BF{sub 4}, where DIM is 2-(1-methyl-1, 2-dihydroimidazol-3-yl)acetonitrile, representing a carbene organic ligand. The title compound was characterized by elemental analysis, IR, MS and single crystal X-ray diffraction. The crystal is of monoclinic system, space group C2/c with a = 14.010(18), b = 8.303(11), c = 14.936(20) Å, β = 93.910(4)°, V = 1639(4) Å{sup 3}, Z = 4, D{sub x} = 1.771 g/cm{sup 3}, F (000) = 864, µ(MoK{sub α}) = 1.278 mm{sup –1}. The final R{sup 1} = 0.0711 and wR{sup 2} = 0.1903 for reflections withmore » I > 2σ(I). In addition, the preliminary biological test showed that the title compound had anti-fungus yeast activity.« less
Laboratory for Computer Science Progress Report 21, July 1983-June 1984.
1984-06-01
Systems 269 4. Distributed Consensus 270 5. Election of a Leader in a Distributed Ring of Processors 273 6. Distributed Network Algorithms 274 7. Diagnosis...multiprocessor systems. This facility, funded by the new!y formed Strategic Computing Program of the Defense Advanced Research Projects Agency, will enable...Academic Staff P. Szo)ovits, Group Leader R. Patil Collaborating Investigators M. Criscitiello, M.D., Tufts-New England Medical Center Hospital R
LLE Review Quarterly Report July-September 2000
DOE Office of Scientific and Technical Information (OSTI.GOV)
NONE
2000-12-01
This volume of the LLE Review, covering July-September 2000, begins with an article by T. R. Boehly, V. N. Goncharov, O. Gotchev, J. P. Knauer, D. D. Meyerhofer, D. Oron, S. P. Regan, Y. Srebro, W. Seka, D. Shvarts, S. Skupsky, and V.A. Smalyuk, who describe measurements of the effect of beam smoothing and pulse shape on imprinting. (Imprinting is defined as the imposition of pressure perturbations on the target by spatial variations in the laser intensity.) A principal result is the observation of reduced levels of imprint with the higher beam smoothing afforded by 1-THz smoothing by spectral dispersionmore » (SSD). Additional highlights of research presented in this issue are: (1) P. W. McKenty, V. N. Goncharov, R. P. J. Town, S. Skupsky, R. Betti, and R. L. McCrory describe calculations of directly driven ignition capsule performance on the National Ignition Facility (NIF). The authors detail how the various contributors to implosion disruption (laser imprint, power imbalance, and target roughness) affect target performance and final gain. The conclusions are obtained by examining the simulated target evolution with the two-dimensional hydrodynamics computer code ORCHID. (2) D. D. Meyerhofer, J. A. Delettrez, R. Epstein, V. Yu. Glebov, V. N. Goncharov, R. L. Keck, R. L. McCrory, P. W. McKenty, F. J. Marshall, P. B. Radha, S. P. Regan, S. Roberts, W. Seka, S. Skupsky, V. A. Smalyuk, C. Sorce, C. Stoeckl, J. M. Soures, R. P. J. Town, B. Yaakobi, J. D. Zuegel, J. Frenje, C. K. L1,R. D. Petrasso, F. Seguin, K. Fletcher, S. Padalino, C. Freeman, N. Izumi, R. Lerche, T. W. Phillips, and T. C. Sangster describe the results of a series of direct-drive implosions of gas-fusion-fuel-filled plastic shells performed on the OMEGA laser system. The experiments include those performed with 1-THZ SSD and high-quality power balance. (3) V. Yu. Glebov, D. D. Meyerhofer, C. Stoeckl, and J. D. Zuegel describe the technique of measuring secondary neutron yield (DT neutron yield from D{sub 2}-filled targets) using current-mode detectors (i.e., many detection events per unit time interval). They show that current-mode detectors can be configured to survey a much larger dynamic range than single-event neutron counters. (4) V. A. Smalyuk, T. R. Boehly, L. S. Iwan, T. J. Kessler, J. P. Knauer, F. J. Marshall, D. D. Meyerhofer, C. Stoeckl, B. Yaakobi, and D. K. Bradley detail a method of measuring the positional dependence of x-ray self-absorption with filtered x-ray framing cameras. They show how compressed shell nonuniformities can be measured by carefully modeling the imaging system. This volume concludes with the LLE's Summer High School Research Program, the FY00 Laser Facility Report, and the National Laser Users' Facility News.« less
Defining Tailored Training Approaches for Army Institutional Training
2013-03-01
teachers object to being assigned to the lower ranking groups, which may further depress academic growth. Finally, critics say that ability grouping...for research, theory, and applications. In D. S. Gorfein and R. R. Hoffman (Eds.), Memory and learning: The Ebbinghaus centennial conference
Liu, Lei-Lei; Yu, Cai-Xia; Ma, Feng-Ji; Li, Ya-Ru; Han, Jing-Jing; Lin, Lu; Ma, Lu-Fang
2015-01-28
Hydrothermal reactions of Cd(OAc)2·2H2O with a flexible V-shaped bipyridyl benzene ligand and five benzenedicarboxylic acid derivatives gave rise to five new coordination polymers i.e., [Cd(1,4-BDC)(bpmb)(H2O)]n (1), {[Cd(1,3-BDC)(bpmb)]·0.125H2O}n (2), [Cd2(5-Me-1,3-BDC)2(bpmb)2]n (3), [Cd(5-NO2-1,3-BDC)(bpmb)(H2O)]n (4) and [Cd(5-OH-1,3-BDC)(bpmb)(H2O)]n (5) (bpmb = 1,3-bis(pyridine-3-ylmethoxy)benzene, 1,4-H2BDC = 1,4-benzenedicarboxylic acid, 1,3-H2BDC = 1,3-benzenedicarboxylic acid, 5-Me-1,3-H2BDC = 5-methyl-1,3-benzenedicarboxylic acid, 5-NO2-1,3-H2BDC = 5-nitro-1,3-benzenedicarboxylic acid, 5-OH-1,3-H2BDC = 5-hydroxy-1,3-benzenedicarboxylic acid). Their structures have been determined by single-crystal X-ray diffraction analyses, elemental analyses, IR spectra, powder X-ray diffraction (PXRD) and thermogravimetric analyses (TGA). Compound 1 is a two-fold interpenetrating network showing the coexistence of polyrotaxane and polycatenane characters. Compounds 2 and 3 exhibit similar 2D (3,5)-connected (4(2)·6(7)·8)(4(2)·6) nets in which the bpmb ligands work as lockers in interlocking 1D [Cd(1,3-BDC/5-Me-1,3-BDC)]n chains. Compound 4 shows a 2D 4-connected (6(6)) sandwich-like structure with differently oriented [Cd(5-NO2-1,3-BDC)]n chains. Compound 5 is a 3D supramolecular pcu net based on a 1D ladder-shaped chain. These results suggest that the substituted positions of carboxylate groups and changes in substituted R groups in the 5-position of BDC ligands have significant effect on the final structures. These compounds exhibited relatively good photocatalytic activity towards the degradation of methylene blue (MB) in aqueous solution under UV irradiation. Moreover, solid-state photoluminescence properties of 1-5 were also investigated.
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.
NASA Astrophysics Data System (ADS)
Simakov, N. N.
2018-04-01
Page 1010, left column, line 4 from bottom should read "radius R APP" instead of "diameter D APP" Page 1010, right column, before the formula (19) should read " R APP" instead of " D APP" Page 1010, in the caption to Fig. 5 should read "radius R APP" instead of "diameter D APP" Page 1011, in the caption to Fig. 6 should read "radius R APP" instead of "diameter D APP" Page 1011, left column, second paragraph after Fig. 6, line 4 from top should read "radius R APP" instead of "diameter D APP" Page 1011, the same paragraph, lines 1, 2 from bottom, in the expression for Qm and after it should read "radius R APP" instead of "diameter D APP" Page 1011, left column, paragraph 3 after Fig. 6, last two lines should read " R APP =" instead of " D APP =" Page 1011, Fig. 7, the notation on the abscissa axis should read " R APP" instead of " D APP" Page 1011, in the caption to Fig. 7 should read "radius R APP" instead of "diameter D APP" Page 1011, in caption to Fig. 8 should read "for both radii R APP" instead of "for both diameters D APP" Page 1012, in caption to Fig. 9 should read "for both radii R APP" instead of "for both diameters D APP"
Involvement with Prior Job, Social Support, and the Perceived Quality of Life Among the Unemployed.
1985-10-01
C ’. .) 0t CL *= 0J$ 3 4 4- =~ 5- E 0- C > 4 0 0 -H,--- 0 04~ D 0 0 4- a) P’ 4 1 M - 1-J a)I r -i cJ C14 H 0 If0 "*~- 0u w U...irstance, and oD¢ychoioqica] counr ixnq. T.,’ aLs;ence o; auiv i- . - . . . . . + + . .+ + + = +- + : .- - -- - - .- -. • ,- e . .- ’ . r ...44 * -4O5- - : 0 r : -4 C1nC r :, C 04a n0 C4-W V)0’. d) 4- ’.o -44 -4 0’ ’-0 U) - - 41 r_~ w~ V0 .. e0P 0 0 nM C .ri4- W - 0r 41 -4- ca a) Aj cu 0
1983-12-01
LONSlZTUDNAL STABILITY DATA FOR Nl F-15 WITH ONLY CFTJ! AND AMl F-13 WITH CFTS AND FIB STRAKES. ., 0-34 -... .4r * CL 1.4. .2 .2 .4 .6 .8 1 1.2 1.4 CO CM...CONFORMAL FUEL TANKS THESIS "AFIT/GAE/AA/83D-7 Terry A. DuncanCaptain USAF DT C SELECTE ca JAN 18 1984 DEPARTMENT OF THE AIR FORCE S AIR UNIVERSITY E AIR...DETERMINE DOMINANT FOREBODY STRAKE DESIGN CHARACTERISTICS FOR AN F-15 EQUIPPED WITH CONFORMAL FUEL TANKS THESIS AFITIGAE/AA/83D-7 Terry A. Duncan
Saitô, Hazime
2004-11-01
We have compared site-directed 13C solid-state NMR spectra of [3-13C]Ala- and/or [1-13C]Val-labeled membrane proteins, including bacteriorhodopsin (bR), pharaonis phoborhodopin (ppR), its cognate transducer (pHtrII) and Escherichia coli diacylglycerol kinase (DGK), in two-dimensional (2D) crystal, lipid bilayers, and detergent. Restricted fluctuation motions of these membrane proteins due to oligomerization of bR by specific protein-protein interactions in the 2D crystalline lattice or protein complex between ppR and pHtrII provide the most favorable environment to yield well-resolved, fully visible 13C NMR signals for [3-13C]Ala-labeled proteins. In contrast, several signals from such membrane proteins were broadened or lost owing to interference of inherent fluctuation frequencies (10(4)-10(5)Hz) with frequency of either proton decoupling or magic angle spinning, if their 13C NMR spectra were recorded as a monomer in lipid bilayers at ambient temperature. The presence of such protein dynamics is essential for the respective proteins to achieve their own biological functions. Finally, spectral broadening found for bR and DGK in detergents were discussed.
Kaushal, Neelam; Vohora, Divya; Jalali, Rajinder K; Jha, Sujeet
2018-01-01
Oxidative stress has been implicated as a fundamental mechanism in the decline of bone mass. Reactive oxygen species are reported to suppress osteoblast generation and differentiation and enhance osteoclast development and activity. Increasing evidence suggests favorable effect of serum uric acid (UA) on bone metabolism due to its antioxidant properties. Therefore, we investigated the association between serum UA levels and bone mineral density (BMD) in healthy adult Indian subjects. We reviewed the medical records of 524 subjects who had undergone preventive health check-ups in a tertiary care hospital that included UA and BMD measurements at femur neck, total femur, and lumbar spine. Subjects concomitantly taking drugs or having a medical condition that would affect the bone metabolism or UA levels were excluded. The final analysis included 310 subjects (mean age: 47.2±12.2 years; females: 43.5%; males: 56.5%). Study population was categorized into two groups based on the group median value for UA (ie, 5.4 mg/dL). BMD was significantly higher at all skeletal sites in subjects with UA >5.4 mg/dL compared to subjects with UA ≤5.4 mg/dL ( p <0.001). On correlation analysis, UA was positively associated with BMD at all skeletal sites ( r =0.211-0.277; p <0.05). The correlation remained significant after controlling for age ( p <0.05) and lifestyle factors (smoking, alcohol use, physical activity, and diet; p <0.05) independently. UA significantly ( p <0.001) accounted for 4.5%-7.7% of the variance in BMD ( r 2 =0.045-0.077) in unadjusted model and 1.6%-3.2% of the variance ( p <0.05) when adjusted for age and body mass index combined at lumbar spine and right femur neck, respectively. We conclude that raised UA levels are associated with higher BMD at all skeletal sites and UA may have a protective role in bone metabolism owing to its antioxidant effect.
Homochiral coordination polymers with helixes and metal clusters based on lactate derivatives
DOE Office of Scientific and Technical Information (OSTI.GOV)
Xu, Zhong-Xuan, E-mail: xuzhongxuan4201@163.com; Ma, Yu-Lu; Lv, Guo-ling
2017-05-15
Utilizing the lactic acid derivatives (R)-4-(1-carboxyethoxy)benzoic acid (denoted: (R)-H{sub 2}CBA) and (S)-4-(1-carboxyethoxy)benzoic acid (denoted: (S)-H{sub 2}CBA)as chiral linkers to self-assemble with 4, 4′-bipyridine (denoted: BIP) and Cd(II) ions, a couple of three-dimensional homochiral coordination polymers, namely [Cd{sub 3}((R)-CBA){sub 3} (BIP){sub 2}(H{sub 2}O)]·xGuest (1-D) and [Cd{sub 3}((S)-CBA){sub 3}(BIP){sub 2}(H{sub 2}O)]·xGuest (1-L), have been synthesized under solvothermal reaction condition. Single crystal X-ray diffraction analysis reveals the two complexes contain single helical chains based on enantiopure ligands and cadmium clusters. Moreover, some physical characteristics such as PXRD, thermal stability, solid-state circular dichroism (CD) and luminescent were also investigated. - Graphical abstract: Utilizing enantiomericmore » lactic acid derivatives (R)-H{sub 2}CBA and (S)-H{sub 2}CBA to assemble with Cd{sup 2+} ions and ancillary BIP ligands, a couple of 3D homochiral coordination polymers with metal clusters and helical chains have been prepared by hydrothermal reaction. - Highlights: • Chiral lactic acid derivative. • Enantiomeric coordination polymer. • Helical chain. • Trinuclear cadmium cluster.« less
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.
MIT Laboratory for Computer Science Progress Report 26
1989-06-01
conteinporary and prospective applications from business to sensory computing. In Sqst.-ns., Languagcs, and Nr/o4orks, our objective is to provide the...numbers 363 through 400. 1,i Advanced Network Architecture Academic Staff D. Clark, Group Leader D. Tennenhouse Restarch Staff J. Davin K. Sollins Graduate...Zurich, Switzerland, May 1989. 23 24 Clinical Decision Making Academic Staff R. Patil P. Szolovits, Group Leader Collaborating Investigators M
76 FR 36871 - Modification of Restricted Areas R-4401A, R-4401B, and R-4401C; Camp Shelby, MS
Federal Register 2010, 2011, 2012, 2013, 2014
2011-06-23
... National Guard (ANG) published a Final Environmental Assessment (FEA) ``Modification of CRTC-Used Airspace..., 2008. The ANG prepared the FEA and associated FONSI in compliance with their obligations under the... 404d, the FAA has independently evaluated the information contained in the FEA and is adopting the...
Final Report for Low Pressure Tests of the CPU-400 Pilot ...
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Gan, Yimei; Liu, Fang; Chen, Dan; Wu, Qiong; Qin, Qin; Wang, Chunying; Li, Shaohui; Zhang, Xiangdi; Wang, Yuhong; Wang, Kunbo
2013-01-01
We investigated the locations of 5S and 45S rDNA in Gossypium diploid A, B, D, E, F, G genomes and tetraploid genome (AD) using multi-probe fluorescent in situ hybridization (FISH) for evolution analysis in Gossypium genus. The rDNA numbers and sizes, and synteny relationships between 5S and 45S were revealed using 5S and 45S as double-probe for all species, and the rDNA-bearing chromosomes were identified for A, D and AD genomes with one more probe that is single-chromosome-specific BAC clone from G. hirsutum (A1D1). Two to four 45S and one 5S loci were found in diploid-species except two 5S loci in G . incanum (E4), the same as that in tetraploid species. The 45S on the 7th and 9th chromosomes and the 5S on the 9th chromosomes seemed to be conserved in A, D and AD genomes. In the species of B, E, F and G genomes, the rDNA numbers, sizes, and synteny relationships were first reported in this paper. The rDNA pattern agrees with previously reported phylogenetic history with some disagreements. Combined with the whole-genome sequencing data from G . raimondii (D5) and the conserved cotton karyotype, it is suggested that the expansion, decrease and transposition of rDNA other than chromosome rearrangements might occur during the Gossypium evolution. PMID:23826377
Gan, Yimei; Liu, Fang; Chen, Dan; Wu, Qiong; Qin, Qin; Wang, Chunying; Li, Shaohui; Zhang, Xiangdi; Wang, Yuhong; Wang, Kunbo
2013-01-01
We investigated the locations of 5S and 45S rDNA in Gossypium diploid A, B, D, E, F, G genomes and tetraploid genome (AD) using multi-probe fluorescent in situ hybridization (FISH) for evolution analysis in Gossypium genus. The rDNA numbers and sizes, and synteny relationships between 5S and 45S were revealed using 5S and 45S as double-probe for all species, and the rDNA-bearing chromosomes were identified for A, D and AD genomes with one more probe that is single-chromosome-specific BAC clone from G. hirsutum (A1D1). Two to four 45S and one 5S loci were found in diploid-species except two 5S loci in G. incanum (E4), the same as that in tetraploid species. The 45S on the 7th and 9th chromosomes and the 5S on the 9th chromosomes seemed to be conserved in A, D and AD genomes. In the species of B, E, F and G genomes, the rDNA numbers, sizes, and synteny relationships were first reported in this paper. The rDNA pattern agrees with previously reported phylogenetic history with some disagreements. Combined with the whole-genome sequencing data from G. raimondii (D5) and the conserved cotton karyotype, it is suggested that the expansion, decrease and transposition of rDNA other than chromosome rearrangements might occur during the Gossypium evolution.
1984-01-01
Ft- Vi9i m4V r i 4 - 4 P. 04" Vie Vi bl I- VilO~~~C 4 44ii ~ ~ V : A Vi". . st~ 04 ie 4N. 0@ PP 4’ A P .. V i itp 4 V? VN V~ -- T Vi~i 37 400...In aD (0110 ffO Inc-an c* c.c- 1 ON d r3’ .In C4 IN c-a. ŝI vn -1~ ’o -. --i c- nON c-.n4 I 1 C!~ N- Ibm --~- -I. 1 ) n r - r4 D1- 10( Ci 4I 1tO1 .9I...have been developed for the IBM 6195 and the Data General S14U systems. A coder for the Corps’ Harris computers should be available shortly. Examples
NASA Astrophysics Data System (ADS)
Van Troeye, Benoit; van Setten, Michiel Jan; Giantomassi, Matteo; Torrent, Marc; Rignanese, Gian-Marco; Gonze, Xavier
2017-01-01
Using density functional theory (DFT) and density functional perturbation theory (DFPT), we investigate the stability and response functions of CsH2PO4 , a ferroelectric material at low temperature. This material cannot be described properly by the usual (semi)local approximations within DFT. The long-range e--e- correlation needs to be properly taken into account, using, for instance, Grimme's DFT-D methods, as investigated in this work. We find that DFT-D3(BJ) performs the best for the members of the dihydrogenated alkali phosphate family (KH2PO4 , RbH2PO4 , CsH2PO4 ), leading to experimental lattice parameters reproduced with an average deviation of 0.5%. With these DFT-D methods, the structural, dielectric, vibrational, and mechanical properties of CsH2PO4 are globally in excellent agreement with the available experiments (<2 % MAPE for Raman-active phonons). Our study suggests the possible existence of a new low-temperature phase of CsH2PO4 , not yet reported experimentally. Finally, we report the implementation of DFT-D contributions to elastic constants within DFPT.
Xiang, Zhimin; Proneth, Bettina; Dirain, Marvin L; Litherland, Sally A; Haskell-Luevano, Carrie
2010-06-08
The melanocortin-4 receptor (MC4R) is a G-protein-coupled receptor (GPCR) that is expressed in the central nervous system and has a role in regulating feeding behavior, obesity, energy homeostasis, male erectile response, and blood pressure. Since the report of the MC4R knockout mouse in 1997, the field has been searching for links between this genetic biomarker and human obesity and type 2 diabetes. More then 80 single nucleotide polymorphisms (SNPs) have been identified from human patients, both obese and nonobese controls. Many significant studies have been performed examining the pharmacological characteristics of these hMC4R SNPs in attempts to identify a molecular defects/insights that might link a genetic factor to the obese phenotype observed in patients possessing these mutations. Our laboratory has previously reported the pharmacological characterization of 40 of these polymorphic hMC4 receptors with multiple endogenous and synthetic ligands. The goal of the current study is to perform a similar comprehensive side-by-side characterization of 30 additional human hMC4R with single nucleotide polymorphisms using multiple endogenous agonists [alpha-, beta-, and gamma(2)-melanocyte stimulating hormones (MSH) and adrenocorticotropin (ACTH)], the antagonist agouti-related protein hAGRP(87-132), and synthetic agonists [NDP-MSH, MTII, and the tetrapeptide Ac-His-dPhe-Arg-Trp-NH(2) (JRH887-9)]. These in vitro data, in some cases, provide a putative molecular link between dysfunctional hMC4R's and human obesity. These 30 hMC4R SNPs include R7H, R18H, R18L, S36Y, P48S, V50M, F51L, E61K, I69T, D90N, S94R, G98R, I121T, A154D, Y157S, W174C, G181D, F202L, A219 V, I226T, G231S, G238D, N240S, C271R, S295P, P299L, E308K, I317V, L325F, and 750DelGA. All but the N240S hMC4R were identified in obese patients. Additionally, we have characterized a double I102T/V103I hMC4R. In addition to the pharmacological characterization, the hMC4R variants were evaluated for cell surface expression by flow cytometry. The F51L, I69T, and A219V hMC4Rs possessed full agonist activity and significantly decreased endogenous agonist ligand potency. At the E61K, D90N, Y157S, and C271R hMC4Rs, all agonist ligands examined were only partially efficacious in generating a maximal signaling response (partial agonists) and possessed significantly decreased endogenous agonist ligand potency. Only the A219V, G238D, and S295P hMC4Rs possessed significantly decreased AGRP(87-132) antagonist potency. These data provide new information for use in GPCR computational development as well as insights into MC4R structure ad function.
Core radial electric field and transport in Wendelstein 7-X plasmas
DOE Office of Scientific and Technical Information (OSTI.GOV)
Pablant, N. A.; Langenberg, A.; Alonso, A.
The results from the investigation of neoclassical core transport and the role of the radial electric field profile (E r) in the first operational phase of the Wendelstein 7-X (W7-X) stellarator are presented. In stellarator plasmas, the details of the E r profile are expected to have a strong effect on both the particle and heat fluxes. Investigation of the radial electric field is important in understanding neoclassical transport and in validation of neoclassical calculations. The radial electric field is closely related to the perpendicular plasma flow (u ⊥) through the force balance equation. This allows the radial electric fieldmore » to be inferred from measurements of the perpendicular flow velocity, which can be measured using the x-ray imaging crystal spectrometer and correlation reflectometry diagnostics. Large changes in the perpendicular rotation, on the order of Δu ⊥~ 5 km/s (ΔE r ~12 kV/m), have been observed within a set of experiments where the heating power was stepped down from 2 MW to 0.6 MW. These experiments are examined in detail to explore the relationship between heating power temperature, and density profiles and the radial electric field. Finally, the inferred E r profiles are compared to initial neoclassical calculations based on measured plasma profiles. The results from several neoclassical codes, sfincs, fortec-3d, and dkes, are compared both with each other and the measurements. Finally, these comparisons show good agreement, giving confidence in the applicability of the neoclassical calculations to the W7-X configuration.« less