Constrained Viscoelastic Layer Damping of Thick Aluminum Plates: Design Analysis, and Testing

DTIC Science & Technology

1990-03-01

1’HO IrC I’= ICI/( 2 . #P1) C CUOiPAPISON OF r AND rCr IF (ABS(1.-FP/FCP).LE. 0.1) THEN GOlD 500 ELSE C-010 501 C COHlPUiE SYSIEMI LOSS FAC7OP 500...To,rRom, mRoT, II,ML , ETF ROLSLSH, CrRUL IC) C C COII ’LRI RESULTs FrRi 1H-I1l LAYER CALCULATIONI 10 TOTAL PLATE C E IA3 0. 0 UP r O II’ 1/ 2. (P I

Polypharmacological profile of 1,2-dihydro-2-oxo-pyridine-3-carboxamides in the endocannabinoid system.

PubMed

Chicca, Andrea; Arena, Chiara; Bertini, Simone; Gado, Francesca; Ciaglia, Elena; Abate, Mario; Digiacomo, Maria; Lapillo, Margherita; Poli, Giulio; Bifulco, Maurizio; Macchia, Marco; Tuccinardi, Tiziano; Gertsch, Jürg; Manera, Clementina

2018-05-14

The endocannabinoid system (ECS) represents one of the major neuromodulatory systems involved in different physiological and pathological processes. Multi-target compounds exert their activities by acting via multiple mechanisms of action and represent a promising pharmacological modulation of the ECS. In this work we report 4-substituted and 4,5-disubstituted 1,2-dihydro-2-oxo-pyridine-3-carboxamide derivatives with a broad spectrum of affinity and functional activity towards both cannabinoid receptors and additional effects on the main components of the ECS. In particular compound B3 showed high affinity for CB1R (K i  = 23.1 nM, partial agonist) and CB2R (K i  = 6.9 nM, inverse agonist) and also significant inhibitory activity (IC 50  = 70 nM) on FAAH with moderate inhibition of ABHD12 (IC 50  = 2.5 μΜ). Compounds B4, B5 and B6 that act as full agonists at CB1R and as partial agonists (B5 and B6) or antagonist (B4) at CB2R, exhibited an additional multi-target property by inhibiting anandamide uptake with sub-micromolar IC 50 values (0.28-0.62 μΜ). The best derivatives showed cytotoxic activity on U937 lymphoblastoid cells. Finally, molecular docking analysis carried out on the three-dimensional structures of CB1R and CB2R and of FAAH allowed to rationalize the structure-activity relationships of this series of compounds. Copyright © 2018 Elsevier Masson SAS. All rights reserved.

U.S. EPA, Pesticide Product Label, , 05/11/1977

EPA Pesticide Factsheets

2011-04-14

... To Control CarEt 8 ... 1 ••• 'fecti.ol, •• ,,1, flit floo. .r ••• anti 'oe .,a •. sp.a, di,ectl, In'''' (ock •• cr •• ic.,,£ and \\#,,4e, co'p." .her. in •• ct, "'01 ... found. ...

Immunomagnetic Separation of Cryptosporidium parvum from Source Water Samples of Various Turbidities

PubMed Central

Bukhari, Z.; McCuin, R. M.; Fricker, C. R.; Clancy, J. L.

1998-01-01

Immunomagnetic separation (IMS) procedures which specifically capture Cryptosporidium oocysts and have the potential to isolate oocysts from debris have become commercially available. We compared two IMS kits (kit DB [Dynabeads anti-Cryptosporidium; product no. 730.01; Dynal A.S., Oslo, Norway] and kit IC1 [Crypto Scan IMS; product no. R10; Clearwater Diagnostics Company, LLC, Portland, Maine]) and a modification of kit IC1 (kit IC2 [Crypto Scan IMS; product no. R10; Clearwater Diagnostics Company, LLC]) at three turbidity levels (50, 500, and 5,000 nephelometric turbidity units [ntu]) by using water matrices obtained from different geographical locations. In deionized water, kit DB yielded recoveries between 68 and 83%, whereas the recoveries obtained with kits IC1 and IC2 were more variable and ranged from 0.2 to 74.5%. In water matrices with turbidity levels up to 500 ntu, the oocyst recoveries were more variable with kit DB; however, the recoveries were similar to those obtained in deionized water. In contrast, there were notable reductions in oocyst recoveries in the turbid matrices with kits IC1 and IC2, and the highest recovery (8.3%) was obtained with a 50-ntu sample. An examination of the effects of age on oocyst recovery with kit DB revealed that oocysts up to 16 weeks old yielded recoveries similar to the recoveries observed with fresh oocysts. These data indicate that all IMS kits do not perform equally well, and it is important to conduct in-house quality assurance work before a commercially available IMS kit is selected to replace flotation procedures for recovery of Cryptosporidium oocysts. PMID:9797313

Structure-based identification and characterisation of structurally novel human P2X7 receptor antagonists.

PubMed

Caseley, Emily A; Muench, Stephen P; Fishwick, Colin W; Jiang, Lin-Hua

2016-09-15

The P2X7 receptor (P2X7R) plays an important role in diverse conditions associated with tissue damage and inflammation, meaning that the human P2X7R (hP2X7R) is an attractive therapeutic target. The crystal structures of the zebrafish P2X4R in the closed and ATP-bound open states provide an unprecedented opportunity for structure-guided identification of new ligands. The present study performed virtual screening of ∼100,000 structurally diverse compounds against the ATP-binding pocket in the hP2X7R. This identified three compounds (C23, C40 and C60) out of 73 top-ranked compounds by testing against hP2X7R-mediated Ca(2+) responses. These compounds were further characterised using Ca(2+) imaging, patch-clamp current recording, YO-PRO-1 uptake and propidium iodide cell death assays. All three compounds inhibited BzATP-induced Ca(2+) responses concentration-dependently with IC50s of 5.1±0.3μM, 4.8±0.8μM and 3.2±0.2μM, respectively. C23 and C40 inhibited BzATP-induced currents in a reversible and concentration-dependent manner, with IC50s of 0.35±0.3μM and 1.2±0.1μM, respectively, but surprisingly C60 did not affect BzATP-induced currents up to 100μM. They suppressed BzATP-induced YO-PRO-1 uptake with IC50s of 1.8±0.9μM, 1.0±0.1μM and 0.8±0.2μM, respectively. Furthermore, these three compounds strongly protected against ATP-induced cell death. Among them, C40 and C60 exhibited strong specificity towards the hP2X7R over the hP2X4R and rP2X3R. In conclusion, our study reports the identification of three novel hP2X7R antagonists with micromolar potency for the first time using a structure-based approach, including the first P2X7R antagonist with preferential inhibition of large pore formation. Copyright © 2016 The Authors. Published by Elsevier Inc. All rights reserved.

Urine Markers Do Not Predict Biopsy Findings or Presence of Bladder Ulcers in Interstitial Cystitis/Painful Bladder Syndrome

PubMed Central

Erickson, Deborah R.; Tomaszewski, John E.; Kunselman, Allen R.; Stetter, Christina M.; Peters, Kenneth M.; Rovner, Eric S.; Demers, Laurence M.; Wheeler, Marcia A.; Keay, Susan K.

2009-01-01

Purpose To test for associations between urine markers, bladder biopsy features and bladder ulcers in interstitial cystitis/painful bladder syndrome (IC/PBS). Materials and Methods Subjects were 72 patients with IC/PBS undergoing bladder distention and biopsy. Urine was collected before the procedure. Urine marker levels were correlated with biopsy and cystoscopic findings. Patients with no previous IC/PBS treatments (n=47) were analyzed separately from previously treated patients (n=25). Results For untreated patients, urine IL-6 and cGMP were associated with urothelial EGF receptor staining (for IL-6 r=0.29, 95% CI (0.07, 0.51), p=0.01; for cGMP r=0.34, 95% CI (0.13, 0.55), p=0.002). Urine IL-8 was negatively associated with urothelial HB-EGF staining (r=-0.34, 95% CI (-0.55, -0.12), p=0.002) and positively associated with lamina propria mast cell count (r=0.29, 95% CI (0.06, 0.52), p=0.01). The latter association also was seen in treated patients (r=0.46, 95% CI (0.20, 0.73), p<0.001). None of the urine markers was significantly different for ulcer vs. nonulcer patients. All of the ulcer patients had extensive inflammation on bladder biopsy: severe mononuclear cell infiltration, moderate or strong IL-6 staining in the urothelium and lamina propria, and LCA staining in >10% of the lamina propria. However, these features also were seen in 24-76% of the nonulcer patients. Conclusions Overall, urine markers did not associate robustly with biopsy findings. The strongest association was a positive association between urine IL-8 levels and bladder mast cell count. Ulcer patients consistently had bladder inflammation, but the cystoscopic finding of ulcers was not a sensitive indicator of inflammation on bladder biopsy. PMID:18353383

Monitoring and predicting the fecal indicator bacteria concentrations from agricultural, mixed land use and urban stormwater runoff.

PubMed

Paule-Mercado, M A; Ventura, J S; Memon, S A; Jahng, D; Kang, J-H; Lee, C-H

2016-04-15

While the urban runoff are increasingly being studied as a source of fecal indicator bacteria (FIB), less is known about the occurrence of FIB in watershed with mixed land use and ongoing land use and land cover (LULC) change. In this study, Escherichia coli (EC) and fecal streptococcus (FS) were monitored from 2012 to 2013 in agricultural, mixed and urban LULC and analyzed according to the most probable number (MPN). Pearson correlation was used to determine the relationship between FIB and environmental parameters (physicochemical and hydrometeorological). Multiple linear regressions (MLR) were used to identify the significant parameters that affect the FIB concentrations and to predict the response of FIB in LULC change. Overall, the FIB concentrations were higher in urban LULC (EC=3.33-7.39; FS=3.30-7.36log10MPN/100mL) possibly because of runoff from commercial market and 100% impervious cover (IC). Also, during early-summer season; this reflects a greater persistence and growth rate of FIB in a warmer environment. During intra-event, however, the FIB concentrations varied according to site condition. Anthropogenic activities and IC influenced the correlation between the FIB concentrations and environmental parameters. Stormwater temperature (TEMP), turbidity, and TSS positively correlated with the FIB concentrations (p>0.01), since IC increased, implying an accumulation of bacterial sources in urban activities. TEMP, BOD5, turbidity, TSS, and antecedent dry days (ADD) were the most significant explanatory variables for FIB as determined in MLR, possibly because they promoted the FIB growth and survival. The model confirmed the FIB concentrations: EC (R(2)=0.71-0.85; NSE=0.72-0.86) and FS (R(2)=0.65-0.83; NSE=0.66-0.84) are predicted to increase due to urbanization. Therefore, these findings will help in stormwater monitoring strategies, designing the best management practice for FIB removal and as input data for stormwater models. Copyright © 2016 Elsevier B.V. All rights reserved.

NAS (HOST/ARTS IIIA) to VME Modem Interface ATC Interface Hardware Manual

DTIC Science & Technology

1990-10-01

SIXT,RXSYNC,RXACTIVE,ALLOWI) IO,C,0,1,O,O1 - > [^bf,1,1,O,0J;vector 104 [o,c,0,1,o,0J -> [^hf,1,1,O,OJ;vector [I,C,0,1,O,0] -> [Abf,1,1,0,OJ;vector IO,C...VFU.T(R 501 C’-35 Io,c,1,1,o,o,o1 -> rhb ,0,01;i [X,C,1,1,0,O,1] -> ["hf,0,0; [1,C,1,I,0,1,01 -> [^ha,0,1];LACT (MTE)-S2 io,C,,1,0,1,01 -> I^ha,0,1; [1

Advanced Imaging Tracker

DTIC Science & Technology

1982-06-01

3oijsteii 14.) v ilson f3 1vj Ar inj~on, VA Ž222JY L. or p AtLnZ: -,iii~iarn Ouriey I d.LU ýu ndoldt i~d txlJlýjLuqucqe, 14,, f. /A i’ Atun : ý...34ivision iY) LiOX d /M ye I v - iv i S i 01-1 I ,/L i r ic u .L Lbr~ J o-r y At~rlt -lex earker 1.i nj .on, A½iI r -I efnLi.) DL-4 NAS’A Aines Atun

Mitochondrial Changes in Platelets Are Not Related to Those in Skeletal Muscle during Human Septic Shock

PubMed Central

Protti, Alessandro; Fortunato, Francesco; Caspani, Maria L.; Pluderi, Mauro; Lucchini, Valeria; Grimoldi, Nadia; Solimeno, Luigi P.; Fagiolari, Gigliola; Ciscato, Patrizia; Zella, Samis M. A.; Moggio, Maurizio; Comi, Giacomo P.; Gattinoni, Luciano

2014-01-01

Platelets can serve as general markers of mitochondrial (dys)function during several human diseases. Whether this holds true even during sepsis is unknown. Using spectrophotometry, we measured mitochondrial respiratory chain biochemistry in platelets and triceps brachii muscle of thirty patients with septic shock (within 24 hours from admission to Intensive Care) and ten surgical controls (during surgery). Results were expressed relative to citrate synthase (CS) activity, a marker of mitochondrial density. Patients with septic shock had lower nicotinamide adenine dinucleotide dehydrogenase (NADH)/CS (p = 0.015), complex I/CS (p = 0.018), complex I and III/CS (p<0.001) and complex IV/CS (p = 0.012) activities in platelets but higher complex I/CS activity (p = 0.021) in triceps brachii muscle than controls. Overall, NADH/CS (r2 = 0.00; p = 0.683) complex I/CS (r2 = 0.05; p = 0.173), complex I and III/CS (r2 = 0.01; p = 0.485), succinate dehydrogenase (SDH)/CS (r2 = 0.00; p = 0.884), complex II and III/CS (r2 = 0.00; p = 0.927) and complex IV/CS (r2 = 0.00; p = 0.906) activities in platelets were not associated with those in triceps brachii muscle. In conclusion, several respiratory chain enzymes were variably inhibited in platelets, but not in triceps brachii muscle, of patients with septic shock. Sepsis-induced mitochondrial changes in platelets do not reflect those in other organs. PMID:24787741

Estrogen Modification of Human Glutamate Dehydrogenases Is Linked to Enzyme Activation State*

PubMed Central

Borompokas, Nikolas; Papachatzaki, Maria-Martha; Kanavouras, Konstantinos; Mastorodemos, Vasileios; Zaganas, Ioannis; Spanaki, Cleanthe; Plaitakis, Andreas

2010-01-01

Mammalian glutamate dehydrogenase (GDH) is a housekeeping enzyme central to the metabolism of glutamate. Its activity is potently inhibited by GTP (IC50 = 0.1–0.3 μm) and thought to be controlled by the need of the cell in ATP. Estrogens are also known to inhibit mammalian GDH, but at relatively high concentrations. Because, in addition to this housekeeping human (h) GDH1, humans have acquired via a duplication event an hGDH2 isoform expressed in human cortical astrocytes, we tested here the interaction of estrogens with the two human isoenzymes. The results showed that, under base-line conditions, diethylstilbestrol potently inhibited hGDH2 (IC50 = 0.08 ± 0.01 μm) and with ∼18-fold lower affinity hGDH1 (IC50 = 1.67 ± 0.06 μm; p < 0.001). Similarly, 17β-estradiol showed a ∼18-fold higher affinity for hGDH2 (IC50 = 1.53 ± 0.24 μm) than for hGDH1 (IC50 = 26.94 ± 1.07 μm; p < 0.001). Also, estriol and progesterone were more potent inhibitors of hGDH2 than hGDH1. Structure/function analyses revealed that the evolutionary R443S substitution, which confers low basal activity, was largely responsible for sensitivity of hGDH2 to estrogens. Inhibition of both human GDHs by estrogens was inversely related to their state of activation induced by ADP, with the slope of this correlation being steeper for hGDH2 than for hGDH1. Also, the study of hGDH1 and hGDH2 mutants displaying different states of activation revealed that the affinity of estrogen for these enzymes correlated inversely (R = 0.99; p = 0.0001) with basal catalytic activity. Because astrocytes are known to synthesize estrogens, these hormones, by interacting potently with hGDH2 in its closed state, may contribute to regulation of glutamate metabolism in brain. PMID:20628048

A novel vaccine against Porcine circovirus type 2 (PCV2) and Streptococcus equi ssp. zooepidemicus (SEZ) co-infection.

PubMed

Lin, Hui-xing; Ma, Zhe; Yang, Xu-qiu; Fan, Hong-jie; Lu, Cheng-ping

2014-06-25

To develop a vaccine against Porcine circovirus type 2 (PCV2) and Streptococcus equi ssp. zooepidemicus (SEZ) co-infection, the genes of porcine IL-18, capsid protein (Cap) of PCV2 and M-like protein (SzP) of SEZ were inserted into the swinepox virus (SPV) genome by homologous recombination. The recombinant swinepox virus rSPV-ICS was verified by PCR and indirect immunofluorescence assays. To evaluate the immunogenicity of rSPV-ICS, 28 PCV2 and SEZ seronegative Bama minipigs were immunized with rSPV-ICS (n=8), commercial PCV2 vaccine and SEZ vaccine (n=8) or wild type SPV (n=8). The results showed that SzP-specific antibody and PCV2 neutralizing antibody of the rSPV-ICS immunized group increased significantly compared to the wild type SPV treated group after vaccination and increased continuously over time. The levels of IL-4 and IFN-γ in the rSPV-ICS immunized group were significantly higher than the other three groups, respectively. After been co-challenged with PCV2 and SEZ, 87.5% piglets in rSPV-ICS immunized group were survived. Significant reductions in gross lung lesion score, histopathological lung lesion score, and lymph node lesion score were noticed in the rSPV-ICS immunized group compared with the wtSPV treated group. The results suggested that the recombinant rSPV-ICS provided piglets with significant protection against PCV2-SEZ co-infection; thus, it offers proof-of-principle for the development of a vaccine for the prevention of these swine diseases. Copyright © 2014 Elsevier B.V. All rights reserved.

Spiral Convection Columns: Improved Estimate Of Apparent Rotation Period(=1333.6 yr) Of Earth's Solid Inner Core

NASA Astrophysics Data System (ADS)

McDonald, Keith L.

1999-11-01

In 1974, an est. was made of turbulence driven rot. period of Earth's inner core(r=R_ic), neglecting forced precession, nutation and assuming core fluid's turbulent differential rot., (T_1c^o)_α, alone drives inner core and has achieved steady state so that viscous boundary condition, Υ_φ(R_ic,θ)=ɛ Υ = Υ_ic - Υ = Υ_φ(R_ic), is closely achieved.^1 Υ is mantle's const. sidereal angular velocity, Υ_ic is inner core's, and Υ_φ(r,θ) is fluid's appar., about Z-axis. In 1st est.^1 we assumed velocity and magnetic modes T_α,P_α and T_β,P_β are stationary random functions of time and deleted classes of modes in simplifying toroidal component eq. of transformed amplification eq.,^2 evaluated for mode (T_2c^o)_β to compute radial function (T_1c^o)_α thru a single integration with respect to r. In making integration we assumed toroidal and poloidal B-field intensities have same radial dependency thru core fluid, R_ic <= r <= 0.9R_c, whereas toroidal mag. field declines monotonely as rarrow 0, where it vanishes. To correct discrepancy, divide T_2c^o(r)_β by f(r) and multiply dr by f(r) and integrate over R_ic,..., R_c; define f(r)=150 gauss × (r/0.9R_c), 0 <= r <= 0.9Rc and f(r)=1500(1-r/R_c) gauss for 0.9Rc <= r <= R_c. Repeating computations^1 gives, for νm = 0.2 × 10^5 esu, rot. period of τ _φ(R_ic)=1768.77 yr, instead of former 812 yr.^1 However, we adopted later Elsasser's 1956 est. electrical conductivity of core fluid, σ = 3 × 10-6 emu, which yields τ_φ=1333.6 yr, as close lower limit since σ continues to increase with depth below mantle's base, R_c. Adopting 0.03 cm sec-1 for upwelling motions we see that spiral motions result that do not influence lifetimes of polar heat sources at Rc but shorten to near 10^3 yr near equator. B_T-,B_P-field replaces turbulance theory to compute τ _φ. ^1 Keith L McDonald, Bul. Am. Phys. Soc., 19(10), 1148, 1974. ^2 K L McDonald, On The Planetary Dynamo Theory, ESSA Tech. Report ERL 64-ESL 3 (Govt. Printing Office, 1968), Eq. 21.

Synergistic effect of sevoflurane and isoflurane on inhibition of the adult-type muscle nicotinic acetylcholine receptor by rocuronium.

PubMed

Liu, Li; Li, Wei; Wei, Ke; Cao, Jun; Luo, Jie; Wang, Bin; Min, Su

2013-06-01

Inhaled anesthetics increase the incidence of postoperative residual neuromuscular blockade, and the mechanism is still unclear. We have investigated the synergistic effect of low-concentration inhaled anesthetics and rocuronium on inhibition of the inward current of the adult-type muscle nicotinic acetylcholine receptor (ε-nAChR). Adult-type mouse muscle ε-nAChR was expressed in HEK293 cells by liposome transfection. The inward current of the ε-nAChR was activated by use of 10 μmol/L acetylcholine alone or in combination with different concentrations of sevoflurane, isoflurane, or rocuronium. The concentration-response curves of five cells were constructed, and the data yielded the 5, 25, and 50 % inhibitory concentrations (IC5, IC25, and IC50, respectively) for single-drug application. Subsequently, the functional channels were perfused by adding 0.5 IC5 of either sevoflurane or isoflurane (aqueous concentrations 140 and 100 μmol/L, respectively) to the solution, followed by addition of IC5, IC25, or IC50 rocuronium. The amount of inhibition was calculated to quantify their synergistic effect. The inhibitory effect of rocuronium was enhanced by sevoflurane or isoflurane in a concentration-dependent manner. Sevoflurane or isoflurane (0.5 IC5) with rocuronium at IC5, IC25, and IC50 synergistically inhibited the current amplitude of adult-type muscle ε-nAChR. When the IC5 of rocuronium was used, isoflurane had a stronger synergistic effect than sevoflurane (p < 0.05). When rocuronium was applied at higher concentrations (IC25 and IC50), sevoflurane had an effect similar to that of isoflurane. For both inhaled anesthetics, the synergistic effect was more intense for rocuronium at IC5 than for rocuronium at IC25 or IC50. Residual-concentration sevoflurane or isoflurane has a strong synergistic effect with rocuronium at clinically relevant residual concentrations. A lower rocuronium concentration resulted in a stronger synergistic effect.

New generation QuIC assays for prion seeding activity.

PubMed

Orrù, Christina D; Wilham, Jason M; Vascellari, Sarah; Hughson, Andrew G; Caughey, Byron

2012-01-01

The ability of abnormal TSE-associated forms of PrP to seed the formation of amyloid fibrils from recombinant PrP(Sen) has served as the basis for several relatively rapid and highly sensitive tests for prion diseases. These tests include rPrP-PMCA (rPMCA), standard quaking-induced conversion (S-QuIC), amyloid seeding assay (ASA), real-time QuIC (RT-QuIC) and enhanced QuIC (eQuIC). Here, we summarize recent improvements in the RT-QuIC-based assays that enhance the practicality, sensitivity and quantitative attributes of assays QuIC and promote the detection of prion seeding activity in dilute, inhibitor-laden fluids such as blood plasma.

All Prime Contract Awards by State or Country, Place, and Contractor, FY 85. Part 6 (Alachua, Florida - Winder, Georgia).

DTIC Science & Technology

1985-01-01

4aC I 00 < M Uz 00(000000cc0000000001. U 0LALLAAOO 104I < 40(0OO0O4NN0.I-C10 ml W N00NNNN-4-I - M I .00 . . ~ .’l ~ C 0 0 .0- . .. . WWW W0r.000O LA...40 -4 -4 -V4I, 0.2c W~n r-. CLn U). C CC rA. IA. I ca 0 sO N 4 r4-4 4 --*L -qU l4 .00)L . m -IU NY mQ 4 *ww4CI www "Mm<)C, C’ oC)Co ) -IC44 -40 .. 40)C...10 ) -4 0 N 0 * C 1) 0 0N0 0 N 0 0 00’ mo oo* 𔃺 (0’ 4-’ in L4)4)-)- -n =0 0 0M- =OO- = 0. 30w~ww -4c) -4w www -40) -4-4n~ - -4mmac L44 0-- 403 01 0

Catalog of Audiovisual Productions. Volume 2. Navy and Marine Corps Productions

DTIC Science & Technology

1984-06-01

O" - _ BEPEFITS IILITMAY S/06 BOISII P/2BETA ARICLES T/06 BONDING, CHEMICAL T/02 RETATROS T/06 BONE... FRACTURES C/02.21 C/E0AES 5 BONES (HUIAN) C...H/O1 ..... ’ *b-]1 FIR , M IC 03 FLOOD cUro F104 FIELDS, LDING 02 FLUIDS HYDRALIC J/07 FIELDS lI C /03 FLM kENT LIGhTS F/02 FAT ’ AliAFT /03.3 FLYING...PIPE Ff11 FGRIS, CRYSTALLINE T/09 FLAX JACKETS ,M/08 FORMULA$ K/0! 1- FLAKE THROWERS R/01 FRACTOGRAPHY (MATERIALS) J/05 FLAETIHROWERS R/01 FRACTURES

An evaluation of the fatigue crack growth and fracture toughness properties of beryllium-copper alloy CDA172

NASA Technical Reports Server (NTRS)

Forman, Royce G.; Henkener, Julie A.

1990-01-01

A series of fracture mechanics tests, using the Be-Cu alloy CDA172 in the round rod product form, was conducted in a lab air environment at room temperature. Tensile data is presented in both the L and C directions and K sub Ic data in both the C-R and C-L orientations. Fracture toughness values were derived from M(T) (center cracked), PS(T) (surface cracked) and CC01 (corner cracked) specimens of varying thickness. Fatigue crack growth data were obtained for the C-R orientation at stress ratio of 0.1, 0.4, and 0.7 and for the C-L orientation at stress ratios of 0.1, 0.3, 0.4, and 0.7.

Persistence of Circulating Hepatitis C Virus Antigens-Specific Immune Complexes in Patients with Resolved HCV Infection.

PubMed

Hu, Ke-Qin; Cui, Wei

2018-05-01

Our recent study indicated the possible presence of detectable hepatitis C virus antigens (HCV-Ags) after denaturation of sera with resolved HCV (R-HCV) infection. The present study determined and characterized persistent HCV-Ags-specific immune complexes (ICs) in these patients. Sixty-eight sera with R-HCV and 34 with viremic HCV (V-HCV) infection were tested for free and IC-bound HCV-Ags using HCV-Ags enzyme immunoassay (EIA), the presence of HCV-Ags-specific ICs by immunoprecipitation and Western blot (IP-WB), HCV ICs containing HCV virions using IP and HCV RNA RT-PCR, and correlation of HCV ICs with clinical presentation in these patients. Using HCV-Ags EIA, we found 57.4% of sera with R-HCV infection were tested positive for bound, but not free HCV-Ags. Using pooled or individual anti-HCV E1/E2, cAg, NS3, NS4b, and/or NS5a to precipitate HCV-specific-Ags, we confirmed persistent HCV-Ags ICs specific to various HCV structural and non-structural proteins not only in V-HCV infection, but also in R-HCV infection. Using IP and HCV RNA PCR, we then confirmed the presence of HCV virions within circulating ICs in V-HCV, but not in R-HCV sera. Multivariable analysis indicated significant and independent associations of persistent circulating HCV-Ags-specific ICs with both age and the presence of cirrhosis in patients with R-HCV infection. Various HCV-Ag-specific ICs, but not virions, persist in 57.4% of patients who had spontaneous or treatment-induced HCV clearance for 6 months to 20 years. These findings enriched our knowledge on HCV pathogenesis and support further study on its long-term clinical relevance, such as extrahepatic manifestation, transfusion medicine, and hepatocarcinogenesis.

Estimating Weight and Moments for Ship Control Design Technical Assessment Team Reviews

DTIC Science & Technology

2016-07-26

01 5/ 02 0 E st im at in g W ei gh t & M om en ts fo r S C D T ec hn ic al A ss es sm en t T ea m R ev ie w s NSWCCD-80-TR-2016/020...currently valid OMB control number. PLEASE DO NOT RETURN YOUR FORM TO THE ABOVE ADDRESS. 1. REPORT DATE (DD-MM-YYYY) 07-26-2016 2. REPORT TYPE...10  3.4.2 Distributive Systems / Other Impacts

Support for the Symposium on the Application of Geophysics to Environmental and Engineering Problems, 2012-2014

DTIC Science & Technology

2014-07-02

Tuesday Morning • March 18 S A G E E P 2 01 1 T E C H N IC A L P R O G R A M B orehole G eophysics C hair: Jam es LoC oco C o-C hair: D aryl Tw...ssib ilities in th e R eservo ir E n g in eerin g , Leo n id A n isim ov, LU K O IL-E n g in eerin g G eo p hysical Flow A n alysis o f A n iso

Essentiality Weighting Models for Wholesale Level Inventory Management

DTIC Science & Technology

1988-12-01

Collection System (MDCS) and the VIDS/MAF (Visual Identification Display System/Maintenance Action Form, OPNAV 4790/ 60 ) to obtain Equipment Operation...4-) oI C. oo >, U r09 09 L C IC d - E- 0 .l . C .P UH 4- 3 0 r r-1 U 4- 0000 0U H Uu) 𔃾-) > 4-) ri Ol U- 0f 01l U >/ a U)) ODL U . t .1 Z 11 U0...the definition in reference (b). The remaining 60 percent, although not all MEC 3 items, must currently be assigned that MEC since none other exists

CXCR4-antagonist Peptide R-liposomes for combined therapy against lung metastasis

NASA Astrophysics Data System (ADS)

Ieranò, Caterina; Portella, Luigi; Lusa, Sara; Salzano, Giuseppina; D'Alterio, Crescenzo; Napolitano, Maria; Buoncervello, Maria; Macchia, Daniele; Spada, Massimo; Barbieri, Antonio; Luciano, Antonio; Barone, Maria Vittoria; Gabriele, Lucia; Caraglia, Michele; Arra, Claudio; De Rosa, Giuseppe; Scala, Stefania

2016-03-01

The chemokine CXCL12 activates CXCR4, initiating multiple pathways that control immune cell trafficking, angiogenesis and embryogenesis; CXCR4 is also overexpressed in multiple tumors affecting metastatic dissemination. While there has been great enthusiasm for exploiting the CXCR4-CXCL12 axis as a target in cancer therapy, to date the promise has yet to be fulfilled. A new class of CXCR4-antagonist cyclic peptides was recently developed and the compound named Peptide R was identified as the most active. With the intent to improve the efficacy and biodistribution of Peptide R, stealth liposomes decorated with Peptide R were developed (PL-Peptide R). In vitro PL-Peptide R efficiently inhibited CXCR4-dependent migration and in vivo it significantly reduced lung metastases and increased overall survival in B16-CXCR4 injected C57BL/6 mice. To evaluate if PL-Peptide R could also be a drug delivery system for CXCR4 expressing tumors, the PL-Peptide R was loaded with doxorubicin (DOX) (PL-Peptide R-DOX). PL-Peptide R-DOX efficiently delivered DOX to CXCR4 expressing cell lines with a consequent decrease in the DOX IC50 efficient dose. In vivo, B16-CXCR4 injected C57BL/6 mice treated with PL-Peptide R-DOX developed fewer lung metastases compared to PL-DOX treated mice. This work provides the proof-of-concept to prevent metastasis by using combined nanomedicine.The chemokine CXCL12 activates CXCR4, initiating multiple pathways that control immune cell trafficking, angiogenesis and embryogenesis; CXCR4 is also overexpressed in multiple tumors affecting metastatic dissemination. While there has been great enthusiasm for exploiting the CXCR4-CXCL12 axis as a target in cancer therapy, to date the promise has yet to be fulfilled. A new class of CXCR4-antagonist cyclic peptides was recently developed and the compound named Peptide R was identified as the most active. With the intent to improve the efficacy and biodistribution of Peptide R, stealth liposomes decorated with Peptide R were developed (PL-Peptide R). In vitro PL-Peptide R efficiently inhibited CXCR4-dependent migration and in vivo it significantly reduced lung metastases and increased overall survival in B16-CXCR4 injected C57BL/6 mice. To evaluate if PL-Peptide R could also be a drug delivery system for CXCR4 expressing tumors, the PL-Peptide R was loaded with doxorubicin (DOX) (PL-Peptide R-DOX). PL-Peptide R-DOX efficiently delivered DOX to CXCR4 expressing cell lines with a consequent decrease in the DOX IC50 efficient dose. In vivo, B16-CXCR4 injected C57BL/6 mice treated with PL-Peptide R-DOX developed fewer lung metastases compared to PL-DOX treated mice. This work provides the proof-of-concept to prevent metastasis by using combined nanomedicine. Electronic supplementary information (ESI) available. See DOI: 10.1039/c5nr06335c

[Comparation study of incidental irradiation dose to the internal mammary chain during postmastectomy radiotherapy for patients treated with different irradiation techniques].

PubMed

Wang, W; Meng, Y T; Song, Y F; Sun, T; Xu, M; Shao, Q; Zhang, Y J; Li, J B

2018-05-23

Objective: To evaluated the unplanned coverage dose to the internal mammary chain (IMC) in patient treated with postmastectomy radiotherapy (PMRT). Methods: One hundred and thirty eight patients with breast cancer receiving radiotherapy (RT) in our hospital were retrospectively analyzed. Patients were divided into three groups: three-dimensional conformal radiotherapy (3D-CRT) group, forward intensity-modulated radiotherapy (F-IMRT) group and inverse IMRT (I-IMRT) group. The IMC were contoured according to Radiation Therapy Oncology Group (RTOG) consensus, and were not include into the planning target volume (PTV). The incidental irradiation dose to IMC among the three groups and the first three intercostal spaces IMC (ICS-IMC 1-3) were all compared, and explored the relationship between the mean doses (Dmean) of IMC and the OARs (ipsilateral lung and heart). Results: The dose delivered to IMC showed no difference in CRT, F-IMRT and I-IMRT(33.80 Gy, 29.65 Gy and 32.95 Gy). And 10.42%, 2.04%, and 9.76% patients achieved ≥45 Gy when treated with CRT, F-IMRT and I-IMRT. For the IMC dose in the first three intercostal spaces (ICS1-3), there was no difference to the three treatment plannings. The Dmean, V(20), V(30), V(40) and V(50) of the ICS-IMC2 and ICS-IMC3 were all obviously superior than ICS-IMC1 for all these three plannings. Moderate positive correlation was founded between Dmean for IMC and Dmean for heart for left breast cancer patients underwent CRT ( r =0.338, P =0.01). Whereas for F-IMRT and I-IMRT groups, positive correlation were founded between Dmean for IMC and Dmean and V(20) for ipsilateral lung for all patients (F-IMRT: r =0.366, P =0.010; r =0.318, P =0.026; I-IMRT: r =0.427, P =0.005; r =0.411, P =0.008). Conclusions: In 3D-CRT, F-IMRT and I-IMRT planning methods, partial patients get IMC irradiated doses that could achieve therapeutic doses. Compared with 3D-CRT, F-IMRT and I-IMRT further reduced the dose of irradiated organs. However, there is no difference in the dose coverage of IMC for the three planned approaches when the IMC made an unplanned target.

SAR (Synthetic Aperture Radar) Data Collection and Processing Summary - 1984 SARSEX (SAR Internal Wave Signature Experiment) Experiment.

DTIC Science & Technology

1985-03-01

DIVISION ;! -0 N xr-0 n 0n4 1 1 I- C) 0 Ic 0 C WIx W Qr - - r -r 01............................. I Cq I1 -a I- I X 0’ an w I w kI~r 1 0r- r- r . 0~~~ Cs CW 1...object from the SAR platform . Ground range, the 102 ~RIM RADAR DIVISION 0 0 sc 0’. C4 C4 Xn en % >4-4 441i V-u -- - W 1-11 04 v4 0o 0 4 0 (A~U Go 4J...Rg = rRF -hy ,(3) for the flat earth or low-altitude case, where h is the platform altitude. Because the range and azimuth scales are not the same

Caries in adolescents in relation to their skeletal status.

PubMed

Kostik, Mikhail M; Kuzmina, Diana A; Novikova, Valeria P; Larionova, Valentina I; Scheplyagina, Larisa A

2015-03-01

Despite well-known evidence of association of caries with bone metabolic diseases, there are only a small number of studies about caries and bone mineral density (BMD) on pediatric population. We evaluated the possibility of bone mineralization and metabolism disturbances in children with caries and compared them with healthy individuals. A total of 123 patients with caries (63 boys and 60 girls), aged 12-15 years, were included. The children were divided according caries stage: the decayed, missing, and filled tooth (DMFT) group (n=73) and the initial caries (IC) group (n=50), which have clinically active initial caries lesions on the enamel ("white spots"). Caries-free (CF) children (n=42) were the healthy controls. Bone mineralization was measured in all children with caries and healthy controls by dual-energy X-ray absorptiometry of the lumbar spine (L1-L4). For the assessment of bone metabolism, osteocalcin, carboxy terminal telopeptide of type I collagen (CTX), parathyroid hormone, Ca²⁺, inorganic phosphate, and total alkaline phosphatase were used. Children with DMFT have low BMD and BMD Z score in association with low osteocalcin and high CTX levels, compared with IC (p=0.008 and p=0.0001, respectively) and CF children (p<0.0000 and p=0.0001, respectively). In DMFT, Ca²⁺ was significantly higher compared with IC (p=0.01) and CF (p=0.003). Caries stages negatively correlated with BMD (r=-0.86, p<0.001). A differently directed correlation between CTX and osteocalcin was detected: CTX was negatively related to osteocalcin in the DMFT group (r=-0.22, p=0.043) and positively related in the IC (r=0.42, p=0.002) and CF children (r=0.58, p=0.0000). Children with any caries stage have decreased BMD accompanied with increased bone resorption. We consider that caries could be a marker of impact bone mineralization and metabolism.

The Role of microRNA miR-101 in Prostate Cancer Progression

DTIC Science & Technology

2011-09-01

13 signature associated with prognosis and progression in chronic lymphocytic leukemia. N Engl J Med, 353, 1793-801. 18. Pallante , P., Visone...June; published online 31 July 2011; doi:10.1038/nbt.1914 © 2 01 1 N at u re A m er ic a, In c. A ll ri g h ts r es er ve d . nature...the design or funding of these studies. The other authors declare that they have no competing interests. Submitted 14 July 2010 Accepted 10 February

A Portable Parallel Implementation of the U.S. Navy Layered Ocean Model

DTIC Science & Technology

1995-01-01

Wallcraft, PhD (I.C. 1981) Planning Systems Inc. & P. R. Moore, PhD (Camb. 1971) IC Dept. Math. DR Moore 1° Encontro de Metodos Numericos...Kendall Square, Hypercube, D R Moore 1 ° Encontro de Metodos Numericos para Equacöes de Derivadas Parciais A. J. Wallcraft IC Mathematics...chips: Chips Machine DEC Alpha CrayT3D/E SUN Sparc Fujitsu AP1000 Intel 860 Paragon D R Moore 1° Encontro de Metodos Numericos para Equacöes

Physicochemical basis for dilated intercellular spaces in non-erosive acid-damaged rabbit esophageal epithelium.

PubMed

Tobey, N A; Gambling, T M; Vanegas, X C; Carson, J L; Orlando, R C

2008-01-01

Dilated intercellular spaces (DIS) within esophageal epithelium (EE) is a histopathologic feature of non-erosive reflux disease and early lesion in acid-damaged rabbit EE associated with increased paracellular permeability. Its cause remains unknown, but the lesion's morphology suggests a significant fluid shift into the intercellular spaces (ICS). Since water follows osmotic forces and consequently ion movements, we explored the role of active (ion) transport and ion gradients in its pathogenesis. This was done by quantifying the effect of inhibited active transport and altered ion gradients on electrical resistance (R(T)) and ICS diameter in acid-exposed Ussing-chambered rabbit EE. Compared with normal Ringer, pH 7.5, 30 minutes of luminal HCl (100 mmol/L), pH 1.1, increased permeability (R(T): +5 +/- 4% vs-52 +/- 4%) and ICS diameter (0.25 +/- 0.01 microm vs 0.42 +/- 0.02 microm), but had no effect on cell morphology or diameter. Ouabain pretreatment significantly reduced active transport but had no effect on the acid-induced changes. However, negating the chloride gradient created by luminal HCl either by adding choline chloride, 100 mmol/L, serosally or by replacing luminal HCl, pH 1.1, with luminal H(2)SO(4), pH 1.1, prevented the development of DIS while maintaining the increase in permeability. DIS was also prevented in the presence of a 100 mmol/L (choline) chloride gradient by luminal exposure at neutral pH. DIS in HCl-damaged EE is caused by an H(+)-induced increase in epithelial permeability; this enables Cl(-) to diffuse along its gradient into the ICS, creating an osmotic force for water movement into and (hydrostatic) dilation of the ICS.

Is Sparing to Availability the Way?

DTIC Science & Technology

1993-06-05

ie itun of nftuMibton si mýTr ted3 to -e ic j I nuw peo r re* refitC,f oil ire trw’ fut 1, -tv n’ ncutr. ’~ n., atI s ’ ,01 a (t . qJaritiy adll...striving to determine the optimal mix and depth of their inventories, thereby better supporting either their production schedules or direct sales to

SPROC: A multiple-processor DSP IC

NASA Technical Reports Server (NTRS)

Davis, R.

1991-01-01

A large, single-chip, multiple-processor, digital signal processing (DSP) integrated circuit (IC) fabricated in HP-Cmos34 is presented. The innovative architecture is best suited for analog and real-time systems characterized by both parallel signal data flows and concurrent logic processing. The IC is supported by a powerful development system that transforms graphical signal flow graphs into production-ready systems in minutes. Automatic compiler partitioning of tasks among four on-chip processors gives the IC the signal processing power of several conventional DSP chips.

Modulating effects of plasma containing anti-malarial antibodies on in vitro anti-malarial drug susceptibility in Plasmodium falciparum.

PubMed

Monatrakul, Preeyaporn; Mungthin, Mathirut; Dondorp, Arjen M; Krudsood, Srivicha; Udomsangpetch, Rachanee; Wilairatana, Polrat; White, Nicholas J; Chotivanich, Kesinee

2010-11-16

The efficacy of anti-malarial drugs is determined by the level of parasite susceptibility, anti-malarial drug bioavailability and pharmacokinetics, and host factors including immunity. Host immunity improves the in vivo therapeutic efficacy of anti-malarial drugs, but the mechanism and magnitude of this effect has not been characterized. This study characterized the effects of 'immune' plasma to Plasmodium falciparumon the in vitro susceptibility of P. falciparum to anti-malarial drugs. Titres of antibodies against blood stage antigens (mainly the ring-infected erythrocyte surface antigen [RESA]) were measured in plasma samples obtained from Thai patients with acute falciparum malaria. 'Immune' plasma was selected and its effects on in vitro parasite growth and multiplication of the Thai P. falciparum laboratory strain TM267 were assessed by light microscopy. The in vitro susceptibility to quinine and artesunate was then determined in the presence and absence of 'immune' plasma using the 3H-hypoxanthine uptake inhibition method. Drug susceptibility was expressed as the concentrations causing 50% and 90% inhibition (IC50 and IC90), of 3H-hypoxanthine uptake. Incubation with 'immune' plasma reduced parasite maturation and decreased parasite multiplication in a dose dependent manner. 3H-hypoxanthine incorporation after incubation with 'immune' plasma was decreased significantly compared to controls (median [range]; 181.5 [0 to 3,269] cpm versus 1,222.5 [388 to 5,932] cpm) (p= 0.001). As a result 'immune' plasma reduced apparent susceptibility to quinine substantially; median (range) IC50 6.4 (0.5 to 23.8) ng/ml versus 221.5 (174.4 to 250.4) ng/ml (p = 0.02), and also had a borderline effect on artesunate susceptibility; IC50 0.2 (0.02 to 0.3) ng/ml versus 0.8 (0.2 to 2.3) ng/ml (p = 0.08). Effects were greatest at low concentrations, changing the shape of the concentration-effect relationship. IC90 values were not significantly affected; median (range) IC90 448.0 (65 to > 500) ng/ml versus 368.8 (261 to 501) ng/ml for quinine (p > 0.05) and 17.0 (0.1 to 29.5) ng/ml versus 7.6 (2.3 to 19.5) ng/ml for artesunate (p = 0.4). 'Immune' plasma containing anti-malarial antibodies inhibits parasite development and multiplication and increases apparent in vitro anti-malarial drug susceptibility of P. falciparum. The IC90 was much less affected than the IC50 measurement.

Correlating subcortical interhemispheric connectivity and cortical hemispheric dominance in brain tumor patients: A repetitive navigated transcranial magnetic stimulation study.

PubMed

Sollmann, Nico; Ille, Sebastian; Tussis, Lorena; Maurer, Stefanie; Hauck, Theresa; Negwer, Chiara; Bauer, Jan S; Ringel, Florian; Meyer, Bernhard; Krieg, Sandro M

2016-02-01

The present study aims to investigate the relationship between transcallosal interhemispheric connectivity (IC) and hemispheric language lateralization by using a novel approach including repetitive navigated transcranial magnetic stimulation (rTMS), hemispheric dominance ratio (HDR) calculation, and rTMS-based diffusion tensor imaging fiber tracking (DTI FT). 31 patients with left-sided perisylvian brain lesions underwent diffusion tensor imaging (DTI) and rTMS language mapping. Cortical language-positive rTMS spots were used to calculate HDRs (HDR: quotient of the left-sided divided by right-sided naming error rates for corresponding left- and right-sided cortical regions) and to create regions of interest (ROIs) for DTI FT. Then, fibers connecting the rTMS-based ROIs of both hemispheres were tracked, and the correlation of IC to HDRs was calculated via Spearman's rank correlation coefficient (rs). Fibers connecting rTMS-based ROIs of both hemispheres were detected in 12 patients (38.7%). Within the patients in which IC was detected, the mean number of subcortical IC fibers ± standard deviation (SD) was 138.0 ± 346.5 (median: 7.5; range: 1-1,217 fibers). Regarding rs for the correlation of HDRs and fiber numbers of patients that showed IC, only moderate correlation was revealed. Our approach might be beneficial and technically feasible for further investigation of the relationship between IC and language lateralization. However, only moderate correlation was revealed in the present study. Copyright © 2015 Elsevier B.V. All rights reserved.

Presence of multiple sites containing polar material in spherical Escherichia coli cells that lack MreB.

PubMed

Nilsen, Trine; Yan, Arthur W; Gale, Gregory; Goldberg, Marcia B

2005-09-01

In rod-shaped bacteria, certain proteins are specifically localized to the cell poles. The nature of the positional information that leads to the proper localization of these proteins is unclear. In a screen for factors required for the localization of the Shigella sp. actin assembly protein IcsA to the bacterial pole, a mutant carrying a transposon insertion in mreB displayed altered targeting of IcsA. The phenotype of cells containing a transposon insertion in mreB was indistinguishable from that of cells containing a nonpolar mutation in mreB or that of wild-type cells treated with the MreB inhibitor A22. In cells lacking MreB, a green fluorescent protein (GFP) fusion to a cytoplasmic derivative of IcsA localized to multiple sites. Secreted full-length native IcsA was present in multiple faint patches on the surfaces of these cells in a pattern similar to that seen for the cytoplasmic IcsA-GFP fusion. EpsM, the polar Vibrio cholerae inner membrane protein, also localized to multiple sites in mreB cells and colocalized with IcsA, indicating that localization to multiple sites is not unique to IcsA. Our results are consistent with the requirement, either direct or indirect, for MreB in the restriction of certain polar material to defined sites within the cell and, in the absence of MreB, with the formation of ectopic sites containing polar material.

Processing of Natural Echolocation Sequences in the Inferior Colliculus of Seba’s Fruit Eating Bat, Carollia perspicillata

PubMed Central

Kordes, Sebastian; Kössl, Manfred

2017-01-01

Abstract For the purpose of orientation, echolocating bats emit highly repetitive and spatially directed sonar calls. Echoes arising from call reflections are used to create an acoustic image of the environment. The inferior colliculus (IC) represents an important auditory stage for initial processing of echolocation signals. The present study addresses the following questions: (1) how does the temporal context of an echolocation sequence mimicking an approach flight of an animal affect neuronal processing of distance information to echo delays? (2) how does the IC process complex echolocation sequences containing echo information from multiple objects (multiobject sequence)? Here, we conducted neurophysiological recordings from the IC of ketamine-anaesthetized bats of the species Carollia perspicillata and compared the results from the IC with the ones from the auditory cortex (AC). Neuronal responses to an echolocation sequence was suppressed when compared to the responses to temporally isolated and randomized segments of the sequence. The neuronal suppression was weaker in the IC than in the AC. In contrast to the cortex, the time course of the acoustic events is reflected by IC activity. In the IC, suppression sharpens the neuronal tuning to specific call-echo elements and increases the signal-to-noise ratio in the units’ responses. When presenting multiple-object sequences, despite collicular suppression, the neurons responded to each object-specific echo. The latter allows parallel processing of multiple echolocation streams at the IC level. Altogether, our data suggests that temporally-precise neuronal responses in the IC could allow fast and parallel processing of multiple acoustic streams. PMID:29242823

Processing of Natural Echolocation Sequences in the Inferior Colliculus of Seba's Fruit Eating Bat, Carollia perspicillata.

PubMed

Beetz, M Jerome; Kordes, Sebastian; García-Rosales, Francisco; Kössl, Manfred; Hechavarría, Julio C

2017-01-01

For the purpose of orientation, echolocating bats emit highly repetitive and spatially directed sonar calls. Echoes arising from call reflections are used to create an acoustic image of the environment. The inferior colliculus (IC) represents an important auditory stage for initial processing of echolocation signals. The present study addresses the following questions: (1) how does the temporal context of an echolocation sequence mimicking an approach flight of an animal affect neuronal processing of distance information to echo delays? (2) how does the IC process complex echolocation sequences containing echo information from multiple objects (multiobject sequence)? Here, we conducted neurophysiological recordings from the IC of ketamine-anaesthetized bats of the species Carollia perspicillata and compared the results from the IC with the ones from the auditory cortex (AC). Neuronal responses to an echolocation sequence was suppressed when compared to the responses to temporally isolated and randomized segments of the sequence. The neuronal suppression was weaker in the IC than in the AC. In contrast to the cortex, the time course of the acoustic events is reflected by IC activity. In the IC, suppression sharpens the neuronal tuning to specific call-echo elements and increases the signal-to-noise ratio in the units' responses. When presenting multiple-object sequences, despite collicular suppression, the neurons responded to each object-specific echo. The latter allows parallel processing of multiple echolocation streams at the IC level. Altogether, our data suggests that temporally-precise neuronal responses in the IC could allow fast and parallel processing of multiple acoustic streams.

Factors Associated With Intestinal Constipation in Chronic Patients With Stroke Sequelae Undergoing Rehabilitation.

PubMed

Engler, Tânia Mara Nascimento de Miranda; Aguiar, Márcia Helena de Assis; Furtado, Íris Aline Brito; Ribeiro, Samile Pereira; de Oliveira, Pérola; Mello, Paulo Andrade; Padula, Marcele Pescuma Capeletti; Beraldo, Paulo Sérgio Siebra

The objective of this study was to define which stroke-related factors constitute independent variables in the incidence of intestinal constipation (IC) of chronic patients admitted to a hospital rehabilitation program. All patients consecutively admitted for rehabilitation were recruited for the study. In the Poisson multiple regression analysis using a hierarchical model, sociodemographic variables, comorbidities, medication, previous history of constipation, life habits, and stroke-related variables were considered for defining factors associated with IC. A 31% prevalence (95% confidence interval [CI]: 25.3-37.1) of IC was detected. Among the factors associated, female gender (adjusted prevalence ratio [PRadjusted] = 1.79; 95% CI: 1.20-2.68), intestinal complaints prior to stroke (PRadjusted = 3.71; 95% CI: 2.60-5.31), intake of less than 800 ml of fluid per day (PRadjusted = 1.72; 95% CI: 1.20- 2.45), age greater than 65 years at brain injury (PRadjusted = 1.67; 95% CI: 1.01-2.75), and partially impaired anterior brain circulation (PRadjusted = 3.35; 95% CI: 1.02-10.97) were associated with IC. Female gender, elderly, prior history of IC, low fluid intake, and partial impairment of anterior brain circulation were factors independently associated with IC in stroke survivors undergoing rehabilitation. These findings require further validation and may serve toward improving bowel retraining programs for this patient group.

The polymeric immunoglobulin receptor (secretory component) mediates transport of immune complexes across epithelial cells: a local defense function for IgA.

PubMed Central

Kaetzel, C S; Robinson, J K; Chintalacharuvu, K R; Vaerman, J P; Lamm, M E

1991-01-01

The polymeric immunoglobulin receptor (pIgR) on mucosal epithelial cells binds dimeric IgA (dIgA) on the basolateral surface and mediates transport of dIgA to the apical surface. Using Madin-Darby canine kidney epithelial cells stably transfected with pIgR cDNA, we found that soluble immune complexes (ICs) of 125I-labeled rat monoclonal antidinitrophenyl (DNP) dIgA (125I-dIgA) and DNP/biotin-bovine serum albumin were transported from the basolateral to the apical surface and then released. Monomeric IgA ICs were not transported, consistent with the specificity of pIgR for polymeric immunoglobulins. Essentially all the 125I-dIgA in apical culture supernatants was streptavidin precipitable, indicating that dIgA remained bound to antigen during transcytosis. While both dIgA and dIgA ICs bound pIgR with equal affinity (Kd approximately 8 nM), the number of high-affinity binding sites per cell was 2- to 3-fold greater for dIgA than for dIgA ICs. The extent of endocytosis of dIgA and dIgA ICs was correlated with the number of high-affinity binding sites. SDS/PAGE analysis of intracellular dIgA and dIgA ICs demonstrated that in both cases IgA remained undegraded during transport. The results suggest that the pathways of epithelial transcytosis of free dIgA and dIgA ICs are the same. Given the high population density of mucosal IgA plasma cells and the enormous surface area of pIgR-expressing mucosal epithelium, it is likely that significant local transcytosis of IgA ICs occurs in vivo. Such a process would allow direct elimination of IgA ICs at the mucosal sites where they are likely to form, thus providing an important defense function for IgA. Images PMID:1924341

Hydrodynamic delivery of plasmid DNA encoding human FcγR-Ig dimers blocks immune-complex mediated inflammation in mice.

PubMed

Shashidharamurthy, R; Machiah, D; Bozeman, E N; Srivatsan, S; Patel, J; Cho, A; Jacob, J; Selvaraj, P

2012-09-01

Therapeutic use and function of recombinant molecules can be studied by the expression of foreign genes in mice. In this study, we have expressed human Fcγ receptor-Ig fusion molecules (FcγR-Igs) in mice by administering FcγR-Ig plasmid DNAs hydrodynamically and compared their effectiveness with purified molecules in blocking immune-complex (IC)-mediated inflammation in mice. The concentration of hydrodynamically expressed FcγR-Igs (CD16A(F)-Ig, CD32A(R)-Ig and CD32A(H)-Ig) reached a maximum of 130 μg ml(-1) of blood within 24 h after plasmid DNA administration. The in vivo half-life of FcγR-Igs was found to be 9-16 days and western blot analysis showed that the FcγR-Igs were expressed as a homodimer. The hydrodynamically expressed FcγR-Igs blocked 50-80% of IC-mediated inflammation up to 3 days in a reverse passive Arthus reaction model. Comparative analysis with purified molecules showed that hydrodynamically expressed FcγR-Igs are more efficient than purified molecules in blocking IC-mediated inflammation and had a higher half-life. In summary, these results suggest that the administration of a plasmid vector with the FcγR-Ig gene can be used to study the consequences of blocking IC binding to FcγRs during the development of inflammatory diseases. This approach may have potential therapeutic value in treating IC-mediated inflammatory autoimmune diseases such as lupus, arthritis and autoimmune vasculitis.

Nutritional supplements modulate fluorescent protein-bound advanced glycation endproducts and digestive enzymes related to type 2 diabetes mellitus.

PubMed

Koch, Emily R; Deo, Permal

2016-09-01

Chronic hyperglycemia enhances the formation of advanced glycation endproducts (AGEs) and reactive oxygen species (ROS), contributing to diabetic complications. Thus, controlling blood glucose levels, inhibiting the formation of AGEs and reducing ROS are key therapeutic targets in early stage type 2 diabetes. The inhibitory effects of seven commercial liquid nutritional supplements against carbohydrate hydrolysing enzymes, α-amylase and α-glucosidase, was determined by dinitrosalicylic (DNS) reagent and p-nitrophenyl-α-D-glucopyranoside solution, respectively. Antiglycation activity was determined using the formation of fluorescent protein-bound AGEs. Total phenolic and flavonoid content and antioxidant properties (1,1-diphenyl-2-picrylhydrazyl antioxidant activity (DPPH) and ferric reducing antioxidant power (FRAP)) were determined for correlation among these components and inhibitory activities. Samoan noni juice showed the greatest inhibitory effects against α-amylase, whereas chlorophyll extracts showed the greatest inhibitory effect against α-glucosidase. Inhibition of α-glucosidase correlated with TFC (r(2) = 0.766; p < 0.01) and FRAP (r(2) = 0.750; p < 0.01) whereas no correlation was observed for α-amylase inhibition. All supplements inhibited fluorescent protein-bound AGEs, with the greatest effect exerted by Olive Leaf Extract, Blood Sugar Support (IC50 = 0.5 mg/ml). The IC50 values negatively correlated with TPC (r(2) = -0.707; p < 0.001) and DPPH scavenging activities (r(2) = 0.515; p < 0.05). The findings of this study highlight the potential of liquid nutritional supplements in managing and treating type 2 diabetes mellitus.

A survey of infection control teaching in U.S. dental schools.

PubMed

Porteous, Nuala B; Bizra, Eamon; Cothron, Annaliese; Yeh, Chih-Ko

2014-02-01

This study was conducted to determine the content of infection control (IC) curricula, the extent of IC monitoring and compliance, and the number of bloodborne pathogen (BBP) exposures/year in U.S. dental schools. A questionnaire was emailed to persons responsible for predoctoral IC programs. The response rate was 60 percent. Most schools did not have an independent course and used classroom lectures and clinic demonstrations to teach IC. Schools with an IC committee were more likely to use online learning (p<0.05), utilize multiple teaching methods (p<0.05), issue written warnings for IC violations (p<0.0001), and use multiple disciplinary actions (p<0.005) than schools without an IC committee. Schools with an IC coordinator were less likely to issue grade reductions for IC violations than schools with no IC coordinator (p<0.05). Thirty-eight percent reported ≥ 16 BBP exposures/year, and 18 percent reported <5. There was significant correlation between BBP exposure incidents and large class size (p<0.005). Respondents were satisfied with their IC curriculum and perceived that dental students had a high level of IC compliance and satisfaction, along with staff IC promotion and compliance. The findings suggest that schools without an IC committee should consider its benefits. Further investigation of schools with high numbers of BBP exposures is recommended.

DE-Cadherin regulates unconventional Myosin ID and Myosin IC in Drosophila left-right asymmetry establishment.

PubMed

Petzoldt, Astrid G; Coutelis, Jean-Baptiste; Géminard, Charles; Spéder, Pauline; Suzanne, Magali; Cerezo, Delphine; Noselli, Stéphane

2012-05-01

In bilateria, positioning and looping of visceral organs requires proper left-right (L/R) asymmetry establishment. Recent work in Drosophila has identified a novel situs inversus gene encoding the unconventional type ID myosin (MyoID). In myoID mutant flies, the L/R axis is inverted, causing reversed looping of organs, such as the gut, spermiduct and genitalia. We have previously shown that MyoID interacts physically with β-Catenin, suggesting a role of the adherens junction in Drosophila L/R asymmetry. Here, we show that DE-Cadherin co-immunoprecipitates with MyoID and is required for MyoID L/R activity. We further demonstrate that MyoIC, a closely related unconventional type I myosin, can antagonize MyoID L/R activity by preventing its binding to adherens junction components, both in vitro and in vivo. Interestingly, DE-Cadherin inhibits MyoIC, providing a protective mechanism to MyoID function. Conditional genetic experiments indicate that DE-Cadherin, MyoIC and MyoID show temporal synchronicity for their function in L/R asymmetry. These data suggest that following MyoID recruitment by β-Catenin at the adherens junction, DE-Cadherin has a twofold effect on Drosophila L/R asymmetry by promoting MyoID activity and repressing that of MyoIC. Interestingly, the product of the vertebrate situs inversus gene inversin also physically interacts with β-Catenin, suggesting that the adherens junction might serve as a conserved platform for determinants to establish L/R asymmetry both in vertebrates and invertebrates.

The efficacy of postoperative incentive spirometry is influenced by the device-specific imposed work of breathing.

PubMed

Weindler, J; Kiefer, R T

2001-06-01

The study evaluated the impact of the additional imposed work of breathing (WBimp) generated by two different spirometers on postoperative incentive spirometry performance in patients at high risk and moderate risk for postoperative pulmonary complications (PPCs). Additionally, we investigated whether maximal inspiratory pressure (PImax) is an easy estimate of the WBimp imposed by incentive spirometers. Prospective, randomized, single-blind clinical trial. ICU of a university hospital. Thirty male patients were assigned to a group at high risk for PPCs (group A; inspiratory capacity [IC], < 1.6 L) or to a group at moderate risk for PPCs (group B; IC, 1.6 to 2.5 L) after upper-abdominal, thoracic, or two-cavity surgery. On the first or second postoperative day WBimp, IC, and PImax were recorded without spirometers (baseline) and during incentive spirometry with the Mediflo spirometer (Medimex; Hamburg, Germany) (high WBimp) and the Coach spirometer (Kendall; Neustadt, Germany) (low WBimp) using a pneumotachograph. In group A, the baseline and the ICs for both spirometers only differed slightly. In group B, the IC was significantly reduced for the Mediflo (p < 0.05), which imposed a WBimp twice as high as the Coach (p < 0.01). PImax was significantly increased for both the Mediflo and the Coach (p < 0.01). PImax was positively correlated with WBimp (r = 0.8). Incentive spirometers differ considerably in their additional Wbimp with a potential impact on the efficacy of postoperative incentive spirometry performance. PImax might be an easy clinical estimate for the WBimp during incentive spirometry. Incentive spirometers with low WBimp permit increased maximal sustained inspiration and, thus, enhanced incentive spirometry performance, and, therefore, it might be more suitable for use in postoperative respiratory care.

Correlation between retinal sensitivity and cystoid space characteristics in diabetic macular edema.

PubMed

Velaga, Swetha B; Nittala, Muneeswar G; Parinitha, B; Sadda, S R; Chhablani, Jay Kumar

2016-06-01

To evaluate the correlation between retinal sensitivity and cystoid space characteristics in eyes with diabetic macular edema (DME). Prospective cross-sectional study of 22 subjects with DME (32 treatment-naïve eyes). All study subjects underwent complete ophthalmic examination, including slit-lamp biomicroscopy and dilated fundus examination. All subjects underwent spectral domain optical coherence tomography (SD-OCT) and microperimetry (MP). Intraretinal cystoid space (ICS) volume was generated after manual delineation of cystoid space boundaries using the three-dimensional-OCT software. Various SD-OCT parameters, including retinal thickness, retinal volume, cystoid space volume, cystoid space intensity, and outer retinal structure integrity, were correlated with MP parameters and best-corrected visual acuity (BCVA). Subject's mean age was 57 ± 9 years. The mean logarithm of minimum angle of resolution BCVA was 0.4 ± 0.2. The intraclass correlation coefficient for inter- and intra-grader assessment of cystoid space volume by manual delineation was 0.99 and 0.99, respectively. Mean total ICS volume was 0.4 ± 0.4 mm 3 and for the foveal center, subfield was 0.1 ± 0.1 mm 3 . Mean retinal sensitivity was 12.89 ± 10 dB; however, foveal retinal sensitivity was 12.3 ± 11.1 dB. We found no significant correlation between BCVA and total cystoid space volume (r = 0.33, P = 0.06). Correlation between total retinal sensitivity and total ICS was negative and nonsignificant (r = -0.17, P = 0.36). Correlation between foveal retinal sensitivity and foveal cystoid space intensity was moderate and marginally significant (r = -0.43, P = 0.05). Total cystoid space volume was not significantly correlated with BCVA or total retinal sensitivity in subjects with DME. Foveal cystoid space optical intensity was negatively correlated with foveal retinal sensitivity. These findings suggest further investigation of cystoid space characteristics in the setting of DME may be of value.

Numerical Analysis of Turbulent Separated Subsonic Diffuser Flows

DTIC Science & Technology

1977-02-01

the s u b l a y e r r eg ion when one a t t e m p t s to use a un i fo rm coord ina te s y s t e m to d e s c r i b e the p r o - f i l es ...s u m e d p ro f i l e in the v ic in i ty of s e p a r a t i o n is ques t ionable . C l e a r l y , an adequate solut ion r e q u i r e s...in an 8-dell conical diffuser. 7.15 m O ,o H l 01 O1 (O AEDC-TR-76-159 1 .0 u~ O k O 4~ eS r-4 a ~4 el 0 . 8 0 . 6 0 . 4

All Prime Contract Awards by State or Country, Place, and Contractor, FY 88. Part 15. (Ada, Oklahoma-Youngwood, Pennsylvania)

DTIC Science & Technology

1988-01-01

1 aI 3 h C 4dl e eN e el c Ne( 0 ZZ mm CI (00 z I10000 I 04" IC N N NN 0 " NNNNN r- NN NN . -4 C04N C, -4-4 CN4 C- "N -4 U001- I "N NNNNNe4 .. . N...0 I 00coo00000 -(4 0 00 00 0 1 en 0 Il 000000 m r- r. - w00 00 0000 00 00 0000 01- -I󈧄 -. 00 0000 0000 cc I.oo 0 I 000000 80 00 00 o0 o0 00 0 z0 00...4co -C W 41 000 I’- -4C( P NNr 00 en ) N N UI) CL 1 030 r- I C)tc’n" (0 mm0’ WW C CN (D -4 4t IA r- 4 N bsJI )0r- 1 1 -4 NC’) -4 -4 N -4 I 𔃺)01 I I

Introduction to Some Fundamental Concepts of General Relativity and to Their Required Use in Some Modern Timekeeping Systems

DTIC Science & Technology

1981-12-01

t e d Riemann Curvature Wnsor and R i s the Curva ture ~ c 2 l ) a r . I n 1917, Karl Schwarzschi ld s o l v e d t h e s e e q u a t i o n...tu re of time a l o n e . I t is t h e Schwarzschild met r ic t h a t leads t o the famous concept n f t h e black h o l e . This is a...01 Well, it can: 2 m - I - - - - - 0 r c 2 Figure 2 4 One calls t h i s va lue of r t h e Schwarzschild b d l u s and o f t e n

Facteurs de risque de faible poids de naissance en milieu semi-rural de Kamina, République Démocratique du Congo

PubMed Central

Kangulu, Ignace Bwana; Umba, Elie Kilolo Ngoy; Nzaji, Michel Kabamba; Kayamba, Prosper Kalenga Mwenze

2014-01-01

Introduction Le faible poids de naissance constitue un problème majeur de santé publique, aussi bien dans les pays développés que dans les pays en développement, de par son ampleur et sa forte association avec la morbidité et la mortalité infantiles. Méthodes Il s’agit d’une étude cas-témoins rétrospective menée sur les différents facteurs de risque de faible poids de naissance(FPN) en milieu semi-rural de Kamina chez les accouchées et leurs nouveau-nés respectifs enregistrés de la période allant de janvier 2009 à décembre 2010. Résultats Cette étude a répertorié 69 cas des nouveau-nés de FPN sur 483 accouchements enregistrés (14,3%). Les facteurs associés au FPN déterminés dans ce travail sont l’âge maternel inférieur à 18 ans (OR=7,62, IC=3.46-16.8) et supérieur à 35 ans (OR=2,04;IC=0.91-4.46), la primiparité(OR=2,48;IC=1.18-5.21) et le non suivi des consultations prénatales (OR=5,50;IC=2.00-15.03), la prématurité avec grossesse âgée de moins de 37 semaines d’aménorrhée, la grossesse multiple (OR=30,94) et le sexe féminin du nouveau-né. Conclusion Cette étude a démontré que l’âge maternel inférieur à 18 ans et supérieur à 35 ans, le non suivi des consultations prénatales, la primiparité et la prématurité, la grossesse multiple et le sexe féminin du nouveau-né sont les facteurs associés au faible poids de naissance. PMID:25237417

Chinese-English Automation and Computer Technology Dictionary, Volume 2.

DTIC Science & Technology

1980-08-01

The purpose of the series is to provide rapid reference tools for translators, abstractors, and research analysts concerned with scientific and...tansuo search; searching; 25 exploration; explore: research ; hunting; trace; seek tansuo dianxian tracer wire 26 884 tansuxd . ., heuristic 01 tansuofa...xunwen -v Ij ;I system interrogation 22 xitong yanjiu A f IC system research 23 xitong yinqyong chengxiud -A, i M 1 R N- #1 , system utility program 24

Protein adsorption to poly(ethylenimine)-modified Sepharose FF: I. a critical ionic capacity for drastically enhanced capacity and uptake kinetics.

PubMed

Yu, Lin-Ling; Tao, Shi-Peng; Dong, Xiao-Yan; Sun, Yan

2013-08-30

To explore the details of protein uptake to polymer-grafted ion exchangers, Sepharose FF was modified with poly(ethylenimine) (PEI) to prepare anion exchanger of 10 different ionic capacities (ICs, 100-1220mmol/L). Adsorption equilibria and kinetics of bovine serum albumin (BSA) were then studied. It is found that ionic capacity, i.e., the coupling density of PEI, had significant effect on both adsorption capacity (qm) and effective protein diffusivity (De). With increasing ionic capacity, the qm value increased rapidly at IC<260mmol/L and then increased slowly till reaching a plateau at IC=600mmol/L. In the IC range of 100-600mmol/L, however, the De values kept at a low level (De/D0<0.07); it first decreased from 0.05±0.01 at IC=100mmol/L to 0.01±0.01 at IC=260mmol/L and then increased to 0.06±0.01 at IC=600mmol/L. Thereafter, sharp increases of the qm and De values [36% (from 201 to 273mg/mL) and 670% (from 0.06±0.01 to 0.49±0.04), respectively] were observed in the narrow range of IC from 600 to 740mmol/L. Finally, at IC>740mmol/L, the qm value decreased significantly while the De value increased moderately with increasing the IC. The results indicate that PEI chains played an important role in protein adsorption and transport. In brief, there was a critical IC (cIC) or PEI chain density, above which protein adsorption and transport behaviors changed drastically. The cIC was identified to be about 600mmol/L. Estimation of PEI grafting-layer thickness suggests that PEI chains formed an extended three-dimensional grafting-layer at IC>cIC, which provided high flexibility as well as accessibility of the chains for protein binding. Therefore, at IC>cIC, the adjacent PEI chains became close and flexible enough, leading to facilitated transport of adsorbed protein molecules by the interactions of neighboring chains mediated by the bound molecules. It is regarded as "chain delivery" effect. At the same time, improved accessibility of binding sites led the significant increase of binding capacity. The decrease of qm value at IC>740mmol/L is considered due to the decrease of effective porosity. The research has thus provided new insight into protein adsorption and transport in polymer-grafted ion-exchange media. Copyright © 2013 Elsevier B.V. All rights reserved.

Epigenetic Basis for the Regulation of Estrogen Receptor Alpha Activity in Breast Cancer Cells

DTIC Science & Technology

2009-04-01

B) GPER and TESK2 expression after CARM1 silencing in MCF7 was determined by reverse transcription-qPCR and revealed the requirement for CARM1 in...the E2-induced repression of GPER and TESK2. siLUC was used as a control. *, P 0.05; **, P 0.01; ***, P 0.001. (C) Enrichment of Ec3 cluster...sites (blue blocks) near GPER and TESK2 E2-downregulated target genes (red blocks). 3416 LUPIEN ET AL. MOL. CELL. BIOL. at A C Q S E R V IC E /S E R IA

R&D100: IC ID

ScienceCinema

Hamlet, Jason; Pierson, Lyndon; Bauer, Todd

2018-06-25

Supply chain security to detect, deter, and prevent the counterfeiting of networked and stand-alone integrated circuits (ICs) is critical to cyber security. Sandia National Laboratory researchers have developed IC ID to leverage Physically Unclonable Functions (PUFs) and strong cryptographic authentication to create a unique fingerprint for each integrated circuit. IC ID assures the authenticity of ICs to prevent tampering or malicious substitution.

MicroRNA miR-30 family regulates non-attachment growth of breast cancer cells

PubMed Central

2013-01-01

Background A subset of breast cancer cells displays increased ability to self-renew and reproduce breast cancer heterogeneity. The characterization of these so-called putative breast tumor-initiating cells (BT-ICs) may open the road for novel therapeutic strategies. As microRNAs (miRNAs) control developmental programs in stem cells, BT-ICs may also rely on specific miRNA profiles for their sustained activity. To explore the notion that miRNAs may have a role in sustaining BT-ICs, we performed a comprehensive profiling of miRNA expression in a model of putative BT-ICs enriched by non-attachment growth conditions. Results We found breast cancer cells grown under non-attachment conditions display a unique pattern of miRNA expression, highlighted by a marked low expression of miR-30 family members relative to parental cells. We further show that miR-30a regulates non-attachment growth. A target screening revealed that miR-30 family redundantly modulates the expression of apoptosis and proliferation-related genes. At least one of these targets, the anti-apoptotic protein AVEN, was able to partially revert the effect of miR-30a overexpression. Finally, overexpression of miR-30a in vivo was associated with reduced breast tumor progression. Conclusions miR30-family regulates the growth of breast cancer cells in non-attachment conditions. This is the first analysis of target prediction in a whole family of microRNAs potentially involved in survival of putative BT-ICs. PMID:23445407

Inhibition of the recombinant cattle tick Rhipicephalus (Boophilus) annulatus glutathione S-transferase.

PubMed

Guneidy, Rasha A; Shahein, Yasser E; Abouelella, Amira M K; Zaki, Eman R; Hamed, Ragaa R

2014-09-01

Rhipicephalus (Boophilus) annulatus is a bloodsucking ectoparasite that causes severe production losses in the cattle industry. This study aims to evaluate the in vitro effects of tannic acid, hematin (GST inhibitors) and different plant extracts (rich in tannic acid) on the activity of the recombinant glutathione S-transferase enzyme of the Egyptian cattle tick R. annulatus (rRaGST), in order to confirm their ability to inhibit the parasitic essential detoxification enzyme glutathione S-transferase. Extraction with 70% ethanol of Hibiscus cannabinus (kenaf flowers), Punica granatum (red and white pomegranate peel), Musa acuminata (banana peel) (Musaceae), Medicago sativa (alfalfa seeds), Tamarindus indicus (seed) and Cuminum cyminum (cumin seed) were used to assess: (i) inhibitory capacities of rRaGST and (ii) their phenolic and flavonoid contents. Ethanol extraction of red pomegranate peel contained the highest content of phenolic compounds (29.95mg gallic acid/g dry tissue) compared to the other studied plant extracts. The highest inhibition activities of rRaGST were obtained with kenaf and red pomegranate peel (P. granatum) extracts with IC50 values of 0.123 and 0.136mg dry tissue/ml, respectively. Tannic acid was the more effective inhibitor of rRaGST with an IC50 value equal to 4.57μM compared to delphinidine-HCl (IC50=14.9±3.1μM). Gossypol had a weak inhibitory effect (IC50=43.7μM), and caffeic acid had almost no effect on tick GST activity. The IC50 values qualify ethacrynic acid as a potent inhibitor of rRaGST activity (IC50=0.034μM). Cibacron blue and hematin showed a considerable inhibition effect on rRaGST activity, and their IC50 values were 0.13μM and 7.5μM, respectively. The activity of rRaGST was highest for CDNB (30.2μmol/min/mg protein). The enzyme had also a peroxidatic activity (the specific activity equals 26.5μmol/min/mg protein). Both tannic acid and hematin inhibited rRaGST activity non-competitively with respect to GSH and competitively with respect to CDNB. While red pomegranate extracts inhibited rRaGST activity competitively with respect to GSH, uncompetitive inhibition was observed with respect to CDNB. Copyright © 2014 Elsevier GmbH. All rights reserved.

The Carnegie Hubble Program: The Infrared Leavitt Law in IC 1613

NASA Technical Reports Server (NTRS)

Scowcroft, Victoria; Freedman, Wendy L.; Madore, Barry F.; Monson, Andrew J.; Persson, S. E.; Seibert, Mark; Rigby, Jane R.; Melbourne, Jason

2013-01-01

We have observed the dwarf galaxy IC 1613 at multiple epochs in the midinfrared using Spitzer and the in the near-infrared using the new FourStar near-IR camera on Magellan. We have constructed Cepheid period luminosity relations in the J, H, Ks, [3.6] and [4.5] bands and have used the run of their apparent distance moduli as a function of wavelength to derive the line of sight reddening and distance to IC 1613. Using a nineband fit, we find E(BV ) = 0.050.01 mag and an extinction corrected distance modulus of 0 = 24.29 0.03statistical 0.03systematic mag. By comparing our multiband and [3.6] distance moduli to results from the tip of the red giant branch and red clump distance indicators, we find that metallicity has no measurable effect on Cepheid distances at 3.6 m in the metallicity range 1.0 [Fe/H] 0.2, hence derivations of the Hubble constant at this wavelength require no correction for metallicity.

Sensitive and specific detection of classical scrapie prions in the brains of goats by real-time quaking-induced conversion.

PubMed

Dassanayake, Rohana P; Orrú, Christina D; Hughson, Andrew G; Caughey, Byron; Graça, Telmo; Zhuang, Dongyue; Madsen-Bouterse, Sally A; Knowles, Donald P; Schneider, David A

2016-03-01

Real-time quaking-induced conversion (RT-QuIC) is a rapid, specific and highly sensitive prion seeding activity detection assay that uses recombinant prion protein (rPrPSen) to detect subinfectious levels of the abnormal isoforms of the prion protein (PrPSc). Although RT-QuIC has been successfully used to detect PrPSc in various tissues from humans and animals, including sheep, tissues from goats infected with classical scrapie have not yet been tested. Therefore, the aims of the present study were to (1) evaluate whether prion seeding activity could be detected in the brain tissues of goats with scrapie using RT-QuIC, (2) optimize reaction conditions to improve scrapie detection in goats, and (3) compare the performance of RT-QuIC for the detection of PrPSc with the more commonly used ELISA and Western blot assays. We further optimized RT-QuIC conditions for sensitive and specific detection of goat scrapie seeding activity in brain tissue from clinical animals. When used with 200  mM sodium chloride, both full-length sheep rPrPSen substrates (PrP genotypes A136R154Q171 and V136R154Q171) provided good discrimination between scrapie-infected and normal goat brain samples at 10(- )3 dilution within 15  h. Our findings indicate that RT-QuIC was at least 10,000-fold more sensitive than ELISA and Western blot assays for the detection of scrapie seeding activity in goat brain samples. In addition to PRNP WT samples, positive RT-QuIC reactions were also observed with three PRNP polymorphic goat brain samples (G/S127, I/M142 and H/R143) tested. Taken together, these findings demonstrate that RT-QuIC sensitively detects prion seeding activity in classical scrapie-infected goat brain samples.

Sensitive and specific detection of classical scrapie prions in the brains of goats by real-time quaking-induced conversion

PubMed Central

Dassanayake, Rohana P.; Orrú, Christina D.; Hughson, Andrew G.; Caughey, Byron; Graça, Telmo; Zhuang, Dongyue; Madsen-Bouterse, Sally A.; Knowles, Donald P.; Schneider, David A.

2016-01-01

Real-time quaking-induced conversion (RT-QuIC) is a rapid, specific and highly sensitive prion seeding activity detection assay that uses recombinant prion protein (rPrPSen) to detect subinfectious levels of the abnormal isoforms of the prion protein (PrPSc). Although RT-QuIC has been successfully used to detect PrPSc in various tissues from humans and animals, including sheep, tissues from goats infected with classical scrapie have not yet been tested. Therefore, the aims of the present study were to (1) evaluate whether prion seeding activity could be detected in the brain tissues of goats with scrapie using RT-QuIC, (2) optimize reaction conditions to improve scrapie detection in goats, and (3) compare the performance of RT-QuIC for the detection of PrPSc with the more commonly used ELISA and Western blot assays. We further optimized RT-QuIC conditions for sensitive and specific detection of goat scrapie seeding activity in brain tissue from clinical animals. When used with 200 mM sodium chloride, both full-length sheep rPrPSen substrates (PrP genotypes A136R154Q171 and V136R154Q171) provided good discrimination between scrapie-infected and normal goat brain samples at 10− 3 dilution within 15 h. Our findings indicate that RT-QuIC was at least 10 000-fold more sensitive than ELISA and Western blot assays for the detection of scrapie seeding activity in goat brain samples. In addition to PRNP WT samples, positive RT-QuIC reactions were also observed with three PRNP polymorphic goat brain samples (G/S127, I/M142 and H/R143) tested. Taken together, these findings demonstrate that RT-QuIC sensitively detects prion seeding activity in classical scrapie-infected goat brain samples. PMID:26653410

30 CFR 57.22203 - Main fan operation (I-C mines).

Code of Federal Regulations, 2010 CFR

2010-07-01

... 30 Mineral Resources 1 2010-07-01 2010-07-01 false Main fan operation (I-C mines). 57.22203... Standards for Methane in Metal and Nonmetal Mines Ventilation § 57.22203 Main fan operation (I-C mines). Main fans shall be operated continuously while ore production is in progress. ...

On the thermodynamics of waste heat recovery from internal combustion engine exhaust gas

NASA Astrophysics Data System (ADS)

Meisner, G. P.

2013-03-01

The ideal internal combustion (IC) engine (Otto Cycle) efficiency ηIC = 1-(1/r)(γ - 1) is only a function of engine compression ratio r =Vmax/Vmin and exhaust gas specific heat ratio γ = cP/cV. Typically r = 8, γ = 1.4, and ηIC = 56%. Unlike the Carnot Cycle where ηCarnot = 1-(TC/TH) for a heat engine operating between hot and cold heat reservoirs at TH and TC, respectively, ηIC is not a function of the exhaust gas temperature. Instead, the exhaust gas temperature depends only on the intake gas temperature (ambient), r, γ, cV, and the combustion energy. The ejected exhaust gas heat is thermally decoupled from the IC engine and conveyed via the exhaust system (manifold, pipe, muffler, etc.) to ambient, and the exhaust system is simply a heat engine that does no useful work. The maximum fraction of fuel energy that can be extracted from the exhaust gas stream as useful work is (1-ηIC) × ηCarnot = 32% for TH = 850 K (exhaust) and TC = 370 K (coolant). This waste heat can be recovered using a heat engine such as a thermoelectric generator (TEG) with ηTEG> 0 in the exhaust system. A combined IC engine and TEG system can generate net useful work from the exhaust gas waste heat with efficiency ηWH = (1-ηIC) × ηCarnot ×ηTEG , and this will increase the overall fuel efficiency of the total system. Recent improvements in TEGs yield ηTEG values approaching 15% giving a potential total waste heat conversion efficiency of ηWH = 4.6%, which translates into a fuel economy improvement approaching 5%. This work is supported by the US DOE under DE-EE0005432.

Characterization of Gasolines, Diesel Fuels and Their Water Soluble Fractions

DTIC Science & Technology

1983-09-01

R.D. Sothern. 1978. Hydrocarbon Composition of Los Angeles Gasolines. California State Air Resources Board, El Monte, California. Myers, M.E., Jr., J...3 7.o .i --.-.-- -- _ .. - -%IcT’J.Pm.. . _________ - - -’I’ 7;o 01 ____________________ o - - - o 1 ..m y .i .---- * I __ S a’ t...Then the approximation, ((C-C )/X) = ( C/ X) y ,z can be substituted for the concentration gradient with C = concentration in solution C = concentration

Reliability and validity of a new scale on internal coherence (ICS) of cancer patients

PubMed Central

Kröz, Matthias; Büssing, Arndt; von Laue, Hans Broder; Reif, Marcus; Feder, Gene; Schad, Friedemann; Girke, Matthias; Matthes, Harald

2009-01-01

Background Current inventories on quality of life used in oncology mainly focus on functional aspects of patients in the context of disease adaption and treatments (side) effects (EORTC QLQ C30) or generically the status of common functions (Medical Outcome Study SF 36). Beyond circumscribed dimensions of quality of life (i.e., physical, emotional, social, cognitive etc.), there is a lack of inventories which also address other relevant dimensions such as the 'sense of coherence' (SOC) in cancer patients. SOC is important because of its potential prognostic relevance in cancer patients, but the current SOC scale has mainly been validated for psychiatric and psychosomatic patients. Our two-step validation study addresses the internal coherence (ICS) scale, which is based on expert rating, using specific items for oncological patients, with respect to its reliability, validity and sensitivity to chemotherapy. Methods The items were tested on 114 participants (57 cancer patients and a matched control group), alongside questions on autonomic regulation (aR), the Hospital Anxiety and Depression Scale (HADS), self-regulation (SRQ) and Karnofsky the Performance-Index (KPI). A retest of 65 participants was carried out after a median time span of four weeks. In the second part of the study, the ICS was used to assess internal coherence during chemotherapy in 25 patients with colorectal carcinoma (CRC) and 17 breast cancer patients. ICS was recorded before, during and 4 – 8 weeks after treatment. Results The 10-item scale of 'internal coherence' (ICS) shows good to very good reliability: Cronbach-α r = 0.91, retest-reliability r = 0.80. The ICS correlates with r = 0.43 – 0.72 to the convergence criteria (all p < 0.001). We are able to show decreased ICS-values after the third cycle for CRC and breast cancer patients, with a subsequent increase of ICS scores after the end of chemotherapy. Conclusion The ICS has good to very good reliability, validity and sensitivity to chemotherapy. PMID:19552807

Sex Differences in Gamma Band Functional Connectivity Between the Frontal Lobe and Cortical Areas During an Auditory Oddball Task, as Revealed by Imaginary Coherence Assessment.

PubMed

Fujimoto, Toshiro; Okumura, Eiichi; Kodabashi, Atsushi; Takeuchi, Kouzou; Otsubo, Toshiaki; Nakamura, Katsumi; Yatsushiro, Kazutaka; Sekine, Masaki; Kamiya, Shinichiro; Shimooki, Susumu; Tamura, Toshiyo

2016-01-01

We studied sex-related differences in gamma oscillation during an auditory oddball task, using magnetoencephalography and electroencephalography assessment of imaginary coherence (IC). We obtained a statistical source map of event-related desynchronization (ERD) / event-related synchronization (ERS), and compared females and males regarding ERD / ERS. Based on the results, we chose respectively seed regions for IC determinations in low (30-50 Hz), mid (50-100 Hz) and high gamma (100-150 Hz) bands. In males, ERD was increased in the left posterior cingulate cortex (CGp) at 500 ms in the low gamma band, and in the right caudal anterior cingulate cortex (cACC) at 125 ms in the mid-gamma band. ERS was increased in the left rostral anterior cingulate cortex (rACC) at 375 ms in the high gamma band. We chose the CGp, cACC and rACC as seeds, and examined IC between the seed and certain target regions using the IC map. IC changes depended on the height of the gamma frequency and the time window in the gamma band. Although IC in the mid and high gamma bands did not show sex-specific differences, IC at 30-50 Hz in males was increased between the left rACC and the frontal, orbitofrontal, inferior temporal and fusiform target regions. Increased IC in males suggested that males may acomplish the task constructively, analysingly, emotionally, and by perfoming analysis, and that information processing was more complicated in the cortico-cortical circuit. On the other hand, females showed few differences in IC. Females planned the task with general attention and economical well-balanced processing, which was explained by the higher overall functional cortical connectivity. CGp, cACC and rACC were involved in sex differences in information processing and were likely related to differences in neuroanatomy, hormones and neurotransmitter systems.

30 CFR 57.22102 - Smoking (I-C mines).

Code of Federal Regulations, 2013 CFR

2013-07-01

... 30 Mineral Resources 1 2013-07-01 2013-07-01 false Smoking (I-C mines). 57.22102 Section 57.22102... Methane in Metal and Nonmetal Mines Fire Prevention and Control § 57.22102 Smoking (I-C mines). (a) Persons shall not smoke or carry smoking materials, matches, or lighters underground or within 50 feet of...

30 CFR 57.22102 - Smoking (I-C mines).

Code of Federal Regulations, 2014 CFR

2014-07-01

... 30 Mineral Resources 1 2014-07-01 2014-07-01 false Smoking (I-C mines). 57.22102 Section 57.22102... Methane in Metal and Nonmetal Mines Fire Prevention and Control § 57.22102 Smoking (I-C mines). (a) Persons shall not smoke or carry smoking materials, matches, or lighters underground or within 50 feet of...

30 CFR 57.22102 - Smoking (I-C mines).

Code of Federal Regulations, 2012 CFR

2012-07-01

... 30 Mineral Resources 1 2012-07-01 2012-07-01 false Smoking (I-C mines). 57.22102 Section 57.22102... Methane in Metal and Nonmetal Mines Fire Prevention and Control § 57.22102 Smoking (I-C mines). (a) Persons shall not smoke or carry smoking materials, matches, or lighters underground or within 50 feet of...

30 CFR 57.22102 - Smoking (I-C mines).

Code of Federal Regulations, 2011 CFR

2011-07-01

... 30 Mineral Resources 1 2011-07-01 2011-07-01 false Smoking (I-C mines). 57.22102 Section 57.22102... Methane in Metal and Nonmetal Mines Fire Prevention and Control § 57.22102 Smoking (I-C mines). (a) Persons shall not smoke or carry smoking materials, matches, or lighters underground or within 50 feet of...

Patterns of Objective and Subjective Burden of Informal Caregivers in Multiple Sclerosis.

PubMed

Bayen, E; Papeix, C; Pradat-Diehl, P; Lubetzki, C; Joël, M E

2015-01-01

Home care for patients with Multiple Sclerosis (MS) relies largely on informal caregivers (ICs). Methods. We assessed ICs objective burden (Resource Utilization in Dementia measuring informal care time (ICT)) and ICs subjective burden (Zarit Burden Inventory (ZBI)). ICs (N = 99) were spouses (70%), mean age 52 years, assisting disabled patients with a mean EDSS (Expanded Disability Status Scale) of 5.5, with executive dysfunction (mean DEX (Dysexecutive questionnaire) of 25) and a duration of MS ranging from 1 to 44 years. burden was high (mean ICT = 6.5 hours/day), mostly consisting of supervision time. Subjective burden was moderate (mean ZBI = 27.3). Multivariate analyses showed that both burdens were positively correlated with higher levels of EDSS and DEX, whereas coresidency and IC's female gender correlated with objective burden only and IC's poor mental health status with subjective burden only. When considering MS aggressiveness, it appeared that both burdens were not correlated with a higher duration of MS but rather increased for patients with severe and early dysexecutive function and for patients classified as fast progressors according to the Multiple Sclerosis Severity Score. Evaluation of MS disability course and IC's personal situation is crucial to understand the burden process and to implement adequate interventions in MS.

Binaries at Birth: Stellar multiplicity in embedded clusters from radial velocity variations in the IN-SYNC survey

NASA Astrophysics Data System (ADS)

Oskar Jaehnig, Karl; Stassun, Keivan; Tan, Jonathan C.; Covey, Kevin R.; Da Rio, Nicola

2016-01-01

We study the nature of stellar multiplicity in young stellar systems using the INfrared Spectroscopy of Young Nebulous Clusters (IN-SYNC) survey, carried out in SDSS III with the APOGEE spectrograph. Multi-epoch observations of thousands of low-mass stars in Orion A, NGC2264, NGC1333 and IC348 have been carried out, yielding H-band spectra with R=22,500 for sources with H<12 mag. Radial velocity sensitivities ~0.3 km/s can be achieved, depending on the spectral type of the star. We search the IN-SYNC radial velocity catalog to identify sources with radial velocity variations indicative of spectroscopically undetected companions, analyze their spectral properties and discuss the implications for the overall multiplicity of stellar populations in young, embedded star clusters.

30 CFR 57.22210 - In-line filters (I-C mines).

Code of Federal Regulations, 2011 CFR

2011-07-01

... 30 Mineral Resources 1 2011-07-01 2011-07-01 false In-line filters (I-C mines). 57.22210 Section... Standards for Methane in Metal and Nonmetal Mines Ventilation § 57.22210 In-line filters (I-C mines). Filters or separators shall be installed on air-lift fan systems to prevent explosive concentrations of...

30 CFR 57.22210 - In-line filters (I-C mines).

Code of Federal Regulations, 2013 CFR

2013-07-01

... 30 Mineral Resources 1 2013-07-01 2013-07-01 false In-line filters (I-C mines). 57.22210 Section... Standards for Methane in Metal and Nonmetal Mines Ventilation § 57.22210 In-line filters (I-C mines). Filters or separators shall be installed on air-lift fan systems to prevent explosive concentrations of...

30 CFR 57.22210 - In-line filters (I-C mines).

Code of Federal Regulations, 2012 CFR

2012-07-01

... 30 Mineral Resources 1 2012-07-01 2012-07-01 false In-line filters (I-C mines). 57.22210 Section... Standards for Methane in Metal and Nonmetal Mines Ventilation § 57.22210 In-line filters (I-C mines). Filters or separators shall be installed on air-lift fan systems to prevent explosive concentrations of...

30 CFR 57.22210 - In-line filters (I-C mines).

Code of Federal Regulations, 2014 CFR

2014-07-01

... 30 Mineral Resources 1 2014-07-01 2014-07-01 false In-line filters (I-C mines). 57.22210 Section... Standards for Methane in Metal and Nonmetal Mines Ventilation § 57.22210 In-line filters (I-C mines). Filters or separators shall be installed on air-lift fan systems to prevent explosive concentrations of...

30 CFR 57.22210 - In-line filters (I-C mines).

Code of Federal Regulations, 2010 CFR

2010-07-01

... 30 Mineral Resources 1 2010-07-01 2010-07-01 false In-line filters (I-C mines). 57.22210 Section... Standards for Methane in Metal and Nonmetal Mines Ventilation § 57.22210 In-line filters (I-C mines). Filters or separators shall be installed on air-lift fan systems to prevent explosive concentrations of...

30 CFR 57.22104 - Open flames (I-C mines).

Code of Federal Regulations, 2011 CFR

2011-07-01

... 30 Mineral Resources 1 2011-07-01 2011-07-01 false Open flames (I-C mines). 57.22104 Section 57... Standards for Methane in Metal and Nonmetal Mines Fire Prevention and Control § 57.22104 Open flames (I-C mines). (a) Open flames, including cutting and welding, shall not be used underground. (b) Welding and...

30 CFR 57.22104 - Open flames (I-C mines).

Code of Federal Regulations, 2012 CFR

2012-07-01

... 30 Mineral Resources 1 2012-07-01 2012-07-01 false Open flames (I-C mines). 57.22104 Section 57... Standards for Methane in Metal and Nonmetal Mines Fire Prevention and Control § 57.22104 Open flames (I-C mines). (a) Open flames, including cutting and welding, shall not be used underground. (b) Welding and...

30 CFR 57.22104 - Open flames (I-C mines).

Code of Federal Regulations, 2014 CFR

2014-07-01

... 30 Mineral Resources 1 2014-07-01 2014-07-01 false Open flames (I-C mines). 57.22104 Section 57... Standards for Methane in Metal and Nonmetal Mines Fire Prevention and Control § 57.22104 Open flames (I-C mines). (a) Open flames, including cutting and welding, shall not be used underground. (b) Welding and...

30 CFR 57.22104 - Open flames (I-C mines).

Code of Federal Regulations, 2013 CFR

2013-07-01

... 30 Mineral Resources 1 2013-07-01 2013-07-01 false Open flames (I-C mines). 57.22104 Section 57... Standards for Methane in Metal and Nonmetal Mines Fire Prevention and Control § 57.22104 Open flames (I-C mines). (a) Open flames, including cutting and welding, shall not be used underground. (b) Welding and...

30 CFR 57.22241 - Advance face boreholes (I-C mines).

Code of Federal Regulations, 2014 CFR

2014-07-01

... 30 Mineral Resources 1 2014-07-01 2014-07-01 false Advance face boreholes (I-C mines). 57.22241... Standards for Methane in Metal and Nonmetal Mines Ventilation § 57.22241 Advance face boreholes (I-C mines). (a) Boreholes shall be drilled at least 25 feet in advance of a face whenever the work place is...

30 CFR 57.22241 - Advance face boreholes (I-C mines).

Code of Federal Regulations, 2012 CFR

2012-07-01

... 30 Mineral Resources 1 2012-07-01 2012-07-01 false Advance face boreholes (I-C mines). 57.22241... Standards for Methane in Metal and Nonmetal Mines Ventilation § 57.22241 Advance face boreholes (I-C mines). (a) Boreholes shall be drilled at least 25 feet in advance of a face whenever the work place is...

30 CFR 57.22241 - Advance face boreholes (I-C mines).

Code of Federal Regulations, 2011 CFR

2011-07-01

... 30 Mineral Resources 1 2011-07-01 2011-07-01 false Advance face boreholes (I-C mines). 57.22241... Standards for Methane in Metal and Nonmetal Mines Ventilation § 57.22241 Advance face boreholes (I-C mines). (a) Boreholes shall be drilled at least 25 feet in advance of a face whenever the work place is...

30 CFR 57.22241 - Advance face boreholes (I-C mines).

Code of Federal Regulations, 2013 CFR

2013-07-01

... 30 Mineral Resources 1 2013-07-01 2013-07-01 false Advance face boreholes (I-C mines). 57.22241... Standards for Methane in Metal and Nonmetal Mines Ventilation § 57.22241 Advance face boreholes (I-C mines). (a) Boreholes shall be drilled at least 25 feet in advance of a face whenever the work place is...

30 CFR 57.22241 - Advance face boreholes (I-C mines).

Code of Federal Regulations, 2010 CFR

2010-07-01

...) Boreholes shall be drilled in such a manner to insure that the advancing face will not accidently break into... 30 Mineral Resources 1 2010-07-01 2010-07-01 false Advance face boreholes (I-C mines). 57.22241... Standards for Methane in Metal and Nonmetal Mines Ventilation § 57.22241 Advance face boreholes (I-C mines...

Multiple Mutations Modulate the Function of Dihydrofolate Reductase in Trimethoprim-Resistant Streptococcus pneumoniae

PubMed Central

Maskell, Jeffrey P.; Sefton, Armine M.; Hall, Lucinda M. C.

2001-01-01

Trimethoprim resistance in Streptococcus pneumoniae can be conferred by a single amino acid substitution (I100-L) in dihydrofolate reductase (DHFR), but resistant clinical isolates usually carry multiple DHFR mutations. DHFR genes from five trimethoprim-resistant isolates from the United Kingdom were compared to susceptible isolates and used to transform a susceptible control strain (CP1015). All trimethoprim-resistant isolates and transformants contained the I100-L mutation. The properties of DHFRs from transformants with different combinations of mutations were compared. In a transformant with only the I100-L mutation (R12/T2) and a D92-A mutation also found in the DHFRs of susceptible isolates, the enzyme was much more resistant to trimethoprim inhibition (50% inhibitory concentration [IC50], 4.2 μM) than was the DHFR from strain CP1015 (IC50, 0.09 μM). However, Km values indicated a lower affinity for the enzyme's natural substrates (Km for dihydrofolate [DHF], 3.1 μM for CP1015 and 27.5 μM for R12/T2) and a twofold decrease in the specificity constant. In transformants with additional mutations in the C-terminal portion of the enzyme, Km values for DHF were reduced (9.2 to 15.2 μM), indicating compensation for the lower affinity generated by I100-L. Additional mutations in the N-terminal portion of the enzyme were associated with up to threefold-increased resistance to trimethoprim (IC50 of up to 13.7 μM). It is postulated that carriage of the mutation M53-I—which, like I100-L, corresponds to a trimethoprim binding site in the Escherichia coli DHFR—is responsible for this increase. This study demonstrates that although the I100-L mutation alone may give rise to trimethoprim resistance, additional mutations serve to enhance resistance and modulate the effects of existing mutations on the affinity of DHFR for its natural substrates. PMID:11257022

An integrated index combined by dynamic hyperinflation and exercise capacity in the prediction of morbidity and mortality in COPD.

PubMed

Ozgür, Eylem Sercan; Nayci, Sibel Atiş; Özge, Cengiz; Taşdelen, Bahar

2012-09-01

Dynamic hyperinflation (DH) and exercise limitation develop in patients with COPD; however, there is lack of knowledge about their long-term clinical consequences. We aimed to assess the impact of DH and exercise capacity in predicting mortality and also morbidity, as evaluated by emergency visits and hospital admissions in COPD patients during a 4-year period. We recruited 73 stable COPD patients. The relationships of different respiratory parameters (FEV(1)%, body mass index, 6 min walk test distance [6MWD], static hyperinflation as measured by the ratio of inspiratory capacity to total lung capacity (IC/TLC) at rest, DH as measured by the change between the post- and pre-exercise values of IC/TLC [ΔIC/TLC], P(aO(2)), and P(aCO(2))) with emergency visits and hospital admissions because of exacerbations and also with respiratory and all-cause mortality were assessed. The median follow-up period was 47 months (IQR 45-48 months, n = 73). During the follow-up there were 8 (11%) deaths. The ΔIC/TLC value was 3.9 ± 4.6%. The Kaplan-Meier survival curve showed that the cumulative survival rate was significantly lower in the patients with ΔIC/TLC > 4 and with 6MWD ≤ 439.56 m, using these values as thresholds. (The rates for sensitivity were 100% and 87.5%, and for specificity were 56.92% and 87.69%, respectively). The Cox proportional hazards model showed that DH (hazard ratio = 1.4, 95% CI = 1.09-1.84, P = .009) and 6MWD (hazard ratio = 0.98, 95% CI = 0.97-0.99, P = .006) were independent predictors of all-cause and respiratory mortality. 6MWD, FEV(1)%, IC/TLC, and ΔIC/TLC were found to be significantly related to emergency visits (r = -0.28, r = -0.41, r = -0.24, and r = 0.38, respectively) and hospital admissions (r = -0.41, r = -0.45, r = -0.36, and r = 0.28, respectively). DH and exercise capacity are reliable and independent predictors for mortality and morbidity in COPD patients. We propose that DH and exercise capacity be considered in the assessment of long-term clinical consequences of COPD patients. Copyright 2012 Daedalus Enterprises

Maximum margin multiple instance clustering with applications to image and text clustering.

PubMed

Zhang, Dan; Wang, Fei; Si, Luo; Li, Tao

2011-05-01

In multiple instance learning problems, patterns are often given as bags and each bag consists of some instances. Most of existing research in the area focuses on multiple instance classification and multiple instance regression, while very limited work has been conducted for multiple instance clustering (MIC). This paper formulates a novel framework, maximum margin multiple instance clustering (M(3)IC), for MIC. However, it is impractical to directly solve the optimization problem of M(3)IC. Therefore, M(3)IC is relaxed in this paper to enable an efficient optimization solution with a combination of the constrained concave-convex procedure and the cutting plane method. Furthermore, this paper presents some important properties of the proposed method and discusses the relationship between the proposed method and some other related ones. An extensive set of empirical results are shown to demonstrate the advantages of the proposed method against existing research for both effectiveness and efficiency.

The helical domain of the EcoR124I motor subunit participates in ATPase activity and dsDNA translocation

PubMed Central

Shamayeva, Katsiaryna; Guzanova, Alena; Řeha, David; Csefalvay, Eva; Carey, Jannette; Weiserova, Marie

2017-01-01

Type I restriction-modification enzymes are multisubunit, multifunctional molecular machines that recognize specific DNA target sequences, and their multisubunit organization underlies their multifunctionality. EcoR124I is the archetype of Type I restriction-modification family IC and is composed of three subunit types: HsdS, HsdM, and HsdR. DNA cleavage and ATP-dependent DNA translocation activities are housed in the distinct domains of the endonuclease/motor subunit HsdR. Because the multiple functions are integrated in this large subunit of 1,038 residues, a large number of interdomain contacts might be expected. The crystal structure of EcoR124I HsdR reveals a surprisingly sparse number of contacts between helicase domain 2 and the C-terminal helical domain that is thought to be involved in assembly with HsdM. Only two potential hydrogen-bonding contacts are found in a very small contact region. In the present work, the relevance of these two potential hydrogen-bonding interactions for the multiple activities of EcoR124I is evaluated by analysing mutant enzymes using in vivo and in vitro experiments. Molecular dynamics simulations are employed to provide structural interpretation of the functional data. The results indicate that the helical C-terminal domain is involved in the DNA translocation, cleavage, and ATPase activities of HsdR, and a role in controlling those activities is suggested. PMID:28133570

An internet-based diabetes management platform improves team care and outcomes in an urban Latino population.

PubMed

Welch, Garry; Zagarins, Sofija E; Santiago-Kelly, Paula; Rodriguez, Zoraida; Bursell, Sven-Erik; Rosal, Milagros C; Gabbay, Robert A

2015-04-01

To compare usual diabetes care (UDC) to a comprehensive diabetes care intervention condition (IC) involving an Internet-based "diabetes dashboard" management tool used by clinicians. We used a parallel-group randomized design. Diabetes nurses, diabetes dietitians, and providers used the diabetes dashboard as a clinical decision support system to deliver a five-visit, 6-month intervention to 199 poorly controlled (HbA1c >7.5% [58 mmol/mol]) Latino type 2 diabetic (T2D) patients (mean age 55 years, 60% female) at urban community health centers. We compared this intervention to an established, in-house UDC program (n = 200) for its impact on blood glucose control and psychosocial outcomes. Recruitment and retention rates were 79.0 and 88.5%, respectively. Compared with UDC, more IC patients reached HbA1c targets of <7% (53 mmol/mol; 15.8 vs. 7.0%, respectively, P < 0.01) and <8% (64 mmol/mol; 45.2 vs. 25.3%, respectively, P < 0.001). In multiple linear regression adjusting for baseline HbA1c, adjusted mean ± SE HbA1c at follow-up was significantly lower in the IC compared with the UDC group (P < 0.001; IC 8.4 ± 0.10%; UDC 9.2 ± 0.10%). The results showed lower diabetes distress at follow-up for IC patients (40.4 ± 2.1) as compared with UDC patients (48.3 ± 2.0) (P < 0.01), and also lower social distress (32.2 ± 1.3 vs. 27.2 ± 1.4, P < 0.01). There was a similar, statistically significant (P < 0.01) improvement for both groups in the proportion of patients moving from depressed status at baseline to nondepressed at follow-up (41.8 vs. 40%; no significance between groups). The diabetes dashboard intervention significantly improved diabetes-related outcomes among Latinos with poorly controlled T2D compared with a similar diabetes team condition without access to the diabetes dashboard. © 2015 by the American Diabetes Association. Readers may use this article as long as the work is properly cited, the use is educational and not for profit, and the work is not altered.

Word Frequency Analysis MOS: 11H. Skill Levels 1 & 2.

DTIC Science & Technology

1981-05-01

I k,4 L t qs 1’ F £U 19 L ’A T 19 5 S r4 19 SQUARE I 1 I i f1 ,41 0 ItLf tD ;- 1 ASSEMBLY ILtl LI’IC 0 iA!,A (.E laID Is EVERY T IC :,.% .IMUtl I nXT...1iwl15ll’G 2 1 ULEUTLR 2 uORtRNfC 2 ’L’ i ,T,.10 2 L 4:.E/14JSH 2p Ls , 01 -.A’LM NT 2 L:’ ZfOET t Te 2~ LI V1 2AL 2 L- E1𔄃TLC2 LA 2 -i’ A JAJ , At 2...11 9 .4’? S ~P ’~II9 1.$ S3 C,: y.T! ON 1; 1 LT 1:1:%L r c " tD S; FI IL 9 1,0q 9 Pq 1 !’. 9 rrInT P. ’"JlLL0 1;1 9; k.I..) J I Ptr1.CS I 9 t,! ’U1E

United States Foreign Policy RE: The Third World - The Economic Dimension.

DTIC Science & Technology

1985-05-06

system is strong and resilient.඙ Although as a banker one might assume these reasons rather parochial he caveats his rationale with the statement that...8217. - (~~~~ ~~ 0.-1 9,,("C CQi C~a ~ lvt. Vlce Piorc ted t nea earcc~ ’es and 12 )’ g u zira rI~ ,E) InJ.a S 0p Y N td e (p ii1 3 APPENDIX 1V JNVFS~hNT r~C~’LPWfIC...Central African Empire NMauritius Zambia Chad Nexico Zimbabwe Chile N.Ongol ia Colombia Norocco Comoro Islands Nozambique Conga Nepal Costa Rica

(3H)-Saxitoxinol Metabolism and Elimination in the Rat

DTIC Science & Technology

1993-01-01

Pnrne cn. 31,a BNo p. 90-)Q,19 T IC PfmnPn t 1Z in I I I Pri imt kntanE L E C T E 3 SEP23 1993I ~E" [3’H-SAXITOXINOL METABOLISM AND ELIMINATION IN... clious , Fort __Detrick. Frederick. MD 21701-501 I. t’.SA. €R ecenred 8 Aprpe 1992: atuepwud 5 January 1993) l H. B. HINES. S. M. NASEEM and R. W...48. 72 and 144 hr post-injection. A 0.1 ml aliquot of each urine sample was assayed for total radioactivity. The remainder was frozen at - 20’ C until

Intelligibility in Context Scale: Normative and Validation Data for English-Speaking Preschoolers.

PubMed

McLeod, Sharynne; Crowe, Kathryn; Shahaeian, Ameneh

2015-07-01

The purpose of this study was to describe normative and validation data on the Intelligibility in Context Scale (ICS; McLeod, Harrison, & McCormack, 2012c) for English-speaking children. The ICS is a 7-item, parent-report measure of children's speech intelligibility with a range of communicative partners. Data were collected from the parents of 803 Australian English-speaking children ranging in age from 4;0 (years;months) to 5;5 (37.0% were multilingual). The mean ICS score was 4.4 (SD = 0.7) out of a possible total score of 5. Children's speech was reported to be most intelligible to their parents, followed by their immediate family, friends, and teachers; children's speech was least intelligible to strangers. The ICS had high internal consistency (α = .94). Significant differences in scores were identified on the basis of sex and age but not on the basis of socioeconomic status or the number of languages spoken. There were significant differences in scores between children whose parents had concerns about their child's speech (M = 3.9) and those who did not (M = 4.6). A sensitivity of .82 and a specificity of .58 were established as the optimal cutoff. Test-retest reliability and criterion validity were established for 184 children with a speech sound disorder. There was a significant low correlation between the ICS mean score and percentage of phonemes correct (r = .30), percentage of consonants correct (r = .24), and percentage of vowels correct (r = .30) on the Diagnostic Evaluation of Articulation and Phonology (Dodd, Hua, Crosbie, Holm, & Ozanne, 2002). Thirty-one parents completed the ICS related to English and another language spoken by their child with a speech sound disorder. The significant correlations between the scores suggest that the ICS may be robust between languages. This article provides normative ICS data for English-speaking children and additional validation of the psychometric properties of the ICS. The robustness of the ICS was suggested because mean ICS scores were not affected by socioeconomic status, number of languages spoken, or whether the ICS was completed in relation to English or another language. The ICS is recommended as a screening measure of children's speech intelligibility.

Plasticity-Related PKMζ Signaling in the Insular Cortex Is Involved in the Modulation of Neuropathic Pain after Nerve Injury

PubMed Central

Han, Jeongsoo; Kwon, Minjee; Cha, Myeounghoon; Tanioka, Motomasa; Hong, Seong-Karp; Bai, Sun Joon; Lee, Bae Hwan

2015-01-01

The insular cortex (IC) is associated with important functions linked with pain and emotions. According to recent reports, neural plasticity in the brain including the IC can be induced by nerve injury and may contribute to chronic pain. Continuous active kinase, protein kinase Mζ (PKMζ), has been known to maintain the long-term potentiation. This study was conducted to determine the role of PKMζ in the IC, which may be involved in the modulation of neuropathic pain. Mechanical allodynia test and immunohistochemistry (IHC) of zif268, an activity-dependent transcription factor required for neuronal plasticity, were performed after nerve injury. After ζ-pseudosubstrate inhibitory peptide (ZIP, a selective inhibitor of PKMζ) injection, mechanical allodynia test and immunoblotting of PKMζ, phospho-PKMζ (p-PKMζ), and GluR1 and GluR2 were observed. IHC demonstrated that zif268 expression significantly increased in the IC after nerve injury. Mechanical allodynia was significantly decreased by ZIP microinjection into the IC. The analgesic effect lasted for 12 hours. Moreover, the levels of GluR1, GluR2, and p-PKMζ were decreased after ZIP microinjection. These results suggest that peripheral nerve injury induces neural plasticity related to PKMζ and that ZIP has potential applications for relieving chronic pain. PMID:26457205

Biological effects of low-dose ionizing radiation exposure on interventional cardiologists.

PubMed

Zakeri, F; Hirobe, T; Akbari Noghabi, K

2010-09-01

Interventional cardiologists (ICs) are likely to receive high radiation exposure as a result of procedures they undertake. To assess the effects of low-dose X-ray radiation exposure on chromosomal damage and on selected indices of cellular and humoral immunity in ICs. The study population consisted of 37 ICs and 37 clinical physicians as the control group with similar age, sex and duration of employment, without any work-related exposure to ionizing radiation. Cytogenetic studies were performed by chromosome aberration analysis and immunological studies by flow cytometry, enzyme-linked immunosorbent assay and immunodiffusion techniques. The frequencies of aberrant cells, chromosome breaks and dicentrics plus centric rings were significantly higher in the exposed group compared to the control group (P < 0.05; P < 0.01; P < 0.001, respectively), without positive correlation between the frequency of dicentric and centric ring aberrations and the cumulative doses of the ICs (r = 0.24, not significant). A significant increase was observed in the expression of activation marker CD69 on TCD4(+) stimulated cells in serum immunoglobulin G and interleukin (IL)-2 (P < 0.05) and a significant decrease in serum IL-10 (P < 0.05) in the ICs compared with that of the control group. There was no statistical difference between the two groups in terms of number of white blood cells and lymphocytes, CD3(+), CD4(+) and CD8(+) T cells, CD19(+) and CD16(+) 56(+) cells and concentrations of interferon (IFN)-gamma, IL-4, IL-6 and IL-8 cytokines. While cytogenetic results show higher chromosomal damage, some immune responses are stimulated or modulated immunologically in ICs.

CXCR4-antagonist Peptide R-liposomes for combined therapy against lung metastasis.

PubMed

Ieranò, Caterina; Portella, Luigi; Lusa, Sara; Salzano, Giuseppina; D'Alterio, Crescenzo; Napolitano, Maria; Buoncervello, Maria; Macchia, Daniele; Spada, Massimo; Barbieri, Antonio; Luciano, Antonio; Barone, Maria Vittoria; Gabriele, Lucia; Caraglia, Michele; Arra, Claudio; De Rosa, Giuseppe; Scala, Stefania

2016-04-14

The chemokine CXCL12 activates CXCR4, initiating multiple pathways that control immune cell trafficking, angiogenesis and embryogenesis; CXCR4 is also overexpressed in multiple tumors affecting metastatic dissemination. While there has been great enthusiasm for exploiting the CXCR4-CXCL12 axis as a target in cancer therapy, to date the promise has yet to be fulfilled. A new class of CXCR4-antagonist cyclic peptides was recently developed and the compound named Peptide R was identified as the most active. With the intent to improve the efficacy and biodistribution of Peptide R, stealth liposomes decorated with Peptide R were developed (PL-Peptide R). In vitro PL-Peptide R efficiently inhibited CXCR4-dependent migration and in vivo it significantly reduced lung metastases and increased overall survival in B16-CXCR4 injected C57BL/6 mice. To evaluate if PL-Peptide R could also be a drug delivery system for CXCR4 expressing tumors, the PL-Peptide R was loaded with doxorubicin (DOX) (PL-Peptide R-DOX). PL-Peptide R-DOX efficiently delivered DOX to CXCR4 expressing cell lines with a consequent decrease in the DOX IC50 efficient dose. In vivo, B16-CXCR4 injected C57BL/6 mice treated with PL-Peptide R-DOX developed fewer lung metastases compared to PL-DOX treated mice. This work provides the proof-of-concept to prevent metastasis by using combined nanomedicine.

30 CFR 57.22233 - Actions at 0.5 percent methane (I-C mines).

Code of Federal Regulations, 2010 CFR

2010-07-01

... 30 Mineral Resources 1 2010-07-01 2010-07-01 false Actions at 0.5 percent methane (I-C mines). 57... MINES Safety Standards for Methane in Metal and Nonmetal Mines Ventilation § 57.22233 Actions at 0.5 percent methane (I-C mines). If methane reaches 0.5 percent in the mine atmosphere, ventilation changes...

30 CFR 57.22233 - Actions at 0.5 percent methane (I-C mines).

Code of Federal Regulations, 2011 CFR

2011-07-01

... 30 Mineral Resources 1 2011-07-01 2011-07-01 false Actions at 0.5 percent methane (I-C mines). 57... MINES Safety Standards for Methane in Metal and Nonmetal Mines Ventilation § 57.22233 Actions at 0.5 percent methane (I-C mines). If methane reaches 0.5 percent in the mine atmosphere, ventilation changes...

Integrating marker-assisted background analysis with foreground selection for pyramiding bacterial blight resistance genes into Basmati rice.

PubMed

Baliyan, Nikita; Malik, Rekha; Rani, Reema; Mehta, Kirti; Vashisth, Urvashi; Dhillon, Santosh; Boora, Khazan Singh

2018-01-01

Bacterial leaf blight (BB), caused by the bacterium Xanthomonas oryzae pv. Oryzae (Xoo), is the major constraint amongst rice diseases in India. CSR-30 is a very popular high-yielding, salt-tolerant Basmati variety widely grown in Haryana, India, but highly susceptible to BB. In the present study, we have successfully introgressed three BB resistance genes (Xa21, xa13 and xa5) from BB-resistant donor variety IRBB-60 into the BB-susceptible Basmati variety CSR-30 through marker-assisted selection (MAS) exercised with stringent phenotypic selection without compromising the Basmati traits. Background analysis using 131 polymorphic SSR markers revealed that recurrent parent genome (RPG) recovery ranged up to 97.1% among 15 BC 3 F 1 three-gene-pyramided genotypes. Based on agronomic evaluation, BB reaction, aroma, percentage recovery of RPG, and grain quality evaluation, four genotypes, viz., IC-R28, IC-R68, IC-R32, and IC-R42, were found promising and advanced to BC 3 F 2 generation. Copyright © 2017 Académie des sciences. Published by Elsevier Masson SAS. All rights reserved.

N2C2M2 Experimentation and Validation: Understanding Its C2 Approaches and Implications

DTIC Science & Technology

2010-06-01

C O N FL IC TE D D EC O N FL IC TE D C O O R D IN A TE D C O LL A B O R A TI...Interactions (Shares and Posts) Log File LE VE L Fa ct oi d Se t Tr ia l TO TA L Va lu e TO TA L Va lu e / Su bj ec t Te nd en cy C TC TL s...80% 90% 100% CO N FL IC TE

Lung Function before and Two Days after Open-Heart Surgery.

PubMed

Urell, Charlotte; Westerdahl, Elisabeth; Hedenström, Hans; Janson, Christer; Emtner, Margareta

2012-01-01

Reduced lung volumes and atelectasis are common after open-heart surgery, and pronounced restrictive lung volume impairment has been found. The aim of this study was to investigate factors influencing lung volumes on the second postoperative day. Open-heart surgery patients (n = 107, 68 yrs, 80% male) performed spirometry both before surgery and on the second postoperative day. The factors influencing postoperative lung volumes and decrease in lung volumes were investigated with univariate and multivariate analyses. Associations between pain (measured by numeric rating scale) and decrease in postoperative lung volumes were calculated with Spearman rank correlation test. Lung volumes decreased by 50% and were less than 40% of the predictive values postoperatively. Patients with BMI >25 had lower postoperative inspiratory capacity (IC) (33 ± 14% pred.) than normal-weight patients (39 ± 15% pred.), (P = 0.04). More pain during mobilisation was associated with higher decreases in postoperative lung volumes (VC: r = 0.33, P = 0.001; FEV(1): r = 0.35, P ≤ 0.0001; IC: r = 0.25, P = 0.01). Patients with high BMI are a risk group for decreased postoperative lung volumes and should therefore receive extra attention during postoperative care. As pain is related to a larger decrease in postoperative lung volumes, optimal pain relief for the patients should be identified.

Lung Function before and Two Days after Open-Heart Surgery

PubMed Central

Urell, Charlotte; Westerdahl, Elisabeth; Hedenström, Hans; Janson, Christer; Emtner, Margareta

2012-01-01

Reduced lung volumes and atelectasis are common after open-heart surgery, and pronounced restrictive lung volume impairment has been found. The aim of this study was to investigate factors influencing lung volumes on the second postoperative day. Open-heart surgery patients (n = 107, 68 yrs, 80% male) performed spirometry both before surgery and on the second postoperative day. The factors influencing postoperative lung volumes and decrease in lung volumes were investigated with univariate and multivariate analyses. Associations between pain (measured by numeric rating scale) and decrease in postoperative lung volumes were calculated with Spearman rank correlation test. Lung volumes decreased by 50% and were less than 40% of the predictive values postoperatively. Patients with BMI >25 had lower postoperative inspiratory capacity (IC) (33 ± 14% pred.) than normal-weight patients (39 ± 15% pred.), (P = 0.04). More pain during mobilisation was associated with higher decreases in postoperative lung volumes (VC: r = 0.33, P = 0.001; FEV1: r = 0.35, P ≤ 0.0001; IC: r = 0.25, P = 0.01). Patients with high BMI are a risk group for decreased postoperative lung volumes and should therefore receive extra attention during postoperative care. As pain is related to a larger decrease in postoperative lung volumes, optimal pain relief for the patients should be identified. PMID:22924127

Evaluation of 7-arylaminopyrazolo[1,5-a]pyrimidines as anti-Plasmodium falciparum, antimalarial, and Pf-dihydroorotate dehydrogenase inhibitors.

PubMed

Azeredo, Luís Felipe S P; Coutinho, Julia P; Jabor, Valquiria A P; Feliciano, Patricia R; Nonato, Maria Cristina; Kaiser, Carlos R; Menezes, Carla Maria S; Hammes, Amanda S O; Caffarena, Ernesto Raul; Hoelz, Lucas V B; de Souza, Nicolli B; Pereira, Glaécia A N; Cerávolo, Isabela P; Krettli, Antoniana U; Boechat, Nubia

2017-01-27

Malaria remains one of the most serious global infectious diseases. An important target for antimalarial chemotherapy is the enzyme dihydroorotate dehydrogenase from Plasmodium falciparum (PfDHODH), which is responsible for the conversion of dihydroorotate to orotate in the de novo pyrimidine biosynthetic pathway. In this study, we have designed and synthesized fifteen 7-arylpyrazolo[1,5-a]pyrimidine derivatives using ring bioisosteric replacement and molecular hybridization of functional groups based on the highly active 5-methyl-N-(naphthalen-2-yl)-2-(trifluoromethyl)- [1,2,4]triazolo[1,5-a]pyrimidin-7-amine. The compounds were tested against Plasmodium falciparum, as antimalarials in mice with P. berghei, and as inhibitors of PfDHODH. Thirteen compounds were found to be active against P. falciparum, with IC 50 values ranging from 1.2 ± 0.3 to 92 ± 26 μM in the anti-HRP2 and hypoxanthine assays. Four compounds showed the highest selective index (SI), which is a ratio between cytotoxicity and activity in vitro. The inhibition of PfDHODH showed that compound 30 (R 2  = CH 3 ; R 5  = CF 3 ; Ar = 7-β-naphthyl) displayed higher and selective inhibitory activity, with IC 50  = 0.16 ± 0.01 μM, followed by 25 (R 2  = CH 3 ; R 5  = CH 3 ; Ar = 7-β-Naphthyl) and 19 (R 2  = CF 3 ; R 5  = CF 3 ; Ar = 7-β-naphthyl), with IC 50  = 4 ± 1 μM and 6 ± 1 μM, respectively. The trifluoromethyl group at the 2- or 5-positions of the pyrazolo[1,5-a]pyrimidine ring led to increased drug activity. The docking results agreed with the values obtained from enzymatic assays. Copyright © 2016 Elsevier Masson SAS. All rights reserved.

Usefulness of inspiratory capacity measurement in COPD patients in the primary care setting

PubMed Central

Madueño, Antonio; Martín, Antonio; Péculo, Juan-Antonio; Antón, Esther; Paravisini, Alejandra; León, Antonio

2009-01-01

Objective: To determine if inspiratory capacity (IC) assessment could be useful for chronic obstructive pulmonary disease (COPD) patient management in the primary care setting. Methods: A descriptive cross-sectional study was conducted in 93 patients diagnosed with COPD according to Spanish Thoracic Society (SEPAR) criteria. Patients were recruited in eight primary care centers in Andalusia, Spain. Anthropometric, sociodemographic, resting lung function (forced expiratory volume in one second [FEV1], forced vital capacity, synchronized vital capacity, IC), and quality of life data based on the Spanish version of Saint George’s Respiratory Questionnaire (SGRQ) were obtained. Results: Lung function results expressed as percentages of the predicted values were as follows: FEV1, 49.04 (standard deviation [SD]: 16.23); IC, 61.73 (SD: 15.42). The SGRQ mean total score was 47.5 (SD 17.98). The Spearman’s Rho correlation between FEV1 and SGRQ was r = −0.36 (95% confidence interval [CI]: −0.529 to −0.166), between IC and SGRQ was r = −0.329 (95% CI −0.502 to −0.131), and between FEV1 and IC was r = −0.561. Conclusions: Measurement of IC at rest could be used as a complementary functional exploration to forced spirometry in the monitorization of patients with COPD in the primary care setting. We found a poor correlation between IC and quality of life at the same level as in FEV1. PMID:20360907

The intelligibility in Context Scale: validity and reliability of a subjective rating measure.

PubMed

McLeod, Sharynne; Harrison, Linda J; McCormack, Jane

2012-04-01

To describe a new measure of functional intelligibility, the Intelligibility in Context Scale (ICS), and evaluate its validity, reliability, and sensitivity using 3 clinical measures of severity of speech sound disorder: (a) percentage of phonemes correct (PPC), (b) percentage of consonants correct (PCC), and (c) percentage of vowels correct (PVC). Speech skills of 120 preschool children (109 with parent-/teacher-identified concern about how they talked and made speech sounds and 11 with no identified concern) were assessed with the Diagnostic Evaluation of Articulation and Phonology (Dodd, Hua, Crosbie, Holm, & Ozanne, 2002). Parents completed the 7-item ICS, which rates the degree to which children's speech is understood by different communication partners (parents, immediate family, extended family, friends, acquaintances, teachers, and strangers) on a 5-point scale. Parents' ratings showed that most children were always (5) or usually (4) understood by parents, immediate family, and teachers, but only sometimes (3) by strangers. Factor analysis confirmed the internal consistency of the ICS items; therefore, ratings were averaged to form an overall intelligibility score. The ICS had high internal reliability (α = .93), sensitivity, and construct validity. Criterion validity was established through significant correlations between the ICS and PPC (r = .54), PCC (r = .54), and PVC (r = .36). The ICS is a promising new measure of functional intelligibility. These data provide initial support for the ICS as an easily administered, valid, and reliable estimate of preschool children's intelligibility when speaking with people of varying levels of familiarity and authority.

Exploring physical and chemical factors influencing the properties of recombinant prion protein and the real-time quaking-induced conversion (RT-QuIC) assay.

PubMed

Cheng, Keding; Sloan, Angela; Avery, Kristen M; Coulthart, Michael; Carpenter, Michael; Knox, J David

2014-01-01

Real-time quaking-induced conversion (RT-QuIC), a highly specific and sensitive assay able to detect low levels of the disease-inducing isoform of the prion protein (PrP(d)) in brain tissue biopsies and cerebral spinal fluid, has great potential to become a method for diagnosing prion disease ante mortem. In order to standardize the assay method for routine analysis, an understanding of how physical and chemical factors affect the stability of the recombinant prion protein (rPrP) substrate and the RT-QuIC assay's sensitivity, specificity, and reproducibility is required. In this study, using sporadic Creutzfeldt-Jakob Disease brain homogenate to seed the reactions and an in vitro-expressed recombinant prion protein, hamster rPrP, as the substrate, the following factors affecting the RT-QuIC assay were examined: salt and substrate concentrations, substrate storage, and pH. Results demonstrated that both the generation of the quality and quantities of rPrP substrate critical to the reaction, as well as the RT-QuIC reaction itself required strict adherence to specific physical and chemical conditions. Once optimized, the RT-QuIC assay was confirmed to be a very specific and sensitive assay method for sCJD detection. Findings in this study indicate that further optimization and standardization of RT-QuIC assay is required before it can be adopted as a routine diagnostic test.

30 CFR 57.22217 - Seals and stoppings (I-A, I-B, and I-C mines).

Code of Federal Regulations, 2011 CFR

2011-07-01

... 30 Mineral Resources 1 2011-07-01 2011-07-01 false Seals and stoppings (I-A, I-B, and I-C mines... NONMETAL MINES Safety Standards for Methane in Metal and Nonmetal Mines Ventilation § 57.22217 Seals and stoppings (I-A, I-B, and I-C mines). All seals, and those stoppings that separate main intake from main...

30 CFR 57.22217 - Seals and stoppings (I-A, I-B, and I-C mines).

Code of Federal Regulations, 2010 CFR

2010-07-01

... 30 Mineral Resources 1 2010-07-01 2010-07-01 false Seals and stoppings (I-A, I-B, and I-C mines... NONMETAL MINES Safety Standards for Methane in Metal and Nonmetal Mines Ventilation § 57.22217 Seals and stoppings (I-A, I-B, and I-C mines). All seals, and those stoppings that separate main intake from main...

30 CFR 57.22228 - Preshift examination (I-A, I-C, II-A, III, and V-A mines).

Code of Federal Regulations, 2010 CFR

2010-07-01

... 30 Mineral Resources 1 2010-07-01 2010-07-01 false Preshift examination (I-A, I-C, II-A, III, and V-A mines). 57.22228 Section 57.22228 Mineral Resources MINE SAFETY AND HEALTH ADMINISTRATION... Preshift examination (I-A, I-C, II-A, III, and V-A mines). (a) Preshift examinations shall be conducted...

30 CFR 57.22212 - Air flow (I-C, II-A, and V-A mines).

Code of Federal Regulations, 2011 CFR

2011-07-01

... 30 Mineral Resources 1 2011-07-01 2011-07-01 false Air flow (I-C, II-A, and V-A mines). 57.22212 Section 57.22212 Mineral Resources MINE SAFETY AND HEALTH ADMINISTRATION, DEPARTMENT OF LABOR METAL AND... Standards for Methane in Metal and Nonmetal Mines Ventilation § 57.22212 Air flow (I-C, II-A, and V-A mines...

30 CFR 57.22228 - Preshift examination (I-A, I-C, II-A, III, and V-A mines).

Code of Federal Regulations, 2011 CFR

2011-07-01

... 30 Mineral Resources 1 2011-07-01 2011-07-01 false Preshift examination (I-A, I-C, II-A, III, and V-A mines). 57.22228 Section 57.22228 Mineral Resources MINE SAFETY AND HEALTH ADMINISTRATION... Preshift examination (I-A, I-C, II-A, III, and V-A mines). (a) Preshift examinations shall be conducted...

Potency and selectivity of carprofen enantiomers for inhibition of bovine cyclooxygenase in whole blood assays.

PubMed

Brentnall, Claire; Cheng, Zhangrui; McKellar, Quintin A; Lees, Peter

2012-12-01

Whole blood in vitro assays were used to determine the potency and selectivity of carprofen enantiomers for inhibition of the isoforms of cyclooxygenase (COX), COX-1 and COX-2, in the calf. S(+)-carprofen possessed preferential activity for COX-2 inhibition but, because the slopes of inhibition curves differed, the COX-1:COX-2 inhibition ratio decreased from 9.04:1 for inhibitory concentration (IC)10 to 1.84:1 for IC95. R(-) carprofen inhibited COX-2 preferentially only for low inhibition of the COX isoforms (IC10 COX-1:COX-2=6.63:1), whereas inhibition was preferential for COX-1 for a high level of inhibition (IC95 COX-1:COX-2=0.20:1). S(+) carprofen was the more potent inhibitor of COX isoforms; potency ratios S(+):R(-) carprofen were 11.6:1 for IC10 and 218:1 for IC90. Based on serum concentrations of carprofen enantiomers obtained after administration of a therapeutic dose of 1.4 mg/kg to calves subcutaneously, S(+)-carprofen concentrations exceeded the in vitro IC80 COX-2 value for 32 h and the IC20 for COX-1 for 33 h. The findings are discussed in relation to efficacy and safety of carprofen in calves. Copyright © 2012 Elsevier Ltd. All rights reserved.

Time course and degree of hyperinflation with metronome-paced tachypnea in COPD patients.

PubMed

Weigt, S Samuel; Abrazado, Marlon; Kleerup, Eric C; Tashkin, Donald P; Cooper, Christopher B

2008-10-01

In COPD patients, tachypnea should increase (dynamic) hyperinflation by shortening expiratory time. We developed a method to evaluate the time course and degree of dynamic hyperinflation during metronome-paced tachypnea. Fourteen patients with stable COPD (FEV(1) 43 +/- 13% predicted) were studied. Inspiratory capacity (IC) was measured breathing through a flow transducer. Subjects paced their respiratory rate (f(R)) at 20/min, 30/min and 40/min for 60-second periods in response to audible tones generated by a computer. IC measurements were obtained at baseline and after 30 and 60 seconds at each f(R). End-tidal carbon dioxide was monitored and f(R) was allowed to return to baseline between periods of tachypnea. Tachypnea produced reductions in IC of 200 +/- 240 ml, 380 +/- 330 ml and 540 +/- 300 ml after 30 seconds at 20/min, 30/min and 40/min, respectively. IC reduction at 60 seconds was similar to 30 seconds for each f(R). In patients with moderate-to-severe COPD, the dynamic hyperinflation induced by metronome-paced tachypnea was shown to occur rapidly and be complete by 30 seconds for a given f(R). Controlled increments in f(R) produced stepwise increases in dynamic hyperinflation. This standardized method could be a useful and easier method of assessing dynamic hyperinflation in COPD patients before and after therapeutic interventions.

Very-high-energy gamma radiation associated with the unshocked wind of the Crab pulsar

NASA Astrophysics Data System (ADS)

Bogovalov, S. V.; Aharonian, F. A.

2000-04-01

We show that the relativistic wind of the Crab pulsar, which is commonly thought to be invisible in the region upstream of the termination shock at r<=rS~0.1pc, in fact could be directly observed through its inverse Compton (IC) γ-ray emission. This radiation is caused by illumination of the wind by low-frequency photons emitted by the pulsar, and consists of two, pulsed and unpulsed, components associated with the non-thermal (pulsed) and thermal (unpulsed) low-energy radiation of the pulsar, respectively. These two components of γ-radiation have distinct spectral characteristics, which depend essentially on the site of formation of the kinetic-energy-dominated wind, as well as on the Lorentz factor and the geometry of propagation of the wind. Thus, the search for such specific radiation components in the spectrum of the Crab Nebula can provide unique information about the unshocked pulsar wind that is not accessible at other wavelengths. In particular, we show that the comparison of the calculated flux of the unpulsed IC emission with the measured γ-ray flux of the Crab Nebula excludes the possibility of formation of a kinetic-energy-dominated wind within 5 light-cylinder radii of the pulsar, Rw>=5RL. The analysis of the pulsed IC emission, calculated under reasonable assumptions concerning the production site and angular distribution of the optical pulsed radiation, yields even tighter restrictions, namely Rw>=30RL.

Magnetic fields in multiple bright-rimmed clouds in different directions of H II region IC 1396

NASA Astrophysics Data System (ADS)

Soam, Archana; Maheswar, G.; Lee, Chang Won; Neha, S.; Kim, Kee-Tae

2018-06-01

Bright-rimmed clouds (BRCs) form on the edges of H II regions affected by high-energy radiation from a central ionizing source. The UV radiation from the ionizing source results in compression and ionization, causing either cloud disruption or further star formation. In this work, we present R-band polarization measurements towards four BRCs, namely IC 1396A, BRC 37, BRC 38 and BRC 39, located in different directions in the H II region, Sh2-131, in order to map the magnetic field (B-field) in the plane of the sky. These BRCs are illuminated by the O star HD 206267 and present a range of projected on-sky geometries. This provides an opportunity to gain an understanding of the magnetized evolution of BRCs. The B-field geometries of the clouds deduced from the polarization data, after correction for foreground contamination by the interstellar medium, are seen to be connected to the ambient B-fields on large scales. They seem to play an important role in shaping the clouds IC 1396A and BRC 37. BRCs 38 and 39 show a broader and snubber head morphology, possibly because the B-fields are aligned with incoming radiation, as revealed in the simulations. A good general agreement is noted on comparing our observational results with the simulations, supporting the importance of B-fields in BRC evolution. This work is the first step towards systematic mapping the B-fields morphology in multiple BRCs in an expanding H II region, extending our previous work.

Seroprevalence and risk factors for Toxoplasma gondii infection on pig farms in central China.

PubMed

Tao, Qing; Wang, Zhengsong; Feng, Huihui; Fang, Rui; Nie, Hao; Hu, Min; Zhou, Yanqin; Zhao, Junlong

2011-04-01

Toxoplasma gondii is a protozoan parasite that causes severe diseases in mammals, including humans, around the world. In China, pork is the main meat source; accordingly, T. gondii in pigs is considered an important source for human toxoplasmosis. Understanding the epidemiology of toxoplasmosis in pig farms is thus important for control of the disease in humans. The purpose of the present study was to investigate the epizootiology of T. gondii infections in pig farms in central China by assessing the seroprevalence and risk factors of this disease. In the present study, 3,558 sera samples were collected from pigs in 37 large-scale pig farms in this region and tested by AG-ELISA. The total seroprevalence was 24.5%, with the greatest prevalence in breeding pigs. The risk factors for toxoplasmosis suggest that high frequency of the contact of pigs with cats (P ≤ 0.01; IC 95%), high density of pig breeding (P ≤ 0.01; IC 95%), the presence of mosquitoes and flies (P ≤ 0.01; IC 95%), semi-patency pens (P ≤ 0.05; IC 95%), and low frequency of scavenging (P ≤ 0.01; IC 95%) were all associated with seroprevalence. In addition, the use of sulfonamides (P ≤ 0.01; IC 95%) significantly decreased seroprevalence. This is the first report of anti- T. gondii antibodies in pigs on large-scale pig farms in central China. The findings will provide useful information for designing control strategies of toxoplasmasis in pig farms.

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

Cseh, David; Corbel, Stephane; Kaaret, Philip

We present new radio, optical, and X-ray observations of three ultraluminous X-ray sources (ULXs) that are associated with large-scale nebulae. We report the discovery of a radio nebula associated with the ULX IC 342 X-1 using the Very Large Array (VLA). Complementary VLA observations of the nebula around Holmberg II X-1, and high-frequency Australia Telescope Compact Array and Very Large Telescope spectroscopic observations of NGC 5408 X-1 are also presented. We study the morphology, ionization processes, and the energetics of the optical/radio nebulae of IC 342 X-1, Holmberg II X-1, and NGC 5408 X-1. The energetics of the optical nebulamore » of IC 342 X-1 is discussed in the framework of standard bubble theory. The total energy content of the optical nebula is 6 Multiplication-Sign 10{sup 52} erg. The minimum energy needed to supply the associated radio nebula is 9.2 Multiplication-Sign 10{sup 50} erg. In addition, we detected an unresolved radio source at the location of IC 342 X-1 at the VLA scales. However, our Very Long Baseline Interferometry (VLBI) observations using the European VLBI Network likely rule out the presence of any compact radio source at milliarcsecond (mas) scales. Using a simultaneous Swift X-ray Telescope measurement, we estimate an upper limit on the mass of the black hole in IC 342 X-1 using the 'fundamental plane' of accreting black holes and obtain M{sub BH} {<=} (1.0 {+-} 0.3) Multiplication-Sign 10{sup 3} M{sub Sun }. Arguing that the nebula of IC 342 X-1 is possibly inflated by a jet, we estimate accretion rates and efficiencies for the jet of IC 342 X-1 and compare with sources like S26, SS433, and IC 10 X-1.« less

30 CFR 57.22235 - Actions at 1.0 percent methane (I-C, II-A, II-B, and IV mines).

Code of Federal Regulations, 2010 CFR

2010-07-01

... 30 Mineral Resources 1 2010-07-01 2010-07-01 false Actions at 1.0 percent methane (I-C, II-A, II-B... AND NONMETAL MINES Safety Standards for Methane in Metal and Nonmetal Mines Ventilation § 57.22235 Actions at 1.0 percent methane (I-C, II-A, II-B, and IV mines). (a) If methane reaches 1.0 percent in the...

30 CFR 57.22235 - Actions at 1.0 percent methane (I-C, II-A, II-B, and IV mines).

Code of Federal Regulations, 2011 CFR

2011-07-01

... 30 Mineral Resources 1 2011-07-01 2011-07-01 false Actions at 1.0 percent methane (I-C, II-A, II-B, and IV mines). 57.22235 Section 57.22235 Mineral Resources MINE SAFETY AND HEALTH ADMINISTRATION... Actions at 1.0 percent methane (I-C, II-A, II-B, and IV mines). (a) If methane reaches 1.0 percent in the...

30 CFR 57.22222 - Ventilation materials (I-A, I-B, I-C, II-A, III, V-A, and V-B mines).

Code of Federal Regulations, 2011 CFR

2011-07-01

... 30 Mineral Resources 1 2011-07-01 2011-07-01 false Ventilation materials (I-A, I-B, I-C, II-A, III, V-A, and V-B mines). 57.22222 Section 57.22222 Mineral Resources MINE SAFETY AND HEALTH....22222 Ventilation materials (I-A, I-B, I-C, II-A, III, V-A, and V-B mines). Brattice cloth and...

30 CFR 57.22222 - Ventilation materials (I-A, I-B, I-C, II-A, III, V-A, and V-B mines).

Code of Federal Regulations, 2010 CFR

2010-07-01

... 30 Mineral Resources 1 2010-07-01 2010-07-01 false Ventilation materials (I-A, I-B, I-C, II-A, III, V-A, and V-B mines). 57.22222 Section 57.22222 Mineral Resources MINE SAFETY AND HEALTH....22222 Ventilation materials (I-A, I-B, I-C, II-A, III, V-A, and V-B mines). Brattice cloth and...

Mindful Self-Care and Secondary Traumatic Stress Mediate a Relationship Between Compassion Satisfaction and Burnout Risk Among Hospice Care Professionals.

PubMed

Hotchkiss, Jason T

2018-01-01

Effective self-care in hospice is anecdotally proclaimed to reduce burnout risk. Yet, the topic has received little empirical attention. This study developed a model for predicting burnout risk from compassion satisfaction (CS), secondary traumatic stress (STS), and mindful self-care. Hospice care professionals (n = 324). Cross-sectional self-report survey. Mindful self-care was correlated with CS ( r = 0.497, p < .01), Burnout ( r = -0.726, p < .01), and STS ( r = -0.276, p < .01). A multiple regression model indicated that the combined effect of CS, STS, and mindful self-care explained 73.7% of the variance in Burnout. Mindful self-care and STS mediated a relationship between CS and Burnout. Each self-care category was statistically significant protective factors against burnout risk ( p < .01). Associations with Burnout in order of strength were self-compassion and purpose (SC; r = -0.673), supportive structure (SS; r = -0.650), mindful self-awareness (MS; r = -0.642), mindful relaxation (MR; r = -0.531), supportive relationships (SR; r = -0.503), and physical care (PC; r = -0.435). However, for STS, only SS ( r = -0.407, p < .01) and MR ( r = -0.285, p < .05) were statistically significant protective factors. Hospice care professional had higher self-care, CS, lower STS, and Burnout compared to published norms. Those who engaged in multiple and frequent self-care strategies experienced higher professional quality of life. Implications for hospice providers and suggestions for future research are discussed.

Partial correlation-based functional connectivity analysis for functional near-infrared spectroscopy signals

NASA Astrophysics Data System (ADS)

Akın, Ata

2017-12-01

A theoretical framework, a partial correlation-based functional connectivity (PC-FC) analysis to functional near-infrared spectroscopy (fNIRS) data, is proposed. This is based on generating a common background signal from a high passed version of fNIRS data averaged over all channels as the regressor in computing the PC between pairs of channels. This approach has been employed to real data collected during a Stroop task. The results show a strong significance in the global efficiency (GE) metric computed by the PC-FC analysis for neutral, congruent, and incongruent stimuli (NS, CS, IcS; GEN=0.10±0.009, GEC=0.11±0.01, GEIC=0.13±0.015, p=0.0073). A positive correlation (r=0.729 and p=0.0259) is observed between the interference of reaction times (incongruent-neutral) and interference of GE values (GEIC-GEN) computed from [HbO] signals.

Prime Contract Awards Over $25,000 by Major System, Contractor and State Part 1 (AAA-NAVY-AVG NAVY)

DTIC Science & Technology

1990-01-01

Q-COC’) -4 M’i (a -4 c"a(aeo - ( D 0 AC 1 -ao f-.r qva 0(%Ioa.4 ()t a. c~cv(vc4 z *Za in -0f (4Jl w -44- m - .41 C,4 Ui 0 C4 IC4 P- -a l~~II I II cLE E...AO-A236 155iiiilulll l I l 1990 ANNUAL Prime Contract Awards Over $25,000 by Major System, Contractor and State Part 1 (AAA-NAVY-AVG NAVY) WHS...Special . 1 -9 __28284 pages I1 ~ . - e21 M(%I% cm -40W -4 I4 m V .. 4 mt WC)a r a- 4-r w~l w zl- qt qt V .4- 01-4 41-4 . 40 o r Lu V) c I OL 9 C U c

Exercise-induced decrease in insular cortex rCBF during postexercise hypotension.

PubMed

Lamb, Kala; Gallagher, Kevin; McColl, Roderick; Mathews, Dana; Querry, Ross; Williamson, Jon W

2007-04-01

The insular cortex (IC), a region of the brain involved in blood pressure (BP) modulation, shows decreases in regional cerebral blood flow (rCBF) during postexercise hypotension (PEH). To determine whether changes in IC neural activity were caused by prior exercise or by changes in BP, this investigation compared patterns of rCBF during periods of hypotension, which was induced by prior exercise (i.e., PEH) and sodium nitroprusside (SNP) infusion and a cold pressor (CP), to restore BP. Ten subjects were studied on three different days with randomly assigned conditions: i) resting baseline; ii) PEH; and iii) SNP-induced hypotension (matched to the PEH BP decrease). Data were collected for heart rate (HR) and mean BP, and rCBF was assessed using single-photon emission computed tomography (SPECT) as an index of brain activation. Using ANOVA across conditions, there were differences (P<0.05; mean +/- SD) from baseline during PEH for HR (+12 +/- 3 bpm) and mean BP (-8 +/- 2 mm Hg) and during SNP-induced hypotension (HR = +15 +/- 4 bpm; MBP = -9 +/- 2 mm Hg), with no differences between PEH and SNP. After exercise, there were decreases (P<0.05) in the leg sensorimotor area, anterior cingulate, and the right and left inferior thalamus, right inferior insula, and left anterior insular regions. During SNP-induced hypotension, there were significant increases in the right and left inferior thalamus and the right and left inferior anterior IC. CP during PEH increased BP and IC activity. Data show that reductions in IC neural activity are not caused by acute BP decreases. Findings suggest that exercise can lead to a temporary decrease in IC neural activity, which may be a significant neural factor contributing to PEH.

Structural analysis of the interaction of IGF I with the IGF types 1 and 2 and insulin receptors

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

Cascieri, M.A.; Chicchi, G.G.; Hayes, N.S.

1987-05-01

A synthetic gene for human IGF I has been synthesized which directs the synthesis and secretion of fully active human IGF I (rIGF I) from yeast. rIGF I inhibits binding of /sup 125/I-IGF I to type 1 IGF receptors from human placenta (IGF-R1, IC50 = 4 nM), binding of /sup 125/I-insulin to insulin receptors (IR, IC50 = 881 nM), binding of /sup 125/I-MSA to type 2 IGF receptors from rat liver (IGF-R2, IC50 = 80 nM), and binding of /sup 125/I-IGF I to crude human serum binding protein (hBP, IC50 = 0.42 nM). rIGF I is equipotent to human IGFmore » I in stimulating glucose transport in murine BC3H1 cells and in stimulating DNA synthesis in rat A10 cells. Site directed mutagenesis of the synthetic gene is being used to characterize the structural requirements for binding to these receptors. IGF I (FFY) B(23-25) is equipotent to rIGF I at the IGF-R1 (6.9 nM), the IGF-R2 (36 nM), and the IR (841 nM) and is less potent at the hBP (1.7 nM). In contrast, IGF I(SFY) B(23-25) is 20-fold less potent than rIGF I at the IGF-R1 and is 10-fold less potent than rIGF I at hBP. This peptide is greater than 10-fold less active at the IGF-R2 and the IR. This peptide is a full agonist in the cell assays but 20-50 fold less potent than rIGF I. These data are consistent with the hypothesis that the F to S change destabilizes the tertiary structure of IGF I.« less

Innovative Teaching of IC Design and Manufacture Using the Superchip Platform

ERIC Educational Resources Information Center

Wilson, P. R.; Wilcock, R.; McNally, I.; Swabey, M.

2010-01-01

This paper describes how an intelligent chip architecture has allowed a large cohort of undergraduate (UG) students to be given effective practical insight into integrated circuit (IC) design by designing and manufacturing their own ICs. To achieve this, an efficient chip architecture, the "Superchip," was developed, which allows multiple student…

Phenolic, flavonoid contents, anticholinesterase and antioxidant evaluation of Iris germanica var; florentina.

PubMed

Ullah, Farhat; Ayaz, Muhammad; Sadiq, Abdul; Hussain, Abid; Ahmad, Sajjad; Imran, Muhammad; Zeb, Anwar

2016-06-01

This study was designed to investigate antioxidant and anticholinesterase potential of Iris germanica var; florentina. Acetylcholinesterase (AChE) and butyrylcholinesterase (BChE) inhibitory potential of plant samples were investigated by Ellman's assay. Antioxidant activity was performed using DPPH, H2O2 and ABTS free radical scavenging assays. Total phenolics and flavonoids contents were expressed in mg GAE/g dry weight and mg RTE/g, respectively. In AChE inhibition assay, Ig.Fl, Ig.Sp and Ig.Cf fractions exhibited highest activity with IC50 values of < 0.1, 5.64 and 19 μg/mL, respectively. In BChE inhibitory assay, Ig.Fl, Ig.Sp, Ig.Cf and Ig.Cr were most active with IC50 of < 0.1, < 0.1, 31 and 78 μg/mL, respectively. In DPPH assay, Ig.Fl and Ig.Cf exhibited highest inhibition of free radicals, 80.52% (IC50 = 9 μg/mL) and 78.30% (IC50 = 8 μg/mL), respectively. In ABTS assay Ig.Cr, Ig.Cf, Ig.Fl and Ig.Sp exhibited IC50 values of < 0.1, 2, 2 and 3 μg/mL, respectively.

Publications - IC 36 | Alaska Division of Geological & Geophysical Surveys

Science.gov Websites

DGGS IC 36 Publication Details Title: Alaska's mineral industry 1992: A summary Authors: Swainbank, R.C ., 1993, Alaska's mineral industry 1992: A summary: Alaska Division of Geological & Geophysical

Publications - IC 40 | Alaska Division of Geological & Geophysical Surveys

Science.gov Websites

DGGS IC 40 Publication Details Title: Alaska's mineral industry 1994: A summary Authors: Swainbank, R.C mineral industry 1994: A summary: Alaska Division of Geological & Geophysical Surveys Information

SIGIR Quarterly and Semiannual Report to the United States Congress

DTIC Science & Technology

2006-01-01

Seraji Substation Basrah $5,709 GRD-PCO Perini Corporation Central 1659 Shat Al...e R em o va l, Fi re Se rv ic e, a n d P u b lic Sa fe ty F ac ili ty a n d Eq u ip m en t R ep ai rs 27 8. 00 20 4. 00 0. 00 20 4. 00 0...th e tr ai ni ng a nd e qu ip pi ng o f th e Ira qi P ol ic e Se rv ic e (IP S) 2. E xa m in e th e ef fe ct iv en es s

Protein adsorption to poly(ethylenimine)-modified Sepharose FF: VI. Partial charge neutralization drastically increases uptake rate.

PubMed

Zhao, Yangyang; Dong, Xiaoyan; Yu, Linling; Sun, Yan

2016-01-04

The adsorption and elution behaviors of bovine serum albumin (BSA) on poly(ethylenimine) (PEI)-grafted Sepharose FF resins were recently studied and a critical ionic capacity (cIC; 600 mmol/L) was found, above which the uptake rate increased drastically due to the occurrence of significant "chain delivery" effect. Moreover, above the cIC value, higher salt concentrations were required for protein elution due to the high charge density of the resins. In this work, we have reduced the charge density on the PEI chains of a PEI-grafted resin by neutralization of the amine groups with sodium acetate. PEI-modified resin with IC of 740 mmol/L (FF-PEI-L740, IC>cIC) was chosen as the starting material, and three resins with residual IC values of 660, 560 and 440 mmol/L (FF-PEI-R440) were obtained. The adsorption and chromatographic behaviors of these resins for BSA were investigated. It was found that, with IC decreasing from 740 to 440 mmol/L, the adsorption capacity kept almost unchanged; the effective protein diffusivity (De) also showed negligible variations as IC decreased from 740 to 560 mmol/L (De/D0=0.38 ± 0.04). However, it was interesting to observe a three-fold increase of the De value for FF-PEI-R440 (De/D0=1.23 ± 0.08). It is considered that the occurrence of the drastic uptake rate increase in FF-PEI-R440 was attributed to the decreased available binding sites for protein molecule, which led to the decrease of binding strength, thus facilitated the happenings of "chain delivery" effect of bound proteins. Besides, a study on the effect of ionic strength clarified that the lower the IC value, the higher the sensitivity of protein binding to salt concentration due to the easily screened electrostatic interactions at low surface charge densities. The ionic strength at the elution peak also decreased with decreasing IC in accordance with the salt sensitivity order. Column breakthrough studies demonstrated that the dynamic adsorption capacity of FF-PEI-R440 was much higher than the other three resins at flow rates higher than 30 cm/h because of its high uptake rate. The findings in this work provided new insights into the effects of the interactions between proteins and grafted polymers on adsorption equilibria and uptake kinetics, which would help the selection and design of suitable media for high-performance protein chromatography. Copyright © 2015. Published by Elsevier B.V.

IC97 Is a Novel Intermediate Chain of I1 Dynein That Interacts with Tubulin and Regulates Interdoublet Sliding

PubMed Central

Wirschell, Maureen; Yang, Chun; Yang, Pinfen; Fox, Laura; Yanagisawa, Haru-aki; Kamiya, Ritsu; Witman, George B.; Porter, Mary E.

2009-01-01

Our goal is to understand the assembly and regulation of flagellar dyneins, particularly the Chlamydomonas inner arm dynein called I1 dynein. Here, we focus on the uncharacterized I1-dynein IC IC97. The IC97 gene encodes a novel IC without notable structural domains. IC97 shares homology with the murine lung adenoma susceptibility 1 (Las1) protein—a candidate tumor suppressor gene implicated in lung tumorigenesis. Multiple, independent biochemical assays determined that IC97 interacts with both α- and β-tubulin subunits within the axoneme. I1-dynein assembly mutants suggest that IC97 interacts with both the IC138 and IC140 subunits within the I1-dynein motor complex and that IC97 is part of a regulatory complex that contains IC138. Microtubule sliding assays, using axonemes containing I1 dynein but devoid of IC97, show reduced microtubule sliding velocities that are not rescued by kinase inhibitors, revealing a critical role for IC97 in I1-dynein function and control of dynein-driven motility. PMID:19420136

Chest Wall Thickness and Decompression Failure: A Systematic Review and Meta-analysis Comparing Anatomic Locations in Needle Thoracostomy

PubMed Central

Laan, Danuel V.; Vu, Trang Diem N.; Thiels, Cornelius A.; Pandian, T. K.; Schiller, Henry J.; Murad, M. Hassan; Aho, Johnathon M.

2015-01-01

Introduction Current Advanced Trauma Life Support guidelines recommend decompression for thoracic tension physiology using a 5-cm angiocatheter at the second intercostal space (ICS) on the midclavicular line (MCL). High failure rates occur. Through systematic review and meta-analysis, we aimed to determine the chest wall thickness (CWT) of the 2nd ICS-MCL, the 4th/5th ICS at the anterior axillary line (AAL), the 4th/5th ICS mid axillary line (MAL) and needle thoracostomy failure rates using the currently recommended 5-cm angiocatheter. Methods A comprehensive search of several databases from their inception to July 24, 2014 was conducted. The search was limited to the English language, and all study populations were included. Studies were appraised by two independent reviewers according to a priori defined PRISMA inclusion and exclusion criteria. Continuous outcomes (CWT) were evaluated using weighted mean difference and binary outcomes (failure with 5-cm needle) were assessed using incidence rate. Outcomes were pooled using the random-effects model. Results The search resulted in 34,652 studies of which 15 were included for CWT analysis, 13 for NT effectiveness. Mean CWT was 42.79 mm (95% CI, 38.78–46.81) at 2nd ICS-MCL, 39.85 mm (95% CI, 28.70–51.00) at MAL, and 34.33 mm (95% CI, 28.20–40.47) at AAL (P=0.08). Mean failure rate was 38% (95% CI, 24–54) at 2nd ICS-MCL, 31% (95% CI, 10–64) at MAL, and 13% (95% CI, 8–22) at AAL (P=0.01). Conclusion Evidence from observational studies suggests that the 4th/5th ICS-AAL has the lowest predicted failure rate of needle decompression in multiple populations. PMID:26724173

Chest wall thickness and decompression failure: A systematic review and meta-analysis comparing anatomic locations in needle thoracostomy.

PubMed

Laan, Danuel V; Vu, Trang Diem N; Thiels, Cornelius A; Pandian, T K; Schiller, Henry J; Murad, M Hassan; Aho, Johnathon M

2016-04-01

Current Advanced Trauma Life Support guidelines recommend decompression for thoracic tension physiology using a 5-cm angiocatheter at the second intercostal space (ICS) on the midclavicular line (MCL). High failure rates occur. Through systematic review and meta-analysis, we aimed to determine the chest wall thickness (CWT) of the 2nd ICS-MCL, the 4th/5th ICS at the anterior axillary line (AAL), the 4th/5th ICS mid axillary line (MAL) and needle thoracostomy failure rates using the currently recommended 5-cm angiocatheter. A comprehensive search of several databases from their inception to July 24, 2014 was conducted. The search was limited to the English language, and all study populations were included. Studies were appraised by two independent reviewers according to a priori defined PRISMA inclusion and exclusion criteria. Continuous outcomes (CWT) were evaluated using weighted mean difference and binary outcomes (failure with 5-cm needle) were assessed using incidence rate. Outcomes were pooled using the random-effects model. The search resulted in 34,652 studies of which 15 were included for CWT analysis, 13 for NT effectiveness. Mean CWT was 42.79 mm (95% CI, 38.78-46.81) at 2nd ICS-MCL, 39.85 mm (95% CI, 28.70-51.00) at MAL, and 34.33 mm (95% CI, 28.20-40.47) at AAL (P=.08). Mean failure rate was 38% (95% CI, 24-54) at 2nd ICS-MCL, 31% (95% CI, 10-64) at MAL, and 13% (95% CI, 8-22) at AAL (P=.01). Evidence from observational studies suggests that the 4th/5th ICS-AAL has the lowest predicted failure rate of needle decompression in multiple populations. Level 3 SR/MA with up to two negative criteria. Therapeutic. Copyright © 2015 Elsevier Ltd. All rights reserved.

Sleep-disordered breathing in patients with COPD and mild hypoxemia: prevalence and predictive variables.

PubMed

Silva, José Laerte Rodrigues; Conde, Marcus Barreto; Corrêa, Krislainy de Sousa; Rabahi, Helena; Rocha, Arthur Alves; Rabahi, Marcelo Fouad

2017-01-01

To infer the prevalence and variables predictive of isolated nocturnal hypoxemia and obstructive sleep apnea (OSA) in patients with COPD and mild hypoxemia. This was a cross-sectional study involving clinically stable COPD outpatients with mild hypoxemia (oxygen saturation = 90-94%) at a clinical center specializing in respiratory diseases, located in the city of Goiânia, Brazil. The patients underwent clinical evaluation, spirometry, polysomnography, echocardiography, arterial blood gas analysis, six-minute walk test assessment, and chest X-ray. The sample included 64 patients with COPD and mild hypoxemia; 39 (61%) were diagnosed with sleep-disordered breathing (OSA, in 14; and isolated nocturnal hypoxemia, in 25). Correlation analysis showed that PaO2 correlated moderately with mean sleep oxygen saturation (r = 0.45; p = 0.0002), mean rapid eye movement (REM) sleep oxygen saturation (r = 0.43; p = 0.001), and mean non-REM sleep oxygen saturation (r = 0.42; p = 0.001). A cut-off point of PaO2 ≤ 70 mmHg in the arterial blood gas analysis was significantly associated with sleep-disordered breathing (OR = 4.59; 95% CI: 1.54-13.67; p = 0.01). The model showed that, for identifying sleep-disordered breathing, the cut-off point had a specificity of 73.9% (95% CI: 51.6-89.8%), a sensitivity of 63.4% (95% CI: 46.9-77.9%), a positive predictive value of 81.3% (95% CI: 67.7-90.0%), and a negative predictive value of 53.1% (95% CI: 41.4-64.4%), with an area under the ROC curve of 0.69 (95% CI: 0.57-0.80), correctly classifying the observations in 67.2% of the cases. In our sample of patients with COPD and mild hypoxemia, the prevalence of sleep-disordered breathing was high (61%), suggesting that such patients would benefit from sleep studies. Inferir a prevalência e as variáveis preditivas de hipoxemia noturna e apneia obstrutiva do sono (AOS) em pacientes portadores de DPOC com hipoxemia leve. Estudo transversal realizado em pacientes ambulatoriais, clinicamente estáveis, portadores de DPOC e hipoxemia leve (saturação de oxigênio = 90-94%) em um centro clínico especializado no atendimento de doenças respiratórias em Goiânia (GO). Os pacientes foram submetidos à avaliação clínica, espirometria, polissonografia, ecocardiografia, gasometria arterial, teste de caminhada de seis minutos e radiografia de tórax. Foram avaliados 64 pacientes com DPOC e hipoxemia leve, e 39 (61%) apresentaram distúrbios respiratórios do sono (14 com AOS e 25 com hipoxemia noturna isolada). A análise de correlação mostrou moderada correlação da PaO2 com saturação média do sono (r = 0,45; p = 0,0002), saturação média do sono rapid eye movement (REM; r = 0,43; p = 0,001) e saturação média do sono não-REM (r = 0,42; p = 0,001). Um ponto de corte de PaO2 ≤ 70 mmHg (OR = 4,59; IC95%: 1,54-13,67; p = 0,01) na gasometria arterial foi significativamente associada com distúrbios respiratórios do sono. O modelo mostrou que, para identificar distúrbios respiratórios do sono, o ponto de corte teve uma especificidade de 73,9% (IC95%: 51,6-89,8%), uma sensibilidade de 63,4% (IC95%: 46,9-77,9%) e valores preditivos positivo e negativo de 81,3% (IC95%: 67,7-90,0%) e 53,1% (IC95%: 41,4-64,4%), respectivamente. A área sob a curva ROC foi de 0,69 (IC95%: 0,57-0,80), e a proporção de observações corretamente classificadas foi de 67,2% dos casos. A elevada prevalência de distúrbios respiratórios do sono em portadores de DPOC e hipoxemia leve nesta amostra (61%) sugere que esses pacientes podem se beneficiar da realização de estudos do sono.

30 CFR 57.22201 - Mechanical ventilation (I-A, I-B, I-C, II-A, II-B, III, IV, V-A, and V-B mines).

Code of Federal Regulations, 2010 CFR

2010-07-01

... 30 Mineral Resources 1 2010-07-01 2010-07-01 false Mechanical ventilation (I-A, I-B, I-C, II-A, II-B, III, IV, V-A, and V-B mines). 57.22201 Section 57.22201 Mineral Resources MINE SAFETY AND HEALTH....22201 Mechanical ventilation (I-A, I-B, I-C, II-A, II-B, III, IV, V-A, and V-B mines). All mines shall...

30 CFR 57.22501 - Personal electric lamps (I-A, I-B, I-C, II-A, II-B, III, IV, V-A, and V-B mines).

Code of Federal Regulations, 2014 CFR

2014-07-01

... 30 Mineral Resources 1 2014-07-01 2014-07-01 false Personal electric lamps (I-A, I-B, I-C, II-A... Illumination § 57.22501 Personal electric lamps (I-A, I-B, I-C, II-A, II-B, III, IV, V-A, and V-B mines). Electric lamps used for personal illumination shall be approved by MSHA under the requirements of 30 CFR...

30 CFR 57.22501 - Personal electric lamps (I-A, I-B, I-C, II-A, II-B, III, IV, V-A, and V-B mines).

Code of Federal Regulations, 2012 CFR

2012-07-01

... 30 Mineral Resources 1 2012-07-01 2012-07-01 false Personal electric lamps (I-A, I-B, I-C, II-A... Illumination § 57.22501 Personal electric lamps (I-A, I-B, I-C, II-A, II-B, III, IV, V-A, and V-B mines). Electric lamps used for personal illumination shall be approved by MSHA under the requirements of 30 CFR...

30 CFR 57.22501 - Personal electric lamps (I-A, I-B, I-C, II-A, II-B, III, IV, V-A, and V-B mines).

Code of Federal Regulations, 2013 CFR

2013-07-01

... 30 Mineral Resources 1 2013-07-01 2013-07-01 false Personal electric lamps (I-A, I-B, I-C, II-A... Illumination § 57.22501 Personal electric lamps (I-A, I-B, I-C, II-A, II-B, III, IV, V-A, and V-B mines). Electric lamps used for personal illumination shall be approved by MSHA under the requirements of 30 CFR...

30 CFR 57.22501 - Personal electric lamps (I-A, I-B, I-C, II-A, II-B, III, IV, V-A, and V-B mines).

Code of Federal Regulations, 2011 CFR

2011-07-01

... 30 Mineral Resources 1 2011-07-01 2011-07-01 false Personal electric lamps (I-A, I-B, I-C, II-A, II-B, III, IV, V-A, and V-B mines). 57.22501 Section 57.22501 Mineral Resources MINE SAFETY AND... Illumination § 57.22501 Personal electric lamps (I-A, I-B, I-C, II-A, II-B, III, IV, V-A, and V-B mines...

30 CFR 57.22501 - Personal electric lamps (I-A, I-B, I-C, II-A, II-B, III, IV, V-A, and V-B mines).

Code of Federal Regulations, 2010 CFR

2010-07-01

... 30 Mineral Resources 1 2010-07-01 2010-07-01 false Personal electric lamps (I-A, I-B, I-C, II-A, II-B, III, IV, V-A, and V-B mines). 57.22501 Section 57.22501 Mineral Resources MINE SAFETY AND... Illumination § 57.22501 Personal electric lamps (I-A, I-B, I-C, II-A, II-B, III, IV, V-A, and V-B mines...

30 CFR 57.22227 - Approved testing devices (I-A, I-B, I-C, II-A, II-B, III, IV, V-A, and V-B mines).

Code of Federal Regulations, 2011 CFR

2011-07-01

... 30 Mineral Resources 1 2011-07-01 2011-07-01 false Approved testing devices (I-A, I-B, I-C, II-A, II-B, III, IV, V-A, and V-B mines). 57.22227 Section 57.22227 Mineral Resources MINE SAFETY AND... Ventilation § 57.22227 Approved testing devices (I-A, I-B, I-C, II-A, II-B, III, IV, V-A, and V-B mines). (a...

30 CFR 57.22201 - Mechanical ventilation (I-A, I-B, I-C, II-A, II-B, III, IV, V-A, and V-B mines).

Code of Federal Regulations, 2011 CFR

2011-07-01

... 30 Mineral Resources 1 2011-07-01 2011-07-01 false Mechanical ventilation (I-A, I-B, I-C, II-A, II-B, III, IV, V-A, and V-B mines). 57.22201 Section 57.22201 Mineral Resources MINE SAFETY AND HEALTH....22201 Mechanical ventilation (I-A, I-B, I-C, II-A, II-B, III, IV, V-A, and V-B mines). All mines shall...

A Feasibility Study for the Development of a Nuclear Moisture Density Measurement System for Marine Use.

DTIC Science & Technology

1977-12-28

n c u c t Ic.: ; coeffi c I e n t s a’- - ‘.- .;.“ra t r fc r a n r- :a c’ ’’s i Cr- can --bloc - -C ‘ J ; I ( a ’ ’) is alo uC .05 C 10 ” ~n i...c - c - ’- c - n l~~~~l j L c i , i t is ( 1 a u - c ’: : - vera - -~ t i c a-, th i s d c c L - a is v a - c r y di :n r — c ’ n L i c c-f

Clinical presentation and blood gas analysis of multiple trauma patients for prediction of standard coagulation parameters at emergency department arrival.

PubMed

Hilbert-Carius, P; Hofmann, G O; Lefering, R; Stuttmann, R; Struck, M F

2016-04-01

Trauma-induced coagulopathy (TIC) in multiple trauma patients is a potentially lethal complication. Whether quickly available laboratory parameters using point-of-care (POC) blood gas analysis (BGA) may serve as surrogate parameters for standard coagulation parameters is unknown. The present study evaluated TraumaRegister DGU® of the German Trauma Society for correlations between POC BGA parameters and standard coagulation parameters. In the setting of 197 trauma centres (172 in Germany), 86,442 patients were analysed between 2005 and 2012. Of these, 40,129 (72% men) with a mean age 46 ± 21 years underwent further analysis presenting with direct admission from the scene of the accident to a trauma centre, injury severity score (ISS) ≥ 9, complete data available for the calculation of revised injury severity classification prognosis, and blood samples with valid haemoglobin (Hb) measurements taken immediately after emergency department (ED) admission. Correlations between standard coagulation parameters and POC BGA parameters (Hb, base excess [BE], lactate) were tested using Pearson's test with a two-tailed significance level of p < 0.05. A subgroup analysis including patients with ISS > 16, ISS > 25, ISS > 16 and shock at ED admission, and patients with massive transfusion was likewise carried out. Correlations were found between Hb and prothrombin time (r = 0.497; p < 0.01), Hb and activated partial thromboplastin time (aPTT; r = -0.414; p < 0.01), and Hb and platelet count (PLT; r = 0.301; p < 0.01). Patients presenting with ISS ≥ 16 and shock (systolic blood pressure < 90 mmHg) at ED admission (n = 4,329) revealed the strongest correlations between Hb and prothrombin time (r = 0.570; p < 0.01), Hb and aPTT (r = -0.457; p < 0.01), and Hb and PLT (r = 0.412; p < 0.01). Significant correlations were also found between BE and prothrombin time (r = -0.365; p < 0.01), and BE and aPTT (r = 0.327, p < 0.01). No correlations were found between Hb, BE and lactate lactate. POC BGA parameters Hb and BE of multiple trauma patients correlated with standard coagulation parameters in a large database analysis. These correlations were particularly strong in multiple trauma patients presenting with ISS > 16 and shock at ED admission. This may be relevant for hospitals with delayed availability of coagulation studies and those without viscoelastic POC devices. Future studies may determine whether clinical presentation/BGA-oriented coagulation therapy is an appropriate tool for improving outcomes after major trauma.

Flavocoxid Inhibits Phospholipase A2, Peroxidase Moieties of the Cyclooxygenases (COX), and 5-Lipoxygenase, Modifies COX-2 Gene Expression, and Acts as an Antioxidant

PubMed Central

Burnett, Bruce P.; Bitto, Alessandra; Altavilla, Domenica; Squadrito, Francesco; Levy, Robert M.; Pillai, Lakshmi

2011-01-01

The multiple mechanisms of action for flavocoxid relating to arachidonic acid (AA) formation and metabolism were studied in vitro. Flavocoxid titrated into rat peritoneal macrophage cultures inhibited cellular phospholipase A2 (PLA2) (IC50 = 60 μg/mL). In in vitro enzyme assays, flavocoxid showed little anti-cyclooxygenase (CO) activity on COX-1/-2 enzymes, but inhibited the COX-1 (IC50 = 12.3) and COX-2 (IC50 = 11.3 μg/mL) peroxidase (PO) moieties as well as 5-lipoxygenase (5-LOX) (IC50 = 110 μg/mL). No detectable 5-LOX inhibition was found for multiple traditional and COX-2 selective NSAIDs. Flavocoxid also exhibited strong and varied antioxidant capacities in vitro and decreased nitrite levels (IC50 = 38 μg/mL) in rat peritoneal macrophages. Finally, in contrast to celecoxib and ibuprofen, which upregulated the cox-2 gene, flavocoxid strongly decreased expression. This work suggests that clinically favourable effects of flavocoxid for management of osteoarthritis (OA) are achieved by simultaneous modification of multiple molecular pathways relating to AA metabolism, oxidative induction of inflammation, and neutralization of reactive oxygen species (ROS). PMID:21765617

Flavocoxid inhibits phospholipase A2, peroxidase moieties of the cyclooxygenases (COX), and 5-lipoxygenase, modifies COX-2 gene expression, and acts as an antioxidant.

PubMed

Burnett, Bruce P; Bitto, Alessandra; Altavilla, Domenica; Squadrito, Francesco; Levy, Robert M; Pillai, Lakshmi

2011-01-01

The multiple mechanisms of action for flavocoxid relating to arachidonic acid (AA) formation and metabolism were studied in vitro. Flavocoxid titrated into rat peritoneal macrophage cultures inhibited cellular phospholipase A2 (PLA(2)) (IC(50) = 60 μg/mL). In in vitro enzyme assays, flavocoxid showed little anti-cyclooxygenase (CO) activity on COX-1/-2 enzymes, but inhibited the COX-1 (IC(50) = 12.3) and COX-2 (IC(50) = 11.3 μg/mL) peroxidase (PO) moieties as well as 5-lipoxygenase (5-LOX) (IC(50) = 110 μg/mL). No detectable 5-LOX inhibition was found for multiple traditional and COX-2 selective NSAIDs. Flavocoxid also exhibited strong and varied antioxidant capacities in vitro and decreased nitrite levels (IC(50) = 38 μg/mL) in rat peritoneal macrophages. Finally, in contrast to celecoxib and ibuprofen, which upregulated the cox-2 gene, flavocoxid strongly decreased expression. This work suggests that clinically favourable effects of flavocoxid for management of osteoarthritis (OA) are achieved by simultaneous modification of multiple molecular pathways relating to AA metabolism, oxidative induction of inflammation, and neutralization of reactive oxygen species (ROS).

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

Taddia, Francesco; Fremling, C.; Sollerman, J.

Type Ic supernovae (SNe Ic) arise from the core-collapse of H- (and He-) poor stars, which could either be single Wolf-Rayet (WR) stars or lower-mass stars stripped of their envelope by a companion. Their light curves are radioactively powered and usually show a fast rise to peak (~10-15 d), without any early (in the first few days) emission bumps (with the exception of broad-lined SNe Ic) as sometimes seen for other types of stripped-envelope SNe (e.g., Type IIb SN 1993J and Type Ib SN 2008D). Here, we have studied iPTF15dtg, a spectroscopically normal SN Ic with an early excess inmore » the optical light curves followed by a long (~30 d) rise to the main peak. It is the first spectroscopically-normal double-peaked SN Ic to be observed. Our aim is to determine the properties of this explosion and of its progenitor star. Methods. Optical photometry and spectroscopy of iPTF15dtg was obtained with multiple telescopes. The resulting light curves and spectral sequence are analyzed and modeled with hydrodynamical and analytical models, with particular focus on the early emission. iPTF15dtg is a slow rising SN Ic, similar to SN 2011bm. Hydrodynamical modeling of the bolometric properties reveals a large ejecta mass (~10 M ⊙) and strong 56Ni mixing. The luminous early emission can be reproduced if we account for the presence of an extended (≳500 R ⊙), low-mass (≳0.045 M ⊙) envelope around the progenitor star. Alternative scenarios for the early peak, such as the interaction with a companion, a shock-breakout (SBO) cooling tail from the progenitor surface, or a magnetar-driven SBO are not favored. In conclusion, the large ejecta mass and the presence of H- and He-free extended material around the star suggest that the progenitor of iPTF15dtg was a massive (≳35 M ⊙) WR star that experienced strong mass loss.« less

Assessment of Xylazine for Euthanasia of Anoles (Anolis carolinensis and Anolis distichus)

PubMed Central

Ascher, Jill M; Bates, Wendy; Ng, Julienne; Messing, Susan; Wyatt, Jeffrey

2012-01-01

Intracoelomic (IC) injection of xylazine was evaluated as a chemical euthanasia method for Anolis lizards (Anolis carolinensis or Anolis distichus). Lizards were allocated into 5 groups of 10 animals each. Each group was euthanized by one of these methods: 10 mg xylazine (100 mg/mL) IC; 10 mg xylazine and 0.5 mg acepromazine (10 mg/mL) IC; 10 mg xylazine IC followed by intracardiac injection of 0.1 mEq KCl (2 mEq/mL) once heart beats were no longer discernable by Doppler; 500 mg/kg 1% NaCO3-buffered MS222 solution IC followed by IC injection of 0.1 mL unbuffered 50% (v/v) MS222 solution (experimental groups); and 1.95 mg sodium pentobarbital, diluted 1:10 in sterile water (38.9 mg/mL) given IC (control group). Compared with those given sodium pentobarbital or MS222, lizards euthanized by using xylazine showed prolonged persistence of purposeful movement after cardiac arrest. Therefore, xylazine is not an acceptable alternative euthanasia agent for use in anoles. PMID:22330873

Assessment of xylazine for euthanasia of anoles (Anolis carolinensis and Anolis distichus).

PubMed

Ascher, Jill M; Bates, Wendy; Ng, Julienne; Messing, Susan; Wyatt, Jeffrey

2012-01-01

Intracoelomic (IC) injection of xylazine was evaluated as a chemical euthanasia method for Anolis lizards (Anolis carolinensis or Anolis distichus). Lizards were allocated into 5 groups of 10 animals each. Each group was euthanized by one of these methods: 10 mg xylazine (100 mg/mL) IC; 10 mg xylazine and 0.5 mg acepromazine (10 mg/mL) IC; 10 mg xylazine IC followed by intracardiac injection of 0.1 mEq KCl (2 mEq/mL) once heart beats were no longer discernable by Doppler; 500 mg/kg 1% NaCO(3)-buffered MS222 solution IC followed by IC injection of 0.1 mL unbuffered 50% (v/v) MS222 solution (experimental groups); and 1.95 mg sodium pentobarbital, diluted 1:10 in sterile water (38.9 mg/mL) given IC (control group). Compared with those given sodium pentobarbital or MS222, lizards euthanized by using xylazine showed prolonged persistence of purposeful movement after cardiac arrest. Therefore, xylazine is not an acceptable alternative euthanasia agent for use in anoles.

Management Control of Flight Operations (OFC-01) Funds

DTIC Science & Technology

1982-12-01

3uide to Badgeta: y an ~~q.jntContro Svst___. -mpi~,~9 Ivancevich, John M. Szilagyi ,, Jr. kndrew D. and Wallace , Jr. Marc J,, OQ~anizational Bhivior...Sz~iagyi., and Wallace term the socio-techn-Ical systems molel. Showai in Figure 2-1, the molel is an input-transfociatior.-oLtpat system. The system...anA Performance, Goo)dyear Publi-hi-Ef ’ComP~ay,-rIc. T~7777 Ivancevich, John M., Szila; yi, Jr. kardrew D., and Wallace Jr. Marc J., Readi~qct In

Joint Optoelectronics Research Scheme (JOERS) Conference Held in England on June 1988

DTIC Science & Technology

1989-03-15

with high electro-opt ic-coefficient conditions of InAsSb lattice matched to GaSb; this is a molec Jles as the guest in a host of cost PVDF copolymer... curved ridges have been made by wet gcncc effects in bow-tie fiber may be enhanced by an chemical etching, curves with radii as lov as 3() m are...The work is now being cxtended to curved waveguides, lcscnc ,Nu i 01. Pl 1 A:h, h lnt. m’k v.\\ , r ( IlCIlo - mirrors, Y-junctions, and crosspoints

Inhibition of Protein Synthesis on the Ribosome by Tildipirosin Compared with Other Veterinary Macrolides

PubMed Central

Andersen, Niels Møller; Poehlsgaard, Jacob; Warrass, Ralf

2012-01-01

Tildipirosin is a 16-membered-ring macrolide developed to treat bacterial pathogens, including Mannheimia haemolytica and Pasteurella multocida, that cause respiratory tract infections in cattle and swine. Here we evaluated the efficacy of tildipirosin at inhibiting protein synthesis on the ribosome (50% inhibitory concentration [IC50], 0.23 ± 0.01 μM) and compared it with the established veterinary macrolides tylosin, tilmicosin, and tulathromycin. Mutation and methylation at key rRNA nucleotides revealed differences in the interactions of these macrolides within their common ribosomal binding site. PMID:22926570

Military Forces in Urban Antiterrorism

DTIC Science & Technology

1989-10-01

not constitule an official eodorýemtnt oi apprcvai of the use of’ s3ch commercial products. UNCLASSIFIED ýEUAITY CLAS .’A71ON; 01 - ~’PAGE J FIorm...Continue on reverse if necessary and identify by block number) ýIFLD GROUP SU1R- AU P urban wlrfare; MOUT, 15 6 ____ ,.rban terrorism LIC J terrorism (see...onclusions and address-ez their impl ic~ati ons for U.S. military forces in future urban aril itrror int operat2.on:?.k 20DiSTRiBUITION /AVAILABILTY OF j .,85

Two novel assays for the detection of haemin-binding properties of antimalarials evaluated with compounds isolated from medicinal plants.

PubMed

Steele, J C P; Phelps, R J; Simmonds, M S J; Warhurst, D C; Meyer, D J

2002-07-01

Forty-two compounds isolated from nine plants used within South America for the treatment of malaria were tested for haemin binding using two novel, rapid screening methods. The data obtained were analysed with respect to IC(50) values for in vitro toxicity to Plasmodium falciparum trophozoites. One method, a multiwell assay based on the inhibition of the interaction of haemin with glutathione (GSH), is sensitive in the 10 microM range, takes c. 1 h and is suitable for either a high throughput screen or rapid assay during natural product isolation. Of 19 compounds showing antiplasmodial activity (IC(50) < 40 microM), 16 (84%) showed >40% inhibition of GSH-haemin reaction. The sensitivity and specificity of the assay were 0.85 and 0.82, respectively. The positive predictive value was 0.81 and the negative predictive value 0.86. A more sensitive assay (0.1 microM range) is based on the reversal by haemin-binding compounds of the haemin inhibition of the L-dopachrome-methyl ester tautomerase activity of human macrophage migration inhibitory factor. This assay gives a better idea of the affinity of interaction and uses very small amounts of test compound. The log[RI(50)] of eight of the compounds that tested positive in the above assays together with those of quinine and chloroquine showed a positive correlation with log[antiplasmodial IC(50)] for strain T9-96 (r = 0.824) and strain K1 (r = 0.904). Several of the antimalarial compounds that bind haemin are isoquinolines, a class not shown previously to interact with haemin.

Enhanced Androgen Signaling with Androgen Receptor Overexpression in the Osteoblast Lineage Controls Skeletal Turnover, Matrix Quality and Bone Architecture

DTIC Science & Technology

2008-12-01

Hounsfield units (HU) to mineral values (mg/cc of HA) through the use of...Ph.D. Russell Turner 5e. TASK NUMBER E-Mail: wirenk@ohsu.edu 5f. WORK UNIT NUMBER 7. PERFORMING ORGANIZATION NAME(S) AND ADDRESS(ES) 8...gn al in g IL -6 S ig n al in g H ep at ic Fi b ro si s/ H ep at ic … IL -1 0 S ig n al in g V D R /R X R A ct iv at io n P PA R S ig n al

PubMed

Zaragoza-Martí, Ana; Sánchez-SanSegundo, Miriam; Ferrer-Cascales, Rosario

2016-11-29

Introducción: el trastorno por atracón o "Binge Eating Disorders" (BED) se caracteriza por el consumo de grandes cantidades de comida en un breve periodo de tiempo acompañado de una sensación de falta de control sobre la ingesta. El BED se relaciona con una alimentación poco equilibrada, contribuyendo a la aparición de diversas patologías. La alimentación y los estilos de vida desempeñan un factor clave en la prevención de estas patologías, siendo la dieta mediterránea (DM) uno de los estándares de la alimentación saludable.Objetivo: analizar la relación entre la DM y el BED en una muestra de estudiantes universitarios.Método: se realizó un estudio descriptivo transversal en una muestra de 120 estudiantes de la Universidad de Alicante. Para establecer la relación entre el patrón de atracón y el grado de adherencia a la DM se determinó el coefi ciente de correlación r de Pearson. Los resultados se expresaron en odds ratios (OR) e intervalo de confi anza (IC) al 95%.Resultados: los sujetos con un patrón de BED presentaron menor adherencia a la DM (OR = 4,03; IC 95%, 1,80-18,69), mayores índices de exceso de peso (OR = 5,31; IC 95%, 1,81-15,64), y vidas más sedentarias (OR = 1,4; IC 95%, 0,52-4,12). El BED correlacionó negativamente con el grado de adherencia DM (r = -0,3, p < 0,01).Conclusión: el patrón de DM se asocia de manera inversa con el riesgo de sufrir trastorno por atracón y además dicho patrón de atracón se asocia significativamente con el riesgo de sufrir exceso de peso en estudiantes universitarios. Son necesarios estudios que confi rmen que la DM reduce el riesgo de sufrir trastorno por atracón.

Publications - IC 54 | Alaska Division of Geological & Geophysical Surveys

Science.gov Websites

DGGS IC 54 Publication Details Title: Alaska's mineral industry 2006: A summary Authors: Szumigala, D.J Bibliographic Reference Szumigala, D.J., and Hughes, R.A., 2007, Alaska's mineral industry 2006: A summary

Information Content Analysis for Selection of Optimal JWST  Observing Modes for Transiting Exoplanet Atmospheres

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

Batalha, Natasha E.; Line, M. R., E-mail: neb149@psu.edu

The James Webb Space Telescope ( JWST ) is nearing its launch date of 2018, and is expected to revolutionize our knowledge of exoplanet atmospheres. In order to specifically identify which observing modes will be most useful for characterizing a diverse range of exoplanetary atmospheres, we use an information content (IC) based approach commonly used in the studies of solar system atmospheres. We develop a system based upon these IC methods to trace the instrumental and atmospheric model phase space in order to identify which observing modes are best suited for particular classes of planets, focusing on transmission spectra. Specifically,more » the atmospheric parameter space we cover is T  = 600–1800 K, C/O = 0.55–1, [M/H] = 1–100 × Solar for an R  = 1.39 R{sub J}, M  = 0.59 M{sub J} planet orbiting a WASP-62-like star. We also explore the influence of a simplified opaque gray cloud on the IC. We find that obtaining broader wavelength coverage over multiple modes is preferred over higher precision in a single mode given the same amount of observing time. Regardless of the planet temperature and composition, the best modes for constraining terminator temperatures, C/O ratios, and metallicity are NIRISS SOSS+NIRSpec G395. If the target’s host star is dim enough such that the NIRSpec prism is applicable, then it can be used instead of NIRISS SOSS+NIRSpec G395. Lastly, observations that use more than two modes should be carefully analyzed because sometimes the addition of a third mode results in no gain of information. In these cases, higher precision in the original two modes is favorable.« less

Low Cost 2-D Heatshield Materials

DTIC Science & Technology

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

A multi-scale PDMS fabrication strategy to bridge the size mismatch between integrated circuits and microfluidics†

PubMed Central

Muluneh, Melaku

2015-01-01

In recent years there has been great progress harnessing the small-feature size and programmability of integrated circuits (ICs) for biological applications, by building microfluidics directly on top of ICs. However, a major hurdle to the further development of this technology is the inherent size-mismatch between ICs (~mm) and microfluidic chips (~cm). Increasing the area of the ICs to match the size of the microfluidic chip, as has often been done in previous studies, leads to a waste of valuable space on the IC and an increase in fabrication cost (>100×). To address this challenge, we have developed a three dimensional PDMS chip that can straddle multiple length scales of hybrid IC/microfluidic chips. This approach allows millimeter-scale ICs, with no post-processing, to be integrated into a centimeter-sized PDMS chip. To fabricate this PDMS chip we use a combination of soft-lithography and laser micromachining. Soft lithography was used to define micrometer-scale fluid channels directly on the surface of the IC, allowing fluid to be controlled with high accuracy and brought into close proximity to sensors for highly sensitive measurements. Laser micromachining was used to create ~50 μm vias to connect these molded PDMS channels to a larger PDMS chip, which can connect multiple ICs and house fluid connections to the outside world. To demonstrate the utility of this approach, we built and demonstrated an in-flow magnetic cytometer that consisted of a 5 × 5 cm2 microfluidic chip that incorporated a commercial 565 × 1145 μm2 IC with a GMR sensing circuit. We additionally demonstrated the modularity of this approach by building a chip that incorporated two of these GMR chips connected in series. PMID:25284502

A multi-scale PDMS fabrication strategy to bridge the size mismatch between integrated circuits and microfluidics.

PubMed

Muluneh, Melaku; Issadore, David

2014-12-07

In recent years there has been great progress harnessing the small-feature size and programmability of integrated circuits (ICs) for biological applications, by building microfluidics directly on top of ICs. However, a major hurdle to the further development of this technology is the inherent size-mismatch between ICs (~mm) and microfluidic chips (~cm). Increasing the area of the ICs to match the size of the microfluidic chip, as has often been done in previous studies, leads to a waste of valuable space on the IC and an increase in fabrication cost (>100×). To address this challenge, we have developed a three dimensional PDMS chip that can straddle multiple length scales of hybrid IC/microfluidic chips. This approach allows millimeter-scale ICs, with no post-processing, to be integrated into a centimeter-sized PDMS chip. To fabricate this PDMS chip we use a combination of soft-lithography and laser micromachining. Soft lithography was used to define micrometer-scale fluid channels directly on the surface of the IC, allowing fluid to be controlled with high accuracy and brought into close proximity to sensors for highly sensitive measurements. Laser micromachining was used to create ~50 μm vias to connect these molded PDMS channels to a larger PDMS chip, which can connect multiple ICs and house fluid connections to the outside world. To demonstrate the utility of this approach, we built and demonstrated an in-flow magnetic cytometer that consisted of a 5 × 5 cm(2) microfluidic chip that incorporated a commercial 565 × 1145 μm(2) IC with a GMR sensing circuit. We additionally demonstrated the modularity of this approach by building a chip that incorporated two of these GMR chips connected in series.

iPTF15dtg: a double-peaked Type Ic supernova from a massive progenitor

DOE PAGES

Taddia, Francesco; Fremling, C.; Sollerman, J.; ...

2016-08-04

Type Ic supernovae (SNe Ic) arise from the core-collapse of H- (and He-) poor stars, which could either be single Wolf-Rayet (WR) stars or lower-mass stars stripped of their envelope by a companion. Their light curves are radioactively powered and usually show a fast rise to peak (~10-15 d), without any early (in the first few days) emission bumps (with the exception of broad-lined SNe Ic) as sometimes seen for other types of stripped-envelope SNe (e.g., Type IIb SN 1993J and Type Ib SN 2008D). Here, we have studied iPTF15dtg, a spectroscopically normal SN Ic with an early excess inmore » the optical light curves followed by a long (~30 d) rise to the main peak. It is the first spectroscopically-normal double-peaked SN Ic to be observed. Our aim is to determine the properties of this explosion and of its progenitor star. Methods. Optical photometry and spectroscopy of iPTF15dtg was obtained with multiple telescopes. The resulting light curves and spectral sequence are analyzed and modeled with hydrodynamical and analytical models, with particular focus on the early emission. iPTF15dtg is a slow rising SN Ic, similar to SN 2011bm. Hydrodynamical modeling of the bolometric properties reveals a large ejecta mass (~10 M ⊙) and strong 56Ni mixing. The luminous early emission can be reproduced if we account for the presence of an extended (≳500 R ⊙), low-mass (≳0.045 M ⊙) envelope around the progenitor star. Alternative scenarios for the early peak, such as the interaction with a companion, a shock-breakout (SBO) cooling tail from the progenitor surface, or a magnetar-driven SBO are not favored. In conclusion, the large ejecta mass and the presence of H- and He-free extended material around the star suggest that the progenitor of iPTF15dtg was a massive (≳35 M ⊙) WR star that experienced strong mass loss.« less

Effect of temperature on the fracture toughness in the nuclear reactor pressure vessel steel (SA508-3)

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

Oh, S.W.; Lim, M.B.; Yoon, H.K.

1994-12-31

The elastic-plastic fracture toughness J{sub IC} of the Nuclear Reactor Pressure Vessel Steel (SA508-3) which has high toughness was obtained at three temperatures (room temperature, {minus}20 C, 200 C) using a 1/2 CT specimen. Especially the two methods recommended in ASTM and JSME were compared. It was found that difficulty exists in obtaining J{sub IC} by ASTM R-curve method, while JSME R-curve method yielded good results. The stretched zone width method gave slightly larger J{sub IC} values than those by the R-curve method for SA508-3 steel and the blunting line was not affected by the test temperatures. The relation betweenmore » SZW and J, SZW and J/E and SZW and J/{sigma}{sub ys} before initiation of a stable crack growth in the fracture toughness test at three temperatures is described.« less

Appraisal of phytochemical and in vitro biological attributes of an unexplored folklore: Rhus Punjabensis Stewart.

PubMed

Tabassum, Saira; Ahmed, Madiha; Mirza, Bushra; Naeem, Muhammad; Zia, Muhammad; Shanwari, Zabta Khan; Khan, Gul Majid

2017-03-09

The role of plants for discovery of therapeutic potential accentuates the need to know their biological attributes. The present study aims to comprehend the biological attributes of Rhus punjabensis, an unexplored traditional medicinal plant. Leaf and stem extracts of R. punjabensis prepared in 11 different organic solvents are evaluated for multimode antioxidant potential, total phenolic and flavonoid contents were determined through colorimetric assays, HPLC-DAD analysis was carried out for quantification of various polyphenols in extracts. Brine shrimp lethality, SRB and MTT assays were used to elucidate plant's cytotoxic and antileishmanial potentials. Disc diffusion assay was used to elucidate the protein kinase inhibitory, antibacterial and antifungal spectrum. Ethanol + ethyl acetate yielded maximum extract recovery from leaf (6.11 ± 1.09% w/w), total phenolic content (80.5 ± 2.18 μg GAE/mg extract) and reducing power potential (165.4 ± 2.29 μg AAE/mg extract). Maximum flavonoid content (30.50 ± 1.11 μg QE/mg extract) and highest DPPH based free radical scavenging activity (IC 50 11.4 ± 2.07) was exhibited by the methanol + chloroform leaf extract. The methanol extract showed maximum total antioxidant capacity (74.5 ± 2.25 μg AAE/mg DW), protein kinase inhibitory (12.5 ± 1.10 bald phenotype at 100 μg/disc) and antifungal (MIC = 25 μg/disc against Aspergillus flavus) potential. Reverse phase HPLC-DAD based quantification reveals presence of gallic acid, apigenin, rutin and catechin in various extracts. Brine shrimp lethality assay demonstrated most extracts as highly cytotoxic (LC 50  < 50 μg/mL) whereas chloroform extract of leaf demonstrated maximuminhibition against human leukemia cell line (IC 50 7.80 ± 0.01 μg/mL). A significant activity against leishmanial promastigotes was demonstrated by n-hexane leaf extract (IC 50  = 15.78 ± 0.15 μg/mL). A better antibacterial activity,by the extracts, against Gram positive strains as compared to Gram negative was observed. Results recommend multiple-solvent system as a critical factor to sumptuous the biological prospective of R. punjabensis and propose it to be a useful natural hub for the discovery of novel antioxidant, anticancer, antileishmanial and antimicrobial agents.

Publications - IC 42 | Alaska Division of Geological & Geophysical Surveys

Science.gov Websites

DGGS IC 42 Publication Details Title: Alaska's mineral industry 1996: A summary Authors: Swainbank, R.C ., Bundtzen, T.K., Clough, A.H., and Henning, M.W., 1997, Alaska's mineral industry 1996: A summary: Alaska

40 CFR 51.119 - Intermittent control systems.

Code of Federal Regulations, 2014 CFR

2014-07-01

..., 1970, and was operated as specified by the operating system of the ICS before December 31, 1970. (3... 40 Protection of Environment 2 2014-07-01 2014-07-01 false Intermittent control systems. 51.119... Intermittent control systems. (a) The use of an intermittent control system (ICS) may be taken into account in...

40 CFR 51.119 - Intermittent control systems.

Code of Federal Regulations, 2011 CFR

2011-07-01

..., 1970, and was operated as specified by the operating system of the ICS before December 31, 1970. (3... 40 Protection of Environment 2 2011-07-01 2011-07-01 false Intermittent control systems. 51.119... Intermittent control systems. (a) The use of an intermittent control system (ICS) may be taken into account in...

40 CFR 51.119 - Intermittent control systems.

Code of Federal Regulations, 2012 CFR

2012-07-01

..., 1970, and was operated as specified by the operating system of the ICS before December 31, 1970. (3... 40 Protection of Environment 2 2012-07-01 2012-07-01 false Intermittent control systems. 51.119... Intermittent control systems. (a) The use of an intermittent control system (ICS) may be taken into account in...

40 CFR 51.119 - Intermittent control systems.

Code of Federal Regulations, 2010 CFR

2010-07-01

..., 1970, and was operated as specified by the operating system of the ICS before December 31, 1970. (3... 40 Protection of Environment 2 2010-07-01 2010-07-01 false Intermittent control systems. 51.119... Intermittent control systems. (a) The use of an intermittent control system (ICS) may be taken into account in...

40 CFR 51.119 - Intermittent control systems.

Code of Federal Regulations, 2013 CFR

2013-07-01

..., 1970, and was operated as specified by the operating system of the ICS before December 31, 1970. (3... 40 Protection of Environment 2 2013-07-01 2013-07-01 false Intermittent control systems. 51.119... Intermittent control systems. (a) The use of an intermittent control system (ICS) may be taken into account in...

Biochemical, Cellular, and Biophysical Characterization of a Potent Inhibitor of Mutant Isocitrate Dehydrogenase IDH1*

PubMed Central

Davis, Mindy I.; Gross, Stefan; Shen, Min; Straley, Kimberly S.; Pragani, Rajan; Lea, Wendy A.; Popovici-Muller, Janeta; DeLaBarre, Byron; Artin, Erin; Thorne, Natasha; Auld, Douglas S.; Li, Zhuyin; Dang, Lenny; Boxer, Matthew B.; Simeonov, Anton

2014-01-01

Two mutant forms (R132H and R132C) of isocitrate dehydrogenase 1 (IDH1) have been associated with a number of cancers including glioblastoma and acute myeloid leukemia. These mutations confer a neomorphic activity of 2-hydroxyglutarate (2-HG) production, and 2-HG has previously been implicated as an oncometabolite. Inhibitors of mutant IDH1 can potentially be used to treat these diseases. In this study, we investigated the mechanism of action of a newly discovered inhibitor, ML309, using biochemical, cellular, and biophysical approaches. Substrate binding and product inhibition studies helped to further elucidate the IDH1 R132H catalytic cycle. This rapidly equilibrating inhibitor is active in both biochemical and cellular assays. The (+) isomer is active (IC50 = 68 nm), whereas the (−) isomer is over 400-fold less active (IC50 = 29 μm) for IDH1 R132H inhibition. IDH1 R132C was similarly inhibited by (+)-ML309. WT IDH1 was largely unaffected by (+)-ML309 (IC50 >36 μm). Kinetic analyses combined with microscale thermophoresis and surface plasmon resonance indicate that this reversible inhibitor binds to IDH1 R132H competitively with respect to α-ketoglutarate and uncompetitively with respect to NADPH. A reaction scheme for IDH1 R132H inhibition by ML309 is proposed in which ML309 binds to IDH1 R132H after formation of the IDH1 R132H NADPH complex. ML309 was also able to inhibit 2-HG production in a glioblastoma cell line (IC50 = 250 nm) and had minimal cytotoxicity. In the presence of racemic ML309, 2-HG levels drop rapidly. This drop was sustained until 48 h, at which point the compound was washed out and 2-HG levels recovered. PMID:24668804

Biochemical, cellular, and biophysical characterization of a potent inhibitor of mutant isocitrate dehydrogenase IDH1.

PubMed

Davis, Mindy I; Gross, Stefan; Shen, Min; Straley, Kimberly S; Pragani, Rajan; Lea, Wendy A; Popovici-Muller, Janeta; DeLaBarre, Byron; Artin, Erin; Thorne, Natasha; Auld, Douglas S; Li, Zhuyin; Dang, Lenny; Boxer, Matthew B; Simeonov, Anton

2014-05-16

Two mutant forms (R132H and R132C) of isocitrate dehydrogenase 1 (IDH1) have been associated with a number of cancers including glioblastoma and acute myeloid leukemia. These mutations confer a neomorphic activity of 2-hydroxyglutarate (2-HG) production, and 2-HG has previously been implicated as an oncometabolite. Inhibitors of mutant IDH1 can potentially be used to treat these diseases. In this study, we investigated the mechanism of action of a newly discovered inhibitor, ML309, using biochemical, cellular, and biophysical approaches. Substrate binding and product inhibition studies helped to further elucidate the IDH1 R132H catalytic cycle. This rapidly equilibrating inhibitor is active in both biochemical and cellular assays. The (+) isomer is active (IC50 = 68 nm), whereas the (-) isomer is over 400-fold less active (IC50 = 29 μm) for IDH1 R132H inhibition. IDH1 R132C was similarly inhibited by (+)-ML309. WT IDH1 was largely unaffected by (+)-ML309 (IC50 >36 μm). Kinetic analyses combined with microscale thermophoresis and surface plasmon resonance indicate that this reversible inhibitor binds to IDH1 R132H competitively with respect to α-ketoglutarate and uncompetitively with respect to NADPH. A reaction scheme for IDH1 R132H inhibition by ML309 is proposed in which ML309 binds to IDH1 R132H after formation of the IDH1 R132H NADPH complex. ML309 was also able to inhibit 2-HG production in a glioblastoma cell line (IC50 = 250 nm) and had minimal cytotoxicity. In the presence of racemic ML309, 2-HG levels drop rapidly. This drop was sustained until 48 h, at which point the compound was washed out and 2-HG levels recovered. © 2014 by The American Society for Biochemistry and Molecular Biology, Inc.

Effect of novel negative allosteric modulators of neuronal nicotinic receptors on cells expressing native and recombinant nicotinic receptors: implications for drug discovery.

PubMed

González-Cestari, Tatiana F; Henderson, Brandon J; Pavlovicz, Ryan E; McKay, Susan B; El-Hajj, Raed A; Pulipaka, Aravinda B; Orac, Crina M; Reed, Damon D; Boyd, R Thomas; Zhu, Michael X; Li, Chenglong; Bergmeier, Stephen C; McKay, Dennis B

2009-02-01

Allosteric modulation of nAChRs is considered to be one of the most promising approaches for drug design targeting nicotinic acetylcholine receptors (nAChRs). We have reported previously on the pharmacological activity of several compounds that seem to act noncompetitively to inhibit the activation of alpha3beta4(*) nAChRs. In this study, the effects of 51 structurally similar molecules on native and recombinant alpha3beta4 nAChRs are characterized. These 51 molecules inhibited adrenal neurosecretion activated via stimulation of native alpha3beta4(*) nAChR, with IC(50) values ranging from 0.4 to 13.0 microM. Using cells expressing recombinant alpha3beta4 nAChRs, these molecules inhibited calcium accumulation (a more direct assay to establish nAChR activity), with IC(50) values ranging from 0.7 to 38.2 microM. Radiolabeled nAChR binding studies to orthosteric sites showed no inhibitory activity on either native or recombinant nAChRs. Correlation analyses of the data from both functional assays suggested additional, non-nAChR activity of the molecules. To test this hypothesis, the effects of the drugs on neurosecretion stimulated through non-nAChR mechanisms were investigated; inhibitory effects ranged from no inhibition to 95% inhibition at concentrations of 10 microM. Correlation analyses of the functional data confirmed this hypothesis. Several of the molecules (24/51) increased agonist binding to native nAChRs, supporting allosteric interactions with nAChRs. Computational modeling and blind docking identified a binding site for our negative allosteric modulators near the orthosteric binding site of the receptor. In summary, this study identified several molecules for potential development as negative allosteric modulators and documented the importance of multiple screening assays for nAChR drug discovery.

Effect of Novel Negative Allosteric Modulators of Neuronal Nicotinic Receptors on Cells Expressing Native and Recombinant Nicotinic Receptors: Implications for Drug Discovery

PubMed Central

González-Cestari, Tatiana F.; Henderson, Brandon J.; Pavlovicz, Ryan E.; McKay, Susan B.; El-Hajj, Raed A.; Pulipaka, Aravinda B.; Orac, Crina M.; Reed, Damon D.; Boyd, R. Thomas; Zhu, Michael X.; Li, Chenglong; Bergmeier, Stephen C.; McKay, Dennis B.

2009-01-01

Allosteric modulation of nAChRs is considered to be one of the most promising approaches for drug design targeting nicotinic acetylcholine receptors (nAChRs). We have reported previously on the pharmacological activity of several compounds that seem to act noncompetitively to inhibit the activation of α3β4* nAChRs. In this study, the effects of 51 structurally similar molecules on native and recombinant α3β4 nAChRs are characterized. These 51 molecules inhibited adrenal neurosecretion activated via stimulation of native α3β4* nAChR, with IC50 values ranging from 0.4 to 13.0 μM. Using cells expressing recombinant α3β4 nAChRs, these molecules inhibited calcium accumulation (a more direct assay to establish nAChR activity), with IC50 values ranging from 0.7 to 38.2 μM. Radiolabeled nAChR binding studies to orthosteric sites showed no inhibitory activity on either native or recombinant nAChRs. Correlation analyses of the data from both functional assays suggested additional, non-nAChR activity of the molecules. To test this hypothesis, the effects of the drugs on neurosecretion stimulated through non-nAChR mechanisms were investigated; inhibitory effects ranged from no inhibition to 95% inhibition at concentrations of 10 μM. Correlation analyses of the functional data confirmed this hypothesis. Several of the molecules (24/51) increased agonist binding to native nAChRs, supporting allosteric interactions with nAChRs. Computational modeling and blind docking identified a binding site for our negative allosteric modulators near the orthosteric binding site of the receptor. In summary, this study identified several molecules for potential development as negative allosteric modulators and documented the importance of multiple screening assays for nAChR drug discovery. PMID:18984653

Non-aqueous electrolyte for lithium-ion battery

DOEpatents

Amine, Khalil; Zhang, Lu; Zhang, Zhengcheng

2016-01-26

A substantially non-aqueous electrolyte solution includes an alkali metal salt, a polar aprotic solvent, and an organophosphorus compound of Formula IA, IB, or IC: ##STR00001## where R.sup.1, R.sup.2, R.sup.3 and R.sup.4 are each independently hydrogen, halogen, alkyl, alkenyl, alkynyl, cycloalkyl, aryl, heterocyclyl, heteroaryl, alkoxy, alkenoxy, alkynoxy, cycloalkoxy, aryloxy, heterocyclyloxy, heteroaryloxy, siloxyl, silyl, or organophosphatyl; R.sup.5 and R.sup.6 are each independently alkyl, alkenyl, alkynyl, cycloalkyl, aryl, heterocyclyl, or heteroaryl; R.sup.7 is ##STR00002## and R.sup.8, R.sup.9 and R.sup.10 are each independently alkyl, cycloalkyl, aryl, heterocyclyl, or heteroaryl; provided that if the organophosphorus compound is of Formula IB, then at least one of R.sup.5, and R.sup.6 are other than hydrogen, alkyl, or alkenyl; and if the organophosphorus compound is of Formula IC, then the electrolyte solution does not include 4-methylene-1,3-dioxolan-2-one or 4,5-dimethylene-1,3-dioxolan-2-one.

The anti-cancer activity of a cationic anti-microbial peptide derived from monomers of polyhydroxyalkanoate.

PubMed

O'Connor, Stephen; Szwej, Emilia; Nikodinovic-Runic, Jasmina; O'Connor, Aisling; Byrne, Annette T; Devocelle, Marc; O'Donovan, Norma; Gallagher, William M; Babu, Ramesh; Kenny, Shane T; Zinn, Manfred; Zulian, Qun Ren; O'Connor, Kevin E

2013-04-01

The biodegradable polymer medium chain length polyhydroxyalkanoate (mclPHA), produced by Pseudomonas putida CA-3, was depolymerised and the predominant monomer (R)-3-hydroxydecanoic acid (R10) purified. R10 was conjugated to a d-peptide DP18 and its derivatives. All peptides conjugated with R10 exhibited greater anti-cancer activity compared to the unconjugated peptides. Unconjugated and conjugated peptides were cytocidal for cancer cells. Conjugation of R10 to peptides was essential for enhanced anti-proliferation activity, as unconjugated mixes did not result in enhancement of anti-cancer activity. The conjugation of R10 resulted in more rapid uptake of peptides into HeLa and MiaPaCa cells compared to unconjugated peptide. Both unconjugated and R10 conjugated peptides localized to the mitochondria of HeLa and MiaPaCa cells and induced apoptosis. Peptide conjugated with a terminally hydroxylated decanoic acid (ω-hydroxydecanoic acid) exhibited 3.3 and 6.3 fold higher IC(50) values compared to R10 conjugated peptide indicating a role for the position of the hydroxyl moiety in enhancement of anti-cancer activity. Conjugation of decanoic acid (C10) to peptides resulted in similar or higher IC(50) values compared to R10 conjugates but C10 conjugates did not exhibit any cancer selectivity. Combination studies showed that R10DP18L exhibited synergy with cisplatin, gemcitabine, and taxotere with IC(50) values in the nanomolar range. Copyright © 2013 Elsevier Ltd. All rights reserved.

TrkB Activators for the Treatment of Traumatic Vision Loss

DTIC Science & Technology

2017-06-01

em ( do i: 10 .1 08 9/ ne u. 20 17 .5 10...Im m un e Sy st em ( do i: 10 .1 08 9/ ne u. 20 17 .5 10 4) T hi s ar tic le h as b ee n pe er -r ev ie w ed a nd a cc ep te d fo r pu bl ic...Sy st em ( do i: 10 .1 08 9/ ne u. 20 17 .5 10 4) T hi s ar tic le h as b ee n pe er -r ev ie w ed a nd a cc ep te d fo r pu bl ic at io

All Prime Contract Awards by State or Country, Place, and Contractor, FY 85. Part 14 (Aberdeen, North Carolina - Zanesville, Ohio).

DTIC Science & Technology

1985-01-01

I nr)MC)C) MeM V r I McI ( MV)CI MMCI C I)MC I) (( 4 N) l 1 MC)c) l< 43 I004COOOOOOOOOO)OOOOOOOOO 000 - -0 I WW C’J(WJ W’J(N C𔃾CNIC’IC’J ww C’.IC’IC’J...N)( OhP .0.( 0 <It (n0ON(0a)t- " -. I-boO( 444~~o N- WZ0n((P0~ r.-I (0 0.4 W LP n aN ODNCj)-la)In 014 NII-0000000000000000000 0 LaJo 040000 W0 4000000

Restoration of central nervous system alpha-N-acetylglucosaminidase activity and therapeutic benefits in mucopolysaccharidosis IIIB mice by a single intracisternal recombinant adeno-associated viral type 2 vector delivery.

PubMed

Fu, Haiyan; DiRosario, Julianne; Kang, Lu; Muenzer, Joseph; McCarty, Douglas M

2010-07-01

Finding efficient central nervous system (CNS) delivery approaches has been the major challenge facing therapeutic development for treating diseases with global neurological manifestation, such as mucopolysaccharidosis (MPS) IIIB, a lysosomal storage disease, caused by autosomal recessive defect of alpha-N-acetylglucosaminidase (NaGlu). Previously, we developed an approach, intracisternal (i.c.) injection, to deliver recombinant adeno-associated viral (rAAV) vector to the CNS of mice, leading to a widespread periventricular distribution of transduction. In the present study, we delivered rAAV2 vector expressing human NaGlu into the CNS of MPS IIIB mice by an i.c. injection approach, to test its therapeutic efficacy and feasibility for treating the neurological manifestation of the disease. We demonstrated significant functional neurological benefits of a single i.c. vector infusion in adult MPS IIIB mice. The treatment slowed the disease progression by mediating widespread recombinant NaGlu expression in the CNS, resulting in the reduction of brain lysosomal storage pathology, significantly improved cognitive function and prolonged survival. However, persisting motor function deficits suggested that pathology in areas outside the CNS contributes to the MPS IIIB behavioral phenotype. The therapeutic benefit of i.c. rAAV2 delivery was dose-dependent and could be attribute solely to the CNS transduction because the procedure did not lead to detectable transduction in somatic tissues. A single IC rAAV2 gene delivery is functionally beneficial for treating the CNS disease of MPS IIIB in mice. It is immediately clinically translatable, with the potential of improving the quality of life for patients with MPS IIIB.

Electronic Principles Inventory, Keesler Technical Training Center

DTIC Science & Technology

1990-03-01

60 WC IC.U 06 VL a a OLIL 044 . 4 04V..a .6 IL I ;- acCa LL CL L L0.40 Z .44. 𔃾 C4’. v.W4 W L LL LC .0𔃾 %. a- L4. L .4 -4 L Lc. L 06 %. w 4. aC I...0014L 0 0 0 -.4 0 0 0. 4 4,0 21 0) .4 4, 0 00 0) .m 4 0 w4 00) L. a 0 0 6 00 (4 m 0 CI C c 0 0) f6 0 > Nj -4 ’A .4 WA 4,4,1 4,.L -W IA 4,4 -W 44 - .4...4 1-4 m r4 CY r4 4 :3 x 10 -C Co 10 Ln wl a 10 LA wl N %T N f, %T Ul in (y 4 4 (Y CD N to 0, 0, in La 0 ’r ?% 0, do do F6 0, P% a co 01 Ln r4 N F-4

Publications - IC 57 v. 1.0.1 | Alaska Division of Geological & Geophysical

Science.gov Websites

content DGGS IC 57 v. 1.0.1 Publication Details Title: Alaska's mineral industry 2007: A summary Authors Bibliographic Reference Szumigala, D.J., and Hughes, R.A., 2008, Alaska's mineral industry 2007: A summary

Excitatory, inhibitory and facilitatory frequency response areas in the inferior colliculus of hearing impaired mice.

PubMed

Felix, Richard A; Portfors, Christine V

2007-06-01

Individuals with age-related hearing loss often have difficulty understanding complex sounds such as basic speech. The C57BL/6 mouse suffers from progressive sensorineural hearing loss and thus is an effective tool for dissecting the neural mechanisms underlying changes in complex sound processing observed in humans. Neural mechanisms important for processing complex sounds include multiple tuning and combination sensitivity, and these responses are common in the inferior colliculus (IC) of normal hearing mice. We examined neural responses in the IC of C57Bl/6 mice to single and combinations of tones to examine the extent of spectral integration in the IC after age-related high frequency hearing loss. Ten percent of the neurons were tuned to multiple frequency bands and an additional 10% displayed non-linear facilitation to the combination of two different tones (combination sensitivity). No combination-sensitive inhibition was observed. By comparing these findings to spectral integration properties in the IC of normal hearing CBA/CaJ mice, we suggest that high frequency hearing loss affects some of the neural mechanisms in the IC that underlie the processing of complex sounds. The loss of spectral integration properties in the IC during aging likely impairs the central auditory system's ability to process complex sounds such as speech.

Single-laboratory validation of the microplate receptor binding assay for paralytic shellfish toxins in shellfish.

PubMed

Van Dolah, Frances M; Leighfield, Tod A; Doucette, Gregory J; Bean, Laurie; Niedzwiadek, Barbara; Rawn, Dorothea F K

2009-01-01

A single-laboratory validation (SLV) study was conducted for the microplate receptor binding assay (RBA) for paralytic shellfish poisoning (PSP) toxins in shellfish. The basis of the assay is the competition between [3H]saxitoxin (STX) and STX in a standard or sample for binding to the voltage dependent sodium channel. A calibration curve is generated by the addition of 0.01-1000 nM STX, which results in the concentration dependent decrease in [3H]STX-receptor complexes formed and serves to quantify STX in unknown samples. This study established the LOQ, linearity, recovery, accuracy, and precision of the assay for determining PSP toxicity in shellfish extracts, as performed by a single analyst on multiple days. The standard curve obtained on 5 independent days resulted in a half-maximal inhibition (IC50) of 2.3 nM STX +/- 0.3 (RSD = 10.8%) with a slope of 0.96 +/- 0.06 (RSD = 6.3%) and a dynamic range of 1.2-10.0 nM. The LOQ was 5.3 microg STX equivalents/100 g shellfish. Linearity, established by quantification of three levels of purified STX (1.5, 3, and 6 nM), yielded an r2 of 0.97. Recovery from mussels spiked with three levels (40, 80, and 120 microg STX/100 g) averaged 121%. Repeatability (RSD(r)), determined on six naturally contaminated shellfish samples on 5 independent days, was 17.7%. A method comparison with the AOAC mouse bioassay yielded r2 = 0.98 (slope = 1.29) in the SLV study. The effects of the extraction method on RBA-based toxicity values were assessed on shellfish extracted for PSP toxins using the AOAC mouse bioassay method (0.1 M HCI) compared to that for the precolumn oxidation HPLC method (0.1% acetic acid). The two extraction methods showed linear correlation (r2 = 0.99), with the HCl extraction method yielding slightly higher toxicity values (slope = 1.23). A similar relationship was observed between HPLC quantification of the HCI- and acetic acid-extracted samples (r2 = 0.98, slope 1.19). The RBA also had excellent linear correlation with HPLC analyses (r2 = 0.98 for HCl, r2 = 0.99 for acetic acid), but gave somewhat higher values than HPLC using either extraction method (slope = 1.39 for HCl extracts, slope = 1.32 for acetic acid). Overall, the excellent linear correlations with the both mouse bioassay and HPLC method and sufficient interassay repeatability suggest that the RBA can be effective as a high throughput screen for estimating PSP toxicity in shellfish.

Comparing dynamic hyperinflation and associated dyspnea induced by metronome-paced tachypnea versus incremental exercise.

PubMed

Calligaro, Gregory L; Raine, Richard I; Bateman, Mary E; Bateman, Eric D; Cooper, Christopher B

2014-02-01

Dynamic hyperinflation (DH) during exercise is associated with both dyspnea and exercise limitation in COPD. Metronome-paced tachypnoea (MPT) is a simple alternative for studying DH. We compared MPT with exercise testing (XT) as methods of provoking DH, and assessed their relationship with dyspnea. We studied 24 patients with moderate COPD (FEV1 59 ± 9% predicted) after inhalation of ipratropium/salbutamol combination or placebo in a double-blind, crossover design. Inspiratory capacity (IC) was measured at baseline and after 30 seconds of MPT with breathing frequencies (fR) of 20, 30 and 40 breaths/min and metronome-defined I:E ratios of 1:1 and 1:2, in random sequence, followed by incremental cycle ergometry with interval determinations of IC. DH was defined as a decline in IC from baseline (∆IC) for both methods. Dyspnea was assessed using a Borg CR-10 scale. ∆IC during MPT was greater with higher fR and I:E ratio of 1:1 versus 1:2, and less when patients were treated with bronchodilator rather than placebo (P = 0.032). DH occurred during 19 (40%) XTs, and during 35 (73%) tests using MPT. Eleven of 18 (61%) non-congruent XTs (where DH occurred on MPT but not XT) terminated before fR of 40 breaths/min was reached. Although greater during XT, the intensity of dyspnea bore no relationship to DH during either MPT and XT. MPT at 40 breaths/min and I:E of 1:1 elicits the greatest ∆IC, and is a more sensitive method for demonstrating DH. The relationship between DH and dyspnea is complex and not determined by DH alone.

Traditional Chinese medicine pharmacovigilance in signal detection: decision tree-based data classification.

PubMed

Wei, Jian-Xiang; Wang, Jing; Zhu, Yun-Xia; Sun, Jun; Xu, Hou-Ming; Li, Ming

2018-03-09

Traditional Chinese Medicine (TCM) is a style of traditional medicine informed by modern medicine but built on a foundation of more than 2500 years of Chinese medical practice. According to statistics, TCM accounts for approximately 14% of total adverse drug reaction (ADR) spontaneous reporting data in China. Because of the complexity of the components in TCM formula, which makes it essentially different from Western medicine, it is critical to determine whether ADR reports of TCM should be analyzed independently. Reports in the Chinese spontaneous reporting database between 2010 and 2011 were selected. The dataset was processed and divided into the total sample (all data) and the subsample (including TCM data only). Four different ADR signal detection methods-PRR, ROR, MHRA and IC- currently widely used in China, were applied for signal detection on the two samples. By comparison of experimental results, three of them-PRR, MHRA and IC-were chosen to do the experiment. We designed several indicators for performance evaluation such as R (recall ratio), P (precision ratio), and D (discrepancy ratio) based on the reference database and then constructed a decision tree for data classification based on such indicators. For PRR: R 1 -R 2  = 0.72%, P 1 -P 2  = 0.16% and D = 0.92%; For MHRA: R 1 -R 2  = 0.97%, P 1 -P 2  = 0.20% and D = 1.18%; For IC: R 1 -R 2  = 1.44%, P 2 -P 1  = 4.06% and D = 4.72%. The threshold of R,Pand Dis set as 2%, 2% and 3% respectively. Based on the decision tree, the results are "separation" for PRR, MHRA and IC. In order to improve the efficiency and accuracy of signal detection, we suggest that TCM data should be separated from the total sample when conducting analyses.

Voxel-based statistical analysis of uncertainties associated with deformable image registration

NASA Astrophysics Data System (ADS)

Li, Shunshan; Glide-Hurst, Carri; Lu, Mei; Kim, Jinkoo; Wen, Ning; Adams, Jeffrey N.; Gordon, James; Chetty, Indrin J.; Zhong, Hualiang

2013-09-01

Deformable image registration (DIR) algorithms have inherent uncertainties in their displacement vector fields (DVFs).The purpose of this study is to develop an optimal metric to estimate DIR uncertainties. Six computational phantoms have been developed from the CT images of lung cancer patients using a finite element method (FEM). The FEM generated DVFs were used as a standard for registrations performed on each of these phantoms. A mechanics-based metric, unbalanced energy (UE), was developed to evaluate these registration DVFs. The potential correlation between UE and DIR errors was explored using multivariate analysis, and the results were validated by landmark approach and compared with two other error metrics: DVF inverse consistency (IC) and image intensity difference (ID). Landmark-based validation was performed using the POPI-model. The results show that the Pearson correlation coefficient between UE and DIR error is rUE-error = 0.50. This is higher than rIC-error = 0.29 for IC and DIR error and rID-error = 0.37 for ID and DIR error. The Pearson correlation coefficient between UE and the product of the DIR displacements and errors is rUE-error × DVF = 0.62 for the six patients and rUE-error × DVF = 0.73 for the POPI-model data. It has been demonstrated that UE has a strong correlation with DIR errors, and the UE metric outperforms the IC and ID metrics in estimating DIR uncertainties. The quantified UE metric can be a useful tool for adaptive treatment strategies, including probability-based adaptive treatment planning.

Sub-anesthetic concentrations of (R,S)-ketamine metabolites inhibit acetylcholine-evoked currents in α7 nicotinic acetylcholine receptors

PubMed Central

Moaddel, Ruin; Abdrakhmanova, Galia; Kozak, Joanna; Jozwiak, Krzysztof; Toll, Lawrence; Jimenez, Lucita; Rosenberg, Avraham; Tran, Thao; Xiao, Yingxian; Zarate, Carlos A.; Wainer, Irving W.

2012-01-01

The effect of the (R,S)-ketamine metabolites (R,S)-norketamine, (R,S)-dehydronorketamine, (2S,6S)-hydroxynorketamine and (2R,6R)- hydroxynorketamine on the activity of α7 and α3β4 neuronal nicotinic acetylcholine receptors was investigated using patch-clamp techniques. The data indicated that (R,S)-dehydronorketamine inhibited acetylcholine-evoked currents in α7-nicotinic acetylcholine receptor, IC50 = 55 ± 6 nM, and that (2S,6S)-hydroxynorketamine, (2R,6R)-hydroxynorketamine and (R,S)-norketamine also inhibited α7-nicotinic acetylcholine receptor function at concentrations ≤1μM, while (R,S)-ketamine was inactive at these concentrations. The inhibitory effect of (R,S)-dehydronorketamine was voltage-independent and the compound did not competitively displace selective α7-nicotinic acetylcholine receptor ligands [125I]-α-bungarotoxin and [3H]-epibatidine indicating that (R,S)-dehydronorketamine is a negative allosteric modulator of the α7-nicotinic acetylcholine receptor. (R,S)-Ketamine and (R,S)-norketamine inhibited (S)-nicotine-induced whole-cell currents in cells expressing α3β4-nicotinic acetylcholine receptor, IC50 3.1 and 9.1μM, respectively, while (R,S)-dehydronorketamine, (2S,6S)-hydroxynorketamine and (2R,6R)-hydroxynorketamine were weak inhibitors, IC50 >100μM. The binding affinities of (R,S)-dehydronorketamine, (2S,6S)-hydroxynorketamine and (2R,6R)-hydroxynorketamine at the NMDA receptor were also determined using rat brain membranes and the selective NMDA receptor antagonist [3H]-MK-801. The calculated Ki values were 38.95 μM for (S)-dehydronorketamine, 21.19 μM for (2S,6S)-hydroxynorketamine and > 100 μM for (2R,6R)-hydroxynorketamine. The results suggest that the inhibitory activity of ketamine metabolites at the α7-nicotinic acetylcholine receptor may contribute to the clinical effect of the drug. PMID:23183107

Optical Follow-Up Observations of PTF10qts, a Luminous Broad-Lined Type Ic Supernova Found by the Palomar Transient Factory

NASA Technical Reports Server (NTRS)

Walker, E. S.; Mazzali, P. A.; Pian, E.; Hurley, K.; Arcavi, I.; Cenko, S. B.; Gal-Yam, A.; Horesh, A.; Kasliwal, M.; Poznanski, D.;

High Plasma Concentrations of Zidovudine (AZT) Do Not Parallel Intracellular Concentrations of AZT-Triphosphates in Infants During Prevention of Mother-to-Child HIV-1 Transmission.

PubMed

Kinai, Ei; Kato, Shingo; Hosokawa, Shinichi; Sadatsuki, Miyuki; Gatanaga, Hiroyuki; Kikuchi, Yoshimi; Lam, Nguyen Van; Ha, Do Quan; Kinh, Nguyen Van; Liem, Nguyen Thanh; Oka, Shinichi

2016-07-01

Zidovudine (AZT) is mainly used to prevent mother-to-child HIV-1 transmission (PMTCT). Despite serious concerns on AZT-associated toxicity, there is little information on pharmacokinetics of intracellular AZT metabolites in infants. We conducted a prospective study in 31 HIV-uninfected infants who received AZT for PMTCT. Blood samples were obtained from 14 infants on postdelivery days (PDD) 1, 7, 14, and 28 and from 17 infants at 0 and 4 hours after dosing on PDD-1. Plasma AZT concentrations (pAZT) and intracellular concentrations of AZT-monophosphate (icAZT-MP), diphosphate (icAZT-DP), and triphosphate (icAZT-TP) were determined. Plasma AZT and icAZT-MP concentrations were 2713 nmol/L and 79 fmol/10 cells in PDD-1, but decreased to 1437 nmol/L and 31 fmol/10 cells by PDD-28 (P = 0.02 and P = 0.07 for all PDDs, respectively), whereas those of icAZT-DP and icAZT-TP remained low throughout the sampling period (P = 0.29 and P = 0.61 for all PDDs, respectively) There were no differences in icAZT-TP between infants of the 2 mg/kg 4 times a day dose and 4 mg/kg twice daily dose (P = 0.25), whereas pAZT and icAZT-MP levels were higher in the latter (P < 0.01 and <0.01, respectively). The pAZT and icAZT-MP significantly increased from 0 to 4 hours after dosing (P < 0.001 and <0.001, respectively), whereas icAZT-DP, icAZT-TP levels were not changed (P = 0.41 and 0.33, respectively). The level of icAZT-TP did not change with age, time, or a single dose despite the wide range of pAZT concentration. A safer dosage needs to be determined because high pAZT levels do not parallel those of icAZT-TP.

Re-Usable Thin-Layer Spectroelectrochemical Cell for Non-Aqueous Solvent Systems.

DTIC Science & Technology

1987-11-01

rapidly reassembied. It can be used under 1-gassei .I I. wIII aquleous solution or a variety of comon rg-an Ic 1 ,+.t r . -, 1 1 soivenrts , u( h as o...for 1 days. Lithium chloride (Anachemia, reagent grade) was dried at 12ooC for 24 h. Water was purified by double distillation over KMnO4, foiluwed by...peak to peaK 3eparatiun witn ;r-’ra.in scan rate from Ib mV at lmV/s to lUU mV at lUU mv/. r-eaK IC , ,:.ik ;eparatiurts measured at several scan rates

Overexpression of Pofut1 and activated Notch1 may be associated with poor prognosis in breast cancer.

PubMed

Wan, Guoxing; Tian, Lin; Yu, Yuandong; Li, Fang; Wang, Xuanbin; Li, Chen; Deng, Shouheng; Yu, Xiongjie; Cai, Xiaojun; Zuo, Zhigang; Cao, Fengjun

2017-09-09

The present study was to evaluate the prognostic value of protein expression of Pofut1 and Notch1 signaling in breast cancer. Formalin-fixed paraffin-embedded 314 breast specimens including 174 infiltrating ductal carcinoma(IDC), 50 ductal carcinoma in situ(DCIS) and 90 adjacent normal tissue(ANT) were immunohistochemically examined to evaluate the protein expression of Pofut1, activated Notch1(N1IC) and Slug on specimens. Survival analysis was performed by Kaplan-Meier method and Cox's proportional-hazards model. A online database was computationally used to further explore the prognostic role of Pofut1 and Notch1 mRNA expression by Kaplan-Meier Plotter. Pofut1, Slug and N1IC expression were significantly increased in IDC compared to ANT(all p < 0.05). High expression of Pofut1, Slug and N1IC were associated with tumor aggressiveness including lymph node metastasis (LNM: p = 0.005 for Pofut1, p < 0.001 for N1IC, p = 0.017 for Slug), advanced stage(p = 0.039 for Pofut1, p = 0.025 for N1IC) and higher histological grade(p = 0.001 for N1IC). Additionally, high expression of Pofut1 was found to be significantly associated with high expressions of N1IC and Slug in IDC(r = 0.244, p = 0.001; r = 0.374, p < 0.001, respectively), similar correlation was also observed between high N1IC and Slug expression(r = 0.496, p < 0.001). Moreover, Kaplan-Meier and Cox's regression analysis indicated the significant prognostic value of elevated Pofut1, N1IC, Slug expressions, positive LNM and advanced tumor stage for the prediction of a shorter disease-free survival (DFS) and overall survival(OS). The web-based analysis also suggested a significant association of high Pofut1 and Notch1 mRNA expression with worse survival outcome. Our findings suggested that overexpression of Pofut1 and activated Notch1 signaling may be associated with a poor prognosis in breast cancer. Copyright © 2017 Elsevier Inc. All rights reserved.

Soybean isoflavones ameliorate ischemic cardiomyopathy by activating Nrf2-mediated antioxidant responses.

PubMed

Li, Yang; Zhang, Haiyan

2017-08-01

Ischemic cardiomyopathy (IC) is the major cause of heart failure. Conventional medicine has been proved ineffective with adverse effects. Soybean presents exciting adjunctive therapies and shows protective benefits for IC. However, the molecular mechanisms remain unclear. Isoflavones are the main bioactive components of soybean and may be protective against heart disease. Isoflavones were extracted by using an acidic-ethanol method and analyzed by HPLC. All patients with ischemic stroke were randomly and evenly assigned to two groups: the isoflavone group (80 mg day -1 , n = 100) and control group (80 mg day -1 placebo, n = 100), and the whole period of the experiment was 24 weeks. The effects of soybean isoflavone on brachial flow-mediated dilatation (FMD) were measured. HPLC fractionation shows that isoflavone extracts are mainly composed of 55% genistein, 23% daidzein, and 14% glycitein. Isoflavone therapy reduced more levels of triglyceride and LDL-c in females than in males. FMD was higher in the isoflavone group than in the control group after 24-week therapy (treatment effect 2.0%, 95% CI 0.18-3.0, P = 0.01). The baseline differences were adjusted in FMD and the isoflavone therapies were closely associated with the reduction of FMD impairment at 24 weeks (odds ratio 0.30, 95% CI 0.14-0.85, P = 0.01). The effects of isoflavone on brachial FMD were negatively associated with base FMD (r = -0.65, P < 0.01). Furthermore, isoflavone therapy caused a significant increase in the levels of erythroid-derived 2-like 2 (Nrf2), superoxide dismutase (SOD) and a significant decrease in serum levels of C-reactive protein, 8-isoprostane, malondialdehyde, interleukin-6 and tumor necrosis factor alpha. In contrast, the isoflavones had no effects on the levels of oxidation-related molecules when Nrf2 was silenced. These results suggest that soybean isoflavones ameliorate IC patients by improving their antioxidant capacities via the upregulation of Nrf2.

Toxic mechanisms of 3-monochloropropane-1,2-diol on progesterone production in R2C rat leydig cells.

PubMed

Sun, Jianxia; Bai, Shun; Bai, Weibin; Zou, Feiyan; Zhang, Lei; Su, Zhijian; Zhang, Qihao; Ou, Shiyi; Huang, Yadong

2013-10-16

3-Monochloropropane-1,2-diol (3-MCPD) is a well-known food processing contaminant that has been shown to impede the male reproductive function. However, its mechanism of action remains to be elucidated. In this study, the effects of 3-MCPD on progesterone production were investigated using R2C Leydig cells. 3-MCPD caused concentration-dependent inhibition of cell viability at the IC25, IC50, and IC75 levels of 1.027, 1.802, and 3.160 mM, respectively. Single cell gel/comet assay and atomic force microscopy assay showed that 3-MCPD significantly induced early apoptosis. In addition, 3-MCPD significantly reduced progesterone production by reducing the expression of cytochrome P450 side-chain cleavage enzyme, steroidogenic acute regulatory protein, and 3β-hydroxysteroid dehydrogenase in R2C cells. The change in steroidogenic acute regulatory protein expression was highly consistent with progesterone production. Furthermore, the mitochondrial membrane potential and cAMP significantly decreased.

Potential dual imaging nanoparticle: Gd2O3 nanoparticle

NASA Astrophysics Data System (ADS)

Ahmad, Md. Wasi; Xu, Wenlong; Kim, Sung June; Baeck, Jong Su; Chang, Yongmin; Bae, Ji Eun; Chae, Kwon Seok; Park, Ji Ae; Kim, Tae Jeong; Lee, Gang Ho

2015-02-01

Gadolinium (Gd) is a unique and powerful element in chemistry and biomedicine which can be applied simultaneously to magnetic resonance imaging (MRI), X-ray computed tomography (CT), and neutron capture therapy for cancers. This multifunctionality can be maximized using gadolinium oxide (Gd2O3) nanoparticles (GNPs) because of the large amount of Gd per GNP, making both diagnosis and therapy (i.e., theragnosis) for cancers possible using only GNPs. In this study, the T1 MRI and CT dual imaging capability of GNPs is explored by synthesizing various iodine compound (IC) coated GNPs (IC-GNPs). All the IC-GNP samples showed stronger X-ray absorption and larger longitudinal water proton relaxivities (r1 = 26-38 s-1mM-1 and r2/r1 = 1.4-1.9) than the respective commercial contrast agents. In vivo T1 MR and CT images of mice were also acquired, supporting that the GNP is a potential dual imaging agent.

H-Canyon Recovery Crawler

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

Kriikku, E. M.; Hera, K. R.; Marzolf, A. D.

The Nuclear Material Disposition Project group asked the Savannah River National Lab (SRNL) Research and Development Engineering (R&DE) department to help procure, test, and deploy a remote crawler to recover the 2014 Inspection Crawler (IC) that tipped over in the H-Canyon Air Exhaust Tunnel. R&DE wrote a Procurement Specification for a Recovery Crawler (RC) and SRNS Procurement Department awarded the contract to Power Equipment Manufacturing Inc. (PEM). The PEM RC was based on their standard sewer inspection crawler with custom arms and forks added to the front. The arms and forks would be used to upright the 2014 Inspection Crawler.more » PEM delivered the RC and associated cable reel, 2014 Inspection Crawler mockup, and manuals in late April 2015. R&DE and the team tested the crawler in May of 2015 and made modifications based on test results and Savannah River Site (SRS) requirements. R&DE delivered the RC to H-Area at the end of May. The team deployed the RC on June 9, 10, and 11, 2015 in the H-Canyon Air Exhaust Tunnel. The RC struggled with some obstacles in the tunnel, but eventually made it to the IC. The team spent approximately five hours working to upright the IC and eventually got it on its wheels. The IC travelled approximately 20 feet and struggled to drive over debris on the air tunnel floor. Unfortunately the IC tripped over trying to pass this obstacle. The team decided to leave the IC in this location and inspect the tunnel with the RC. The RC passed the IC and inspected the tunnel as it travelled toward H-Canyon. The team turned the RC around when it was about 20 feet from the H-Canyon crossover tunnel. From that point, the team drove the RC past the manway towards the new sand filter and stopped approximately 20 feet from the new sand filter. The team removed the RC from the tunnel, decontaminated the RC, and stored it the manway building, 294-2H. The RC deployment confirmed the IC was not in a condition to perform useful tunnel inspections and would require significant maintenance to become inspection ready. The RC traveled approximately 660 feet in the tunnel and viewed the tunnel and ceiling wall surfaces that were not blocked by existing ducts. This deployment also documented the tunnel obstacles for future inspections. Overall, the RC deployment was a success.« less

VizieR Online Data Catalog: Gaia DR1 open cluster members (Gaia Collaboration+, 2017)

NASA Astrophysics Data System (ADS)

Gaia Collaboration; van Leeuwen F.; Vallenari, A.; Jordi, C.; Lindegren, L.; Bastian, U.; Prusti, T.; de Bruijne, J. H. J.; Brown, A. G. A.; Babusiaux, C.; Bailer-Jones, C. A. L.; Biermann, M.; Evans, D. W.; Eyer, L.; Jansen, F.; Klioner, S. A.; Lammers, U.; Luri, X.; Mignard, F.; Panem, C.; Pourbaix, D.; Randich, S.; Sartoretti, P.; Siddiqui, H. I.; Soubiran, C.; Valette, V.; Walton, N. A.; Aerts, C.; Arenou, F.; Cropper, M.; Drimmel, R.; Hog, E.; Katz, D.; Lattanzi, M. G.; O'Mullane, W.; Grebel, E. K.; Holland, A. D.; Huc, C.; Passot, X.; Perryman, M.; Bramante, L.; Cacciari, C.; Castaneda, J.; Chaoul, L.; Cheek, N.; de Angeli, F.; Fabricius, C.; Guerra, R.; Hernandez, J.; Jean-Antoine-Piccolo, A.; Masana, E.; Messineo, R.; Mowlavi, N.; Nienartowicz, K.; Ordonez-Blanco, D.; Panuzzo, P.; Portell, J.; Richards, P. J.; Riello, M.; Seabroke, G. M.; Tanga, P.; Thevenin, F.; Torra, J.; Els, S. G.; Gracia-Abril, G.; Comoretto, G.; Garcia-Reinaldos, M.; Lock, T.; Mercier, E.; Altmann, M.; Andrae, R.; Astraatmadja, T. L.; Bellas-Velidis, I.; Benson, K.; Berthier, J.; Blomme, R.; Busso, G.; Carry, B.; Cellino, A.; Clementini, G.; Cowell, S.; Creevey, O.; Cuypers, J.; Davidson, M.; De Ridder, J.; de Torres, A.; Delchambre, L.; Dell'Oro, A.; Ducourant, C.; Fremat, Y.; Garcia-Torres, M.; Gosset, E.; Halbwachs, J.-L.; Hambly, N. C.; Harrison, D. L.; Hauser, M.; Hestroffer, D.; Hodgkin, S. T.; Huckle, H. E.; Hutton, A.; Jasniewicz, G.; Jordan, S.; Kontizas, M.; Korn, A. J.; Lanzafame, A. C.; Manteiga, M.; Moitinho, A.; Muinonen, K.; Osinde, J.; Pancino, E.; Pauwels, T.; Petit, J.-M.; Recio-Blanco, A.; Robin, A. C.; Sarro, L. M.; Siopis, C.; Smith, M.; Smith, K. W.; Sozzetti, A.; Thuillot, W.; van Reeven, W.; Viala, Y.; Abbas, U.; Abreu Aramburu, A.; Accart, S.; Aguado, J. J.; Allan, P. M.; Allasia, W.; Altavilla, G.; Alvarez, M. A.; Alves, J.; Anderson, R. I.; Andrei, A. H.; Anglada Varela, E.; Antiche, E.; Antoja, T.; Anton, S.; Arcay, B.; Bach, N.; Baker, S. G.; Balaguer-Nunez, L.; Barache, C.; Barata, C.; Barbier, A.; Barblan, F.; Barrado, Y. Navascues D.; Barros, M.; Barstow, M. A.; Becciani, U.; Bellazzini, M.; Bello Garcia, A.; Belokuro, V. V.; Ben Djoya, P.; Berihuete, A.; Bianchi, L.; Bienayme, O.; Billebaud, F.; Blagorodnova, N.; Blanco-Cuaresma, S.; Boch, T.; Bombrun, A.; Borrachero, R.; Bouquillon, S.; Bourda, G.; Bouy, H.; Bragaglia, A.; Breddels, M. A.; Brouillet, N.; Bruesemeister, T.; Bucciarelli, B.; Burgess, P.; Burgon, R.; Burlacu, A.; Busonero, D.; Buzzi, R.; Caffau, E.; Cambras, J.; Campbell, H.; Cancelliere, R.; Cantat-Gaudin, T.; Carlucci, T.; Carrasco, J. M.; Castellani, M.; Charlot, P.; Charnas, J.; Chiavassa, A.; Clotet, M.; Cocozza, G.; Collins, R. S.; Costigan, G.; Crifo, F.; Cross, N. J. G.; Crosta, M.; Crowley, C.; Dafonte, C.; Damerdji, Y.; Dapergolas, A.; David, P.; David, M.; De Cat, P.; de Felice, F.; de Laverny, P.; de Luise, F.; de March, R.; de Martino, D.; de Souza, R.; Debosscher, J.; Del Pozo, E.; Delbo, M.; Delgado, A.; Delgado, H. E.; Di Matteo, P.; Diakite, S.; Distefano, E.; Dolding, C.; Dos Anjos, S.; Drazinos, P.; Duran, J.; Dzigan, Y.; Edvardsson, B.; Enke, H.; Evans, N. W.; Eynard Bontemps, G.; Fabre, C.; Fabrizio, M.; Faigler, S.; Falcao, A. J.; Farras Casas, M.; Federici, L.; Fedorets, G.; Fernandez-Hernandez, J.; Fernique, P.; Fienga, A.; Figueras, F.; Filippi, F.; Findeisen, K.; Fonti, A.; Fouesneau, M.; Fraile, E.; Fraser, M.; Fuchs, J.; Gai, M.; Galleti, S.; Galluccio, L.; Garabato, D.; Garcia-Sedano, F.; Garofalo, A.; Garralda, N.; Gavras, P.; Gerssen, J.; Geyer, R.; Gilmore, G.; Girona, S.; Giuffrida, G.; Gomes, M.; Gonzalez-Marcos, A.; Gonzalez-Nunez, J.; Gonzalez-Vidal, J. J.; Granvik, M.; Guerrier, A.; Guillout, P.; Guiraud, J.; Gurpide, A.; Gutierrez-Sanchez, R.; Guy, L. P.; Haigron, R.; Hatzidimitriou, D.; Haywood, M.; Heiter, U.; Helmi, A.; Hobbs, D.; Hofmann, W.; Holl, B.; Holland, G.; Hunt, J. A. S.; Hypki, A.; Icardi, V.; Irwin, M.; Jevardat de Fombelle, G.; Jofre, P.; Jonker, P. G.; Jorissen, A.; Julbe, F.; Karampelas, A.; Kochoska, A.; Kohley, R.; Kolenberg, K.; Kontizas, E.; Koposov, S. E.; Kordopatis, G.; Koubsky, P.; Krone-Martins, A.; Kudryashova, M.; Kull, I.; Bachchan, R. K.; Lacoste-Seris, F.; Lanza, A. F.; Lavigne, J.-B.; Le Poncin-Lafitte, C.; Lebreton, Y.; Lebzelter, T.; Leccia, S.; Lecler, C. N.; Lecoeur-Taibi, I.; Lemaitre, V.; Lenhardt, H.; Leroux, F.; Liao, S.; Licata, E.; Lindstrom, H. E. P.; Lister, T. A.; Livanou, E.; Lobel, A.; Loeffler, W.; Lopez, M.; Lorenz, D.; MacDonald, I.; Magalhaes Fernandes, T.; Managau, S.; Mann, R. G.; Mantelet, G.; Marchal, O.; Marchant, J. M.; Marconi, M.; Marinoni, S.; Marrese, P. M.; Marschalko, G.; Marshall, D. J.; Martin-Fleitas, J. M.; Martino, M.; Mary, N.; Matijevic, G.; Mazeh, T.; McMillan, P. J.; Messina, S.; Michalik, D.; Millar, N. R.; Miranda, B. M. H.; Molina, D.; Molinaro, R.; Molinaro, M.; Molnar, L.; Moniez, M.; Montegriffo, P.; Mor, R.; Mora, A.; Morbidelli, R.; Morel, T.; Morgenthaler, S.; Morris, D.; Mulone, A. F.; Muraveva, T.; Musella, I.; Narbonne, J.; Nelemans, G.; Nicastro, L.; Noval, L.; Ordenovic, C.; Ordieres-Mere, J.; Osborne, P.; Pagani, C.; Pagano, I.; Pailler, F.; Palacin, H.; Palaversa, L.; Parsons, P.; Pecoraro, M.; Pedrosa, R.; Pentikaeinen, H.; Pichon, B.; Piersimoni, A. M.; Pineau, F.-X.; Plachy, E.; Plum, G.; Poujoulet, E.; Prsa, A.; Pulone, L.; Ragaini, S.; Rago, S.; Rambaux, N.; Ramos-Lerate, M.; Ranalli, P.; Rauw, G.; Read, A.; Regibo, S.; Reyle, C.; Ribeiro, R. A.; Rimoldini, L.; Ripepi, V.; Riva, A.; Rixon, G.; Roelens, M.; Romero-Gomez, M.; Rowell, N.; Royer, F.; Ruiz-Dern, L.; Sadowski, G.; Sagrista Selles, T.; Sahlmann, J.; Salgado, J.; Salguero, E.; Sarasso, M.; Savietto, H.; Schultheis, M.; Sciacca, E.; Segol, M.; Segovia, J. C.; Segransan, D.; Shih, I.-C.; Smareglia, R.; Smart, R. L.; Solano, E.; Solitro, F.; Sordo, R.; Soria Nieto, S.; Souchay, J.; Spagna, A.; Spoto, F.; Stampa, U.; Steele, I. A.; Steidelmueller, H.; Stephenson, C. A.; Stoev, H.; Suess, F. F.; Sueveges, M.; Surdej, J.; Szabados, L.; Szegedi-Elek, E.; Tapiador, D.; Taris, F.; Tauran, G.; Taylor, M. B.; Teixeira, R.; Terrett, D.; Tingley, B.; Trager, S. C.; Turon, C.; Ulla, A.; Utrilla, E.; Valentini, G.; van Elteren, A.; van Hemelryck, E.; Vanleeuwen, M.; Varadi, M.; Vecchiato, A.; Veljanoski, J.; Via, T.; Vicente, D.; Vogt, S.; Voss, H.; Votruba, V.; Voutsinas, S.; Walmsley, G.; Weiler, M.; Weingrill, K.; Wevers, T.; Wyrzykowski, L.; Yoldas, A.; Zerjal, M.; Zucker, S.; Zurbach, C.; Zwitter, T.; Alecu, A.; Allen, M.; Allende Prieto, C.; Amorim, A.; Anglada-Escude, G.; Arsenijevic, V.; Azaz, S.; Balm, P.; Beck, M.; Bernstein, H.-H.; Bigot, L.; Bijaoui, A.; Blasco, C.; Bonfigli, M.; Bono, G.; Boudreault, S.; Bressan, A.; Brown, S.; Brunet, P.-M.; Bunclark, P.; Buonanno, R.; Butkevich, A. G.; Carret, C.; Carrion, C.; Chemin, L.; Chereau, F.; Corcione, L.; Darmigny, E.; de Boer, K. S.; de Teodoro, P.; de Zeeuw, P. T.; Delle Luche, C.; Domingues, C. D.; Dubath, P.; Fodor, F.; Frezouls, B.; Fries, A.; Fustes, D.; Fyfe, D.; Gallardo, E.; Gallegos, J.; Gardiol, D.; Gebran, M.; Gomboc, A.; Gomez, A.; Grux, E.; Gueguen, A.; Heyrovsky, A.; Hoar, J.; Iannicola, G.; Isasi Parache, Y.; Janotto, A.-M.; Joliet, E.; Jonckheere, A.; Keil, R.; Kim, D.-W.; Klagyivik, P.; Klar, J.; Knude, J.; Kochukhov, O.; Kolka, I.; Kos, J.; Kutka, A.; Lainey, V.; Lebouquin, D.; Liu, C.; Loreggia, D.; Makarov, V. V.; Marseille, M. G.; Martayan, C.; Martinez-Rubi, O.; Massart, B.; Meynadier, F.; Mignot, S.; Munari, U.; Nguyen, A.-T.; Nordlander, T.; O'Flaherty, K. S.; Ocvirk, P.; Olias Sanz, A.; Ortiz, P.; Osorio, J.; Oszkiewicz, D.; Ouzounis, A.; Palmer, M.; Park, P.; Pasquato, E.; Peltzer, C.; Peralta, J.; Peturaud, F.; Pieniluoma, T.; Pigozzi, E.; Poels, J.; Prat, G.; Prod'homme, T.; Raison, F.; Rebordao, J. M.; Risquez, D.; Rocca-Volmerange, B.; Rosen, S.; Ruiz-Fuertes, M. I.; Russo, F.; Sembay, S.; Serraller Vizcaino, I.; Short, A.; Siebert, A.; Silva, H.; Sinachopoulos, D.; Slezak, E.; Soffel, M.; Sosnowska, D.; Straizys, V.; Ter Linden, M.; Terrell, D.; Theil, S.; Tiede, C.; Troisi, L.; Tsalmantza, P.; Tur, D.; Vaccari, M.; Vachier, F.; Valles, P.; van Hamme, W.; Veltz, L.; Virtanen, J.; Wallut, J.-M.; Wichmann, R.; Wilkinson, M. I.; Ziaeepour, H.; Zschocke, S.

2017-04-01

We have determined and examined the astrometric data for 19 open clusters, ranging from the Hyades at just under 47pc to NGC 2422 at nearly 440pc. The clusters are : the Hyades, Coma Berenices, the Pleiades, Praesepe, alpha Per, IC 2391, IC 2602, Blanco 1, NGC 2451, NGC 6475, NGC 7092, NGC 2516, NGC 2232, IC 4665, NGC 6633, Collinder 140, NGC 2422, NGC 3532 and NGC 2547. (2 data files).

Synthesis and exploration of novel curcumin analogues as anti-malarial agents.

PubMed

Mishra, Satyendra; Karmodiya, Krishanpal; Surolia, Namita; Surolia, Avadhesha

2008-03-15

Curcumin, a major yellow pigment and active component of turmeric, has been shown to possess anti-inflammatory and anti-cancer activities. Recent studies have indicated that curcumin inhibits chloroquine-sensitive (CQ-S) and chloroquine-resistant (CQ-R) Plasmodium falciparum growth in culture with an IC(50) of approximately 3.25 microM (MIC=13.2 microM) and IC(50) 4.21 microM (MIC=14.4 microM), respectively. In order to expand their potential as anti-malarials a series of novel curcumin derivatives were synthesized and evaluated for their ability to inhibit P. falciparum growth in culture. Several curcumin analogues examined show more effective inhibition of P. falciparum growth than curcumin. The most potent curcumin compounds 3, 6, and 11 were inhibitory for CQ-S P. falciparum at IC(50) of 0.48, 0.87, 0.92 microM and CQ-R P. falciparum at IC(50) of 0.45 microM, 0.89, 0.75 microM, respectively. Pyrazole analogue of curcumin (3) exhibited sevenfold higher anti-malarial potency against CQ-S and ninefold higher anti-malarial potency against CQ-R. Curcumin analogues described here represent a novel class of highly selective P. falciparum inhibitors and promising candidates for the design of novel anti-malarial agents.

Heterostructure-based high-speed/high-frequency electronic circuit applications

NASA Astrophysics Data System (ADS)

Zampardi, P. J.; Runge, K.; Pierson, R. L.; Higgins, J. A.; Yu, R.; McDermott, B. T.; Pan, N.

1999-08-01

With the growth of wireless and lightwave technologies, heterostructure electronic devices are commodity items in the commercial marketplace [Browne J. Power-amplifier MMICs drive commercial circuits. Microwaves & RF, 1998. p. 116-24.]. In particular, HBTs are an attractive device for handset power amplifiers at 900 MHz and 1.9 GHz for CDMA applications [Lum E. GaAs technology rides the wireless wave. Proceedings of the 1997 GaAs IC Symposium, 1997. p. 11-13; "Rockwell Ramps Up". Compound Semiconductor, May/June 1997.]. At higher frequencies, both HBTs and p-HEMTs are expected to dominate the marketplace. For high-speed lightwave circuit applications, heterostructure based products on the market for OC-48 (2.5 Gb/s) and OC-192 (10 Gb/s) are emerging [http://www.nb.rockwell.com/platforms/network_access/nahome.html#5.; http://www.nortel.com/technology/opto/receivers/ptav2.html.]. Chips that operate at 40 Gb/ have been demonstrated in a number of research laboratories [Zampardi PJ, Pierson RL, Runge K, Yu R, Beccue SM, Yu J, Wang KC. hybrid digital/microwave HBTs for >30 Gb/s optical communications. IEDM Technical Digest, 1995. p. 803-6; Swahn T, Lewin T, Mokhtari M, Tenhunen H, Walden R, Stanchina W. 40 Gb/s 3 Volt InP HBT ICs for a fiber optic demonstrator system. Proceedings of the 1996 GaAs IC Symposium, 1996. p. 125-8; Suzuki H, Watanabe K, Ishikawa K, Masuda H, Ouchi K, Tanoue T, Takeyari R. InP/InGaAs HBT ICs for 40 Gbit/s optical transmission systems. Proceedings of the 1997 GaAs IC Symposium, 1997. p. 215-8]. In addition to these two markets, another area where heterostructure devices are having significant impact is for data conversion [Walden RH. Analog-to digital convertor technology comparison. Proceedings of the 1994 GaAs IC Symposium, 1994. p. 217-9; Poulton K, Knudsen K, Corcoran J, Wang KC, Nubling RB, Chang M-CF, Asbeck PM, Huang RT. A 6-b, 4 GSa/s GaAs HBT ADC. IEEE J Solid-State Circuits 1995;30:1109-18; Nary K, Nubling R, Beccue S, Colleran W, Penney J, Wang KC. An 8-bit, 2 gigasample per second analog to digital converter. Proceedings of the 1995 GaAs IC Symposium, 1995. p. 303-6.]. In this paper, we will discuss the present and future trends of heterostructure device applications to these areas.

Desformylflustrabromine (dFBr) and [3H]dFBr-Labeled Binding Sites in a Nicotinic Acetylcholine Receptor

PubMed Central

Hamouda, Ayman K.; Wang, Ze-Jun; Stewart, Deirdre S.; Jain, Atul D.; Glennon, Richard A.

2015-01-01

Desformylflustrabromine (dFBr) is a positive allosteric modulator (PAM) of α4β2 and α2β2 nAChRs that, at concentrations >1 µM, also inhibits these receptors and α7 nAChRs. However, its interactions with muscle-type nAChRs have not been characterized, and the locations of its binding site(s) in any nAChR are not known. We report here that dFBr inhibits human muscle (αβεδ) and Torpedo (αβγδ) nAChR expressed in Xenopus oocytes with IC50 values of ∼1 μM. dFBr also inhibited the equilibrium binding of ion channel blockers to Torpedo nAChRs with higher affinity in the nAChR desensitized state ([3H]phencyclidine; IC50 = 4 μM) than in the resting state ([3H]tetracaine; IC50 = 60 μM), whereas it bound with only very low affinity to the ACh binding sites ([3H]ACh, IC50 = 1 mM). Upon irradiation at 312 nm, [3H]dFBr photoincorporated into amino acids within the Torpedo nAChR ion channel with the efficiency of photoincorporation enhanced in the presence of agonist and the agonist-enhanced photolabeling inhibitable by phencyclidine. In the presence of agonist, [3H]dFBr also photolabeled amino acids in the nAChR extracellular domain within binding pockets identified previously for the nonselective nAChR PAMs galantamine and physostigmine at the canonical α-γ interface containing the transmitter binding sites and at the noncanonical δ-β subunit interface. These results establish that dFBr inhibits muscle-type nAChR by binding in the ion channel and that [3H]dFBr is a photoaffinity probe with broad amino acid side chain reactivity. PMID:25870334

Knee Proprioception and Strength and Landing Kinematics During a Single-Leg Stop-Jump Task

PubMed Central

Nagai, Takashi; Sell, Timothy C; House, Anthony J; Abt, John P; Lephart, Scott M

2013-01-01

Context The importance of the sensorimotor system in maintaining a stable knee joint has been recognized. As individual entities, knee-joint proprioception, landing kinematics, and knee muscles play important roles in functional joint stability. Preventing knee injuries during dynamic tasks requires accurate proprioceptive information and adequate muscular strength. Few investigators have evaluated the relationship between knee proprioception and strength and landing kinematics. Objective To examine the relationship between knee proprioception and strength and landing kinematics. Design Cross-sectional study. Setting University research laboratory. Patients or Other Participants Fifty physically active men (age = 26.4 ± 5.8 years, height = 176.5 ± 8.0 cm, mass = 79.8 ± 16.6 kg). Intervention(s) Three tests were performed. Knee conscious proprioception was evaluated via threshold to detect passive motion (TTDPM). Knee strength was evaluated with a dynamometer. A 3-dimensional biomechanical analysis of a single-legged stop-jump task was used to calculate initial contact (IC) knee-flexion angle and knee-flexion excursion. Main Outcome Measure(s) The TTDPM toward knee flexion and extension, peak knee flexion and extension torque, and IC knee-flexion angle and knee flexion excursion. Linear correlation and stepwise multiple linear regression analyses were used to evaluate the relationships of both proprioception and strength against landing kinematics. The α level was set a priori at .05. Results Enhanced TTDPM and greater knee strength were positively correlated with greater IC knee-flexion angle (r range = 0.281–0.479, P range = .001–.048). The regression analysis revealed that 27.4% of the variance in IC knee-flexion angle could be accounted for by knee-flexion peak torque and TTDPM toward flexion (P = .001). Conclusions The current research highlighted the relationship between knee proprioception and strength and landing kinematics. Individuals with enhanced proprioception and muscular strength had better control of IC knee-flexion angle during a dynamic task. PMID:23672323

The Bruton tyrosine kinase inhibitor PCI-32765 ameliorates autoimmune arthritis by inhibition of multiple effector cells

PubMed Central

2011-01-01

Introduction The aim was to determine the effect of the Bruton tyrosine kinase (Btk)-selective inhibitor PCI-32765, currently in Phase I/II studies in lymphoma trials, in arthritis and immune-complex (IC) based animal models and describe the underlying cellular mechanisms. Methods PCI-32765 was administered in a series of murine IC disease models including collagen-induced arthritis (CIA), collagen antibody-induced arthritis (CAIA), reversed passive anaphylactic reaction (RPA), and passive cutaneous anaphylaxis (PCA). Clinical and pathologic features characteristic of each model were examined following treatment. PCI-32765 was then examined in assays using immune cells relevant to the pathogenesis of arthritis, and where Btk is thought to play a functional role. These included proliferation and calcium mobilization in B cells, cytokine and chemokine production in monocytes/macrophages, degranulation of mast cells and its subsequent cytokine/chemokine production. Results PCI-32765 dose-dependently and potently reversed arthritic inflammation in a therapeutic CIA model with an ED50 of 2.6 mg/kg/day. PCI-32765 also prevented clinical arthritis in CAIA models. In both models, infiltration of monocytes and macrophages into the synovium was completely inhibited and importantly, the bone and cartilage integrity of the joints were preserved. PCI-32765 reduced inflammation in the Arthus and PCA assays. In vitro, PCI-32765 inhibited BCR-activated primary B cell proliferation (IC50 = 8 nM). Following FcγR stimulation, PCI-32765 inhibited TNFα, IL-1β and IL-6 production in primary monocytes (IC50 = 2.6, 0.5, 3.9 nM, respectively). Following FcεRI stimulation of cultured human mast cells, PCI-32765 inhibited release of histamine, PGD2, TNF-α, IL-8 and MCP-1. Conclusions PCI-32765 is efficacious in CIA, and in IC models that do not depend upon autoantibody production from B cells. Thus PCI-32765 targets not only B lymphocytes but also monocytes, macrophages and mast cells, which are important Btk-expressing effector cells in arthritis. PMID:21752263

EVIDENCE FOR A COMPACT WOLF-RAYET PROGENITOR FOR THE TYPE Ic SUPERNOVA PTF 10vgv

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

Corsi, A.; Ofek, E. O.; Gal-Yam, A.

We present the discovery of PTF 10vgv, a Type Ic supernova (SN) detected by the Palomar Transient Factory, using the Palomar 48 inch telescope (P48). R-band observations of the PTF 10vgv field with P48 probe the SN emission from its very early phases (about two weeks before R-band maximum) and set limits on its flux in the week prior to the discovery. Our sensitive upper limits and early detections constrain the post-shock-breakout luminosity of this event. Via comparison to numerical (analytical) models, we derive an upper-limit of R {approx}< 4.5 R{sub Sun} (R {approx}< 1 R{sub Sun }) on themore » radius of the progenitor star, a direct indication in favor of a compact Wolf-Rayet star. Applying a similar analysis to the historical observations of SN 1994I yields R {approx}< 1/4 R{sub Sun} for the progenitor radius of this SN.« less

Josephson current in ballistic graphene Corbino disk

NASA Astrophysics Data System (ADS)

Abdollahipour, Babak; Mohammadkhani, Ramin; Khalilzadeh, Mina

2018-06-01

We solve Dirac-Bogoliubov-De-Gennes (DBdG) equation in a superconductor-normal graphene-superconductor (SGS) junction with Corbino disk structure to investigate the Josephson current through this junction. We find that the critical current Ic has a nonzero value at Dirac point in which the concentration of the carriers is zero. We show this nonzero critical current depends on the system geometry and it decreases monotonically to zero by decreasing the ratio of the inner to outer radii of the Corbino disk (R1 /R2), while in the limit of R1 /R2 → 1 it scales like a diffusive Corbino disk. The product of the critical current and the normal-state resistance IcRN increases by increasing R1 /R2 and attains the same value for the wide and short rectangular structure at the limit of R1 /R2 → 1 at zero doping. These results reveals the pseudodiffusive behavior of the graphene Corbino Josephson junction similar to the rectangular structure at the zero doping.

[Influence of the DNA integrity of optimized sperm on the embryonic development and clinical outcomes of in vitro fertilization and embryo transfer].

PubMed

Jiang, Wei-jie; Jin, Fan; Zhou, Li-ming

2016-05-01

To investigate the influence of the DNA integrity of optimized sperm on the embryonic development and clinical outcomes of in vitro fertilization and embryo transfer (IVF-ET). This study included 605 cycles of conventional IVF-ET for pure oviductal infertility performed from January 1, 2013 to December 31, 2014. On the day of retrieval, we examined the DNA integrity of the sperm using the sperm chromatin dispersion method. According to the ROC curve and Youden index, we grouped the cycles based on the sperm DNA fragmentation index (DFI) threshold value for predicting implantation failure, early miscarriage, and fertilization failure, followed by analysis of the correlation between DFI and the outcomes of IVF-ET. According to the DFI threshold values obtained, the 605 cycles fell into four groups (DFI value < 5%, 5-10%, 10-15%, and ≥ 15%). Statistically significant differences were observed among the four groups in the rates of fertilization, cleavage, high-quality embryo, implantation, clinical pregnancy, early miscarriage, and live birth (P < 0.05), but not in the rates of multiple pregnancy, premature birth, and low birth weight (P > 0.05). DFI was found to be correlated negatively with the rates of fertilization (r = -0.32, P < 0.01), cleavage (r = -0.19, P < 0.01), high-quality embryo (r = -0.40, P < 0.01), clinical pregnancy (r = -0.20, P < 0.01), and live birth (r = -0.09 P = 0.04), positively with the rate of early miscarriage (r = 0.23, P < 0.01), but not with the rates of multiple pregnancy (r = -0.01, P = 0.83), premature birth (r = 0.04, P = 0.54), and low birth weight (r = 0.03, P = 0.62). The DNA integrity of optimized sperm influences fertilization, embryonic development, early miscarriage, and live birth of IVF-ET, but its correlation with premature birth and low birth weight has to be further studied.

Evaluation of 111In-Labeled Cyclic RGD Peptides: Effects of Peptide and Linker Multiplicity on Their Tumor Uptake, Excretion Kinetics and Metabolic Stability

PubMed Central

Shi, Jiyun; Zhou, Yang; Chakraborty, Sudipta; Kim, Young-Seung; Jia, Bing; Wang, Fan; Liu, Shuang

2011-01-01

Purpose: The purpose of this study was to demonstrate the valence of cyclic RGD peptides, P-RGD (PEG4-c(RGDfK): PEG4 = 15-amino-4,710,13-tetraoxapentadecanoic acid), P-RGD2 (PEG4-E[c(RGDfK)]2, 2P-RGD4 (E{PEG4-E[c(RGDfK)]2}2, 2P4G-RGD4 (E{PEG4-E[G3-c(RGDfK)]2}2: G3 = Gly-Gly-Gly) and 6P-RGD4 (E{PEG4-E[PEG4-c(RGDfK)]2}2) in binding to integrin αvβ3, and to assess the impact of peptide and linker multiplicity on biodistribution properties, excretion kinetics and metabolic stability of their corresponding 111In radiotracers. Methods: Five new RGD peptide conjugates (DOTA-P-RGD (DOTA =1,4,7,10-tetraazacyclododecane-1,4,7,10-tetracetic acid), DOTA-P-RGD2, DOTA-2P-RGD4, DOTA-2P4G-RGD4, DOTA-6P-RGD4), and their 111In complexes were prepared. The integrin αvβ3 binding affinity of cyclic RGD conjugates were determined by a competitive displacement assay against 125I-c(RGDyK) bound to U87MG human glioma cells. Biodistribution, planar imaging and metabolism studies were performed in athymic nude mice bearing U87MG human glioma xenografts. Results: The integrin αvβ3 binding affinity of RGD conjugates follows the order of: DOTA-6P-RGD4 (IC50 = 0.3 ± 0.1 nM) ~ DOTA-2P4G-RGD4 (IC50 = 0.2 ± 0.1 nM) ~ DOTA-2P-RGD4 (IC50 = 0.5 ± 0.1 nM) > DOTA-3P-RGD2 (DOTA-PEG4-E[PEG4-c(RGDfK)]2: IC50 = 1.5 ± 0.2 nM) > DOTA-P-RGD2 (IC50 = 5.0 ± 1.0 nM) >> DOTA-P-RGD (IC50 = 44.3 ± 3.5 nM) ~ c(RGDfK) (IC50 = 49.9 ± 5.5 nM) >> DOTA-6P-RGK4 (IC50 = 437 ± 35 nM). The fact that DOTA-6P-RGK4 had much lower integrin αvβ3 binding affinity than DOTA-6P-RGD4 suggests that the binding of DOTA-6P-RGD4 to integrin αvβ3 is RGD-specific. This conclusion is consistent with the lower tumor uptake for 111In(DOTA-6P-RGK4) than that for 111In(DOTA-6P-RGD4). It was also found that the G3 and PEG4 linkers between RGD motifs have a significant impact on the integrin αvβ3-targeting capability, biodistribution characteristics, excretion kinetics and metabolic stability of 111In-labeled cyclic RGD peptides. Conclusion: On the basis of their integrin αvβ3 binding affinity and tumor uptake of their corresponding 111In radiotracers, it was conclude that 2P-RGD4, 2P4G-RGD4 and 6P-RGD4 are most likely bivalent in binding to integrin αvβ3, and extra RGD motifs might contribute to the long tumor retention times of 111In(DOTA-2P-RGD4), 111In(DOTA-2P4G-RGD4) and 111In(DOTA-6P-RGD4) than that of 111In(DOTA-3P-RGD3) at 72 h p.i. Among the 111In-labeled cyclic RGD tetramers evaluated in the glioma model, 111In(DOTA-2P4G-RGD4) has very high tumor uptake with the best tumor/kidney and tumor/liver ratios, suggesting that 90Y(DOTA-2P4G-RGD4) and 177Lu(DOTA-2P4G-RGD4) might have the potential for targeted radiotherapy of integrin αvβ3-positive tumors. PMID:21850213

Synthesis and anti-parasitic activity of a novel quinolinone-chalcone series.

PubMed

Roussaki, Marina; Hall, Belinda; Lima, Sofia Costa; da Silva, Anabela Cordeiro; Wilkinson, Shane; Detsi, Anastasia

2013-12-01

A series of novel quinolinone-chalcone hybrids and analogues were designed, synthesized and their biological activity against the mammalian stages of Trypanosoma brucei and Leishmania infantum evaluated. Promising molecular scaffolds with significant microbicidal activity and low cytotoxicity were identified. Quinolinone-chalcone 10 exhibited anti-parasitic properties against both organisms, being the most potent anti-L. infantum agent of the entire series (IC50 value of 1.3±0.1 μM). Compounds 4 and 11 showed potency toward the intracellular, amastigote stage of L. infantum (IC50 values of 2.1±0.6 and 3.1±1.05 μM, respectively). Promising trypanocidal compounds include 5 and 10 (IC50 values of 2.6±0.1 and 3.3±0.1 μM, respectively) as well as 6 and 9 (both having IC50 values of <5 μM). Chemical modifications on the quinolinone-chalcone scaffold were performed on selected compounds in order to investigate the influence of these structural features on antiparasitic activity. Copyright © 2013 Elsevier Ltd. All rights reserved.

Structure Guided Chemical Modifications of Propylthiouracil Reveal Novel Small Molecule Inhibitors of Cytochrome b5 Reductase 3 That Increase Nitric Oxide Bioavailability*

PubMed Central

Rahaman, Md. Mizanur; Reinders, Fabio G.; Koes, David; Nguyen, Anh T.; Mutchler, Stephanie M.; Sparacino-Watkins, Courtney; Alvarez, Roger A.; Miller, Megan P.; Cheng, Dongmei; Chen, Bill B.; Jackson, Edwin K.; Camacho, Carlos J.; Straub, Adam C.

2015-01-01

NADH cytochrome b5 reductase 3 (CYB5R3) is critical for reductive reactions such as fatty acid elongation, cholesterol biosynthesis, drug metabolism, and methemoglobin reduction. Although the physiological and metabolic importance of CYB5R3 has been established in hepatocytes and erythrocytes, emerging investigations suggest that CYB5R3 is critical for nitric oxide signaling and vascular function. However, advancement toward fully understanding CYB5R3 function has been limited due to a lack of potent small molecule inhibitors. Because of this restriction, we modeled the binding mode of propylthiouracil, a weak inhibitor of CYB5R3 (IC50 = ∼275 μm), and used it as a guide to predict thiouracil-biased inhibitors from the set of commercially available compounds in the ZINC database. Using this approach, we validated two new potent derivatives of propylthiouracil, ZINC05626394 (IC50 = 10.81 μm) and ZINC39395747 (IC50 = 9.14 μm), both of which inhibit CYB5R3 activity in cultured cells. Moreover, we found that ZINC39395747 significantly increased NO bioavailability in renal vascular cells, augmented renal blood flow, and decreased systemic blood pressure in response to vasoconstrictors in spontaneously hypertensive rats. These compounds will serve as a new tool to examine the biological functions of CYB5R3 in physiology and disease and also as a platform for new drug development. PMID:26001785

Sirolimus induces apoptosis and reverses multidrug resistance in human osteosarcoma cells in vitro via increasing microRNA-34b expression.

PubMed

Zhou, Yan; Zhao, Rui-hua; Tseng, Kuo-fu; Li, Kun-peng; Lu, Zhi-gang; Liu, Yuan; Han, Kun; Gan, Zhi-hua; Lin, Shu-chen; Hu, Hai-yan; Min, Da-liu

2016-04-01

Multi-drug resistance poses a critical bottleneck in chemotherapy. Given the up-regulation of mTOR pathway in many chemoresistant cancers, we examined whether sirolimus (rapamycin), a first generation mTOR inhibitor, might induce human osteosarcoma (OS) cell apoptosis and increase the sensitivity of OS cells to anticancer drugs in vitro. Human OS cell line MG63/ADM was treated with sirolimus alone or in combination with doxorubicin (ADM), gemcitabine (GEM) or methotrexate (MTX). Cell proliferation and apoptosis were detected using CCK-8 assay and flow cytometry, respectively. MiRNAs in the cells were analyzed with miRNA microarray. The targets of miR-34b were determined based on TargetScan analysis and luciferase reporter assays. The expression of relevant mRNA and proteins was measured using qRT-PCR and Western blotting. MiR-34, PAK1 and ABCB1 levels in 40 tissue samples of OS patients were analyzed using qRT-PCR and in situ hybridization assays. Sirolimus (1-100 nmol/L) dose-dependently suppressed the cell proliferation (IC50=23.97 nmol/L) and induced apoptosis. Sirolimus (10 nmol/L) significantly sensitized the cells to anticancer drugs, leading to decreased IC50 values of ADM, GEM and MTX (from 25.48, 621.41 and 21.72 μmol/L to 4.93, 73.92 and 6.77 μmol/L, respectively). Treatment of with sirolimus increased miR-34b levels by a factor of 7.5 in the cells. Upregulation of miR-34b also induced apoptosis and increased the sensitivity of the cells to the anticancer drugs, whereas transfection with miR-34b-AMO, an inhibitor of miR-34b, reversed the anti-proliferation effect of sirolimus. Two key regulators of cell cycle, apoptosis and multiple drug resistance, PAK1 and ABCB1, were demonstrated to be the direct targets of miR-34b. In 40 tissue samples of OS patients, significantly higher miR-34 ISH score and lower PAK5 and ABCB1 scores were detected in the chemo-sensitive group. Sirolimus increases the sensitivity of human OS cells to anticancer drugs in vitro by up-regulating miR-34b interacting with PAK1 and ABCB1. A low miR-34 level is an indicator of poor prognosis in OS patients.

In vitro propagation of the medicinal plant Ziziphora tenuior L. and evaluation of its antioxidant activity

PubMed Central

Dakah, Abdulkarim; Zaid, Salim; Suleiman, Mohamad; Abbas, Sami; Wink, Michael

2014-01-01

Ziziphora tenuior L. (Lamiaceae) is an aromatic herb used for its medicinal values against fungi, bacteria. Micropropagation can be used for large-scale multiplication of essential oil producing plants thus avoiding an overexploitation of natural resources. This work aims to develop a reliable protocol for the in vitro propagation of Z. tenuior, and to compare the antioxidant activity between in vitro propagated and wild plants. The explants were sterilized and cultured on MS medium containing different concentrations of growth regulators naphthalene acetic acid (NAA) or indole-3-butyric acid (IBA) with 0.5 mg/L of kinetin (Kin) callus formation was 70.2% after 45 days of incubation in dark on medium supplemented with 1.5 mg/L of NAA. After one month of callus culture on medium supplemented with 2 mg/L BA the shoot number was 5.12 and for the multiplication stage. The shoot number was 4.21 and length was 6.17 cm on medium supplemented with 1 mg/L Kin + 0.1 mg/L NAA. DPPH• reagent was used to test the antioxidant activity. The aqueous and methanol extracts of in vitro plants which were treated with 1.5 and 1 mg/L of kin plus 0.1 mg/L of NAA showed a strong DPPH• scavenging activity where IC50 was 0.307 and 0.369 mg/ml, respectively, while the IC50 of aqueous and methanol extracts of wild plants was 0.516 and 9.229 mg/ml, respectively. Our results suggested that plant growth regulators and in vitro culture conditions increased the antioxidant activity. PMID:25183942

In vitro propagation of the medicinal plant Ziziphora tenuior L. and evaluation of its antioxidant activity.

PubMed

Dakah, Abdulkarim; Zaid, Salim; Suleiman, Mohamad; Abbas, Sami; Wink, Michael

2014-09-01

Ziziphora tenuior L. (Lamiaceae) is an aromatic herb used for its medicinal values against fungi, bacteria. Micropropagation can be used for large-scale multiplication of essential oil producing plants thus avoiding an overexploitation of natural resources. This work aims to develop a reliable protocol for the in vitro propagation of Z. tenuior, and to compare the antioxidant activity between in vitro propagated and wild plants. The explants were sterilized and cultured on MS medium containing different concentrations of growth regulators naphthalene acetic acid (NAA) or indole-3-butyric acid (IBA) with 0.5 mg/L of kinetin (Kin) callus formation was 70.2% after 45 days of incubation in dark on medium supplemented with 1.5 mg/L of NAA. After one month of callus culture on medium supplemented with 2 mg/L BA the shoot number was 5.12 and for the multiplication stage. The shoot number was 4.21 and length was 6.17 cm on medium supplemented with 1 mg/L Kin + 0.1 mg/L NAA. DPPH• reagent was used to test the antioxidant activity. The aqueous and methanol extracts of in vitro plants which were treated with 1.5 and 1 mg/L of kin plus 0.1 mg/L of NAA showed a strong DPPH• scavenging activity where IC50 was 0.307 and 0.369 mg/ml, respectively, while the IC50 of aqueous and methanol extracts of wild plants was 0.516 and 9.229 mg/ml, respectively. Our results suggested that plant growth regulators and in vitro culture conditions increased the antioxidant activity.

U.S. EPA, Pesticide Product Label, MALEIC HYDRAZIDE 2P, 11/21/1972

EPA Pesticide Factsheets

2011-04-14

... " .,' . cot< .. ·. r" . '\\, f'" ~ ,,r.. v: \\' .' it:: . . :i-\\ L c .. Bpf""""J"[- "_U J ... f () r .: ,"1'\\ - • \\ 1 :1 of Th~ ":'\\ 0':,ui C:c}: thi·j pr.,)rh-,Ci, :i\\:C" frettJr' .. ...

Stool-based biomarkers of interstitial cystitis/bladder pain syndrome.

PubMed

Braundmeier-Fleming, A; Russell, Nathan T; Yang, Wenbin; Nas, Megan Y; Yaggie, Ryan E; Berry, Matthew; Bachrach, Laurie; Flury, Sarah C; Marko, Darlene S; Bushell, Colleen B; Welge, Michael E; White, Bryan A; Schaeffer, Anthony J; Klumpp, David J

2016-05-18

Interstitial cystitis/bladder pain syndrome (IC) is associated with significant morbidity, yet underlying mechanisms and diagnostic biomarkers remain unknown. Pelvic organs exhibit neural crosstalk by convergence of visceral sensory pathways, and rodent studies demonstrate distinct bacterial pain phenotypes, suggesting that the microbiome modulates pelvic pain in IC. Stool samples were obtained from female IC patients and healthy controls, and symptom severity was determined by questionnaire. Operational taxonomic units (OTUs) were identified by16S rDNA sequence analysis. Machine learning by Extended Random Forest (ERF) identified OTUs associated with symptom scores. Quantitative PCR of stool DNA with species-specific primer pairs demonstrated significantly reduced levels of E. sinensis, C. aerofaciens, F. prausnitzii, O. splanchnicus, and L. longoviformis in microbiota of IC patients. These species, deficient in IC pelvic pain (DIPP), were further evaluated by Receiver-operator characteristic (ROC) analyses, and DIPP species emerged as potential IC biomarkers. Stool metabolomic studies identified glyceraldehyde as significantly elevated in IC. Metabolomic pathway analysis identified lipid pathways, consistent with predicted metagenome functionality. Together, these findings suggest that DIPP species and metabolites may serve as candidates for novel IC biomarkers in stool. Functional changes in the IC microbiome may also serve as therapeutic targets for treating chronic pelvic pain.

Ionocovalency and Applications 1. Ionocovalency Model and Orbital Hybrid Scales

PubMed Central

Zhang, Yonghe

2010-01-01

Ionocovalency (IC), a quantitative dual nature of the atom, is defined and correlated with quantum-mechanical potential to describe quantitatively the dual properties of the bond. Orbiotal hybrid IC model scale, IC, and IC electronegativity scale, XIC, are proposed, wherein the ionicity and the covalent radius are determined by spectroscopy. Being composed of the ionic function I and the covalent function C, the model describes quantitatively the dual properties of bond strengths, charge density and ionic potential. Based on the atomic electron configuration and the various quantum-mechanical built-up dual parameters, the model formed a Dual Method of the multiple-functional prediction, which has much more versatile and exceptional applications than traditional electronegativity scales and molecular properties. Hydrogen has unconventional values of IC and XIC, lower than that of boron. The IC model can agree fairly well with the data of bond properties and satisfactorily explain chemical observations of elements throughout the Periodic Table. PMID:21151444

U.S. EPA, Pesticide Product Label, HERCON INSECTAPE HIGH-TECH WITH PROPOXUR, 03/26/1990

EPA Pesticide Factsheets

2011-04-21

... I 'I I , I --~J:c- - - . - i [] I~~~~il ['~~I (1 /~j ~;[rLp) AAA. Customer Interlace Cable Interface / f (1 I I I I I .. --- j 'I r-/ \\ , I,-c-' - f r t' '/ ,~J I ,r . ...

Determination of the appropriate catheter length and place for needle thoracostomy by using computed tomography scans of pneumothorax patients.

PubMed

Akoglu, Haldun; Akoglu, Ebru Unal; Evman, Serdar; Akoglu, Tayfun; Altinok, Arzu Denizbasi; Guneysel, Ozlem; Onur, Ozge Ecmel; Eroglu, Serkan Emre

2013-09-01

The primary goal of this study was to compare the chest wall thicknesses (CWT) at the 2nd intercostal space (ICS) at the mid-clavicular line (MCL) and 5th ICS at the mid-axillary line (MAL) in a population of patients with a CT confirmed pneumothorax (PTX). This result will help physicians to determine the optimum needle thoracostomy (NT) puncture site in patients with a PTX. All trauma patients who presented consecutively to A&E over a 12-month period were included. Among all the trauma patients with a chest CT (4204 patients), 160 were included in the final analysis. CWTs were measured at both sides and were compared in all subgroup of patients. The average CWT for men on the 2nd ICS-MCL was 38mm and for women was 52mm; on the other hand, on the 5th ICS-MAL was 33mm for men and 38mm for women. On the 2nd ICS-MCL 17% of men and 48% of women; on the 5th ICS-MAL 13% of men and 33% of women would be inaccessible with a routine 5-cm catheter. Patients with trauma, subcutaneous emphysema and multiple rib fractures would have thicker CWT on the 2nd ICS-MCL. Patients with trauma, lung contusion, sternum fracture, subcutaneous emphysema and multiple rib fractures would have thicker CWT on the 5th ICS-MAL. This study confirms that a 5.0-cm catheter would be unlikely to access the pleural space in at least 1/3 of female and 1/10 of male Turkish trauma patients, regardless of the puncture site. If NT is needed, the 5th ICS-MAL is a better option for a puncture site with thinner CWT. Copyright © 2012 Elsevier Ltd. All rights reserved.

Gas-Phase Chemistry of Arylimido-Functionalized Hexamolybdates [Mo6O19]2-

NASA Astrophysics Data System (ADS)

Cao, Jie; Wang, QianQian; Liu, Chang; An, ShuQi

2018-04-01

The gas-phase fragmentations of a series of arylimido derivatives of hexamolybdate [Mo6O18(NC6H5-n R n )]2- (2-10, where R = CH3, i-C3H7, OCH3, NO2; n = 1 or 2) versus the parent species [Mo6O19]2- (1) were systematically studied using electrospray tandem mass spectrometry (ESI). Fragmentation of 1 generates two molybdate fragments only, [Mo3O10]2- and [Mo4O13]2-, whereas decomposition of 2-10 went through two dissociation pathways in which path A generates a variety of molybdate fragments via breaking the Mo-N bond followed by the cleavages of the multiple Mo-O bonds, whereas path B produces a range of molybdate fragments with arylimido group via breaking the multiple Mo-O bonds on POM framework. Moreover, the presences of mixed-oxidation-state molybdate fragments are characteristic for the fragmentation. The gas-phase stability order obtained by energy-variable collision-induced dissociation (CID) experiment reveals that 2-10 are generally less stable than 1 and substitution on the benzene ring exerts a considerable effect on the stabilization of the hybrid clusters. [Figure not available: see fulltext.

Sirc-cvs cytotoxicity test: an alternative for predicting rodent acute systemic toxicity.

PubMed

Kitagaki, Masato; Wakuri, Shinobu; Hirota, Morihiko; Tanaka, Noriho; Itagaki, Hiroshi

2006-10-01

An in vitro crystal violet staining method using the rabbit cornea-derived cell line (SIRC-CVS) has been developed as an alternative to predict acute systemic toxicity in rodents. Seventy-nine chemicals, the in vitro cytotoxicity of which was already reported by the Multicenter Evaluation of In vitro Toxicity (MEIC) and ICCVAM/ECVAM, were selected as test compounds. The cells were incubated with the chemicals for 72 hrs and the IC(50) and IC(35) values (microg/mL) were obtained. The results were compared to the in vivo (rat or mouse) "most toxic" oral, intraperitoneal, subcutaneous and intravenous LD(50) values (mg/kg) taken from the RTECS database for each of the chemicals by using Pearson's correlation statistics. The following parameters were calculated: accuracy, sensitivity, specificity, prevalence, positive predictability, and negative predictability. Good linear correlations (Pearson's coefficient; r>0.6) were observed between either the IC(50) or the IC(35) values and all the LD(50) values. Among them, a statistically significant high correlation (r=0.8102, p<0.001) required for acute systemic toxicity prediction was obtained between the IC(50) values and the oral LD(50) values. By using the cut-off concentrations of 2,000 mg/kg (LD(50)) and 4,225 microg/mL (IC(50)), no false negatives were observed, and the accuracy was 84.8%. From this, it is concluded that this method could be used to predict the acute systemic toxicity potential of chemicals in rodents.

Targeting of Escherichia coli F4 fimbriae to Fcgamma receptors enhances the maturation of porcine dendritic cells.

PubMed

Devriendt, Bert; Verdonck, Frank; Summerfield, Artur; Goddeeris, Bruno M; Cox, Eric

2010-06-15

F4(+) enterotoxigenic Escherichia coli (ETEC) infections are an important cause of postweaning diarrhoea in piglets and an oral immunization of piglets with purified F4 fimbriae protects them from a subsequent F4(+) ETEC infection. However, oral immunization of suckling piglets is hampered due to the immature status of their immune system. Targeting of antigens to Fcgamma receptors (FcgammaR) on human and murine dendritic cells (DC) has been shown to enhance DC maturation and both humoral and cellular immune responses. To investigate the effect of F4 fimbriae incorporated in immune complexes (F4-IC) on porcine DC, we used porcine monocytic-derived DC (MoDC) as a model system. The results in this study demonstrate that FcgammaRI, II and III mRNA is expressed by porcine MoDC. Furthermore, we show that FcgammaRII and III are expressed on the cell surface and that F4-IC are internalized by MoDC via FcgammaR. This FcgammaR ligation induced a significantly enhanced expression of Major Histocompatibility complex (MHCII) class II and the costimulatory molecules CD80/86 and CD40 by MoDC compared with immature MoDC. Furthermore, the phagocytic capacity of F4-IC stimulated MoDC was reduced as evidenced by a reduced uptake of DQ-ovalbumin and FITC-dextran. In an allogenic and autologous mixed lymphocyte reaction, these F4-IC-activated MoDC showed an improved T cell stimulatory capacity in comparison with immature MoDC. The F4-IC induced DC maturation correlated with significant higher expression levels of several pro-inflammatory cytokines such as interleukine (IL) 1beta, IL-6 and Tumor necrosis factor alpha, the chemokine IL-8 and IL-12p40 in comparison with immature MoDC. Altogether, these results clearly demonstrate that FcgammaR engagement enhances the maturation of porcine MoDC, which may suggest that antigen targeting to FcgammaR on DC could improve vaccine design against infections. Copyright 2009 Elsevier B.V. All rights reserved.

Integrated readout electronics for Belle II pixel detector

NASA Astrophysics Data System (ADS)

Blanco, R.; Leys, R.; Perić, I.

2018-03-01

This paper describes the readout components for Belle II that have been designed as integrated circuits. The ICs are connected to DEPFET sensor by bump bonding. Three types of ICs have been developed: SWITCHER for pixel matrix control, DCD for readout and digitizing of sensor signals and DHP for digital data processing. The ICs are radiation tolerant and use several novel features, such as the multiple-input differential amplifiers and the fast and radiation hard high-voltage drivers. SWITCHER and DCD have been developed at University of Heidelberg, Karlsruhe Institute of Technology (KIT) and DHP at Bonn University. The IC-development started in 2009 and was accomplished in 2016 with the submissions of final designs. The final ICs for Belle II pixel detector and the related measurement results will be presented in this contribution.

Method and apparatus to debug an integrated circuit chip via synchronous clock stop and scan

DOEpatents

Bellofatto, Ralph E [Ridgefield, CT; Ellavsky, Matthew R [Rochester, MN; Gara, Alan G [Mount Kisco, NY; Giampapa, Mark E [Irvington, NY; Gooding, Thomas M [Rochester, MN; Haring, Rudolf A [Cortlandt Manor, NY; Hehenberger, Lance G [Leander, TX; Ohmacht, Martin [Yorktown Heights, NY

2012-03-20

An apparatus and method for evaluating a state of an electronic or integrated circuit (IC), each IC including one or more processor elements for controlling operations of IC sub-units, and each the IC supporting multiple frequency clock domains. The method comprises: generating a synchronized set of enable signals in correspondence with one or more IC sub-units for starting operation of one or more IC sub-units according to a determined timing configuration; counting, in response to one signal of the synchronized set of enable signals, a number of main processor IC clock cycles; and, upon attaining a desired clock cycle number, generating a stop signal for each unique frequency clock domain to synchronously stop a functional clock for each respective frequency clock domain; and, upon synchronously stopping all on-chip functional clocks on all frequency clock domains in a deterministic fashion, scanning out data values at a desired IC chip state. The apparatus and methodology enables construction of a cycle-by-cycle view of any part of the state of a running IC chip, using a combination of on-chip circuitry and software.

Mucosal CXCR4+ IgG plasma cells contribute to the pathogenesis of human ulcerative colitis through FcγR-mediated CD14 macrophage activation.

PubMed

Uo, Michihide; Hisamatsu, Tadakazu; Miyoshi, Jun; Kaito, Daiki; Yoneno, Kazuaki; Kitazume, Mina T; Mori, Maiko; Sugita, Akira; Koganei, Kazutaka; Matsuoka, Katsuyoshi; Kanai, Takanori; Hibi, Toshifumi

2013-12-01

Chronic inflammation characterised by IgG-producing plasma cell infiltration of colonic mucosa is a histological hallmark of ulcerative colitis (UC); however, whether its function is pathogenic or protective remains unclear. To explore the contribution of intestinal IgG plasma cells to UC pathogenesis. We isolated lamina propria mononuclear cells (LPMCs) from intestinal mucosa of UC patients and analysed the characteristics of intestinal plasma cells (expression profiles of differentiation molecules and chemokine receptors). We investigated the involvement of IgG-immune complex (IC)-Fc gamma receptor (FcγR) signalling in intestinal inflammation by examining the cytokine production by LPMCs in response to IgG-IC stimulation. IgG plasma cells that were markedly increased in number in the inflamed mucosa of UC patients showed a distinct expression profile (CD19(+)CD27(low), CCR10(low)CXCR4(high)) compared with IgA plasma cells (CD19(+/-)CD27(high), CCR10(high)CXCR4(-/low)). In vitro IgG-IC stimulation activated intestinal CD14 macrophages that were increased in number in the inflamed mucosa of UC patients via FcγRI and FcγRII, and induced the extensive production of pro-inflammatory cytokines such as tumour necrosis factor (TNF) and interleukin-1β (IL-1β), comparable to the effect of commensal bacteria stimulation. Co-stimulation with IgG-IC and commensal bacteria increased TNF and IL-1β production more than stimulation with the latter alone. Furthermore, IgG-IC notably up-regulated the expression of TL1A, whereas commensal bacteria specifically induced IL-23. Collectively, these results demonstrate a novel aspect of UC pathogenesis in which unique IgG plasma cells infiltrate the inflamed mucosa via CXCR4, and critically influence UC pathogenesis by exacerbating mucosal inflammation through the activation of 'pathogenic' intestinal CD14 macrophages via IgG-IC-FcγR signalling.

Molecular modeling and cytotoxicity of diffractaic acid: HP-β-CD inclusion complex encapsulated in microspheres.

PubMed

Silva, Camilla V N S; Barbosa, Jéssica A P; Ferraz, Milena S; Silva, Nicácio H; Honda, Neli K; Rabello, Marcelo M; Hernandes, Marcelo Z; Bezerra, Beatriz P; Cavalcanti, Isabella M F; Ayala, Alejandro P; Santos, Noemia P S; Santos-Magalhães, Nereide S

2016-11-01

In this pioneer study, 2-hydroxypropyl-β-cyclodextrin (HP-β-CD) was used to improve the solubility of the diffractaic acid (DA) via inclusion complex (DA:HP-β-CD). Subsequently, DA:HP-β-CD was incorporated into poly-ε-caprolactone (PCL) microspheres (DA:HP-β-CD-MS). Microspheres containing DA (DA-MS) or DA:HP-β-CD (DA:HP-β-CD-MS) were prepared using the multiple W/O/W emulsion-solvent evaporation technique. The phase-solubility diagram of DA in HP-β-CD (10-50mM) showed an A L type curve with a stability constant K 1:1 =821M -1 . 1 H NMR, FTIR, X-ray diffraction and thermal analysis showed changes in the molecular environment of DA in DA:HP-β-CD. The molecular modeling approach suggests a guest-host complex formation between the carboxylic moiety of both DA and the host (HP-β-CD). The mean particle size of the microspheres were ∅ DA-MS =5.23±1.65μm and ∅ DA:HP-β-CD-MS =4.11±1.39μm, respectively. The zeta potential values of the microspheres were ζ DA-MS =-7.85±0.32mV and ζ DA:HP-β-CD-MS =-6.93±0.46mV. Moreover, the encapsulation of DA:HP-β-CD into microspheres resulted in a more slower release (k 2 =0.042±0.001; r 2 =0.996) when compared with DA-MS (k 2 =0.183±0.005; r 2 =0.996). The encapsulation of DA or DA:HP-β-CD into microspheres reduced the cytotoxicity of DA (IC 50 =43.29μM) against Vero cells (IC 50 of DA-MS=108.48μM and IC 50 of DA:HP-β-CD-MS=142.63μM). Copyright © 2016 Elsevier B.V. All rights reserved.

Morphological changes of bladder mucosa in patients who underwent instillation with combined sodium hyaluronic acid-chondroitin sulphate (Ialuril®).

PubMed

Costantini, E; Lazzeri, M; Pistolesi, D; Del Zingaro, M; Frumenzio, E; Boni, A; Pietropaolo, A; Fragalà, E; Porena, M

2013-01-01

To investigate what changes are endoscopically evident after glycosaminoglycans (GAGs) therapy by hyaluronic acid (HA) and chondroitin sulphate (CS) (Ialuril®) in female patients affected by bladder pain syndrome(BPS)/ interstitial cystitis (IC) or recurrent urinary tract infections (rUTIs). 21 female patients over 18 years affected by rUTIs or BPS/IC received intravesical instillation of HA and CS (4 weekly instillations followed by 2 instillations every 2 weeks and 2 instillation monthly). Post-treatment evaluation included cystoscopy and patient assessment of improvement in symptoms and satisfaction on a visual analogue scale (VAS) from 0 to 10. The post-treatment endoscopy showed a positive effect on bladder mucosa morphology. In 2 cases, treatment did not change endoscopic findings and clinical symptoms. In the other patients, when macroscopic features of the bladder mucosa normalized, the clinical picture improved. GAGs therapy by HA and CS (Ialuril) improves the morphology of bladder mucosa in patients with rUTI or BPS/IC. Copyright © 2013 S. Karger AG, Basel.

Bond of Reinforcemen Under Controlled Confinement.

DTIC Science & Technology

1991-06-01

motivated the design of a new testing device and specimen that allow for the control and measurement of the four variables identified. STEEL-CONCRETE... Ps4 At r = r, the internal radius of the concrete cylinder increases by: Arc = rs(a t - ic Or)/Ec (5) r r(1 - Vc) + r2(1 -[) -2 rc P/pp] (6) --2

Integrated circuit detector technology in abdominal CT: added value in obese patients.

PubMed

Morsbach, Fabian; Bickelhaupt, Sebastian; Rätzer, Susan; Schmidt, Bernhard; Alkadhi, Hatem

2014-02-01

The purpose of this article was to assess the effect of an integrated circuit (IC) detector for abdominal CT on image quality. In the first study part, an abdominal phantom was scanned with various extension rings using a CT scanner equipped with a conventional discrete circuit (DC) detector and on the same scanner with an IC detector (120 kVp, 150 effective mAs, and 75 effective mAs). In the second study part, 20 patients were included who underwent abdominal CT both with the IC detector and previously at similar protocol parameters (120 kVp tube current-time product and 150 reference mAs using automated tube current modulation) with the DC detector. Images were reconstructed with filtered back projection. Image quality in the phantom was higher for images acquired with the IC compared with the DC detector. There was a gradually increasing noise reduction with increasing phantom sizes, with the highest (37% in the largest phantom) at 75 effective mAs (p < 0.001). In patients, noise was overall significantly (p = 0.025) reduced by 6.4% using the IC detector. Similar to the phantom, there was a gradual increase in noise reduction to 7.9% in patients with a body mass index of 25 kg/m(2) or lower (p = 0.008). Significant correlation was found in patients between noise and abdominal diameter in DC detector images (r = 0.604, p = 0.005), whereas no such correlation was found for the IC detector (r = 0.427, p = 0.060). Use of an IC detector in abdominal CT improves image quality and reduces image noise, particularly in overweight and obese patients. This noise reduction has the potential for dose reduction in abdominal CT.

Identification of homemade inorganic explosives by ion chromatographic analysis of post-blast residues.

PubMed

Johns, Cameron; Shellie, Robert A; Potter, Oscar G; O'Reilly, John W; Hutchinson, Joseph P; Guijt, Rosanne M; Breadmore, Michael C; Hilder, Emily F; Dicinoski, Greg W; Haddad, Paul R

2008-02-29

Anions and cations of interest for the post-blast identification of homemade inorganic explosives were separated and detected by ion chromatographic (IC) methods. The ionic analytes used for identification of explosives in this study comprised 18 anions (acetate, benzoate, bromate, carbonate, chlorate, chloride, chlorite, chromate, cyanate, fluoride, formate, nitrate, nitrite, perchlorate, phosphate, sulfate, thiocyanate and thiosulfate) and 12 cations (ammonium, barium(II), calcium(II), chromium(III), ethylammonium, magnesium(II), manganese(II), methylammonium, potassium(I), sodium(I), strontium(II), and zinc(II)). Two IC separations are presented, using suppressed IC on a Dionex AS20 column with potassium hydroxide as eluent for anions, and non-suppressed IC for cations using a Dionex SCS 1 column with oxalic acid/acetonitrile as eluent. Conductivity detection was used in both cases. Detection limits for anions were in the range 2-27.4ppb, and for cations were in the range 13-115ppb. These methods allowed the explosive residue ions to be identified and separated from background ions likely to be present in the environment. Linearity (over a calibration range of 0.05-50ppm) was evaluated for both methods, with r(2) values ranging from 0.9889 to 1.000. Reproducibility over 10 consecutive injections of a 5ppm standard ranged from 0.01 to 0.22% relative standard deviation (RSD) for retention time and 0.29 to 2.16%RSD for peak area. The anion and cation separations were performed simultaneously by using two Dionex ICS-2000 chromatographs served by a single autoinjector. The efficacy of the developed methods was demonstrated by analysis of residue samples taken from witness plates and soils collected following the controlled detonation of a series of different inorganic homemade explosives. The results obtained were also confirmed by parallel analysis of the same samples by capillary electrophoresis (CE) with excellent agreement being obtained.

Aggressive Behaviors in Young Siblings: Associations with Executive Functions and Maternal Characteristics.

PubMed

Spann, Catherine A; Gagne, Jeffrey R

2016-04-01

Aggressive behaviors in early childhood are associated with multiple undesirable outcomes, including juvenile delinquency, academic failure, and substance abuse. This investigation employed a family study design to examine child, mother and sibling predictors of early-emerging aggressive behaviors. These predictors included several indices of executive functioning within children, depression symptoms and education level of mothers, and inhibitory control (IC) of siblings. The sample consisted of 95 families (191 children; boys = 100) with at least two, typically developing children between 30 and 66 months of age (M(age) = 45.93 months, SD = 12.40). Measures included laboratory-assessed working memory and IC, parent-reported aggressive behaviors, as well as self-reported maternal depression symptoms and education. Results revealed that children showed substantial sibling similarity in aggressive behaviors. Using multilevel regression analyses, low child IC and greater maternal depression symptoms were associated with increased child aggressive behaviors. Child working memory, maternal education, and sibling IC did not uniquely predict child aggressive behaviors. Moderation analyses revealed an interaction between maternal depression symptoms and maternal education, such that the effect of depression symptoms on child aggressive behaviors was particularly evident amongst highly educated mothers. The current analysis moved beyond a main effects model of maternal depression and extended previous findings on the importance of child IC to aggressive behaviors by using a multiple-child-per-family framework. A promising direction for future research includes assessing whether efforts to increase child IC are successful in reducing child aggressive behaviors.

Broad spectrum anti-infective properties of benzisothiazolones and the parallels in their anti-bacterial and anti-fungal effects.

PubMed

Gopinath, P; Yadav, R K; Shukla, P K; Srivastava, K; Puri, S K; Muraleedharan, K M

2017-03-01

Various mono- and bis-benzisothiazolone derivatives were synthesized and screened against different strains of bacteria and fungi in order to understand the effect of multiple electrophilic sulfur atoms and substitution pattern in the immediate vicinity of reactive sulfur. Staphyllococcus aureus-ATCC 7000699, MRSA and S. aureus-ATCC 29213 (Quality Control strain) were more susceptible to this class of compounds, and the most potent derivative 1.15 had MIC 50 of 0.4μg/mL (cf. Gentamicin=0.78μg/mL). CLogP value, optimally in the range of 2.5-3.5, appeared to contribute more to the activity than the steric and electronic effects of groups attached at nitrogen. By and large, their anti-fungal activities also followed a similar trend with respect to the structure and CLogP values. The best potency of IC 50 =0.1μg/mL was shown by N-benzyl derivative (1.7) against Aspergillus fumigatus; it was also potent against Candida albicans, Cryptococcus neoformans, Sporothrix schenckii, and Candida parapsilosis with IC 50 values ranging from 0.4 to 1.3μg/mL. Preliminary studies also showed that this class of compounds have the ability to target malaria parasite with IC 50 values in low micromolar range, and improvement of selectivity is possible through structure optimization. Copyright © 2017 Elsevier Ltd. All rights reserved.

Straight-chain alcohols exhibit a cutoff in potency for the inhibition of recombinant glutamate receptor subunits

PubMed Central

Akinshola, B Emmanuel

2001-01-01

The effects of n-alcohols (methanol to 1-decanol) on kainate-activated AMPA receptor subunit GluR1 and GluR3 ion currents were studied in Xenopus oocytes using the two-electrode voltage-clamp recording technique. For short-chain alcohols from methanol to 1-hexanol, potency for inhibition of GluR1 and GluR3 receptor-mediated current increased in proportion to the chain length or hydrophobicity of the alcohol. The IC50 values of these alcohols for GluR1 were: methanol, 702 mM; ethanol, 170 mM; 1-propanol, 69 mM; 1-butanol, 20 mM; 1-pentanol, 17 mM; and 1-hexanol, 10 mM. For GluR3, IC50 values were: methanol, 712 mM; ethanol, 238 mM; 1-propanol, 50 mM; 1-butanol, 32 mM; 1-pentanol, 13 mM; and 1-hexanol, 7 mM. For long-chain alcohols, 1-heptanol was less potent than 1-hexanol (estimated IC50: 19 mM for GluR1 and 18 mM for GluR3), 1-octanol had little effect only on GluR3, and 1-nonanol and 1-decanol did not significantly inhibit both GluR1 and GluR3 responses. The observations indicate that straight-chain n-alcohols exhibit a cutoff in their potency for inhibition of the function of non-NMDA glutamate receptor subunits, GluR1 and GluR3. The cutoff in potency of n-alcohols for inhibition of non-NMDA glutamate receptor function is consistent with the interpretation that alcohols affect the function of these receptor-channels by interacting with an alcohol binding site of specific dimensions on the receptor protein. PMID:11429388

Conformations and properties of O-Alkyl- S-(2- N, N-dialkylamino)-ethylmethylthiophosphonates

NASA Astrophysics Data System (ADS)

Strukov, O. G.; Kondrat'ev, V. B.; Vlasova, Z. V.; Petrunin, V. A.

2017-01-01

Conformers of the biologically active compounds CH3P(O)(OR)(SCH2CH2NR 2 ' ), where ( I) R = i-C4H9, R' = C2H5 and ( II) R = C2H5, R' = i-C3H7, are calculated within the AM1 level of theory. The elongated and twisted forms with maximum and minimum distances between a nitrogen atom and those of a phosphorus tetrahedron, respectively, and bearing a syn and anti oriented alkoxy group relative to a phosphoryl oxygen, are studied. It is found that the differences between the energy, electronic, and geometric parameters of these forms are apparent in differences between their properties, e.g., the ability to participate in complexation and protonation, reactions that to some extent simulate the interaction between a substance and a biological object.

The Influence of Task and Personality Characteristics on Employee Turnover and Absenteeism Incidents.

DTIC Science & Technology

1981-01-01

E oc vc li.’ r .IIuaJry 1.981 Office of’ Nav;il Rcs,.il vh Q# ,. 4 ,lL1 , 0r4i gT...Ic It, toil ill Who, (-, o) r i n partC ~S lort’Iic L o i f. 111V llll~ of tIc Ul ilLI7 )LA . .. L: 0 I [Ile:; . Sb c ~ T c It A I 1’: 1 w1 -iid ex...UlmA ioctlt.y Vc v jn- Ilic . P’or c v i ) L c1) 1 W I S I I t’,.ItL IV e y 10r- ILI I L v J c o 1) t, )I c rflv or ind ah- - tce isi - W 4i e L

CLONING, EXPRESSION, AND HEMOSTATIC ACTIVITIES OF A DISINTEGRIN, r-MOJASTIN 1, FROM THE MOHAVE RATTLESNAKE (Crotalus scutulatus scutulatus)

PubMed Central

Sánchez, Elda E.; Lucena, Sara E.; Reyes, Steven; Soto, Julio G.; Cantu, Esteban; Lopez-Johnston, Juan Carlos; Guerrero, Belsy; Salazar, Ana Maria; Rodríguez-Acosta, Alexis; Galán, Jacob A.; Tao, W. Andy; Pérez, John C.

2012-01-01

Interactions with exposed subendothelial extracellular proteins and cellular integrins (endothelial cells, platelets and lymphocytes) can cause alterations in the hemostatic system associated with atherothrombotic processes. Many molecules found in snake venoms induce pathophysiological changes in humans, cause edema, hemorrhage, and necrosis. Disintegrins are low molecular weight, non-enzymatic proteins found in snake venom that mediate changes by binding to integrins of platelets or other cells and prevent binding of the natural ligands such as fibrinogen, fibronectin or vitronectin. Disintegrins are of great biomedical importance due to their binding affinities resulting in the inhibition of platelet aggregation, adhesion of cancer cells, and induction of signal transduction pathways. RT-PCR was used to obtain a 216 bp disintegrin cDNA from a C. s. scutulatus snake venom gland. The cloned recombinant disintegrin called r-mojastin 1 codes for 71 amino acids, including 12 cysteines, and an RGD binding motif. r-Mojastin 1 inhibited platelet adhesion to fibronectin with an IC50 of 58.3 nM and ADP-induced platelet aggregation in whole blood with an IC50 of 46 nM. r-Mojastin 1 was also tested for its ability to inhibit platelet ATP release using PRP resulting with an IC50 of 95.6 nM. MALDI-TOF mass spectrum analysis showed that r-mojastin has a mass of 7.9509 kDa. PMID:20598348

Statistical Signal Process in R Language in the Pharmacovigilance Programme of India.

PubMed

Kumar, Aman; Ahuja, Jitin; Shrivastava, Tarani Prakash; Kumar, Vipin; Kalaiselvan, Vivekanandan

2018-05-01

The Ministry of Health & Family Welfare, Government of India, initiated the Pharmacovigilance Programme of India (PvPI) in July 2010. The purpose of the PvPI is to collect data on adverse reactions due to medications, analyze it, and use the reference to recommend informed regulatory intervention, besides communicating the risk to health care professionals and the public. The goal of the present study was to apply statistical tools to find the relationship between drugs and ADRs for signal detection by R programming. Four statistical parameters were proposed for quantitative signal detection. These 4 parameters are IC 025 , PRR and PRR lb , chi-square, and N 11 ; we calculated these 4 values using R programming. We analyzed 78,983 drug-ADR combinations, and the total count of drug-ADR combination was 4,20,060. During the calculation of the statistical parameter, we use 3 variables: (1) N 11 (number of counts), (2) N 1. (Drug margin), and (3) N .1 (ADR margin). The structure and calculation of these 4 statistical parameters in R language are easily understandable. On the basis of the IC value (IC value >0), out of the 78,983 drug-ADR combination (drug-ADR combination), we found the 8,667 combinations to be significantly associated. The calculation of statistical parameters in R language is time saving and allows to easily identify new signals in the Indian ICSR (Individual Case Safety Reports) database.

VizieR Online Data Catalog: IN-SYNC. III. Radial velocities of IC348 stars (Cottaar+, 2015)

NASA Astrophysics Data System (ADS)

Cottaar, M.; Covey, K. R.; Foster, J. B.; Meyer, M. R.; Tan, J. C.; Nidever, D. L.; Drew Chojnowski, S.; da Rio, N.; Flaherty, K. M.; Frinchaboy, P. M.; Majewski, S.; Skrutskie, M. F.; Wilson, J. C.; Zasowski, G.

2015-11-01

Cottaar et al. (Paper I, 2014, J/ApJ/794/125) describes the analysis of the high-resolution near-infrared spectra obtained by the APOGEE multi-object spectrograph from stars in IC 348, NGC 1333, NGC 2264, and Orion A as part of the INfrared Spectroscopy of Young Nebulous Clusters (IN-SYNC) ancillary program. Using radial velocities determined from APOGEE spectra of 380 likely cluster members, we have measured the radial velocity distribution of the young (2-6Myr) cluster IC 348. (2 data files).

Live Cell Imaging Reveals Differential Modifications to Cytoplasmic Dynein Properties by Phospho- and Dephospho-mimic Mutations of the Intermediate Chain 2C S84

PubMed Central

Blasier, Kiev R.; Humsi, Michael K.; Ha, Junghoon; Ross, Mitchell W.; Smiley, W. Russell; Inamdar, Nirja A.; Mitchell, David J.; Lo, Kevin W.-H.; Pfister, K. Kevin

2014-01-01

Cytoplasmic dynein is a multi-subunit motor protein responsible for intracellular cargo transport toward microtubule minus ends. There are multiple isoforms of the dynein intermediate chain (DYNC1I, IC) which is encoded by two genes. One way to regulate cytoplasmic dynein is by IC phosphorylation. The IC-2C isoform is expressed in all cells and the functional significance of phosphorylation on IC-2C serine 84 was investigated using live cell imaging of fluorescent protein-tagged wild type IC-2C (WT) and phospho- and dephospho-mimic mutant isoforms in axonal transport model systems. Both mutations modulated dynein functional properties. The dephospho-mimic mutant IC-2C S84A had greater co-localization with mitochondria than IC-2C wild-type (WT) or the phospho-mimic mutant IC-2C S84D. The dephospho-mimic mutant IC-2C S84A was also more likely to be motile than the phospho-mimic mutant IC-2C S84D or IC-2C WT. In contrast, the phospho-mimic mutant IC-2C S84D mutant was more likely to move in the retrograde direction than was the IC-2C S84A mutant. The phospho-mimic IC-2C S84D was also as likely as IC-2C WT to co-localize with mitochondria. Both the S84D phospho- and S84A, dephospho-mimic mutants were found to be capable of microtubule minus end directed (retrograde) movement in axons. They were also observed to be passively transported in the anterograde direction. These data suggest that the IC-2C S84 has a role in modulating dynein properties. PMID:24798412

U.S. EPA, Pesticide Product Label, MAB-250, 04/23/1985

EPA Pesticide Factsheets

2011-04-21

... ': (./ _.1" :--- Ic,;d -".n r.. f'. r"~tl11"" rn)(~lH'-t: ,~an.:'\\qPl (17) ~iSl nfpC'tf1.nt q Brand' pr"Ql!--f-rr-ttl'''JI l\\iVl~:l(\\r' rTS-/fll(') J: ~ .. T .~~,~t ~IJ~~ j ...

Response Protocol Toolbox: Planning for and Responding to Drinking Water Contamination Threats and Incidents. Response Guidelines

DTIC Science & Technology

2004-08-01

sp ec if ic ra d io n u cl id es 9 0 0 S er ie s 3 2 In te ri m F in al – A u g u st 2 0 0 4 R E S...in je ct io n , h ea d sp ac e S ee M o d u le 4 A n a ly si s: G C /M S , G C , H P L C , L C -M S U n k n o w n in o rg an ic s 1 L...er f o r th e m et er o r k it u se d d u ri n g s

PIG (partially ionized globule) anatomy - Density and temperature structure of the bright-rimmed globule IC 1396E

NASA Technical Reports Server (NTRS)

Serabyn, E.; Guesten, R.; Mundy, L.

1993-01-01

The density and temperature structure of the bright-rimmed cometary globule IC 1396E is estimated, and the possibility that recent internal star formation was triggered by the ionization front in its southern surface is assessed. On the basis of NH3 data, gas temperatures in the globule are found to increase outward from the center, from a minimum of 17 K in its tail to a maximum of 26 K on the surface most directly facing the stars ionizing IC 1396. On the basis of a microturbulent radiative transfer code to model the radial dependence of the CS line intensities, and also the intensities of the optically thin 2-1 and 5-4 lines toward the cloud center, a radial density dependence of r exp -1.55 to r exp -1.75 is found.

Epstein-Barr virus-encoded EBNA2 alters immune checkpoint PD-L1 expression by downregulating miR-34a in B-cell lymphomas.

PubMed

Anastasiadou, Eleni; Stroopinsky, Dina; Alimperti, Stella; Jiao, Alan L; Pyzer, Athalia R; Cippitelli, Claudia; Pepe, Giuseppina; Severa, Martina; Rosenblatt, Jacalyn; Etna, Marilena P; Rieger, Simone; Kempkes, Bettina; Coccia, Eliana M; Sui, Shannan J Ho; Chen, Christopher S; Uccini, Stefania; Avigan, David; Faggioni, Alberto; Trivedi, Pankaj; Slack, Frank J

2018-06-26

Cancer cells subvert host immune surveillance by altering immune checkpoint (IC) proteins. Some Epstein-Barr virus (EBV)-associated tumors have higher Programmed Cell Death Ligand, PD-L1 expression. However, it is not known how EBV alters ICs in the context of its preferred host, the B lymphocyte and in derived lymphomas. Here, we found that latency III-expressing Burkitt lymphoma (BL), diffuse large B-cell lymphomas (DLBCL) or their EBNA2-transfected derivatives express high PD-L1. In a DLBCL model, EBNA2 but not LMP1 is sufficient to induce PD-L1. Latency III-expressing DLBCL biopsies showed high levels of PD-L1. The PD-L1 targeting oncosuppressor microRNA miR-34a was downregulated in EBNA2-transfected lymphoma cells. We identified early B-cell factor 1 (EBF1) as a repressor of miR-34a transcription. Short hairpin RNA (shRNA)-mediated knockdown of EBF1 was sufficient to induce miR-34a transcription, which in turn reduced PD-L1. MiR-34a reconstitution in EBNA2-transfected DLBCL reduced PD-L1 expression and increased its immunogenicity in mixed lymphocyte reactions (MLR) and in three-dimensional biomimetic microfluidic chips. Given the importance of PD-L1 inhibition in immunotherapy and miR-34a dysregulation in cancers, our findings may have important implications for combinatorial immunotherapy, which include IC inhibiting antibodies and miR-34a, for EBV-associated cancers.

An Analysis of the Multiple Objective Capital Budgeting Problem via Fuzzy Linear Integer (0-1) Programming.

DTIC Science & Technology

1980-05-31

34 International Journal of Man- Machine Studies , Vol. 9, No. 1, 1977, pp. 1-68. [16] Zimmermann, H. J., Theory and Applications of Fuzzy Sets, Institut...Boston, Inc., Hingham, MA, 1978. [18] Yager, R. R., "Multiple Objective Decision-Making Using Fuzzy Sets," International Journal of Man- Machine Studies ...Professor of Industria Engineering ... iv t TABLE OF CONTENTS page ABSTRACT .. .. . ...... . .... ...... ........ iii LIST OF TABLES

A study of H-alpha velocities in NGC 1499, NGC 7000, and IC 1318B/C

NASA Technical Reports Server (NTRS)

Fountain, W. F.; Gary, G. A.; Odell, C. R.

1983-01-01

Multiple slit echelle spectrograph observations of the H-alpha emission line are used to map the radial velocities of the California Nebula (NGC 1499), the North American Nebula complex (NGC 7000 and IC 5070), and IC 1318B/C. The California Nebula is singularly constant in velocity, considering its geometry. The North American Nebula complex reflects a very simple, classical dynamical picture. The expansion discovered earlier in IC 1318B/C is confirmed, detailed, and the model refined. The new data, along with that in earlier papers of this series, show that stellar wind acceleration and champagne flow mechanisms both play important roles in determining the evolution of H II regions.

SU-G-TeP4-07: Automatic EPID-Based 2D Measurement of MLC Leaf Offset as a Quality Control Tool

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

Ritter, T; Moran, J; Schultz, B

Purpose: The MLC dosimetric leaf gap (DLG) and transmission are measured parameters which impact the dosimetric accuracy of IMRT and VMAT plans. This investigation aims to develop an efficient and accurate routine constancy check of the physical DLG in two dimensions. Methods: The manufacturer’s recommended DLG measurement method was modified by using 5 fields instead of 11 and by utilizing the Electronic Portal Imaging Device (EPID). Validations were accomplished using an ion chamber (IC) in solid water and a 2D IC array. EPID data was collected for 6 months on multiple TrueBeam linacs using both Millennium and HD MLCs atmore » 5 different clinics in an international consortium. Matlab code was written to automatically analyze the images and calculate the 2D results. Sensitivity was investigated by introducing deliberate leaf position errors. MLC calibration and initialization history was recorded to allow quantification of their impact. Results were analyzed using statistical process control (SPC). Results: The EPID method took approximately 5 minutes. Due to detector response, the EPID measured DLG and transmission differed from the IC values but were reproducible and consistent with changes measured using the ICs. For the Millennium MLC, the EPID measured DLG and transmission were both consistently lower than IC results. The EPID method was implemented as leaf offset and transmission constancy tests (LOC and TC). Based on 6 months of measurements, the initial leaf-specific action thresholds for changes from baseline were set to 0.1 mm. Upper and lower control limits for variation were developed for each machine. Conclusion: Leaf offset and transmission constancy tests were implemented on Varian HD and Millennium MLCs using an EPID and found to be efficient and accurate. The test is effective for monitoring MLC performance using dynamic delivery and performing process control on the DLG in 2D, thus enhancing dosimetric accuracy. This work was supported by a grant from Varian Medical Systems.« less

Gene Cluster Responsible for Secretion of and Immunity to Multiple Bacteriocins, the NKR-5-3 Enterocins

PubMed Central

Ishibashi, Naoki; Himeno, Kohei; Masuda, Yoshimitsu; Perez, Rodney Honrada; Iwatani, Shun; Wilaipun, Pongtep; Leelawatcharamas, Vichien; Nakayama, Jiro; Sonomoto, Kenji

2014-01-01

Enterococcus faecium NKR-5-3, isolated from Thai fermented fish, is characterized by the unique ability to produce five bacteriocins, namely, enterocins NKR-5-3A, -B, -C, -D, and -Z (Ent53A, Ent53B, Ent53C, Ent53D, and Ent53Z). Genetic analysis with a genome library revealed that the bacteriocin structural genes (enkA [ent53A], enkC [ent53C], enkD [ent53D], and enkZ [ent53Z]) that encode these peptides (except for Ent53B) are located in close proximity to each other. This NKR-5-3ACDZ (Ent53ACDZ) enterocin gene cluster (approximately 13 kb long) includes certain bacteriocin biosynthetic genes such as an ABC transporter gene (enkT), two immunity genes (enkIaz and enkIc), a response regulator (enkR), and a histidine protein kinase (enkK). Heterologous-expression studies of enkT and ΔenkT mutant strains showed that enkT is responsible for the secretion of Ent53A, Ent53C, Ent53D, and Ent53Z, suggesting that EnkT is a wide-range ABC transporter that contributes to the effective production of these bacteriocins. In addition, EnkIaz and EnkIc were found to confer self-immunity to the respective bacteriocins. Furthermore, bacteriocin induction assays performed with the ΔenkRK mutant strain showed that EnkR and EnkK are regulatory proteins responsible for bacteriocin production and that, together with Ent53D, they constitute a three-component regulatory system. Thus, the Ent53ACDZ gene cluster is essential for the biosynthesis and regulation of NKR-5-3 enterocins, and this is, to our knowledge, the first report that demonstrates the secretion of multiple bacteriocins by an ABC transporter. PMID:25149515

Hubble’s Spirograph

NASA Image and Video Library

2017-12-08

Hubble’s Spirograph In this classic Hubble image from 2000, the planetary nebula IC 418 glows like a multifaceted jewel with enigmatic patterns. IC 418 lies about 2,000 light-years from Earth in the direction of the constellation Lepus. A planetary nebula represents the final stage in the evolution of a star similar to our sun. The star at the center of IC 418 was a red giant a few thousand years ago, but then ejected its outer layers into space to form the nebula, which has now expanded to a diameter of about 0.1 light-year. The stellar remnant at the center is the hot core of the red giant, from which ultraviolet radiation floods out into the surrounding gas, causing it to fluoresce. Over the next several thousand years, the nebula will gradually disperse into space, and then the star will cool and fade away for billions of years as a white dwarf. Our own sun is expected to undergo a similar fate, but fortunately, this will not occur until some 5 billion years from now. The Hubble image of IC 418 is shown with colors added to represent the different camera filters used that isolate light from various chemical elements. Red shows emission from ionized nitrogen (the coolest gas in the nebula, located furthest from the hot nucleus), green shows emission from hydrogen and blue traces the emission from ionized oxygen (the hottest gas, closest to the central star). The remarkable textures seen in the nebula are newly revealed by the Hubble Space Telescope, and their origin is still uncertain. Read more: go.nasa.gov/2roofKS Credit: NASA and The Hubble Heritage Team (STScI/AURA); Acknowledgment: Dr. Raghvendra Sahai (JPL) and Dr. Arsen R. Hajian (USNO)

The stereoselective sulfate conjugation of 4'-methoxyfenoterol stereoisomers by sulfotransferase enzymes.

PubMed

Iyer, Lalitha V; Ramamoorthy, Anuradha; Rutkowska, Ewelina; Furimsky, Anna M; Tang, Liang; Catz, Paul; Green, Carol E; Jozwiak, Krzysztof; Wainer, Irving W

2012-10-01

The presystemic sulfate conjugation of the stereoisomers of 4'-methoxyfenoterol, (R,R')-MF, (S,S')-MF, (R,S')-MF, and (S,R')-MF, was investigated using commercially available human intestinal S9 fractions, a mixture of sulfotransferase (SULT) enzymes. The results indicate that the sulfation was stereospecific and that an S-configuration at the β-OH carbon of the MF molecule enhanced the maximal formation rates with (S,R')-MF  (S,S')-MF  (R,S')-MF ≈ (R,R')-MF, and competition studies demonstrated that (S,R')-MF is an effective inhibitor of (R,R')-MF sulfation (IC(50) = 60 μM). In addition, the results from a cDNA-expressed human SULT isoform screen indicated that SULT1A1, SULT1A3, and SULT1E1 can mediate the sulfation of all four MF stereoisomers. Previously published molecular models of SULT1A3 and SULT1A1 were used in docking simulations of the MF stereoisomers using Molegro Virtual Docker. The models of the MF-SULT1A3 and MF-SULT1A1 complexes indicate that each of the two chiral centers of MF molecule plays a role in the observed relative stabilities. The observed stereoselectivity is the result of multiple hydrogen bonding interactions and induced conformational changes within the substrate-enzyme complex. In conclusion, the results suggest that a formulation developed from a mixture of (R,R')-MF and (S,R')-MF may increase the oral bioavailability of (R,R')-MF. Copyright © 2012 Wiley Periodicals, Inc.

Synthesis and in vitro acetylcholinesterase and butyrylcholinesterase inhibitory potential of hydrazide based Schiff bases.

PubMed

Rahim, Fazal; Ullah, Hayat; Taha, Muhammad; Wadood, Abdul; Javed, Muhammad Tariq; Rehman, Wajid; Nawaz, Mohsan; Ashraf, Muhammad; Ali, Muhammad; Sajid, Muhammad; Ali, Farman; Khan, Muhammad Naseem; Khan, Khalid Mohammed

2016-10-01

To discover multifunctional agents for the treatment of Alzheimer's disease, a series of hydrazide based Schiff bases were designed and synthesized based on multitarget-directed strategy. We have synthesized twenty-eight analogs of hydrazide based Schiff bases, characterized by various spectroscopic techniques and evaluated in vitro for acetylcholinesterase and butyrylcholinesterase inhibition. All compounds showed varied degree of acetylcholinesterase and butyrylcholinesterase inhibition when compared with standard Eserine. Among the series, compounds 10, 3 and 24 having IC50 values 4.12±0.01, 8.12±0.01 and 8.41±0.06μM respectively showed potent acetylcholinesterase inhibition when compared with Eserine (IC50=0.85±0.0001μM). Three compounds 13, 24 and 3 having IC50 values 6.51±0.01, 9.22±0.07 and 37.82±0.14μM respectively showed potent butyrylcholinesterase inhibition by comparing with eserine (IC50=0.04±0.0001μM). The remaining compounds also exhibited moderate to weak inhibitory potential. Structure activity relationship has been established. Through molecular docking studies the binding interaction was confirmed. Copyright © 2016 Elsevier Inc. All rights reserved.

Applicability of the DPPH assay for evaluating the antioxidant capacity of food additives - inter-laboratory evaluation study -.

PubMed

Shimamura, Tomoko; Sumikura, Yoshihiro; Yamazaki, Takeshi; Tada, Atsuko; Kashiwagi, Takehiro; Ishikawa, Hiroya; Matsui, Toshiro; Sugimoto, Naoki; Akiyama, Hiroshi; Ukeda, Hiroyuki

2014-01-01

An inter-laboratory evaluation study was conducted in order to evaluate the antioxidant capacity of food additives by using a 1,1-diphenyl-2-picrylhydrazyl (DPPH) assay. Four antioxidants used as existing food additives (i.e., tea extract, grape seed extract, enju extract, and d-α-tocopherol) and 6-hydroxy-2,5,7,8-tetramethylchroman-2-carboxylic acid (Trolox) were used as analytical samples, and 14 laboratories participated in this study. The repeatability relative standard deviation (RSD(r)) of the IC50 of Trolox, four antioxidants, and the Trolox equivalent antioxidant capacity (TEAC) were 1.8-2.2%, 2.2-2.9%, and 2.1-2.5%, respectively. Thus, the proposed DPPH assay showed good performance within the same laboratory. The reproducibility relative standard deviation (RSD(R)) of IC50 of Trolox, four antioxidants, and TEAC were 4.0-7.9%, 6.0-11%, and 3.7-9.3%, respectively. The RSD(R)/RSD(r) values of TEAC were lower than, or nearly equal to, those of IC50 of the four antioxidants, suggesting that the use of TEAC was effective for reducing the variance among the laboratories. These results showed that the proposed DPPH assay could be used as a standard method to evaluate the antioxidant capacity of food additives.

Alterations of microbiota in urine from women with interstitial cystitis

PubMed Central

2012-01-01

Background Interstitial Cystitis (IC) is a chronic inflammatory condition of the bladder with unknown etiology. The aim of this study was to characterize the microbial community present in the urine from IC female patients by 454 high throughput sequencing of the 16S variable regions V1V2 and V6. The taxonomical composition, richness and diversity of the IC microbiota were determined and compared to the microbial profile of asymptomatic healthy female (HF) urine. Results The composition and distribution of bacterial sequences differed between the urine microbiota of IC patients and HFs. Reduced sequence richness and diversity were found in IC patient urine, and a significant difference in the community structure of IC urine in relation to HF urine was observed. More than 90% of the IC sequence reads were identified as belonging to the bacterial genus Lactobacillus, a marked increase compared to 60% in HF urine. Conclusion The 16S rDNA sequence data demonstrates a shift in the composition of the bacterial community in IC urine. The reduced microbial diversity and richness is accompanied by a higher abundance of the bacterial genus Lactobacillus, compared to HF urine. This study demonstrates that high throughput sequencing analysis of urine microbiota in IC patients is a powerful tool towards a better understanding of this enigmatic disease. PMID:22974186

[The correlation between serum uric acid level and early-phase insulin secretion in subjects with normal glucose regulation].

PubMed

Lu, L; Zheng, F P; Li, H

2016-05-01

To investigate the correlation between serum uric acid (SUA) level and early-phase insulin secretion in subjects with normal glucose regulation (NGR). Totally 367 community NGR residents confirmed by a 75g oral glucose tolerance test were enrolled. The insulin resistance index (HOMA-IR) and the early-phase insulin secretion index after a glucose load (ΔI30/ΔG30) were used to estimate the insulin sensitivity and the early-phase insulin secretion, respectively. The subjects were divided into 4 groups according to the SUA level quartiles. Differences in early-phase insulin levels, ΔI30/ΔG30, and HOMA-IR were compared among the 4 groups. Age, BMI, waist circumference, systolic blood pressure, diastolic blood pressure, fasting insulin (FINS), 30 minutes postprandial insulin(30 minINS), 2 hours postprandial insulin(2hINS), HOMA-IR and TG levels increased across the rising categories of SUA levels, while the HDL-C was decreased across the SUA groups (P<0.01). The SUA level was positively correlated with age(r=0.157, P<0.01), BMI(r=0.262, P<0.01), waist circumference(r=0.372, P<0.01), systolic blood pressure(r=0.200, P<0.01), diastolic blood pressure(r=0.254, P<0.01), 30 minutes postprandial plasma glucose(r=0.118, P=0.023), FINS(r=0.249, P<0.01), 30minINS(r=0.189, P<0.01), 2hINS(r=0.206, P<0.01), glycosylated hemoglobin(HbA1c, r=0.106, P=0.042), HOMA-IR(r=0.244, P<0.01), TG(r=0.350, P<0.01), ΔI30/ΔG30(r=0.144, P<0.01), and negatively correlated with HDL-C level(r=-0.321, P<0.01). Multiple stepwise regression analysis showed that SUA(β=0.292, P<0.01) and HOMA-IR(β=29.821, P<0.01) were positively associated with ΔI30/ΔG30. SUA level is closely related with the early-phase insulin secretion in NGR subjects.

The relationship between combination inhaled corticosteroid and long-acting beta-agonist use and severe asthma exacerbations in a diverse population

PubMed Central

Wells, Karen E.; Peterson, Edward L.; Ahmedani, Brian K.; Severson, Richard K.; Gleason-Comstock, Julie; Williams, L. Keoki

2012-01-01

Background Safety concerns surround the use of long-acting beta agonists (LABA) for the treatment of asthma, even in combination with inhaled corticosteroids (ICS) and particularly in high-risk subgroups. Objective To estimate the effect ICS therapy and fixed-dose ICS/LABA combination therapy on severe asthma exacerbations in a racially diverse population. Methods Inhaled corticosteroid and ICS/LABA exposure was estimated from pharmacy data for patients with asthma age 12 to 56 years who were members of a large health maintenance organization. Inhaled corticosteroid and ICS/LABA use was estimated for each day of follow-up to create a moving window of exposure. Proportional hazard models were used to assess the relationship between ICS and ICS/LABA combination therapy and severe asthma exacerbations (i.e., use of oral corticosteroids, asthma-related emergency department visit, or asthma-related hospitalization). Results Among the 1,828 patients who met the inclusion criteria, 37% were African American, 46% were treated with ICS therapy alone, and 54% were treated with an ICS/LABA combination. Models assessing the risk of severe asthma exacerbations among individuals using ICS treatment alone and ICS/LABA combination therapy suggested that the overall protective effect was as good or better for ICS/LABA combination therapy when compared with ICS treatment alone (hazard ratio [HR]=0.65 vs. HR=0.72, respectively). Analyses in several subgroups, including African American patients, showed a similar statistically significant protective association for combination therapy. Conclusion Treatment with ICS/LABA fixed combination therapy appeared to perform as well or better than ICS alone in reducing severe asthma exacerbations; this included multiple high-risk subgroups. PMID:22281166

The quest for solvable multistate Landau-Zener models

DOE PAGES

Sinitsyn, Nikolai A.; Chernyak, Vladimir Y.

2017-05-24

Recently, integrability conditions (ICs) in mutistate Landau-Zener (MLZ) theory were proposed. They describe common properties of all known solved systems with linearly time-dependent Hamiltonians. Here we show that ICs enable efficient computer assisted search for new solvable MLZ models that span complexity range from several interacting states to mesoscopic systems with many-body dynamics and combinatorially large phase space. This diversity suggests that nontrivial solvable MLZ models are numerous. Additionally, we refine the formulation of ICs and extend the class of solvable systems to models with points of multiple diabatic level crossing.

Intracellular Insulin-like Growth Factor-I Induces Bcl-2 Expression in Airway Epithelial Cells 1

PubMed Central

Chand, Hitendra S.; Harris, Jennifer Foster; Mebratu, Yohannes; Chen, Yangde; Wright, Paul S.; Randell, Scott H.; Tesfaigzi, Yohannes

2012-01-01

Bcl-2, a prosurvival protein, regulates programmed cell death during development and repair processes, and can be oncogenic when cell proliferation is deregulated. The present study investigated what factors modulate Bcl-2 expression in airway epithelial cells and identified the pathways involved. Microarray analysis of mRNA from airway epithelial cells captured by laser microdissection showed that increased expression of IL-1β and IGF-1 coincided with induced Bcl-2 expression compared to controls. Treatment of cultured airway epithelial cells with IL-1β and IGF-1 induced Bcl-2 expression by increasing Bcl-2 mRNA stability with no discernible changes in promoter activity. Silencing the IGF-1 expression using shRNA showed that intracellular (IC)-IGF-1 was increasing Bcl-2 expression. Blocking EGFR or IGF-1R activation also suppressed IC-IGF-1, and abolished the Bcl-2 induction. Induced expression and co-localization of IC-IGF-1 and Bcl-2 were observed in airway epithelial cells of mice exposed to LPS or cigarette smoke and of patients with cystic fibrosis and chronic bronchitis but not in the respective controls. These studies demonstrate that IC-IGF-1 induces Bcl-2 expression in epithelial cells via IGF-1R and EGFR pathways, and targeting IC-IGF-1 could be beneficial to treat chronic airway diseases. PMID:22461702

Development of an Immunochromatography Assay (QuickNavi-Ebola) to Detect Multiple Species of Ebolaviruses

PubMed Central

Yoshida, Reiko; Muramatsu, Shino; Akita, Hiroshi; Saito, Yuji; Kuwahara, Miwa; Kato, Daisuke; Changula, Katendi; Miyamoto, Hiroko; Kajihara, Masahiro; Manzoor, Rashid; Furuyama, Wakako; Marzi, Andrea; Feldmann, Heinz; Mweene, Aaron; Masumu, Justin; Kapeteshi, Jimmy; Muyembe-Tamfum, Jean-Jacques; Takada, Ayato

2016-01-01

The latest outbreak of Ebola virus disease (EVD) in West Africa has highlighted the urgent need for the development of rapid and reliable diagnostic assays. We used monoclonal antibodies specific to the ebolavirus nucleoprotein to develop an immunochromatography (IC) assay (QuickNavi-Ebola) for rapid diagnosis of EVD. The IC assay was first evaluated with tissue culture supernatants of infected Vero E6 cells and found to be capable of detecting 103–104 focus-forming units/mL of ebolaviruses. Using serum samples from experimentally infected nonhuman primates, we confirmed that the assay could detect the viral antigen shortly after disease onset. It was also noted that multiple species of ebolaviruses could be detected by the IC assay. Owing to the simplicity of the assay procedure and absence of requirements for special equipment and training, QuickNavi-Ebola is expected to be a useful tool for rapid diagnosis of EVD. PMID:27462094

Pralidoxime inhibits paraoxon-induced depression of rocuronium-neuromuscular block in a time-dependent fashion.

PubMed

Narimatsu, Eichi; Niiya, Tomohisa; Takahashi, Kazunobu; Yamauchi, Masanori; Yamakage, Michiaki

2012-07-01

The composite effects of organophosphorus (OP)-cholinesterase (ChE) inhibitors and oximes on the actions of nondepolarizing neuromuscular blockers in acute OP-ChE inhibitor intoxication have not been evaluated in detail. We investigated the effects of paraoxon (Pox) (an OP-ChE inhibitor) and pralidoxime (PAM) (an oxime) on the nondepolarizing neuromuscular blocking action of rocuronium. Isometric twitch tensions of rat left phrenic nerve-hemidiaphragm preparations elicited by indirect (phrenic nerve) supramaximal stimulation at 0.1 Hz were evaluated. Analysis of variance with post hoc testing was used for statistical comparison, and P < .05 was accepted as significant. Rocuronium reduced the indirectly elicited twitch tensions in normal (50% inhibitory concentration [IC(50)], 9.84 [9.64-10.04] μM, mean [95% confidence interval]) and all pretreated diaphragms (P < .01, n = 6) in a concentration-dependent fashion. Paraoxon caused a rightward shift in the rocuronium concentration-twitch tension curve (IC(50), 15.48 [15.24-15.72] μM). The rightward shift was completely inhibited by previous copretreatment (IC(50), 9.98 [9.77-10.20] μM) and partially inhibited by simultaneous copretreatment (IC(50), 11.68 [11.45-11.91] μM) with PAM but was not inhibited by subsequent copretreatment (IC(50), 13.69 [13.39-13.99] μM) with PAM (P < .01, n = 6). Atropine did not influence the rightward shift (P < .01, n = 6). Paraoxon depressed rocuronium-induced neuromuscular block by inhibiting ChEs, and the action of Pox was inhibited by PAM. Pralidoxime acts more intensely when applied earlier. The time-dependent effect of PAM indicates that the preceding presence of PAM in proximity to ChEs before Pox is necessary for definite suppression of the Pox-induced ChE inhibition. Copyright © 2012 Elsevier Inc. All rights reserved.

Histamine receptors in human detrusor smooth muscle cells: physiological properties and immunohistochemical representation of subtypes.

PubMed

Neuhaus, Jochen; Weimann, Annett; Stolzenburg, Jens-Uwe; Dawood, Waled; Schwalenberg, Thilo; Dorschner, Wolfgang

2006-06-01

The potent inflammatory mediator histamine is released from activated mast cells in interstitial cystitis (IC). Here, we report on the histamine receptor subtypes involved in the intracellular calcium response of cultured smooth muscle cells (cSMC). Fura-2 was used to monitor the calcium response in cSMC, cultured from human detrusor biopsies. The distribution of histamine receptor subtypes was addressed by immunocytochemistry in situ and in vitro. Histamine stimulated a maximum of 92% of the cells (n=335), being more effective than carbachol (70%, n=920). HTMT (H1R-agonist), dimaprit (H2R) and MTH (H3R) lead to significant lower numbers of reacting cells (60, 48 and 54%). Histamine receptor immunoreactivity (H1R, H2R, H3R, H4R) was found in situ and in vitro. Histamine-induced calcium increase is mediated by distinct histamine receptors. Thus, pre-therapeutic evaluation of histamine receptor expression in IC patients may help to optimize therapy by using a patient-specific cocktail of subtype-specific histamine receptor antagonists.

An evaluation of the inhibitory effects against rotavirus infection of edible plant extracts

PubMed Central

2012-01-01

Background Rotaviruses are the single most important cause of severe diarrhea in young children worldwide. The developments of specific, potent and accessible antiviral treatments that restrain rotavirus infection remain important to control rotavirus disease. Methods 150 plant extracts with nutritional applications were screened in vitro on MA-104 cells for their antiviral activity against rhesus rotavirus (RRV). One extract (Aspalathus linearis (Burm.f.) R.Dahlgren) was also tested for its effect on the loss of transepithelial resistance (TER) of Caco-2 cells caused by simian rotavirus (SA-11) infection. Results Aqueous extracts of Nelumbo nucifera Gaertn. fruit, Urtica dioica L. root, Aspalathus linearis (Burm.f.) R.Dahlgren leaves, Glycyrrhiza glabra L. root and Olea europaea L. leaves were found to have strong significant antiviral activity with a 50% inhibitory concentration (IC50) < 300 μg/ml. The pure compound 18ß-glycyrrhetinic acid from Glycyrrhiza glabra was found to have the strongest antiviral activity (IC50 46 μM), followed by luteolin and vitexin from Aspalathus linearis (IC50 respectively 116 μM and 129 μM) and apigenin-7-O-glucoside from Melissa officinalis (IC50 150 μM). A combination of Glycyrrhiza glabra L. + Nelumbo nucifera Gaertn. and Urtica dioica L. + Nelumbo nucifera Gaertn. showed synergy in their anti-viral activities. Aspalathus linearis (Burm.f.) R.Dahlgren showed no positive effect on the maintenance of the TER. Conclusions These results indicate that nutritional intervention with extracts of Nelumbo nucifera Gaertn., Aspalathus linearis (Burm.f.) R.Dahlgren, Urtica dioica L., Glycyrrhiza glabra L. and Olea europaea L. might be useful in the treatment of diarrhea caused by rotavirus infection. PMID:22834653

An evaluation of the inhibitory effects against rotavirus infection of edible plant extracts.

PubMed

Knipping, Karen; Garssen, Johan; van't Land, Belinda

2012-07-26

Rotaviruses are the single most important cause of severe diarrhea in young children worldwide. The developments of specific, potent and accessible antiviral treatments that restrain rotavirus infection remain important to control rotavirus disease. 150 plant extracts with nutritional applications were screened in vitro on MA-104 cells for their antiviral activity against rhesus rotavirus (RRV). One extract (Aspalathus linearis (Burm.f.) R.Dahlgren) was also tested for its effect on the loss of transepithelial resistance (TER) of Caco-2 cells caused by simian rotavirus (SA-11) infection. Aqueous extracts of Nelumbo nucifera Gaertn. fruit, Urtica dioica L. root, Aspalathus linearis (Burm.f.) R.Dahlgren leaves, Glycyrrhiza glabra L. root and Olea europaea L. leaves were found to have strong significant antiviral activity with a 50% inhibitory concentration (IC50) < 300 μg/ml. The pure compound 18ß-glycyrrhetinic acid from Glycyrrhiza glabra was found to have the strongest antiviral activity (IC50 46 μM), followed by luteolin and vitexin from Aspalathus linearis (IC50 respectively 116 μM and 129 μM) and apigenin-7-O-glucoside from Melissa officinalis (IC50 150 μM). A combination of Glycyrrhiza glabra L. + Nelumbo nucifera Gaertn. and Urtica dioica L. + Nelumbo nucifera Gaertn. showed synergy in their anti-viral activities. Aspalathus linearis (Burm.f.) R.Dahlgren showed no positive effect on the maintenance of the TER. These results indicate that nutritional intervention with extracts of Nelumbo nucifera Gaertn., Aspalathus linearis (Burm.f.) R.Dahlgren, Urtica dioica L., Glycyrrhiza glabra L. and Olea europaea L. might be useful in the treatment of diarrhea caused by rotavirus infection.

A conformational restriction approach to the development of dual inhibitors of acetylcholinesterase and serotonin transporter as potential agents for Alzheimer's disease.

PubMed

Toda, Narihiro; Tago, Keiko; Marumoto, Shinji; Takami, Kazuko; Ori, Mayuko; Yamada, Naho; Koyama, Kazuo; Naruto, Shunji; Abe, Kazumi; Yamazaki, Reina; Hara, Takao; Aoyagi, Atsushi; Abe, Yasuyuki; Kaneko, Tsugio; Kogen, Hiroshi

2003-10-01

Alzheimer's disease (AD) has been treated with acetylcholinesterase (AChE) inhibitors such as donepezil. However, the clinical usefulness of AChE inhibitors is limited mainly due to their adverse peripheral effects. Depression seen in AD patients has been treated with serotonin transporter (SERT) inhibitors. We considered that combining SERT and AChE inhibition could improve the clinical usefulness of AChE inhibitors. In a previous paper, we found a potential dual inhibitor, 1, of AChE (IC50=101 nM) and SERT (IC50=42 nM), but its AChE inhibition activity was less than donepezil (IC50=10 nM). Here, we report the conformationally restricted (R)-18a considerably enhanced inhibitory activity against AChE (IC50=14 nM) and SERT (IC50=6 nM).

Inertial cavitation dose produced ex vivo in rabbit ear arteries with optison

NASA Astrophysics Data System (ADS)

Tu, Juan; Brayman, Andrew; Matula, Thomas

2004-05-01

Ultrasound-induced inertial cavitation (IC) effects were studied ex vivo in rabbit ear arteries with the addition of ultrasound contrast agents (UCAs). Ears were removed from New Zealand white rabbits immediately after being euthanized under a protocol approved by the University of Washington IACUC. The auricular arteries were perfused with varying concentration of UCA (Optison) in saline and exposed to 1.155-MHz pulsed high-intensity focused ultrasound (HIFU) with constant PRF (10 Hz), pulse length (20 cycles), and total treatment time (20 s). Experiments were performed for variable peak negative acoustic pressure (P-) (from 0.19 to 3.31 Mpa) and Optison volume concentration (0% [saline only], 0.1%, 0.2%, 0.5%, and 1%). Cavitation activity was quantified by IC Dose (cumulated root-mean-squared [rms] broadband noise amplitude in a particular band in the frequency domain). The results showed that (1) IC activity was induced much more easily with the addition of Optison, even at low volume concentration, such as 0.1%. (2) IC dose increased significantly with the increasing acoustic pressure and Optison concentration. (3) Higher concentrations of Optison decreased the IC threshold. [Work supported by NIH 8RO1 EB00350-2.

Sensitive and specific detection of classical scrapie prions in the brain of goats by real-time quaking-induced conversion

USDA-ARS?s Scientific Manuscript database

The real-time quaking-induced conversion (RT-QuIC) is a rapid, specific, and sensitive prion seeding activity detection assay that uses recombinant prion protein (rPrPSen) to detect sub-infectious levels of the abnormal isoforms of the prion protein (PrPSc). Although RT-QuIC has been successfully us...

Carbon Monoxide Exposure in Youth Ice Hockey.

PubMed

Macnow, Theodore; Mannix, Rebekah; Meehan, William P

2017-11-01

To examine the effect of ice resurfacer type on carboxyhemoglobin levels in youth hockey players. We hypothesized that players in arenas with electric resurfacers would have normal, stable carboxyhemoglobin levels during games, whereas those in arenas with internal combustion engine (IC) resurfacers would have an increase in carboxyhemoglobin levels. Prospective cohort study. Enclosed ice arenas in the northeastern United States. Convenience sample of players aged 8 to 18 years old in 16 games at different arenas. Eight arenas (37 players) used an IC ice resurfacer and 8 arenas (36 players) an electric resurfacer. Carboxyhemoglobin levels (SpCO) were measured using a pulse CO-oximeter before and after the game. Arena air was tested for carbon monoxide (CO) using a metered gas detector. Players completed symptom questionnaires. The change in SpCO from pregame to postgame was compared between players at arenas with electric versus IC resurfacers. Carbon monoxide was present at 6 of 8 arenas using IC resurfacers, levels ranged from 4 to 42 parts per million. Carbon monoxide was not found at arenas with electric resurfacers. Players at arenas with IC resurfacers had higher median pregame SpCO levels compared with those at electric arenas (4.3% vs 1%, P < 0.01). Players in the IC group also had a significant increase in their SpCO level during a hockey game compared with those in the electric group (2.8% vs 1%, P = 0.01). There were no significant differences in symptom scores. Players at arenas operating IC resurfacers had significantly higher SpCO levels. Youth hockey players in arenas with IC resurfacers have an increase in carboxyhemoglobin during games and have elevated baseline carboxyhemoglobin levels compared with players at arenas with electric resurfacers. Electric resurfacers decrease the risk of CO exposure.

Mapping Direct Observations From Objective Structured Clinical Examinations to the Milestones Across Specialties.

PubMed

Baker-Genaw, Kimberly; Kokas, Maria S; Ahsan, Syed F; Darnley-Fisch, Deborah; Drake, Sean; Goyal, Nikhil; Inamdar, Kedar; Moutzouros, Vasilios; Prabhakar, Deepak; Rolland, Laurie; Sangha, Roopina; Shreve, Maria; Woodward, Ann

2016-07-01

Little is known about residents' performance on the milestones at the institutional level. Our institution formed a work group to explore this using an institutional-level curriculum and residents' evaluation of the milestones. We assessed whether beginner-level milestones for interpersonal and communication skills (ICS) related to observable behaviors in ICS-focused objective structured clinical examinations (OSCEs) for postgraduate year (PGY) 1 residents across specialties. The work group compared ICS subcompetencies across 12 programs to identify common beginner-level physician-patient communication milestones. The selected ICS milestone sets were compared for common language with the ICS-OSCE assessment tool-the Kalamazoo Essential Elements of Communication Checklist-Adapted (KEECC-A). To assess whether OSCE scores related to ICS milestone scores, all PGY-1 residents from programs that were part of Next Accreditation System Phase 1 were identified; their OSCE scores from July 2013 to June 2014 and ICS subcompetency scores from December 2014 were compared. The milestones for 10 specialties and the transitional year had at least 1 ICS subcompetency that related to physician-patient communication. The language of the ICS beginner-level milestones appears similar to behaviors outlined in the KEECC-A. All 60 residents with complete data received at least a beginner-level ICS subcompetency score and at least a satisfactory score on all 3 OSCEs. The ICS-OSCE scores for PGY-1 residents appear to relate to beginner-level milestones for physician-patient communication across multiple specialties.

Simultaneous control of multiple instruments at the Advanced Technology Solar Telescope

NASA Astrophysics Data System (ADS)

Johansson, Erik M.; Goodrich, Bret

2012-09-01

The Advanced Technology Solar Telescope (ATST) is a 4-meter solar observatory under construction at Haleakala, Hawaii. The simultaneous use of multiple instruments is one of the unique capabilities that makes the ATST a premier ground based solar observatory. Control of the instrument suite is accomplished by the Instrument Control System (ICS), a layer of software between the Observatory Control System (OCS) and the instruments. The ICS presents a single narrow interface to the OCS and provides a standard interface for the instruments to be controlled. It is built upon the ATST Common Services Framework (CSF), an infrastructure for the implementation of a distributed control system. The ICS responds to OCS commands and events, coordinating and distributing them to the various instruments while monitoring their progress and reporting the status back to the OCS. The ICS requires no specific knowledge about the instruments. All information about the instruments used in an experiment is passed by the OCS to the ICS, which extracts and forwards the parameters to the appropriate instrument controllers. The instruments participating in an experiment define the active instrument set. A subset of those instruments must complete their observing activities in order for the experiment to be considered complete and are referred to as the must-complete instrument set. In addition, instruments may participate in eavesdrop mode, outside of the control of the ICS. All instrument controllers use the same standard narrow interface, which allows new instruments to be added without having to modify the interface or any existing instrument controllers.

Facteurs associés à la non observance thérapeutique des sujets adultes infectés par le VIH sous antirétroviraux dans un hôpital de référence à Douala

PubMed Central

Essomba, Emmanuel Noel; Adiogo, Dieudonné; Koum, Danielle Christiane Kedy; Amang, Baudouin; Lehman, Leopold Gustave; Coppieters, Yves

2015-01-01

Introduction Le succès du traitement antirétroviral repose sur l'observance. Elle est nécessaire pour réduire la mortalité, diminuer le risque de résistance et restaurer l'immunité. Cette étude a pour but d'identifier et analyser les différents facteurs associés à la non observance thérapeutique des patients infectés par le VIH sous traitement antirétroviraux à l'hôpital de référence Laquintinie de Douala. Méthodes Il s'agit d'une étude transversale et analytique effectuée de mars à juin 2014. La non observance est mesurée à travers les déclarations du patient et sur consultation des registres de renouvellement des ordonnances. Etaient non observant, ceux ayant consommé moins de 95% de médicaments et ceux ne s’étant pas présentés pour le renouvellement de l'ordonnance. L'analyse bivariée et le modèle de régression logistique ont été utilisés pour la détermination des facteurs associés à la non observance. Résultats Au total, 524 patients ont été enrôlés dans l’étude;l’âge moyen était de 43,0 ± 10,7 ans et le sexe ratio H/F de 0,54. De ces patients, 49,0% étaient non observant, majoritairement des femmes (61,9%). Les principales raisons avancées de la non observance sont: l'oubli (32,9%), la rupture de médicaments (14,0%), les occupations (12,8%). Les personnes veuves(IC 95% OR= 1,31-5,22, p= 0,006), la consommation des excitants (IC 95%, OR= 2,30-6,90, p= 0,0001) et la présence d'infection opportuniste (IC 95%, OR= 1,41-17,54, p= 0,01) ont fortement été associés à la non observance. Conclusion Le taux d'observance était faible, lié à plusieurs facteurs. Des mesures sont nécessaires pour résoudre ce problème, y compris des stratégies tendant à l'amélioration du soutien psycho-social, et la limitation des ruptures de stock de médicaments. La recherche qualitative est souhaitée pour comprendre les raisons de la non observance afin de mettre au point des interventions fondées sur des données probantes. PMID:26301016

Efficient dynamic molecular simulation using QSAR model to know inhibition activity in breast cancer medicine

NASA Astrophysics Data System (ADS)

Zharifah, A.; Kusumowardani, E.; Saputro, A.; Sarwinda, D.

2017-07-01

According to data from GLOBOCAN (IARC) at 2012, breast cancer was the highest rated of new cancer case by 43.3 % (after controlled by age), with mortality rated as high as 12.9 %. Oncology is a major field which focusing on improving the development of drug and therapeutics cancer in pharmaceutical and biotechnology companies. Nowadays, many researchers lead to computational chemistry and bioinformatic for pharmacophore generation. A pharmacophore describes as a group of atoms in the molecule which is considered to be responsible for a pharmacological action. Prediction of biological function from chemical structure in silico modeling reduces the use of chemical reagents so the risk of environmental pollution decreased. In this research, we proposed QSAR model to analyze the composition of cancer drugs which assumed to be homogenous in character and treatment. Atomic interactions which analyzed are learned through parameters such as log p as descriptors hydrophobic, n_poinas descriptor contour strength and molecular structure, and also various concentrations inhibitor (micromolar and nanomolar) from NCBI drugs bank. The differences inhibitor activity was observed by the presence of IC 50 residues value from inhibitor substances at various concentration. Then, we got a general overview of the state of safety for drug stability seen from its IC 50 value. In our study, we also compared between micromolar and nanomolar inhibitor effect from QSAR model results. The QSAR model analysis shows that the drug concentration with nanomolar is better than micromolar, related with the content of inhibitor substances concentration. This QSAR model got the equation: Log 1/IC50 = (0.284) (±0.195) logP + (0.02) (±0.012) n_poin + (-0.005) (±0.083) Inhibition10.2nanoM + (0.1) (±0.079) Inhibition30.5nanoM + (-0.016) (±0.045) Inhibition91.5nanoM + (-2.572) (±1.570) (n = 13; r = 0.813; r2 = 0.660; s = 0.764; F = 2.720; q2 = 0.660).

Serial interactome capture of the human cell nucleus.

PubMed

Conrad, Thomas; Albrecht, Anne-Susann; de Melo Costa, Veronica Rodrigues; Sauer, Sascha; Meierhofer, David; Ørom, Ulf Andersson

2016-04-04

Novel RNA-guided cellular functions are paralleled by an increasing number of RNA-binding proteins (RBPs). Here we present 'serial RNA interactome capture' (serIC), a multiple purification procedure of ultraviolet-crosslinked poly(A)-RNA-protein complexes that enables global RBP detection with high specificity. We apply serIC to the nuclei of proliferating K562 cells to obtain the first human nuclear RNA interactome. The domain composition of the 382 identified nuclear RBPs markedly differs from previous IC experiments, including few factors without known RNA-binding domains that are in good agreement with computationally predicted RNA binding. serIC extends the number of DNA-RNA-binding proteins (DRBPs), and reveals a network of RBPs involved in p53 signalling and double-strand break repair. serIC is an effective tool to couple global RBP capture with additional selection or labelling steps for specific detection of highly purified RBPs.

Chemical composition and in vitro antitrypanosomal activity of fractions of essential oil from Cymbopogon nardus L.

PubMed

Muhd Haffiz, J; Norhayati, I; Getha, K; Nor Azah, M A; Mohd Ilham, A; Lili Sahira, H; Roshan Jahn, M S; Muhd Syamil, A

2013-03-01

Essential oil from Cymbopogon nardus was evaluated for activity against Trypanosoma brucei brucei BS221 (IC50 = 0.31 ± 0.03 μg/mL) and cytotoxic effect on normal kidney (Vero) cells (IC50 = >100 μg/mL). The crude essential oil was subjected to various chromatography techniques afforded active sub fractions with antitrypanosomal activity; F4 (IC50 = 0.61 ± 0.06 μg/mL), F6 (IC50= 0.73 ± 0.33 μg/mL), F7 (IC50 = 1.15 ± 0 μg/mL) and F8 (IC50 = 1.11 ± 0.01 μg/mL). These active fractions did not exhibit any toxic effects against Vero cell lines and the chemical profiles investigation indicated presence of α-and γ-eudesmol, elemol, α-cadinol and eugenol by GC/MS analysis.

Increased alternate splicing of Htr2c in a mouse model for Prader-Willi syndrome leads disruption of 5HT2C receptor mediated appetite.

PubMed

Garfield, Alastair S; Davies, Jennifer R; Burke, Luke K; Furby, Hannah V; Wilkinson, Lawrence S; Heisler, Lora K; Isles, Anthony R

2016-12-08

Alternate splicing of serotonin (5-hydroxytryptamine; 5-HT) 2C receptor (5-HT 2C R) pre-RNA is negatively regulated by the small nucleolar RNA, Snord115, loss of which is observed in nearly all individuals with Prader-Willi Syndrome (PWS), a multigenic disorder characterised by hyperphagia and obesity. Given the role of the 5-HT 2C R in the regulation of ingestive behaviour we investigated the pathophysiological implications of Snord115 deficiency on 5-HT 2C R regulated appetite in a genotypically relevant PWS mouse model (PWS-IC). Specifically, we demonstrate that loss of Snord115 expression is associated with increased levels of hypothalamic truncated 5-HT 2C R pre-mRNA. The 5-HT 2C R promotes appetite suppression via engagement of the central melanocortin system. Pro-opiomelancortin (Pomc) mRNA levels within the arcuate nucleus of the hypothalamus (ARC) were reduced in PWS-IC mice. We then went on to assess the functional consequences of these molecular changes, demonstrating that PWS-IC mice are unresponsive to an anorectic doses of a 5-HT 2C R agonist and that this is associated with attenuated activation of POMC neurons within the ARC. These data provide new insight into the significance of Htr2c pre-mRNA processing to the physiological regulation of appetite and potentially the pathological manifestation of hyperphagia in PWS. Furthermore, these findings have translational relevance for individuals with PWS who may seek to control appetite with another 5-HT 2C R agonist, the new obesity treatment lorcaserin.

Detection of kanamycin and gentamicin residues in animal-derived food using IgY antibody based ic-ELISA and FPIA.

PubMed

Li, Cui; Zhang, Yaoyao; Eremin, Sergei A; Yakup, Omar; Yao, Gang; Zhang, Xiaoying

2017-07-15

Our aim in this study is to show that IgY antibody based immunoassays could be used to detect antibiotic residues in animal-derived food. Briefly, full antigens of gentamicin (Gent) and kanamycin (Kana) were used to immunize the laying chickens to prepare IgY antibodies. Then, these antibodies were evaluated by FPIA and ic-ELISA to detect Gent/Kana in animal-derived samples. The IC 50 of FPIA and ic-ELISA based anti-Gent IgY were 7.70±0.6μg/mL and 0.32±0.06μg/mL, respectively. The IC 50 of FPIA and ic-ELISA based anti-Kana IgY were 7.97±0.9μg/mL and 0.15±0.01μg/mL. The limits of detection (LOD, IC 10 ) for FPIA based anti-Gent/Kana IgY were 0.17 and 0.007μg/mL, respectively. The LOD for ic-ELISA were both 0.001μg/mL. These results indicated that the ic-ELISA might more suitable for antibiotic residues detection than FPIA. Copyright © 2017 Elsevier Ltd. All rights reserved.

An Elastic-Plastic Finite Element Analysis of Notched Aluminum Panels.

DTIC Science & Technology

1981-03-01

p- I - 41 - m Lux Lux wb 01- -a 1- On 4-u 4. oil 4i ..J 0 I0IltI-flIw III- Q. ... ucj 4W 0U 0 0.J f- < -W -4 0- u. 0 WO I -- 0-= LU to z 0 r WW.WW..a W...sto - PQ NJ . 0-0 WWU 00 M-. a~ a-p 0 ft N 0 .0 S. pu p ppi 90 -1- at f.wL -+0 IN,~ ZLU .AW-W).’-= 000 0W-W..-a. %.Uh" *.- i XI-00 a- 0 OIL *0. .0.O...W0..JC4$4 -L ...- P-4-~. C(.0 ZZO.0.Z<ZOOZWji IOnizest N - If I .- Luv .0 11 01-W0.IC If C-WJII1 I ’- ~% 1I It 1 &h to _0. I ;_2 1# CA--ɟn-.-0. 1 ;)ZO.-4

Current statins show calcium channel blocking activity through voltage gated channels.

PubMed

Ali, Niaz; Begum, Robina; Faisal, Muhammad Saleh; Khan, Aslam; Nabi, Muhammad; Shehzadi, Gulfam; Ullah, Shakir; Ali, Waqar

2016-09-21

Statins are used for treatment of hypercholestremia. Common adverse reports associated with use of statins are generalized bodyache, rhabdomyolysis, muscles weakness and gastrointestinal disorders. The current work is an attempt to explain how smooth muscles of gastrointestinal tissues are affected by the current statins (Simvastatin, atorvastatin, fluvastatin and rosuvastatin). Effects of the current statins were studied on spontaneous activity of isolated rabbits' jejunal preparations. Different molar concentrations (10(-12)-10(-2)M) of the statins were applied on spontaneously contracting rabbits' jejunal preparations. As statins relaxed spontaneous activity, so we tested the statins on KCl (80 mM) induced contractions in similar test concentrations. Positive relaxant statins were tested again through construction of Calcium Concentration Response Curves (CCRCs) in the absence and presence of the statins using verapamil, a standard calcium channel blocker. CCRCs of statins were compared with CCRCs of verapamil. Simvastatin, atorvastatin, fluvastatin and rosuvastatin relaxed the spontaneous and KCl-induced contractions. IC50 for simvastatin on spontaneous rabbit's jejunal preparations is -5.08 ± 0.1 Log 10 M. Similarly, IC50 for KCl-induced contractions is -4.25 ± 0.01 Log 10 M. Mean IC50 (Log 10 M) for atorvastatin on spontaneous rabbit's jejunal preparations and KCl-induced contractions are -5.19 ± 0.07 and -4.37 ± 0.09, respectively. Fluvastatin relaxed spontaneous activity of rabbits' jejunal preparations with an IC50 (Log 10 M) -4.5 ± 0.03. Rosuvastatin relaxed spontaneous as well as KCl (80 mM) induced contractions with respective IC50 (Log 10 M) -3.62 ± 0.04 and -4.57 ± 0.06. In case of CCRCs, tissues pre-treated with 4.6 μg/ml of simvastatin, have IC50 = -1.84 ± 0.03 [log (Ca(++)) M] vs control IC50 = -2.54 ± 0.04 [log (Ca(++)) M]. Similarly, atorvastatin, fluvastatin and rosuvastatin produced significant right shift in IC50 for CCRCs (P ≤ 0.05). In case of verapamil, IC50 for control curves is -2.45 ± 0.06 [log (Ca (++)) M], while IC50 in presence of verapamil (0.1 μM) is -1.69 ± 0.05 [log (Ca (++)) M]. Statins produced right shift in the IC50 of CCRCs. The effects of statins are like that of effects of verapamil, a standard calcium channel blocker. Our findings suggest that current statins have calcium antagonistic effects that act on voltage gated calcium channels that may provide a rationale for cause muscle weakness and gastrointestinal disorders.

Pulsed Power Bibliography. Volume 2. Annotated Bibliography.

DTIC Science & Technology

1983-08-01

grounded wires and lower t a-so;Roou.- Loop, Currt Transcur ~r Pull "Iv~rs oo d buring nvrro in orc ned fbec ar Sttfeto ey dl Prb evv-.on d - the .opera...ineno01 -,.oocmv,,p. areto has bees develope Thrt toa p.a Ic--el "’c IIT rea:idAl n us o Onviii:1 wIt p0 toO men-nun1-- Fr’-or--V nan High Pulled owr Cih...PERMISSilUic-o.orr tlvi0 tent icg .e Neo "nePrforme on 10 b., vulro-nit L1C ci.iit usini- a VAS Singla1 pull . tens t T t put nf ’~n cavuan copy srcacsal

Installation Restoration Program. Phase 2. Confirmation/Quantification Stage 1. US Air Force Plant Number 42, Palmdale, California. Volume 2.

DTIC Science & Technology

1987-02-20

Dnor:)c7i’,orotneane .0i fN D____ __I______ C,-icniorcetnyene 0.10 N:DO.02 ____ ____ ____ I n1 ic o cni e -i - ---ii 1- - - 1 Di c roreae_____...n -c 0a r~e~n’ 0.010 NDɘ.010 _____ --- H I().01-0 1z0 0 c ND 7*, 5 was nUJVC.. ceteize ; the _ _ limit__ of deec iofrhiaalsi i _____ ,a t- s-Ie...PASADENA CALIF 20 FEB 87 U N LASF IE F31615-84-D -448 2 F/G 24/7 M N1 . - 1111_1 % . .- 1511 1*% EncineerinQ Science Page 11 ANALYTICAL RESULTS SUMMARY

Efficacy of artemisinin-based combination therapies and prevalence of molecular markers associated with artemisinin, piperaquine and sulfadoxine-pyrimethamine resistance in Sierra Leone.

PubMed

Smith, Samuel J; Kamara, Anitta R Y; Sahr, Foday; Samai, Mohamed; Swaray, Alpha S; Menard, Didier; Warsame, Marian

2018-06-19

Currently, the national malaria control programme (NMCP) of Sierra Leone recommends artesunate-amodiaquine (ASAQ) and artemether-lumefantrine (AL) as first- and second-line treatment for uncomplicated malaria, respectively, and artesunate + sulfadoxine-pyrimethamine (SP) for intermittent preventive treatment during pregnancy and for infants. In 2016, the NMCP conducted a study to assess the clinical and parasitological responses of children under five years to ASAQ, AL and dihydroartemisinin-piperaquine (DHA/PPQ) according to the WHO protocol. Day-0 samples were tested for mutations in the Kelch 13 gene (pfk13) and dihydrofolate reductase/dihydropteroate synthase (dhfr/dhps) genes associated with artemisinin and SP resistance, respectively, and amplification in the Pfplasmepsin2 gene for piperaquine resistance. A total of 295 (ASAQ = 128, AL = 64 and DHA/PPQ = 103) eligible children were enrolled at three sites. PCR-corrected 100% adequate clinical and parasitological response and no parasitaemia on day-3 were observed for all patients in each treatment group. Of the 278 samples with interpretable molecular data, only 2.2% carried non-synonymous pfk13 mutants (A578S, I646T), which are not associated with artemisinin resistance. None of the 103 day-0 samples from the DAH/PPQ group had Pfplasmepsin2 gene amplification, confirming the absence of piperaquine resistance. The prevalence of the triple pfdhfr mutant (N51I/C59R/S108N) was close to or reached fixation (97.4-100%). For combined pfdhfr/pfdhps mutation, 55-71% carried the quadruple (N51I/C59R/S108N+A437G) mutant and about 10% the quintuple mutant N51I/C59R/S108N+A437G/K540E. Our findings confirm that ASAQ, AL and DHA/PPQ were highly effective for the treatment of uncomplicated malaria in the study areas, and neither pfk13 validated mutations nor Pfplasmepsin2 multiple copies were found. The very low prevalence of the quintuple mutant in this study supports the NMCP's decision to introduce intermittent preventive treatment for infants with SP in the districts with high malaria transmission. Copyright © 2018. Published by Elsevier B.V.

Dimensions of self-leadership: a German replication and extension.

PubMed

Müller, Güonter F

2006-10-01

In a sample of 167 German students three dimensions of self-leadership, i.e., constructive thoughts, natural reward creation, and proactive behavior, were replicated as when scale values of a German self-leadership questionnaire were subjected to confirmatory factor analysis very satisfactory fit-indices were obtained. In addition, dimensions of self-leadership correlated with entrepreneurial trait disposition (multiple R=0.46, p < .01), and entrepreneurial job orientation (multiple R=0.23, p < .05). Conclusions for further research and practical applications are discussed.

Prime Contract Awards by State or Country, Place and Contractor. Part 2 (Murfreesboro, Arkansas - Livermore, California), FY1991

DTIC Science & Technology

1991-01-01

0 01 01010 01 CD01 00 01 010 0 < % 5 N0 I 0000 H 01 01 0 0 --00-4 -4 C> 0 -00. 00 o %00 10 %- I 0000...I’-001t- 0 -4 00 0 K I0Mon If N4 -4-IC’-I 0P 5 1 0 4NN C4 I <-4 "iM’)-4 -4 M 04 004JNN-4N-4 -4 -4-4 cc Ks I 0 (i on It 00 IC’)o0 W W0 Oc’-4NS C 0 ...it 1-- - Oil 00000000 -4 -4 -- 0 ) ()00) 0 - S -4 o 5 (-N IS 0001 . o C 0 000 0 0 0 100C,00 0

An Investigation of the Fantasy Predisposition and Fantasy Style of Children with Imaginary Companions

ERIC Educational Resources Information Center

Bouldin, Paula

2006-01-01

In this study, the author tested whether children with imaginary companions (ICs) have a different fantasy life than do children without ICs. To measure the fantasy life of the 74 children aged 3.2 to 8.7 years, the author modified the Children's Fantasy Interview (E. Rosenfeld, L. R. Huesmann, L. D. Eron, & J. V. Torney-Purta, 1982) to make…

Inhibition of Aspergillus parasiticus and cancer cells by marine actinomycete strains

NASA Astrophysics Data System (ADS)

Li, Ping; Yan, Peisheng

2014-12-01

Ten actinomycete strains isolated from the Yellow Sea off China's coasts were identified as belonging to two genera by 16S rDNA phylogenetic analysis: Streptomyces and Nocardiopsis. Six Streptomyces strains (MA10, 2SHXF01-3, MA35, MA05-2, MA05-2-1 and MA08-1) and one Nocardiopsis strain (MA03) were predicted to have the potential to produce aromatic polyketides based on the analysis of the KSα (ketoacyl-synthase) gene in the type II PKS (polyketides synthase) gene cluster. Four strains (MA03, MA01, MA10 and MA05-2) exhibited significant inhibitory effects on mycelia growth (inhibition rate >50%) and subsequent aflatoxin production (inhibition rate >75%) of the mutant aflatoxigenic Aspergillus parasiticus NFRI-95. The ethyl acetate extracts of the broth of these four strains displayed significant inhibitory effects on mycelia growth, and the IC50 values were calculated (MA03: 0.275 mg mL-1, MA01: 0.106 mg mL-1, MA10: 1.345 mg mL-1 and MA05-2: 1.362 mg mL-1). Five strains (2SHXF01-3, MA03, MA05-2, MA01 and MA08-1) were selected based on their high cytotoxic activities. The ethyl acetate extract of the Nocardiopsis strain MA03 was particularly noted for its high antitumor activity against human carcinomas of the cervix (HeLa), lung (A549), kidney (Caki-1) and liver (HepG2) (IC50: 2.890, 1.981, 3.032 and 2.603 μg mL-1, respectively). The extract also remarkably inhibited colony formation of HeLa cells at an extremely low concentration (0.5 μg mL-1). This study highlights that marine-derived actinomycetes are a huge resource of compounds for the biological control of aflatoxin contamination and the development of novel drugs for human carcinomas.

Temperature and Concentration Profiles in Hydrogen-Nitrous Oxide Flames.

DTIC Science & Technology

1986-07-01

SECumvY CLASSIFICATION CF TIS PAGOE(hn Date. 3.,OCO 20. Abstract (Cont’d): est for flame modeler UNCLASSIFIED * SECURITY CL ASSIrIC ATION Or THIS P...Commander Naval Surface Weapons Center Commander ATTN: R. Bernecker, R-13 US Army Tank Automotive G.B. Wilmot , R-16 Command Silver Spring, MD 20902

Glycidamide inhibits progesterone production through reactive oxygen species-induced apoptosis in R2C Rat Leydig Cells.

PubMed

Li, Mingwei; Sun, Jianxia; Zou, Feiyan; Bai, Shun; Jiang, Xinwei; Jiao, Rui; Ou, Shiyi; Zhang, Hui; Su, Zhijian; Huang, Yadong; Bai, Weibin

2017-10-01

The food contaminant acrylamide (AA) is usually recognized as a probable human carcinogen. In addition, AA has also been found able to induce male infertility in animals. Interestingly, resent research work revealed that the toxic effect of AA on the ability of male reproduction in vivo may due to glycidamide (GA) which is the metabolite of AA. In this study, R2C Leydig cells was used to investigate the toxic effects of GA on progesterone production. GA caused dose-dependent inhibition on the cell growth, with IC 25 , IC 50, and IC 75 values found at 0.635, 0.872, and 1.198 mM, respectively. The results of single cell gel/Comet assay showed that GA significantly induced early-phase cell apoptosis, reduced progesterone production, as well as decreasing the protein expression of steroidogenic acute regulatory (StAR) in R2C cells. Furthermore, GA induced overproduction of intracellular reactive oxygen species (ROS), upregulated Bax expression, decreased mitochondrial membrane potential, and triggered mitochondria-mediated cell apoptosis. Consequently, the downstream effector caspase-3 was activated, resulting in Leydig cells apoptosis. Overall, our results showed that GA could damage R2C Leydig cells by the lesion of the ability of progesterone genesis and inducing cells apoptosis. Copyright © 2016 Elsevier Ltd. All rights reserved.

A virtual screening method for inhibitory peptides of Angiotensin I-converting enzyme.

PubMed

Wu, Hongxi; Liu, Yalan; Guo, Mingrong; Xie, Jingli; Jiang, XiaMin

2014-09-01

Natural small peptides from foods have been proven to be efficient inhibitors of Angiotensin I-converting enzyme (ACE) for the regulation of blood pressure. The traditional ACE inhibitory peptides screening method is both time consuming and money costing, to the contrary, virtual screening method by computation can break these limitations. We establish a virtual screening method to obtain ACE inhibitory peptides with the help of Libdock module of Discovery Studio 3.5 software. A significant relationship between Libdock score and experimental IC(50) was found, Libdock score = 10.063 log(1/IC(50)) + 68.08 (R(2) = 0.62). The credibility of the relationship was confirmed by testing the coincidence of the estimated log(1/IC(50)) and measured log(1/IC(50)) (IC(50) is 50% inhibitory concentration toward ACE, in μmol/L) of 5 synthetic ACE inhibitory peptides, which was virtual hydrolyzed and screened from a kind of seafood, Phascolosoma esculenta. Accordingly, Libdock method is a valid IC(50) estimation tool and virtual screening method for small ACE inhibitory peptides. © 2014 Institute of Food Technologists®

Phase II Trial of Preoperative Irinotecan-Cisplatin Followed by Concurrent Irinotecan-Cisplatin and Radiotherapy for Resectable Locally Advanced Gastric and Esophagogastric Junction Adenocarcinoma

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

Rivera, Fernando, E-mail: oncrhf@humv.e; Galan, Maica; Tabernero, Josep

Purpose: To determine in a Phase II trial whether preoperative irinotecan-cisplatin (IC) followed by concurrent IC therapy and radiotherapy (IC/RT) improved outcome in patients with resectable, locally advanced gastric adenocarcinoma (GC) or esophagogastric junction cancer (EGJC). Patients and Methods: Patients with resectable Stage II-IV, M0 GC or EGJC made up the study population. The primary endpoint was pathologic complete response (pCR). Two courses of IC (irinotecan, 65mg/m{sup 2}; cisplatin, 30mg/m{sup 2} on Days 1 and 8 every 21 days) were given. Patients without progression then received IC/RT, consisting of daily radiotherapy (45Gy) with concurrent IC (irinotecan, 65mg/m{sup 2}; cisplatin, 30mg/m{supmore » 2} on Days 1, 8, 15, and 22). Surgical resection was performed, if feasible, 5-8 weeks after the end of radiotherapy. Results: Twenty-three patients were included in the study: 10 with EGJC and 13 with GC. Two patients (9%) achieved pCR. The incidences of Grade 3-4 toxicities were as follows: IC: neutropenia 35% (febrile 13%), anemia 22%, diarrhea 22%, emesis 8%; IC/RT: neutropenia 52% (febrile 5%), asthenia 19%, anemia 9%, emesis 9%, diarrhea 5%, cardiotoxicity 5%. No patients died during IC or IC/RT. R0 resection was achieved in 15 patients (65%). Median survival was 14.5 months, and the actuarial 2-year survival rate was 35%. Conclusions: Preoperative IC followed by IC/RT resulted in moderate response and resection rates with mild toxicity in patients with GC and EGJC.« less

Chemical composition and anticancer, antiinflammatory, antioxidant and antimalarial activities of leaves essential oil of Cedrelopsis grevei.

PubMed

Afoulous, Samia; Ferhout, Hicham; Raoelison, Emmanuel Guy; Valentin, Alexis; Moukarzel, Béatrice; Couderc, François; Bouajila, Jalloul

2013-06-01

The essential oil from Cedrelopsis grevei leaves, an aromatic and medicinal plant from Madagascar, is widely used in folk medicine. Essential oil was characterized by GC-MS and quantified by GC-FID. Sixty-four components were identified. The major constituents were: (E)-β-farnesene (27.61%), δ-cadinene (14.48%), α-copaene (7.65%) and β-elemene (6.96%). The essential oil contained a complex mixture consisting mainly sesquiterpene hydrocarbons (83.42%) and generally sesquiterpenes (98.91%). The essential oil was tested cytotoxic (on human breast cancer cells MCF-7), antimalarial (Plasmodium falciparum), antiinflammatory and antioxidant (ABTS and DPPH assays) activities. C. grevei essential oil was active against MCF-7 cell lines (IC50=21.5 mg/L), against P. falciparum, (IC50=17.5mg/L) and antiinflammatory (IC50=21.33 mg/L). The essential oil exhibited poor antioxidant activity against DPPH (IC50>1000 mg/L) and ABTS (IC50=110 mg/L) assays. A bibliographical review was carried out of all essential oils identified and tested with respect to antiplasmodial, anticancer and antiinflammatory activities. The aim was to establish correlations between the identified compounds and their biological activities (antiplasmodial, anticancer and antiinflammatory). According to the obtained correlations, 1,4-cadinadiene (R(2)=0.61) presented a higher relationship with antimalarial activity. However, only (Z)-β-farnesene (R(2)=0.73) showed a significant correlation for anticancer activity. Copyright © 2013 Elsevier Ltd. All rights reserved.

Altered regulation of Fc gamma RII on aged follicular dendritic cells correlates with immunoreceptor tyrosine-based inhibition motif signaling in B cells and reduced germinal center formation.

PubMed

Aydar, Yüksel; Balogh, Péter; Tew, John G; Szakal, Andras K

2003-12-01

Aging is associated with reduced trapping of Ag in the form of in immune complexes (ICs) by follicular dendritic cells (FDCs). We postulated that this defect was due to altered regulation of IC trapping receptors. The level of FDC-M1, complement receptors 1 and 2, FcgammaRII, and FDC-M2 on FDCs was immunohistochemically quantitated in draining lymph nodes of actively immunized mice for 10 days after Ag challenge. Initially, FDC FcgammaRII levels were similar but by day 3 a drastic reduction in FDC-FcgammaRII expression was apparent in old mice. FDC-M2 labeling, reflecting IC trapping, was also reduced and correlated with a dramatic reduction in germinal center (GC) B cells as indicated by reduced GC size and number. Nevertheless, labeling of FDC reticula with FDC-M1 and anti-complement receptors 1 and 2 was preserved, indicating that FDCs were present. FDCs in active GCs normally express high levels of FcRs that are thought to bind Fc portions of Abs in ICs and minimize their binding to FcRs on B cells. Thus, cross-linking of B cell receptor and FcR via IC is minimized, thereby reducing signaling via the immunoreceptor tyrosine-based inhibition motif. Old FDCs taken at day 3, when they lack FcgammaRII, were incapable of preventing immunoreceptor tyrosine-based inhibition motif signaling in wild-type B cells but old FDCs stimulated B cells from FcgammaRIIB(-/-) mice to produce near normal levels of specific Ab. The present data support the concept that FcR are regulated abnormally on old FDCs. This abnormality correlates with a reduced IC retention and with a reduced capacity of FDCs to present ICs in a way that will activate GC B cells.

Male gender and renal dysfunction are predictors of adverse outcome in nonpostoperative ischemic colitis patients.

PubMed

Lee, Tsung-Chun; Wang, Hsiu-Po; Chiu, Han-Mo; Lien, Wan-Ching; Chen, Mei-Jyh; Yu, Linda C H; Sun, Chia-Tung; Lin, Jaw-Town; Wu, Ming-Shiang

2010-01-01

Ischemic colitis (IC) spans a broad spectrum from self-limiting illness to intestinal gangrene and mortality. Prognostic factors specifically for nonpostoperative IC were not fully characterized. We aim to focus on nonpostoperative IC in patients with renal dysfunction and try to identify prognostic factors for adverse outcomes. We conducted a retrospective analysis at a university-affiliated tertiary medical center in Taiwan. From January 2003 to August 2008, 25 men and 52 women (mean age: 66 y) had colonoscopic biopsy-proven IC without prior culprit surgery. We estimated glomerular filtration rate with simplified Modification of Diet in Renal Disease equation. Nine patients with glomerular filtration rate below 30 mL per minute per 1.73 m were classified as renal dysfunction group (including 7 dialysis patients). Adverse outcomes were defined as need for surgery and mortality. Predictors for adverse outcomes were captured by univariate and multivariate analysis. Research ethical committee approved the study protocol. Patients with renal dysfunction more often had: diabetes mellitus (56% vs. 16%, P=0.02), prolonged symptoms (6.8 d vs. 3.5 d, P=0.01), lower hemoglobin (11.1 g/dL vs. 13.4 g/dL, P=0.01), and more often right colonic involvement (56% vs. 19%, P=0.03). Renal dysfunction patients also had longer hospitalization days (median 15 d vs. 4 d, P=0.045). However, there was no statistical significance in the rate of either surgery or mortality between these 2 groups (P>0.05). Univariate analysis showed that renal dysfunction, sex, emergency department referral, presentation with abdominal pain were significant for adverse outcome (P<0.1). Multivariate analysis revealed that male sex conveyed 9.5-fold risk (P=0.01) and renal dysfunction conveyed 8.5-fold risk (P=0.03) for adverse outcomes. Nonpostoperative IC patients with concurrent renal dysfunction had distinct clinical profiles. Multivariate analysis showed that male patients had 9.5-fold and renal dysfunction patients had 8.5-fold increased risk for adverse outcomes. Although IC is often self-limited, our data warrants special attention and aggressive therapy in treating these patients.

Variable rainfall intensity and tillage effects on runoff, sediment, and carbon losses from a loamy sand under simulated rainfall.

PubMed

Truman, C C; Strickland, T C; Potter, T L; Franklin, D H; Bosch, D D; Bednarz, C W

2007-01-01

The low-carbon, intensively cropped Coastal Plain soils of Georgia are susceptible to runoff, soil loss, and drought. Reduced tillage systems offer the best management tool for sustained row crop production. Understanding runoff, sediment, and chemical losses from conventional and reduced tillage systems is expected to improve if the effect of a variable rainfall intensity storm was quantified. Our objective was to quantify and compare effects of a constant (Ic) intensity pattern and a more realistic, observed, variable (Iv) rainfall intensity pattern on runoff (R), sediment (E), and carbon losses (C) from a Tifton loamy sand cropped to conventional-till (CT) and strip-till (ST) cotton (Gossypium hirsutum L.). Four treatments were evaluated: CT-Ic, CT-Iv, ST-Ic, and ST-Iv, each replicated three times. Field plots (n=12), each 2 by 3 m, were established on each treatment. Each 6-m2 field plot received simulated rainfall at a constant (57 mm h(-1)) or variable rainfall intensity pattern for 70 min (12-run ave.=1402 mL; CV=3%). The Iv pattern represented the most frequent occurring intensity pattern for spring storms in the region. Compared with CT, ST decreased R by 2.5-fold, E by 3.5-fold, and C by 7-fold. Maximum runoff values for Iv events were 1.6-fold higher than those for Ic events and occurred 38 min earlier. Values for Etot and Ctot for Iv events were 19-36% and 1.5-fold higher than corresponding values for Ic events. Values for Emax and Cmax for Iv events were 3-fold and 4-fold higher than corresponding values for Ic events. Carbon enrichment ratios (CER) were or=1.0 for CT plots (except for first 20 min). Maximum CER for CT-Ic, CT-Iv, ST-Ic, and ST-Iv were 2.0, 2.2, 1.0, and 1.2, respectively. Transport of sediment, carbon, and agrichemicals would be better understood if variable rainfall intensity patterns derived from natural rainfall were used in rainfall simulations to evaluate their fate and transport from CT and ST systems.

[Interval cancers and episode sensitivity in population-based screening programmes for colorectal cancer: a systematic review].

PubMed

Domènech, Xènia; Garcia, Montse; Benito, Llúcia; Binefa, Gemma; Vidal, Carmen; Milà, Núria; Moreno, Víctor

2015-01-01

To describe interval cancers (IC) and the sensitivity of colorectal cancer (CRC) screening programmes. A systematic review of the literature was conducted through a MEDLINE (PubMed) search. The search strategy combined the terms 'interval cancer', 'false negative', 'mass screening', 'screening' 'early detection of cancer', 'colorectal cancer' and 'bowel cancer'. Inclusion criteria consisted of population-based screening programmes, original articles written in English or Spanish and publication dates between 1999/01/01 and 2015/02/28. A narrative synthesis of the included articles was performed detailing the characteristics of the screening programmes, the IC rate, and the information sources used in each study. Thirteen articles were included. The episode sensitivity of CRC screening programmes ranged from 42.2% to 65.3% in programmes using the guaiac test and between 59.1% and 87.0% with the immunochemical test. We found a higher proportion of women who were diagnosed with IC and these lesions were mainly located in the proximal colon. There is wide variability in the IC rate in CRC programmes. To ensure comparability between programmes, there is a need for consensus on the working definition of IC and the methods used for their identification and quantification. Copyright © 2014 SESPAS. Published by Elsevier Espana. All rights reserved.

Interdisciplinary collaboration: the role of the clinical nurse leader.

PubMed

Bender, Miriam; Connelly, Cynthia D; Brown, Caroline

2013-01-01

  To explore the feasibility and acceptability of a clinical nurse leader (CNL) role to improve interdisciplinary collaboration (IC) within a fragmented acute-care microsystem.   Fragmented patient care is associated with preventable adverse healthcare outcomes. IC decreases fragmentation and improves patient care quality. The CNL role is theorized to provide the necessary leadership and competency skill base to impact IC at the optimal organizational level, the point of care where most healthcare decisions are made.   This study used a descriptive non-experimental design. CNL daily workflow was developed to target empirical determinants of IC. Descriptive data were collected from multiple stakeholders using an investigator-developed survey.   Findings indicate the integration of the role is feasible and acceptable to the microsystem healthcare team.   Preliminary evidence suggests the CNL role may be an effective intervention to facilitate IC. More research is needed to support the CNL role's association with microsystem IC.   The CNL role presents an innovative opportunity for clinical and administrative leadership to partner together to redesign a healthcare delivery system and improve patient care quality. © 2012 Blackwell Publishing Ltd.

Modeling the Diffuse Cloud-Top Optical Emissions from Ground and Cloud Flashes

NASA Technical Reports Server (NTRS)

Solakiewicz, Richard; Koshak, William

2008-01-01

A number of studies have indicated that the diffuse cloud-top optical emissions from intra-cloud (IC) lightning are brighter than that from normal negative cloud-to-ground (CG) lightning, and hence would be easier to detect from a space-based sensor. The primary reason provided to substantiate this claim has been that the IC is at a higher altitude within the cloud and therefore is less obscured by the cloud multiple scattering medium. CGs at lower altitudes embedded deep within the cloud are more obscured, so CG detection is thought to be more difficult. However, other authors claim that because the CG source current (and hence luminosity) is typically substantially larger than IC currents, the greater CG source luminosity is large enough to overcome the effects of multiple scattering. These investigators suggest that the diffuse cloud top emissions from CGs are brighter than from ICs, and hence are easier to detect from space. Still other investigators claim that the detection efficiency of CGs and ICs is about the same because modern detector sensitivity is good enough to "see" either flash type no matter which produces a brighter cloud top emission. To better assess which of these opinions should be accepted, we introduce an extension of a Boltzmann lightning radiative transfer model previously developed. It considers characteristics of the cloud (geometry, dimensions, scattering properties) and specific lightning channel properties (length, geometry, location, current, optical wave front propagation speed/direction). As such, it represents the most detailed modeling effort to date. At least in the few cases studied thus far, it was found that IC flashes appear brighter at cloud top than the lower altitude negative ground flashes, but additional model runs are to be examined before finalizing our general conclusions.

Phenolic contents, antioxidant and anticholinesterase potentials of crude extract, subsequent fractions and crude saponins from Polygonum hydropiper L

PubMed Central

2014-01-01

Background We investigated Polygonum hydropiper L. (P. hydropiper) for phenolic contents, antioxidant, anticholinesterase activities, in an attempt to rationalize its use in neurological disorders. Methods Plant crude extract (Ph.Cr), its subsequent fractions: n-hexane (Ph.Hex), chloroform (Ph.Chf), ethyl acetate (Ph.EtAc), n-Butanol (Ph.Bt), aqueous (Ph.Aq) and saponins (Ph.Sp) were evaluated for 1,1-diphenyl,2-picrylhydrazyl (DPPH), 2,2-azinobis[3-ethylbenzthiazoline]-6-sulfonic acid (ABTS) free radical scavenging potential. Further, acetylcholinesterase (AChE) & butyrylcholinesterase (BChE) inhibitory activities were performed using Ellman's assay. Moreover, total phenolic contents of plant extracts were determined and expressed in mg of gallic acid equivalent per gram of dry sample (mg GAE/g dry weight). Results Among different fractions, Ph.Cr (90.82), Ph.Chf (178.16), Ph.EtAc (203.44) and Ph.Bt (153.61) exhibited high phenolic contents. All fractions showed concentration dependent DPPH scavenging activity, with Ph.EtAc 71.33% (IC50 15 μg/ml), Ph.Bt 71.40% (IC50 3 μg/ml) and Ph.Sp 71.40% (IC50 35 μg/ml) were most potent. The plant extracts exhibited high ABTS scavenging ability i.e. Ph.Bt (91.03%), Ph.EtAc (90.56%), Ph.Sp (90.84%), Ph.Aq (90.56%) with IC50 < 0.01 μg/ml. All fractions showed moderate to high AChE inhibitory activity as; Ph.Cr, 86.87% (IC50 330 μg/ml), Ph.Hex, 87.49% (IC50 35 μg/ml), Ph.Chf, 84.76% (IC50 55 μg/ml), Ph.Sp, 87.58% (IC50 108 μg/ml) and Ph.EtAc 79.95% (IC50 310 μg/ml) at 1 mg/ml). Furthermore the BChE inhibitory activity was most prominent in Ph.Hex 90.30% (IC50 40 μg/ml), Ph.Chf 85.94% (IC50 215 μg/ml), Ph.Aq 87.62% (IC50 3 μg/ml) and Ph.EtAc 81.01% (IC50 395 μg/ml) fractions. Conclusions In this study, for the first time, we determined phenolic contents, isolated crude saponins, investigated antioxidant and anticholinestrase potential of P. hydropiper extracts. The results indicate that P. hydropiper is enriched with potent bioactive compounds and warrant further investigation by isolation and structural elucidation to find novel and affordable compounds for the treatment of various neurological disorders. PMID:24884823

Phenolic contents, antioxidant and anticholinesterase potentials of crude extract, subsequent fractions and crude saponins from Polygonum hydropiper L.

PubMed

Ayaz, Muhammad; Junaid, Muhammad; Ahmed, Jawad; Ullah, Farhat; Sadiq, Abdul; Ahmad, Sajjad; Imran, Muhammad

2014-05-03

We investigated Polygonum hydropiper L. (P. hydropiper) for phenolic contents, antioxidant, anticholinesterase activities, in an attempt to rationalize its use in neurological disorders. Plant crude extract (Ph.Cr), its subsequent fractions: n-hexane (Ph.Hex), chloroform (Ph.Chf), ethyl acetate (Ph.EtAc), n-Butanol (Ph.Bt), aqueous (Ph.Aq) and saponins (Ph.Sp) were evaluated for 1,1-diphenyl,2-picrylhydrazyl (DPPH), 2,2-azinobis[3-ethylbenzthiazoline]-6-sulfonic acid (ABTS) free radical scavenging potential. Further, acetylcholinesterase (AChE) & butyrylcholinesterase (BChE) inhibitory activities were performed using Ellman's assay. Moreover, total phenolic contents of plant extracts were determined and expressed in mg of gallic acid equivalent per gram of dry sample (mg GAE/g dry weight). Among different fractions, Ph.Cr (90.82), Ph.Chf (178.16), Ph.EtAc (203.44) and Ph.Bt (153.61) exhibited high phenolic contents. All fractions showed concentration dependent DPPH scavenging activity, with Ph.EtAc 71.33% (IC50 15 μg/ml), Ph.Bt 71.40% (IC50 3 μg/ml) and Ph.Sp 71.40% (IC50 35 μg/ml) were most potent. The plant extracts exhibited high ABTS scavenging ability i.e. Ph.Bt (91.03%), Ph.EtAc (90.56%), Ph.Sp (90.84%), Ph.Aq (90.56%) with IC50<0.01 μg/ml. All fractions showed moderate to high AChE inhibitory activity as; Ph.Cr, 86.87% (IC50 330 μg/ml), Ph.Hex, 87.49% (IC50 35 μg/ml), Ph.Chf, 84.76% (IC50 55 μg/ml), Ph.Sp, 87.58% (IC50 108 μg/ml) and Ph.EtAc 79.95% (IC50 310 μg/ml) at 1 mg/ml). Furthermore the BChE inhibitory activity was most prominent in Ph.Hex 90.30% (IC50 40 μg/ml), Ph.Chf 85.94% (IC50 215 μg/ml), Ph.Aq 87.62% (IC50 3 μg/ml) and Ph.EtAc 81.01% (IC50 395 μg/ml) fractions. In this study, for the first time, we determined phenolic contents, isolated crude saponins, investigated antioxidant and anticholinestrase potential of P. hydropiper extracts. The results indicate that P. hydropiper is enriched with potent bioactive compounds and warrant further investigation by isolation and structural elucidation to find novel and affordable compounds for the treatment of various neurological disorders.

Kinetics of interior loop formation in semiflexible chains.

PubMed

Hyeon, Changbong; Thirumalai, D

2006-03-14

Loop formation between monomers in the interior of semiflexible chains describes elementary events in biomolecular folding and DNA bending. We calculate analytically the interior distance distribution function for semiflexible chains using a mean field approach. Using the potential of mean force derived from the distance distribution function we present a simple expression for the kinetics of interior looping by adopting Kramers theory. For the parameters, that are appropriate for DNA, the theoretical predictions in comparison with the case are in excellent agreement with explicit Brownian dynamics simulations of wormlike chain (WLC) model. The interior looping times (tauIC) can be greatly altered in the cases when the stiffness of the loop differs from that of the dangling ends. If the dangling end is stiffer than the loop then tauIC increases for the case of the WLC with uniform persistence length. In contrast, attachment of flexible dangling ends enhances rate of interior loop formation. The theory also shows that if the monomers are charged and interact via screened Coulomb potential then both the cyclization (tauc) and interior looping (tauIC) times greatly increase at low ionic concentration. Because both tauc and tauIC are determined essentially by the effective persistence length [lp(R)] we computed lp(R) by varying the range of the repulsive interaction between the monomers. For short range interactions lp(R) nearly coincides with the bare persistence length which is determined largely by the backbone chain connectivity. This finding rationalizes the efficacy of describing a number of experimental observations (response of biopolymers to force and cyclization kinetics) in biomolecules using WLC model with an effective persistence length.

Evaluation of the ex vivo antimalarial activity of organotin (IV) ethylphenyldithiocarbamate on erythrocytes infected with Plasmodium berghei NK 65.

PubMed

Awang, Normah; Jumat, Hafizah; Ishak, Shafariatul Akmar; Kamaludin, Nurul Farahana

2014-06-01

Malaria is the most destructive and dangerous parasitic disease. The commonness of this disease is getting worse mainly due to the increasing resistance of Plasmodium falciparum against antimalarial drugs. Therefore, the search for new antimalarial drug is urgently needed. This study was carried out to evaluate the effects of dibutyltin (IV) ethylphenyldithiocarbamate (DBEP), diphenyltin (IV) ethylphenyldithiocarbamate (DPEP) and triphenyltin (IV) ethylphenyldithiocarbamate (TPEP) compounds as antimalarial agents. These compounds were evaluated against erythrocytes infected with Plasmodium berghei NK65 via ex vivo. Organotin (IV) ethylphenyldithiocarbamate, [R(n)Sn(C9H10NS2)(4-n)] with R = C4H9 and C6H5 for n = 2; R = C6H5 for n = 3 is chemically synthesised for its potential activities. pLDH assay was employed for determination of the concentration that inhibited 50% of the Plasmodium's activity (IC50) after 24 h treatment at concentration range of 10-0.0000001 mg mL(-1). Plasmodium berghei NK65 was cultured in vitro to determine the different morphology of trophozoite and schizont. Only DPEP and TPEP compounds have antimalarial activity towards P. berghei NK65 at IC50 0.094±0.011 and 0.892±0.088 mg mL(-1), respectively. The IC50 of DPEP and TPEP were lowest at 30% parasitemia with IC50 0.001±0.00009 and 0.0009±0.0001 mg mL(-1), respectively. In vitro culture showed that TPEP was effective towards P. berghei NK65 in trophozoite and schizont morphology with IC50 0.0001±0.00005 and 0.00009±0.00003 μg mL(-1), respectively. In conclusion, DPEP and TPEP have antimalarial effect on erythrocytes infected with P. berghei NK65 and have potential as antimalarial and schizonticidal agents.

SIGIR Quarterly Report to the United States Congress

DTIC Science & Technology

2006-04-01

Seraji Substation Basrah $5,709 PCO Perini Corporation Central sigir oversight 10 i SPECIAL INSPECTOR GENERAL FOR IRAQ...e 63 2( b ) tr an sf er s to D O J. Fa ci lit ie s Pr o te ct io n , M in e R em o va l, Fi re Se rv ic e, a n d P u b lic Sa fe ty F...ra in in g an d eq ui pp in g of t he Ir aq i P ol ic e Se rv ic e (IP S) 02 . E xa m in e th e ef fe

Special Inspector General for Iraq Reconstruction (SIGIR): April 2006 Quarterly Report

DTIC Science & Technology

2006-04-30

Seraji Substation Basrah $5,709 PCO Perini Corporation Central sigir oversight 10 i SPECIAL INSPECTOR GENERAL FOR IRAQ...tr an sf er s to D O J. Fa ci lit ie s Pr o te ct io n , M in e R em o va l, Fi re Se rv ic e, a n d P u b lic Sa fe ty F ac ili ty...an d eq ui pp in g of t he Ir aq i P ol ic e Se rv ic e (IP S) 02 . E xa m in e th e ef fe ct iv en es s of

Analysis of Vibratory Driven Pile.

DTIC Science & Technology

1987-10-01

DF ) . Deiier. CO.I Smioak. F)ctl er. ( (C (odite IS. Port IlierICeme. (A; (odeC 155. Port I Iienemeri. (A..: COdIC 156. P’oll F Ficiciiic. (NA...23C;~.i~ ode F)LNA OF19424(1.\\ N i’i nu, toil. F C: ocO’’lK \\;~i~oi .(d ( CGARF R&D(’ Fijbrir\\. (irotoit CI( (I INWI, IANI COdIC S.31F, Norfolk.V

Development of a direct competitive enzyme-linked immunosorbent assay for parathion residue in food samples.

PubMed

Gui, Wen-Jun; Liu, Yi-Hua; Wang, Chun-Mei; Liang, Xiao; Zhu, Guo-Nian

2009-10-01

A heterologous direct competitive enzyme-linked immunosorbent assay (ELISA) for parathion residue determination is described based on a monoclonal antibody and a new competitor. The effects of several physicochemical factors, such as methanol concentration, ionic strength, pH value, and sample matrix, on the performance of the ELISA were optimized for the sake of obtaining a satisfactory assay sensitivity. Results showed that when the assay medium was in the optimized condition (phosphate buffer solution [PBS] containing 10% [v/v] methanol and 0.2 mol/L NaCl at a pH value of 5.0), the sensitivity (estimated as the IC(50) value) and the limit of detection (LOD, estimated as the IC(10) value) were 1.19 and 0.08 ng/ml, respectively. The precision investigation indicated that the intraassay precision values all were below 10% and that the interassay precision values ranged from 4.89 to 19.12%. In addition, the developed ELISA showed a good linear correlation (r(2)=0.9962) to gas chromatography within the analyte's concentration range of 0.1 to 16 ng/ml. When applied to the fortified samples (parathion adding level: 5-15 microg/kg), the developed ELISA presented mean recoveries of 127.46, 122.52, 91.92, 124.01, 129.72, 99.37, and 87.17% for tomato, cucumber, banana, apple, orange, pear, and sugarcane, respectively. Results indicated that the established ELISA is a potential tool for parathion residue determination.

TOPAS/Geant4 configuration for ionization chamber calculations in proton beams

NASA Astrophysics Data System (ADS)

Wulff, Jörg; Baumann, Kilian-Simon; Verbeek, Nico; Bäumer, Christian; Timmermann, Beate; Zink, Klemens

2018-06-01

Monte Carlo (MC) calculations are a fundamental tool for the investigation of ionization chambers (ICs) in radiation fields, and for calculations in the scope of IC reference dosimetry. Geant4, as used for the toolkit TOPAS, is a major general purpose code, generally suitable for investigating ICs in primary proton beams. To provide reliable results, the impact of parameter settings and the limitations of the underlying condensed history (CH) algorithm need to be known. A Fano cavity test was implemented in Geant4 (10.03.p1) for protons, based on the existing version for electrons distributed with the Geant4 release. This self-consistent test allows the calculation to be compared with the expected result for the typical IC-like geometry of an air-filled cavity surrounded by a higher density material. Various user-selectable parameters of the CH implementation in the EMStandardOpt4 physics-list were tested for incident proton energies between 30 and 250 MeV. Using TOPAS (3.1.p1) the influence of production cuts was investigated for bare air-cavities in water, irradiated by primary protons. Detailed IC geometries for an NACP-02 plane-parallel chamber and an NE2571 Farmer-chamber were created. The overall factor f Q as a ratio between the dose-to-water and dose to the sensitive air-volume was calculated for incident proton energies between 70 and 250 MeV. The Fano test demonstrated the EMStandardOpt4 physics-list with the WentzelIV multiple scattering model as appropriate for IC calculations. If protons start perpendicular to the air cavity, no further step-size limitations are required to pass the test within 0.1%. For an isotropic source, limitations of the maximum step length within the air cavity and its surrounding as well as a limitation of the maximum fractional energy loss per step were required to pass within 0.2%. A production cut of  ⩽5 μm or  ∼15 keV for all particles yielded a constant result for f Q of bare air-filled cavities. The overall factor f Q for the detailed NACP-02 and NE2571 chamber models calculated with TOPAS agreed with the values of Gomà et al (2016 Phys. Med. Biol. 61 2389) within statistical uncertainties (1σ) of  <0.3% for almost all energies with a maximum deviation of 0.6% at 250 MeV for the NE2571. The selection of hadronic scattering models (QGSP_BIC versus QGSP_BERT) in TOPAS impacted the results at the highest energies by 0.3%  ±  0.1%. Based on the Fano cavity test, the Geant4/TOPAS Monte Carlo code, in its investigated version, can provide reliable results for IC calculations. Agreement with the detailed IC models and the published values of Gomà et al can be achieved when production cuts are reduced from the TOPAS default values. The calculations confirm the reported agreement of Gomà et al for with IAEA-TRS398 values within the given uncertainties. An additional uncertainty for the MC-calculated of  ∼0.3% by hadronic interaction models should be considered.

TOPAS/Geant4 configuration for ionization chamber calculations in proton beams.

PubMed

Wulff, Jörg; Baumann, Kilian-Simon; Verbeek, Nico; Bäumer, Christian; Timmermann, Beate; Zink, Klemens

2018-06-07

Monte Carlo (MC) calculations are a fundamental tool for the investigation of ionization chambers (ICs) in radiation fields, and for calculations in the scope of IC reference dosimetry. Geant4, as used for the toolkit TOPAS, is a major general purpose code, generally suitable for investigating ICs in primary proton beams. To provide reliable results, the impact of parameter settings and the limitations of the underlying condensed history (CH) algorithm need to be known. A Fano cavity test was implemented in Geant4 (10.03.p1) for protons, based on the existing version for electrons distributed with the Geant4 release. This self-consistent test allows the calculation to be compared with the expected result for the typical IC-like geometry of an air-filled cavity surrounded by a higher density material. Various user-selectable parameters of the CH implementation in the EMStandardOpt4 physics-list were tested for incident proton energies between 30 and 250 MeV. Using TOPAS (3.1.p1) the influence of production cuts was investigated for bare air-cavities in water, irradiated by primary protons. Detailed IC geometries for an NACP-02 plane-parallel chamber and an NE2571 Farmer-chamber were created. The overall factor f Q as a ratio between the dose-to-water and dose to the sensitive air-volume was calculated for incident proton energies between 70 and 250 MeV. The Fano test demonstrated the EMStandardOpt4 physics-list with the WentzelIV multiple scattering model as appropriate for IC calculations. If protons start perpendicular to the air cavity, no further step-size limitations are required to pass the test within 0.1%. For an isotropic source, limitations of the maximum step length within the air cavity and its surrounding as well as a limitation of the maximum fractional energy loss per step were required to pass within 0.2%. A production cut of  ⩽5 μm or  ∼15 keV for all particles yielded a constant result for f Q of bare air-filled cavities. The overall factor f Q for the detailed NACP-02 and NE2571 chamber models calculated with TOPAS agreed with the values of Gomà et al (2016 Phys. Med. Biol. 61 2389) within statistical uncertainties (1σ) of  <0.3% for almost all energies with a maximum deviation of 0.6% at 250 MeV for the NE2571. The selection of hadronic scattering models (QGSP_BIC versus QGSP_BERT) in TOPAS impacted the results at the highest energies by 0.3%  ±  0.1%. Based on the Fano cavity test, the Geant4/TOPAS Monte Carlo code, in its investigated version, can provide reliable results for IC calculations. Agreement with the detailed IC models and the published values of Gomà et al can be achieved when production cuts are reduced from the TOPAS default values. The calculations confirm the reported agreement of Gomà et al for [Formula: see text] with IAEA-TRS398 values within the given uncertainties. An additional uncertainty for the MC-calculated [Formula: see text] of  ∼0.3% by hadronic interaction models should be considered.

Serbo-Croatian. SC-15A. Part 2. Grammar,

DTIC Science & Technology

1983-09-01

may be 1) a national or ethnic group Bugarin Bulgarian 2) a religious group mulImanin Moslem 3) an occupational group berberin barber 4) a family...raven flat ravuica plain -n-ic-a berberin barber berbernica barber shop 3) nouns of instrument V 01 -a-l-Ic-a slusati to listen slusalica receiver

Characterization of a New Flavone and Tyrosinase Inhibition Constituents from the Twigs of Morus alba L.

PubMed

Zhang, Long; Tao, Guanjun; Chen, Jie; Zheng, Zong-Ping

2016-09-02

The twigs of Morus alba L. were found to show strong tyrosinase inhibition activity, and the responsible active components in the extract were further investigated in this study. A flavone, named morusone (1), and sixteen known compounds 2-17 were isolated from M. alba twigs and their structures were identified by interpretation of the corresponding ESI-MS and NMR spectral data. In the tyrosinase inhibitory test, the compounds steppogenin (IC50 0.98 ± 0.01 µM), 2,4,2',4'-tetrahydroxychalcone (IC50 0.07 ± 0.02 µM), morachalcone A (IC50 0.08 ± 0.02 µM), oxyresveratrol (IC50 0.10 ± 0.01 µM), and moracin M (8.00 ± 0.22 µM) exhibited significant tyrosinase inhibition activities, much stronger than that of the positive control kojic acid. These results suggest that M. alba twig extract should served as a good source of natural tyrosinase inhibitors for use in foods as antibrowning agents or in cosmetics as skin-whitening agents.

Self-determination and goal orientation in track and field.

PubMed

Chin, Ngien-Siong; Khoo, Selina; Low, Wah-Yun

2012-06-01

This study investigated gender, age group and locality differences in adolescent athletes' self-determination motivation and goal orientations in track and field. It also examined the relationship between the self-determination theory and achievement goal theory. A total of 632 (349 boys, 283 girls) adolescent athletes (aged 13-18 years) completed the Sports Motivation Scale and Task and Ego Orientation in Sport Questionnaire. Results indicated significant differences between gender on intrinsic motivation, extrinsic motivation, amotivation (t(630) = 4.10, p < 0.05) and ego orientation (t(630) = 2.48, p < 0.05). Male students reported higher intrinsic motivation, extrinsic motivation, amotivation and ego orientation. A significant difference was found between age groups on task orientation (t(630) = 1.94, p < 0.05) and locality on ego orientation (t(630) = 1.94, p < 0.05). Older athletes showed significantly higher task orientation. Rural athletes had higher ego orientation whereas urban athletes have higher intrinsic motivation. Task orientation was related to intrinsic motivation (r = 0.55, p < 0.01), extrinsic motivation (r = 0.55, p < 0.01), but weakly related to amotivation (r = 0.10, p < 0.01). Ego orientation was related to intrinsic motivation (r = 0.30, p < 0.01), extrinsic motivation (r = 0.36, p < 0.01) and amotivaion (r = 0.36, p < 0.01). Task orientation was related to ego orientation (r = 0.29, p < 0.01). Multiple regression analysis showed intrinsic motivation, extrinsic motivation and amotivation accounted for 30.5% of the variances in task orientation.

Self-Determination and Goal Orientation in Track and Field

PubMed Central

Chin, Ngien-Siong; Khoo, Selina; Low, Wah-Yun

2012-01-01

This study investigated gender, age group and locality differences in adolescent athletes’ self-determination motivation and goal orientations in track and field. It also examined the relationship between the self-determination theory and achievement goal theory. A total of 632 (349 boys, 283 girls) adolescent athletes (aged 13–18 years) completed the Sports Motivation Scale and Task and Ego Orientation in Sport Questionnaire. Results indicated significant differences between gender on intrinsic motivation, extrinsic motivation, amotivation (t(630) = 4.10, p < 0.05) and ego orientation (t(630) = 2.48, p < 0.05). Male students reported higher intrinsic motivation, extrinsic motivation, amotivation and ego orientation. A significant difference was found between age groups on task orientation (t(630) = 1.94, p < 0.05) and locality on ego orientation (t(630) = 1.94, p < 0.05). Older athletes showed significantly higher task orientation. Rural athletes had higher ego orientation whereas urban athletes have higher intrinsic motivation. Task orientation was related to intrinsic motivation (r = 0.55, p < 0.01), extrinsic motivation (r = 0.55, p < 0.01), but weakly related to amotivation (r = 0.10, p < 0.01). Ego orientation was related to intrinsic motivation (r = 0.30, p < 0.01), extrinsic motivation (r = 0.36, p < 0.01) and amotivaion (r = 0.36, p < 0.01). Task orientation was related to ego orientation (r = 0.29, p < 0.01). Multiple regression analysis showed intrinsic motivation, extrinsic motivation and amotivation accounted for 30.5% of the variances in task orientation. PMID:23486244

Differential effectiveness of Serratia plymuthica IC1270-induced systemic resistance against hemibiotrophic and necrotrophic leaf pathogens in rice

PubMed Central

De Vleesschauwer, David; Chernin, Leonid; Höfte, Monica M

2009-01-01

Background Induced resistance is a state of enhanced defensive capacity developed by a plant reacting to specific biotic or chemical stimuli. Over the years, several forms of induced resistance have been characterized, including systemic acquired resistance, which is induced upon localized infection by an avirulent necrotizing pathogen, and induced systemic resistance (ISR), which is elicited by selected strains of nonpathogenic rhizobacteria. However, contrary to the relative wealth of information on inducible defense responses in dicotyledoneous plants, our understanding of the molecular mechanisms underlying induced resistance phenomena in cereal crops is still in its infancy. Using a combined cytomolecular and pharmacological approach, we analyzed the host defense mechanisms associated with the establishment of ISR in rice by the rhizobacterium Serratia plymuthica IC1270. Results In a standardized soil-based assay, root treatment with IC1270 rendered foliar tissues more resistant to the hemibiotrophic pathogen Magnaporthe oryzae, causal agent of the devastating rice blast disease. Analysis of the cytological and biochemical alterations associated with restriction of fungal growth in IC1270-induced plants revealed that IC1270 primes rice for enhanced attacker-induced accumulation of reactive oxygen species (ROS) and autofluorescent phenolic compounds in and near epidermal cells displaying dense cytoplasmic granulation. Similar, yet more abundant, phenotypes of hypersensitively dying cells in the vicinity of fungal hyphae were evident in a gene-for-gene interaction with an avirulent M. oryzae strain, suggesting that IC1270-inducible ISR and R protein conditioned effector-triggered immunity (ETI) target similar defense mechanisms. Yet, this IC1270-inducible ISR response seems to act as a double-edged sword within the rice defense network as induced plants displayed an increased vulnerability to the necrotrophic pathogens Rhizoctonia solani and Cochliobolus miyabeanus. Artificial enhancement of ROS levels in inoculated leaves faithfully mimicked the opposite effects of IC1270 bacteria on aforementioned pathogens, suggesting a central role for oxidative events in the IC1270-induced resistance mechanism. Conclusion Besides identifying ROS as modulators of antagonistic defense mechanisms in rice, this work reveals the mechanistic similarities between S. plymuthica-mediated ISR and R protein-dictated ETI and underscores the importance of using appropriate innate defense mechanisms when breeding for broad-spectrum rice disease resistance. PMID:19161601

Differential effectiveness of Serratia plymuthica IC1270-induced systemic resistance against hemibiotrophic and necrotrophic leaf pathogens in rice.

PubMed

De Vleesschauwer, David; Chernin, Leonid; Höfte, Monica M

2009-01-22

Induced resistance is a state of enhanced defensive capacity developed by a plant reacting to specific biotic or chemical stimuli. Over the years, several forms of induced resistance have been characterized, including systemic acquired resistance, which is induced upon localized infection by an avirulent necrotizing pathogen, and induced systemic resistance (ISR), which is elicited by selected strains of nonpathogenic rhizobacteria. However, contrary to the relative wealth of information on inducible defense responses in dicotyledoneous plants, our understanding of the molecular mechanisms underlying induced resistance phenomena in cereal crops is still in its infancy. Using a combined cytomolecular and pharmacological approach, we analyzed the host defense mechanisms associated with the establishment of ISR in rice by the rhizobacterium Serratia plymuthica IC1270. In a standardized soil-based assay, root treatment with IC1270 rendered foliar tissues more resistant to the hemibiotrophic pathogen Magnaporthe oryzae, causal agent of the devastating rice blast disease. Analysis of the cytological and biochemical alterations associated with restriction of fungal growth in IC1270-induced plants revealed that IC1270 primes rice for enhanced attacker-induced accumulation of reactive oxygen species (ROS) and autofluorescent phenolic compounds in and near epidermal cells displaying dense cytoplasmic granulation. Similar, yet more abundant, phenotypes of hypersensitively dying cells in the vicinity of fungal hyphae were evident in a gene-for-gene interaction with an avirulent M. oryzae strain, suggesting that IC1270-inducible ISR and R protein conditioned effector-triggered immunity (ETI) target similar defense mechanisms. Yet, this IC1270-inducible ISR response seems to act as a double-edged sword within the rice defense network as induced plants displayed an increased vulnerability to the necrotrophic pathogens Rhizoctonia solani and Cochliobolus miyabeanus. Artificial enhancement of ROS levels in inoculated leaves faithfully mimicked the opposite effects of IC1270 bacteria on aforementioned pathogens, suggesting a central role for oxidative events in the IC1270-induced resistance mechanism. Besides identifying ROS as modulators of antagonistic defense mechanisms in rice, this work reveals the mechanistic similarities between S. plymuthica-mediated ISR and R protein-dictated ETI and underscores the importance of using appropriate innate defense mechanisms when breeding for broad-spectrum rice disease resistance.

2005 Tri-Service Infrastructure Systems Conference and Exhibition. Volume 10, Track 12

DTIC Science & Technology

2005-08-04

Schmidt Track 12 Greenup L&D Miter Gate Repair and...j uv en ile fi sh p as sa ge o n ty pi ca l d es ig n cr ite ria R ob er t B uc hh ol z H yd ra ul ic d es ig n of ju ve ni le fis h pa ss...C hi ca go se w er sy st em s E rn es to G o T R A C K 1 8 C iv il M e ch a n ic a l S e ss io n 1 8 D N ew c oa tin g pr od uc ts fo

Training Extract AFSC 791X0 Public Affairs.

DTIC Science & Technology

1985-09-01

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Giant Spherical Cluster with I-C140 Fullerene Topology.

PubMed

Heinl, Sebastian; Peresypkina, Eugenia; Sutter, Jörg; Scheer, Manfred

2015-11-02

We report on an effective cluster expansion of CuBr-linked aggregates by the increase of the steric bulk of the Cp(R) ligand in the pentatopic molecules [Cp(R)Fe(η(5)-P5)]. Using [Cp(BIG)Fe(η(5)-P5)] (Cp(BIG)=C5(4-nBuC6H4)5), the novel multishell aggregate [{Cp(BIG)Fe(η(5:2:1:1:1:1:1)-P5)}12(CuBr)92] is obtained. It shows topological analogy to the theoretically predicted I-C140 fullerene molecule. The spherical cluster was comprehensively characterized by various methods in solution and in the solid state. © 2015 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

Novel coumarin derivatives bearing N-benzyl pyridinium moiety: potent and dual binding site acetylcholinesterase inhibitors.

PubMed

Alipour, Masoumeh; Khoobi, Mehdi; Foroumadi, Alireza; Nadri, Hamid; Moradi, Alireza; Sakhteman, Amirhossein; Ghandi, Mehdi; Shafiee, Abbas

2012-12-15

A novel series of coumarin derivatives linked to benzyl pyridinium group were synthesized and biologically evaluated as inhibitors of both acetylcholinesterase (AChE) and butyrylcholinesterase (BuChE). The enzyme inhibitory activity of synthesized compounds was measured using colorimetric Ellman's method. It was revealed that compounds 3e, 3h, 3l, 3r and 3s have shown higher activity compared with donepezil hydrochloride as standard drug. Most of the compounds in these series had nanomolar range IC(50) in which compound 3r (IC(50) = 0.11 nM) was the most active compound against acetylcholinesterase enzyme. Copyright © 2012 Elsevier Ltd. All rights reserved.

Synthesis, docking and ADMET studies of novel chalcone triazoles for anti-cancer and anti-diabetic activity.

PubMed

Chinthala, Yakaiah; Thakur, Sneha; Tirunagari, Shalini; Chinde, Srinivas; Domatti, Anand Kumar; Arigari, Niranjana Kumar; K V N S, Srinivas; Alam, Sarfaraz; Jonnala, Kotesh Kumar; Khan, Feroz; Tiwari, Ashok; Grover, Paramjit

2015-03-26

A series of novel chalcone-triazole derivatives were synthesized and screened for in vitro anticancer activity on the human cancer cell lines IMR32 (neuroblastoma), HepG2 (hepatoma) and MCF-7 (breast adenocarcinoma), DU-145 (prostate carcinoma), and A549 (lung adenocarcinoma). Among the tested compounds, 4r showed the most promising anticancer activity in all the cell lines whereas, compounds 4c (IC50 65.86 μM), 4e (IC50 66.28 μM), 4o (IC50 35.81 μM), 4q (IC50 50.82 μM) and 4s (IC50 48.63 μM) showed better activity than the standard doxorubicin (IC50 69.33 μM) in A549 cell line alone. Rat intestinal α-glucosidase inhibitory activity of the synthesized derivatives showed 4m (IC50 67.77 μM), 4p (IC50 74.94 in μM) and 4s (IC50 102.10 μM) as most active compared to others. The in silico docking of synthesized derivatives 4a-4t with DNA topoisomerase IIα revealed the LibDock score in the range of 71.2623-118.29 whereas, compounds 4h, 4m, 4p and 4s with docking target α-glucosidase were in the range of 100.372-107.784. Copyright © 2015 Elsevier Masson SAS. All rights reserved.

Genetic Resistance to Scrapie Infection in Experimentally Challenged Goats

PubMed Central

Lacroux, Caroline; Perrin-Chauvineau, Cécile; Corbière, Fabien; Aron, Naima; Aguilar-Calvo, Patricia; Torres, Juan Maria; Costes, Pierrette; Brémaud, Isabelle; Lugan, Séverine; Schelcher, François; Barillet, Francis

2014-01-01

In goats, several field studies have identified coding mutations of the gene encoding the prion protein (I/M142, N/D146, S/D146, R/Q211, and Q/K222) that are associated with a lower risk of developing classical scrapie. However, the data related to the levels of resistance to transmissible spongiform encephalopathies (TSEs) of these different PRNP gene mutations are still considered insufficient for developing large-scale genetic selection against scrapie in this species. In this study, we inoculated wild-type (WT) PRNP (I142R154R211Q222) goats and homozygous and/or heterozygous I/M142, R/H154, R/Q211, and Q/K222 goats with a goat natural scrapie isolate by either the oral or the intracerebral (i.c.) route. Our results indicate that the I/M142 PRNP polymorphism does not provide substantial resistance to scrapie infection following intracerebral or oral inoculation. They also demonstrate that H154, Q211, and K222 PRNP allele carriers are all resistant to scrapie infection following oral exposure. However, in comparison to WT animals, the H154 and Q211 allele carriers displayed only moderate increases in the incubation period following i.c. challenge. After i.c. challenge, heterozygous K222 and a small proportion of homozygous K222 goats also developed the disease, but with incubation periods that were 4 to 5 times longer than those in WT animals. These results support the contention that the K222 goat prion protein variant provides a strong but not absolutely protective effect against classical scrapie. PMID:24284317

Characterization of linear mimetic peptides of Interleukin-22 from dissection of protein interfaces.

PubMed

La Manna, Sara; Scognamiglio, Pasqualina Liana; Di Natale, Concetta; Leone, Marilisa; Mercurio, Flavia Anna; Malfitano, Anna Maria; Cianfarani, Francesca; Madonna, Stefania; Caravella, Sergio; Albanesi, Cristina; Novellino, Ettore; Marasco, Daniela

2017-07-01

Interleukin-22 (IL-22) belongs to the family of IL-10 cytokines and is involved in a wide number of human diseases, including inflammatory disorders and cancer pathology. The ligand-receptor complex IL-22/IL-22R plays a key role in several pathways especially in the regulation and resolution of immune responses. The identification of novel compounds able to modulate IL-22/IL-22R complex could open the route to new therapeutic strategies in multiple human diseases. In this study, we designed and characterized IL-22 derived peptides at protein interface regions: several sequences revealed able to interfere with the protein complex with IC 50 in the micromolar range as evaluated through Surface Plasmon Resonance (SPR) experiments. Their conformational characterization was carried out through Circular Dichroism (CD) and Nuclear Magnetic Resonance (NMR) spectroscopies, shedding new light into the features of IL-22 fragments and on structural determinants of IL-22/IL-22R1 recognition. Finally, several peptides were tested on human keratinocyte cultures for evaluating their ability to mimic the activation of molecular pathways downstream to IL-22R in response to IL-22 binding. Copyright © 2017 Elsevier B.V. and Société Française de Biochimie et Biologie Moléculaire (SFBBM). All rights reserved.

Maternal and neonatal factors related to prematurity.

PubMed

Oliveira, Laura Leismann de; Gonçalves, Annelise de Carvalho; Costa, Juvenal Soares Dias da; Bonilha, Ana Lucia de Lourenzi

2016-01-01

To identify maternal and neonatal factors associated with prematurity in the municipality of Porto Alegre. This was a population-based case-control study. The cases were newborns under 37 weeks of gestation and the controls were newborns over 37 weeks. The data came from the records of 19,457 births in the city of Porto Alegre in the year 2012 from the Information System on Live Births of the Municipal Health Department. The analysis was carried outand adjusted by a Logistic Regression according to a hierarchical model. The variables studied were allocated into three hierarchy levels: sociodemographic variables; reproductive history; and gestational and birth factors. There were 767 cases allocated and 1,534 controls in a design of a case for two controls (1:2) by simple randomization. In the final model, a statistically significant association was found for prematurity for the following variables: mother's age under 19 years old (OR=1.32; CI 95%: 1.02-1.71) or over 34 years old (OR=1.39; CI 95%: 1.12-1.72); inadequate maternal schooling for age (OR=2.11; CI 95%: 1.22-3.65); multiple pregnancies (OR=1.14; CI 95%: 1.01-1.29); C-section (OR=1.15; CI 95%: 1.03-1.29); birth weights under 2,500g (OR=4.04; CI 95%: 3.64-4.49); Apgar score at five minutes between zero and three (OR=1.47; CI 95%: 1.12-1.91); and inadequate prenatal care (OR=1.18; CI 95%: 1.02-1.36). The present study showed the most immediate consequence of prematurity for newborns by evidencing its association with worse Apgar scores and low birth weight. The following factors were also shown as possible more distal determinants of prematurity: mother's age; inadequate maternal education; multiple gestation; inadequate prenatal care; and C-section. Identificar fatores maternos e neonatais associados à prematuridade no município de Porto Alegre. Estudo do tipo caso-controle de base populacional. Os casos foram recém-nascidos com menos de 37 semanas de gestação, e os controles foram os recém-nascidos com 37 semanas ou mais. Os dados provieram dos registros de 19.457 nascimentos do município de Porto Alegre, no ano de 2012, no Sistema de Informações sobre Nascidos Vivos da Secretaria Municipal da Saúde. Foi realizada análise ajustada mediante Regressão Logística segundo modelo hierárquico. As variáveis estudadas foram alocadas em três níveis de hierarquia: variáveis sociodemográficas; história reprodutiva; fatores gestacionais e de nascimento. Foram alocados 767 casos e 1.534 controles, em um desenho de um caso para dois controles (1:2), mediante randomização simples. No modelo final, foi encontrada associação estatisticamente significante para prematuridade para as seguintes variáveis: idade materna menor que 19 anos (OR=1,32; IC 95%: 1,02 - 1,71) e maior que 34 anos (OR=1,39; IC 95%: 1,12 - 1,72); escolaridade materna inadequada para a idade (OR=2,11; IC 95%: 1,22 - 3,65); gravidez múltipla (OR=1,14; IC 95%: 1,01 - 1,29); cesariana (OR=1,15; IC 95%: 1,03 - 1,29); peso ao nascer menor a 2.500g (OR=4,04; IC 95%: 3,64 - 4,49); Índice de Apgar no 5° minuto de zero a três (OR=1,47; IC 95%: 1,12 - 1,91) e pré-natal inadequado (OR=1,18; IC 95%: 1,02 - 1,36). O presente estudo evidenciou as consequências mais imediatas da prematuridade para os recém-nascidos ao revelar sua associação com piores escores de Apgar e baixo peso ao nascimento. Mostrou como possíveis determinantes mais distais de prematuridade: idade materna, educação materna inadequada, gestação múltipla, pré-natal inadequado e realização de cesariana.

Identification of small-molecule antagonists of the Pseudomonas aeruginosa transcriptional regulator PqsR: biophysically guided hit discovery and optimization.

PubMed

Klein, Tobias; Henn, Claudia; de Jong, Johannes C; Zimmer, Christina; Kirsch, Benjamin; Maurer, Christine K; Pistorius, Dominik; Müller, Rolf; Steinbach, Anke; Hartmann, Rolf W

2012-09-21

The Gram-negative pathogen Pseudomonas aeruginosa produces an intercellular alkyl quinolone signaling molecule, the Pseudomonas quinolone signal. The pqs quorum sensing communication system that is characteristic for P. aeruginosa regulates the production of virulence factors. Therefore, we consider the pqs system a novel target to limit P. aeruginosa pathogenicity. Here, we present small molecules targeting a key player of the pqs system, PqsR. A rational design strategy in combination with surface plasmon resonance biosensor analysis led to the identification of PqsR binders. Determination of thermodynamic binding signatures and functional characterization in E. coli guided the hit optimization, resulting in the potent hydroxamic acid derived PqsR antagonist 11 (IC(50) = 12.5 μM). Remarkably it displayed a comparable potency in P. aeruginosa (IC(50) = 23.6 μM) and reduced the production of the virulence factor pyocyanin. Beyond this, site-directed mutagenesis together with thermodynamic analysis provided insights into the energetic characteristics of protein-ligand interactions. Thus the identified PqsR antagonists are promising scaffolds for further drug design efforts against this important pathogen.

The Link between Reduced Inspiratory Capacity and Exercise Intolerance in Chronic Obstructive Pulmonary Disease.

PubMed

O'Donnell, Denis E; Elbehairy, Amany F; Webb, Katherine A; Neder, J Alberto

2017-07-01

Low inspiratory capacity (IC), chronic dyspnea, and reduced exercise capacity are inextricably linked and are independent predictors of increased mortality in chronic obstructive pulmonary disease. It is no surprise, therefore, that a major goal of management is to improve IC by reducing lung hyperinflation to improve respiratory symptoms and health-related quality of life. The negative effects of lung hyperinflation on respiratory muscle and cardiocirculatory function during exercise are now well established. Moreover, there is growing appreciation that a key mechanism of exertional dyspnea in chronic obstructive pulmonary disease is critical mechanical constraints on tidal volume expansion during exercise when resting IC is reduced. Further evidence for the importance of lung hyperinflation comes from multiple studies, which have reported the clinical benefits of therapeutic interventions that reduce lung hyperinflation and increase IC. A reduced IC in obstructive pulmonary disease is further eroded by exercise and contributes to ventilatory limitation and dyspnea. It is an important outcome for both clinical and research studies.

Informatics in radiology (infoRAD): Vendor-neutral case input into a server-based digital teaching file system.

PubMed

Kamauu, Aaron W C; DuVall, Scott L; Robison, Reid J; Liimatta, Andrew P; Wiggins, Richard H; Avrin, David E

2006-01-01

Although digital teaching files are important to radiology education, there are no current satisfactory solutions for export of Digital Imaging and Communications in Medicine (DICOM) images from picture archiving and communication systems (PACS) in desktop publishing format. A vendor-neutral digital teaching file, the Radiology Interesting Case Server (RadICS), offers an efficient tool for harvesting interesting cases from PACS without requiring modifications of the PACS configurations. Radiologists push imaging studies from PACS to RadICS via the standard DICOM Send process, and the RadICS server automatically converts the DICOM images into the Joint Photographic Experts Group format, a common desktop publishing format. They can then select key images and create an interesting case series at the PACS workstation. RadICS was tested successfully against multiple unmodified commercial PACS. Using RadICS, radiologists are able to harvest and author interesting cases at the point of clinical interpretation with minimal disruption in clinical work flow. RSNA, 2006

High operating temperature interband cascade focal plane arrays

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

Tian, Z.-B.; Godoy, S. E.; Kim, H. S.

2014-08-04

In this paper, we report the initial demonstration of mid-infrared interband cascade (IC) photodetector focal plane arrays with multiple-stage/junction design. The merits of IC photodetectors include low noise and efficient photocarrier extraction, even for zero-bias operation. By adopting enhanced electron barrier design and a total absorber thickness of 0.7 μm, the 5-stage IC detectors show very low dark current (1.10 × 10{sup −7} A/cm{sup 2} at −5 mV and 150 K). Even with un-optimized fabrication and standard commercial (mis-matched) read-out circuit technology, infrared images are obtained by the 320 × 256 IC focal plane array up to 180 K with f/2.3 optics. The minimum noise equivalent temperature differencemore » of 28 mK is obtained at 120 K. These initial results indicate great potential of IC photodetectors, particularly for high operating temperature applications.« less

SESNPCA: Principal Component Analysis Applied to Stripped-Envelope Core-Collapse Supernovae

NASA Astrophysics Data System (ADS)

Williamson, Marc; Bianco, Federica; Modjaz, Maryam

2018-01-01

In the new era of time-domain astronomy, it will become increasingly important to have rigorous, data driven models for classifying transients, including supernovae (SNe). We present the first application of principal component analysis (PCA) to stripped-envelope core-collapse supernovae (SESNe). Previous studies of SNe types Ib, IIb, Ic, and broad-line Ic (Ic-BL) focus only on specific spectral features, while our PCA algorithm uses all of the information contained in each spectrum. We use one of the largest compiled datasets of SESNe, containing over 150 SNe, each with spectra taken at multiple phases. Our work focuses on 49 SNe with spectra taken 15 ± 5 days after maximum V-band light where better distinctions can be made between SNe type Ib and Ic spectra. We find that spectra of SNe type IIb and Ic-BL are separable from the other types in PCA space, indicating that PCA is a promising option for developing a purely data driven model for SESNe classification.

Elaborate ligand-based modeling reveal new submicromolar Rho kinase inhibitors

NASA Astrophysics Data System (ADS)

Shahin, Rand; AlQtaishat, Saja; Taha, Mutasem O.

2012-02-01

Rho Kinase (ROCKII) has been recently implicated in several cardiovascular diseases prompting several attempts to discover and optimize new ROCKII inhibitors. Towards this end we explored the pharmacophoric space of 138 ROCKII inhibitors to identify high quality pharmacophores. The pharmacophoric models were subsequently allowed to compete within quantitative structure-activity relationship (QSAR) context. Genetic algorithm and multiple linear regression analysis were employed to select an optimal combination of pharmacophoric models and 2D physicochemical descriptors capable of accessing self-consistent QSAR of optimal predictive potential ( r 77 = 0.84, F = 18.18, r LOO 2 = 0.639, r PRESS 2 against 19 external test inhibitors = 0.494). Two orthogonal pharmacophores emerged in the QSAR equation suggesting the existence of at least two binding modes accessible to ligands within ROCKII binding pocket. Receiver operating characteristic (ROC) curve analyses established the validity of QSAR-selected pharmacophores. Moreover, the successful pharmacophores models were found to be comparable with crystallographically resolved ROCKII binding pocket. We employed the pharmacophoric models and associated QSAR equation to screen the national cancer institute (NCI) list of compounds Eight submicromolar ROCKII inhibitors were identified. The most potent gave IC50 values of 0.7 and 1.0 μM.

Neurons in the inferior colliculus of the rat show stimulus-specific adaptation for frequency, but not for intensity

PubMed Central

Duque, Daniel; Wang, Xin; Nieto-Diego, Javier; Krumbholz, Katrin; Malmierca, Manuel S.

2016-01-01

Electrophysiological and psychophysical responses to a low-intensity probe sound tend to be suppressed by a preceding high-intensity adaptor sound. Nevertheless, rare low-intensity deviant sounds presented among frequent high-intensity standard sounds in an intensity oddball paradigm can elicit an electroencephalographic mismatch negativity (MMN) response. This has been taken to suggest that the MMN is a correlate of true change or “deviance” detection. A key question is where in the ascending auditory pathway true deviance sensitivity first emerges. Here, we addressed this question by measuring low-intensity deviant responses from single units in the inferior colliculus (IC) of anesthetized rats. If the IC exhibits true deviance sensitivity to intensity, IC neurons should show enhanced responses to low-intensity deviant sounds presented among high-intensity standards. Contrary to this prediction, deviant responses were only enhanced when the standards and deviants differed in frequency. The results could be explained with a model assuming that IC neurons integrate over multiple frequency-tuned channels and that adaptation occurs within each channel independently. We used an adaptation paradigm with multiple repeated adaptors to measure the tuning widths of these adaption channels in relation to the neurons’ overall tuning widths. PMID:27066835

Understanding desisting and persisting forms of delinquency: the unique contributions of disruptive behavior disorders and interpersonal callousness

PubMed Central

Byrd, Amy L.; Loeber, Rolf; Pardini, Dustin A.

2013-01-01

Background While associations between conduct disorder (CD), oppositional defiant disorder (ODD), attention deficit hyperactivity disorder (ADHD), and interpersonal callousness (IC) symptoms and delinquency onset are well established, less is known about whether these characteristics differentiate desisting and persisting delinquency. The current study examined whether childhood and adolescent CD, ODD, ADHD, and IC symptoms uniquely distinguished boys who exhibited persisting versus desisting delinquency from adolescence into adulthood. Methods Participants were 503 boys (57% African American) repeatedly assessed from ages 7 to 25. Associations between childhood and adolescent CD, ODD, ADHD, and IC symptoms and desisting and persisting delinquency were examined independently and after controlling for their co-occurrence and multiple covariates. Results Conduct disorder and IC symptoms in childhood and adolescence were higher among boys whose delinquency persisted into adulthood relative to those boys whose delinquency desisted across time. After controlling for the overlap between symptoms of ADHD, ODD, CD and IC, only adolescent CD and IC symptoms emerged as unique predictors of the differentiation between persisters and desisters. Moreover, adolescent CD and IC symptoms continued to contribute unique variance even after childhood levels of these characteristics were accounted for. Conclusions Boys with elevated levels of CD and IC symptoms in childhood and adolescence are at risk for exhibiting a pattern of delinquency that persists from adolescence into adulthood. Intervention efforts designed to prevent chronic delinquency should target youth with co-occurring CD and IC symptoms in childhood and adolescence. PMID:22176342

Interpersonal Callousness and Co-Occurring Anxiety: Developmental Validity of an Adolescent Taxonomy

PubMed Central

2016-01-01

Growing evidence suggests heterogeneity within interpersonal-callous (IC) youth based on co-occurring anxiety. The developmental validity of this proposed taxonomy remains unclear however, as most previous research is cross-sectional and/or limited to adolescence. We aimed to identify low-anxiety (IC/ANX−) and high-anxiety (IC/ANX+) IC variants, and compare these groups on (a) early risk exposures, (b) psychiatric symptoms from midchildhood to early adolescence, and (c) school-based functioning. Using the Avon Longitudinal Study of Parents and Children (ALSPAC), a prospective epidemiological birth cohort, model-based cluster analysis was performed on children with complete age-13 IC and anxiety scores (n = 6,791). Analysis of variance was used to compare resulting clusters on (a) prenatal and postnatal family adversity and maternal psychopathology, and harsh parenting; (b) developmental differences in attention-deficit/hyperactivity disorder (ADHD), conduct disorder (CD), oppositional defiant disorder (ODD), emotional difficulties, and low pro-social behavior at 7, 10, and 13 years; and (c) teacher-reported discipline problems, along with standardized test performance. We identified a 4-cluster solution: “typical,” “low,” “IC/ANX−”, and “IC/ANX+.” IC/ANX+ youth showed the highest prenatal and postnatal levels of family adversity and maternal psychopathology, highest levels of ADHD, CD, ODD, and emotional difficulties, greatest discipline problems, and lowest national test scores (all p < .001). IC/ANX+ also showed a distinct pattern of increasing psychopathology from age 7 to 13 years. Adolescent IC subtypes were successfully validated in ALSPAC across multiple raters using prenatal and early postnatal risk, repeated measures of psychopathology, and school-based outcomes. Greater prenatal environmental risk among IC/ANX+ youth suggests an important target for early intervention. PMID:27977232

The effect of red-allotrope selenium nanoparticles on head and neck squamous cell viability and growth

PubMed Central

Hassan, Christopher E; Webster, Thomas J

2016-01-01

Given their low toxicity and natural presence in the human diet, selenium nanoparticles have been established as potential candidates for the treatment of numerous cancers. Red-allotrope selenium nanoparticles (rSeNPs) were synthesized and characterized in this study. Head and neck squamous cell carcinoma (HNSCC) and human dermal fibroblast (HDF) cells were cultured and exposed to rSeNPs at concentrations ranging from 0.01 to 100 μg rSeNP/mL media for 1–3 days. The toxicity of rSeNP toward HNSCC and HDFs was analyzed. Results indicated that the particles were approximately four times as cytotoxic toward HNSCC compared to HDFs, with their respective IC50 values at 19.22 and 59.61 μg rSeNP/mL media. Using statistical analysis, an effective dosage range for killing HNSCC cells while simultaneously minimizing damage to HDFs over a 3-day incubation period was established at 20–55 μg rSeNP/mL media. Observations showed that doses of rSeNP <5 μg rSeNP/mL media resulted in cell proliferation. Transmission electron microscopy images of HNSCC and HDF cells, both treated with rSeNPs, revealed that the rSeNPs became localized in the cytoplasm near the lysosomes and mitochondria. Analysis of cell morphology showed that the rSeNPs primarily induced HNSCC apoptosis. Collectively, these results indicated that rSeNPs are a promising option for treating HNSCC without adversely affecting healthy cells and without resorting to the use of harmful chemotherapeutics. PMID:27536104

Microcystin-LR nanobody screening from an alpaca phage display nanobody library and its expression and application.

PubMed

Xu, Chongxin; Yang, Ying; Liu, Liwen; Li, Jianhong; Liu, Xiaoqin; Zhang, Xiao; Liu, Yuan; Zhang, Cunzheng; Liu, Xianjin

2018-04-30

Microcystin-LR (MC-LR) is a type of biotoxin that pollutes the ecological environment and food. The study aimed to obtain new nanobodies from phage nanobody library for determination of MC-LR. The toxin was conjugated to keyhole limpet haemocyanin (KLH) and bovine serum albumin (BSA), respectively, then the conjugates were used as coated antigens for enrichment (coated MC-LR-KLH) and screening (coated MC-LR-BSA) of MC-LR phage nanobodies from an alpaca phage display nanobody library. The antigen-specific phage particles were enriched effectively with four rounds of biopanning. At the last round of enrichment, total 20 positive monoclonal phage nanobodies were obtained from the library, which were analyzed after monoclonal phage enzyme linked immunosorbent assay (ELISA), colony PCR and DNA sequencing. The most three positive nanobody genes, ANAb12, ANAb9 and ANAb7 were cloned into pET26b vector, then the nanobodies were expressed in Escherichia coli BL21 respectively. After being purified, the molecular weight (M.W.) of all nanobodies were approximate 15kDa with sodium dodecyl sulfate polyacrylamide gel electrophoresis (SDS-PAGE). The purified nanobodies, ANAb12, ANAb9 and ANAb7 were used to establish the indirect competitive ELISA (IC-ELISA) for MC-LR, and their half-maximum inhibition concentrations (IC 50 ) were 0.87, 1.17 and 1.47μg/L, their detection limits (IC 10 ) were 0.06, 0.08 and 0.12μg/L, respectively. All of them showed strong cross-reactivity (CRs) of 82.7-116.9% for MC-RR, MC-YR and MC-WR, and weak CRs of less than 4.56% for MC-LW, less than 0.1% for MC-LY and MC-LF. It was found that all the IC-ELISAs for MC-LR spiked in tap water samples detection were with good accuracy, stability and repeatability, their recoveries were 84.0-106.5%, coefficient of variations (CVs) were 3.4-10.6%. These results showed that IC-ELISA based on the nanobodies from the alpaca phage display antibody library were promising for high sensitive determination of multiple MCs. Copyright © 2018 Elsevier Inc. All rights reserved.

VizieR Online Data Catalog: OGLE-II. Cepheids in IC 1613 (Udalski+, 2001)

NASA Astrophysics Data System (ADS)

Udalski, A.; Wyrzykowski, L.; Pietrzynski, G.; Szewczyk, O.; Szymanski, M.; Kubiak, M.; Soszynski, I.; Zebrun, K.

2003-01-01

We present results of the search for Cepheids in the galaxy IC 1613 carried out as a sub-project of the OGLE-II microlensing survey. 138 Cepheids were found in the 14.2'x14.2' region in the center of the galaxy. We present light curves, VI photometry and basic data for all these objects, as well as color-magnitude diagram of the observed field. (4 data files).

Installation Restoration Program. Phase 2. Confirmation/Quantification. Stage 1. Air Force Plant 4, Fort Worth, Texas. Volume 3. Appendix A-1 (Continued).

DTIC Science & Technology

1987-12-01

GAO 0 2L -4e- - Lq*Lio rol -4 1 IOU CI S W a G-v a. IV0 0 J= C. Ic LG 4sa C...8217 ’ ~ -i CIj -43j ~LU . l co r I_- z3 335 0- C= cu w- CDP aIC. *I lr_ - CkIJ LA-. n= C G C=> gao ’ GeL) =31 CAEl = C- C-10. LLaJ 1= w CL -* I t CI or SLLJ...6- Z u - a a qcrLLJ < nC Liu~ LI i LL.J CL. w <r LL <r 03 440 -x C= cn z4 -. - XM Z~ A ~ ’’ ~ "~’ , 4 *.\\~.S~4’N’~~’ - Iz JINI 1 *~ I- LLW W, a,

J{sub IC} evaluation of the smooth and the side-grooved CT specimen in the reactor pressure vessel steel (SA508-3)

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

Oh, S.W.; Lim, M.B.; Kim, T.H.

1993-12-31

The elastic-plastic fracture toughness J{sub IC} of SA508-3 forging steel was investigated by using CT-type specimens. The thickness of the smooth specimen is B{sub 0} = 25.4 mm and the side groove specimen is B{sub N} = 20.4 mm and the side groove deep is S{center_dot}G = [(B{sub 0} {minus} B{sub N})/B{sub 0}] {times} 100 = 19.7% and the groove angle is 90{degree}. The J{sub IC} tests estimated according to the method proposed in the ASTM E813-81 and JSME S001-81. The side-grooved specimen have the advantage of J{sub IC} estimation, it is much easier to determine the onset of ductilemore » tearing by the R-curve method and it improved accuracy and scatter of the toughness values thus determined, provided all the size-requirements for the specimen prescribed in the JSME method were satisfied. But it is difficult to find by the ASTM method. The critical stretched zone width (SZW{sub C}) of the side-grooved specimens found to be smaller than that previously determined for the standard CT specimens without side-grooves. This was attributed to higher triaxiality produced by the side-grooves. The stretched zone width method gave slightly larger J{sub IC} values than those by the R-curve method for SA508-3, as has been observed for the standard specimen without side-groove.« less

A sensitive monoclonal antibody-based enzyme-linked immunosorbent assay for chlorpyrifos residue determination in Chinese agricultural smaples

USDA-ARS?s Scientific Manuscript database

A monoclonal antibody-based competitive antibody-coated enzyme-linked immunosorbent assay (ELISA) was developed and optimized for determining chlorpyrifos residue in agricultural products. The IC50 and IC10 of this ELISA were 3.3 ng/mL and 0.1 ng/mL respectively. The average recoveries recovery rate...

Time-dependent inhibition of CYP3A4 by gallic acid in human liver microsomes and recombinant systems.

PubMed

Pu, Qiang-Hong; Shi, Liang; Yu, Chao

2015-03-01

1.Gallic acid is a main polyphenol in various fruits and plants. Inhibitory characteristics of gallic acid on CYP3A4 were still unclear. The objective of this work is hence to investigate inhibitory characteristics of gallic acid on CYP3A4 using testosterone as the probe substrate in human liver microsomes (HLMs) and recombinant CYP3A4 (rCYP3A4) systems. 2.Gallic acid caused concentration-dependent loss of CYP3A4 activity with IC50 values of 615.2 μM and 669.5 μM in HLM and rCYP3A4 systems, respectively. IC50-shift experiments showed that pre-incubation with gallic acid in the absence of NADPH contributed to 12- or 14-fold reduction of IC50 in HLM and rCYP3A4 systems, respectively, supporting a time-dependent inhibition. In HLM, time-dependent inactivation variables KI and Kinact were 485.8 μM and 0.05 min(-1), respectively. 3.Compared with the presence of NADPH, pre-incubation of gallic acid in the absence of NADPH markedly increased its inhibitory effects in HLM and rCYP3A4 systems. Those results indicate that CYP3A4 inactivation by gallic acid was independent on NADPH and was mainly mediated its oxidative products. 4.In conclusion, we showed that gallic acid weakly and time-dependently inactivated CYP3A4 via its oxidative products.

All Prime Contract Awards by State or Country, Place and Contractor. Part 19. (Abbot, Virginia-Yorktown, Virginia)

DTIC Science & Technology

1989-01-01

C C.CV)i 17)0 4*0 1"-ooO 0 ooOO0-0oooO0 00 1-NN W on XIIOI0 0-4 of4( NOwO (004000a . w 000) -400) 0) 0) )0) 0) 0)0(4 ) )0)0 CY ( -4 00Q WC> Co- if < 1...11 04 0-4 --- C’m 0)-4 ?.-4 0)00tMo (D C𔃾 ONN -*-* 0C’)I i W11< 347 ) 61IC-N -4NNN"NN 0-4 LO -4 4 -4 00.4-4 t-- 4 -4 -4 -4 Ni-4 -4 a) 0 011-01 <m’ t 𔃽r

Independent component analysis of DTI data reveals white matter covariances in Alzheimer's disease

NASA Astrophysics Data System (ADS)

Ouyang, Xin; Sun, Xiaoyu; Guo, Ting; Sun, Qiaoyue; Chen, Kewei; Yao, Li; Wu, Xia; Guo, Xiaojuan

2014-03-01

Alzheimer's disease (AD) is a progressive neurodegenerative disease with the clinical symptom of the continuous deterioration of cognitive and memory functions. Multiple diffusion tensor imaging (DTI) indices such as fractional anisotropy (FA) and mean diffusivity (MD) can successfully explain the white matter damages in AD patients. However, most studies focused on the univariate measures (voxel-based analysis) to examine the differences between AD patients and normal controls (NCs). In this investigation, we applied a multivariate independent component analysis (ICA) to investigate the white matter covariances based on FA measurement from DTI data in 35 AD patients and 45 NCs from the Alzheimer's Disease Neuroimaging Initiative (ADNI) database. We found that six independent components (ICs) showed significant FA reductions in white matter covariances in AD compared with NC, including the genu and splenium of corpus callosum (IC-1 and IC-2), middle temporal gyral of temporal lobe (IC-3), sub-gyral of frontal lobe (IC-4 and IC-5) and sub-gyral of parietal lobe (IC-6). Our findings revealed covariant white matter loss in AD patients and suggest that the unsupervised data-driven ICA method is effective to explore the changes of FA in AD. This study assists us in understanding the mechanism of white matter covariant reductions in the development of AD.

A qualitative exploration of the informed consent process in hematopoietic cell transplantation clinical research and opportunities for improvement.

PubMed

Raj, M; Choi, S W; Platt, J

2017-02-01

Informed consent (IC) struggles to meet the ethical principles it strives to embody in the context of hematopoietic cell transplantation (HCT). Patients often participate in multiple clinical trials making it difficult to effectively inform the participants and fulfill complex regulations. The recent Notice of Proposed Rule Making would make major changes to federal requirements, providing a timely opportunity to evaluate existing practice. Twenty health care professionals within a Midwest Academic Medical Center involved in obtaining IC in the HCT clinic or involved in patient care during or after the IC process were interviewed to understand: (1) how they approached the IC process; (2) how they described a 'successful' IC process; and (3) opportunities for innovation. Narrative and discourse analyses of interviews indicate that providers understand IC to be a collaborative process requiring engagement and participation of providers, patients and caregivers. 'Markers of success' were identified including cognitive, affective and procedural markers focusing on patient understanding and comfort with the decision to participate. Opportunities for innovating the process included use of decision aids and tablet-based technology, and better use of patient portals. Our findings suggest specific interventions for the IC process that could support the process of consent for providers, patients and caregivers.

Pain threshold is achieved at intensity above anaerobic threshold in patients with intermittent claudication.

PubMed

Ritti-Dias, Raphael Mendes; de Moraes Forjaz, Cláudia Lúcia; Cucato, Gabriel Grizzo; Costa, Luis Augusto Riani; Wolosker, Nelson; de Fátima Nunes Marucci, Maria

2009-01-01

Walking training is considered as the first treatment option for patients with peripheral arterial disease and intermittent claudication (IC). Walking exercise has been prescribed for these patients by relative intensity of peak oxygen uptake (VO2peak), ranging from 40% to 70% VO2peak, or pain threshold (PT). However, the relationship between these methods and anaerobic threshold (AT), which is considered one of the best metabolic markers for establishing training intensity, has not been analyzed. Thus, the aim of this study was to compare, in IC patients, the physiological responses at exercise intensities usually prescribed for training (% VO2peak or % PT) with the ones observed at AT. Thirty-three IC patients performed maximal graded cardiopulmonary treadmill test to assess exercise tolerance. During the test, heart rate (HR), VO2, and systolic blood pressure were measured and responses were analyzed at the following: 40% of VO2peak; 70% of VO2peak; AT; and PT. Heart rate and VO2 at 40% and 70% of VO2peak were lower than those at AT (HR: -13 +/- 9% and -3 +/- 8%, P < .01, respectively; VO2: -52 +/- 12% and -13 +/- 15%, P < .01, respectively). Conversely, HR and VO2 at PT were slightly higher than those at AT (HR: +3 +/- 8%, P < .01; VO2: +6 +/- 15%, P = .04). None of the patients achieved the respiratory compensation point. Prescribing exercise for IC patients between 40% and 70% of VO2peak will induce a lower stimulus than that at AT, whereas prescribing exercise at PT will result in a stimulus above AT. Thus, prescribing exercise training for IC patients on the basis of PT will probably produce a greater metabolic stimulus, promoting better cardiovascular benefits.

Phytotoxic and antifungal metabolites from Curvularia sp. FH01 isolated from the gut of Atractomorpha sinensis.

PubMed

Zhang, Ying-lao; Kong, Li-chun; Jiang, Dong-hua; Yin, Cai-ping; Cai, Qi-min; Chen, Qiong; Zheng, Jiang-yan

2011-02-01

Two main phytotoxic and antifungal phthalic acid butyl isobutyl ester (1) and radicinin (2) were isolated from the culture of Curvularia sp. FH01, a fungus residing in the Atractomorpha sinensis gut. The structures of isolated metabolites were established on the basis of spectral analysis. Metabolites 1 and 2 exhibited significant phytotoxic activity against the radical growth of Echinochloa crusgalli with their IC(50) values of 61.9 and 5.9 μg/mL, respectively, which were comparable to that 2,4-dichlorophenoxyacetic acid (2.0 μg/mL) used as a positive control. The antifungal test results showed that compound 2 possessed strong antifungal activity against Magnaporthe grisea (IC(50)=16.3 μg/mL) and Valsa mali (IC(50)=18.2 μg/mL). The findings of the present study suggest that bioactive properties of the fungus FH01 can be attributed to its major components, phthalic acid butyl isobutyl ester and radicinin, and both agents have a potential to be used as herbicide and fungicide. Copyright © 2010 Elsevier Ltd. All rights reserved.

Systematic review and practice policy statements on urinary tract infection prevention in adults with spina bifida

PubMed Central

Tradewell, Michael; Pariser, Joseph J.; Nimeh, Tony

2018-01-01

Urinary tract infection (UTI) is a source of morbidity and healthcare costs in adults with spina bifida (ASB). UTI prevention strategies are often recommended, but the evidence of various approaches remains unclear. We performed a systematic review to inform a best practice policy statement for UTI prevention in ASB. On behalf of the Neurogenic Bladder Research Group (NBRG.org), we developed an a priori protocol and searched the published English literature for 30 outcomes questions addressing UTI prevention in ASB. The questions spanned the categories of antibiotics, oral supplements, bladder management factors and social support. Where there was little literature in ASB, we included literature from similar populations with neurogenic bladder (NB). Data was abstracted and then reviewed with recommendations made by consensus of all authors. Level of Evidence (LoE) and Grade of Recommendation (GoR) were according to the Oxford grading system. Of 6,433 articles identified by our search, we included 99 publications. There was sufficient evidence to support use of the following: saline bladder irrigation (LoE 1, GoR B), gentamicin bladder instillation (LoE 3, GoR C), single-use intermittent catheterization (IC) (LoE 2, GoR B), hydrophilic catheters for IC (LoE 2, GoR C), intradetrusor onabotulinumtoxinA injection (LoE 3, GoR C), hyaluronic acid (HA) instillation (LoE 1, GoR B), and care coordination (LoE 3, GoR C). There was sufficient evidence to recommend against use of the following: sterile IC (LoE 1, GoR B), oral antibiotic prophylaxis (LoE 2, GoR B), treatment of asymptomatic bacteriuria (LoE 2, GoR B), cranberry (LoE 2, GoR B), methenamine salts (LoE 1, GoR B), and ascorbic acid (LoE1, GoR B). There was insufficient evidence to make a recommendation for other outcomes. Overall, there are few studies in UTI prevention in the specific population of ASB. Research in populations similar to ASB helps to guide recommendations for UTI prevention in the challenging patient group of ASB. Future studies in UTI prevention specific to ASB are needed and should focus on areas shown to be of benefit in similar populations. PMID:29928619

Performance of a Quantitative PCR-Based Assay and Beta-d-Glucan Detection for Diagnosis of Invasive Candidiasis in Very-Low-Birth-Weight Preterm Neonatal Patients (CANDINEO Study)

PubMed Central

Ramos, Jose Tomas; Villar, Sonia; Bouza, Emilio; Bergon-Sendin, Elena; Perez Rivilla, Alfredo; Collados, Caridad Tapia; Andreu, Mariano; Reyes, Candelaria Santana; Campos-Herrero, María Isolina; de Heredia, Jon López; Herrera, María Cruz López; Alonso, Paloma Anguita; Pallás-Alonso, Carmen Rosa

2017-01-01

ABSTRACT An epidemiological, multicenter, noninterventional, observational case-control study was conducted to describe the performance of serum beta-d-glucan (BDG) and Candida PCR in blood, serum, and sterile samples for the diagnosis of invasive candidiasis (IC) in very-low-birth-weight (VLBW) preterm neonates and to compare these techniques with culture of samples from blood and other sterile sites. Seventeen centers participated in the study, and the number of episodes analyzed was 159. A total of 9 episodes of IC from 9 patients (7 confirmed and 2 probable) and 150 episodes of suspected sepsis from 117 controls were identified. The prevalence of IC was 5.7% (95% confidence interval [95% CI], 2.1 to 9.3). The mortality was significantly higher in episodes of IC (44.4%) than in the non-IC episodes (11.1%, P < 0.01). The sensitivity and specificity of the PCR performed on blood/serum samples were 87.5% and 81.6%, respectively. The sensitivity and specificity of the BDG results were lower (75.0% and 64.6%). For cases with negative culture results, the PCR and the BDG results were positive in 27 (17.4%) and 52 (33.5%) episodes, respectively. The presence of multiorgan failure, improvement with empirical antifungal therapy, thrombocytopenia, and Candida colonization were significantly associated (P < 0.01) with PCR or BDG positivity regardless of the results of the cultures. Serum BDG analysis and Candida PCR could be used as complementary diagnostic techniques to detect IC in VLBW neonates. PMID:28659321

VizieR Online Data Catalog: Absorption velocities for 21 super-luminous SNe Ic (Liu+, 2017)

NASA Astrophysics Data System (ADS)

Liu, Y.-Q.; Modjaz, M.; Bianco, F. B.

2018-04-01

We have collected the spectra of all available super-luminous supernovae (SLSNe) Ic that have a date of maximum light published before April of 2016. These SLSNe Ic were mainly discovered and observed by the All-Sky Automated Survey for Supernovae (ASAS-SN), the Catalina Real-Time Transient Survey, the Dark Energy Survey (DES), the Hubble Space Telescope Cluster Supernova Survey, the Pan-STARRS1 Medium Deep Survey (PS1), the Public ESO Spectroscopic Survey of Transient Objects (PESSTO), the Intermediate Palomar Transient Factory (iPTF) as well as the Palomar Transient Factory (PTF), and the Supernova Legacy Survey (SNLS). See table 1. (2 data files).

VizieR Online Data Catalog: BV(RI)c light curves of NSVS 5066754 (Samec+, 2016)

NASA Astrophysics Data System (ADS)

Samec, R. G.; Nyaude, R.; Caton, D. B.; Faulkner, D. R.

2017-01-01

Our BVRcIc light curves were taken with the Dark 0.81m reflector at Philips Gap, North Carolina, on 17-20 inclusive, 2014 May with a thermoelectrically cooled (-40°C) 2K*2K Apogee Alta U44 CCD using standard Johnson-Cousins BVRcIc filters (320 observations with an exposure time of 60s in B, 333 observations with an exposure time of 24s in V, 338 observations with an exposure time of 20s in Rc, and 258 observations with an exposure time of 20s in Ic). Our complete set of observations is given in Table2. (1 data file).

Geographic List of Prime Contract Awards. Oct 91 - Sep 92. FY92. (Fort Hood Texas - Northfield Vermont)

DTIC Science & Technology

1993-01-01

00N00LALAm00)LA0 -- n, o-, nc4-- n( )m-zTI o-ir -- * 0)CIO 1C) -- i-s a) CI W N 1wo jini nI-I 0 o o01 o ,w 4-1t in WL L L L 0 00 0 0 A 0 01"C4 0 ’ ~ 0C14r...411 N ,N 1`4 NJ I Q -4-4 to >-.-- zzzzzzz z zz ZZ ZZ> >>--> - Uf C41I 0-40 11 au Mə <<- JINI 4- (04 4N014INN Uf 00(n o U n (inl ý4 - I4-4- 4 -4 i...N Is 1(000o atoz z z z z z z z zz z motto00 It 7) 00 0U)..VN(to-4 N l (a0 000 0 0 In01C* an 0 Ga I(00 Gao If 0)C0an.0(0 In O0NC 0 0 0 -*MM’ N o A IC

Design, synthesis and biological evaluation of 7H-pyrrolo[2,3-d]pyrimidin-4-amine derivatives as selective Btk inhibitors with improved pharmacokinetic properties for the treatment of rheumatoid arthritis.

PubMed

He, Linhong; Pei, Heying; Zhang, Chufeng; Shao, Mingfeng; Li, Dan; Tang, Mingli; Wang, Taijing; Chen, Xiaoxin; Xiang, Mingli; Chen, Lijuan

2018-02-10

Bruton's tyrosine kinase (Btk) is a Tec family kinase with a well-defined role in the B cell receptor (BCR) and Fcγ receptor (FcR) signaling pathways, which makes it a uniquely attractive target for the treatment of autoimmune diseases, such as rheumatoid arthritis (RA). We reported a series of compounds bearing 7H-pyrrolo [2,3-d]pyrimidin-4-amine scaffold that potently inhibited Btk in vitro. Analysis of the structure-activity relationships (SAR) and drug-like profiles led to the discovery of the optimal compound B16. B16 preferentially inhibited Btk (IC 50  = 21.70 ± 0.82 nM) over closely related kinases with moderate selectivity. Cell-based tests also confirmed that B16 significantly inhibited Btk Y223 auto-phosphorylation and PLCγ2 Y1217 phosphorylation. MTT revealed that B16 displayed weak suppression against normal LO2, HEK293 and THP-1 cell lines with IC 50 values over 30 μM. Moreover, B16 showed very weak potential to block the hERG channel (IC 50  = 11.10 μM) in comparison to ibrutinib (IC 50  = 0.97 μM). Owing to its favorable physicochemical properties (ClogP = 2.53, aqueous solubility ≈ 0.1 mg/mL), pharmacokinetic profiles (F = 49.15%, t 1/2  = 7.02 h) and reasonable CYP450 profile, B16 exhibited potent anti-arthritis activity and similar efficacy to ibrutinib in reducing paw thickness in CIA mice. In conclusion, B16 is a potent, selective and durable inhibitor of Btk and has the potential to a safe and efficacious treatment for arthritis. Copyright © 2017 Elsevier Masson SAS. All rights reserved.

Comparative analysis of antioxidant and antiproliferative activities of Rhodomyrtus tomentosa extracts prepared with various solvents.

PubMed

Abd Hamid, Hazrulrizawati; Mutazah, Roziasyahira; Yusoff, Mashitah M; Abd Karim, Nurul Ashikin; Abdull Razis, Ahmad Faizal

2017-10-01

Rhodomyrtus tomentosa (Aiton) Hassk. has a wide spectrum of pharmacological effects and has been used to treat wounds, colic diarrhoea, heartburns, abscesses and gynaecopathy. The potential antiproliferative activities of R. tomentosa extracts from different solvents were evaluated in vitro on HepG2, MCF-7 and HT 29 cell lines while antioxidant activity was monitored by radical scavenging assay (DPPH), copper reducing antioxidant capacity (CUPRAC) and β-carotene bleaching assay. Extracts from R. tomentosa show the viability of the cells in concentration-dependent manner. According to the IC50 obtained, the ethyl acetate extracts showed significant antiproliferative activity on HepG2 (IC50 11.47 ± 0.280 μg/mL), MCF-7 (IC50 2.68 ± 0.529 μg/mL) and HT 29 (IC50 16.18 ± 0.538 μg/mL) after 72 h of treatment. Bioassay guided fractionation of the ethyl acetate extract led to the isolation of lupeol. Methanol extracts show significant antioxidant activities in DPPH (EC50 110.25 ± 0.005 μg/ml), CUPRAC (EC50 53.84 ± 0.004) and β-carotene bleaching (EC50 58.62 ± 0.001) due to the presence of high total flavonoid and total phenolic content which were 110.822 ± 0.017 mg butylated hydroxytoluene (BHT)/g and 190.467 ± 0.009 mg gallic acid (GAE)/g respectively. Taken together, the results extracts show the R. tomentosa as a potential source of antioxidant and antiproliferative efficacy. Copyright © 2016 Elsevier Ltd. All rights reserved.

The influence of Y-TZP surface treatment on topography and ceramic/resin cement interfacial fracture toughness.

PubMed

Paes, P N G; Bastian, F L; Jardim, P M

2017-09-01

Consider the efficacy of glass infiltration etching (SIE) treatment as a procedure to modify the zirconia surface resulting in higher interfacial fracture toughness. Y-TZP was subjected to 5 different surface treatments conditions consisting of no treatment (G1), SIE followed by hydrofluoric acid treatment (G2), heat treated at 750°C (G3), hydrofluoric acid treated (G4) and airborne-particle abrasion with alumina particles (G5). The effect of surface treatment on roughness was evaluated by Atomic Force Microscopy providing three different parameters: R a , R sk and surface area variation. The ceramic/resin cement interface was analyzed by Fracture Mechanics K I test with failure mode determined by fractographic analysis. Weibull's analysis was also performed to evaluate the structural integrity of the adhesion zone. G2 and G4 specimens showed very similar, and high R a values but different surface area variation (33% for G2 and 13% for G4) and they presented the highest fracture toughness (K IC ). Weibull's analysis showed G2 (SIE) tendency to exhibit higher K IC values than the other groups but with more data scatter and a higher early failure probability than G4 specimens. Selective glass infiltration etching surface treatment was effective in modifying the zirconia surface roughness, increasing the bonding area and hence the mechanical imbrications at the zirconia/resin cement interface resulting in higher fracture toughness (K IC ) values with higher K IC values obtained when failure probability above 20% was expected (Weibull's distribution) among all the experimental groups. Copyright © 2017 The Academy of Dental Materials. Published by Elsevier Ltd. All rights reserved.

High-pitched breath sounds indicate airflow limitation in asymptomatic asthmatic children.

PubMed

Habukawa, Chizu; Nagasaka, Yukio; Murakami, Katsumi; Takemura, Tsukasa

2009-04-01

Asthmatic children may have airway dysfunction even when asymptomatic, indicating that their long-term treatment is less than optimal. Although airway dysfunction can be identified on lung function testing, performing these tests can be difficult in infants. We studied whether breath sounds reflect subtle airway dysfunction in asthmatic children. The highest frequency of inspiratory breaths sounds (HFI) and the highest frequency of expiratory breath sounds (HFE) were measured in 131 asthmatic children while asymptomatic and with no wheezes for more than 2 weeks. No child was being treated with inhaled corticosteroids (ICS). Breath sounds were recorded and analysed by sound spectrography and compared with spirometric parameters. After initial evaluation, cases with more than step 2 (mild persistent) asthma were treated using inhaled fluticasone (100-200 microg/day) for 1 month, and then breath sound analysis and pulmonary function testing were repeated. On initial evaluation, HFI correlated with the percentage of predicted FEF(50) (%FEF(50)), (r = -0.45, P < 0.001), the percentage of predicted FEF(75) (%FEF(75)) (r = -0.456, P < 0.001), and FEV(1) as a percentage of FVC (FEV(1)/FVC (%)) (r = -0.32, P < 0.001). HFI did not correlate with the percentage of predicted PEF (%PEF). The 69 children with lower than normal %FEF(50) were then treated with ICS. The %FEF(50) and %FEF(75) improved after ICS treatment, and increases in %FEF(50) (P < 0.005) correlated with decreases in HFI (P < 0.001). Higher HFI in asymptomatic asthmatic children may indicate small airway obstruction. Additional ICS treatment may improve the pulmonary function indices representing small airway function with simultaneous HFI decreases in such patients.

Caregiving and Its Resulting Effects-The Care Study to Evaluate the Effects of Caregiving on Caregivers of Patients with Advanced Cancer in Singapore.

PubMed

Chua, Cheryl Kai Ting; Wu, Jun Tian; Wong, Yin Yee; Qu, Limin; Tan, Yung Ying; Neo, Patricia Soek Hui; Pang, Grace Suyin

2016-11-15

Informal caregivers (IC) are key to enabling home deaths, where preferred, at the end-of-life. Significant morbidity from advanced cancer can make caregiving burdensome. However, knowledge about the nature of the caregiving burden for caregivers in Singapore is limited. Hence, the key objective in this study was to examine the impact of the caregiving burden on quality of life (QOL), mental health and work capacity among local ICs. Eligible English-speaking ICs of hospitalized advanced cancer patients were recruited through non-random sampling. The Zarit Burden Interview (ZBI), Caregiver Quality of Life Index-Cancer (CQOLC), Center for Epidemiologic Studies Depression Scale-Revised (CESD-R), and Work Productivity and Activity Impairment Questionnaire (WPAI) were interviewer-administered to eligible ICs. Altogether, 16 ICs were surveyed. The mean age of ICs was 43.8 years. Most were children of patients (43.8%), and eight ICs had high burden (ZBI > 17). Those with ZBI > 17 had lower QOL, higher depression scores as well as greater work and activity impairment. In conclusion, high caregiver burden has adverse effects on QOL, mental health and work productivity. Non-physical elements of caregiving (particularly financial and decision-making) and increased number of care roles undertaken by a single IC contribute to high burden. Future interventions for caregiving burden in Singapore should also address the financial and decision-making aspects of caregiving. Outsourcing selected aspects of the caregiving role to community services may reduce the number of caregiving aspects undertaken by a single IC and caregiver burden.

Evaluación de la utilidad diagnóstica de la versión española del cuestionario al informador «AD8»☆

PubMed Central

Pardo, C. Carnero; de la Vega Cotarelo, R.; Alcalde, S. López; Aparicio, C. Martos; Carrillo, R. Vílchez; Gavilán, E. Mora; Galvin, J.E.

2012-01-01

Introducción El AD8 es un cuestionario al informador breve que puede ser autoaplicado y facilita la identificación de deterioro cognitivo (DC); nuestro objetivo es evaluar la utilidad diagnóstica (UD) de una versión española. Material y métodos Estudio transversal en una muestra clínica de díadas paciente/ informador, 330 sujetos con sospecha de DC o demencia (DEM) y 71 controles. Se ha evaluado la consistencia interna (α de Cronbach) y la validez (correlaciones parciales con estadio GDS, Fototest e índice funcional [IF]). La UD se ha evaluado para no DC vs DC (GDS 3–4) por medio del área bajo la curva ROC (aROC) y se ha considerado mejor punto de corte aquel que hacía máximo el índice de Youden. Resultados En la muestra, 105 no tenían DC, 99 tenían DC sin DEM y 203 DEM. La consistencia interna es alta (α 0,90, IC del 95%, 0,89–0,92), al igual que las correlaciones con GDS (r = 0,72, p < 0,001), Fototest (r = −0,61, p < 0,001) e IF (r = 0,59, p < 0,001). El aROC del AD8 es 0,90 (IC del 95%, 0,86–0,93), sin diferencia significativa con la del Fototest (aROC 0,93, IC del 95%, 0,89–0,96); el mejor punto de corte es 3/4 con sensibilidad de 0,93 (IC del 95%, 0,88–0,96), especificidad de 0,81 (IC del 95%, 0,72–0,88) y el 88,8% de las clasificaciones correctas. El uso conjunto de AD8 y Fototest mejora de forma significativa la UD de ambos (aROC 0,96, IC del 95%, 0,93–0,98, p < 0,05). Conclusiones La versión española del AD8 conserva las cualidades psicométricas y la UD de la versión original; su uso combinado con el Fototest mejora de forma significativa la UD de ambos. PMID:22652137

Structure-activity relations of successful pharmacologic chaperones for rescue of naturally occurring and manufactured mutants of the gonadotropin-releasing hormone receptor.

PubMed

Janovick, Jo Ann; Goulet, Mark; Bush, Eugene; Greer, Jonathan; Wettlaufer, David G; Conn, P Michael

2003-05-01

We expressed a test system of wild-type (WT) rat (r) and human (h) gonadotropin-releasing hormone (GnRH) receptors (GnRHRs), including naturally occurring (13) and manufactured (five) "loss-of-function" mutants of the GnRHR. These were used to assess the ability of different GnRH peptidomimetics to rescue defective GnRHR mutants and determine their effect on the level of membrane expression of the WT receptors. Among the manufactured mutants were the shortest rGnRHR C-terminal truncation mutant that resulted in receptor loss-of-function (des(325-327)-rGnRHR), two nonfunctional deletion mutants (des(237-241)-rGnRHR and des(260-265)-rGnRHR), two nonfunctional Cys mutants (C(229)A-rGnRHR and C(278)A-rGnRHR); the naturally occurring mutants included all 13 full-length GnRHR point mutations reported to date that result in full or partial human hypogonadotropic hypogonadism. The 10 peptidomimetics assessed as potential rescue molecules ("pharmacoperones") are from three differing chemical pedigrees (indoles, quinolones, and erythromycin-derived macrolides) and were originally developed as GnRH peptidomimetic antagonists. These structures were selected for this study because of their predicted ability to permeate the cell membrane and interact with a defined affinity with the GnRH receptor. All peptidomimetics studied with an IC(50) value (for hGnRHR)

Mastery versus the standard proficiency target for basic laparoscopic skill training: effect on skill transfer and retention.

PubMed

Kolozsvari, Nicoleta O; Kaneva, Pepa; Brace, Chantalle; Chartrand, Genevieve; Vaillancourt, Marilou; Cao, Jiguo; Banaszek, Daniel; Demyttenaere, Sebastian; Vassiliou, Melina C; Fried, Gerald M; Feldman, Liane S

2011-07-01

Little evidence exists to guide educators in the best way to implement simulation within surgical skills curricula. This study investigated whether practicing a basic Fundamentals of Laparoscopic Surgery (FLS) simulator task [peg transfer (PT)] facilitates learning a more complex skill [intracorporeal suturing (ICS)] and compared the effect of PT training to mastery with training to the passing level on PT retention and on learning ICS. For this study, 98 surgically naïve subjects were randomized to one of three PT training groups: control, standard training, and overtraining. All the participants then trained in ICS. The learning curves for ICS were analyzed by estimating the learning plateau and rate using nonlinear regression. Skill retention was assessed by retesting participants 1 month after training. The groups were compared using analysis of variance (ANOVA). Effectiveness of skill transfer was calculated using the transfer effectiveness ratio (TER). Data are presented as mean±standard deviation (p<0.05). The study was completed by 77 participants (28 control, 26 standard, and 23 overtrained subjects). The ICS learning plateau rose with increasing PT training (452±10 vs. 459±10 vs. 467±10; p<0.01). Increased PT training was associated with a trend toward higher initial ICS scores (128±107 vs. 127±110 vs. 183±106; p=0.13) and faster learning rates (15±4 vs. 14±4 vs. 13±4 trials; p=0.10). At retention, there were no differences in PT scores (p=0.5). The PT training took 20±10 min for standard training and 39±20 min for overtraining (p<0.01). Overtrained participants saved 11±5 min in ICS training compared with the control subjects (p=0.04). However, TER was 0.165 for the overtraining group and 0.160 for the standard training group, suggesting that PT overtraining took longer than the time saved on ICS training. For surgically naïve subjects, part-task training with PT alone was associated with slight improvements in the learning curve for ICS. However, overtraining with PT did not improve skill retention, and peg training alone was not an efficient strategy for learning ICS.

Circulating immune complexes contain citrullinated fibrinogen in rheumatoid arthritis

PubMed Central

Zhao, Xiaoyan; Okeke, Nwora Lance; Sharpe, Orr; Batliwalla, Franak M; Lee, Annette T; Ho, Peggy P; Tomooka, Beren H; Gregersen, Peter K; Robinson, William H

2008-01-01

Introduction There is increasing evidence that autoantibodies and immune complexes (ICs) contribute to synovitis in rheumatoid arthritis (RA), yet the autoantigens incorporated in ICs in RA remain incompletely characterised. Methods We used the C1q protein to capture ICs from plasma derived from human RA and control patients. Antibodies specific for immunoglobulin were used to detect ICs, and fibrinogen antibodies were used to detect fibrinogen-containing ICs. RA and control plasma were separated by liquid chromatography, and fractions then characterised by ELISA, immunoblotting and mass spectrometry. Immunohistochemical staining was performed on rheumatoid synovial tissue. Results C1q-immunoassays demonstrated increased levels of IgG (p = 0.01) and IgM (p = 0.0002) ICs in plasma derived from RA patients possessing anti-cyclic citrullinated peptide (CCP+) autoantibodies as compared with healthy controls. About one-half of the anti-CCP+ RA possessed circulating ICs containing fibrinogen (p = 0.0004). Fractionation of whole RA plasma revealed citrullinated fibrinogen in the high molecular weight fractions that contained ICs. Positive correlations were observed between fibrinogen-containing ICs and anti-citrullinated fibrinogen autoantibodies, anti-CCP antibody, rheumatoid factor and certain clinical characteristics. Immunohistochemical staining demonstrated co-localisation of fibrinogen, immunoglobulin and complement component C3 in RA pannus tissue. Mass spectrometry analysis of immune complexes immunoprecipitated from RA pannus tissue lysates demonstrated the presence of citrullinated fibrinogen. Conclusion Circulating ICs containing citrullinated fibrinogen are present in one-half of anti-CCP+ RA patients, and these ICs co-localise with C3 in the rheumatoid synovium suggesting that they contribute to synovitis in a subset of RA patients. PMID:18710572

Beliefs about inhaled corticosteroids: Comparison of community pharmacists, pharmacy technicians and patients with asthma.

PubMed

Driesenaar, Jeanine A; De Smet, Peter A G M; van Hulten, Rolf; Horne, Rob; Zwikker, Hanneke; van den Bemt, Bart; van Dulmen, Sandra

2016-12-01

To compare pharmacists' and pharmacy technicians' perceptions of patients' beliefs regarding inhaled corticosteroids (ICS) with those of patients and to compare the ICS beliefs of pharmacists and technicians with those of patients with asthma. 1269 community pharmacies were approached to fill out an online questionnaire; 1952 patients were sent a questionnaire by post. Beliefs (i.e., necessity and concerns) regarding ICS were measured using (an adapted version of) the Beliefs about Medicines Questionnaire (BMQ-specific). Pharmacists and technicians were instructed to fill out the BMQ for themselves, and to fill it out in the way they thought most of their patients would complete it. 136 pharmacists, 90 pharmacy technicians and 161 patients with asthma completed the questionnaire. Pharmacists and technicians thought patients had more concerns about ICS than patients themselves reported (p < 0.0001). They also thought that patients had stronger beliefs in their personal need for ICS than patients reported (p < 0.01). Pharmacists reported lower levels of concerns than patients (p < 0.05) and both providers attributed a higher level of necessity to ICS than patients did (p < 0.0001). Pharmacists and technicians overestimate the personal need for treatment as well as the concerns patients with asthma have regarding ICS. They also have, to some extent, stronger positive beliefs about ICS than patients. If pharmacists and technicians expect that patients share their positive views about ICS, they might be less likely to elicit and address patients' doubts and concerns about ICS, which might be relevant for effective ICS treatment and subsequent patient outcomes.

CheckMate 141: 1-Year Update and Subgroup Analysis of Nivolumab as First-Line Therapy in Patients with Recurrent/Metastatic Head and Neck Cancer.

PubMed

Gillison, Maura L; Blumenschein, George; Fayette, Jerome; Guigay, Joel; Colevas, A Dimitrios; Licitra, Lisa; Harrington, Kevin J; Kasper, Stefan; Vokes, Everett E; Even, Caroline; Worden, Francis; Saba, Nabil F; Iglesias Docampo, Lara Carmen; Haddad, Robert; Rordorf, Tamara; Kiyota, Naomi; Tahara, Makoto; Monga, Manish; Lynch, Mark; Li, Li; Ferris, Robert L

2018-06-04

Nivolumab significantly improved overall survival (OS) vs investigator's choice (IC) of chemotherapy at the primary analysis of randomized, open-label, phase 3 CheckMate 141 in patients with recurrent or metastatic (R/M) squamous cell carcinoma of the head and neck (SCCHN). Here, we report that OS benefit with nivolumab was maintained at a minimum follow-up of 11.4 months. Further, OS benefit with nivolumab vs IC was also noted among patients who received first-line treatment for R/M SCCHN after progressing on platinum therapy for locally advanced disease in the adjuvant or primary (i.e., with radiation) setting. The Oncologist 2018. © AlphaMed Press 2018.

Determinants of dynamic hyperinflation during metronome-paced tachypnea in COPD and normal subjects.

PubMed

Cooper, C B; Calligaro, G L; Quinn, M M; Eshaghian, P; Coskun, F; Abrazado, M; Bateman, E D; Raine, R I

2014-01-01

In COPD, dynamic hyperinflation (DH) occurs during exercise and during metronome-paced tachypnea (MPT). We investigated the relationship of DH with breathing pattern and ventilation (V˙E) in COPD and normal subjects (NS). In 35 subjects with moderate COPD and 17 younger healthy volunteers we measured inspiratory capacity (IC), breathing frequency (fR), expiratory time (TE), ventilation (V˙E) and end-tidal carbon dioxide tension (PETCO2) at baseline and after 30s of MPT at 40breaths/min with metronome-defined I:E ratios of 1:1 and 1:2. A reduction in IC (ΔIC) was taken to indicate DH. In COPD subjects, DH correlated with TE but not with V˙E or PETCO2, and was best predicted by total lung capacity. NS also showed DH (although less than in COPD), which correlated with PETCO2 but not with fR, TE or V˙E. We conclude that MPT evokes DH in both NS and patients with COPD. TE is the most important determinant of DH during MPT in patients with COPD. Copyright © 2013 Elsevier B.V. All rights reserved.

Ruthenium(II) Complexes with 2-Phenylimidazo[4,5-f][1,10]phenanthroline Derivatives that Strongly Combat Cisplatin-Resistant Tumor Cells

NASA Astrophysics Data System (ADS)

Zeng, Leli; Chen, Yu; Liu, Jiangping; Huang, Huaiyi; Guan, Ruilin; Ji, Liangnian; Chao, Hui

2016-01-01

Cisplatin was the first metal-based therapeutic agent approved for the treatment of human cancers, but its clinical activity is greatly limited by tumor drug resistance. This work utilized the parent complex [Ru(phen)2(PIP)]2+ (1) to develop three Ru(II) complexes (2-4) with different positional modifications. These compounds exhibited similar or superior cytotoxicities compared to cisplatin in HeLa, A549 and multidrug-resistant (A549R) tumor cell lines. Complex 4, the most potent member of the series, was highly active against A549R cancer cells (IC50 = 0.8 μM). This complex exhibited 178-fold better activity than cisplatin (IC50 = 142.5 μM) in A549R cells. 3D multicellular A549R tumor spheroids were also used to confirm the high proliferative and cytotoxic activity of complex 4. Complex 4 had the greatest cellular uptake and had a tendency to accumulate in the mitochondria of A549R cells. Further mechanistic studies showed that complex 4 induced A549R cell apoptosis via inhibition of thioredoxin reductase (TrxR), elevated intracellular ROS levels, mitochondrial dysfunction and cell cycle arrest, making it an outstanding candidate for overcoming cisplatin resistance.

Experimental and Theoretical Study of the Temperature Performance of Type-II Quantum Well Lasers

DTIC Science & Technology

2007-05-31

performance of type-II Interband Cascade (IC) GaSb-based semiconductor lasers has been developed. The method includes comparing the temperature-concentration... dependence at the laser threshold with steady-state carrier heating characteristics. The number of cascades in prototype type-II IC lasers has been...Monroy, and R.L.Tober, "Wavelength Tuning of Interband Cascade Laser Based on the Stark Effect", in “Future Trends in Microelectronics” ed. by

Health care service utilization among patients with bladder pain syndrome/interstitial cystitis in a single payer healthcare system.

PubMed

Chung, Shiu-Dong; Liu, Shih-Ping; Li, Hsien-Chang; Lin, Herng-Ching

2014-01-01

This study aims to investigate the differences in the utilization of healthcare services between patients with bladder pain syndrome/interstitial cystitis (BPS/IC) and patients without using a population-based database in Taiwan. This study comprised of 350 patients with BPS/IC and 1,750 age-matched controls. Healthcare resource utilization was evaluated in the one-year follow-up period as follows: number of outpatient visits and inpatient days, and the mean costs of outpatient and inpatient treatment. A multivariate regression analysis was used to evaluate the relationship between BPS/IC and total costs of health care services. For urological services, patients with BPS/IC had a significantly higher number of outpatient visits (2.5 vs. 0.2, p<0.001) as well as significantly higher outpatient costs ($US166 vs. $US6.8, p<0.001) than the controls. For non-urologic services, patients with BPS/IC had a significantly high number of outpatient visits (35.0 vs. 21.3, p<0.001) as well as significantly higher outpatient cots ($US912 vs. $US675, p<0.001) as compared to the controls. Overall, patients with BPS/IC had 174% more outpatient visits and 150% higher total costs than the controls. Multiple-regression-analyses also showed that the patients with BPS/IC had significantly higher total costs for all healthcare services than the controls. This study found that patients with BPS/IC have a significantly higher number of healthcare related visits, and have significantly higher healthcare related costs than age-matched controls. The high level of healthcare services utilization accrued with BPS/IC was not necessarily exclusive for BPS/IC, but may have also been associated with medical co-morbidities.

Network interactions within the canine intrinsic cardiac nervous system: implications for reflex control of regional cardiac function

PubMed Central

Beaumont, Eric; Salavatian, Siamak; Southerland, E Marie; Vinet, Alain; Jacquemet, Vincent; Armour, J Andrew; Ardell, Jeffrey L

2013-01-01

The aims of the study were to determine how aggregates of intrinsic cardiac (IC) neurons transduce the cardiovascular milieu versus responding to changes in central neuronal drive and to determine IC network interactions subsequent to induced neural imbalances in the genesis of atrial fibrillation (AF). Activity from multiple IC neurons in the right atrial ganglionated plexus was recorded in eight anaesthetized canines using a 16-channel linear microelectrode array. Induced changes in IC neuronal activity were evaluated in response to: (1) focal cardiac mechanical distortion; (2) electrical activation of cervical vagi or stellate ganglia; (3) occlusion of the inferior vena cava or thoracic aorta; (4) transient ventricular ischaemia, and (5) neurally induced AF. Low level activity (ranging from 0 to 2.7 Hz) generated by 92 neurons was identified in basal states, activities that displayed functional interconnectivity. The majority (56%) of IC neurons so identified received indirect central inputs (vagus alone: 25%; stellate ganglion alone: 27%; both: 48%). Fifty per cent transduced the cardiac milieu responding to multimodal stressors applied to the great vessels or heart. Fifty per cent of IC neurons exhibited cardiac cycle periodicity, with activity occurring primarily in late diastole into isovolumetric contraction. Cardiac-related activity in IC neurons was primarily related to direct cardiac mechano-sensory inputs and indirect autonomic efferent inputs. In response to mediastinal nerve stimulation, most IC neurons became excessively activated; such network behaviour preceded and persisted throughout AF. It was concluded that stochastic interactions occur among IC local circuit neuronal populations in the control of regional cardiac function. Modulation of IC local circuit neuronal recruitment may represent a novel approach for the treatment of cardiac disease, including atrial arrhythmias. PMID:23818689

Caffeic acid, a coffee-related organic acid, inhibits infection by severe fever with thrombocytopenia syndrome virus in vitro.

PubMed

Ogawa, Motohiko; Shirasago, Yoshitaka; Ando, Shuji; Shimojima, Masayuki; Saijo, Masayuki; Fukasawa, Masayoshi

2018-04-05

Severe fever with thrombocytopenia syndrome (SFTS) virus (SFTSV) causes tick-borne hemorrhagic fever in East Asia. The disease is characterized by high morbidity and mortality. Here, we evaluated the effects of caffeic acid (CA), a coffee-related organic acid with antiviral effects, against SFTSV infection. CA dose-dependently inhibited SFTSV infection in permissive human hepatoma Huh7.5.1-8 cells when SFTSV was added into the culture medium with CA. However, quinic acid (QA), another coffee-related organic acid, did not inhibit SFTSV infection. The 50% inhibitory concentration (IC 50 ) of CA against SFTSV was 0.048 mM, whereas its 50% cytotoxic concentration was 7.6 mM. The selectivity index (SI) was 158. Pre-incubation of SFTSV with CA for 4 h resulted in a greater inhibition of SFTSV infection (IC 50  = 0.019 mM; SI = 400). The pre-incubation substantially decreased viral attachment to the cells. CA treatment of the SFTSV-infected cells also inhibited the infection, albeit less effectively. CA activity after cell infection with SFTSV was more pronounced at a low multiplicity of infection (MOI) of 0.01 per cell (IC 50  = 0.18 mM) than at a high MOI of 1 per cell (IC 50  > 1 mM). Thus, CA inhibited virus spread by acting directly on the virus rather than on the infected cells. In conclusion, CA acted on SFTSV and inhibited viral infection and spread, mainly by inhibiting the binding of SFTSV to the cells. We therefore demonstrated CA to be a potential anti-SFTSV drug for preventing and treating SFTS. Copyright © 2018 Japanese Society of Chemotherapy and The Japanese Association for Infectious Diseases. Published by Elsevier Ltd. All rights reserved.

Time efficient 124I-PET volumetry in benign thyroid disorders by automatic isocontour procedures: mathematic adjustment using manual contoured measurements in low-dose CT.

PubMed

Freesmeyer, Martin; Kühnel, Christian; Westphal, Julian G

2015-01-01

Benign thyroid diseases are widely common in western societies. However, the volumetry of the thyroid gland, especially when enlarged or abnormally formed, proves to be a challenge in clinical routine. The aim of this study was to develop a simple and rapid threshold-based isocontour extraction method for thyroid volumetry from (124)I-PET/CT data in patients scheduled for radioactive iodine therapy. PET/CT data from 45 patients were analysed 30 h after 1 MBq (124)I administration. Anatomical reference volume was calculated using manually contoured data from low-dose CT images of the neck (MC). In addition, we applied an automatic isocontour extraction method (IC0.2/1.0), with two different threshold values (0.2 and 1.0 kBq/ml), for volumetry of the PET data-set. IC0.2/1.0 shape data that showed significant variation from MC data were excluded. Subsequently, a mathematical correlation using a model of linear regression with multiple variables and step-wise elimination (mIC0.2/1.0), between IC0.2/1.0 and MC, was established. Data from 41 patients (IC0.2), and 32 patients (IC1.0) were analysed. The mathematically calculated volume, mIC, showed a median deviation from the reference (MC), of ±9 % (1-54 %) for mIC0.2 and of ±8.2 % (1-50 %) for mIC1.0 CONCLUSION: Contour extraction with both, mIC1.0 and mIC0.2 gave rapid and reliable results. However, mIC0.2 can be applied to significantly more patients (>90 %) and is, therefore, deemed to be more suitable for clinical routine, keeping in mind the potential advantages of using (124)I-PET/CT for the preparation of patients scheduled for radioactive iodine therapy.

AhR and Arnt differentially regulate NF-κB signaling and chemokine responses in human bronchial epithelial cells

PubMed Central

2014-01-01

Background The aryl hydrocarbon receptor (AhR) has gradually emerged as a regulator of inflammation in the lung and other tissues. AhR may interact with the p65-subunit of the nuclear factor (NF)-κB transcription factors, but reported outcomes of AhR/NF-κB-interactions are conflicting. Some studies suggest that AhR possess pro-inflammatory activities while others suggest that AhR may be anti-inflammatory. The present study explored the impact of AhR and its binding partner AhR nuclear translocator (Arnt) on p65-activation and two differentially regulated chemokines, CXCL8 (IL-8) and CCL5 (RANTES), in human bronchial epithelial cells (BEAS-2B). Results Cells were exposed to CXCL8- and CCL5-inducing chemicals, 1-nitropyrene (1-NP) and 1-aminopyrene (1-AP) respectively, or the synthetic double-stranded RNA analogue, polyinosinic-polycytidylic acid (Poly I:C) which induced both chemokines. Only CXCL8, and not CCL5, appeared to be p65-dependent. Yet, constitutively active unligated AhR suppressed both CXCL8 and CCL5, as shown by siRNA knock-down and the AhR antagonist α-naphthoflavone. Moreover, AhR suppressed activation of p65 by TNF-α and Poly I:C as assessed by luciferase-assay and p65-phosphorylation at serine 536, without affecting basal p65-activity. In contrast, Arnt suppressed only CXCL8, but did not prevent the p65-activation directly. However, Arnt suppressed expression of the NF-κB-subunit RelB which is under transcriptional regulation by p65. Furthermore, AhR-ligands alone at high concentrations induced a moderate CXCL8-response, without affecting CCL5, but suppressed both CXCL8 and CCL5-responses by Poly I:C. Conclusion AhR and Arnt may differentially and independently regulate chemokine-responses induced by both inhaled pollutants and pulmonary infections. Constitutively active, unligated AhR suppressed the activation of p65, while Arnt may possibly interfere with the action of activated p65. Moreover, ligand-activated AhR suppressed CXCL8 and CCL5 responses by other agents, but AhR ligands alone induced CXCL8 responses when given at sufficiently high concentrations, thus underscoring the duality of AhR in regulation of inflammation. We propose that AhR-signaling may be a weak activator of p65-signaling that suppresses p65-activity induced by strong activators of NF-κB, but that its anti-inflammatory properties also are due to interference with additional pathways. PMID:25201625

Using in situ pore water concentrations to estimate the phytotoxicity of nicosulfuron in soils to corn (Zea mays L.).

PubMed

Liu, Kailin; Cao, Zhengya; Pan, Xiong; Yu, Yunlong

2012-08-01

The phytotoxicity of an herbicide in soil is typically dependent on the soil characteristics. To obtain a comparable value of the concentration that inhibits growth by 50% (IC50), 0.01 M CaCl(2) , excess pore water (EPW) and in situ pore water (IPW) were used to extract the bioavailable fraction of nicosulfuron from five different soils to estimate the nicosulfuron phytotoxicity to corn (Zea mays L.). The results indicated that the phytotoxicity of nicosulfuron in soils to corn depended on the soil type, and the IC50 values calculated based on the amended concentration of nicosulfuron ranged from 0.77 to 9.77 mg/kg among the five tested soils. The range of variation in IC50 values for nicosulfuron was smaller when the concentrations of nicosulfuron extracted with 0.01 M CaCl(2) and EPW were used instead of the amended concentration. No significant difference was observed among the IC50 values calculated from the IPW concentrations of nicosulfuron in the five tested soils, suggesting that the concentration of nicosulfuron in IPW could be used to estimate the phytotoxicity of residual nicosulfuron in soils. Copyright © 2012 SETAC.

Sources of Variability in Physical Activity Among Inactive People with Multiple Sclerosis.

PubMed

Uszynski, Marcin K; Herring, Matthew P; Casey, Blathin; Hayes, Sara; Gallagher, Stephen; Motl, Robert W; Coote, Susan

2018-04-01

Evidence supports that physical activity (PA) improves symptoms of multiple sclerosis (MS). Although application of principles from Social Cognitive Theory (SCT) may facilitate positive changes in PA behaviour among people with multiple sclerosis (pwMS), the constructs often explain limited variance in PA. This study investigated the extent to which MS symptoms, including fatigue, depression, and walking limitations combined with the SCT constructs, explained more variance in PA than SCT constructs alone among pwMS. Baseline data, including objectively assessed PA, exercise self-efficacy, goal setting, outcome expectations, 6-min walk test, fatigue and depression, from 65 participants of the Step It Up randomized controlled trial completed in Ireland (2016), were included. Multiple regression models quantified variance explained in PA and independent associations of (1) SCT constructs, (2) symptoms and (3) SCT constructs and symptoms. Model 1 included exercise self-efficacy, exercise goal setting and multidimensional outcomes expectations for exercise and explained ~14% of the variance in PA (R 2 =0.144, p < 0.05). Model 2 included walking limitations, fatigue and depression and explained 20% of the variance in PA (R 2 =0.196, p < 0.01). Model 3 combined models 1 and 2 and explained variance increased to ~29% (R 2 =0.288; p<0.01). In Model 3, exercise self-efficacy (β=0.30, p < 0.05), walking limitations (β=0.32, p < 0.01), fatigue (β = -0.41, p < 0.01) and depression (β = 0.34, p < 0.05) were significantly and independently associated with PA. Findings suggest that relevant MS symptoms improved by PA, including fatigue, depression and walking limitations, and SCT constructs together explained more variance in PA than SCT constructs alone, providing support for targeting both SCT constructs and these symptoms in the multifactorial promotion of PA among pwMS.

Understanding desisting and persisting forms of delinquency: the unique contributions of disruptive behavior disorders and interpersonal callousness.

PubMed

Byrd, Amy L; Loeber, Rolf; Pardini, Dustin A

2012-04-01

  While associations between conduct disorder (CD), oppositional defiant disorder (ODD), attention deficit hyperactivity disorder (ADHD), and interpersonal callousness (IC) symptoms and delinquency onset are well established, less is known about whether these characteristics differentiate desisting and persisting delinquency. The current study examined whether childhood and adolescent CD, ODD, ADHD, and IC symptoms uniquely distinguished boys who exhibited persisting versus desisting delinquency from adolescence into adulthood.   Participants were 503 boys (57% African American) repeatedly assessed from ages 7 to 25. Associations between childhood and adolescent CD, ODD, ADHD, and IC symptoms and desisting and persisting delinquency were examined independently and after controlling for their co-occurrence and multiple covariates.   Conduct disorder and IC symptoms in childhood and adolescence were higher among boys whose delinquency persisted into adulthood relative to those boys whose delinquency desisted across time. After controlling for the overlap between symptoms of ADHD, ODD, CD and IC, only adolescent CD and IC symptoms emerged as unique predictors of the differentiation between persisters and desisters. Moreover, adolescent CD and IC symptoms continued to contribute unique variance even after childhood levels of these characteristics were accounted for.   Boys with elevated levels of CD and IC symptoms in childhood and adolescence are at risk for exhibiting a pattern of delinquency that persists from adolescence into adulthood. Intervention efforts designed to prevent chronic delinquency should target youth with co-occurring CD and IC symptoms in childhood and adolescence. © 2011 The Authors. Journal of Child Psychology and Psychiatry © 2011 Association for Child and Adolescent Mental Health.

Mouse neutrophils lacking lamin B receptor expression exhibit aberrant development and lack critical functional responses

PubMed Central

Gaines, Peter; Tien, Chiung W.; Olins, Ada L.; Olins, Donald E.; Shultz, Leonard D.; Carney, Lisa; Berliner, Nancy

2008-01-01

Objective The capacity of neutrophils to eradicate bacterial infections is dependent on normal development and the activation of functional responses, which include chemotaxis and the generation of oxygen radicals during the respiratory burst. A unique feature of the neutrophil is its highly lobulated nucleus, which is thought to facilitate chemotaxis but may also play a role in other critical neutrophil functions. Nuclear lobulation is dependent on the expression of the inner nuclear envelope protein, the lamin B receptor (LBR), mutations of which cause hypolobulated neutrophil nuclei in human Pelger-Huët anomaly (PHA) and the "ichthyosis" (ic) phenotype in mice. In this study we have investigated roles for LBR in mediating neutrophil development and the activation of multiple neutrophil functions, including chemotaxis and the respiratory burst. Materials and Methods A progenitor EML cell line was generated from an ic/ic mouse, and derived cells that lacked LBR expression were induced to mature neutrophils and then examined for abnormal morphology and functional responses. Results Neutrophils derived from EML-ic/ic cells exhibited nuclear hypolobulation identical to that observed in ichthyosis mice. The ic/ic neutrophils also displayed abnormal chemotaxis, supporting the notion that nuclear segmentation augments neutrophil extravasation. Furthermore, promyelocytic forms of ic/ic cells displayed decreased proliferative responses and produced a deficient respiratory burst upon terminal maturation. Conclusions Our studies of promyelocytes that lack LBR expression have identified roles for LBR in regulating not only the morphologic maturation of the neutrophil nucleus but also proliferative and functional responses that are critical to innate immunity. PMID:18550262

Discovery of spiropiperidine-based potent and selective Orexin-2 receptor antagonists.

PubMed

Fujimoto, Tatsuhiko; Tomata, Yoshihide; Kunitomo, Jun; Hirozane, Mariko; Marui, Shogo

2011-11-01

To generate novel human Orexin-2 Receptor (OX2R) antagonists, a spiropiperidine based scaffold was designed and a SAR study was carried out. Compound 4f possessed the highest OX2R antagonistic activity with an IC(50) value of 3nM with 450-fold selectivity against Orexin-1 Receptor (OX1R). Copyright © 2011 Elsevier Ltd. All rights reserved.

Development of a Highly Specific Fluorescence Immunoassay for Detection of Diisobutyl Phthalate in Edible Oil Samples.

PubMed

Cui, Xiping; Wu, Panpan; Lai, Dan; Zheng, Shengwu; Chen, Yingshan; Eremin, Sergei A; Peng, Wei; Zhao, Suqing

2015-10-28

The diisobutyl phthalate (DiBP) hapten containing an amino group was synthesized successfully, and the polyclonal antibody against 4-amino phthalate-bovine serum albumin (BSA) was developed. On the basis of the polyclonal antibody, a rapid and sensitive indirect competitive fluorescence immunoassay (icFIA) has been established to detect DiBP in edible oil samples for the first time. Under the optimized conditions, the quantitative working range of the icFIA was from 10.47 to 357.06 ng/mL (R(2) = 0.991), exhibiting a detection limit of 5.82 ng/mL. In this assay, the specific results showed that other similar phthalates did not significantly interfere with the analysis, with the cross-reactivity less than 1.5%, except for that of DiBAP. Thereafter, DiBP contamination in edible oil samples was detected by icFIA, with the recovery being from 79 to 103%. Furthermore, the reliability of icFIA was validated by gas chromatography-mass spectrometry (GC-MS). Therefore, the developed icFIA is suitable for monitoring DiBP in some edible oil samples.

In situ high-resolution thermal microscopy on integrated circuits.

PubMed

Zhuo, Guan-Yu; Su, Hai-Ching; Wang, Hsien-Yi; Chan, Ming-Che

2017-09-04

The miniaturization of metal tracks in integrated circuits (ICs) can cause abnormal heat dissipation, resulting in electrostatic discharge, overvoltage breakdown, and other unwanted issues. Unfortunately, locating areas of abnormal heat dissipation is limited either by the spatial resolution or imaging acquisition speed of current thermal analytical techniques. A rapid, non-contact approach to the thermal imaging of ICs with sub-μm resolution could help to alleviate this issue. In this work, based on the intensity of the temperature-dependent two-photon fluorescence (TPF) of Rhodamine 6G (R6G) material, we developed a novel fast and non-invasive thermal microscopy with a sub-μm resolution. Its application to the location of hotspots that may evolve into thermally induced defects in ICs was also demonstrated. To the best of our knowledge, this is the first study to present high-resolution 2D thermal microscopic images of ICs, showing the generation, propagation, and distribution of heat during its operation. According to the demonstrated results, this scheme has considerable potential for future in situ hotspot analysis during the optimization stage of IC development.

Identifying reliable independent components via split-half comparisons

PubMed Central

Groppe, David M.; Makeig, Scott; Kutas, Marta

2011-01-01

Independent component analysis (ICA) is a family of unsupervised learning algorithms that have proven useful for the analysis of the electroencephalogram (EEG) and magnetoencephalogram (MEG). ICA decomposes an EEG/MEG data set into a basis of maximally temporally independent components (ICs) that are learned from the data. As with any statistic, a concern with using ICA is the degree to which the estimated ICs are reliable. An IC may not be reliable if ICA was trained on insufficient data, if ICA training was stopped prematurely or at a local minimum (for some algorithms), or if multiple global minima were present. Consequently, evidence of ICA reliability is critical for the credibility of ICA results. In this paper, we present a new algorithm for assessing the reliability of ICs based on applying ICA separately to split-halves of a data set. This algorithm improves upon existing methods in that it considers both IC scalp topographies and activations, uses a probabilistically interpretable threshold for accepting ICs as reliable, and requires applying ICA only three times per data set. As evidence of the method’s validity, we show that the method can perform comparably to more time intensive bootstrap resampling and depends in a reasonable manner on the amount of training data. Finally, using the method we illustrate the importance of checking the reliability of ICs by demonstrating that IC reliability is dramatically increased by removing the mean EEG at each channel for each epoch of data rather than the mean EEG in a prestimulus baseline. PMID:19162199

Three-dimensional brain reconstruction of in vivo electrode tracks for neuroscience and neural prosthetic applications

PubMed Central

Markovitz, Craig D.; Tang, Tien T.; Edge, David P.; Lim, Hubert H.

2012-01-01

The brain is a densely interconnected network that relies on populations of neurons within and across multiple nuclei to code for features leading to perception and action. However, the neurophysiology field is still dominated by the characterization of individual neurons, rather than simultaneous recordings across multiple regions, without consistent spatial reconstruction of their locations for comparisons across studies. There are sophisticated histological and imaging techniques for performing brain reconstructions. However, what is needed is a method that is relatively easy and inexpensive to implement in a typical neurophysiology lab and provides consistent identification of electrode locations to make it widely used for pooling data across studies and research groups. This paper presents our initial development of such an approach for reconstructing electrode tracks and site locations within the guinea pig inferior colliculus (IC) to identify its functional organization for frequency coding relevant for a new auditory midbrain implant (AMI). Encouragingly, the spatial error associated with different individuals reconstructing electrode tracks for the same midbrain was less than 65 μm, corresponding to an error of ~1.5% relative to the entire IC structure (~4–5 mm diameter sphere). Furthermore, the reconstructed frequency laminae of the IC were consistently aligned across three sampled midbrains, demonstrating the ability to use our method to combine location data across animals. Hopefully, through further improvements in our reconstruction method, it can be used as a standard protocol across neurophysiology labs to characterize neural data not only within the IC but also within other brain regions to help bridge the gap between cellular activity and network function. Clinically, correlating function with location within and across multiple brain regions can guide optimal placement of electrodes for the growing field of neural prosthetics. PMID:22754502

Simulation of a class of hazardous situations in the ICS «INM RAS - Baltic Sea»

NASA Astrophysics Data System (ADS)

Zakharova, Natalia; Agoshkov, Valery; Aseev, Nikita; Parmuzin, Eugene; Sheloput, Tateana; Shutyaev, Victor

2017-04-01

Development of Informational Computational Systems (ICS) for data assimilation procedures is one of multidisciplinary problems. To study and solve these problems one needs to apply modern results from different disciplines and recent developments in mathematical modeling, theory of adjoint equations and optimal control, inverse problems, numerical methods theory, numerical algebra, scientific computing and processing of satellite data. In this work the results on the ICS development for PC-ICS "INM RAS - Baltic Sea" are presented. We discuss practical problems studied by ICS. The System includes numerical model of the Baltic Sea thermodynamics, the new oil spill model describing the propagation of a slick at the Sea surface (Agoshkov, Aseev et al., 2014) and the optimal ship route calculating block (Agoshkov, Zayachkovsky et al., 2014). The ICS is based on the INMOM numerical model of the Baltic Sea thermodynamics (Zalesny et al., 2013). It is possible to calculate main hydrodynamic parameters (temperature, salinity, velocities, sea level) using user-friendly interface of the ICS. The System includes data assimilation procedures (Agoshkov, 2003, Parmuzin, Agoshkov, 2012) and one can use the block of variational assimilation of the sea surface temperature in order to obtain main hydrodynamic parameters. Main possibilities of the ICS and several numerical experiments are presented in the work. By the problem of risk control is meant a problem of determination of optimal resources quantity which are necessary for decreasing the risk to some acceptable value. Mass of oil slick is chosen as a function of control. For the realization of the random variable the quadratic "functional of cost" is introduced. It comprises cleaning costs and deviation of damage of oil pollution from its acceptable value. The problem of minimization of this functional is solved based on the methods of optimal control and the theory of adjoint equations. The solution of this problem is explicitly found. The study was supported by the Russian Foundation for Basic Research (project 16-31-00510) and by the Russian Science Foundation (project №14-11-00609). V. I. Agoshkov, Methods of Optimal Control and Adjoint Equations in Problems of Mathematical Physics. INM RAS, Moscow, 2003 (in Russian). V. B. Zalesny, A. V. Gusev, V. O. Ivchenko, R. Tamsalu, and R. Aps, Numerical model of the Baltic Sea circulation. Russ. J. Numer. Anal. Math. Modelling 28 (2013), No. 1, 85-100. V.I. Agoshkov, A.O. Zayachkovskiy, R. Aps, P. Kujala, and J. Rytkönen. Risk theory based solution to the problem of optimal vessel route // Russian Journal of Numerical Analysis and Mathematical Modelling. 2014. Volume 29, Issue 2, Pages 69-78. Agoshkov, V., Aseev, N., Aps, R., Kujala, P., Rytkönen, J., Zalesny, V. The problem of control of oil pollution risk in the Baltic Sea // Russian Journal of Numerical Analysis and Mathematical Modelling. 2014. Volume 29, Issue 2, Pages 93-105. E. I. Parmuzin and V. I. Agoshkov, Numerical solution of the variational assimilation problem for sea surface temperature in the model of the Black Sea dynamics. Russ. J. Numer. Anal. Math. Modelling 27 (2012), No. 1, 69-94. Olof Liungman and Johan Mattsson. Scientic Documentation of Seatrack Web; physical processes, algorithms and references, 2011.

Development of an Immunochromatography Assay (QuickNavi-Ebola) to Detect Multiple Species of Ebolaviruses.

PubMed

Yoshida, Reiko; Muramatsu, Shino; Akita, Hiroshi; Saito, Yuji; Kuwahara, Miwa; Kato, Daisuke; Changula, Katendi; Miyamoto, Hiroko; Kajihara, Masahiro; Manzoor, Rashid; Furuyama, Wakako; Marzi, Andrea; Feldmann, Heinz; Mweene, Aaron; Masumu, Justin; Kapeteshi, Jimmy; Muyembe-Tamfum, Jean-Jacques; Takada, Ayato

2016-10-15

The latest outbreak of Ebola virus disease (EVD) in West Africa has highlighted the urgent need for the development of rapid and reliable diagnostic assays. We used monoclonal antibodies specific to the ebolavirus nucleoprotein to develop an immunochromatography (IC) assay (QuickNavi-Ebola) for rapid diagnosis of EVD. The IC assay was first evaluated with tissue culture supernatants of infected Vero E6 cells and found to be capable of detecting 10 3 -10 4 focus-forming units/mL of ebolaviruses. Using serum samples from experimentally infected nonhuman primates, we confirmed that the assay could detect the viral antigen shortly after disease onset. It was also noted that multiple species of ebolaviruses could be detected by the IC assay. Owing to the simplicity of the assay procedure and absence of requirements for special equipment and training, QuickNavi-Ebola is expected to be a useful tool for rapid diagnosis of EVD. © The Author 2016. Published by Oxford University Press for the Infectious Diseases Society of America. All rights reserved. For permissions, e-mail journals.permissions@oup.com.

Concept and benefits of the Inverted Classroom method for a competency-based biochemistry course in the pre-clinical stage of a human medicine course of studies

PubMed Central

Kühl, Susanne J.; Toberer, Matthias; Keis, Oliver; Tolks, Daniel; Fischer, Martin R.; Kühl, Michael

2017-01-01

Background: Medical students often have a problem recognising the relevance of basic science subjects for their later professional work in the pre-clinical stage of their studies. This can lead to a lower motivation to learn biochemical content and dissatisfaction in the courses amongst the students. Alternative teaching methods such as the Inverted Classroom (IC) method can address this deficiency. The goal of this study was: to analyse the motivation and satisfaction of the students in a biochemistry seminar through the use of the e-learning-based IC method, to investigate the acceptance against the IC teaching method in biochemistry, and to compare the learning success achieved using the IC approach with that of a traditional course. We also investigated how a biochemistry course in the pre-clinical stage of a human medicine course of studies can be successfully organised according to the IC method. Furthermore, we examined the benefits of the IC method over conventional teaching formats. Method: The IC method was implemented in accordance with the guidelines of the GMA committee “New Media” [30] in a biochemistry seminar for two student IC intervention groups with 42 students. A part of the factual knowledge from the on-site phase in the form of teaching videos together with self-learning control tasks were provided online before the seminar for both IC intervention groups. Exporting content to the self-learning phase creates new free time in the on-site phase, during which the content can be critically considered and processed and additional competency-based learning objectives can be taught. Identical biochemistry teaching content was taught in parallel control groups (14 student groups with n=299 students), but no material was handed out beforehand for a self-learning phase. These students only received the materials after the on-site phase. Motivation and satisfaction as well as the acceptance for the teaching methods were recorded by questionnaires, the acquisition of knowledge by MC exams. Results: On a Likert scale from 1 (strongly disagree) to 6 (strongly agree), the students in the IC intervention groups could be seen to be much more motivated (5.53) than students in the control group (4.01). Students in the IC intervention groups also recognised the relevance of the learning content much more clearly (5.44) than students in the control group (4.01). Furthermore, the IC group also observed that additional competencies were trained in addition to the biochemistry content. In addition, the IC intervention group award the event a school grade of 1.53, the traditional control group a grade of 2.96. The teaching videos were rated very positively by both groups with an average school grade of 1.3 in each case. A qualitative analysis showed that the motivation and a positive attitude of the lecturers played a decisive role in the successful implementation of the IC method. Discussion and conclusion: Pre-clinical students display a high acceptance of the e-learning-based IC method. Teaching communication competencies in a biochemistry seminar was also rated very positively by the students. The quality of the teaching video and the motivation of the lecturers were shown to be a critical parameter for the successful performance of the IC method. What’s more, the IC method can contribute to implementing a competence orientation in medical studies. PMID:28890922

Concept and benefits of the Inverted Classroom method for a competency-based biochemistry course in the pre-clinical stage of a human medicine course of studies.

PubMed

Kühl, Susanne J; Toberer, Matthias; Keis, Oliver; Tolks, Daniel; Fischer, Martin R; Kühl, Michael

2017-01-01

Background: Medical students often have a problem recognising the relevance of basic science subjects for their later professional work in the pre-clinical stage of their studies. This can lead to a lower motivation to learn biochemical content and dissatisfaction in the courses amongst the students. Alternative teaching methods such as the Inverted Classroom (IC) method can address this deficiency. The goal of this study was: to analyse the motivation and satisfaction of the students in a biochemistry seminar through the use of the e-learning-based IC method, to investigate the acceptance against the IC teaching method in biochemistry, and to compare the learning success achieved using the IC approach with that of a traditional course. We also investigated how a biochemistry course in the pre-clinical stage of a human medicine course of studies can be successfully organised according to the IC method. Furthermore, we examined the benefits of the IC method over conventional teaching formats. Method: The IC method was implemented in accordance with the guidelines of the GMA committee "New Media" [30] in a biochemistry seminar for two student IC intervention groups with 42 students. A part of the factual knowledge from the on-site phase in the form of teaching videos together with self-learning control tasks were provided online before the seminar for both IC intervention groups. Exporting content to the self-learning phase creates new free time in the on-site phase, during which the content can be critically considered and processed and additional competency-based learning objectives can be taught. Identical biochemistry teaching content was taught in parallel control groups (14 student groups with n=299 students), but no material was handed out beforehand for a self-learning phase. These students only received the materials after the on-site phase. Motivation and satisfaction as well as the acceptance for the teaching methods were recorded by questionnaires, the acquisition of knowledge by MC exams. Results: On a Likert scale from 1 (strongly disagree) to 6 (strongly agree), the students in the IC intervention groups could be seen to be much more motivated (5.53) than students in the control group (4.01). Students in the IC intervention groups also recognised the relevance of the learning content much more clearly (5.44) than students in the control group (4.01). Furthermore, the IC group also observed that additional competencies were trained in addition to the biochemistry content. In addition, the IC intervention group award the event a school grade of 1.53, the traditional control group a grade of 2.96. The teaching videos were rated very positively by both groups with an average school grade of 1.3 in each case. A qualitative analysis showed that the motivation and a positive attitude of the lecturers played a decisive role in the successful implementation of the IC method. Discussion and conclusion: Pre-clinical students display a high acceptance of the e-learning-based IC method. Teaching communication competencies in a biochemistry seminar was also rated very positively by the students. The quality of the teaching video and the motivation of the lecturers were shown to be a critical parameter for the successful performance of the IC method. What's more, the IC method can contribute to implementing a competence orientation in medical studies.

Benthic and Nektonic Studies of Winyah Bay for the Proposed Channel Deepening Project and Dredging of the Western Channel Turning Basin,

DTIC Science & Technology

1981-02-01

relaitive abundance for Dasv-atis- sab Ina Collected trami the Winyah Bay. sys tem, durine October 1930.................... 51 List of Figures (Con’t...r n e rnI lv eh 1:, i o r i,_ r tu ni t ic *----------- r;talo.uo w.’ id nabe temto recolaIini ze denuded substrates l: . yr’ -1eoey ra:nna a-illtisa

Development of an On-Line Biological Detector

DTIC Science & Technology

1976-07-31

ib . Pert...chemical (Kit 0510). This kit uses the enzymes, glucose oxidase ( Aspergillus niger) and peroxidase (horseradish). In the presence of glucose oxidase, "D...tt -h l o)w the(m to( peteltl rate bt v 1tn t ;w I ib r .I "Flow i i | ;t t r ,I h--Ut cii I r’. 2 Iit I ii I iii t icý, ind M - ) i n i I.t r, i

PSMA-targeted polyinosine/polycytosine vector induces prostate tumor regression and invokes an antitumor immune response in mice.

PubMed

Langut, Yael; Talhami, Alaa; Mamidi, Samarasimhareddy; Shir, Alexei; Zigler, Maya; Joubran, Salim; Sagalov, Anna; Flashner-Abramson, Efrat; Edinger, Nufar; Klein, Shoshana; Levitzki, Alexander

2017-12-26

There is an urgent need for an effective treatment for metastatic prostate cancer (PC). Prostate tumors invariably overexpress prostate surface membrane antigen (PSMA). We designed a nonviral vector, PEI-PEG-DUPA (PPD), comprising polyethylenimine-polyethyleneglycol (PEI-PEG) tethered to the PSMA ligand, 2-[3-(1, 3-dicarboxy propyl)ureido] pentanedioic acid (DUPA), to treat PC. The purpose of PEI is to bind polyinosinic/polycytosinic acid (polyIC) and allow endosomal release, while DUPA targets PC cells. PolyIC activates multiple pathways that lead to tumor cell death and to the activation of bystander effects that harness the immune system against the tumor, attacking nontargeted neighboring tumor cells and reducing the probability of acquired resistance and disease recurrence. Targeting polyIC directly to tumor cells avoids the toxicity associated with systemic delivery. PPD selectively delivered polyIC into PSMA-overexpressing PC cells, inducing apoptosis, cytokine secretion, and the recruitment of human peripheral blood mononuclear cells (PBMCs). PSMA-overexpressing tumors in nonobese diabetic/severe combined immunodeficiency (NOD/SCID) mice with partially reconstituted immune systems were significantly shrunken following PPD/polyIC treatment, in all cases. Half of the tumors showed complete regression. PPD/polyIC invokes antitumor immunity, but unlike many immunotherapies does not need to be personalized for each patient. The potent antitumor effects of PPD/polyIC should spur its development for clinical use.

PSMA-targeted polyinosine/polycytosine vector induces prostate tumor regression and invokes an antitumor immune response in mice

PubMed Central

Langut, Yael; Talhami, Alaa; Mamidi, Samarasimhareddy; Shir, Alexei; Zigler, Maya; Joubran, Salim; Sagalov, Anna; Flashner-Abramson, Efrat; Edinger, Nufar; Klein, Shoshana; Levitzki, Alexander

2017-01-01

There is an urgent need for an effective treatment for metastatic prostate cancer (PC). Prostate tumors invariably overexpress prostate surface membrane antigen (PSMA). We designed a nonviral vector, PEI-PEG-DUPA (PPD), comprising polyethylenimine–polyethyleneglycol (PEI–PEG) tethered to the PSMA ligand, 2-[3-(1, 3-dicarboxy propyl)ureido] pentanedioic acid (DUPA), to treat PC. The purpose of PEI is to bind polyinosinic/polycytosinic acid (polyIC) and allow endosomal release, while DUPA targets PC cells. PolyIC activates multiple pathways that lead to tumor cell death and to the activation of bystander effects that harness the immune system against the tumor, attacking nontargeted neighboring tumor cells and reducing the probability of acquired resistance and disease recurrence. Targeting polyIC directly to tumor cells avoids the toxicity associated with systemic delivery. PPD selectively delivered polyIC into PSMA-overexpressing PC cells, inducing apoptosis, cytokine secretion, and the recruitment of human peripheral blood mononuclear cells (PBMCs). PSMA-overexpressing tumors in nonobese diabetic/severe combined immunodeficiency (NOD/SCID) mice with partially reconstituted immune systems were significantly shrunken following PPD/polyIC treatment, in all cases. Half of the tumors showed complete regression. PPD/polyIC invokes antitumor immunity, but unlike many immunotherapies does not need to be personalized for each patient. The potent antitumor effects of PPD/polyIC should spur its development for clinical use. PMID:29229829

The impact of different scenarios for intermittent bladder catheterization on health state utilities: results from an internet-based time trade-off survey.

PubMed

Averbeck, Márcio Augusto; Krassioukov, Andrei; Thiruchelvam, Nikesh; Madersbacher, Helmut; Bøgelund, Mette; Igawa, Yasuhiko

2018-06-08

Intermittent catheterization (IC) is the gold standard for bladder management in patients with chronic urinary retention. Despite its medical benefits, IC-users experience a negative impact on their quality of life (QoL). For health economics based decision making, this impact is normally measured using generic QoL measures (such as EQ-5D) that estimate a single utility score which can be used to calculate Quality-Adjusted Life Years (QALYs). But these generic measures may not be sensitive to all relevant aspects of QoL affected by intermittent catheters. This study used alternative methods to estimate the health state utilities associated with different scenarios: using a multiple-use catheter, one-time-use catheter, pre-lubricated one-time-use catheter, and pre-lubricated one-time-use catheter with one less urinary tract infection (UTI) per year. Health state utilities were elicited through an internet-based Time Trade-Off (TTO) survey in adult volunteers representing the general population in Canada and the UK. Health states were developed to represent the catheters based on the following four attributes: steps and time needed for IC process, pain and the frequency of UTIs. The survey was completed by 956 respondents. One-time-use catheters, pre-lubricated one-time-use catheters and ready-to-use catheters were preferred to multiple-use catheters. The utility gains were associated with the following features: one-time-use (Canada: +0.013, UK: +0.021), ready-to-use (all: +0.017), and one less UTI/year (all: +0.011). Internet-based survey responders may have valued health states differently than the rest of the population: this might be a source of bias. Steps and time needed for the IC process, pain related to IC, and the frequency of UTIs have a significant impact on IC related utilities. These values could be incorporated into a cost utility analysis.

Performance of two immunochromatographic tests for diagnosis of visceral leishmaniasis in patients coinfected with HIV.

PubMed

da Silva, Mauro Roberto Biá; Brandão, Natália Alberto Alves; Colovati, Marco; de Sousa, Margella Marconcine Pinheiro; de Lima, Larissa Coelho; Dorta, Miriam Leandro; Ribeiro-Dias, Fátima; Costa, Dorcas Lamounier; Costa, Carlos Henrique Nery; de Oliveira, Milton Adriano Pelli

2018-02-01

Because of visceral leishmaniasis (VL) urbanization and spreading of the human immunodeficiency virus (HIV) infection to rural areas, coinfection has become more common. Here, we compared the accuracy of Kalazar Detect® (KD), an rK39-based immunochromatographic (IC) test, and OrangeLife® (OL), an rK39 + rK28 IC test, for diagnosing VL in patients coinfected with HIV in an endemic area in Brazil. Seventy-six VL patients and 40 patients with other diseases, of which 31 and 21 patients, respectively, were infected with HIV, were examined. The sensitivity of OL and KD tests was 88.89 and 95.45%, respectively, in patients without HIV. The sensitivity dropped to 67.74 and 61.29%, respectively, in coinfected patients. The decrease in sensitivity was not related to a decrease in the production of Leishmania-specific IgG. Because of the low sensitivity of rk39 test in HIV-infected patients, we suggest that patients with negative rK39 results should undergo further investigation with additional serological tests that are not based only on the rK39 antigen and examination of bone marrow aspirates.

Discovery of 2,4-diarylaminopyrimidines bearing a resorcinol motif as novel ALK inhibitors to overcome the G1202R resistant mutation.

PubMed

Geng, Kaijun; Xia, Zongjun; Ji, Yinchun; Zhang, Ruisi Ruthy; Sun, Deqiao; Ai, Jing; Song, Zilan; Geng, Meiyu; Zhang, Ao

2018-01-20

To address drug resistance caused by ALK kinase mutations, especially the most refractory and predominant mutation G1202R for the second-generation ALK inhibitor, a series of new diarylaminopyrimidine analogues were designed by incorporating a resorcinol moiety (A-ring) to interact the ALK kinase domain where the G1202R is located. Compound 12d turns out as the most potent with IC 50 values of 1.7, 3.5, and 1.8 nM against ALK wild type, gatekeeper mutant L1196M, and the G1202R mutant, respectively. More importantly, compound 12d has excellent inhibitory effects against the proliferation of BaF3 cells specifically expressing ALK wild type, gatekeeper L1196M, and the most challenging mutant G1202R, with IC 50 values all less than 1.5 nM. Collectively, compound 12d is worthy of further investigation as a new more potent third-generation ALK inhibitor to circumvent drug resistance of both the first-generation and the second-generation inhibitors. Copyright © 2017. Published by Elsevier Masson SAS.

Pesticides in Ground Water Database A Compilation of ...

EPA Pesticide Factsheets

... t •-; i.j'ic? ... c-.ji ¦$ t.-e : -c* ., ~ . j «-3 jra ctrc $f*a :"^;i •fct-Of* of "¦*'Z""*Jt'C^ >?r3 ,i,:d,:-rj ss^/Ci' ~ ..t • i ¦ .2'iir4 \\'s ' ' • r; "• s .vnr *¦<;>p ica ^ •••* ...

Ergopeptines bromocriptine and ergovaline and the dopamine type-2 receptor inhibitor domperidone inhibit bovine equilibrative nucleoside transporter 1-like activity.

PubMed

Miles, Edwena D; Xue, Yan; Strickland, James R; Boling, James A; Matthews, James C

2011-09-14

Neotyphodium coenophialum-infected tall fescue contains ergopeptines. Except for interactions with biogenic amine receptors (e.g., dopamine type-2 receptor, D2R), little is known about how ergopeptines affect animal metabolism. The effect of ergopeptines on bovine nucleoside transporters (NT) was evaluated using Madin-Darby bovine kidney (MDBK) cells. Equilibrative NT1 (ENT1)-like activity accounted for 94% of total NT activity. Inhibitory competition (IC(50)) experiments found that this activity was inhibited by both bromocriptine (a synthetic model ergopeptine and D2R agonist) and ergovaline (a predominant ergopeptine of tall fescue). Kinetic inhibition analysis indicated that bromocriptine inhibited ENT1-like activity through a competitive and noncompetitive mechanism. Domperidone (a D2R antagonist) inhibited ENT1 activity more in the presence than in the absence of bromocriptine and displayed an IC(50) value lower than that of bromocriptine or ergovaline, suggesting that inhibition was not through D2R-mediated events. These novel mechanistic findings imply that cattle consuming endophyte-infected tall fescue have reduced ENT1 activity and, thus, impaired nucleoside metabolism.

Performance of a Quantitative PCR-Based Assay and Beta-d-Glucan Detection for Diagnosis of Invasive Candidiasis in Very-Low-Birth-Weight Preterm Neonatal Patients (CANDINEO Study).

PubMed

Ramos, Jose Tomas; Villar, Sonia; Bouza, Emilio; Bergon-Sendin, Elena; Perez Rivilla, Alfredo; Collados, Caridad Tapia; Andreu, Mariano; Reyes, Candelaria Santana; Campos-Herrero, María Isolina; de Heredia, Jon López; Herrera, María Cruz López; Alonso, Paloma Anguita; Pallás-Alonso, Carmen Rosa; Cuenca-Estrella, Manuel

2017-09-01

An epidemiological, multicenter, noninterventional, observational case-control study was conducted to describe the performance of serum beta-d-glucan (BDG) and Candida PCR in blood, serum, and sterile samples for the diagnosis of invasive candidiasis (IC) in very-low-birth-weight (VLBW) preterm neonates and to compare these techniques with culture of samples from blood and other sterile sites. Seventeen centers participated in the study, and the number of episodes analyzed was 159. A total of 9 episodes of IC from 9 patients (7 confirmed and 2 probable) and 150 episodes of suspected sepsis from 117 controls were identified. The prevalence of IC was 5.7% (95% confidence interval [95% CI], 2.1 to 9.3). The mortality was significantly higher in episodes of IC (44.4%) than in the non-IC episodes (11.1%, P < 0.01). The sensitivity and specificity of the PCR performed on blood/serum samples were 87.5% and 81.6%, respectively. The sensitivity and specificity of the BDG results were lower (75.0% and 64.6%). For cases with negative culture results, the PCR and the BDG results were positive in 27 (17.4%) and 52 (33.5%) episodes, respectively. The presence of multiorgan failure, improvement with empirical antifungal therapy, thrombocytopenia, and Candida colonization were significantly associated ( P < 0.01) with PCR or BDG positivity regardless of the results of the cultures. Serum BDG analysis and Candida PCR could be used as complementary diagnostic techniques to detect IC in VLBW neonates. Copyright © 2017 Ramos et al.

Is GABA neurotransmission enhanced in auditory thalamus relative to inferior colliculus?

PubMed Central

Cai, Rui; Kalappa, Bopanna I.; Brozoski, Thomas J.; Ling, Lynne L.

2013-01-01

Gamma-aminobutyric acid (GABA) is the major inhibitory neurotransmitter in the central auditory system. Sensory thalamic structures show high levels of non-desensitizing extrasynaptic GABAA receptors (GABAARs) and a reduction in the redundancy of coded information. The present study compared the inhibitory potency of GABA acting at GABAARs between the inferior colliculus (IC) and the medial geniculate body (MGB) using quantitative in vivo, in vitro, and ex vivo experimental approaches. In vivo single unit studies compared the ability of half maximal inhibitory concentrations of GABA to inhibit sound-evoked temporal responses, and found that GABA was two to three times (P < 0.01) more potent at suppressing MGB single unit responses than IC unit responses. In vitro whole cell patch-clamp slice recordings were used to demonstrate that gaboxadol, a δ-subunit selective GABAAR agonist, was significantly more potent at evoking tonic inhibitory currents from MGB neurons than IC neurons (P < 0.01). These electrophysiological findings were supported by an in vitro receptor binding assay which used the picrotoxin analog [3H]TBOB to assess binding in the GABAAR chloride channel. MGB GABAARs had significantly greater total open chloride channel capacity relative to GABAARs in IC (P < 0.05) as shown by increased total [3H]TBOB binding. Finally, a comparative ex vivo measurement compared endogenous GABA levels and suggested a trend towards higher GABA concentrations in MGB than in IC. Collectively, these studies suggest that, per unit GABA, high affinity extrasynaptic and synaptic GABAARs confer a significant inhibitory GABAAR advantage to MGB neurons relative to IC neurons. This increased GABA sensitivity likely underpins the vital filtering role of auditory thalamus. PMID:24155003

Increased use of inhaled corticosteroids among young Danish adult asthmatics: an observational study.

PubMed

Davidsen, Jesper Rømhild; Søndergaard, Jens; Hallas, Jesper; Siersted, Hans Christian; Lykkegaard, Jesper; Andersen, Morten

2010-12-01

This population-based longitudinal study aimed to investigate trends in use of inhaled corticosteroids (ICS) and determinants of ICS use in young Danish adults with asthma. 106 757 users, aged 18-44 years, of anti-asthmatic drugs were identified in the Danish Register of Medical Product Statistics during 1997-2006. One year prevalences of ICS use were calculated in categories of gender, age, and annual consumption of inhaled beta-2-agonists (IBA) in defined daily doses (DDD) per year. Determinants of ICS use were estimated by logistic regression models. The one year prevalence of ICS use was constant, approximately 64%, during 1997-2000. An annual increase was observed from 67% in 2001 to 77% in 2006. This trend also existed when stratifying on gender, age and IBA use. Using 1997 as baseline, the adjusted odds ratios (ORs) of ICS use in 2000 was 0.98 (95% CI 0.96-1.01) compared to 1.12 (95% CI 1.09-1.15) in 2001, and 1.81 (95% CI 1.75-1.87) in 2006. Other determinants of high ICS use were female gender, young age, and high annual IBA consumption. Among those using at least 400 DDD of IBA per year (corresponding to 4.4 powder inhalations daily), nearly 20% had no ICS prescriptions in 2006. Treatment with ICS among young Danish adult asthmatics has increased since 2001. This apparent improvement was associated with the introduction of fixed dose combination inhalers with ICS and inhaled long-acting beta-2-agonists. However, there is still room for improvement. Copyright © 2010 Elsevier Ltd. All rights reserved.

Structure-Activity Relationships of Agents Modifying Cholinergic Transmissions

DTIC Science & Technology

1983-09-01

t .Li ,.L,: "."c’S .!Cetylchoiine vithin a choliner .,-ic synapse. 3o*e poss~lle .n~r.Ic:,. .- .ire I lecrease the content of acecylcholine wiithia the... choliner .,iLc tu,.,I’, by •nterfering aith synthesis, (2) desensitizing cholinergic receptors I.t 7o-’--n..tic qites, (3) decreasing the release of...method of Potter et al (1983). This method uses reverse phase HPLC to .;eparate acetylcholine and choline . The effluent S emerging from the column is

Flood Plain Information, Oneida Creek, New York.

DTIC Science & Technology

1973-07-01

0 of 1 voi t NA willI alo W seimet anII)Xd debr~lis ,car iled a lon1g, atI hig-her ellit I t ICS, I) set Ic’ ( It Most (i tire 2 1 hr1 Ilges," wiric...NOTES 1~ N MAP ’o SPEE SYLV, ,.-- w I- A~iL CL 2 LIMII I w FPFpvMz EXPL- AREA I- susj 4 VERA ~ CONT SYLV NTE BUF rI LEGEND OVERFzOW LIMiTS FINTERMEDIATE

Spectroscopic classification of AT 2018adg as a Type Ic supernova

NASA Astrophysics Data System (ADS)

Williams, S. C.; Nordin, J.; Hook, I. M.

2018-03-01

We obtained a spectrum of the transient AT 2018adg (see TNS) with the SPRAT spectrograph (resolution R 350; Piascik et al. 2014) on the 2-m Liverpool Telescope (LT; Steele et al. 2004) on 2018 Mar 11.13 UT. The spectrum is consistent with AT 2018adg being a Type Ic supernova around peak brightness, at a redshift of z 0.02 to 0.03, in agreement with the host galaxy redshift of z = 0.022 (da Costa et al. 1998).

Collection, processing, and reporting of damage tolerant design data for non-aerospace structural materials

NASA Technical Reports Server (NTRS)

Huber, P. D.; Gallagher, J. P.

1994-01-01

This report describes the organization, format and content of the NASA Johnson damage tolerant database which was created to store damage tolerant property data for non aerospace structural materials. The database is designed to store fracture toughness data (K(sub IC), K(sub c), J(sub IC) and CTOD(sub IC)), resistance curve data (K(sub R) VS. delta a (sub eff) and JR VS. delta a (sub eff)), as well as subcritical crack growth data (a vs. N and da/dN vs. delta K). The database contains complementary material property data for both stainless and alloy steels, as well as for aluminum, nickel, and titanium alloys which were not incorporated into the Damage Tolerant Design Handbook database.

Subcritical crack growth in porcelains, glass-ceramics, and glass-infiltrated alumina composite for dental restorations.

PubMed

Gonzaga, Carla Castiglia; Yoshimura, Humberto Naoyuki; Cesar, Paulo Francisco; Miranda, Walter Gomes

2009-05-01

The objective was to compare fracture toughness (K(Ic)), stress corrosion susceptibility coefficient (n), and stress intensity factor threshold for crack propagation (K(I0)) of two porcelains [VM7/Vita (V) and d.Sign/Ivoclar (D)], two glass-ceramics [Empress/Ivolcar (E1) and Empress2/Ivlocar (E2)] and a glass-infiltrated alumina composite [In-Ceram Alumina/Vita (IC)]. Disks were constructed according to each manufacturer's processing method, and polished before induction of cracks by a Vickers indenter. Crack lengths were measured under optical microscopy at times between 0.1 and 100 h. Specimens were stored in artificial saliva at 37 degrees C during the whole experiment. K(Ic) and n were determined using indentation fracture method. K(I0) was determined by plotting log crack velocity versus log K(I). Microstructure characterization was carried out under SEM, EDS, X-ray diffraction and X-ray fluorescence. IC and E2 presented higher K(Ic) and K(I0) compared to E1, V, and D. IC presented the highest n value, followed by E2, D, E1, and V in a decreasing order. V and D presented similar K(Ic), but porcelain V showed higher K(I0) and lower n compared to D. Microstructure features (volume fraction, size, aspect ratio of crystalline phases and chemical composition of glassy matrix) determined K(Ic). The increase of K(Ic) value favored the increases of n and K(I0).

Fatigue in Advanced Cancer Patients: Congruence Between Patients and Their Informal Caregivers About Patients' Fatigue Severity During Cancer Treatment With Palliative Intent and Predictors of Agreement.

PubMed

Poort, Hanneke; Peters, Marlies E W J; Gielissen, Marieke F M; Verhagen, Constans A H H V M; Bleijenberg, Gijs; van der Graaf, Winette T A; Wearden, Alison J; Knoop, Hans

2016-09-01

Informal caregivers (ICs) are increasingly involved in the monitoring of symptoms during advanced cancer patients' treatment with palliative intent. A common but subjective symptom during this extended treatment phase is fatigue. This exploratory longitudinal study aimed to determine agreement between patients and ICs about patients' fatigue severity. In addition, predictors of agreement over time were studied. A sample of 107 patients with advanced cancer (life expectancy ≥ six months) and their ICs completed the subscale fatigue severity of the Checklist Individual Strength based on the patient's status at baseline and six months later. This eight-item subscale has a validated cutoff to determine the presence of clinically relevant levels of fatigue. ICs' own fatigue severity, strain, self-esteem, and relationship satisfaction were examined as predictors of agreement. A total of 107 dyads completed measures at baseline and 69 dyads six months later. At baseline, ICs' significantly overestimated patients' fatigue severity (P < 0.001) with a moderate amount of bias (Cohen's d = 0.48). In 81 of the 107 dyads (76%), there was congruence about the presence or absence of severe fatigue. On a group level, congruence did not significantly change over time. On a dyad level, there was a tendency to either remain congruent or reach congruence. Next to baseline congruence, ICs' fatigue severity and strain predicted ICs' fatigue ratings (R(2) = 0.22). Most ICs accurately predict presence or absence of clinically relevant levels of patients' fatigue. ICs' own fatigue severity and strain should be taken into account as they influence agreement. Copyright © 2016 American Academy of Hospice and Palliative Medicine. Published by Elsevier Inc. All rights reserved.

Application of Receiver Operating Characteristic Analysis to Refine the Prediction of Potential Digoxin Drug Interactions

PubMed Central

Ellens, Harma; Deng, Shibing; Coleman, JoAnn; Bentz, Joe; Taub, Mitchell E.; Ragueneau-Majlessi, Isabelle; Chung, Sophie P.; Herédi-Szabó, Krisztina; Neuhoff, Sibylle; Palm, Johan; Balimane, Praveen; Zhang, Lei; Jamei, Masoud; Hanna, Imad; O’Connor, Michael; Bednarczyk, Dallas; Forsgard, Malin; Chu, Xiaoyan; Funk, Christoph; Guo, Ailan; Hillgren, Kathleen M.; Li, LiBin; Pak, Anne Y.; Perloff, Elke S.; Rajaraman, Ganesh; Salphati, Laurent; Taur, Jan-Shiang; Weitz, Dietmar; Wortelboer, Heleen M.; Xia, Cindy Q.; Xiao, Guangqing; Yamagata, Tetsuo

2013-01-01

In the 2012 Food and Drug Administration (FDA) draft guidance on drug-drug interactions (DDIs), a new molecular entity that inhibits P-glycoprotein (P-gp) may need a clinical DDI study with a P-gp substrate such as digoxin when the maximum concentration of inhibitor at steady state divided by IC50 ([I1]/IC50) is ≥0.1 or concentration of inhibitor based on highest approved dose dissolved in 250 ml divide by IC50 ([I2]/IC50) is ≥10. In this article, refined criteria are presented, determined by receiver operating characteristic analysis, using IC50 values generated by 23 laboratories. P-gp probe substrates were digoxin for polarized cell-lines and N-methyl quinidine or vinblastine for P-gp overexpressed vesicles. Inhibition of probe substrate transport was evaluated using 15 known P-gp inhibitors. Importantly, the criteria derived in this article take into account variability in IC50 values. Moreover, they are statistically derived based on the highest degree of accuracy in predicting true positive and true negative digoxin DDI results. The refined criteria of [I1]/IC50 ≥ 0.03 and [I2]/IC50 ≥ 45 and FDA criteria were applied to a test set of 101 in vitro-in vivo digoxin DDI pairs collated from the literature. The number of false negatives (none predicted but DDI observed) were similar, 10 and 12%, whereas the number of false positives (DDI predicted but not observed) substantially decreased from 51 to 40%, relative to the FDA criteria. On the basis of estimated overall variability in IC50 values, a theoretical 95% confidence interval calculation was developed for single laboratory IC50 values, translating into a range of [I1]/IC50 and [I2]/IC50 values. The extent by which this range falls above the criteria is a measure of risk associated with the decision, attributable to variability in IC50 values. PMID:23620486

A comparison of the fragmentation thresholds and inertial cavitation doses of different ultrasound contrast agents

NASA Astrophysics Data System (ADS)

Chen, Wen-Shiang; Matula, Thomas J.; Brayman, Andrew A.; Crum, Lawrence A.

2003-01-01

Contrast bubble destruction is important in several new diagnostic and therapeutic applications. The pressure threshold of destruction is determined by the shell material, while the propensity for of the bubbles to undergo inertial cavitation (IC) depends both on the gas and shell properties of the ultrasound contrast agent (UCA). The ultrasonic fragmentation thresholds of three specific UCAs (Optison, Sonazoid, and biSpheres), each with different shell and gas properties, were determined under various acoustic conditions. The acoustic emissions generated by the agents, or their derivatives, characteristic of IC after fragmentation, was also compared, using cumulated broadband-noise emissions (IC ``dose''). Albumin-shelled Optison and surfactant-shelled Sonazoid had low fragmentation thresholds (mean=0.13 and 0.15 MPa at 1.1 MHz, 0.48 and 0.58 MPa at 3.5 MHz, respectively), while polymer-shelled biSpheres had a significant higher threshold (mean=0.19 and 0.23 MPa at 1.1 MHz, 0.73 and 0.96 MPa for thin- and thick-shell biSpheres at 3.5 MHz, respectively, p<0.01). At comparable initial concentrations, surfactant-shelled Sonazoid produced a much larger IC dose after shell destruction than did either biSpheres or Optison (p<0.01). Thick-shelled biSpheres had the highest fragmentation threshold and produced the lowest IC dose. More than two and five acoustic cycles, respectively, were necessary for the thin- and thick-shell biSpheres to reach a steady-state fragmentation threshold.

Regulatory Elements Associated with Paternally-Expressed Genes in the Imprinted Murine Angelman/Prader-Willi Syndrome Domain

PubMed Central

Khadake, Jyoti; Heggestad, Arnold D.; Ma, Xiaojie; Johnstone, Karen A.; Resnick, James L.; Yang, Thomas P.

2013-01-01

The Angelman/Prader-Willi syndrome (AS/PWS) domain contains at least 8 imprinted genes regulated by a bipartite imprinting center (IC) associated with the SNRPN gene. One component of the IC, the PWS-IC, governs the paternal epigenotype and expression of paternal genes. The mechanisms by which imprinting and expression of paternal genes within the AS/PWS domain – such as MKRN3 and NDN – are regulated by the PWS-IC are unclear. The syntenic region in the mouse is organized and imprinted similarly to the human domain with the murine PWS-IC defined by a 6 kb interval within the Snrpn locus that includes the promoter. To identify regulatory elements that may mediate PWS-IC function, we mapped the location and allele-specificity of DNase I hypersensitive (DH) sites within the PWS-IC in brain cells, then identified transcription factor binding sites within a subset of these DH sites. Six major paternal-specific DH sites were detected in the Snrpn gene, five of which map within the 6 kb PWS-IC. We postulate these five DH sites represent functional components of the murine PWS-IC. Analysis of transcription factor binding within multiple DH sites detected nuclear respiratory factors (NRF's) and YY1 specifically on the paternal allele. NRF's and YY1 were also detected in the paternal promoter region of the murine Mrkn3 and Ndn genes. These results suggest that NRF's and YY1 may facilitate PWS-IC function and coordinately regulate expression of paternal genes. The presence of NRF's also suggests a link between transcriptional regulation within the AS/PWS domain and regulation of respiration. 3C analyses indicated Mkrn3 lies in close proximity to the PWS-IC on the paternal chromosome, evidence that the PWS-IC functions by allele-specific interaction with its distal target genes. This could occur by allele-specific co-localization of the PWS-IC and its target genes to transcription factories containing NRF's and YY1. PMID:23390487

Coastal Oceanography in the Beaufort Sea, Summer 1985.

DTIC Science & Technology

1987-07-01

Laboratory University of Washington Li -- and 1: R. K. Perry The Arctic Submarine Laboratory Naval Ocean Systems Center 1. . .. DT IC .ELECTE J 27 V...Applied Physics Laboratory Arctic Submarine Laboratory University of Washington Naval Ocean Systems Center Seattle, Washington 98105 San Diego, California...Becker and G. R. Garrison N The Applied Physics Laboratory University of Washington and R. K. Perry The Arctic Submarine Laboratory Naval Ocean Systems

Research for Improved Health: Variability and Impact of Structural Characteristics in Federally Funded Community Engaged Research

PubMed Central

Pearson, Cythina R.; Duran, Bonnie; Oetzel, John; Margarati, Maya; Villegas, Malia; Lucero, Julie; Wallerstein, Nina

2016-01-01

Background Although there is strong scientific, policy, and community support for community-engaged research (CEnR)—including community-based participatory research (CBPR)—the science of CEnR is still developing. Objective To describe structural differences in federally funded CEnR projects by type of research (i.e., descriptive, intervention, or dissemination/policy change) and race/ethnicity of the population served. Methods We identified 333 federally funded projects in 2009 that potentially involved CEnR, 294 principal investigators/project directors (PI/PD) were eligible to participate in a key informant (KI) survey from late 2011 to early 2012 that asked about partnership structure (68% response rate). Results The National Institute on Minority Health & Health Disparities (19.1%), National Cancer Institute (NCI; 13.3%), and the Centers for Disease Control and Prevention (CDC; 12.6%) funded the most CEnR projects. Most were intervention projects (66.0%). Projects serving American Indian or Alaskan Native (AIAN) populations (compared with other community of color or multiple-race/unspecified) were likely to be descriptive projects (p < .01), receive less funding (p < .05), and have higher rates of written partnership agreements (p < .05), research integrity training (p < .05), approval of publications (p < .01), and data ownership (p < .01). AIAN-serving projects also reported similar rates of research productivity and greater levels of resource sharing compared with those serving multiple-race/unspecified groups. Conclusions There is clear variability in the structure of CEnR projects with future research needed to determine the impact of this variability on partnering processes and outcomes. In addition, projects in AIAN communities receive lower levels of funding yet still have comparable research productivity to those projects in other racial/ethnic communities. PMID:25981421

Incremental validity of the Minnesota Multiphasic Personality Inventory-2 and symptom checklist-90-revised with mental health inpatients.

PubMed

Simonds, Elise C; Handel, Richard W; Archer, Robert P

2008-03-01

This study evaluated the incremental validity of scores from the Minnesota Multiphasic Personality Inventory-2 (MMPI-2) and the Symptom Checklist-90-Revised (SCL-90-R) in a sample of mental health inpatients originally published by Archer, Griffin, and Aiduk (1995). The incremental validity of scores from the SCL-90-R primary symptom dimensions and MMPI-2 Clinical, Content, and Restructured Clinical scales was assessed in a sample of 544 mental health inpatients using conceptually related items from the Brief Psychiatric Rating Scale (BPRS) as criteria. A series of hierarchical multiple regressions indicated that scores from the SCL-90-R primary symptom dimensions exhibited limited incremental validity (Mdn DeltaR(2) = .01, range = 0-.01), whereas scores from MMPI-2 scales contributed additional information in the prediction of ratings on all but one BPRS item (Mdn DeltaR( 2) = .08, range = .04-.12).

Application of Balanced Scorecard in the Evaluation of a Complex Health System Intervention: 12 Months Post Intervention Findings from the BHOMA Intervention: A Cluster Randomised Trial in Zambia

PubMed Central

Mutale, Wilbroad; Stringer, Jeffrey; Chintu, Namwinga; Chilengi, Roma; Mwanamwenge, Margaret Tembo; Kasese, Nkatya; Balabanova, Dina; Spicer, Neil; Lewis, James; Ayles, Helen

2014-01-01

Introduction In many low income countries, the delivery of quality health services is hampered by health system-wide barriers which are often interlinked, however empirical evidence on how to assess the level and scope of these barriers is scarce. A balanced scorecard is a tool that allows for wider analysis of domains that are deemed important in achieving the overall vision of the health system. We present the quantitative results of the 12 months follow-up study applying the balanced scorecard approach in the BHOMA intervention with the aim of demonstrating the utility of the balanced scorecard in evaluating multiple building blocks in a trial setting. Methods The BHOMA is a cluster randomised trial that aims to strengthen the health system in three rural districts in Zambia. The intervention aims to improve clinical care quality by implementing practical tools that establish clear clinical care standards through intensive clinic implementations. This paper reports the findings of the follow-up health facility survey that was conducted after 12 months of intervention implementation. Comparisons were made between those facilities in the intervention and control sites. STATA version 12 was used for analysis. Results The study found significant mean differences between intervention(I) and control (C) sites in the following domains: Training domain (Mean I:C; 87.5.vs 61.1, mean difference 23.3, p = 0.031), adult clinical observation domain (mean I:C; 73.3 vs.58.0, mean difference 10.9, p = 0.02 ) and health information domain (mean I:C; 63.6 vs.56.1, mean difference 6.8, p = 0.01. There was no gender differences in adult service satisfaction. Governance and motivation scores did not differ between control and intervention sites. Conclusion This study demonstrates the utility of the balanced scorecard in assessing multiple elements of the health system. Using system wide approaches and triangulating data collection methods seems to be key to successful evaluation of such complex health intervention. Trial number ClinicalTrials.gov NCT01942278 PMID:24751780

Application of balanced scorecard in the evaluation of a complex health system intervention: 12 months post intervention findings from the BHOMA intervention: a cluster randomised trial in Zambia.

PubMed

Mutale, Wilbroad; Stringer, Jeffrey; Chintu, Namwinga; Chilengi, Roma; Mwanamwenge, Margaret Tembo; Kasese, Nkatya; Balabanova, Dina; Spicer, Neil; Lewis, James; Ayles, Helen

2014-01-01

In many low income countries, the delivery of quality health services is hampered by health system-wide barriers which are often interlinked, however empirical evidence on how to assess the level and scope of these barriers is scarce. A balanced scorecard is a tool that allows for wider analysis of domains that are deemed important in achieving the overall vision of the health system. We present the quantitative results of the 12 months follow-up study applying the balanced scorecard approach in the BHOMA intervention with the aim of demonstrating the utility of the balanced scorecard in evaluating multiple building blocks in a trial setting. The BHOMA is a cluster randomised trial that aims to strengthen the health system in three rural districts in Zambia. The intervention aims to improve clinical care quality by implementing practical tools that establish clear clinical care standards through intensive clinic implementations. This paper reports the findings of the follow-up health facility survey that was conducted after 12 months of intervention implementation. Comparisons were made between those facilities in the intervention and control sites. STATA version 12 was used for analysis. The study found significant mean differences between intervention(I) and control (C) sites in the following domains: Training domain (Mean I:C; 87.5.vs 61.1, mean difference 23.3, p = 0.031), adult clinical observation domain (mean I:C; 73.3 vs.58.0, mean difference 10.9, p = 0.02 ) and health information domain (mean I:C; 63.6 vs.56.1, mean difference 6.8, p = 0.01. There was no gender differences in adult service satisfaction. Governance and motivation scores did not differ between control and intervention sites. This study demonstrates the utility of the balanced scorecard in assessing multiple elements of the health system. Using system wide approaches and triangulating data collection methods seems to be key to successful evaluation of such complex health intervention. ClinicalTrials.gov NCT01942278.

Corchorus olitorius (jute) extract induced cytotoxicity and genotoxicity on human multiple myeloma cells (ARH-77).

PubMed

İşeri, Özlem Darcansoy; Yurtcu, Erkan; Sahin, Feride Iffet; Haberal, Mehmet

2013-06-01

Corchorus olitorius L. (Malvaceae) has industrial importance in world jute production and is a widely cultivated and consumed crop in Cyprus and in some Arabic countries. The present study investigated cytotoxic and genotoxic effects of leaf extracts (LE) and seed extracts (SE) of the C. olitorius on the multiple myeloma-derived ARH-77 cells. The extracts were also evaluated for their total phenol content (TPC) and free radical scavenging activity (FRSA). C. olitorius was collected from Nicosia, Cyprus. TPC and FRSA were measured by Folin-Ciocalteu and DPPH free radical methods, respectively. Cytotoxicity was evaluated by the MTT assay (4-2048 µg/mL range), and DNA damage (at IC50 and ½IC50) was measured by the comet assay. The LE had significantly higher total phenol (78 mg GAE/g extract) than the SE (2 mg GAE/g extract) with significantly higher FRSA (IC50 LE: 23 µg/mL and IC50 SE: 10 401 µg/mL). Both LE and SE exerted cytotoxic effects on cells after 48 h. The IC50 of SE (17 µg/mL) was lower than LE (151 µg/mL), which demonstrates its higher cytotoxicity on cells. The extracts were applied at 150 and 75 µg/mL for LE and at 17 and 8.5 µg/mL for SE, and the results of the comet assay revealed that the extracts induced genotoxic damage on ARH-77 cells. In both 48 h leaf and seed extract treatments, genotoxic damage significantly increased with increasing concentrations at relevant cytotoxic concentrations. To our knowledge, this is the first report demonstrating the high cytotoxic potential of C. olitorius SE and the genotoxic potential of LE and SE.

Prime Contractors with Awards Over $25,000 by Name, Location, and Contract Number. Fiscal Year 1993. (1079 Construction Corp-Centre Manufacturing Co Inc.). Part 1

DTIC Science & Technology

1994-03-01

EZ 8 44 1- 1.. z 4L ZP u u 0 w Pa8 d 4i) 0 4.z’ 04 ~u 0 4 ) 4.~0 0:. 0W .w- w A.0 tD U.4 0) 0 4 4 4 0W IEu 40 IA. 0 W 42 4n z 4E ww W ta U4 m 4 4 U L...N 0 0kI ~II~(~ ( ~0~c ~IC I N I~(~I~0 01C 4 N( 04i..4 II .4 󈧄W00 IC0 Q 44 -4 0ൈ 00 00 0 1 .Z0 0 00ZZ 4 Is,00 00 0 0 ZI0I wc > 0 3a I Q I4b oo...1 m 3t 024.223 E g r 𔃺 4 to wi L8 z- z . 4L c o Wm 4l H z " E. w 0~ 4lL 44 W a U3 TD W xP 4 j 4 ) W V) F-4 4 4 1 w2 C. : 40 ’s U Q IN 0 1 0 0 0 0

Isoindolinone inhibitors of the murine double minute 2 (MDM2)-p53 protein-protein interaction: structure-activity studies leading to improved potency.

PubMed

Hardcastle, Ian R; Liu, Junfeng; Valeur, Eric; Watson, Anna; Ahmed, Shafiq U; Blackburn, Timothy J; Bennaceur, Karim; Clegg, William; Drummond, Catherine; Endicott, Jane A; Golding, Bernard T; Griffin, Roger J; Gruber, Jan; Haggerty, Karen; Harrington, Ross W; Hutton, Claire; Kemp, Stuart; Lu, Xiaohong; McDonnell, James M; Newell, David R; Noble, Martin E M; Payne, Sara L; Revill, Charlotte H; Riedinger, Christiane; Xu, Qing; Lunec, John

2011-03-10

Inhibition of the MDM2-p53 interaction has been shown to produce an antitumor effect, especially in MDM2 amplified tumors. The isoindolinone scaffold has proved to be versatile for the discovery of MDM2-p53 antagonists. Optimization of previously reported inhibitors, for example, NU8231 (7) and NU8165 (49), was guided by MDM2 NMR titrations, which indicated key areas of the binding interaction to be explored. Variation of the 2-N-benzyl and 3-alkoxy substituents resulted in the identification of 3-(4-chlorophenyl)-3-((1-(hydroxymethyl)cyclopropyl)methoxy)-2-(4-nitrobenzyl)isoindolin-1-one (74) as a potent MDM2-p53 inhibitor (IC(50) = 0.23 ± 0.01 μM). Resolution of the enantiomers of 74 showed that potent MDM2-p53 activity primarily resided with the (+)-R-enantiomer (74a; IC(50) = 0.17 ± 0.02 μM). The cellular activity of key compounds has been examined in cell lines with defined p53 and MDM2 status. Compound 74a activates p53, MDM2, and p21 transcription in MDM2 amplified cells and shows moderate selectivity for wild-type p53 cell lines in growth inhibition assays.

Predictors of dynamic hyperinflation during the 6-minute walk test in stable chronic obstructive pulmonary disease patients

PubMed Central

Chen, Rui; Lin, Lin; Tian, Jing-Wei; Zeng, Bin; Zhang, Lei

2015-01-01

Background Dynamic hyperinflation (DH) is a major contributor to exercise limitation in chronic obstructive pulmonary disease (COPD). Therefore, we aimed to elucidate the physiological factors responsible for DH development during the 6-minute walk test (6MWT) in COPD patients and compare ventilatory response to the 6MWT in hyperinflators and non-hyperinflators. Methods A total of 105 consecutive subjects with stable COPD underwent a 6MWT, and the Borg dyspnea scale, oxygen saturation (SpO2), breathing pattern, and inspiratory capacity (IC) were recorded before and immediately after walking. The change in IC was measured, and subjects were divided into hyperinflators (ΔIC >0.0 L) and non-hyperinflators (ΔIC ≤0.0 L). Spirometry, the Modified Medical Research Council (MMRC) dyspnea scale and St George’s Respiratory Questionnaire (SGRQ) were also assessed. Results DH was present in 66.67% of subjects. ΔIC/IC was significantly and negatively correlated with the small airway function. On multiple stepwise regression analysis forced expiratory flow after exhaling 50% of the forced vital capacity (FEF50%) was the only predictor of ΔIC/IC. Non-hyperinflators had a higher post-walking VT (t=2.419, P=0.017) and post-walking VE (t=2.599, P=0.011) than the hyperinflators did. Age and resting IC were independent predictors of the 6-minute walk distance (6MWD) in hyperinflators. Conclusions DH was considerably common in subjects with COPD. Small airway function may partly contribute to the DH severity during walking. The ventilator response to the 6MWT differed between hyperinflators and non-hyperinflators. Resting hyperinflation is an important predictor of functional exercise capacity in hyperinflators. PMID:26380729

Application of Incident Command Structure to clinical trial management in the academic setting: principles and lessons learned.

PubMed

Reynolds, Penny S; Michael, Mary J; Spiess, Bruce D

2017-02-09

Clinical trial success depends on appropriate management, but practical guidance to trial organisation and planning is lacking. The Incident Command System (ICS) is the 'gold standard' management system developed for managing diverse operations in major incident and public health arenas. It enables effective and flexible management through integration of personnel, procedures, resources, and communications within a common hierarchical organisational structure. Conventional ICS organisation consists of five function modules: Command, Planning, Operations, Logistics, and Finance/Administration. Large clinical trials will require a separate Regulatory Administrative arm, and an Information arm, consisting of dedicated data management and information technology staff. We applied ICS principles to organisation and management of the Prehospital Use of Plasma in Traumatic Haemorrhage (PUPTH) trial. This trial was a multidepartmental, multiagency, randomised clinical trial investigating prehospital administration of thawed plasma on mortality and coagulation response in severely injured trauma patients. We describe the ICS system as it would apply to large clinical trials in general, and the benefits, barriers, and lessons learned in utilising ICS principles to reorganise and coordinate the PUPTH trial. Without a formal trial management structure, early stages of the trial were characterised by inertia and organisational confusion. Implementing ICS improved organisation, coordination, and communication between multiple agencies and service groups, and greatly streamlined regulatory compliance administration. However, unfamiliarity of clinicians with ICS culture, conflicting resource allocation priorities, and communication bottlenecks were significant barriers. ICS is a flexible and powerful organisational tool for managing large complex clinical trials. However, for successful implementation the cultural, psychological, and social environment of trial participants must be accounted for, and personnel need to be educated in the basics of ICS. ClinicalTrials.gov, NCT02303964 . Registered on 28 November 2014.

Informal caregivers experience of supplemental oxygen in pulmonary fibrosis.

PubMed

Graney, Bridget A; Wamboldt, Frederick S; Baird, Susan; Churney, Tara; Fier, Kaitlin; Korn, Marjorie; McCormick, Mark; Vierzba, Thomas; Swigris, Jeffrey J

2017-07-01

Patients prescribed supplemental oxygen (O 2 ) therapy face challenges as they adjust to being constantly "tethered" to an oxygen delivery device. Informal caregivers (ICs) of patients with pulmonary fibrosis (PF) face their own, often overlooked hardships when O 2 is brought into their home and added to their lives. Our aim was to understand the multiple effects of supplemental oxygen therapy on ICs of patients with PF. We conducted single, semi-structured telephone interviews with twenty ICs of patients with PF who were using O 2 for at least 8 months. We performed a qualitative, content analysis based in grounded theory to examine data across subjects. ICs initially reacted to O 2 with trepidation and sadness as they came to recognize the changes it would cause in the lives of their patient-loved one (PLO). ICs recognized both beneficial and negative effects of O 2 on their PLOs. ICs also realized that O 2 created significant changes in their own lives, including introducing new roles and responsibilities for them, altering their home environments and significantly impacting their relationships with their PLOs. Although O 2 was a tangible and constant reminder of disease progression, over time ICs were able to adapt and accept their new lives with O 2 . ICs of patients with PF experience many life changes when their PLO is prescribed O 2 . Having O 2 prescribers anticipate and recognize these challenges provides an opportunity to give support and guidance to ICs of PF patients who require O 2 in the hopes of limiting the negative impact of O 2 on their lives. Clinicaltrials.gov , registration number NCT01961362 . Registered 9 October 2013.

Toxicity evaluation and prediction of toxic chemicals on activated sludge system.

PubMed

Cai, Bijing; Xie, Li; Yang, Dianhai; Arcangeli, Jean-Pierre

2010-05-15

The gaps of data for evaluating toxicity of new or overloaded organic chemicals on activated sludge system resulted in the requirements for methodology of toxicity estimation. In this study, 24 aromatic chemicals typically existed in the industrial wastewater were selected and classified into three groups of benzenes, phenols and anilines. Their toxicity on activated sludge was then investigated. Two indexes of IC(50-M) and IC(50-S) were determined respectively from the respiration rates of activated sludge with different toxicant concentration at mid-term (24h) and short-term (30min) time intervals. Experimental results showed that the group of benzenes was the most toxic, followed by the groups of phenols and anilines. The values of IC(50-M) of the tested chemicals were higher than those of IC(50-S). In addition, quantitative structure-activity relationships (QSARs) models developed from IC(50-M) were more stable and accurate than those of IC(50-S). The multiple linear models based on molecular descriptors and K(ow) presented better reliability than single linear models based on K(ow). Among these molecular descriptors, E(lumo) was the most important impact factor for evaluation of mid-term toxicity. Copyright (c) 2009 Elsevier B.V. All rights reserved.

User Perspectives of Characteristics of Improved Cookstoves from a Field Evaluation in Western Kenya

PubMed Central

Loo, Jennifer D.; Hyseni, Lirije; Ouda, Rosebel; Koske, Selline; Nyagol, Ronald; Sadumah, Ibrahim; Bashin, Michelle; Sage, Mike; Bruce, Nigel; Pilishvili, Tamara; Stanistreet, Debbi

2016-01-01

Over half of the world’s population uses biomass fuels; these households cook on open fires indoors, increasing their risk of adverse health effects due to household air pollution (HAP) from biomass combustion. This study evaluated six improved cookstoves (ICS) for effectiveness and acceptability in a rural community in Western Kenya. This paper describes women’s views on each ICS compared to the traditional three-stone fire. Views on stove characteristics, fuel consumption, health effects and acceptability were assessed through structured interviews and focus group discussions. Data were coded and analyzed using a thematic approach. In total, 262 interviews and 11 focus groups were conducted from 43 women. Overall, women preferred the ICS over the traditional three-stone fire for various reasons including ease of use, efficiency, fuel efficiency and perceived reduction in smoke and improved health. However, there were clear preferences for specific ICS with almost half of women preferring a Philips stove. Despite acceptance and use of ICS, women used multiple stoves to meet their daily needs. Qualitative studies are essential to field evaluations to provide insight into user perspectives and acceptability of ICS and to inform research and development of technologies that are both effective in reducing HAP and practical in use. PMID:26828505

Evaluation of Advanced Microwave Landing System Procedures in the New York Terminal Area

DTIC Science & Technology

1991-03-01

sector controller called the CAMRN sector who must then sequence that traffic with multiple feeders from the south before handing off to the final...Right (13R) were all being used by landing traffic, the final controller handled the runway 22 arrivals and the CAMRN controller handled the runway 13R...Feeder Fix AAL678 DC10 H 00:09:00 AAL68 B767 H 00:23:00 AAL588 A300 H 00:27:00 PAA224 A300 H 01:20:00 4/ TWAll L101 H 01:34:00 CAMRN Feeder Fix DAL144

Employees' communication attitudes and dislike for working in a group.

PubMed

Madlock, Paul E; Kennedy-Lightsey, Carrie D; Myers, Scott A

2007-12-01

This study examined 128 working adults' attitudes of tolerance for disagreement, tolerance for ambiguity, and argumentativeness in relation to their dislike for working in a group. They completed the Revised Tolerance for Disagreement Scale, the Multiple Stimulus Types Ambiguity Tolerance Scale, the Argumentativeness Scale, and the Grouphate Scale. Dislike for working in a group correlated negatively with Tolerance for Disagreement (r = -.28, p < .01, r2 = .08), Tolerance for Ambiguity (r = -.21, p < .05, r2 = .04), and Argumentativeness (r = -.21, p < .05, r2 = .04). Although these correlations are in the expected directions, magnitudes are very weak; unaccounted for variance should be examined.

Discovery of novel, potent and low-toxicity angiotensin II receptor type 1 (AT1) blockers: Design, synthesis and biological evaluation of 6-substituted aminocarbonyl benzimidazoles with a chiral center.

PubMed

Han, Xiao-Feng; He, Xing; Wang, Miao; Xu, Di; Hao, Li-Ping; Liang, Ai-Hua; Zhang, Jun; Zhou, Zhi-Ming

2015-10-20

Novel angiotensin II receptor type 1 (AT1) blockers bearing 6-substituted carbamoyl benzimidazoles with a chiral center were designed and synthesized as the first step to develop new antihypertensive agents and understand their pharmacodynamic and pharmacokinetic properties. The newly synthesized compounds were tested for their potential ability to displace [(125)I] Sar(1) Ile(8)-Ang II, which was specifically bound to human AT1 receptor. Radioligand binding assays revealed nanomolar affinity in several compounds under study. The IC50 values of nine ligands were higher than those of Losartan. The screening of decreased blood pressure in spontaneous hypertensive rats displayed that compound 8S (IC₅₀ = 5.0 nM) was equipotent with Losartan, whereas compounds 13R (IC₅₀ = 7.3 nM), 14R (IC₅₀ = 6.3 nM), and 14S (IC₅₀ = 3.5 nM) were slightly ahead of Losartan, and the most significant activity was demonstrated by compound 8R (IC₅₀ = 1.1 nM). Candidate 8R was identified for its excellent efficacy in antihypertension and fairly low toxicity based on plasma analyses, toxicology studies, and chronic oral tests. Finally, compound 8R exhibited strong and multiple interactions with target active sites of the theoretical AT1 receptor model in docking study. Copyright © 2015 Elsevier Masson SAS. All rights reserved.

Quiet Time Lowest Observable Frequency (QLOF) Calculation Program.

DTIC Science & Technology

1979-04-01

sorption controlled effect. The major cause of absorption at low and midlatitudes is the solar created ionospheric D-region. During quiet solar...1• t~~’~ CL~~F ‘ PFA L IC rI ,r 4r,~~~~u’~ ~ pa~~~,~~n p .r I3P1(7 . In , .1CF( ,n, , -~~p( , ) L W ‘5 t 1PFNS i” ~. cC y o ) .MII F c I n~~.nc1

JS-K has potent anti-angiogenic activity in vitro and inhibits tumour angiogenesis in a multiple myeloma model in vivo.

PubMed

Kiziltepe, Tanyel; Anderson, Kenneth C; Kutok, Jeffery L; Jia, Lee; Boucher, Kenneth M; Saavedra, Joseph E; Keefer, Larry K; Shami, Paul J

2010-01-01

Glutathione S-transferases (GSTs) play an important role in multidrug resistance and are upregulated in multiple cancers. We have designed a prodrug class that releases nitric oxide on metabolism by GST. O(2)-(2,4-Dinitrophenyl) 1-[(4-ethoxycarbonyl)piperazin-1-yl]diazen-1-ium-1,2-diolate (JS-K, a member of this class) has potent antineoplastic activity. We studied the effect of JS-K on angiogenesis in human umbilical vein endothelial cells (HUVECs), OPM1 multiple myeloma cells, chick aortic rings and in mice. JS-K inhibited the proliferation of HUVECs with a 50% inhibitory concentration (IC50) of 0.432, 0.466 and 0.505 microm at 24, 48 and 72 h, respectively. In the cord formation assay, JS-K led to a decrease in the number of cord junctions and cord length with an IC50 of 0.637 and 0.696 microm, respectively. JS-K inhibited cell migration at 5 h using VEGF as a chemoattractant. Migration inhibition occurred with an IC50 of 0.493 microm. In the chick aortic ring assay using VEGF or FGF-2 for vessel growth stimulation, 0.5 microm JS-K completely inhibited vessel growth. JS-K inhibited tumour angiogenesis in vivo in NIH III mice implanted subcutaneously with OPM1 multiple myeloma cells. JS-K is a potent inhibitor of angiogenesis in vitro and tumour vessel growth in vivo. As such, it establishes a new class of antineoplastic agent that targets the malignant cells directly as well as their microenvironment.

A Linear-Programming-Based Coal Preparation and Blending Technique.

DTIC Science & Technology

1985-04-10

ti Im- m .. stri ctiol .]s. ore-,sent prob Ims f()r model f ormu I at ion howv r. Thi srecci: ic (rav ty, , can take on 2() va tlues ranqi n; from 1...icuqn i < to prhl emP at v"xessx walsh I it- Vt r 1 b1t, si t 1aI e’r Orp il an a1ccer. f ’ ii r"Itv ) t h 14 (d-,I ormu IAtior. vrfr 1n1(_ish -I iiis

Useful Immunochromatographic Assay of Calprotectin in Gingival Crevicular Fluid for Diagnosis of Diseased Sites in Patients with Periodontal Diseases.

PubMed

Kido, Jun-Ichi; Murakami, Shinya; Kitamura, Masahiro; Yanagita, Manabu; Tabeta, Koichi; Yamazaki, Kazuhisa; Yoshie, Hiromasa; Watanabe, Hisashi; Izumi, Yuichi; Suda, Reiko; Yamamoto, Matsuo; Shiba, Hideki; Fujita, Tsuyoshi; Kurihara, Hidemi; Mizuno, Mitsuharu; Mishima, Akihiro; Kawahara, Nobumasa; Hashimoto, Kazuhiro; Naruishi, Koji; Nagata, Toshihiko

2017-09-06

Calprotectin, an inflammation-related protein, is present in gingival crevicular fluid (GCF) and the determination of calprotectin is useful for diagnosing periodontal diseases. We have recently developed a novel immunochromatographic (IC) chip system (SI-101402) to determine calprotectin levels in GCF. In the present study, the usefulness of this diagnostic system was investigated in patients with periodontal diseases. Thirty-six patients with periodontal diseases participated in this clinical test at multiple centers. Periodontitis sites (n=118) and non-periodontitis (healthy) sites (n=120) were selected after periodontal examination. GCF collection and periodontal examination were performed at baseline, after supragingival and subgingival scaling and root planing. Calprotectin amount in GCF was determined using a novel IC chip system and evaluated as a visual score and an IC reader value. The correlation between GCF calprotectin levels, clinical indicators and changes in calprotectin levels by periodontal treatments were investigated. Receiver operating characteristic (ROC) analysis of IC reader value for GCF calprotectin was performed to predict periodontal diseases. The visual score of GCF calprotectin was highly correlated the IC reader value. IC reader values of GCF calprotectin in periodontitis group were higher than those of healthy group at three dental examination stages and they significantly decreased with periodontal treatments. Visual scores and IC reader values of GCF calprotectin were correlated to the levels of clinical indicators. ROC analysis for GCF calprotectin showed an optimal cutoff value to predict periodontal diseases. Determination of GCF calprotectin using a novel IC chip system is useful for diagnosis of periodontal diseases.

Attachment of toxigenic Vibrio cholerae 01 to various freshwater plants and survival with a filamentous green alga, Rhizoclonium fontanum.

PubMed

Islam, M S; Drasar, B S; Bradley, D J

1989-12-01

In Bangladesh, cholera epidemics occur twice a year. V. cholerae 01 are readily isolated from the environment only during epidemics. The interepidemic reservoirs or sites of survival and multiplication of V. cholerae are still unknown. Investigations were carried out with various fresh-water plants as possible reservoirs of V. cholerae in the environment. Attachment to and acute population changes of V. cholerae on various plant surfaces was used as a screening technique to screen a particular plant species for survival studies. Five plant species, Anabaena variabilis, Rhizoclonium fontanum, Cladophora sp., Fontinalis antipyretica and Elodea canadensis were used for attachment experiments. Among these plants, R. fontanum showed the best attachment. On the basis of attachment results, survival experiments were carried out with R. fontanum. At 0.05% salinity toxigenic V. cholerae 01 survive longer in the presence of R. fontanum than in medium without algae.

miR-659-3p is involved in the regulation of the chemotherapy response of colorectal cancer via modulating the expression of SPHK1

PubMed Central

Li, Shuyuan; Fang, Ying; Qin, Hai; Fu, Wenzheng; Zhang, Xipeng

2016-01-01

Colorectal cancer (CRC) is one of most prevalent malignant diseases worldwide. Metastasis and chemo-resistance are the two prominent death-related factors of CRCs. Thus, it is urgent to understand the mechanism responsible for the chemo-resistant properties of CRC and develop new therapeutic methods. Here, we found that the expression of miR-659-3p was significantly reduced in cisplatin (CDDP)-resistant HT29 and LOVO colorectal cancer cells and in CDDP-resistant clinical colorectal cancer samples compared with respective CDDP-sensitive counterparts. Sphingosine kinase 1 (SPHK1) is a direct target of miR-659-3p in colorectal cancer cells, and it is negatively regulated by miR-659-3p. We found that anti-miR-659-3p could increase the IC50 of CDDP in parental HT29 and LOVO colorectal cancer cells; additionally, miR-659-3p mimics decreased the IC50 of CDDP in HT29/CDDP and LOVO/CDDP colorectal cancer cells. Furthermore, we showed that the miR-659-3p/SPHK1 pathway was involved in the regulation of chemotherapy responses of colorectal cancer cells in vivo. In all, our findings suggest a new mechanism involved in the regulation of the chemotherapy response of CRC and might provide new targets for CRC prevention and treatment. PMID:27725903

Increased Antibody Affinity Confers Broad In Vitro Protection against Escape Mutants of Severe Acute Respiratory Syndrome Coronavirus

PubMed Central

Rani, Mridula; Bolles, Meagan; Donaldson, Eric F.; Van Blarcom, Thomas; Baric, Ralph; Iverson, Brent

2012-01-01

Even though the effect of antibody affinity on neutralization potency is well documented, surprisingly, its impact on neutralization breadth and escape has not been systematically determined. Here, random mutagenesis and DNA shuffling of the single-chain variable fragment of the neutralizing antibody 80R followed by bacterial display screening using anchored periplasmic expression (APEx) were used to generate a number of higher-affinity variants of the severe acute respiratory syndrome coronavirus (SARS-CoV)-neutralizing antibody 80R with equilibrium dissociation constants (KD) as low as 37 pM, a >270-fold improvement relative to that of the parental 80R single-chain variable fragment (scFv). As expected, antigen affinity was shown to correlate directly with neutralization potency toward the icUrbani strain of SARS-CoV. Additionally, the highest-affinity antibody fragment displayed 10-fold-increased broad neutralization in vitro and completely protected against several SARS-CoV strains containing substitutions associated with antibody escape. Importantly, higher affinity also led to the suppression of viral escape mutants in vitro. Escape from the highest-affinity variant required reduced selective pressure and multiple substitutions in the binding epitope. Collectively, these results support the hypothesis that engineered antibodies with picomolar dissociation constants for a neutralizing epitope can confer escape-resistant protection. PMID:22696652

Systematic assessment of survey scan and MS2-based abundance strategies for label-free quantitative proteomics using high-resolution MS data.

PubMed

Tu, Chengjian; Li, Jun; Sheng, Quanhu; Zhang, Ming; Qu, Jun

2014-04-04

Survey-scan-based label-free method have shown no compelling benefit over fragment ion (MS2)-based approaches when low-resolution mass spectrometry (MS) was used, the growing prevalence of high-resolution analyzers may have changed the game. This necessitates an updated, comparative investigation of these approaches for data acquired by high-resolution MS. Here, we compared survey scan-based (ion current, IC) and MS2-based abundance features including spectral-count (SpC) and MS2 total-ion-current (MS2-TIC), for quantitative analysis using various high-resolution LC/MS data sets. Key discoveries include: (i) study with seven different biological data sets revealed only IC achieved high reproducibility for lower-abundance proteins; (ii) evaluation with 5-replicate analyses of a yeast sample showed IC provided much higher quantitative precision and lower missing data; (iii) IC, SpC, and MS2-TIC all showed good quantitative linearity (R(2) > 0.99) over a >1000-fold concentration range; (iv) both MS2-TIC and IC showed good linear response to various protein loading amounts but not SpC; (v) quantification using a well-characterized CPTAC data set showed that IC exhibited markedly higher quantitative accuracy, higher sensitivity, and lower false-positives/false-negatives than both SpC and MS2-TIC. Therefore, IC achieved an overall superior performance than the MS2-based strategies in terms of reproducibility, missing data, quantitative dynamic range, quantitative accuracy, and biomarker discovery.

Systematic Assessment of Survey Scan and MS2-Based Abundance Strategies for Label-Free Quantitative Proteomics Using High-Resolution MS Data

PubMed Central

2015-01-01

Survey-scan-based label-free method have shown no compelling benefit over fragment ion (MS2)-based approaches when low-resolution mass spectrometry (MS) was used, the growing prevalence of high-resolution analyzers may have changed the game. This necessitates an updated, comparative investigation of these approaches for data acquired by high-resolution MS. Here, we compared survey scan-based (ion current, IC) and MS2-based abundance features including spectral-count (SpC) and MS2 total-ion-current (MS2-TIC), for quantitative analysis using various high-resolution LC/MS data sets. Key discoveries include: (i) study with seven different biological data sets revealed only IC achieved high reproducibility for lower-abundance proteins; (ii) evaluation with 5-replicate analyses of a yeast sample showed IC provided much higher quantitative precision and lower missing data; (iii) IC, SpC, and MS2-TIC all showed good quantitative linearity (R2 > 0.99) over a >1000-fold concentration range; (iv) both MS2-TIC and IC showed good linear response to various protein loading amounts but not SpC; (v) quantification using a well-characterized CPTAC data set showed that IC exhibited markedly higher quantitative accuracy, higher sensitivity, and lower false-positives/false-negatives than both SpC and MS2-TIC. Therefore, IC achieved an overall superior performance than the MS2-based strategies in terms of reproducibility, missing data, quantitative dynamic range, quantitative accuracy, and biomarker discovery. PMID:24635752

Different Culture Metabolites of the Red Sea Fungus Fusarium equiseti Optimize the Inhibition of Hepatitis C Virus NS3/4A Protease (HCV PR).

PubMed

Hawas, Usama W; Al-Farawati, Radwan; Abou El-Kassem, Lamia T; Turki, Adnan J

2016-10-20

The endophytic fungus Fusarium equiseti was isolated from the brown alga Padina pavonica , collected from the Red Sea. The fungus was identified by its morphology and 18S rDNA. Cultivation of this fungal strain in biomalt-peptone medium led to isolation of 12 known metabolites of diketopeprazines and anthraquinones. The organic extract and isolated compounds were screened for their inhibition of hepatitis C virus NS3/4A protease (HCV PR). As a result, the fungal metabolites showed inhibition of HCV protease (IC 50 from 19 to 77 μM), and the fungus was subjected to culture on Czapek's (Cz) media, with a yield of nine metabolites with potent HCV protease inhibition ranging from IC 50 10 to 37 μM. The Cz culture extract exhibited high-level inhibition of HCV protease (IC 50 27.6 μg/mL) compared to the biomalt culture extract (IC 50 56 μg/mL), and the most potent HCV PR isolated compound (Griseoxanthone C, IC 50 19.8 μM) from the bio-malt culture extract showed less of an inhibitory effect compared to isolated ω-hydroxyemodin (IC 50 10.7 μM) from the optimized Cz culture extract. Both HCV PR active inhibitors ω-hydroxyemodin and griseoxanthone C were considered as the lowest selective safe constituents against Trypsin inhibitory effect with IC 50 48.5 and 51.3 μM, respectively.

3- and 4-pyridylalkyl adamantanecarboxylates: inhibitors of human cytochrome P450(17 alpha) (17 alpha-hydroxylase/C17,20-lyase). Potential nonsteroidal agents for the treatment of prostatic cancer.

PubMed

Chan, F C; Potter, G A; Barrie, S E; Haynes, B P; Rowlands, M G; Houghton, J; Jarman, M

1996-08-16

Various 3- and 4-pyridylalkyl 1-adamantanecarboxylates have been synthesized and tested for inhibitory activity toward the 17 alpha-hydroxylase and C17,20-lyase activities of human testicular cytochrome P450(17 alpha). The 4-pyridylalkyl esters were much more inhibitory than their 3-pyridylalkyl counterparts. The most potent was (S)-1-(4-pyridyl)ethyl 1-adamantanecarboxylate (3b; IC50 for lyase, 1.8 nM), whereas the (R)-enantiomer 3a was much less inhibitory (IC50 74 nM). Nearly as potent as 3b was the dimethylated counterpart, the 2-(4-pyridylpropan-2-yl) ester 5 (IC50 2.7 nM), which was also more resistant to degradation by esterases. In contrast to their 4-pyridyl analogs, the enantiomers of the 1-(3-pyridyl)ethyl ester were similarly inhibitory (IC50 for lyase; (R)-isomer 8a 150 nM, (S)-isomer 8b 230 nM). Amides corresponding to the 4-pyridylmethyl ester 1 and the (S)-1-(4-pyridyl)ethyl ester 3b, respectively 11 and 15b, were much less inhibitory than their ester counterparts. On the basis of a combination of inhibitory potency and resistance to esterases, the ester 5 was the best candidate for further development as a potential nonsteroidal inhibitor of cytochrome P450(17 alpha) for the treatment of prostate cancer.

Two novel bioactive glucosinolates from Broccoli (Brassica oleracea L. var. italica) florets.

PubMed

Survay, Nazneen Shaik; Kumar, Brajesh; Jang, Mi; Yoon, Do-Young; Jung, Yi-Sook; Yang, Deok-Chun; Park, Se Won

2012-09-01

Two novel glucosinolates along with one known glucosinolate were isolated from Broccoli (Brassica oleracea L. var. italica) florets. Their structures were established mainly by 1D ((1)H and (13)C NMR), 2D NMR ((1)H-(1)H COSY, DEPT 135°, HSQC and HMBC), and Tandem MS-MS spectrometric data as 2-mercaptomethyl sulfinyl glucosinolate [(Z)-4-(methylsulfinyl)-N-(sulfooxy)-2-((2'S,3'R,4'S,5'S,6'R)-3',4',5'-trihydroxy-6'(hydroxylmethyl)-2'-mercapto tetrahydro-2H-pyran-2-yl) butane amide] 1, (Z)-1-((2S,5S)-5-hydroxytetra-hydro-2H-pyran-2-ylthio)-2-(1H-indol-3-yl) ethylidene amino sulfate 2 and a known cinnamoyl [6'-O-trans-(4″-hydroxy cinnamoyl)4-(methylsulphinyl)butyl glucosinolate] 3. Compound 1 exhibited scavenging activity against DPPH with an inhibitory concentration IC(50) of 20 mM, whereas compound 3 was a weak antioxidant when compared to the standard quercetin (5 mM) as a positive control. Both the compounds showed a significant and similar antimicrobial activity against Staphylococcus aureus with an IC(50) of <625 μg/mL when compared to antibiotic duricef. Against Salmonella typhimurium the IC(50) of 1 and 3 was determined as <625 μg/mL and <1250 μg/mL, respectively, when compared to ampicillin (IC(50) ≤ 39 μg/mL) as a positive control. Copyright © 2012 Elsevier Ltd. All rights reserved.

Design, synthesis and biological evaluation of novel FGFR inhibitors bearing an indazole scaffold.

PubMed

Liu, Jian; Peng, Xia; Dai, Yang; Zhang, Wei; Ren, Sumei; Ai, Jing; Geng, Meiyu; Li, Yingxia

2015-07-28

Fibroblast growth factor receptor (FGFR) is a potential target for cancer therapy. Based on the structure of AZD4547 and NVPBGJ-398, we designed novel 1H-indazol-3-amine scaffold derivatives by utilizing scaffold hopping and molecular hybridization strategies. Consequently, twenty-eight new compounds were synthesized and evaluated for their inhibitory activity against FGFR1. Compound 7n bearing a 6-(3-methoxyphenyl)-1H-indazol-3-amine scaffold was first identified as a potent FGFR1 inhibitor, with good enzymatic inhibition (IC50 = 15.0 nM) and modest cellular inhibition (IC50 = 642.1 nM). The crystal structure of 7n bound to FGFR1 was obtained, which might provide a new basis for potent inhibitor design. Further structural optimization revealed that compound 7r stood out as the most potent FGFR1 inhibitor with the best enzyme inhibitory (IC50 = 2.9 nM) and cellular activity (IC50 = 40.5 nM).

Industri-Plex, OU-1, Master Cover Certification Report: Industri-Plex Site: September 30, 2008: Appendix C, C.1-C.2

EPA Pesticide Factsheets

2012-04-22

... Sincerely, \\ -/) I iJ/;5.~~.k. -r--7~.~~- ... 2.i:

U.S. EPA, Pesticide Product Label, MISTY GENERAL PURPOSE FLYING INSECT KILLER, 10/04/1995

EPA Pesticide Factsheets

2011-04-19

... f"!',lI,a! aI!rflllon INHALATION, f'c'·"',r wl,,,, to fIC~'l JI' r ... oj 3 N:I!'on~ PI'll~.'lnI n'sr"'~lfJ(' nm"'~tlon Sy ... 1 h'c! or' '!'(I '","' 1' ~~' .1",,~ e,,:., 1' !'lr I fen 1.1"" '.11 ...

An Optical and Infrared Time-domain Study of the Supergiant Fast X-Ray Transient Candidate IC 10 X-2

NASA Astrophysics Data System (ADS)

Kwan, Stephanie; Lau, Ryan M.; Jencson, Jacob; Kasliwal, Mansi M.; Boyer, Martha L.; Ofek, Eran; Masci, Frank; Laher, Russ

2018-03-01

We present an optical and infrared (IR) study of IC 10 X-2, a high-mass X-ray binary in the galaxy IC 10. Previous optical and X-ray studies suggest that X-2 is a Supergiant Fast X-ray Transient: a large-amplitude (factor of ∼100), short-duration (hours to weeks) X-ray outburst on 2010 May 21. We analyze R- and g-band light curves of X-2 from the intermediate Palomar Transient Factory taken between 2013 July 15 and 2017 February 14 that show high-amplitude (≳1 mag), short-duration (≲8 days) flares and dips (≳0.5 mag). Near-IR spectroscopy of X-2 from Palomar/TripleSpec show He I, Paschen-γ, and Paschen-β emission lines with similar shapes and amplitudes as those of luminous blue variables (LBVs) and LBV candidates (LBVc). Mid-IR colors and magnitudes from Spitzer/Infrared Array Camera photometry of X-2 resemble those of known LBV/LBVcs. We suggest that the stellar companion in X-2 is an LBV/LBVc and discuss possible origins of the optical flares. Dips in the optical light curve are indicative of eclipses from optically thick clumps formed in the winds of the stellar counterpart. Given the constraints on the flare duration (0.02–0.8 days) and the time between flares (15.1 ± 7.8 days), we estimate the clump volume filling factor in the stellar winds, f V , to be 0.01< {f}V< 0.71, which overlaps with values measured from massive star winds. In X-2, we interpret the origin of the optical flares as the accretion of clumps formed in the winds of an LBV/LBVc onto the compact object.

4D flow MRI assessment of extracranial-intracranial bypass: qualitative and quantitative evaluation of the hemodynamics.

PubMed

Sekine, Tetsuro; Takagi, Ryo; Amano, Yasuo; Murai, Yasuo; Orita, Erika; Matsumura, Yoshio; Kumita, Shin-Ichiro

2016-03-01

Our aim was to assess the feasibility of using time-resolved 3D phase-contrast (4D flow) MRI to characterize extracranial-intracranial (EC-IC) bypass. We enrolled 32 patients who underwent EC-IC bypass (15 men, 17 women; mean age 66.4 years). In all, 16 underwent radial artery graft (RAG) bypass and 16 underwent superficial temporal artery (STA) bypass. 4D flow MRI, time-of-flight (TOF) magnetic resonance angiography (MRA), and computed tomography angiography (CTA) were performed. Bypass patency, flow direction, and blood flow volume (BFV) of each artery were determined by 4D flow MRI. Arterial diameters were measured by TOF-MRA and CTA. We compared RAG and STA bypasses by evaluating the flow direction and BFV of each artery. We evaluated the correlation between arterial diameters (measured by CTA or MRA) and the BFV and the detectability of flow direction (measured by 4D flow MRI) of each artery. 4D flow MRI confirmed the patency of each bypass artery. Flow direction of the M1 segment of the middle cerebral artery and BFV in the bypass artery differed between RAG and STA groups (p < 0.01). BFV in the bypass slightly correlated with the diameters on CTA (p < 0.05, R (2) = 0.287). Of the 29 arteries in the circle of Willis, nine were not depicted on 4D flow MRI. Cutoff values for arterial diameters on CTA and TOF-MRA for detecting the artery on 4D flow MRI were 2.4 and 1.8 mm, respectively. 4D flow MRI provided unique information for characterizing EC-IC bypasses, although this detectability is limited when addressing small arteries with slow flow.

Self-assembled carrageenan/protamine polyelectrolyte nanoplexes-Investigation of critical parameters governing their formation and characteristics.

PubMed

Dul, Maria; Paluch, Krzysztof J; Kelly, Hazel; Healy, Anne Marie; Sasse, Astrid; Tajber, Lidia

2015-06-05

The aim of this work was to investigate the feasibility of cross-linker free polyelectrolyte complex formation at the nanoscale between carrageenan (CAR) and protamine (PROT). The properties of CAR/PROT nanoparticles (NPs) were dependent on the carrageenan type: kappa (KC), iota (IC) and lambda (LC), concentration of components, addition of divalent cations, weight mixing ratio (WMR) of constituents and mode of component addition. In the case of 0.1% w/v solutions, IC-based NPs had the smallest particle sizes (100-150nm) and low polydispersity indices (0.1-0.4). A decrease in the solution concentration from 0.1% to 0.05% w/v enabled the formation of KC/PROT NPs. All carrageenans exhibited the ability to form NPs with surface charge ranging from -190 to 40mV. The inclusion of divalent cations caused an increase in the particle size and zeta potential. Infrared analysis confirmed the presence of a complex between CAR and PROT and showed that IC chains undergo structural changes when forming NPs. Colloidal stability of NPs was related to the initial surface charge of particles and was time- and pH-dependent. IC was found to be the most suitable type of CAR when forming nanoplexes with PROT. Copyright © 2015 Elsevier Ltd. All rights reserved.

The Influence of Cyst Emptying, Lymph Node Resection and Chemotherapy on Survival in Stage IA and IC1 Epithelial Ovarian Cancer.

PubMed

Rosendahl, Mikkel; Mosgaard, Berit Jul; Høgdall, Claus

2016-10-01

To determine if survival in stage I ovarian cancer is influenced by cyst emptying, lymph node resection and chemotherapy. A survival analysis of 607 patients with ovarian cancer in stage IA, IA with cyst emptying (IAempty) and IC1 was performed. There was no difference in five-year survival between IA (87%) and IC1 (87%) (p=0.899), between IA and IAempty (86%) (p=0.500) nor between IA+IAempty (87%) and IC1 without IAempty (84%) (p=0.527). Five-year survival rate (5YSR) was significantly higher after lymph node resection in stage IA (94% vs. 85%; p=0.01) and IA+IC1 (93% vs. 85%; p=0.004). In multivariate analysis, lymph node resection improved prognosis significantly for all sub-stages, whereas stage and chemotherapy did not affect survival. In stage IA ovarian cancer, controlled cyst emptying without spill does not worsen prognosis. Lymph node resection is associated with improved survival in stage IA and IC1. Chemotherapy should only be offered where randomized controlled studies have shown a benefit. Copyright© 2016 International Institute of Anticancer Research (Dr. John G. Delinassios), All rights reserved.

Measurements of Mode I Interlaminar Properties of Carbon Fiber Reinforced Polymers Using Digital Image Correlation

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

Merzkirch, Matthias; Ahure Powell, Louise; Foecke, Tim

Numerical models based on cohesive zones are usually used to model and simulate the mechanical behavior of laminated carbon fiber reinforced polymers (CFRP) in automotive and aerospace applications and require different interlaminar properties. This work focuses on determining the interlaminar fracture toughness (G IC) under Mode I loading of a double cantilever beam (DCB) specimen of unidirectional CFRP, serving as prototypical material. The novelty of this investigation is the improvement of the testing methodology by introducing digital image correlation (DIC) as an extensometer and this tool allows for crack growth measurement, phenomenological visualization and quantification of various material responses tomore » Mode I loading. Multiple methodologies from different international standards and other common techniques are compared for the determination of the evolution of G IC as crack resistance curves (R-curves). The primarily metrological sources of uncertainty, in contrast to material specific related uncertainties, are discussed through a simple sensitivity analysis. Additionally, the current work offers a detailed insight into the constraints and assumptions to allow exploration of different methods for the determination of material properties using the DIC measured data. The main aim is an improvement of the measurement technique and an increase in the reliability of measured data during static testing, in advance of future rate dependent testing for crashworthiness simulations.« less

Measurements of Mode I Interlaminar Properties of Carbon Fiber Reinforced Polymers Using Digital Image Correlation

DOE PAGES

Merzkirch, Matthias; Ahure Powell, Louise; Foecke, Tim

2017-07-01

Numerical models based on cohesive zones are usually used to model and simulate the mechanical behavior of laminated carbon fiber reinforced polymers (CFRP) in automotive and aerospace applications and require different interlaminar properties. This work focuses on determining the interlaminar fracture toughness (G IC) under Mode I loading of a double cantilever beam (DCB) specimen of unidirectional CFRP, serving as prototypical material. The novelty of this investigation is the improvement of the testing methodology by introducing digital image correlation (DIC) as an extensometer and this tool allows for crack growth measurement, phenomenological visualization and quantification of various material responses tomore » Mode I loading. Multiple methodologies from different international standards and other common techniques are compared for the determination of the evolution of G IC as crack resistance curves (R-curves). The primarily metrological sources of uncertainty, in contrast to material specific related uncertainties, are discussed through a simple sensitivity analysis. Additionally, the current work offers a detailed insight into the constraints and assumptions to allow exploration of different methods for the determination of material properties using the DIC measured data. The main aim is an improvement of the measurement technique and an increase in the reliability of measured data during static testing, in advance of future rate dependent testing for crashworthiness simulations.« less

Comparative Efficacy of Intracoronary Allogeneic Mesenchymal Stem Cells and Cardiosphere-Derived Cells in Swine with Hibernating Myocardium

PubMed Central

Weil, Brian R.; Suzuki, Gen; Leiker, Merced M.; Fallavollita, James A.; Canty, John M.

2015-01-01

Rationale Allogeneic bone marrow-derived mesenchymal stem cells (MSCs) and cardiosphere-derived cells (CDCs) have each entered clinical trials but a direct comparison of these cell types has not been performed in a large animal model of hibernating myocardium. Objective Using completely blinded methodology, compare the efficacy of global intracoronary allogeneic MSCs (icMSCs, ~35×106) and CDCs (icCDCs, ~35×106) vs. vehicle in cyclosporine-immunosuppressed swine with a chronic LAD stenosis (n=26). Methods and Results Studies began 3-months after instrumentation when wall-thickening (%WT) was reduced (LAD%WT 38±11% (mean ± SD) vs. 83±26% in remote, p<0.01) and similar among groups. Four-weeks after treatment, LAD%WT increased similarly following icCDCs and icMSCs, while it remained depressed in vehicle-treated controls (icMSCs: 51±13%; icCDCs: 51±17%; vehicle: 34±3%, treatments p<0.05 vs. vehicle). There was no change in myocardial perfusion. Both icMSCs and icCDCs increased LAD myocyte nuclear density (icMSCs: 1601±279 nuclei/mm2, icCDCs: 1569±294 nuclei/mm2, vehicle: 973±181 nuclei/mm2, treatments p<0.05 vs. vehicle) and reduced myocyte diameter (icMSCs: 16.4±1.5 μm, icCDCs: 16.8±1.2 μm, vehicle: 20.2±3.7 μm, treatments p<0.05 vs. vehicle) to the same extent. Similar changes in myocyte nuclear density and diameter were observed in the remote region of cell-treated animals. Cell fate analysis using Y-FISH demonstrated rare cells from sex-mismatched donors. Conclusions Allogeneic icMSCs and icCDCs exhibit comparable therapeutic efficacy in a large animal model of hibernating myocardium. Both cell types produced equivalent increases in regional function and stimulated myocyte regeneration in ischemic and remote myocardium. The activation of endogenous myocyte proliferation and regression of myocyte cellular hypertrophy support a common mechanism of cardiac repair. PMID:26271689

Reforming the Joint Chiefs of Staff.

DTIC Science & Technology

1983-08-01

i . 1. 1 e, * vJ. r ŗi. - .- F-S.., Ar;:it:d ’t i . i . A i r For -::. r ic c.r .m’, I 蟙 a...understandi rig of Lhe Is i ev c:i. tt i on c-f u?e i r -. i t L jon,, Wi thoh U t he benef it of a hi t:or i c.- 1 n-Ii :z I s, there i s a tendency...by criticez- of t. he JCS L i gl IDre t s or i . gi i al purpose& and 1 i mi tat i ons. e r

Dynein and dynactin leverage their bivalent character to form a high-affinity interaction.

PubMed

Siglin, Amanda E; Sun, Shangjin; Moore, Jeffrey K; Tan, Sarah; Poenie, Martin; Lear, James D; Polenova, Tatyana; Cooper, John A; Williams, John C

2013-01-01

Cytoplasmic dynein and dynactin participate in retrograde transport of organelles, checkpoint signaling and cell division. The principal subunits that mediate this interaction are the dynein intermediate chain (IC) and the dynactin p150(Glued); however, the interface and mechanism that regulates this interaction remains poorly defined. Herein, we use multiple methods to show the N-terminus of mammalian dynein IC, residues 10-44, is sufficient for binding p150(Glued). Consistent with this mapping, monoclonal antibodies that antagonize the dynein-dynactin interaction also bind to this region of the IC. Furthermore, double and triple alanine point mutations spanning residues 6 to 19 in the yeast IC homolog, Pac11, produce significant defects in spindle positioning. Using the same methods we show residues 381 to 530 of p150(Glued) form a minimal fragment that binds to the dynein IC. Sedimentation equilibrium experiments indicate that these individual fragments are predominantly monomeric, but admixtures of the IC and p150(Glued) fragments produce a 2:2 complex. This tetrameric complex is sensitive to salt, temperature and pH, suggesting that the binding is dominated by electrostatic interactions. Finally, circular dichroism (CD) experiments indicate that the N-terminus of the IC is disordered and becomes ordered upon binding p150(Glued). Taken together, the data indicate that the dynein-dynactin interaction proceeds through a disorder-to-order transition, leveraging its bivalent-bivalent character to form a high affinity, but readily reversible interaction.

Physical activity, sedentary behavior, and aerobic capacity in persons with multiple sclerosis.

PubMed

Motl, Robert W; Sandroff, Brian M; Pilutti, Lara A; Klaren, Rachel E; Baynard, Tracy; Fernhall, Bo

2017-01-15

There is substantial evidence that exercise training improves aerobic capacity among people with multiple sclerosis (MS), but less is known about the associations between physical activity and sedentary behaviors with aerobic capacity. This study examined if objectively-measured moderate-to-vigorous (MVPA) and light (LPA) physical activity and sedentary behavior were associated with peak aerobic capacity (VO 2 peak) measured using an established protocol for conducting a maximal, incremental exercise test in persons with MS. The study involved a cross-sectional, observational study design and included 49 persons with MS. Participants wore an accelerometer around the waist during the waking hours for a 7-day period as a measure of physical activity and sedentary behaviors, and completed a maximal, incremental exercise test on an electronically-braked, computer-controlled cycle ergometer with open-circuit spirometry for measuring VO 2 peak. VO 2 peak was significantly correlated with MVPA (r=0.53, p<0.001) and LPA (r=0.39, p<0.01), but not sedentary behavior (r=-0.12, p=0.44). Linear regression analysis indicated that MVPA (B=0.19, SE B=0.04, β=0.51, p<0.001) and LPA (B=0.02, SE B=0.01, β=0.30, p<0.05), but not sedentary behavior (B=-0.01, SE B=0.01, β=-0.14, p=0.26), explained significant variance in VO 2 peak (R 2 =0.40). We provide the first evidence that MVPA and LPA represent concurrent correlates of VO 2 peak and both could be targeted for improving aerobic capacity in persons with MS. Copyright © 2016 Elsevier B.V. All rights reserved.

An integrated control and readout circuit for implantable multi-target electrochemical biosensing.

PubMed

Ghoreishizadeh, Sara S; Baj-Rossi, Camilla; Cavallini, Andrea; Carrara, Sandro; De Micheli, Giovanni

2014-12-01

We describe an integrated biosensor capable of sensing multiple molecular targets using both cyclic voltammetry (CV) and chronoamperometry (CA). In particular, we present our custom IC to realize voltage control and current readout of the biosensors. A mixed-signal circuit block generates sub-Hertz triangular waveform for the biosensors by means of a direct-digital-synthesizer to control CV. A current to pulse-width converter is realized to output the data for CA measurement. The IC is fabricated in 0.18 μm technology. It consumes 220 μW from 1.8 V supply voltage, making it suitable for remotely-powered applications. Electrical measurements show excellent linearity in sub- μA current range. Electrochemical measurements including CA measurements of glucose and lactate and CV measurements of the anti-cancer drug Etoposide have been acquired with the fabricated IC and compared with a commercial equipment. The results obtained with the fabricated IC are in good agreement with those of the commercial equipment for both CV and CA measurements.

["Hope Dies Last …" - Cross-Sectoral Cooperation in Integrated Care].

PubMed

Ruppert, Daniel; Stegbauer, Constanze; Bramesfeld, Anke; Bestmann, Beate; Szecsenyi, Joachim; Götz, Katja

2017-04-01

Objective Multiple models of Integrated Care (IC) have been implemented in German mental health services in the last decade in order to improve cross-sectoral, interdisciplinary cooperation. This study investigates an IC network model providing home treatment, case management and a 24/7 hotline. The aim of the study was to explore how health professionals working in this service model perceive both cooperation within their facilities and with external stakeholders. Methods 5 focus groups with 39 health professionals working in an IC mental health network were conducted and analyzed with qualitative content analysis. Results Focus groups participants reported on excellent cooperation within their facilities. The cooperation with external stakeholders, i. e. physicians, psychotherapists and psychiatric clinics, leaves room for improvement. Conclusions Until now little consideration has been given to the perspectives of health professionals. Cooperation within IC mental health networks seems to be effective. Cooperation with stakeholders outside the networks needs to be enhanced. © Georg Thieme Verlag KG Stuttgart · New York.

The optical design of 3D ICs for smartphone and optro-electronics sensing module

NASA Astrophysics Data System (ADS)

Huang, Jiun-Woei

2018-03-01

Smartphone require limit space for image system, current lens, used in smartphones are refractive type, the effective focal length is limited the thickness of phone physical size. Other, such as optro-electronics sensing chips, proximity optical sensors, and UV indexer chips are integrated into smart phone with limit space. Due to the requirement of multiple lens in smartphone, proximity optical sensors, UV indexer and other optro-electronics sensing chips in a limited space of CPU board in future smart phone, optro-electronics 3D IC's integrated with optical lens or components may be a key technology for 3 C products. A design for reflective lens is fitted to CMOS, proximity optical sensors, UV indexer and other optro-electronics sensing chips based on 3-D IC. The reflective lens can be threes times of effective focal lens, and be able to resolve small object. The system will be assembled and integrated in one 3-D IC more easily.

Hit-to-lead evaluation of a novel class of sphingosine 1-phosphate lyase inhibitors.

PubMed

Dinges, Jurgen; Harris, Christopher M; Wallace, Grier A; Argiriadi, Maria A; Queeney, Kara L; Perron, Denise C; Dominguez, Eric; Kebede, Tegest; Desino, Kelly E; Patel, Hetal; Vasudevan, Anil

2016-05-01

Inhibition of sphingosine-1-phosphate lyase has recently been proposed as a potential treatment option for inflammatory disorders such as multiple sclerosis, rheumatoid arthritis, and inflammatory bowel disease. In this report we describe our hit-to-lead evaluation of the isoxazolecarboxamide 6, a high-throughput screening hit (in vitro IC50=1.0 μM, cell IC50=1.8 μM), as a novel S1P lyase inhibitor. We were able to establish basic structure-activity relationships around 6 and succeeded in obtaining X-ray structural information which enabled structure-based design. With the discovery of 28, enzyme activity was quickly improved to IC50=120 nM and cell potency to IC50=230 nM. The main liability in the established isoxazolecarboxamide hit series was determined to be metabolic stability. In particular we identified that future lead-optimization efforts to overcome this problem should focus on blocking the N-dealkylation on the secondary amine. Copyright © 2016 Elsevier Ltd. All rights reserved.

Relating illness complexity to reimbursement in CKD patients.

PubMed

Bessette, Russell W; Carter, Randy L

2011-01-01

Despite significant investments of federal and state dollars to transition patient medical records to an all-electronic system, a chasm still exists between health care quality and payment for it. A major reason for this gap is the difficulty in evaluating health care outcomes based on claims data. Since both payers and patients may not appreciate how illness complexity impacts treatment outcomes, it is difficult to determine fair provider compensation. Chronic kidney disease (CKD) typifies these problems and is often associated with comorbidities that impact cost, health, and work productivity. Thus, the objective of this study was to evaluate an illness complexity score (ICS) based on a linear regression of select blood values that might assist in predicting average monthly reimbursements in CKD patients. A second objective was to compare the results of this ICS prediction to results obtained by prediction of average monthly reimbursement using CKD stage. A third objective was to analyze the relationship between the change in ICS, estimated glomerular filtration rate (eGFR), and CKD stage over time to average monthly reimbursement. We calculated parsimonious values for select variables associated with CKD patients and compared the ICS to ordinal staging of renal disease. Data from 177 de-identified patients over 13 months was collected, which included 15 blood chemistry observations along with complete claims data for all medical expenses. To test for the relationship between average blood chemistry values, stages of CKD, age, and average monthly reimbursement, we modeled an association through a linear regression function of age, eGFR, and the Z-scores calculated from average monthly values of phosphorus, parathyroid hormone, glucose, hemoglobin, bicarbonate, albumin, creatinine, blood urea nitrogen, potassium, calcium, sodium, alkaline phosphatase, alanine aminotransferase, and white blood cells. The results of our study demonstrated that the association between average ICS values throughout the entire study period predicted average monthly reimbursements with an R(2) value of 0.41. Comparing that value to the association between the average CKD stage and average monthly reimbursement demonstrated an R(2) value of 0.08. Thus, ICS offers five times greater sensitivity over CKD staging as a measure of illness complexity. Sorting the patient population by changes in CKD stage or ICS over the entire study period revealed significant differences between the two scoring methods. Groups scored by ICS demonstrated greater sensitivity by capturing dysfunction in other organ systems and had a better association with reimbursement than groups scored by CKD staging.

NMR Insights into the Structure-Function Relationships in the Binding of Melanocortin Analogues to the MC1R Receptor.

PubMed

Morais, Maurício; Zamora-Carreras, Héctor; Raposinho, Paula D; Oliveira, Maria Cristina; Pantoja-Uceda, David; Correia, João D G; Jiménez, M Angeles

2017-07-15

Linear and cyclic analogues of the α-melanocyte stimulating hormone (α-MSH) targeting the human melanocortin receptor 1 (MC1R) are of pharmacological interest for detecting and treating melanoma. The central sequence of α-MSH (His-Phe-Arg-Trp) has been identified as being essential for receptor binding. To deepen current knowledge on the molecular basis for α-MSH bioactivity, we aimed to understand the effect of cycle size on receptor binding. To that end, we synthesised two macrocyclic isomeric α-MSH analogues, c[NH-NO₂-C₆H₃-CO-His-DPhe-Arg-Trp-Lys]-Lys-NH₂ ( CycN-K6 ) and c[NH-NO₂-C₆H₃-CO-His-DPhe-Arg-Trp-Lys-Lys]-NH₂ ( CycN-K7 ). Their affinities to MC1R receptor were determined by competitive binding assays, and their structures were analysed by ¹H and 13 C NMR. These results were compared to those of the previously reported analogue c[S-NO₂-C₆H₃-CO-His-DPhe-Arg-Trp-Cys]-Lys-NH₂ ( CycS-C6 ). The MC1R binding affinity of the 22-membered macrocyclic peptide CycN-K6 (IC 50 = 155 ± 16 nM) is higher than that found for the 25-membered macrocyclic analogue CycN-K7 (IC 50 = 495 ± 101 nM), which, in turn, is higher than that observed for the 19-membered cyclic analogue CycS-C6 (IC 50 = 1770 ± 480 nM). NMR structural study indicated that macrocycle size leads to changes in the relative dispositions of the side chains, particularly in the packing of the Arg side chain relative to the aromatic rings. In contrast to the other analogues, the 22-membered cycle's side chains are favorably positioned for receptor interaction.

Dual energy X-ray absorptiometry spine scans to determine abdominal fat in post-menopausal women

PubMed Central

Bea, J. W.; Blew, R. M.; Going, S. B.; Hsu, C-H; Lee, M. C.; Lee, V. R.; Caan, B.J.; Kwan, M.L.; Lohman, T. G.

2016-01-01

Body composition may be a better predictor of chronic disease risk than body mass index (BMI) in older populations. Objectives We sought to validate spine fat fraction (%) from dual energy X-ray absorptiometry (DXA) spine scans as a proxy for total abdominal fat. Methods Total body DXA scan abdominal fat regions of interest (ROI) that have been previously validated by magnetic resonance imaging were assessed among healthy, postmenopausal women who also had antero-posterior spine scans (n=103). ROIs were 1) lumbar vertebrae L2-L4 and 2) L2-Iliac Crest (L2-IC), manually selected by two independent raters, and 3) trunk, auto-selected by DXA software. Intra-class correlation coefficients evaluated intra and inter-rater reliability on a random subset (N=25). Linear regression models, validated by bootstrapping, assessed the relationship between spine fat fraction (%) and total abdominal fat (%) ROIs. Results Mean age, BMI and total body fat were: 66.1 ± 4.8y, 25.8 ± 3.8kg/m2 and 40.0 ± 6.6%, respectively. There were no significant differences within or between raters. Linear regression models adjusted for several participant and scan characteristics were equivalent to using only BMI and spine fat fraction. The model predicted L2-L4 (Adj. R2: 0.83) and L2-IC (Adj.R2:0.84) abdominal fat (%) well; the adjusted R2 for trunk fat (%) was 0.78. Model validation demonstrated minimal over-fitting (Adj. R2: 0.82, 0.83, and 0.77 for L2-L4, L2-IC, and trunk fat respectively). Conclusions The strong correlation between spine fat fraction and DXA abdominal fat measures make it suitable for further development in post-menopausal chronic disease risk prediction models. PMID:27416964

Discovery of Lacosamide Affinity Bait Agents That Exhibit Potent Voltage-Gated Sodium Channel Blocking Properties

PubMed Central

2012-01-01

Lacosamide ((R)-1) is a recently marketed, first-in-class, antiepileptic drug. Patch-clamp electrophysiology studies are consistent with the notion that (R)-1 modulates voltage-gated Na+ channel function by increasing and stabilizing the slow inactivation state without affecting fast inactivation. The molecular pathway(s) that regulate slow inactivation are poorly understood. Affinity baits are chemical reactive units, which when appended to a ligand (drug) can lead to irreversible, covalent modification of the receptor thus permitting drug binding site identification including, possibly, the site of ligand function. We describe, herein, the synthesis of four (R)-1 affinity baits, (R)-N-(4″-isothiocyanatobiphenyl-4′-yl)methyl 2-acetamido-3-methoxypropionamide ((R)-8), (S)-N-(4″-isothiocyanatobiphenyl-4′-yl)methyl 2-acetamido-3-methoxypropionamide ((S)-8), (R)-N-(3″-isothiocyanatobiphenyl-4′-yl)methyl 2-acetamido-3-methoxypropionamide ((R)-9), and (R)-N-(3″-acrylamidobiphenyl-4′-yl)methyl 2-acetamido-3-methoxypropionamide ((R)-10). The affinity bait compounds were designed to interact with the receptor(s) responsible for (R)-1-mediated slow inactivation. We show that (R)-8 and (R)-9 are potent inhibitors of Na+ channel function and function by a pathway similar to that observed for (R)-1. We further demonstrate that (R)-8 function is stereospecific. The calculated IC50 values determined for Na+ channel slow inactivation for (R)-1, (R)-8, and (R)-9 were 85.1, 0.1, and 0.2 μM, respectively. Incubating (R)-9 with the neuronal-like CAD cells led to appreciable levels of Na+ channel slow inactivation after cellular wash, and the level of slow inactivation only modestly decreased with further incubation and washing. Collectively, these findings have identified a promising structural template to investigate the voltage-gated Na+ channel slow inactivation process. PMID:23509982

Multimodal neuroimaging in presurgical evaluation of drug-resistant epilepsy☆

PubMed Central

Zhang, Jing; Liu, Weifang; Chen, Hui; Xia, Hong; Zhou, Zhen; Mei, Shanshan; Liu, Qingzhu; Li, Yunlin

2013-01-01

Intracranial EEG (icEEG) monitoring is critical in epilepsy surgical planning, but it has limitations. The advances of neuroimaging have made it possible to reveal epileptic abnormalities that could not be identified previously and improve the localization of the seizure focus and the vital cortex. A frequently asked question in the field is whether non-invasive neuroimaging could replace invasive icEEG or reduce the need for icEEG in presurgical evaluation. This review considers promising neuroimaging techniques in epilepsy presurgical assessment in order to address this question. In addition, due to large variations in the accuracies of neuroimaging across epilepsy centers, multicenter neuroimaging studies are reviewed, and there is much need for randomized controlled trials (RCTs) to better reveal the utility of presurgical neuroimaging. The results of multiple studies indicate that non-invasive neuroimaging could not replace invasive icEEG in surgical planning especially in non-lesional or extratemporal lobe epilepsies, but it could reduce the need for icEEG in certain cases. With technical advances, multimodal neuroimaging may play a greater role in presurgical evaluation to reduce the costs and risks of epilepsy surgery, and provide surgical options for more patients with drug-resistant epilepsy. PMID:24282678

A Concept Analysis of Patient Participation in Intermediate Care.

PubMed

Kvæl, Linda Aimée Hartford; Debesay, Jonas; Langaas, Anne; Bye, Asta; Bergland, Astrid

2018-03-05

Although the concept of patient participation has been discussed for a number of years, there is still no clear definition of what constitutes the multidimensional concept, and the application of the concept in an intermediate care (IC) context lacks clarity. Therefore this paper seeks to identify and explore the attributes of the concept, to elaborate ways of understanding the concept of patient participation for geriatric patients in the context of IC. Walker and Avant's model of Concept analysis [1] based on a literature review. Patient participation in the context of IC can be defined as a dynamic process emphasizing the person as a whole, focusing on the establishment of multiple alliances that facilitate individualized information and knowledge exchange, and ensuring a reciprocal engagement in activities within flexible and interactive/dynamic organizational structures. Patient participation in IC means involving patients and their relatives in holistic interdisciplinary collaborative decision-making. The results highlight the complexity of patient participation and contribute to a greater understanding of the influence of organizational structure and management. The present study may provide a practical framework for researchers, policy makers and health professionals to facilitate patient participation in IC services. Copyright © 2018 Elsevier B.V. All rights reserved.

High Resolution X-ray Spectroscopy and Star Formation: HETG Observations of the Pre-Main Sequence Stellar Cluster IC 348

NASA Astrophysics Data System (ADS)

Principe, David; Huenemoerder, David P.; Schulz, Norbert; Kastner, Joel H.; Weintraub, David; Preibisch, Thomas

2018-01-01

We present Chandra High Energy Transmission Grating (HETG) observations of the ∼3 Myr old pre-main sequence (pre-MS) stellar cluster IC 348. With 400-500 cluster members at a distance of ∼300 pc, IC 348 is an ideal target to observe a large number of X-ray sources in a single pointing and is thus an extremely efficient use of Chandra-HETG. High resolution X-ray spectroscopy offers a means to investigate detailed spectral characteristic of X-ray emitting plasmas and their surrounding environments. We present preliminary results where we compare X-ray spectral signatures (e.g., luminosity, temperature, column density, abundance) of the X-ray brightest pre-MS stars in IC 348 with spectral type, multiwavelength signatures of accretion, and the presence of circumstellar disks at multiple stages of pre-MS stellar evolution. Assuming all IC 348 members formed from the same primordial molecular cloud, any disparity between coronal abundances of individual members, as constrained by the identification and strength of emission lines, will constrain the source(s) of coronal chemical evolution at a stage of pre-MS evolution vital to the formation of planets.

[Clinical efficacy of alternating chemo-radiotherapy for locally advanced nasopharyngeal carcinoma].

PubMed

You, Xi; Yang, Yucheng

2014-03-01

The purpose of this study is to investigate the effective of alternating Chemo-radiotherapy for locally Advanced Nasopharyngeal Carcinoma. Retrospective analysis 106 cases of patients with locally advanced nasopharyngeal carcinoma between November 2005 and March 2007. All patients received cisplatin-based chemotherapy but 15 patients received radiotherapy(RT) alone. Inducing chemotherapy (IC) + RT + adju-vant chemotherapy (AC) regimen in 36 patients, IC+RT regimen was delivered in 25 patients and AC + RT regimen in 30 patients. 61 patients received 1 to 2 cycles of inducing chemotherapy and 66 patients received 3 to 6 cycles of adjuvant chemotherapy after radiotherapy. Chemotherapy started on the first day after the end of the induction chemotherapy, adjuvant chemotherapy begun after radiotherapy for a week. All patients were treated by radiotherapy using 60 Co r-ray, the nasophyarynx primary site was given a total does of 68 -74 Gy. The lymph nodes of the neck was given 60 to 70 Gy. The prophylactic irradiation does of the neck was 48-50 Gy. RESCULT: The median follow up time was 51 months. A total of 58 patients died, the overall survival rate was 45% in whole groups. The 5-year overall survival rates were 33%, 63%, 60% and 50% in RT, IC + RT + AC, IC + RT and RT+AC group, respectively. The 5-year disease-free survival rates were 13%, 56%, 48% and 40% in RT, IC + RT + AC, IC + RT and RT + AC group, respectively. The 5-year relapse-free survival rates were 13%, 53%, 48% and 50% in RT, IC + RT + AC, IC + RT and RT + AC group, respectively. The 5-year metastasis-free survival rates were 6%, 50%, 44% and 47% in RT, IC + RT + AC, IC+ RT and RT + AC group, respectively. There was significant difference in all groups (P < 0.05). The median time to relapses were 22 months, 29 months, 28 months and 25 months in RT, IC + RT + AC, IC + RT and RT + AC group, respectively. The median time to first distant metastasis were 10 months, 19 months, 15 months and 12 months in RT, IC + RT + AC, IC + RT and RT + AC group, respectively. There was no significant difference in all groups (P > 0.05). IC + RT + AC group had heavier acute toxicity effects than other groups, but it did not affect the treatment process, all patients could be tolerated. This retrospective study has demonstrated that alternating Chemo-radiotherapy and early radiotherapy not only can improve the survival rate for locally Advanced Nasopharyngeal Carcinoma, but also have slight toxicities and side reaction, all patients may tolerated.

Antarctic Ice Charts 1989-1990

DTIC Science & Technology

1992-01-01

DEVI-x ICNS -tXA kwk-q/z \\\\ I’ 3t i V o* 103m NORTHRN IC LIMI [O tI--Il 10 10 ;cl. ~~~~’-7 (X4 kAVA POLARW Ca NORAt CtNntR SUI A !2,,o i...8217 eW I / . 8 All - * N ’~ _X NV 2’j~St NS TAIA) - rh 4 ~ ~ ~~-..T SEA I / * p 4-~IC 1 / "lu$4----I / Nv ’~~T ’ A 7 IJLLIEDIOUCCD~cOYS //7 / ; n NOTHRAC

Measuring and imaging diffusion with multiple scan speed image correlation spectroscopy.

PubMed

Gröner, Nadine; Capoulade, Jérémie; Cremer, Christoph; Wachsmuth, Malte

2010-09-27

The intracellular mobility of biomolecules is determined by transport and diffusion as well as molecular interactions and is crucial for many processes in living cells. Methods of fluorescence microscopy like confocal laser scanning microscopy (CLSM) can be used to characterize the intracellular distribution of fluorescently labeled biomolecules. Fluorescence correlation spectroscopy (FCS) is used to describe diffusion, transport and photo-physical processes quantitatively. As an alternative to FCS, spatially resolved measurements of mobilities can be implemented using a CLSM by utilizing the spatio-temporal information inscribed into the image by the scan process, referred to as raster image correlation spectroscopy (RICS). Here we present and discuss an extended approach, multiple scan speed image correlation spectroscopy (msICS), which benefits from the advantages of RICS, i.e. the use of widely available instrumentation and the extraction of spatially resolved mobility information, without the need of a priori knowledge of diffusion properties. In addition, msICS covers a broad dynamic range, generates correlation data comparable to FCS measurements, and allows to derive two-dimensional maps of diffusion coefficients. We show the applicability of msICS to fluorophores in solution and to free EGFP in living cells.

Remedial Investigation/Feasibility Study, Operable Unit 5, Elmendorf AFB, Anchorage, Alaska. Volume 3. Appendices K - T

DTIC Science & Technology

1994-03-04

WalerQC METHOD BANK 30104 79-0146 TRHICLOROE1Ifl.BEE(TE) 0.j U11.01 WalerQC UShODSBAIN 301 04W 79-0146 TRIILMOROBHYLBEE (TCE) IU 1101.. alerQC METHOD...OOUL1!ANE -SS 89 %IC WSWeQC METHOD BANK 3020(1400 22M 0-Si-S 2*OOCLOROBUTANE -SI 902 sm WalerQC METHOD BLANK 8020(1400 22M 0-365 1.4003C2LOROSUfANE...SS 920 %wI WmerQC METHMOD BANK 0102(1400 CH 10-56-5 I.OX4-D01OOSUANE -SI IisBc WaNer C METHOD BLANK 8100(1400 22 10-5&5 2.40 EHOROSUTANE -SI 92 IC

Initial Correction versus Negative Marking in Multiple Choice Examinations

ERIC Educational Resources Information Center

Van Hecke, Tanja

2015-01-01

Optimal assessment tools should measure in a limited time the knowledge of students in a correct and unbiased way. A method for automating the scoring is multiple choice scoring. This article compares scoring methods from a probabilistic point of view by modelling the probability to pass: the number right scoring, the initial correction (IC) and…

AAV-expressed eCD4-Ig provides durable protection from multiple SHIV challenges

PubMed Central

Gardner, Matthew R.; Kattenhorn, Lisa M.; Kondur, Hema R.; von Schaewen, Markus; Dorfman, Tatyana; Chiang, Jessica J.; Haworth, Kevin G.; Decker, Julie M.; Alpert, Michael D.; Bailey, Charles C.; Neale, Ernest S.; Fellinger, Christoph H.; Joshi, Vinita R.; Fuchs, Sebastian P.; Martinez-Navio, Jose M.; Quinlan, Brian D.; Yao, Annie Y.; Mouquet, Hugo; Gorman, Jason; Zhang, Baoshan; Poignard, Pascal; Nussenzweig, Michel C.; Burton, Dennis R.; Kwong, Peter D.; Piatak, Michael; Lifson, Jeffrey D.; Gao, Guangping; Desrosiers, Ronald C.; Evans, David T.; Hahn, Beatrice H.; Ploss, Alexander; Cannon, Paula M.; Seaman, Michael S.; Farzan, Michael

2015-01-01

Long-term in vivo expression of a broad and potent entry inhibitor could circumvent the need for a conventional vaccine for HIV-1. Adeno-associated virus (AAV) vectors can stably express HIV-1 broadly neutralizing antibodies (bNAbs)1,2. However even the best bNAbs neutralize 10–50% of HIV-1 isolates inefficiently (IC80 > 5 μg/ml), suggesting that high concentrations of these antibodies would be necessary to achieve general protection3–6. Here we show that eCD4-Ig, a fusion of CD4-Ig with a small CCR5-mimetic sulfopeptide, binds avidly and cooperatively to the HIV-1 envelope glycoprotein (Env) and is more potent than the best bNAbs (geometric mean IC50 < 0.05 μg/ml). Because eCD4-Ig binds only conserved regions of Env, it is also much broader than any bNAb. For example, eCD4-Ig efficiently neutralized 100% of a diverse panel of neutralization-resistant HIV-1, HIV-2, and SIV isolates, including a comprehensive set of isolates resistant to the CD4-binding site bNAbs VRC01, NIH45-46, and 3BNC117. Rhesus macaques inoculated with an AAV vector stably expressed 17 to 77 μg/ml of fully functional rhesus eCD4-Ig for 40 weeks, and these macaques were protected from multiple infectious challenges with SHIV-AD8. Rhesus eCD4-Ig was also markedly less immunogenic than rhesus forms of four well characterized bNAbs. Our data suggest that AAV-delivered eCD4-Ig can function like an effective HIV-1 vaccine. PMID:25707797

Multiple cells express interleukin 17 in oral squamous cell carcinoma.

PubMed

Avadhani, Avadhoot V; Parachuru, Venkata P B; Milne, Trudy; Seymour, Gregory J; Rich, Alison M

2017-01-01

Interleukin (IL)-17 is a pro-inflammatory cytokine with pro- and antitumour effects. The aim of this study was to investigate the presence and potential sources of IL-17 in oral squamous cell carcinoma (OSCC). Immunohistochemistry was used to label and compare IL-17 + cells in the tissue sections of OSCC and inflammatory controls (IC), n = 14 for both. In OSCC, the comparison was made between the number of IL-17 + cells in the tumoral islands (TI), tumour-stroma interface (TS) and more distant stroma (DS). Cells expressing IL-17 were identified using double-labelling immunofluorescence and examined using laser scanning microscopy. The production of IL-17 from tumour cells was determined in the culture supernatants of OSCC cell lines, SCC4, SCC15 and SCC25, using sandwich ELISA. Significantly more IL-17 + cells were observed in OSCC compared with IC (Mann-Whitney, P < 0.0001). In OSCC, the numbers of IL-17 + cells were not significantly different in three compartments, TI, TS and DS (one-way ANOVA, P > 0.05). However, the TI had significantly fewer IL-17 + cells than the combined stroma (both TS and DS together, Mann-Whitney, P < 0.01). Laser scanning microscopy revealed helper T cells, cytotoxic T cells, macrophages and mast cells co-expressed IL-17. ELISA experiments did not detect IL-17 in the supernatants of OSCC cell lines. Although the tumour cells themselves did not express IL-17, a range of cell types did, suggesting multiple cellular sources for IL-17 in OSCC. The spatial distribution of IL-17 + cells suggests specific interactions with cells within the tumour microenvironment, implying that IL-17 + cells are likely to play a role in the pathogenesis of OSCC. © 2016 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

Inhibitory effect of Rosa damascena Mill flower essential oil, geraniol and citronellol on rat ileum contraction.

PubMed

Sadraei, H; Asghari, G; Emami, S

2013-01-01

Flower of Rosa damascena Mill is widely used in Iran for gastrointestinal (GI) disorders. However, its pharmacological action on ileum contraction has not been studied. In this research we have investigated ileum motility effect of essential oil of flower petals of R. damascena growing in Kashan, Iran, and two of its constituents. The essential oils obtained by hydrodistillation were investigated by a combination of GC and GC/MS. More than 34 compounds have been identified. The main constituents of the essential oil were β-citronellol (23%), nonadecane (16%), geraniol (16%) and heneicosane (5%). A portion of rat isolated ileum was suspended under 1g tension in Tyrode's solution at 37°C and gassed with O2. Effect of the R. damascena essential oil (2.5-160 μg/ml), geraniol (0.2-3.2 μg/ml) and citronellol (0.8-6.4 μg/ml) were studied on ileum contractions induced by KCl, acetylcholine (ACh) and electrical field stimulation (EFS) and compared with standard drugs atropine and loperamide. The contractile response of EFS was mediated mainly through the intramural nerve plexuses, because its response was inhibited by loperamide and partially reduced by atropine. The essential oil concentration dependently inhibited the response to KCl (IC50=67 ± 8.4μg/ml) and EFS (IC50=47 ± 10.6 μg/ml). Geraniol (IC50=1.7 ± 0.15 μg/ml for KCl) and citronellol (IC50=2.9 ± 0.3 μg/ml for KCl) also had inhibitory effect of ileum contraction and both were more potent than the essential oil. It was concluded that R. damascena essential oil mainly had an inhibitory effect on ileum contractions and geraniol and citronellol had a major role in inhibitory effect of the essential.

Structural and functional characterization of recombinant napin-like protein of Momordica charantia expressed in methylotrophic yeast Pichia pastoris.

PubMed

Yadav, Shailesh Kumar R; Sahu, Tejram; Dixit, Aparna

2016-08-01

Napin and napin-like proteins belong to the 2S albumin seed storage family of proteins and have been shown to display a variety of biological activities. However, due to a high degree of polymorphism, purification of a single napin or napin-like protein exhibiting biological activity is extremely difficult. In the present study, we have produced the napin-like protein of Momordica charantia using the methylotrophic Pichia pastoris expression system. The recombinant napin-like protein (rMcnapin) secreted in the extracellular culture supernatant was enriched by ammonium sulfate precipitation, and purified using size exclusion chromatography at a yield of ∼290 mg/L of culture. Secondary structure analysis of the purified rMcnapin revealed it to be predominantly α-helical with minimal β strand content. CD spectroscopic and fluorescence spectroscopic analyses revealed the rMcnapin to be stable at a wide range of temperatures and pH. The rMcnapin exhibited antifungal activity against Trichoderma viride with an IC50 of ∼3.7 μg/ml and trypsin inhibitor activity with an IC50 of 4.2 μM. Thus, large amounts of homogenous preparations of the biologically active rMcnapin could be obtained at shake flask level, which is otherwise difficult from its natural source.

Online detection of potential duplicate medications and changes of physician behavior for outpatients visiting multiple hospitals using national health insurance smart cards in Taiwan.

PubMed

Hsu, Min-Huei; Yeh, Yu-Ting; Chen, Chien-Yuan; Liu, Chien-Hsiang; Liu, Chien-Tsai

2011-03-01

Doctor shopping (or hospital shopping), which means changing doctors (or hospitals) without professional referral for the same or similar illness conditions, is common in Hong Kong, Taiwan and Japan. Due to the lack of infrastructure for sharing health information and medication history among hospitals, doctor-shopping patients are more likely to receive duplicate medications and suffer adverse drug reactions. The Bureau of National Health Insurance (BNHI) adopted smart cards (or NHI-IC cards) as health cards in Taiwan. With their NHI-IC cards, patients can freely access different medical institutions. Because an NHI-IC card carries information about a patient's prescribed medications received from different hospitals nationwide, we used this system to address the problem of duplicate medications for outpatients visiting multiple hospitals. A computerized physician order entry (CPOE) system was enhanced with the capability of accessing NHI-IC cards and providing alerts to physicians when the system detects potential duplicate medications at the time of prescribing. Physician responses to the alerts were also collected to analyze changes in physicians' behavior. Chi-square tests and two-sided z-tests with Bonferroni adjustments for multiple comparisons were used to assess statistical significance of differences in actions taken by physicians over the three months. The enhanced CPOE system for outpatient services was implemented and installed at the Pediatric and Urology Departments of Taipei Medical University Wan-Fang Hospital in March 2007. The "Change Log" that recorded physician behavior was activated during a 3-month study period from April to June 2007. In 67.93% of patient visits, the physicians read patient NHI-IC cards, and in 16.76% of the reads, the NHI-IC card contained at least one prescribed medication that was taken by the patient. Among the prescriptions issued by physicians, on average, there were 2.36% prescriptions containing at least one medication that might be duplicative to the prior prescriptions stored in NHI-IC cards. The rate of potential duplicate medication alerts for the Pediatric Department was higher than that for the Urology Department (2.78% versus 1.67%). However, the rate of revisions to prescriptions was higher in the Urology Department than the Pediatric Department. Overall, the rate of physicians reviewing and revising their prescriptions was 29.25%; the rate of physicians reviewing without revising their prescriptions was 43.62%; the rate of physicians turning off the alert screens right after the screens popped up (overridden) was 27.13%. Thus, physicians accepted alerts to review their prescriptions with patients in most situations (72.87%). Moreover, over the study period, the rate of total revisions made to prescriptions increased and the "overridden" rate decreased. Our approach enhances the capability of CPOE systems using NHI-IC cards as a nationwide infrastructure to provide more complete patient health information and medication history sharing among hospitals in Taiwan. Thus, our system can provide a better prescribing tool to help physicians detect potential duplicate medications for frequent doctor-shopping patients and hence enhance patient safety across hospital boundaries. However, the effectiveness of detecting duplicate medications with our approach is very much dependent on the completeness of NHI-IC cards, which in turn primarily depends on physician use of the cards when prescribing. Copyright © 2010 Elsevier Ireland Ltd. All rights reserved.

[Association between sleep and leukocyte telomere length in middle-aged and older adults].

PubMed

Liu, H F; Li, F; Wang, Y H; Chen, J H; Peng, D X; Chen, J; Tan, L H; Mi, X; Zhao, B H

2017-07-10

Objective: To understand the association between peripheral leukocytes telomere length (TL) and sleep in middle-aged and old adults. Methods: A total of 176 middle-aged and old adults were investigated by using the Pittsburgh Sleep Quality Index and questionnaire. TL was measured by fluorescence quantitative PCR. The correlation and regression analysis between sleep and telomere length was performed. Results: TL had a mean T/S ratio of 0.995±0.23. There was a negative correlation between TL and age ( r =-0.241, P =0.003). With increasing age, sleep quality became worse ( r =-0.230, P <0.01), the time to fall asleep became longer ( r =0.227, P <0.01), sleep duration was shorter ( r =-0.486, P <0.01), sleep efficiency became worse ( r =-0.226, P <0.01). After controlling for the effects of gender, age, marital status, income level, residence, smoking, drinking, physical exercise and disease status, multiple linear regression analysis indicated that sleep quality ( β =0.057, P <0.01), time to fall asleep ( β =-0.046, P <0.01), sleep duration ( β =0.086, P <0.01) were independent influencing factors of telomere length, suggesting that the people who had better sleep quality, the shorter time to fall asleep, the longer sleep time would have longer telomere length. Conclusions: Sleep is a relevant factor affecting TL in middle-aged and elderly population. Good sleep may delay aging by slowing TL. We encourage to conduct health education about the importance of sleep quality in community.

Factors associated with vaginal birth after cesarean in a maternity hospital of Rio de Janeiro.

PubMed

d'Orsi, E; Chor, D; Giffin, K; Barbosa, G P; Angulo-Tuesta, A J; Gama, A S; Pessoa, L G; Shiraiwa, T; Fonseca, M J

2001-08-01

Identifying characteristics associated with vaginal birth after cesarean. Case-control study based on medical records. women with previous cesarean, who had delivered in a public Rio de Janeiro maternity hospital between 1992 and 1996. 141 cases (vaginal births after cesarean) and 304 controls (a new cesarean after other(s)). Multivariate analysis with logistic regression was carried out. The following characteristics were associated with greater probability of vaginal birth (IC=95%): only one previous cesarean (OR=19.05; IC=6.88-52.76); cervical dilatation at admission above 3 cm (OR=8.86; IC=4.93-15.94); gestational age below 37 weeks (OR=3.01; IC=1.40-6.46); history of at least one previous vaginal birth (OR=2.12; IC=1.18-3.82); level of education below high school (OR=1.94; IC=1.02-3.69). Chronic hypertension reduced the chances of vaginal birth (OR=0.44; IC=0.22-0.88). Among the factors that can be modified to reduce the number of repeated cesareans are: trial of labor promotion, reducing admission of women at early stages of labor and adequate hypertension management during pregnancy. Among the factors that can be modified to reduce the number of repeated cesareans are: the trial of labor promotion for women who present previous cesarean, reducing admission of women at early stages of labor and adequate hypertension management during pregnancy.

Young Low-Mass Stars and Brown Dwarfs in IC 348

NASA Astrophysics Data System (ADS)

Luhman, K. L.

1999-11-01

I present new results from a continuing program to identify and characterize the low-mass stellar and substellar populations in the young cluster IC 348 (0.5-10 Myr). Optical spectroscopy has revealed young objects with spectral types as late as M8.25. The intrinsic J-H and H-K colors of these sources are dwarflike, whereas the R-I and I-J colors appear intermediate between the colors of dwarfs and giants. Furthermore, the spectra from 6500 to 9500 Å are reproduced well with averages of standard dwarf and giant spectra, suggesting that such averages should be used in the classification of young late-type sources. An H-R diagram is constructed for the low-mass population in IC 348 (K6-M8). The presumably coeval components of the young quadruple system GG Tau (White et al.) and the locus of stars in IC 348 are used as empirical isochrones to test the theoretical evolutionary models. The calculations of Burrows et al. do not appear to be consistent with the data at these earliest stages of stellar evolution. There is fair agreement between the data and the model isochrones of D'Antona & Mazzitelli, except near the hydrogen-burning limit. The agreement cannot be improved by changing the conversion between spectral types and effective temperatures. On the other hand, for the models of Baraffe et al., an adjustment of the temperature scale to progressively warmer temperatures at later M types, intermediate between dwarfs and giants, brings all components of GG Tau onto the same model isochrone and gives the population of IC 348 a constant age and age spread as a function of mass. When other observational constraints are considered, such as the dynamical masses of GM Aur, DM Tau, and GG Tau A, the models of Baraffe et al. are the most consistent with observations of young systems. With compatible temperature scales, the models of both D'Antona & Mazzitelli and Baraffe et al. suggest that the hydrogen-burning mass limit occurs near M6 at ages of <~10 Myr. Thus, several likely brown dwarfs are discovered in this study of IC 348, with masses down to ~20-30 MJ.

Sleep disturbances and nocturnal symptoms: relationships with quality of life in a population-based sample of women with interstitial cystitis/bladder pain syndrome.

PubMed

Troxel, Wendy M; Booth, Marika; Buysse, Daniel J; Elliott, Marc N; Suskind, Anne M; Clemens, J Quentin; Berry, Sandra H

2014-12-15

To characterize the nature and impact of sleep disturbances on quality of life (QOL) in women with interstitial cystitis/bladder pain syndrome (IC/BPS). Participants were 3,397 women from a telephone probability survey who met IC/BPS symptom criteria. Sleep quality, duration, and IC/BPS nocturnal symptoms (i.e., trouble sleeping due to bladder pain, urgency, or needing to use the bathroom), general QOL (mental and physical health and sexual functioning), and IC/BPS QOL impairment were assessed via self-report during telephone interview. Over half of the sample reported poor sleep quality, sleep duration ≤ 6 hours, or trouble sleeping due to IC/BPS symptoms. After covariate adjustment, short sleep duration was significantly associated with greater IC/BPS QOL impairment (β = -0.04; p < 0.001) and poorer self-reported physical health (β = 1.86; p < 0.001). Poor sleep quality was significantly associated with greater IC/BPS QOL impairment (β = 0.06; p < 0.001), poorer self-reported physical health (β = -2.86; p < 0.001), and greater sexual dysfunction (β = -0.04; p < 0.05). IC/BPS nocturnal symptoms were significantly associated with greater IC/BPS impairment (β = 0.14; p < 0.001), poorer physical health (β = -2.76; p < 0.001) and mental health (β = 0.52; p < 0.01), and greater sexual dysfunction (β = -0.10; p < 0.001), after covariate adjustment. After further adjustment for IC/BPS nocturnal symptoms, we found that poor sleep quality and short sleep duration were independent correlates of poor self-reported physical health. Poor sleep quality and short sleep duration, as well as disorder-specific sleep disturbances, are highly prevalent in women with IC/BPS and are associated with poorer disease-specific and general QOL. © 2014 American Academy of Sleep Medicine.

Prime Contract Awards Alphabetically by Contractor, by State or Country, and Place. Part 12 (International Insignia Corp -Korea Guano Co Ltd)

DTIC Science & Technology

1990-01-01

LAO LADO 0000c, C1 -jI1(D I )-f 6r liI> P.- -It -IC(DC(0C0 DwwwwDD -14(D0(D ( 1 n0 Cl 000 NO> 11 < I 0c-l I -0Z N"U- C4 WZZZZZ Wzzzzzz uz Z (D z CDZ...00 000,-I 4 (1 1) 1 -1 of enc - -j cn 0o o( .>00 0)000000 0 - C, Q enCN 10 0- 0 0 0 - C 0- 00 0- 0 C 05C - C. 7 0000 0-r.4 Z0C0 I MC-i 11 (K -~.1 C...M( -40a (D > -0a H Eu10 I CO -f f𔃺-40> L- C in ENc -4M LN 01 4 L-C’) (0 c .4I(4 I -4 LN C 0 0 0( DI’-. L(0 0(c 0 -4 oco 00 H * .. :I (0 -4 <-4 z -1

Prime Contract Awards Alphabetically by Contractor, by State or Country, and Place, Fiscal Year 1987. Part 9. Hawthorne Srvc. & Medical U SC-Input Output Technology.

DTIC Science & Technology

1987-01-01

0 0 m 0 V7 a Mo00tI 04 aF 04 0 U..04 0 0 4 0004 000 0004 00v4l A a 1 o < 1 - 08- 0 m 4N00ŕ-1.- 0 0o1-) 000-) CN 00- co D W -co 00- W- ca 0 0 4 004...a 00 0 ’nw 000 gr Go00 C- 4)NN 01?--(- ... J 40 CAD 00 00- -40-00 0 000 3 4 ’- m- -A4 (D a- E ’ w- Cl m- 0 0 M4 0-l (14 af ((0-C’N 0A (4 V) 0 0 0)0...4, -4-4 lin n in -4 (00(4 I -- 10-4( IC) Mum0 1 r a I0 > 0 0. ) 0 1C 04 ’ -4 = tC z -4 4 ( )- 4. J I M 04 N af .- C.-4- C14 If,4 cl UI 0, C r

Prime Contract Awards Alphabetically by Contractor, by State or Country, and Place. Part 3. (Beachy Lumber Co.-Campanova, Richard MD)

DTIC Science & Technology

1989-01-01

34ᝰ >w 00 C In --4 C4 -ONN4r- N0-0 11 a M-0 cg< i 1.10 -4 l 9 1 L go ~t00 -40 B LA. ZEZ Z Z Z Z Z Z Z ZZ Z L to01000 z 2 Z0ZZZZZZZZ, (00~t II0. O)41...00 0) 0) 07 ’) n N0) C) 0) 44r- 0 M’ U.n U dw01 44 I -4 000 0OC 0D 0 00 0 0 Is4 ( 9 O J WIn 114IC tax H UJ WC) :14 H WCJ 44 2Z2 2 Z 22 z Z z H 000 4’ M0...4 -4-4 m -4 .- 4 .- 4 -4 -4 -4 -4 -4 404 4- 4W 0000 WWWWWW C(((0000(( u0 N - (0 ) -0)0) 0000 ~--CL If to I 0000 W 4 00000000to "D 00 MC0 -4 .- 4 . 9

The Capabilities of the U.S. Government to Collect and Analyze Economic Intelligence

DTIC Science & Technology

1994-01-01

by management ? Some economic and business aspects might not be critically time sensitive; however, knowledge about a competitor’s contract bid and...such a relationship include: reduced product research and development (R&D) timelines, reduced R&D costs, accelerated time from R&D to product marketing...intelligence that business cannot obtain on its own? 19 IimtIinua. Can the IC provide timely information to business in time for it to be used effectively

AFHRL Annual Report FY 81.

DTIC Science & Technology

1981-01-01

iiruI. sulihrur~. arid comtiije iii-aro’ d~ namny rallier- than slin’. ’I’ll(-% nralt oilwulf-d’’I’r tip li[’ I Lahioraiorn s R&D~ I) rezar ’ I .I s...XI)- \\093) 2831. fl’/I. ide anfgle’ ifi/lifil P pIc v"isuafl s.Iovin. Xf1lfM.- TH-81-51. \\D - \\105l 50I8. Idrn ). It.. & kaii r. J. F.. Ii rffflafif

Herpes simplex virus vector-mediated gene delivery for the treatment of lower urinary tract pain

PubMed Central

Goins, WF; Goss, JR; Chancellor, MB; de Groat, WC; Glorioso, JC; Yoshimura, N

2009-01-01

Interstitial cystitis (IC)/painful bladder syndrome (PBS) is a painful debilitating chronic visceral pain disorder of unknown etiology that affects an estimated 1 million people in the, United States alone. It is characterized by inflammation of the bladder that results in chronic pelvic pain associated with bladder symptoms of urinary frequency and urgency. Regardless of the etiology, IC/PBS involves either increased and/or abnormal activity in afferent nociceptive sensory neurons. Pain-related symptoms in patients with IC/PBS are often very difficult to treat. Both medical and surgical therapies have had limited clinical utility in this debilitating disease and numerous drug treatments, such as heparin, dimethylsulfoxide and amitriptyline, have proven to be palliative at best, and in some IC/PBS patients provide no relief whatsoever. Although opiate narcotics have been employed to help alleviate IC/PBS pain, this strategy is fraught with problems as systemic narcotic administration causes multiple unwanted side effects including mental status change and constipation. Moreover, chronic systemic narcotic use leads to dependency and need for dose escalation due to tolerance: therefore, new therapies are desperately needed to treat refractory IC/PBS. This has led our group to develop a gene therapy strategy that could potentially alleviate chronic pelvic pain using the herpes simplex virus-directed delivery of analgesic proteins to the bladder. PMID:19242523

Bank Vole Prion Protein As an Apparently Universal Substrate for RT-QuIC-Based Detection and Discrimination of Prion Strains.

PubMed

Orrú, Christina D; Groveman, Bradley R; Raymond, Lynne D; Hughson, Andrew G; Nonno, Romolo; Zou, Wenquan; Ghetti, Bernardino; Gambetti, Pierluigi; Caughey, Byron

2015-06-01

Prions propagate as multiple strains in a wide variety of mammalian species. The detection of all such strains by a single ultrasensitive assay such as Real Time Quaking-induced Conversion (RT-QuIC) would facilitate prion disease diagnosis, surveillance and research. Previous studies have shown that bank voles, and transgenic mice expressing bank vole prion protein, are susceptible to most, if not all, types of prions. Here we show that bacterially expressed recombinant bank vole prion protein (residues 23-230) is an effective substrate for the sensitive RT-QuIC detection of all of the different prion types that we have tested so far--a total of 28 from humans, cattle, sheep, cervids and rodents, including several that have previously been undetectable by RT-QuIC or Protein Misfolding Cyclic Amplification. Furthermore, comparison of the relative abilities of different prions to seed positive RT-QuIC reactions with bank vole and not other recombinant prion proteins allowed discrimination of prion strains such as classical and atypical L-type bovine spongiform encephalopathy, classical and atypical Nor98 scrapie in sheep, and sporadic and variant Creutzfeldt-Jakob disease in humans. Comparison of protease-resistant RT-QuIC conversion products also aided strain discrimination and suggested the existence of several distinct classes of prion templates among the many strains tested.

Patient characteristics associated with improved outcomes with use of an inhaled corticosteroid in preschool children at risk for asthma.

PubMed

Bacharier, Leonard B; Guilbert, Theresa W; Zeiger, Robert S; Strunk, Robert C; Morgan, Wayne J; Lemanske, Robert F; Moss, Mark; Szefler, Stanley J; Krawiec, Marzena; Boehmer, Susan; Mauger, David; Taussig, Lynn M; Martinez, Fernando D

2009-05-01

Maintenance inhaled corticosteroid (ICS) therapy in preschool children with recurrent wheezing at high-risk for development of asthma produces multiple clinical benefits. However, determination of baseline features associated with ICS responsiveness may identify children most likely to benefit from ICS treatment. To determine if demographic and atopic features predict response to ICS in preschool children at high risk for asthma. Two years of treatment with an ICS, fluticasone propionate (88 microg twice daily), was compared with matching placebo in a double-masked, randomized, multicenter study of 285 children 2 and 3 years old at high risk for asthma development. Baseline demographic and atopic features were related to clinical outcomes in a post hoc subgroup analysis. Multivariate analysis demonstrated significantly greater improvement with fluticasone than placebo in terms of episode-free days among boys, white subjects, participants with an emergency department (ED) visit or hospitalization within the past year, and those who experienced more symptomatic days at baseline. Children with aeroallergen sensitization experienced greater benefits in terms of oral corticosteroid use, urgent care and ED visits, and use of supplemental controller medications. More favorable responses to ICS than placebo in high-risk preschool children over a 2-year period were more likely in those with a ED visit or hospitalization for asthma within the past year, children with aeroallergen sensitization, boys, and white subjects.

Synthesis and biological evaluation of novel thiadiazole amides as potent Cdc25B and PTP1B inhibitors.

PubMed

Li, Yingjun; Yu, Yang; Jin, Kun; Gao, Lixin; Luo, Tongchuan; Sheng, Li; Shao, Xin; Li, Jia

2014-09-01

A series of novel thiadiazole amide derivatives have been synthesized and evaluated for inhibitory activities against Cdc25B and PTP1B. Most of them showed inhibitory activities against Cdc25B (IC50=1.18-8.01 μg/mL) and PTP1B (IC50=0.85-8.75 μg/mL), respectively. Moreover, compounds 5b and 4l were most potent with IC50 values of 1.18 and 0.85 μg/mL for Cdc25B and PTP1B, respectively, compared with reference drugs Na3VO4 (IC50=0.93 μg/mL) and oleanolic acid (IC50=0.85 μg/mL). The results of selectivity experiments showed that the target compounds were selective inhibitors against PTP1B and Cdc25B. Enzyme kinetic experiments demonstrated that compound 5k was a specific inhibitor with the typical characteristics of a mixed inhibitor. Copyright © 2014 Elsevier Ltd. All rights reserved.

Fatigue-life behavior and matrix fatigue crack spacing in unnotched SCS-6/Timetal 21S metal matrix composites

NASA Technical Reports Server (NTRS)

Ward, G. T.; Herrmann, D. J.; Hillberry, B. M.

1993-01-01

Fatigue tests of the SCS-6/Timetal 21S composite system were performed to characterize the fatigue behavior for unnotched conditions. The stress-life behavior of the unnotched (9/90)2s laminates was investigated for stress ratios of R = 0.1 and R = 0.3. The occurrence of matrix cracking was also examined in these specimens. This revealed multiple matrix crack initiation sites throughout the composite, as well as evenly spaced surface cracks along the length of the specimens. No difference in fatigue lives were observed for stress ratios of R = 0.1 and R = 0.3 when compared on a stress range basis. The unnotched SCS-6/Timetal 21S composites had shorter fatigue lives than the SCS-6/Ti-15-3 composites, however the neat Timetal 21S matrix material had a longer fatigue life than the neat Ti-15-3.

Blockade of rat alpha3beta4 nicotinic receptor function by methadone, its metabolites, and structural analogs.

PubMed

Xiao, Y; Smith, R D; Caruso, F S; Kellar, K J

2001-10-01

The opioid agonist properties of (+/-)-methadone are ascribed almost entirely to the (-)-methadone enantiomer. To extend our knowledge of the pharmacological actions of methadone at ligand-gated ion channels, we investigated the effects of the two enantiomers of methadone and its metabolites R-(+)-2-ethyl-1,5-dimethyl-3,3-diphenylpyrrolinium perchlorate (EDDP) and R-(+)-2-ethyl-5-methyl-3,3-diphenyl-1-pyrroline hydrochloride (EMDP), as well as structural analogs of methadone, including (-)-alpha-acetylmethadol hydrochloride (LAAM) and (+)-alpha-propoxyphene, on rat alpha3beta4 neuronal nicotinic acetylcholine receptors (nAChRs) stably expressed in a human embryonic kidney 293 cell line, designated KXalpha3beta4R2. (+/-)-methadone inhibited nicotine-stimulated 86Rb+ efflux from the cells in a concentration-dependent manner with an IC50 value of 1.9 +/- 0.2 microM, indicating that it is a potent nAChR antagonist. The (-)- and (+)-enantiomers of methadone have similar inhibitory potencies on nicotine-stimulated 86Rb+ efflux, with IC50 values of approximately 2 microM. EDDP, the major metabolite of methadone, is even more potent, with an IC50 value of approximately 0.5 microM, making it one of the most potent nicotinic receptor blockers reported. In the presence of (+/-)-methadone, EDDP, or LAAM, the maximum nicotine-stimulated 86Rb+ efflux was markedly decreased, but the EC50 value for nicotine stimulation was altered only slightly, if at all, indicating that these compounds block alpha3beta4 nicotinic receptor function by a noncompetitive mechanism. Consistent with a noncompetitive mechanism, (+/-)-methadone, its metabolites, and structural analogs have very low affinity for nicotinic receptor agonist binding sites in membrane homogenates from KXalpha3beta4R2 cells. We conclude that both enantiomers of methadone and its metabolites as well as LAAM and (+)-alpha-propoxyphene are potent noncompetitive antagonists of alpha3beta4 nAChRs.

Oral picropodophyllin (PPP) is well tolerated in vivo and inhibits IGF-1R expression and growth of uveal melanoma.

PubMed

Economou, Mario A; Andersson, Sandra; Vasilcanu, Diana; All-Ericsson, Charlotta; Menu, Eline; Girnita, Ada; Girnita, Leonard; Axelson, Magnus; Seregard, Stefan; Larsson, Olle

2008-06-01

The cyclolignan picropodophyllin (PPP) efficiently blocks the activity of insulinlike growth factor-1 receptor (IGF-1R) and inhibits the growth of uveal melanoma cells in vitro and in vivo. In this study, the authors investigated the efficiency of orally administered PPP on the growth of uveal melanoma xenografts. In addition, they focused on the effect of PPP on vascular endothelial growth factor (VEGF) in vivo and evaluated its effects in combination with other established antitumor agents in vitro. Four different uveal melanoma cell lines (OCM-1, OCM-3, OCM-8, 92-1) were treated with PPP alone and in combination with imatinib mesylate, cisplatin, 5-fluorouracil, and doxorubicin. Cell viability was determined by XTT assay. SCID mice that underwent xenografting with uveal melanoma cells were used to determine antitumor efficacy of oral PPP in vivo. Five mice were used per group. Tumor samples obtained from the in vivo experiments were analyzed for VEGF and IGF-1R expression by Western blotting. PPP was found to be superior to the other antitumor agents in killing uveal melanoma cells in all four cell lines (IC50 < 0.05 microM). Oral PPP inhibited uveal melanoma growth in vivo in OCM-3 (P = 0.03) and OCM-8 (P = 0.01) xenografts and was well tolerated by the animals. PPP decreased VEGF expression in the OCM-1 (P = 0.006) and OCM-8 (P = 0.01) tumors. Oral PPP was well tolerated in vivo, caused total growth inhibition of uveal melanoma xenografts, and decreased VEGF levels in the tumors.

Characterization of Human Hippocampal Neural Stem/Progenitor Cells and Their Application to Physiologically Relevant Assays for Multiple Ionotropic Glutamate Receptors.

PubMed

Fukushima, Kazuyuki; Tabata, Yoshikuni; Imaizumi, Yoichi; Kohmura, Naohiro; Sugawara, Michiko; Sawada, Kohei; Yamazaki, Kazuto; Ito, Masashi

2014-09-01

The hippocampus is an important brain region that is involved in neurological disorders such as Alzheimer disease, schizophrenia, and epilepsy. Ionotropic glutamate receptors-namely,N-methyl-D-aspartate (NMDA) receptors (NMDARs), α-amino-3-hydroxy-5-methyl-4-isoxazolepropionate (AMPA) receptors (AMPARs), and kainic acid (KA) receptors (KARs)-are well known to be involved in these diseases by mediating long-term potentiation, excitotoxicity, or both. To predict the therapeutic efficacy and neuronal toxicity of drug candidates acting on these receptors, physiologically relevant systems for assaying brain region-specific human neural cells are necessary. Here, we characterized the functional differentiation of human fetal hippocampus-derived neural stem/progenitor cells-namely, HIP-009 cells. Calcium rise assay demonstrated that, after a 4-week differentiation, the cells responded to NMDA (EC50= 7.5 ± 0.4 µM; n= 4), AMPA (EC50= 2.5 ± 0.1 µM; n= 3), or KA (EC50= 33.5 ± 1.1 µM; n= 3) in a concentration-dependent manner. An AMPA-evoked calcium rise was observed in the absence of the desensitization inhibitor cyclothiazide. In addition, the calcium rise induced by these agonists was inhibited by antagonists for each receptor-namely, MK-801 for NMDA stimulation (IC50= 0.6 ± 0.1 µM; n= 4) and NBQX for AMPA and KA stimulation (IC50= 0.7 ± 0.1 and 0.7 ± 0.03 µM, respectively; n= 3). The gene expression profile of differentiated HIP-009 cells was distinct from that of undifferentiated cells and closely resembled that of the human adult hippocampus. Our results show that HIP-009 cells are a unique tool for obtaining human hippocampal neural cells and are applicable to systems for assay of ionotropic glutamate receptors as a physiologically relevant in vitro model. © 2014 Society for Laboratory Automation and Screening.

Antimicrobial, antiplasmodial, haemolytic and antioxidant activities of crude extracts from three selected Togolese medicinal plants.

PubMed

Karou, Simplice D; Tchacondo, Tchadjobo; Ouattara, Lassina; Anani, Kokou; Savadogo, Aly; Agbonon, Amegnona; Attaia, Mossaclok Ben; de Souza, Comlan; Sakly, Mohsen; Simpore, Jacques

2011-10-01

To investigate the antioxidant, antimicrobial, antiplasmodial, acute toxicity and haemolytic activities of methanolic extracts of three plants. Phytochemical analysis to determine the phenolic contents was also carried out. The 2,2-diphenyl-1-picryl-hydrazyl (DPPH) free radical scavenging, NCCLS broth microdilution and Plasmodium Lactate Dehydrogenase (pLDH) assays were used to determine antioxidant, antimicrobial and antiplasmodial activities, respectively. Haemolysis assay was conducted on A(+) human red blood cells and acute toxicity on male Swiss albino mice. Phenolics were quantitatively determined using spectrophotometric methods. The DPPH assay yielded interesting antioxidant activities of methanolic extract of Parinari curatellifolia (P. curatellifolia) and Entada africana (E. africana) (IC(50) were 0.20±0.01 μg/mL and 0.47±0.01 μg/mL, respectively). This activity was highly correlated with phenolic contents of extracts. The antimicrobial tests displayed minimal inhibitory concentrations (MICs) values ranging from 0.90 to 1.80 mg/mL for Serratia marcescens (S. marcescens) the most susceptible bacterial strain. MIC value was 1.20 mg/mL for susceptible fungal strains including Mucor rouxi (M. rouxi), Fusarium oxyporum (F. oxyporum) and Rhizopus nigricans (R. nigricans). pLDH assay showed moderate antiplasmodial activity of Balanites aegyptiaca (B. aegyptiaca) (IC(50) = 24.56±3.45 μg/mL), however this extract was highly haemolytic and toxic in mice (LD(50) = 625±128 mg/kg). Our results support in part the use of the selected plants in the treatment of microbial infections. In addition the plant showed interesting antioxidant activity that could be useful in the management of oxidative stress. Copyright © 2011 Hainan Medical College. Published by Elsevier B.V. All rights reserved.

Official Guard and Reserve Manpower Strengths and Statistics. FY 2000 Summary

DTIC Science & Technology

2000-01-01

t- 0- at UJ UJ 1/1 oo X LULO > < o Z r- u. or O O Z O. < a: oe S»5 < r- O corvi mo -q-m HHfnSin^ Is-. r** rococo m...1- r^ •=!•-ŗ-•<!• rH rHCTirH to »T O rsi Tfrgr^rH ino rH *j- I— iH m m rsirHinm ro rsi rH rsi COCO Lnoo -1 <r m LnoOf\\IC7l rococo r-^ 1- TJ...i a. t i 1 cn > lOolOIN^ioooooolcoHHrrnj-ttiALOLDiflfnOcoOHHONNO rococo in inmioi£)CT1n-i^-inco CTCOOOCOCOOOCOOOCOCOC71CTlCTlCTlC71C71CT

Concise synthesis and PTP1B inhibitory activity of (R)- and (S)-dihydroresorcylide.

PubMed

Jiang, Cheng-Shi; Zhang, Li; Gong, Jing-Xu; Li, Jing-Ya; Yao, Li-Gong; Li, Jia; Guo, Yue-Wei

2017-12-01

The present study was designed to develop a concise synthetic route for macrolide, with the purpose of confirming the absolute configuration of natural dihydroresorcylide (1) and making it more easily accessible for biological evaluation. The absolute configuration of C-3 in natural 1 was revised to be R by comparison of the rotation sign of synthetic (R)- and (S)-1. The synthetic (R)-1 was found to be a novel highly specific PTP1B inhibitor with an IC 50 value of 17.06 μM.

JS-K has Potent Anti-Angiogenic Activity in vitro and Inhibits Tumor Angiogenesis in a Multiple Myeloma Model in vivo

PubMed Central

Kaur, Gurmeet; Kiziltepe, Tanyel; Anderson, Kenneth C.; Kutok, Jeffery L.; Jia, Lee; Boucher, Kenneth M.; Saavedra, Joseph E.; Keefer, Larry K.; Shami, Paul J.

2009-01-01

Glutathione S-Transferases (GST) play an important role in multidrug resistance and are upregulated in multiple cancers. We have designed a prodrug class that releases NO on metabolism by GST. O2-(2,4-Dinitrophenyl) 1-[(4-ethoxycarbonyl)piperazin-1-yl]diazen-1-ium-1,2-diolate (JS-K, a member of this class) has potent anti-neoplastic activity. We studied the effect of JS-K on angiogenesis. JS-K inhibited the proliferation of HUVEC’s with a 50% inhibitory concentration (IC50) of 0.432, 0.466, and 0.505 µM at 24, 48, and 72 hours, respectively. In the cord formation assay, JS-K led to a decrease in the number of cord junctions and cord length with an IC50 of 0.637 and 0.696 µM, respectively. JS-K inhibited cell migration at 5 hours using VEGF as a chemoattractant. Migration inhibition occurred with an IC50 of 0.493 µM. In the chick aortic ring assay using VEGF or FGF-b for vessel growth stimulation, 0.5 µM JS-K completely inhibited vessel growth. JS-K inhibited tumor angiogenesis in vivo in NIH III mice implanted subcutaneously with OPM1 multiple myeloma cells. JS-K is a potent inhibitor of angiogenesis in vitro and tumor vessel growth in vivo. As such, it establishes a new class of anti-neoplastic agents that target the malignant cells directly as well as their microenvironment. PMID:20723011

Post-inhaled corticosteroid pulmonary tuberculosis and pneumonia increases lung cancer in patients with COPD.

PubMed

Wu, Ming-Fang; Jian, Zhi-Hong; Huang, Jing-Yang; Jan, Cheng-Feng; Nfor, Oswald Ndi; Jhang, Kai-Ming; Ku, Wen-Yuan; Ho, Chien-Chang; Lung, Chia-Chi; Pan, Hui-Hsien; Wu, Min-Chen; Liaw, Yung-Po

2016-10-10

Inhaled corticosteroids (ICS) have been associated with decreased lung cancer risk. However, they have been associated with pulmonary infections (tuberculosis [TB] and pneumonia) in patients with chronic obstructive pulmonary disease (COPD). TB and pneumonia have increased lung cancer risk. The association between post-ICS pulmonary infections and lung cancer remains unclear. We conducted a retrospective cohort study from 2003 to 2010 using the Taiwan National Health Insurance Research Database. Among the 1,089,955 patients with COPD, we identified 8813 new users of ICS prescribed for a period of 3 months or more and 35,252 non-ICS users who were randomly matched for sex, age and date of ICS use from 2003 to 2005. Cox proportional hazard regression was used to estimate the hazard ratio (HR) of pulmonary infections in patients with/without ICS use. The HRs for lung cancer in ICS users with sequential lung infections were as follows; 2.42 (95 % confidence interval [CI], 1.28-4.58) for individuals with TB, 2.37 (95 % CI, 1.01-5.54) for TB and pneumonia, and 1.17(95 % CI, 0.69-1.98) for those with pneumonia. For non-ICS users with pulmonary infections, the HRs were 1.68 (95 % CI, 0.78-3.65) for individual with TB and pneumonia, 1.42 (95 % CI, 0.89-2.26) for TB, and 0.95 (95 % CI, 0.62-1.46) for individuals with pneumonia. COPD patients with TB /or pneumonia who used ICS had increased risk of lung cancer. Because the overall prognosis of lung cancer remains poor, screening tests are recommended for patients with these conditions.

Inhaled corticosteroids and asthma control in adult-onset asthma: 12-year follow-up study.

PubMed

Vähätalo, Iida; Ilmarinen, Pinja; Tuomisto, Leena E; Niemelä, Onni; Kankaanranta, Hannu

2018-04-01

Prescribed inhaled corticosteroid (ICS) doses in asthma have been studied in cross-sectional settings whereas long-term follow-up studies have not been carried out. To evaluate prescribed medication longitudinally by calculating cumulative ICS doses and dose changes in a cohort of new-onset adult asthma during 12 years and in different groups of asthma control. A total of 203 patients were followed for 12 years as part of Seinäjoki Adult Asthma Study (SAAS). All asthma-related visits and prescribed medication over the study period were collected from medical records. Total cumulative ICS dose for the 12-year follow-up period was 3.4g (±SEM 0.1) per patient. Both respiratory specialists and GPs prescribed step-ups and step-downs in ICS treatment and in total 649 dose changes were noted during the follow-up (median 3(1-5) per patient). Patients with uncontrolled asthma received higher ICS doses throughout the follow-up period, and therefore, cumulative 12-year ICS dose (3.8g ± SEM 0.2) in this group was higher than that in those with partially controlled (3.4g ± SEM 0.2) or controlled disease (2.9g ± SEM 0.2) (p = 0.0001). Patients with uncontrolled asthma were also prescribed a higher number of ICS dose changes than patients with controlled disease. Despite frequent dose changes and high ICS doses during the 12-year follow-up, the level of asthma control remained poor in patients with uncontrolled asthma. This suggests that high ICS doses may not be effective enough for management of disease in patients with uncontrolled adult-onset asthma and novel targeted treatments are required. Copyright © 2018 Elsevier Ltd. All rights reserved.

High Resolution Transmission Measurements of the Atmosphere in the Infrared.

DTIC Science & Technology

1978-04-28

modifications to the various spect rorn et r ic installations , cu r r en t l y operated to obtain very hi g h resolution solar spectra in the in f r a...record the solar spectrum in the ~‘. 3000 to ~ 10 , 000 A reg ion , has also been equipped with an InSb detector to recorc various series of spectra near...in~ s c o n c e r n i n & HF , HC 1, also met hy l-ch lor ide (CH 3C1), e t c . . . L t h e r s tudies oased on our i n f r a r e d solar ou se

Unique structure of iC3b resolved at a resolution of 24 Å by 3D-electron microscopy.

PubMed

Alcorlo, Martin; Martínez-Barricarte, Ruben; Fernández, Francisco J; Rodríguez-Gallego, César; Round, Adam; Vega, M Cristina; Harris, Claire L; de Cordoba, Santiago Rodríguez; Llorca, Oscar

2011-08-09

Activation of C3, deposition of C3b on the target surface, and subsequent amplification by formation of a C3-cleaving enzyme (C3-convertase; C3bBb) triggers the effector functions of complement that result in inflammation and cell lysis. Concurrently, surface-bound C3b is proteolyzed to iC3b by factor I and appropriate cofactors. iC3b then interacts with the complement receptors (CR) of the Ig superfamily, CR2 (CD21), CR3 (CD11b/CD18), and CR4 (CD11c/CD18) on leukocytes, down-modulating inflammation, enhancing B cell-mediated immunity, and targeting pathogens for clearance by phagocytosis. Using EM and small-angle X-ray scattering, we now present a medium-resolution structure of iC3b (24 Å). iC3b displays a unique conformation with structural features distinct from any other C3 fragment. The macroglobulin ring in iC3b is similar to that in C3b, whereas the TED (thioester-containing domain) domain and the remnants of the CUB (complement protein subcomponents C1r/C1s, urchin embryonic growth factor and bone morphogenetic protein 1) domain have moved to locations more similar to where they were in native C3. A consequence of this large conformational change is the disruption of the factor B binding site, which renders iC3b unable to assemble a C3-convertase. This structural model also justifies the decreased interaction between iC3b and complement regulators and the recognition of iC3b by the CR of the Ig superfamily, CR2, CR3, and CR4. These data further illustrate the extraordinary conformational versatility of C3 to accommodate a great diversity of functional activities.

McGuire AFB, New Jersey. Revised Uniform Summary of Surface Weather Observations (RUSSWO). Parts A-F.

DTIC Science & Technology

1987-12-01

Air Weather Service (MAC) IS e REVISED UNIFORM SUMMARY OF SURFACE WEATHER OBSERVATIONS MCGUIRE AFB NJ MSC 724096 N 40 01 W 074 36 ELEV 133 FT KWRI...OCCUCRECVCL OF ’,UP F CE 4 1NU L DI ACT ICN v[ISSi *14U SFEEU ,,&FEICAC $AQM WOUkEY OhSFPVAIOS’ A Ti! L.ATIEP 5 3441ICE/ MSC $TA IC’. NUMFPP: 7,4𔄃t STATION...AI AELF I TOTALS I IT~ I2. .. 1 1 100.0 6.7 I19 I ’,ALNuI ~MP OF 0O"SEKhOA T I NS: ’K LLQL tL 4(L IMAI OO G’ 6Rf,H rLrCLNIIfCGE F iL CuENC9 Of uC (u