Design and synthesis of novel insecticides based on the serotonergic ligand 1-[(4-aminophenyl)ethyl]-4-[3-(trifluoromethyl)phenyl]piperazine (PAPP).

PubMed

Cai, Mingyi; Li, Zhong; Fan, Feng; Huang, Qingchun; Shao, Xusheng; Song, Gonghua

2010-03-10

1-[(4-Aminophenyl)ethyl]-4-[3-(trifluoromethyl)phenyl]piperazine (PAPP) is a 5-HT(1A) agonist and was reported to display high affinity for serotonin (5-HT) receptor from the parasitic nematode Haemonchus contortus . The present investigation explored the possibility of using PAPP as a lead compound of new insecticides with novel mode of action. On the basis of the PAPP scaffold, a series of 1-arylmethyl-4-[(trifluoromethyl)pyridin-2-yl]piperazine derivatives were designed, synthesized, and evaluated for biological activities against the armyworm Pseudaletia separata (Walker). Bioassays showed that most of the target compounds displayed certain growth-inhibiting activities or larvicidal activities against armyworm. The quantitative structure-activity relationship (QSAR) for growth-inhibiting activities was also analyzed and established.

Prediction of first-trimester preeclampsia: Relevance of the oxidative stress marker MDA in a combination model with PP-13, PAPP-A and beta-HCG.

PubMed

Asiltas, Burak; Surmen-Gur, Esma; Uncu, Gurkan

2018-02-27

Early diagnosis of preeclampsia (PE) is very important and various parameters, individually or in combined models, are reported useful for prediction of PE. The objective of this study is to investigate the predictive value of pregnancy-associated plasma protein-A (PAPP-A), placental protein-13 (PP-13), human Chorionic Gonadotropin (B-HCG), and oxidative stress marker malondialdehyde (MDA), individually and in combination. Maternal sera of 38 cases with PE and 122 controls were collected for first trimester screening and tested for PAPP-A and B-HCG by chemiluminescence, for PP-13 by using ELISA, and for MDA by high-performance liquid chromatography. Combined models of parameters were constituted as "MDA + PP-13", "PP-13 + PAPP-A + B-HCG" and "MDA + PP-13 + PAPP-A + B-HCG". The diagnostic performances of serum markers of preeclampsia were examined by nonparametric receiver-operator characteristics (ROC) analysis. PP-13 levels were significantly lower (p < 0.001) and MDA levels were significantly higher (p < 0.001) in PE. The area under the ROC curve (AUC) for MDA and PP-13 were greater than those for PAPP-A and B-HCG (p < 0.001). The AUCs of the combined models were significantly larger than those of individual parameters. The combined model "MDA + PP-13 + PAPP-A + B-HCG" exhibited the best predictive outcome with an AUC of 0.91 [95% CI 0.86-0.95], 97% [95% CI 86.2-99.9] sensitivity and 75% [95% CI 66.5-82.6] specificity, and was significantly different from that of "PAPP-A + PP-13 + B-HCG" model, but similar to that of "MDA + PP-13" model. Combined models consisting of various parameters of different origin, may provide better predictive outcomes, and oxidative markers should be considered in combination with other placental biomarkers in prediction of PE. Copyright © 2018 Elsevier B.V. All rights reserved.

CircRNA-0004904, CircRNA-0001855, and PAPP-A: Potential Novel Biomarkers for the Prediction of Preeclampsia.

PubMed

Jiang, Min; Lash, Gendie E; Zhao, Xueqing; Long, Yan; Guo, Caijiao; Yang, Hongling

2018-05-07

Circular RNAs (circRNAs) are transcribed prevalently in the genome; however, their potential roles in multiple cardiovascular diseases, particularly preeclampsia (PE), are not yet well understood. This study investigated the expression profiles of circRNAs and explored circRNA-mediated pregnancy-associated plasma protein A (PAPP-A) expression as a potential biomarker for PE before 20 weeks of pregnancy. A nested case-control two-phase screening/validation study was performed in pregnant women before 20 weeks of gestation (before clinical diagnosis) at Guangzhou Women and Children's Medical Center from 2012 to 2015. In the screening phase, circRNA expression profiles of blood cells were assessed using a human circRNA microarray, which was designed to detect simultaneously 5396 circRNAs, in 5 patients with PE and 5 age- and gestational week-matched controls. In the validation phase, 18 circRNAs in blood cells predicted by bioinformatics tools were validated by quantitative reverse transcription PCR in a cohort of 60 patients (PE and age-, gestational week-, and sample storage time-matched controls). Then, we examined the involvement of circRNAs in PE-related pathways via interactions with miRNAs by multiple bioinformatics approaches. Bioinformatics analysis predicted that hsa_circ_0004904 and hsa_circ_0001855 miRNA sponges directly target PAPP-A. PAPP-A was verified in the serum of the same cohort of patients using an enzyme-linked immunosorbent assay. Finally, we combined PAPP-A with circRNAs to create a novel preclinical diagnostic model for PE with logistic regression and evaluated the efficiency of this model with receiver operating curve analysis. Volcano plot analysis using various parameters showed that circRNAs were differentially expressed among both groups (P < 0.01, fold change > 2). In the screening phase, we found that 2178 circRNAs were differentially expressed between the control and PE groups, in which 884 circRNAs were downregulated and 1294 circ

LLE 2010 Annual Report October 2009 - September 2010

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

None

2011-01-01

The fiscal year ending September 2010 (FY10) concluded the third year of the third five-year renewal of Cooperative Agreement DE-FC52-08NA28302 with the U.S. Department of Energy (DOE). This annual report summarizes progress in inertial fusion research at the Laboratory for Laser Energetics (LLE) during the past fiscal year including work on the National Ignition Campaign (NIC). It also reports on LLE's progress on laboratory basic science research; laser, optical materials, and advanced technology development; operation of OMEGA and OMEGA EP for the NIC and high-energy density (HED) campaigns, the National Laser Users Facility (NLUF), and for other external users; andmore » programs focusing on the education of high school, undergraduate, and graduate students during the year.« less

The Efficiency of First-Trimester Uterine Artery Doppler, ADAM12, PAPP-A and Maternal Characteristics in the Prediction of Pre-Eclampsia

PubMed Central

GOETZINGER, Katherine R.; ZHONG, Yan; CAHILL, Alison G.; ODIBO, Linda; MACONES, George A.; ODIBO, Anthony O.

2014-01-01

Objective To estimate the efficiency of first-trimester uterine artery Doppler, A-disintegrin and metalloprotease 12 (ADAM12), pregnancy-associated plasma protein A (PAPP-A) and maternal characteristics in the prediction of pre-eclampsia. Methods This is a prospective cohort study of patients presenting for first-trimester aneuploidy screening between 11-14 weeks’ gestation. Maternal serum ADAM12 and PAPP-A levels were measured by immunoassay, and mean uterine artery Doppler pulsatility indices (PI) were calculated. Outcomes of interest included pre-eclampsia, early pre-eclampsia, defined as requiring delivery at <34 weeks’ gestation, and gestational hypertension. Logistic regression analysis was used to model the prediction of pre-eclampsia using ADAM12 multiples of the median (MoM), PAPP-A MoM, and uterine artery Doppler PI MoM, either individually or in combination. Sensitivity, specificity, and area under the receiver-operating characteristic curves (AUC) were used to compare the screening efficiency of the models using non-parametric U-statistics. Results Of 578 patients with complete outcome data, there were 54 (9.3%) cases of preeclampsia and 13 (2.2%) cases of early pre-eclampsia. Median ADAM12 levels were significantly lower in patients who developed pre-eclampsia compared to those who did not. (0.81 v. 1.01 MoMs; p<0.04) For a fixed false positive rate (FPR) of 10%, ADAM12, PAPP-A, and uterine artery Doppler in combination with maternal characteristics identified 50%, 48%, and 52% of patients who developed pre-eclampsia, respectively. Combining these first-trimester parameters did not improve the predictive efficiency of the models. Conclusion First-trimester ADAM12, PAPP-A, and uterine artery Doppler are not sufficiently predictive of pre-eclampsia. Combinations of these parameters do not further improve their screening efficiency. PMID:23980220

LLE Review Quarterly Report (April-June 1989). Volume 39

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

Simon, A.

1989-06-01

This volume of the LLE Review, covering the period April-June 1989, includes the second part of a two-part series dealing with the preliminary design of the OMEGA Upgrade. One article provides a general overview of the current upgrade system configuration and another article describes the target system. Future issues of the LLE Review will cover other aspects of the OMEGA Upgrade as the detailed system design develops. In addition, the advanced technology section of this issue contains an article discussing the interaction of a picosecond optical pulse with high temperature superconductors. Finally, the activities of the National Laser Users Facilitymore » and the GDL and OMEGA laser facilities are summarized.« less

First-trimester ADAM12 and PAPP-A as markers for intrauterine fetal growth restriction through their roles in the insulin-like growth factor system.

PubMed

Cowans, Nicholas J; Spencer, Kevin

2007-03-01

PAPP-A is a marker used as part of the most effective method of screening for chromosomal anomalies in the first trimester. ADAM12 is a recently discovered pregnancy associated member of the ADAM (a multidomain glycoprotein metalloprotease) family. Recently, ADAM12 has been shown as a potential marker for early screening for chromosomal anomalies. Both PAPP-A and ADAM12 have been identified as proteases to insulin-like growth factor binding proteins. In this role, they may have a regulatory function in controlling the amount of free bioactive insulin-like growth factor (IGF). We therefore wish to examine if the levels of either of these proteases are related to various growth related adverse pregnancy outcomes. PAPP-A and ADAM12 were measured in a subset of samples collected at 11 to 14 weeks as part of an OSCAR clinic screening for chromosomal anomalies. Follow-up of pregnancies screened between September 1999 and August 2003 identified 1705 pregnancies with an outcome of intrauterine fetal demise on or after 24 weeks, preterm delivery at 24-34 weeks or 35-36 weeks, very low birthweight (<1.5 kg), low birthweight (<2.5 kg), large birthweight (>4.5 kg), and birth weight below the 3rd or 5th or 10th centile for gestation. A series of 414 normal outcome pregnancies constituted the control group. Marker levels were adjusted for gestation and maternal weight and the log MoM of the markers were compared using t-test of unequal variance between the control group and the various adverse outcome groups. ADAM12 and PAPP-A concentrations were reduced in low for gestational age birth weights and in all births with weights below 2.5 kg. There was a linear relationship between the severity of the IUGR and the decrease in PAPP-A and ADAM12. In the larger babies, only ADAM12 was found to be significantly increased in babies above the 90th centile of weight for gestation. The results of our study are compatible with the proposed role of ADAM12 and PAPP-A in promoting growth and

Association of serum PAPP-A levels in first trimester with small for gestational age and adverse pregnancy outcomes: systematic review and meta-analysis.

PubMed

Morris, R Katie; Bilagi, Ashwini; Devani, Pooja; Kilby, Mark D

2017-03-01

To determine association, and predictive ability, of first trimester maternal serum pregnancy associated plasma protein A (PAPP-A) with adverse pregnancy outcomes. Searches of Medline, Embase and CINAHL (inception September 2015) for studies including pregnant women with first trimester PAPP-A and assessment of pregnancy outcomes. Study characteristics, quality and results extracted. Meta-analysis of odds ratios (ORs), and likelihood ratios (LRs) and 95% confidence intervals (CI). Thirty-two studies including 175 240 pregnancies. PAPP-A <5th centile had a moderate association with: birth weight <10th centile OR 2.08 (95% CI 1.89-2.29), <5th centile OR 2.83 (95% CI 2.52-3.18); pre-eclampsia OR 1.94 (95% CI 1.63-2.30), preterm birth <37 weeks OR 2.09 (95% CI 1.87-2.33), and composite adverse outcome OR 3.31 (95% CI 1.80-5.11). The predictive ability was poor: Birth weight <10th centile LR + ve 1.96 (95% CI 1.58-2.43), LR-ve 0.93 (95% CI 0.89-0.98); birth weight <5th centile LR + ve 2.65 (95% CI 2.35-2.99), LR-ve 0.85 (95% CI 0.74-0.98); PTB <37 weeks LR + ve 1.84 (95% CI 1.41-2.39), LR-ve 0.92 (95% CI 0.87-0.98). First trimester low maternal serum PAPP-A is associated with adverse pregnancy outcome, but predictive values are poor. Further work should address PAPP-A as a continuous variable in combination with other prognostic markers as a prediction model. © 2016 John Wiley & Sons, Ltd. © 2016 John Wiley & Sons, Ltd.

The role of maternal serumbeta-HCG and PAPP-A levels at gestational weeks 10 to 14 in the prediction of pre-eclampsia

PubMed Central

Ozdamar, Ozkan; Gun, Ismet; Keskin, Ugur; Kocak, Necmettin; Mungen, Ercument

2014-01-01

Objective: We aimed to detect whether maternal serum free β-hCG and PAPP-A levels and NT measurements vary between normal pregnancies and those that subsequently develop pre-eclampsia and to evaluate the role of these screening serum analytes in the prediction of pre-eclampsia. Methods: Using a case-control study design, we identified all women who had been screened by double test within 11+0 and 13+6 weeks of gestation and who had developed pre-eclampsia during the subsequent pregnancy course, over a 6-year period between January 2006 and December 2012 at two tertiary referral hospital. All women who had undergone a double test during that time, without a diagnosis of pre-eclampsia and who had not had any adverse obstetric outcomes, were also identified, and three women among them were randomly selected as controls for each case. Maternal and neonatal data were abstracted from the medical records and PAPP-A, β-hCG, NT and CRL MoM values were compared between the two groups. Results: Although β-hCG values show no statistically significant difference (p=0.882), PAPP-A levels were significantly reduced in the pre-eclampsia group compared to the control group (p<0.001). NT and CRL values showed no significant difference between the two groups (p=0.674 and p=0.558, respectively). Conclusion: Measuring PAPP-A in the first trimester may be useful in the prediction of pre-eclampsia. PMID:24948981

In vitro and in vivo characterization of p-amino-phenethyl-m-trifluoromethylphenyl piperazine (PAPP), a novel serotonergic agonist with anthelmintic activity against Haemonchus contortus, Teladorsagia circumcincta and Trichostrongylus colubriformis.

PubMed

White, W Hunter; Gutierrez, Jesus A; Naylor, Sharon A; Cook, Carolyn A; Gonzalez, Isabel C; Wisehart, Mark A; Smith, Charles K; Thompson, William A

2007-05-15

The neurotransmitter serotonin (5-hydroxy tryptamine or 5HT) regulates key physiological processes in nematodes such as locomotion and feeding. PAPP (p-amino-phenethyl-m-trifluoromethylphenyl piperazine) is a known agonist of the 5-HT(1Hc) receptor of the barber pole worm, Haemonchus contortus. In this study, PAPP was highly active against L3-stage larvae of H. contortus and Trichostrongylus colubriformis in an in vitro larval migration assay, with EC50 values of 9.36 and 11.8 microM, respectively, that were comparable to levamisole (10.2 microM) and superior to pyrantel (55.39 microM). When administered orally or subcutaneously to nematode infected gerbils, PAPP provided >99% efficacy against H. contortus and >98% efficacy against Teladorsagia circumcincta at 100 mg/kg, comparable to levamisole at 10 mg/kg. Drug titration revealed significant activity down to 50 mg/kg against these two species. Spectrum was limited, however, with somewhat lower efficacy (83%) in T. colubriformis infected gerbils at 100 mg/kg. Oral delivery of hydrochloride, acetate and phosphate salts of PAPP to nematode infected gerbils did not result in an increase in either potency or spectrum. The finding that PAPP exhibits significant anthelmintic activity suggests that the nematode-specific serotonergic system is a viable target for future anthelmintic discovery.

[Neurousurpation--the expropriation and suppression of Dölle's neurobiological pioneer work].

PubMed

Bertram, Wulf

2011-08-01

The discovery of a hitherto unpublished dissertational thesis in the archive of a publishing house has lead to a lost publication by Ernst August Dölle. In this manuscript, the author reports on the stimulation of a cerebral libido area in the dog, long before Olds and Milner published their work on the discovery of the rewarding area. The reasons for the suppression of this early publication by Dölle are investigated and are ascribed to an effort to use his neurobiologic research for secret mental manipulation experiments of the CIA at the beginning of the Cold War. George Thieme Verlag KG Stuttgart · New York.

LLE 2004 annual report, October 2003-September 2004

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

None, None

2005-01-01

This report summarizes research at the Laboratory for Laser Energetics (LLE) conducted during the year, operation of the National Laser Users’ Facility (NLUF), a status report of the new OMEGA Extended Performance (EP) laser project, and programs concerning the education of high school, undergraduate, and graduate students during the year.

LLE Review 117 (October-December 2008)

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

Bittle, W., editor

2009-05-28

This volume of the LLE Review, covering October-December 2008, features 'Demonstration of the Shock-Timing Technique for Ignition Targets at the National Ignition Facility' by T. R. Boehly, V. N. Goncharov, S. X. Hu, J. A. Marozas, T. C. Sangster, D. D. Meyerhofer (LLE), D. Munro, P. M. Celliers, D. G. Hicks, G. W. Collins, H. F. Robey, O. L. Landen (LLNL), and R. E. Olson (SNL). In this article (p. 1) the authors report on a technique to measure the velocity and timing of shock waves in a capsule contained within hohlraum targets. This technique is critical for optimizing themore » drive profiles for high-performance inertial-confinement-fusion capsules, which are compressed by multiple precisely timed shock waves. The shock-timing technique was demonstrated on OMEGA using surrogate hohlraum targets heated to 180 eV and fitted with a re-entrant cone and quartz window to facilitate velocity measurements using velocity interferometry. Cryogenic experiments using targets filled with liquid deuterium further demonstrated the entire timing technique in a hohlraum environment. Direct-drive cryogenic targets with multiple spherical shocks were also used to validate this technique, including convergence effects at relevant pressures (velocities) and sizes. These results provide confidence that shock velocity and timing can be measured in NIF ignition targets, thereby optimizing these critical parameters.« less

Dried blood spot measurement of pregnancy-associated plasma protein A (PAPP-A) and free β-subunit of human chorionic gonadotropin (β-hCG) from a low-resource setting.

PubMed

Browne, J L; Schielen, P C J I; Belmouden, I; Pennings, J L A; Klipstein-Grobusch, K

2015-06-01

The objectives of the article is to compare pregnancy-associated plasma protein A (PAPP-A) and free β-subunit of human chorionic gonadotropin (β-hCG) concentrations in dried blood spots (DBSs) with serum of samples obtained from a public hospital in a low-resource setting and to evaluate their stability. Serum and DBS samples were obtained by venipuncture and finger prick from 50 pregnant participants in a cohort study in a public hospital in Accra, Ghana. PAPP-A and β-hCG concentrations from serum and DBS were measured with an AutoDELFIA® (PerkinElmer, PerkinElmer, Turku, Finland) automatic immunoassay. Correlation and Passing-Bablok regression analyses were performed to compare marker levels. High correlation (>0.9) was observed for PAPP-A and β-hCG levels between various sampling techniques. The β-hCG concentration was stable between DBS and serum, PAPP-A concentration consistently lower in DBS. Our findings suggest that β-hCG can be reliably collected from DBS in low-resource tropical settings. The exact conditions of the clinical workflow necessary for reliable PAPP-A measurement in these settings need to be further developed in the future. These findings could have implications for prenatal screening programs feasibility in low-income and middle-income countries, as DBS provides an alternative minimally invasive sampling method, with advantages in sampling technique, stability, logistics, and potential application in low-resource settings. © 2015 John Wiley & Sons, Ltd.

Second trimester amniotic fluid adiponectin level is affected by maternal tobacco exposure, insulin, and PAPP-A level.

PubMed

De Leon-Luis, Juan; Perez, Ricardo; Pintado Recarte, Pilar; Avellaneda Fernandez, Alfredo; Romero Roman, Carlos; Antolin Alvarado, Eugenia; Ortiz-Quintana, Luis; Izquierdo Martinez, Maravillas

2012-12-01

Adiponectin is an adipocyte-derived plasma protein with insulin-sensitizing and antiatherosclerotic properties. The objectives of the present study were to determine the amniotic fluid (AF) concentration of adiponectin during the second trimester of pregnancy and to demonstrate its association with maternal and fetal variables and AF concentrations of insulin, leptin, and pregnancy-associated-plasma-protein A (PAPP-A). We performed a cross-sectional study of 222 pregnant women who underwent amniocentesis at 15-18 weeks for genetic reasons. No malformation or chromosomal disorder was found in the newborn after birth. AF adiponectin, leptin, PAPP-A, and insulin concentrations were measured using commercially available assays. All maternal, fetal, and biochemical variables were studied using univariate and multivariate linear regression analysis to determine their association with the AF concentration of adiponectin. Adiponectin concentration was negatively correlated with maternal smoking status (β=-5.208; p<0.001) and positively correlated with levels of insulin (β=0.621; p=0.002) and PAPP-A (β=40.150; p<0.001). Non-significant correlations were found between adiponectin concentration and maternal age, maternal body mass index, gestational age at amniocentesis, fetal gender, and AF level of leptin. These findings suggest that the fetus and its membrane adipocytokines, in relationship with maternal and other fetal variables, play a dynamic role in the regulation of energy and oxidative stress homeostasis due to its insulin-sensitizing and antiatherosclerotic effects. The association of these molecules with maternal tobacco consumption during pregnancy could have perinatal implications. Copyright © 2012 Elsevier Ireland Ltd. All rights reserved.

Life beyond the limits of knowledge: crystalline life in the popular science of Desiderius Papp (1895-1993).

PubMed

Brandstetter, Thomas

2012-10-01

The aim of this article is to show how, and in which context, astrobiological reasoning was employed before the establishment of astrobiology as a scientific discipline. By way of an example, I will discuss a popular science book published in 1931 by the Hungarian journalist Desiderius Papp. The author claims that this book represents an innovation in astrobiological reasoning, as it draws on contemporary biological research to conduct thought experiments, thereby coming up with concrete forms of possible extraterrestrial life. One of the most interesting of these forms was crystalline life. After a short overview on the history of this concept, this article will show how Papp drew on recent research by Otto Lehmann on liquid crystals to convey the idea that life may be based on other elements than carbon. The author concludes by arguing that popular science did not only make specialist knowledge accessible to a general public but also served to probe the limits of knowledge and point toward the situatedness of established categories and definitions.

LLE Review 120 (July-September 2009)

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

Edgell, D.H., editor

2001-02-19

This issue has the following articles: (1) The Omega Laser Facility Users Group Workshop; (2) The Effect of Condensates and Inner Coatings on the Performance of Vacuum Hohlraum Targets; (3) Zirconia-Coated-Carbonyl-Iron-Particle-Based Magnetorheological Fluid for Polishing Optical Glasses and Ceramics; (4) All-Fiber Optical Magnetic Field Sensor Based on Faraday Rotation in Highly Terbium Doped Fiber; (5) Femtosecond Optical Pump-Probe Characterization of High-Pressure-Grown Al{sub 0.86}Ga{sub 0.14}N Single Crystals; (6) LLE's Summer High School Research Program; (7) Laser Facility Report; and (8) National Laser Users Facility and External Users Programs.

Evaluation of the appropriate time range for estimating the apparent permeability coefficient (P(app)) in a transcellular transport study.

PubMed

Ozeki, Kazuhisa; Kato, Motohiro; Sakurai, Yuuji; Ishigai, Masaki; Kudo, Toshiyuki; Ito, Kiyomi

2015-11-30

In a transcellular transport study, the apparent permeability coefficient (Papp) of a compound is evaluated using the range by which the amount of compound accumulated on the receiver side is assumed to be proportional to time. However, the time profile of the concentration of the compound in receiver (C3) often shows a lag time before reaching the linear range and later changes from linear to steady state. In this study, the linear range needed to calculate Papp in the C3-time profile was evaluated by a 3-compartment model. C3 was described by an equation with two steady states (C3=A3(1-e(-αt))+B3(1-e(-βt)), α>β), and by a simple approximate line (C3=A3-A3×αt) in the time range of 3/αPapp was 3/α

LLE Review 116 (July-September 2008)

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

Marozas, J.A., editor

2010-03-12

This issue has the following articles: (1) Optimizing Electron-Positron Pair Production on kJ-Class High-Intensity Lasers for the Purpose of Pair-Plasma Creation; (2) Neutron Yield Study of Direct-Drive, Low-Adiabat Cryogenic D2 Implosions on OMEGA; (3) Al 1s-2p Absorption Spectroscopy of Shock-Wave Heating and Compression in Laser-Driven Planar Foil; (4) A Measurable Lawson Criterion and Hydro-Equivalent Curves for Inertial Confinement Fusion; (5) Pulsed-THz Characterization of Hg-Based, High-Temperature Superconductors; (6) LLE's Summer High School Research Program; (7) FY08 Laser Facility Report; and (8) National Laser Users Facility and External Users Programs.

The Effect of the Immediate Feedback by the Collaborative Education Tool ViLLE on Learning for Business Mathematics in Higher Education

ERIC Educational Resources Information Center

Kuikka, Matti; Laakso, Mikko-Jussi; Joshi, Marjo

2016-01-01

This article outlines the effect of the collaborative educational tool ViLLE when learning business mathematics in higher education. ViLLE validates students' answers during the assessment process and provides immediate feedback, enabling students to receive feedback and guidance about the correctness of their answers. The learning results in the…

Determination of DDT and metabolites in surface water and sediment using LLE, SPE, ACE and SE.

PubMed

Sibali, Linda L; Okonkwo, Jonathan O; Zvinowanda, Caliphs

2009-12-01

Surface water and sediment samples collected from Jukskei River in South Africa, were subjected to different extraction techniques, liquid-liquid (LLE), solid-phase extraction (SPE), activated carbon extraction (ACE) and soxhlet extraction (SE) for sediment. The samples were extracted with dichloromethane, cleaned in a silica gel column and the extracts quantified using a Varian 3800 GC-ECD. The percentage recovery test for 2,4'DDT, DDE and DDD and 4,4'DDT, DDE and DDD in water ranged from 80%-96% and 76%-95% (LLE); 56%-76% and 56%-70% (SPE) and 75%-84% (ACE), respectively; while that recoveries for sediment samples varied from 65%-95% for 2,4'DDT, DDE and DDD and 80%-91% for 4,4'DDT, DDE and DDD. The high recoveries exhibited by ACE compared very well with LLE and SE. This was not the case with SPE which exhibited the lowest value of recoveries for both 2,4 and 4,4'DDD, DDE and DDT standard samples. The mean concentrations of DDT and metabolites ranged from nd-1.10 μg/L, nd-0.80 μg/L, nd-1.21 μg/L and 1.92 μg/L for LLE, SPE, ACE and SE, respectively. The total DDT (2,4' and 4,4'-DDT) in water and sediment samples ranged from 1.20-3.25 μg/L and 1.82-5.24 μg/L, respectively. The low concentrations of the DDT metabolites obtained in the present study may suggest a recent contamination of the river by DDT.

A first trimester trisomy 13/trisomy 18 risk algorithm combining fetal nuchal translucency thickness, maternal serum free beta-hCG and PAPP-A.

PubMed

Spencer, Kevin; Nicolaides, Kypros H

2002-10-01

This study examines 45 cases of trisomy 13 and 59 cases of trisomy 18 and reports an algorithm to identify pregnancies with a fetus affected by trisomy 13 or 18 by a combination of maternal age fetal nuchal translucency (NT) thickness, and maternal serum free beta-hCG and PAPP-A at 11-14 weeks of gestation. In this mixed trisomy group the median MoM NT was increased at 2.819, whilst the median MoMs for free beta-hCG and PAPP-A were reduced at 0.375 and 0.201 respectively. We predict that with the use of the combined trisomy 13 and 18 algorithm and a risk cut-off of 1 in 150 will for a 0.3% false positive rate allow 95% of these chromosomal defects to be identified at 11-14 weeks. Such algorithms will enhance existing first trimester screening algorithms for trisomy 21. Copyright 2002 John Wiley & Sons, Ltd.

First Trimester Maternal Serum Screening Using Biochemical Markers PAPP-A and Free β-hCG for Down Syndrome, Patau Syndrome and Edward Syndrome.

PubMed

Shiefa, S; Amargandhi, M; Bhupendra, J; Moulali, S; Kristine, T

2013-01-01

The first trimester screening programme offers a noninvasive option for the early detection of aneuploidy pregnancies. This screening is done by a combination of two biochemical markers i.e. serum free β-human chorionic gonadotrophin (free β-hCG) and pregnancy associated plasma protein A (PAPP-A), maternal age and fetal nuchal translucency (NT) thickness at 11 + 0-13 + 6 weeks of gestation. A beneficial consequence of screening is the early diagnosis or trisomies 21, 18 and 13. At 11 + 0-13 + 6 weeks, the relative prevalence of trisomies 18 and 13 to trisomy 21 are found to be one to three and one to seven, respectively. All three trisomies are associated with increased maternal age, increased fetal NT and decreased PAPP-A, but in trisomy 21 serum free β-hCG is increased whereas in trisomies 18 and 13 free β-hCG is decreased.

LLE 2009 annual report, October 2008-September 2009

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

none, none

2010-01-01

The fiscal year ending September 2009 (FY2009) concluded the second year of the third five-year renewal of Cooperative Agreement DE-FC52-08NA28302 with the U.S. Department of Energy (DOE). This annual report summarizes progress in inertial fusion research at the Laboratory for Laser Energetics (LLE) during the past fiscal year. It also reports on LLE’s progress on laboratory basic science research; laser, optical materials, and advanced technology development; operation of OMEGA and OMEGA EP for the National Laser Users’ Facility (NLUF), and other external users; and programs focusingon the education of high school, undergraduate, and graduate students during the year.

LLE review

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

Bradley, D.K.

1989-01-01

This volume of the LLE Review, covering the period October--December 1989, contains an article discussing saturation effects and power-balance considerations in the design of high-power lasers and an article describing numerical modeling of the effects of power imbalances on target behavior. The advanced technology section reports on the development of a liquid crystal laser-beam apodizer and an experiment to study the high-intensity ionization of noble gases. Finally, the activities of the National Laser Users Facility and the GDL and OMEGA laser facilities are summarized. The highlights of this issue are: The problem of achieving power balance in high-efficiency, multibeam lasersmore » has been studied in terms of gain-saturation effects and the nonlinear nature of harmonic frequency conversion. It is shown that power imbalance can be minimized by balancing the gains and losses in equivalent amplification stages in each beamline. The effects of target implosion behavior of various power-imbalance sources in the OMEGA laser system have been studied using the two-dimensional hydrodynamics code ORCHID. The simulations show good agreement with an experiment in which a deliberate power imbalance was applied to the target drive. Laser-beam apodizers with large clear apertures have been fabricated using cholesteric liquid crystals. A soft-edge profile has been achieved by filling a cell with two separate liquid crystals with different selective-reflection bands, and allowing them to partially mix at the interface. A study of the ionization of noble gases in the tunneling regime using high- intensity, 1-ps pulses from the tabletop terawatt laser (T{sup 3}) has been carried out. The measured ion production is well predicted by a Coulomb barrier suppression ionization theory.« less

Prognostic relevance and performance characteristics of serum IGFBP-2 and PAPP-A in women with breast cancer: a long-term Danish cohort study.

PubMed

Espelund, Ulrick; Renehan, Andrew G; Cold, Søren; Oxvig, Claus; Lancashire, Lee; Su, Zhenqiang; Flyvbjerg, Allan; Frystyk, Jan

2018-05-03

Measurement of circulating insulin-like growth factors (IGFs), in particular IGF-binding protein (IGFBP)-2, at the time of diagnosis, is independently prognostic in many cancers, but its clinical performance against other routinely determined prognosticators has not been examined. We measured IGF-I, IGF-II, pro-IGF-II, IGF bioactivity, IGFBP-2, -3, and pregnancy-associated plasma protein A (PAPP-A), an IGFBP regulator, in baseline samples of 301 women with breast cancer treated on four protocols (Odense, Denmark: 1993-1998). We evaluated performance characteristics (expressed as area under the curve, AUC) using Cox regression models to derive hazard ratios (HR) with 95% confidence intervals (CIs) for 10-year recurrence-free survival (RFS) and overall survival (OS), and compared those against the clinically used Nottingham Prognostic Index (NPI). We measured the same biomarkers in 531 noncancer individuals to assess multidimensional relationships (MDR), and evaluated additional prognostic models using survival artificial neural network (SANN) and survival support vector machines (SSVM), as these enhance capture of MDRs. For RFS, increasing concentrations of circulating IGFBP-2 and PAPP-A were independently prognostic [HR biomarker doubling : 1.474 (95% CIs: 1.160, 1.875, P = 0.002) and 1.952 (95% CIs: 1.364, 2.792, P < 0.001), respectively]. The AUC RFS for NPI was 0.626 (Cox model), improving to 0.694 (P = 0.012) with the addition of IGFBP-2 plus PAPP-A. Derived AUC RFS using SANN and SSVM did not perform superiorly. Similar patterns were observed for OS. These findings illustrate an important principle in biomarker qualification-measured circulating biomarkers may demonstrate independent prognostication, but this does not necessarily translate into substantial improvement in clinical performance. © 2018 The Authors. Cancer Medicine published by John Wiley & Sons Ltd.

Three new species of Pambolus (Braconidae: Pambolinae) from Mexico, with comments on the variation of P. oblongispina Papp.

PubMed

Aguilera-Uribe, Magali; MartÍnez, Juan josÉ; ZaldÍvar-riverÓn, Alejandro

2018-01-31

Three species of the braconid genus Pambolus (Braconidae) are described from Mexico: P. jarocho sp. n., P. chinanteco sp. n. and P. bizelab sp. n. The external morphological variation in males and females of P. oblongispina Papp, previously known only by two females from Honduras and northern Mexico, is described based on material from Jalisco and Oaxaca in central and southeast Mexico. Molecular characterisation of the examined species was carried out based on the 28S nuclear ribosomal and the COI mitochondrial DNA gene markers.

Headspace solid-phase microextraction (HS-SPME) and liquid-liquid extraction (LLE): comparison of the performance in classification of ecstasy tablets. Part 2.

PubMed

Bonadio, Federica; Margot, Pierre; Delémont, Olivier; Esseiva, Pierre

2008-11-20

Headspace solid-phase microextraction (HS-SPME) is assessed as an alternative to liquid-liquid extraction (LLE) currently used for 3,4-methylenedioxymethampethamine (MDMA) profiling. Both methods were compared evaluating their performance in discriminating and classifying samples. For this purpose 62 different seizures were analysed using both extraction techniques followed by gas chromatography-mass spectroscopy (GC-MS). A previously validated method provided data for HS-SPME, whereas LLE data were collected applying a harmonized methodology developed and used in the European project CHAMP. After suitable pre-treatment, similarities between sample pairs were studied using the Pearson correlation. Both methods enable to distinguish between samples coming from the same pre-tabletting batches and samples coming from different pre-tabletting batches. This finding emphasizes the use of HS-SPME as an effective alternative to LLE, with additional advantages such as sample preparation and a solvent-free process.

Placental protein-13 (PP13) in combination with PAPP-A and free leptin index (fLI) in first trimester maternal serum screening for severe and early preeclampsia.

PubMed

De Villiers, Carin P; Hedley, Paula L; Placing, Sophie; Wøjdemann, Karen R; Shalmi, Anne-Cathrine; Carlsen, Anting L; Rode, Line; Sundberg, Karin; Tabor, Ann; Christiansen, Michael

2017-11-27

Placental protein-13 (PP13) is involved in placental invasion and has been suggested as a maternal serum marker of preeclampsia (PE) development. However, the discriminatory ability of PP13 in first trimester has not been completely clarified. PP13 was measured in first trimester (week 10+3-13+6) maternal serum from 120 PE pregnancies and 267 control pregnancies and was correlated with clinical parameters. The population screening performance of PP13 in combination with the PE markers pregnancy associated plasma protein A (PAPPA) and free leptin index (fLI) was assessed by Monte Carlo simulation. In severe PE (including HELLP) cases (n=26) the median PP13 concentration was 35.8 pg/mL (range: 17.8-85.5 pg/mL) and in PE pregnancies (n=10) with birth prior to week 34, the median PP13 concentration was 30.6 pg/mL (13.1-50.1 pg/mL), compared to controls with a median of 54.8 pg/mL (range: 15.4-142.6 pg/mL) (p<0.04). The population screening detection rate (DR) for a false-positive rate of 10% for severe PE and HELLP was 26% for PP13, 28% for PP13+PAPP-A, 33% for PP13+fLI, and 40% for PP13+PAPP-A+fLI. PP13 is a marker of severe PE and HELLP syndrome. The screening performance of PP13 can be markedly improved by combining it with fLI and PAPP-A.

LLE review. Quarterly report, January 1994--March 1994, Volume 58

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

Simon, A.

1994-07-01

This volume of the LLE Review, covering the period Jan - Mar 1994, contains articles on backlighting diagnostics; the effect of electron collisions on ion-acoustic waves and heat flow; using PIC code simulations for analysis of ultrashort laser pulses interacting with solid targets; creating a new instrument for characterizing thick cryogenic layers; and a description of a large-aperture ring amplifier for laser-fusion drivers. Three of these articles - backlighting diagnostics; characterizing thick cryogenic layers; and large-aperture ring amplifier - are directly related to the OMEGA Upgrade, now under construction. Separate abstracts have been prepared for articles from this report.

Lower placental growth factor and higher free β-hCG and PAPP-A levels in the fetal circulation of near-term pregnancies complicated with severe preeclampsia.

PubMed

Paredes, Verónica; Espinoza-Caicedo, Jasson A; Salazar-Pousada, Danny; Escobar, Gustavo S; Pérez-López, Faustino R; Chedraui, Peter

2017-01-01

An imbalance between anti- and angiogenic factors during early placentation is key for the development of preeclampsia. Nevertheless, the majority of studies addressing this issue relate to maternal blood and not the fetal circulation. To measure placental growth factor (PlGF), free beta human chorionic gonadotropin (β-hCG), and pregnancy-associated plasma protein-A (PAPP-A) levels in the fetal circulation of near-term pregnancies complicated with severe preeclampsia (n = 20), and their controls matched for parity, and maternal and gestational age. Upon delivery, a blood sample was withdrawn from the umbilical artery and vein of each case and its control in order to measure the proposed analytes using direct fluoroimmunoassay. Preeclampsia cases showed significantly lower median PlGF levels in fetal circulation as compared to controls (25.2 versus 36.9 and 23.6 versus 33.9 pg/mL, artery and vein, respectively, p < 0.05). Contrarily, cases displayed higher concentrations of PAPP-A (1024.0 versus 720.9 [median] and 1027.0 ± 298.4 versus 690.3 ± 401.9 mIU/L, artery and vein, respectively, p < 0.05), and free β-hCG (mean: 33.9 ± 4.3 versus 17.2 ± 4.0 and 30.1 ± 5.2 versus 13.7 ± 3.3 ng/mL, artery, and vein respectively, p < 0.05). Lower PlGF and higher PAPP-A and free β-hCG levels were found in the fetal circulation of near-term severe preeclamptic pregnancies. There is a need for more research in this regard.

LLE Review 98 (January-March 2004)

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

Goncharov, V.N.

2004-08-10

This volume of the LLE Review, covering January-March 2004, features ''Performance of 1-THz-Bandwidth, 2-D Smoothing by Spectral Dispersion and Polarization Smoothing of High-Power, Solid-State Laser Beams'', by S. P. Regan, J. A. Marozas, R. S. Craxton, J. H. Kelly, W. R. Donaldson, P. A. Jaanimagi, D. Jacobs-Perkins, R. L. Keck, T. J. Kessler, D. D. Meyerhofer, T. C. Sangster, W. Seka, V.A. Smalyuk, S. Skupsky, and J. D. Zuegel (p. 49). Laser-beam smoothing achieved with 1-THz-bandwidth, two-dimensional smoothing by spectral dispersion and polarization smoothing on the 60-beam, 30-kJ, 351-nm OMEGA laser system is reported. These beam-smoothing techniques are directly applicablemore » to direct-drive ignition target designs for the 192-beam, 1.8-MJ, 351-nm National Ignition Facility. Equivalent-target-plane images for constant-intensity laser pulses of varying duration were used to determine the smoothing. The properties of the phase plates, frequency modulators, and birefringent wedges were simulated and found to be in good agreement with the measurements.« less

LLE review. Volume 61, Quarterly report, October--December 1994

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

NONE

1994-12-31

This volume of the LLE review, covering the period of October--December 1994, contains articles on a diagnostic method employing krypton spectroscopy for measurement of temperature and shell-fuel mixing in high-temperature implosions; the first direct assessment of the ion-acoustic decay instability in a large-scale length, hot plasma; measurements of polarization mode dispersion and group-velocity walkaway in birefringent media using a frequency domain interferometer; an evaluation of the magnetic flux dynamics occurring in an optically triggered, thin-film superconducting switch; the effect of slurry fluid chemistry on particle size distribution during aqueous polishing of optical glass; and the influence of thermal and mechanicalmore » processing history in the preparation of well-ordered liquid crystal elastomer systems.« less

rhIGF-1 Treatment Increases Bone Mineral Density and Trabecular Bone Structure in Children with PAPP-A2 Deficiency.

PubMed

Hawkins-Carranza, Federico G; Muñoz-Calvo, María T; Martos-Moreno, Gabriel Á; Allo-Miguel, Gonzalo; Del Río, Luis; Pozo, Jesús; Chowen, Julie A; Pérez-Jurado, Luis A; Argente, Jesús

2018-01-01

Our objective was to determine changes in bone mineral density (BMD), trabecular bone score (TBS), and body composition after 2 years of therapy with recombinant human insulin-like growth factor-1 (rhIGF-1) in 2 prepubertal children with a complete lack of circulating PAPP-A2 due to a homozygous mutation in PAPP-A2 (p.D643fs25*) resulting in a premature stop codon. Body composition, BMD, and bone structure were determined by dual-energy X-ray absorptiometry at baseline and after 1 and 2 years of rhIGF-1 treatment. Height increased from 132 to 145.5 cm (patient 1) and from 111.5 to 124.5 cm (patient 2). Bone mineral content increased from 933.40 to 1,057.97 and 1,152.77 g in patient 1, and from 696.12 to 773.26 and 911.51 g in patient 2, after 1 and 2 years, respectively. Whole-body BMD also increased after 2 years of rhIGF-1 from baseline 0.788 to 0.869 g/cm2 in patient 1 and from 0.763 to 0.829 g/cm2 in patient 2. After 2 years of treatment, both children had an improvement in TBS. During therapy, a slight increase in body fat mass was seen, with a concomitant increase in lean mass. No adverse effects were reported. Two years of rhIGF-1 improved growth, with a tendency to improve bone mass and bone microstructure and to modulate body composition. © 2018 S. Karger AG, Basel.

[Integrated health service research of the epiphenomenon (IVF-E)--paradigm shift or Dölle's wine in new skins?].

PubMed

Herzog, Wolfgang

2011-08-01

The meaning of epiphenomenalism for psychosomatic medicine and psychotherapy is analyzed. It may be concluded that Ernst-August Dölle was one of the first researchers to describe and to use the Alpha and Omega of epiphenomenalism. Georg Thieme Verlag KG Stuttgart · New York.

The impact of fetal gender on first trimester nuchal translucency and maternal serum free beta-hCG and PAPP-A MoM in normal and trisomy 21 pregnancies.

PubMed

Cowans, Nicholas J; Stamatopoulou, Anastasia; Maiz, Nerea; Spencer, Kevin; Nicolaides, Kypros H

2009-06-01

To investigate if fetal sex has an impact on 1st trimester combined screening for aenuploidy. We studied the first trimester PAPP-A, free beta-human chorionic gonadatropin (beta-hCG) and nuchal translucency levels in 56,024 normal, singleton pregnancies with known fetal sex at birth. We also examined the distributions in 722 pregnancies with trisomy 21 of known fetal sex. We have found a 14.74% increase in first trimester maternal serum (MS) median free beta-hCG MoM, 6.25% increase of PAPP-A and a 9.41% decrease in delta NT, when the fetus was female. Analysis of data has shown that women carrying a female fetus were 1.084 times more likely to be in the 'at risk' group than those carrying a male fetus. In examining data from 722 pregnancies in which the fetus was affected by trisomy 21, we observed a similar 20.8% increase in free beta-hCG MoM, 5.7% increase in PAPP-A and a 12% decrease in delta NT when the fetus was female. Amongst the trisomy 21 cases, 88.8% of male trisomy 21 cases were detected compared with 91.2% in female cases, this difference was not statistically significant. Correcting for fetal sex redressed the balance in screen-positive rate between the sexes and had a minimal impact on detection rate. Correcting for fetal sex may be a worthwhile consideration. A cost-benefit analysis would be required to determine if it is feasible to introduce fetal gender assignment into the routine first trimester scan for the purpose of marker correction and whether this would have any significant impact. (c) 2009 John Wiley & Sons, Ltd.

LLE 1998 annual report, October 1997--September 1998. Inertial fusion program and National Laser Users` Facility program

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

NONE

1999-01-01

This report summarizes research at the Laboratory for Laser Energetics (LLE), the operation of the National Laser Users` Facility (NLUF), and programs involving the education of high school, undergraduate, and graduate students for FY98. Research summaries cover: progress in laser fusion; diagnostic development; laser and optical technology; and advanced technology for laser targets.

LLE Review Quarterly Report July-September 2000

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

NONE

2000-12-01

This volume of the LLE Review, covering July-September 2000, begins with an article by T. R. Boehly, V. N. Goncharov, O. Gotchev, J. P. Knauer, D. D. Meyerhofer, D. Oron, S. P. Regan, Y. Srebro, W. Seka, D. Shvarts, S. Skupsky, and V.A. Smalyuk, who describe measurements of the effect of beam smoothing and pulse shape on imprinting. (Imprinting is defined as the imposition of pressure perturbations on the target by spatial variations in the laser intensity.) A principal result is the observation of reduced levels of imprint with the higher beam smoothing afforded by 1-THz smoothing by spectral dispersionmore » (SSD). Additional highlights of research presented in this issue are: (1) P. W. McKenty, V. N. Goncharov, R. P. J. Town, S. Skupsky, R. Betti, and R. L. McCrory describe calculations of directly driven ignition capsule performance on the National Ignition Facility (NIF). The authors detail how the various contributors to implosion disruption (laser imprint, power imbalance, and target roughness) affect target performance and final gain. The conclusions are obtained by examining the simulated target evolution with the two-dimensional hydrodynamics computer code ORCHID. (2) D. D. Meyerhofer, J. A. Delettrez, R. Epstein, V. Yu. Glebov, V. N. Goncharov, R. L. Keck, R. L. McCrory, P. W. McKenty, F. J. Marshall, P. B. Radha, S. P. Regan, S. Roberts, W. Seka, S. Skupsky, V. A. Smalyuk, C. Sorce, C. Stoeckl, J. M. Soures, R. P. J. Town, B. Yaakobi, J. D. Zuegel, J. Frenje, C. K. L1,R. D. Petrasso, F. Seguin, K. Fletcher, S. Padalino, C. Freeman, N. Izumi, R. Lerche, T. W. Phillips, and T. C. Sangster describe the results of a series of direct-drive implosions of gas-fusion-fuel-filled plastic shells performed on the OMEGA laser system. The experiments include those performed with 1-THZ SSD and high-quality power balance. (3) V. Yu. Glebov, D. D. Meyerhofer, C. Stoeckl, and J. D. Zuegel describe the technique of measuring secondary neutron yield (DT neutron yield

LLE 1995 annual report, October 1994--September 1995

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

NONE

1996-01-01

The fiscal year ending September 1995 (FY95) concluded the third year of the cooperative agreement (DE-FC03-92SF19460) with the U.S. Department of Energy (DOE). This report summarizes research at the Laboratory for Laser Energetics (LLE) and reports on the successful completion of the OMEGA Upgrade. Previous annual reports describe the OMEGA Upgrade design. The preliminary design for the system was complete in October 1989 and the detailed design started in October 1990. The original 24-beam OMEGA system was decommissioned in December 1992 as construction for the OMEGA Upgrade began. We discuss the initial performance results (p. 99) of the upgraded OMEGAmore » laser system. All acceptance tests were completed, and we demonstrated that all 60 beams can irradiate a target with more energy and better beam balance than was required by DOE`s acceptance criteria. We are most proud that all program milestones were met or exceeded, and that the system was completed on time and on budget.« less

The influence of fetal sex in screening for trisomy 21 by fetal nuchal translucency, maternal serum free beta-hCG and PAPP-A at 10-14 weeks of gestation.

PubMed

Spencer, K; Ong, C Y; Liao, A W; Papademetriou, D; Nicolaides, K H

2000-08-01

In a study of 2923 normal pregnancies and 203 pregnancies affected by trisomy 21 we have shown a significant difference in the median MoM of the markers: fetal nuchal translucency, maternal serum free beta-hCG and PAPP-A in the presence of a female fetus compared with a male fetus. For maternal serum free beta-hCG levels are higher by 15% if the fetus is chromosomally normal and by 11% if the fetus has trisomy 21. For maternal serum PAPP-A the levels in chromosomally normal fetuses are 10% higher in the presence of a female fetus and 13% higher if the fetus has trisomy 21. In contrast, fetal nuchal translucency is 3-4% lower in both chromosomally normal and trisomy 21 female fetuses. The consequence of such changes when screening for trisomy 21 will be a reduction in the detection rate in female fetuses by a factor of 1-2%. Correction of risk algorithms for fetal sex, however, is probably not feasible, since ultrasound detection of fetal sex is only 70-90% accurate in the 10-14 week period. Copyright 2000 John Wiley & Sons, Ltd.

LLE Review Quarterly Report (October - December 2007). Volume 113

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

Zuegel, Jonathan D.

2007-12-01

This volume of the LLE Review, covering October–December 2007, features “High-Intensity Laser–Plasma Interactions in the Refluxing Limit,” by P. M. Nilson, W. Theobald, J. Myatt, C. Stoeckl, M. Storm, O. V. Gotchev, J. D. Zuegel, R. Betti, D. D. Meyerhofer, and T. C. Sangster. In this article (p. 1), the authors report on target experiments using the Multi-Terawatt (MTW) Laser Facility to study isochoric heating of solid-density targets by fast electrons produced from intense, short-pulse laser irradiation. Electron refluxing occurs due to target-sheath field effects and contains most of the fast electrons within the target volume. This efficiently heats themore » solid-density plasma through collisions. X-ray spectroscopic measurements of absolute K α (x-radiation) photon yields and variations of the K β/K α b emission ratio both indicate that laser energy couples to fast electrons with a conversion efficiency of approximately 20%. Bulk electron temperatures of at least 200 eV are inferred for the smallest mass targets.« less

Variable Spaced Grating (VSG) Snout, Rotator and Rails for use at LLE

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

Mukherjee, S K; Emig, J A; Griffith, L V

2010-01-25

The Variable Spaced Grating (VSG) is a spectrometer snout mounted to an X-Ray Framing Camera (XRFC) through the Unimount flange. This equipment already exists and is used at the University of Rochester, Laboratory for Laser Energetics (LLE) facility. The XRFC and the Unimount flange are designed by LLE. The Tilt Rotator fixture that mounts next to the XRFC and the cart rails are designed by LLNL, and are included in this safety note. The other related components, such as the TIM rails and the Unimount flange, are addressed in a separate safety note, EDSN09-500005-AA. The Multipurpose Spectrometer (MSPEC) and VSGmore » are mounted on the TIM Boat through the cart rails that are very similar in design. The tilt rotator combination with the Unimount flange is also a standard mounting procedure. The later mounting system has been included in this safety note. Figure-1 shows the interface components and the VSG snout. Figure-2 shows the VSG assembly mounted on the Unimount flange. The calibration pointer attachment is shown in place of the snout. There are two types of VSG, one made of 6061-T6 aluminum, weighing approximately 3 pounds, and the other made of 304 stainless steel, weighing approximately 5.5 pounds. This safety note examines the VSG steel design. Specific experiments may require orienting the VSG snout in 90 degrees increment with respect to the Unimount flange. This is done by changing the bolts position on the VSG-main body adapter flange to the Unimount adapter plate. There is no hazard involved in handling the VSG during this procedure as it is done outside the target chamber on the cart rail before installing on the TIM. This safety note addresses the mechanical integrity of the VSG structure, the tilt rotating fixture, the cart rails with handle and their connections. Safety Factors are also calculated for the MSPEC in place of the VSG.« less

Surgically Induced Necrotizing Scleritis Following Strabismus Surgery Treated Successfully with Topical N-acetylcysteine in a Child with Congenital Fibrosis of Extraocular Muscles and Varadi Papp Syndrome.

PubMed

Rajamani, Muralidhar; Nagasubramanian, Vidhya; Ayyavoo, Ahila; Raghupathy, Palany; Dandapani, Ramamurthy

2017-03-01

Surgically induced necrotizing scleritis (SINS) is a rare but serious disorder that can develop many years after strabismus surgery. It is generally treated with high-dose steroids or immunosuppression. We describe a patient with Varadi Papp syndrome and congenital fibrosis of the extraocular muscles, who developed surgically induced necrotizing scleritis a month after strabismus surgery and was successfully managed by oral vitamin C and topical N-acetylcysteine 10%. While SINS is conventionally treated with steroids/immunosuppression, a conservative approach may be tried in milder cases. The role of topical N-acetylcysteine in managing this complication needs to be explored.

LLE Review Quarterly Report (January-March 1999). Volume 78

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

Regan, Sean P.

1999-03-01

This volume of the LLE Review, covering the period January-March 1999, features two articles concerning issues relevant to 2-D SSD laser-beam smoothing on OMEGA. In the first article J. D. Zuegel and J. A. Marozas present the design of an efficient, bulk phase modulator operating at approximately 10.5 GHz, which can produce substantial phase-modulated bandwidth with modest microwave drive power. This modulator is the cornerstone of the 1-THz UV bandwidth operation planned for OMEGA this year. In the second article J. A. Marozas and J. H. Kelly describe a recently developed code -- Waasese -- that simulates the collective behaviormore » of the optical components in the SSD driver line. The measurable signatures predicted by the code greatly enhance the diagnostic capability of the SSD driver line. Other articles in this volume are titled: Hollow-Shell Implosion Studies on the 60-Beam, UC OMEGA Laser System; Simultaneous Measurements of Fuel Areal Density, Shell Areal Density, and Fuel Temperature in D 3He-Filled Imploding Capsules; The Design of Optical Pulse Shapes with an Aperture-Coupled-Stripline Pulse-Shaping System; Measurement Technique for Characterization of Rapidly Time- and Frequency-Varying Electronic Devices; and, Damage to Fused-Silica, Spatial-Filter Lenses on the OMEGA Laser System.« less

LLE Review Quarterly Report (October-December 2001). Volume 89

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

Donaldson, William R.

2001-12-01

This volume of the LLE Review, covering October-December 2001, features “Time-Integrated Light Images of OMEGA Implosions” by P. Morley and W. Seka (p. 1). E. Kowaluk initiated this project for aesthetic rather than scientific reasons when he began taking visible light photographs of imploding OMEGA targets. These beautiful images are used to communicate LLE’s mission to the general public. A closer examination of the images revealed a one-to-one correspondence between the bright spots in the image and each of the 60 laser beams. The intensity of the bright spots has been related to refraction and absorption in the plasma surroundingmore » the imploding target. These photographs are now proving to be the basis of a new laser-plasma interaction diagnostic. Other articles in this volume are titled the following: Analytical Model of Nonlinear, Single-Mode, Classical Rayleigh-Taylor Instability at Arbitrary Atwood Numbers; A High-Pass Phase Plate Design for OMEGA and the NIF; Advanced Tritium Recovery System; Establishing Links Between Single Gold Nanoparticles Buried Inside SiO 2 Thin Film and 351-nm Pulsed-Laser-Damage Morphology; Resistive Switching Dynamics in Current-Biased Y-Ba-Cu-O Microbridges Excited by Nanosecond Electrical Pulses; and, Properties of Amorphous Carbon Films.« less

Novel Measures of Volume Status and Cardiac Function in Traumatic Shock

DTIC Science & Technology

2016-06-01

cardio -protective, fluid-limited method of resuscitation. In addition to providing insight into fluid management and cardiac function, the data indicate... cardio -protective method of resuscitation. 8.0 REFERENCES 1. Marik PE, Monnet X, Teboul JL. Hemodynamic parameters to guide fluid therapy. Ann

LLE Review Quarterly Report (January-March 2002). Volume 90

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

Donaldson, William R.

2002-03-01

This volume of the LLE Review, covering January-March 2002, features “First Results from Cryogenic Target Implosions on OMEGA” by C. Stoeckl et al. (p. 49). This article describes initial results from direct-drive spherical cryogenic target implosions on the 60-beam OMEGA laser system. These experiments are part of the scientific base leading to direct-drive ignition implosions planned for the National Ignition Facility (NIF). Results shown include neutron yield, secondary-neutron and proton yields, the time of peak neutron emission, and both time-integrated and time-resolved x-ray images of the imploding core. The experimental values are compared with 1-D numerical simulations. The target withmore » an ice-layer nonuniformity of srms = 9 mm showed 30% of the 1-D predicted neutron yield. These initial results are encouraging for future cryogenic implosions on OMEGA and the NIF. Other articles in this issue are titled the following: Equation-of-State Measurements of Porous Materials on OMEGA: Numerical Modeling; Observations of Modulated Shock Waves in Solid Targets Driven by Spatially Modulated Laser Beams; Time-Dependent Electron Thermal Flux Inhibition in direct-Drive Laser Implosions; Precision Spectral Sculpting of Broadband FM Pulses Amplified in a Narrowband Medium; Electric-Field-Induced Motion of Polymer Cholesteric Liquid Crystal Flakes in a Moderately Conductive Fluid; and, Femtosecond Response of a Freestanding LT-GaAs Photoconductive Switch.« less

LLE Review 83, Quarterly Report

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

None

2000-12-01

This volume of the LLE Review, covering April-June 2000, features an article by F. J. Marshall, T. Ohki, D. McInnis, Z. Ninkov, and J. Carbone, who detail the conversion of the OMEGA time-integrated x-ray diagnostics to electronic readout using direct-detection x-ray cameras [charge-injection devices (CID's)]. Pinhole and x-ray microscope images are shown along with inferred calibration measurements of the CID cameras. Currently, the same cameras are being used to obtain x-ray spectra in a TIM-based spectrometer, extending their use to all time-integrated imaging and spectroscopic x-ray instruments used on OMEGA. Additional highlights of the research presented in this issue are:more » (1) V. A. Smalyuk, B. Yaakobi, F. J. Marshall, and D. D. Meyerhofer investigate the spatial structure of the temperature and density of target-shell plasmas at peak compression (stagnation). This is accomplished by examining the energy dependence of the x-ray emission using narrow-band x-ray filters and the known absorption properties of the shell dopant (Ti). (2) F. Sequin, C. K. Ll, D. G. Hicks, J. A. Frenje, K. M. Green, R. D. Petrasso, J. M. Soures, V. Yu. Glebov, C. Stoeckl, P. B. Radha, D. D. Meyerhofer, S. Roberts, C. Sorce, T. C. Sangster, M. D. Cable, S. Padalino, and K. Fletcher detail the physics and instrumentation used to obtain and interpret secondary D-{sup 3}He proton spectra from current gas-filled-target and future cryogenic-target experiments. Through a novel extension of existing charged-particle detection techniques with track detectors, the authors demonstrate the ability to obtain secondary proton spectra with increased sensitivity. (3) M. Guardelben, L. Ning, N. Jain, D. Battaglia, and K. Marshall compare the utility of a novel liquid-crystal-based, point-diffraction interferometer (LCPDI) with the commercial standard phase-shifting interferometer and conclude that the LCPDI is a viable low-cost alternative. (4) A. B. Shorey, S. D. Jacobs, W. I. Kordonski

Inducible knockdown of pregnancy-associated plasma protein-A gene expression in adult female mice extends life span.

PubMed

Bale, Laurie K; West, Sally A; Conover, Cheryl A

2017-08-01

Pregnancy-associated plasma protein-A (PAPP-A) knockout (KO) mice, generated through homologous recombination in embryonic stem cells, have a significantly increased lifespan compared to wild-type littermates. However, it is unknown whether this longevity advantage would pertain to PAPP-A gene deletion in adult animals. In the present study, we used tamoxifen (Tam)-inducible Cre recombinase-mediated excision of the floxed PAPP-A (fPAPP-A) gene in mice at 5 months of age. fPAPP-A mice, which were either positive (pos) or negative (neg) for Tam-Cre, received Tam treatment with quarterly boosters. Only female mice could be used with this experimental design. fPAPP-A/neg and fPAPP-A/pos mice had similar weights at the start of the experiment and showed equivalent weight gain. We found that fPAPP-A/pos mice had a significant extension of life span (P = 0.005). The median life span was increased by 21% for fPAPP-A/pos compared to fPAPP-A/neg mice. Analysis of mortality in life span quartiles indicated that the proportion of deaths of fPAPP-A/pos mice were lower than fPAPP-A/neg mice at young adult ages (P = 0.002 for 601-800 days) and higher than fPAPP-A/neg mice at older ages (P = 0.004 for >1000 days). Thus, survival curves and age-specific mortality indicate that female mice with knockdown of PAPP-A gene expression as adults have an extended healthy life span. © 2017 The Authors. Aging Cell published by the Anatomical Society and John Wiley & Sons Ltd.

Letter to the Editor: History and clinical implications of PAPP-A2 in human growth: When reflecting on idiopathic short stature leads to a specific and new diagnosis: Understanding the concept of "low IGF-I availability".

PubMed

Argente, Jesús; Pérez-Jurado, Luis A

2018-06-01

As a result of our publication of the first patients with short stature due to a mutation in the gene for PAPP-A2 the question, "Why did you continue to study these patients when they were not more than 2 SDS below normal?" has been proposed surprisingly frequently. We would like to communicate our opinions on why these patients were studied and share the experience on how this process took place. In addition, the choice of treatment is also discussed. We believe that this discovery process is a good example of good clinical practice and international collaboration. Copyright © 2018 Elsevier Ltd. All rights reserved.

Myocardial and Peripheral Ischemia Causes an Increase in Circulating Pregnancy-Associated Plasma Protein-A in Non-atherosclerotic, Non-heparinized Pigs.

PubMed

Steffensen, Lasse Bach; Poulsen, Christian Bo; Shim, Jeong; Bek, Marie; Jacobsen, Kevin; Conover, Cheryl A; Bentzon, Jacob Fog; Oxvig, Claus

2015-12-01

The usefulness of circulating pregnancy-associated plasma protein-A (PAPP-A) as a biomarker for acute coronary syndrome (ACS) is widely debated. We used the pig as a model to assess PAPP-A dynamics in the setting of myocardial ischemia. Induction of myocardial ischemia by ligation of the left anterior descending (LAD) coronary artery caused a systemic rise in PAPP-A. However, the ischemic myocardium was excluded as the source of PAPP-A. Interestingly, induction of ischemia in peripheral tissues by ligation of the left femoral artery caused a systemic rise in PAPP-A originating from the left hind limb. This is the first study to demonstrate PAPP-A elevations in the absence of atherosclerosis or heparin during myocardial ischemia. Our findings thus add to the current discussion of the usefulness of PAPP-A as a biomarker for ACS.

LLE Review Quarterly Report January - March 2012. Volume 130

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

Shvydky, Alex

2012-03-01

This volume of the LLE Review, covering January–March 2012, features “OMEGA Polar-Drive Target Designs,” by P. B. Radha, J. A. Marozas, F. J. Marshall, A. Shvydky, T. J. B. Collins, V. N. Goncharov, R. L. McCrory, P. W. McKenty, D. D. Meyerhofer, T. C. Sangster, and S. Skupsky. This article (p. 57) describes low-adiabat, cryogenic-deuterium–tritium, and warm-plastic-shell polar-drive (PD)–implosion designs for the OMEGA laser. The designs are at two different on-target laser intensities, each at a different in-flight aspect ratio (IFAR). The first design permits one to study implosion energetics and target performance closer to ignition-relevant intensities (7 X 10more » 14 W/cm 2 at the quarter-critical surface), where nonlocal heat conduction and laser–plasma interactions can play an important role, but at lower values of IFAR (~22). The second design permits one to study implosion energetics and target performance at a lower intensity (3 X 10 14 W/cm 2) but at higher IFAR (~32), where the shell instability can play an important role. The higher IFAR designs are accessible on the existing OMEGA Laser System only at lower intensities. Implosions at ignition-relevant intensities can be obtained only by reducing target radius, although only at smaller values of IFAR. Polar-drive geometry requires repointing the laser beams to improve shell symmetry. The higher-intensity designs optimize target performance by repointing beams to a lesser extent and compensate for the reduced equatorial drive by increasing beam energies for the repointed beams and using custom beam profiles that improve equatorial illumination at the expense of irradiation at higher latitudes. These designs will be studied when new phase plates for the OMEGA Laser System, corresponding to the smaller target radii and custom beam profiles, are obtained. Implosion results from the combined set of high-intensity and high-IFAR implosions should yield valuable data to validate models of laser

Oxidative Damage in Parkinson’s Disease.

DTIC Science & Technology

1999-10-01

with a monoclonal antibody column. Proc. Natl. Acad. Sei. USA 89:3375-3379; 1992. [34] Deegan , P.; Shigenaga, M. K.; Park, E. M.; Alperin, P. E...Malonate and MPTP Neurotoxicity Russell T Matthews,* Peter Klivenyi,* Gerald Mueller,* Lichuan Yang,* Marike Wermer,* Craig E. Thomas,t and M. Flint...Biochemicals (Wayland, MA). MDL 101,002 was generously supplied by Dr. Craig Thomas of Hoechst Marion Roussell. Male Sprague-Dawley rats (Charles River

Determination of lamivudine and zidovudine permeability using a different ex vivo method in Franz cells.

PubMed

Dezani, André Bersani; Pereira, Thaisa Marinho; Caffaro, Arthur Massabki; Reis, Juliana Mazza; Serra, Cristina Helena Dos Reis

2013-01-01

The major processes that control the absorption of orally administered drugs are dissolution and gastrointestinal permeation. These processes depend on two main properties: solubility and permeability. Based on these characteristics, the Biopharmaceutical Classification System (BCS) was proposed as a tool to assist in biowaiver and bioavailability prediction of drugs. The purpose of the present study was to evaluate the permeability of lamivudine (3TC) and zidovudine (AZT) using a different ex vivo method in Franz cells. A segment of jejunum was inserted in a Franz cells apparatus, in order to assess drug permeability in the apical-basolateral (A-B) and basolateral-apical (B-A) directions. Each drug was added to the donor chamber, collected from the acceptor chamber and analyzed by HPLC. Fluorescein (FLU) and metoprolol (METO) were used as low and high permeability markers, respectively. The apparent permeability (Papp) results for the A-B direction were: Papp FLU A-B=0.54×10(-4)cm·s(-1), Papp METO A-B=7.99×10(-4)cm·s(-1), Papp 3TC A-B=4.58×10(-4)cm·s(-1) and Papp AZT A-B=5.34×10(-4)cm·s(-1). For the B-A direction, the Papp results were: Papp FLU B-A=0.56×10(-4)cm·s(-1), Papp METO B-A=0.25×10(-4)cm·s(-1), Papp 3TC B-A=0.24×10(-4)cm·s(-1) and Papp AZT B-A=0.19×10(-4)cm·s(-1). For the A-B direction, the Papp results of fluorescein and metoprolol show low and high permeability, respectively, indicating that the membranes were appropriate for permeability studies. For the A-B direction, the Papp results of 3TC and AZT suggest that these antiretroviral drugs have permeability values close to metoprolol. Nevertheless, for the B-A direction the Papp results do not suggest efflux mechanism for any of the drugs. Thereby, the different ex vivo methods using Franz cells can be successfully applied in drug permeability studies, in particular for drug biopharmaceutical classification. Copyright © 2013 Elsevier Inc. All rights reserved.

Stanniocalcin-2 overexpression reduces atherosclerosis in hypercholesterolemic mice.

PubMed

Steffensen, Lasse B; Conover, Cheryl A; Bjørklund, Martin M; Ledet, Thomas; Bentzon, Jacob F; Oxvig, Claus

2016-05-01

The metalloproteinase pregnancy-associated plasma protein-A (PAPP-A) has been suggested as a proatherogenic molecule by its ability to locally increase insulin-like growth factor signaling. Stanniocalcin-2 (STC2) was recently discovered to be a potent inhibitor of PAPP-A activity, but has not previously been implicated in vascular disease. The aim of this study was to substantiate the interaction between PAPP-A and STC2 as a potential local regulatory mechanism in the artery wall. We found that PAPP-A is secreted from cultured primary smooth muscle cells obtained from human aortas as a covalent complex with STC2, devoid of proteolytic activity. Extracts of human carotid atherosclerotic plaques contain both complexed and uncomplexed PAPP-A, and we show by immunohistochemistry that PAPP-A and STC2 are present in the tissue throughout early human lesion development. We then used adeno-associated virus-mediated expression of STC2 to increase the fraction of PAPP-A present in the inhibited state and found that it decreased the development of atherosclerosis by 47% (P = 0.0005) in apolipoprotein E-deficient mice challenged with a Western type diet compared to controls. This study is the first to suggest the involvement of STC2 in regulating PAPP-A activity during the development of atherosclerosis. Furthermore, we demonstrate that lesion development can be inhibited in an experimental model by driving the balance towards inhibited PAPP-A. Copyright © 2016 Elsevier Ireland Ltd. All rights reserved.

Pregnancy Associated Plasma Protein-A and Placental Growth Factor in a Sub-Saharan African Population: A Nested Cross-Sectional Study

PubMed Central

Klipstein-Grobusch, Kerstin; Koster, Maria P. H.; Ramamoorthy, Dhivya; Antwi, Edward; Belmouden, Idder; Franx, Arie; Grobbee, Diederick E.; Schielen, Peter C. J. I.

2016-01-01

Background Baseline distributions of pregnancy disorders’ biomarkers PlGF and PAPP-A levels are primarily based on Western European populations of Caucasian ethnicity. Differences in PAPP-A and PlGF concentrations by ethnicity have been observed, with increased levels in Afro-Caribbean, East Asian, and South Asian women. Baseline concentrations of sub-Saharan African women have not been evaluated. Objectives To investigate PlGF and PAPP-A in a sub-Saharan African population and assess the performance of existing reference values of PAPP-A and PlGF. Methods A nested cross-sectional study was conducted in two public hospitals in Accra, Ghana. Out of the original 1010 women enrolled in the cohort, 398 participants were eligible for inclusion with a normotensive singleton gestation and serum samples taken between 56–97 days of pregnancy. PAPP-A and PlGF concentrations were measured with an automated immunoassay. Multiple of the median (MoM) values corrected for gestation and maternal weight for PAPP-A and PlGF were calculated using reference values of a Dutch perinatal screening laboratory based on over 10.000 samples, and PlGF manufacturer reference values, respectively. Results The PAPP-A median MoM was 2.34 (interquartile range (IQR) 1.24–3.97). Median PlGF MoM was 1.25 (IQR 0.95–1.80). Median MoM values for PAPP-A and PlGF tended to be slightly different for various Ghanaian ethnic subgroups. Conclusions PAPP-A and PlGF MoM values appear to be substantially higher in a sub-Saharan African population compared to the Caucasian or Afro-Caribbean MoM values previously reported. The difference suggests the need for a specific correction factor for this population to avoid underestimation of risk for fetal aneuploidies or placental disorders when using PAPP-A and PlGF MoM for screening purposes. PMID:27532602

Serum pregnancy-associated plasma protein A levels in the first, second and third trimester of pregnancy: relation to newborn anthropometric parameters and maternal tobacco smoking.

PubMed

Chełchowska, Magdalena; Gajewska, Joanna; Mazur, Joanna; Ambroszkiewicz, Jadwiga; Maciejewski, Tomasz M; Leibschang, Jerzy

2016-12-01

The purpose of this study was to evaluate the associations of the first, second and third trimester serum pregnancy-associated plasma protein A (PAPP-A) concentrations with neonatal anthropometric parameters. The effect of tobacco smoking during pregnancy on PAPP-A level was also studied. One hundred and fifty healthy pregnant women were divided into smoking and tobacco-abstinent groups. Serum PAPP-A level was measured with the KRYPTOR rapid random-access immunoassay analyzer. The relationship between PAPP-A and newborn related outcome as well as markers of estimated intensity of cigarette smoking was evaluated by univariate and multivariate linear regression. Pregnancy-associated plasma protein A concentration was positively correlated with birth weight in the first (β = 31.6; p < 0.001), second (β = 10.6; p < 0.05), and third (β = 4.6; p < 0.001) trimester of gestation. A significant association between PAPP-A and birth body length and head circumference in the second (β = 0.02; p < 0.05) and third trimester (β = 0.01; p < 0.01) was also found. The serum PAPP-A levels were significantly lower in the smoking than in the tobacco-abstinent group in each trimester of pregnancy ( p < 0.001). The largest impact of the number of cigarettes smoked per day on PAPP-A level was found in the second (β = -1.2; p = 0.004) and third trimester (β = -2.6; p = 0.001). Maternal serum PAPP-A levels during gestation might be significant predictors for birth weight. Increased PAPP-A concentrations in the second and third trimester appeared to also be predictive for newborn body length and head circumference. Smoking alters maternal PAPP-A levels in all trimesters, with the greatest impact related to the number of cigarettes smoked per day.

Association between serum pregnancy-associated plasma protein-A and bicarbonate in hemodialysis patients.

PubMed

Bicik, Zerrin; Coskun, Abdurrahman; Serteser, Mustafa; Bulur, Atilla; Mese, Meral; Unsal, Ibrahim

2014-03-01

Acidosis is associated with protein-energy malnutrition, inflammation, and bone disease, and low bicarbonate levels have been implicated in higher mortality rates in chronic kidney disease. Recently, the concentration of serum pregnancy-associated plasma protein-A (PAPP-A) has become accepted as a prognostic marker in hemodialysis patients. This study determined the relationship between PAPP-A and bicarbonate levels in these patients. The study enrolled 65 hemodialysis patients (41 males, 24 females) and 26 control subjects (11 males, 15 females). Serum PAPP-A, intact parathormone (iPTH), calcium, phosphorus (P), and bicarbonate levels were measured. Correlations between PAPP-A and bicarbonate, iPTH, calcium, and phosphorus were evaluated. Median PAPP-A levels were significantly higher in hemodialysis patients [15.1 (<0.03-158.8) ng/ml] than in control subjects [6.6 (<0.03-16.4) ng/ml] (P < 0.05). There were statistically significant correlations between serum PAPP-A and bicarbonate, iPTH, and P in hemodialysis patients but not in control subjects. Elevation of serum PAPP-A has been found in hemodialysis patients and its significant correlation with bicarbonate suggests that it may be a prognostic factor. © 2014 Wiley Periodicals, Inc.

Maternal serum placental growth factor and pregnancy-associated plasma protein A measured in the first trimester as parameters of subsequent pre-eclampsia and small-for-gestational-age infants: A prospective observational study

PubMed Central

Sung, Kyung Uk; Roh, Jeong A; Eoh, Kyung Jin

2017-01-01

Objective To examine the first-trimester maternal serum placental growth factor (PlGF) and pregnancy-associated plasma protein A (PAPP-A) levels in pregnancies associated with pre-eclampsia (PE) or small-for-gestational-age (SGA) infants, and determine the predictive accuracy of PlGF and of PAPP-A for either PE or SGA infants. Methods This prospective, observational study included 175 pregnant women, and of these women, due to participant withdrawal or loss to follow-up, delivery data were collected from the medical records of 155 women, including 4 who had twin pregnancies. The women's maternal history was recorded, and the PlGF and PAPP-A levels at 11 to 13 gestational weeks were measured. During the second trimester, the maternal uterine artery's systolic/diastolic ratio was measured. Multiples of the median (MoM) of PlGF and PAPP-A were determined, and the associations of these values with the risk factors of SGA and PE were evaluated. Logistic regression analysis was used to determine whether PlGF and PAPP-A are useful markers for predicting SGA infants. Results The PAPP-A MoM level was significantly lower in women with advanced maternal age, multipara women, and women with gestational diabetes than in their counterparts. The PlGF and PAPP-A MoM levels were higher in women with a twin pregnancy than in those with a singleton pregnancy. There was a significant relationship between the maternal serum PAPP-A MoM level in the first trimester and the uterine artery systolic/diastolic ratio in the second trimester. Results of logistic regression analysis showed that low PlGF and PAPP-A MoM levels were predictors of SGA infants (odds ratio, 0.143; 95% confidence interval, 0.025 to 0.806; odds ratio, 0.191; 95% confidence interval, 0.051 to 0.718, respectively). Conclusion PlGF and PAPP-A are potentially useful as first-trimester markers for SGA infants and some hypertensive disorders of pregnancy. PMID:28344956

Pregnancy-associated plasma protein-A modulates the anabolic effects of parathyroid hormone in mouse bone.

PubMed

Clifton, Kari B; Conover, Cheryl A

2015-12-01

Intermittent parathyroid hormone (PTH) is a potent anabolic therapy for bone, and several studies have implicated local insulin-like growth factor (IGF) signaling in mediating this effect. The IGF system is complex and includes ligands and receptors, as well as IGF binding proteins (IGFBPs) and IGFBP proteases. Pregnancy-associated plasma protein-A (PAPP-A) is a metalloprotease expressed by osteoblasts in vitro that has been shown to enhance local IGF action through cleavage of inhibitory IGFBP-4. This study was set up to test two specific hypotheses: 1) Intermittent PTH treatment increases the expression of IGF-I, IGFBP-4 and PAPP-A in bone in vivo, thereby increasing local IGF activity. 2) In the absence of PAPP-A, local IGF activity and the anabolic effects of PTH on bone are reduced. Wild-type (WT) and PAPP-A knock-out (KO) mice were treated with 80 μg/kg human PTH 1-34 or vehicle by subcutaneous injection five days per week for six weeks. IGF-I, IGFBP-4 and PAPP-A mRNA expression in bone were significantly increased in response to PTH treatment. PTH treatment of WT mice, but not PAPP-A KO mice, significantly increased expression of an IGF-responsive gene. Bone mineral density (BMD), as measured by DEXA, was significantly decreased in femurs of PAPP-A KO compared to WT mice with PTH treatment. Volumetric BMD, as measured by pQCT, was significantly decreased in femoral midshaft (primarily cortical bone), but not metaphysis (primarily trabecular bone), of PAPP-A KO compared to WT mice with PTH treatment. These data suggest that stimulation of PAPP-A expression by intermittent PTH treatment contributes to PTH bone anabolism in mice. Copyright © 2015 Elsevier Inc. All rights reserved.

A sensitive time-resolved fluoroimmunoassay for determination of median levels of pregnancy-associated plasma protein a in pregnant women in China.

PubMed

Yu, Ting; Gao, Shangxian; Yin, Aihua; Tang, Yongping; Wu, Yingsong; Li, Lili; Li, Ming

2013-01-01

Pregnancy-associated plasma protein A (PAPP-A) is an important serum marker for first trimester screening. Its weekly median value varies with ethnicity. A one-step time-resolved fluoroimmunoassay (TRFIA) using two monoclonal antibodies against PAPP-A with Eu(3+) chelates as labels has been developed. Using the assay described here, we evaluated 5,301 normal serum samples from Chinese women at 7-13 weeks of gestation. The detection limit using this assay was 1.2 mIU/L, and the maximum detection range was up to 10,000 mIU/L. The intra-assay and inter-assay coefficients of variation were <3.0% and <5.0%, respectively, and the mean recovery rate was 98.0%. PAPP-A concentrations measured in 516 maternal serum samples correlated well with those obtained by Dissociation-Enhanced Lanthanide Fluorescent Immunoassay (DELFIA) PAPP-A assay (r=0.988, P<0.001). The medians for 7-13 weeks of maternal serum PAPP-A were higher in the women from China compared to reports from other countries. The present assay possesses accuracy and high sensitivity and exhibits great potential for the clinical analysis of PAPP-A. Our investigation on the median concentrations of PAPP-A will help establish reference values that are specific for China and study the importance of ethnic factors in biochemical screening.

Pregnancy-associated plasma protein-A is a stronger predictor for adverse cardiovascular outcomes after acute coronary syndrome in type-2 diabetes mellitus.

PubMed

Li, Wei-Ping; Neradilek, Moni B; Gu, Fu-Sheng; Isquith, Daniel A; Sun, Zhi-Jun; Wu, Xing; Li, Hong-Wei; Zhao, Xue-Qiao

2017-04-05

The risk prediction of pregnancy-associated plasma protein-A (PAPP-A) for future cardiovascular (CV) events post acute coronary syndrome (ACS) in patients with type-2 diabetes mellitus (T2DM) was investigated in comparison to other risk factors. PAPP-A was measured at hospital admission in 320 consecutive ACS patients (136 with T2DM and 184 without). All patients were followed for 2 years for occurrence of CV death, non-fatal MI or stroke. Effect of PAPP-A on the CV event risk was estimated using Cox regression models. Receiver operating characteristics (ROC) curves were generated to demonstrate the sensitivity and specificity of PAPP-A in predicting CV events. ACS patients with T2DM had higher PAPP-A (19.29 ± 16.36 vs. 13.29 ± 13.90 ng/ml, p < 0.001) and higher rate of CV events 2 years post ACS (27.2 vs. 13.6%, p = 0.002) than those without. Higher levels of PAPP-A were significantly associated with increased risk of CV events during 2-year follow-up [HR = 2.97 for 1 SD increase in log 10 (PAPP-A), 95% CI 2.11-4.18, p < 0.001] in T2DM and (HR = 3.16, 95% CI 2.27-4.39, p < 0.001) in non-T2DM. Among patients with T2DM, PAPP-A showed a larger area under the curve (AUC 0.79) that was significantly more predictive than hsCRP (AUC 0.64), eGFR (AUC 0.66) and LVEF < 50% (AUC 0.52); predictive ability did not improve significantly by including those factors into the model. Patients with T2DM had higher levels of PAPP-A and increased risk of CV events. Elevated PAPP-A compared to other risk factors was a stronger predictor for future CV events 2 years post ACS in patients with T2DM. Trial registration ISRCTN10805074. Registered on 20 January 2017, retrospectively registered.

Oral toxicity of p-aminopropiophenone to brushtail possums (Trichosurus vulpecula), dama wallabies (Macropus eugenii), and mallards (Anas platyrhynchos).

PubMed

Fisher, P; O'Connor, C E; Morriss, G

2008-07-01

Development of p-aminopropiophenone (PAPP) as a toxicant for pest predator management in New Zealand and Australia prompted investigation of its toxicity to potential nontarget species. Acute oral toxicity of PAPP in brushtail possums (Trichosurus vulpecula), dama wallabies (Macropus eugenii), and Mallards (Anas platyrhynchos) was estimated in pen trials, carried out between February 2000 and September 2001. The susceptibility of possums (LD50>or=500 mg kg(-1)) and wallabies (LD50 89 mg kg(-1)) to PAPP was low in comparison to noncarnivorous placental mammal species, but ducks (LD50 38 mg kg(-1)) were more susceptible than other bird species. These results suggest that the nontarget hazard to possums and wallabies from PAPP bait applied for pest predator control would be low. However, future development of PAPP as a vertebrate pest control agent should include rigorous assessments of the hazard posed by bait formulations to bird species and provision for delivery techniques that could mitigate exposure of nontarget birds.

Pregnancy-Associated Plasma Protein A Levels in Late First Trimester Pregnancies with Small-for-Gestational Age Neonates: A Prospective Case-Control Study.

PubMed

Agarwal, Rachna; Kumari, Radhika; Mehndiratta, Mohit; Radhakrishnan, Gita; Faridi, M M A; Chandra, Nilesh

2017-08-01

We aimed to investigate the association of pregnancy associated plasma protein A (PAPP-A) levels in late first trimester with small for gestational age (SGA) neonates and adverse pregnancy outcomes in a low-income setting. The inclusion criteria were late first trimester (11-13 + 6 weeks) women with singleton and non-anomalous pregnancy. Enrolled participants were sampled for PAPP-A and prospectively followed up for delivery outcome and antenatal complications. A multiple of median (MoM) was calculated and statistically compared between groups. Out of total 284 subjects, 14.54% delivered SGA babies and formed cases (Group A), 66.5% delivered appropriate for gestational age (AGA) neonates with uneventful antenatal period (controls, Group B), and 19.3% were AGA group with adverse pregnancy complications (Group C). The late first trimester median PAPP-A MoM was significantly lower (0.61) in Group A compared to Group B (1.47). Using receiver operating characteristic (ROC) curve for PAPP-A MoM, optimal cutoff value was found at 0.45 MoM, with positive predictive value of 56.2%, specificity of 92.6% and sensitivity of 45%. The median interquartile range (IQR) of PAPP-A MoM value in Group C in comparison with Group B was significantly lower except for abruption. At PAPP-A MoM cutoff value <1, <0.8, <0.6 and <0.4, the odds ratio for adverse pregnancy outcome was 8.30, 7.29, 10.97 and 10.60, respectively, indicating an inverse relationship. With 0.45 MoM cutoff of PAPP-A, the detection rate, specificity and positive predictive value for SGA were 45, 92.6 and 56.2%, respectively. As PAPP-A MoM values decreased, the odds ratio of having adverse pregnancy outcomes increased.

Development of a new humane toxin for predator control in New Zealand.

PubMed

Eason, Charles T; Murphy, Elaine C; Hix, Steve; Macmorran, Duncan B

2010-03-01

The endemic fauna of New Zealand evolved in the absence of mammalian predators and their introduction has been responsible for many extinctions and declines. Introduced species including possums (Trichosurus vulpecula Kerr), ship rats (Rattus rattus L.) and stoats (Mustela erminea L.) are targeted to protect native birds. Control methodologies currently rely largely on labor-intensive trapping or the use of increasingly unpopular poisons, or poisons that are linked with low welfare standards. Hence, the development of safer humane predator toxins and delivery systems is highly desirable. Para-aminopropiophenone (PAPP) is being developed as a toxin for feral cats (Felis catus L.) and stoats. Carnivores appear to be much more susceptible to PAPP than birds, so it potentially has high target specificity, at least in New Zealand. Pen trials with 20 feral cats and 15 stoats have been undertaken using meat baits containing a proprietary formulation of PAPP. A PAPP dose of 20-34 mg kg(-1) was lethal for feral cats and 37-95 mg kg(-1) was lethal for stoats. Our assessments suggest that PAPP, for the control of feral cats and stoats, is a humane and effective toxin. PAPP causes methaemoglobinaemia, resulting in central nervous system anoxia, lethargy and death. © 2010 ISZS, Blackwell Publishing and IOZ/CAS.

Longitudinal changes in C-reactive protein, proform of eosinophil major basic protein, and pregnancy-associated plasma protein-A during weight changes in obese children.

PubMed

Lausten-Thomsen, Ulrik; Gamborg, Michael; Bøjsøe, Christine; Hedley, Paula L; Hagen, Christian Munch; Christiansen, Michael; Holm, Jens-Christian

2015-03-01

Childhood obesity is associated with several complications, including cardiovascular comorbidity. Several biomarkers, such as high-sensitive C-reactive protein (hs-CRP), proform of eosinophil major basic protein (Pro-MBP) and pregnancy associated plasma protein-A (PAPP-A), have equally been linked to increased cardiovascular susceptibility. This study investigates these biomarkers during weight loss and regain in obese children. A longitudinal study during a 12-week weight loss program with a 28 months follow-up was conducted. Anthropometrics and plasma concentrations of hs-CRP, Pro-MBP, and PAPP-A were measured at baseline; at days 14, 33 and 82 during weight loss; and at months 10, 16, and 28 during follow-up. Fifty-three boys and 62 girls aged 8-15 years with a median body mass index (BMI) standard deviation score (SDS) at baseline of 2.78 (boys), and 2.70 (girls) were included. Ninety children completed the weight loss program and 68 children entered the follow-up program. Pro-MBP and PAPP-A, but not hs-CRP, exhibited individual-specific levels (tracking) during weight loss and regain. The PAPP-A/Pro-MBP correlation was strong, whereas the hs-CRP/PAPP-A correlation was weak during weight fluctuations. Hs-CRP changes reflect weight changes. PAPP-A and Pro-MBP exhibited tracking during weight perturbations and may contribute as early risk markers of cardiovascular susceptibility.

Unfallaufnahme und Datenerhebung

NASA Astrophysics Data System (ADS)

Brösdorf, Klaus-Dieter; Moser, Andreas; Burg, Jürgen

Unfälle ereignen sich in unterschiedlichen Schweregraden. Man unterscheidet zwischen Unfälle mit nur Sachschaden und in Unfälle mit Personenschaden. Gemäß Statistik [1] machten in Deutschland im Jahr 2005 Unfälle mit Personenschaden (336.619) etwa 15 % der Gesamtanzahl der polizeilich erfassten Unfälle (2.253.992) aus. In den amtlichen Statistiken sind nur polizeilich erfasste Unfälle enthalten. Eine größere Zahl von Unfällen, insbesondere leichtere Unfälle, wird offensichtlich polizeilich nicht gemeldet. Mit den Daten der Versicherungswirtschaft wird die Anzahl der Kfz-Schäden pro Jahr in Deutschland mit 8.673.000 angegeben [2].

Disruption of insulin-like growth factor-II imprinting during embryonic development rescues the dwarf phenotype of mice null for pregnancy-associated plasma protein-A.

PubMed

Bale, Laurie K; Conover, Cheryl A

2005-08-01

Pregnancy-associated plasma protein-A (PAPP-A), an insulin-like growth factor-binding protein (IGFBP) protease, increases insulin-like growth factor (IGF) activity through cleavage of inhibitory IGFBP-4 and the consequent release of IGF peptide for receptor activation. Mice homozygous for targeted disruption of the PAPP-A gene are born as proportional dwarfs and exhibit retarded bone ossification during fetal development. Phenotype and in vitro data support a model in which decreased IGF-II bioavailability during embryogenesis results in growth retardation and reduction in overall body size. To test the hypothesis that an increase in IGF-II during embryogenesis would overcome the growth deficiencies, PAPP-A-null mice were crossed with DeltaH19 mutant mice, which have increased IGF-II expression and fetal overgrowth due to disruption of IgfII imprinting. DeltaH19 mutant mice were 126% and PAPP-A-null mice were 74% the size of controls at birth. These size differences were evident at embryonic day 16.5. Importantly, double mutants were indistinguishable from controls both in terms of size and skeletal development. Body size programmed during embryo development persisted post-natally. Thus, disruption of IgfII imprinting and consequent elevation in IGF-II during fetal development was associated with rescue of the dwarf phenotype and ossification defects of PAPP-A-null mice. These data provide strong genetic evidence that PAPP-A plays an essential role in determining IGF-II bioavailability for optimal fetal growth and development.

A role for a lithium-inhibited Golgi nucleotidase in skeletal development and sulfation

PubMed Central

Frederick, Joshua P.; Tafari, A. Tsahai; Wu, Sheue-Mei; Megosh, Louis C.; Chiou, Shean-Tai; Irving, Ryan P.; York, John D.

2008-01-01

Sulfation is an important biological process that modulates the function of numerous molecules. It is directly mediated by cytosolic and Golgi sulfotransferases, which use 3′-phosphoadenosine 5′-phosphosulfate to produce sulfated acceptors and 3′-phosphoadenosine 5′-phosphate (PAP). Here, we identify a Golgi-resident PAP 3′-phosphatase (gPAPP) and demonstrate that its activity is potently inhibited by lithium in vitro. The inactivation of gPAPP in mice led to neonatal lethality, lung abnormalities resembling atelectasis, and dwarfism characterized by aberrant cartilage morphology. The phenotypic similarities of gPAPP mutant mice to chondrodysplastic models harboring mutations within components of the sulfation pathway lead to the discovery of undersulfated chondroitin in the absence of functional enzyme. Additionally, we observed loss of gPAPP leads to perturbations in the levels of heparan sulfate species in lung tissue and whole embryos. Our data are consistent with a model that clearance of the nucleotide product of sulfotransferases within the Golgi plays an important role in glycosaminoglycan sulfation, provide a unique genetic basis for chondrodysplasia, and define a function for gPAPP in the formation of skeletal elements derived through endochondral ossification. PMID:18695242

Stanniocalcin-2 Inhibits Mammalian Growth by Proteolytic Inhibition of the Insulin-like Growth Factor Axis*

PubMed Central

Jepsen, Malene R.; Kløverpris, Søren; Mikkelsen, Jakob H.; Pedersen, Josefine H.; Füchtbauer, Ernst-Martin; Laursen, Lisbeth S.; Oxvig, Claus

2015-01-01

Mammalian stanniocalcin-2 (STC2) is a secreted polypeptide widely expressed in developing and adult tissues. However, although transgenic expression in mice is known to cause severe dwarfism, and targeted deletion of STC2 causes increased postnatal growth, its precise biological role is still unknown. We found that STC2 potently inhibits the proteolytic activity of the growth-promoting metalloproteinase, pregnancy-associated plasma protein-A (PAPP-A). Proteolytic inhibition requires covalent binding of STC2 to PAPP-A and is mediated by a disulfide bond, which involves Cys-120 of STC2. Binding of STC2 prevents PAPP-A cleavage of insulin-like growth factor-binding protein (IGFBP)-4 and hence release within tissues of bioactive IGF, required for normal growth. Concordantly, we show that STC2 efficiently inhibits PAPP-A-mediated IGF receptor signaling in vitro and that transgenic mice expressing a mutated variant of STC2, STC2(C120A), which is unable to inhibit PAPP-A, grow like wild-type mice. Our work identifies STC2 as a novel proteinase inhibitor and a previously unrecognized extracellular component of the IGF system. PMID:25533459

Ketoconazole and the modulation of multidrug resistance-mediated transport in Caco-2 and MDCKII-MDR1 drug transport models.

PubMed

Fan, Y; Rodriguez-Proteau, R

2008-02-01

The hypothesis tested was that ketoconazole can modulate P-glycoprotein, thereby altering cellular uptake and apparent permeability (P(app)) of multidrug-resistant substrates, such as cyclosporin A (CSA) and digoxin, across Caco-2, MDCKII-MDR1, and MDCKII wild-type cell transport models. (3)H-CSA/(3)H-digoxin transport experiments were performed with and without co-exposure to ketoconazole, and (3)H-ketoconzole transport experiments were performed with and without co-exposure to dietary flavonoids, epigallocatechin-3-gallate, and xanthohumol. Ketoconazole (3 microM) reduced the P(app) efflux of CSA and digoxin from 5.07 x 10(-6) to 2.91 x 10(-6) cm s(-1) and from 2.60 x 10(-6) to 1.41 x 10(-6) cm s(-1), respectively, in Caco-2 cells. In the MDCKII-MDR1 cells, ketoconazole reduced the P(app) efflux of CSA and increased the P(app) absorption of digoxin. Cellular uptake of ketoconazole in the Caco-2 cells was significantly inhibited by CSA and digoxin, whereas epigallocatechin-3-gallate and xanthohumol exhibited biphasic responses. In conclusion, ketoconazole modulates the P(app) of P-glycoprotein substrates by interacting with MDR1 protein. Epigallocatechin-3-gallate and xanthohumol modulate the transport and uptake of ketoconazole.

Maternal serum placental growth factor (PlGF) in small for gestational age pregnancy at 11(+0) to 13(+6) weeks of gestation.

PubMed

Poon, Leona C Y; Zaragoza, Edgar; Akolekar, Ranjit; Anagnostopoulos, Evangelos; Nicolaides, Kypros H

2008-12-01

To investigate the pathogenesis of pregnancies delivering small for gestational age (SGA) neonates by examining biochemical and Doppler indices of placental development during the first trimester of pregnancy. The concentration of placental growth factor (PlGF) at 11(+0)-13(+6) weeks was measured in 296 cases, which delivered SGA neonates, and 609 controls. The newborn was considered to be SGA if the birth weight was less than the fifth percentile after correction for gestation at delivery and sex, maternal racial origin, weight, height and parity. The distributions of uterine artery pulsatility index (PI), PlGF and PAPP-A, expressed in multiples of the median (MoM), in the control and SGA groups were compared. Logistic regression analysis was used to determine if significant contribution is provided by maternal factors, PlGF, PAPP-A and uterine artery PI in predicting SGA. The median PlGF (0.900 MoM) and PAPP-A (0.778 MoM) were lower and uterine artery PI was higher (1.087 MoM) in the SGA group than in the controls (PlGF: 0.991 MoM; PAPP-A: 1.070 MoM; uterine artery PI: 1.030 MoM). In the SGA group there was a significant association between PlGF and PAPP-A (r = 0.368, p < 0.0001) and uterine artery PI (r = 0.191, p = 0.001). Significant contributions for the prediction of SGA were provided by maternal factors, PlGF and PAPP-A and with combined screening the detection rate was 27% at a false-positive rate of 5%. Birth weight is predetermined by placental development during the first trimester of pregnancy. Copyright (c) 2008 John Wiley & Sons, Ltd.

Regional Morphology and Transport of PAMAM Dendrimers Across Isolated Rat Intestinal Tissue.

PubMed

Hubbard, Dallin; Bond, Tanner; Ghandehari, Hamidreza

2015-12-01

Intestinal permeability of PAMAM dendrimers has been observed, giving rationale for their use in oral drug delivery as potential carriers of associated molecules. This study assessed the apparent permeability coefficients (Papp) of dendrimers across isolated rat intestinal regional mucosae, along with estimation of the maximum non-toxic concentration. Caco-2 monolayers were also used to assess the comparative Papp values between isolated mucosae and cell culture models. Concentrations from 0.1 to 10 mM of anionic and cationic dendrimers were tested in mucosae to assess their Papp, membrane TEER, [(14)C]-mannitol Papp, and histology. 0.1 mM concentrations of dendrimers were assessed over 120 min in Caco-2 cell monolayers as concentrations above that were cytotoxic. Jejunal transport of dendrimers was higher than transport in colonic epithelium. Monolayer Papp values of dendrimers were comparable to those of jejunal mucosae. Mucosae exposed to dendrimer concentrations of 10 mM for 120 min caused significant reduction in TEER and changes in tissue morphology; however, G3.5 was the only analogue that caused significant TEER reduction and morphological changes at 1 mM concentrations. Transport in jejunal mucosae appears to be the greatest indicating that the small intestinal will be the most likely region to target for oral drug delivery using PAMAM dendrimers. © 2015 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

Developing a tissue-engineered neural-electrical relay using encapsulated neuronal constructs on conducting polymer fibers.

PubMed

Cullen, D Kacy; R Patel, Ankur; Doorish, John F; Smith, Douglas H; Pfister, Bryan J

2008-12-01

Neural-electrical interface platforms are being developed to extracellularly monitor neuronal population activity. Polyaniline-based electrically conducting polymer fibers are attractive substrates for sustained functional interfaces with neurons due to their flexibility, tailored geometry and controlled electro-conductive properties. In this study, we addressed the neurobiological considerations of utilizing small diameter (<400 microm) fibers consisting of a blend of electrically conductive polyaniline and polypropylene (PA-PP) as the backbone of encapsulated tissue-engineered neural-electrical relays. We devised new approaches to promote survival, adhesion and neurite outgrowth of primary dorsal root ganglion neurons on PA-PP fibers. We attained a greater than ten-fold increase in the density of viable neurons on fiber surfaces to approximately 700 neurons mm(-2) by manipulating surrounding surface charges to bias settling neuronal suspensions toward fibers coated with cell-adhesive ligands. This stark increase in neuronal density resulted in robust neuritic extension and network formation directly along the fibers. Additionally, we encapsulated these neuronal networks on PA-PP fibers using agarose to form a protective barrier while potentially facilitating network stability. Following encapsulation, the neuronal networks maintained integrity, high viability (>85%) and intimate adhesion to PA-PP fibers. These efforts accomplished key prerequisites for the establishment of functional electrical interfaces with neuronal populations using small diameter PA-PP fibers-specifically, improved neurocompatibility, high-density neuronal adhesion and neuritic network development directly on fiber surfaces.

Partitioning of light lithophile elements during basalt eruptions on Earth and application to Martian shergottites

NASA Astrophysics Data System (ADS)

Edmonds, Marie

2015-02-01

An enigmatic record of light lithophile element (LLE) zoning in pyroxenes in basaltic shergottite meteorites, whereby LLE concentrations decrease dramatically from the cores to the rims, has been interpreted as being due to partitioning of LLE into a hydrous vapor during magma ascent to the surface on Mars. These trends are used as evidence that Martian basaltic melts are water-rich (McSween et al., 2001). Lithium and boron are light lithophile elements (LLE) that partition into volcanic minerals and into vapor from silicate melts, making them potential tracers of degassing processes during magma ascent to the surface of Earth and of other planets. While LLE degassing behavior is relatively well understood for silica-rich melts, where water and LLE concentrations are relatively high, very little data exists for LLE abundance, heterogeneity and degassing in basaltic melts. The lack of data hampers interpretation of the trends in the shergottite meteorites. Through a geochemical study of LLE, volatile and trace elements in olivine-hosted melt inclusions from Kilauea Volcano, Hawaii, it can be demonstrated that lithium behaves similarly to the light to middle rare Earth elements during melting, magma mixing and fractionation. Considerable heterogeneity in lithium and boron is inherited from mantle-derived primary melts, which is dominant over the fractionation and degassing signal. Lithium and boron are only very weakly volatile in basaltic melt erupted from Kilauea Volcano, with vapor-melt partition coefficients <0.1. Degassing of LLE is further inhibited at high temperatures. Pyroxene and associated melt inclusion LLE concentrations from a range of volcanoes are used to quantify lithium pyroxene-melt partition coefficients, which correlate negatively with melt H2O content, ranging from 0.13 at low water contents to <0.08 at H2O contents >4 wt%. The observed terrestrial LLE partitioning behavior is extrapolated to Martian primitive melts through modeling. The zoning

Maternal serum pregnancy-associated plasma protein A and fetal nuchal translucency thickness for the prediction of fetal trisomies in early pregnancy.

PubMed

Brizot, M L; Snijders, R J; Bersinger, N A; Kuhn, P; Nicolaides, K H

1994-12-01

To determine if the risk for fetal trisomies during the first trimester of pregnancy can be derived by combining data from maternal serum pregnancy-associated plasma protein A (PAPP-A) and fetal nuchal translucency thickness. Pregnancy-associated plasma protein A was measured in samples from 87 singleton pregnancies with fetal chromosomal abnormalities (45 trisomy 21, 19 trisomy 18, eight trisomy 13, 11 sex chromosome aneuploidies, four triploidies) and 348 chromosomally normal controls at 10-13 weeks' gestation. Likelihood ratios for trisomies 21, 18, and 13 in relation to PAPP-A, in multiples of the normal median (MoM) for crown-rump length, were derived from the overlapping gaussian frequency distribution curves for normal and abnormal pregnancies. In the chromosomally normal group, maternal serum PAPP-A correlated significantly with fetal crown-rump length (r = 0.421, P < .0001). In the chromosomally abnormal group, the median PAPP-A was significantly lower than in the normal controls. The respective median values expressed in MoM for trisomies 21, 18, and 13 and other aneuploidies were 0.5 MoM (90% confidence interval [CI] 0.09-1.67, z = 6.0, P < .001), 0.17 MoM (90% CI 0.06-1.45, z = 6.6, P < .001), 0.25 MoM (90% CI 0.10-0.62, z = 4.5, P < .001), and 0.72 MoM (90% CI 0.09-2.48, z = 2.2, P < .05), respectively. There was no significant linear association between PAPP-A and fetal nuchal translucency thickness in either the chromosomally normal (r = -0.01, P = .89) or abnormal groups (r = -0.19, P = .08). The risks for fetal trisomies at 10-13 weeks' gestation can be derived by combining data on maternal age, maternal serum PAPP-A, and fetal nuchal translucency thickness.

Engineering of dendrimer surfaces to enhance transepithelial transport and reduce cytotoxicity.

PubMed

Jevprasesphant, Rachaneekorn; Penny, Jeffrey; Attwood, David; McKeown, Neil B; D'Emanuele, Antony

2003-10-01

To evaluate the cytotoxicity, permeation, and transport mechanisms of PAMAM dendrimers and surface-modified cationic PAMAM dendrimers using monolayers of the human colon adenocarcinoma cell line, Caco-2. Cytotoxicity was determined using the MTT assay. The effect of dendrimers on monolayer integrity was determined from measurements of transepithelial electrical resistance (TEER) and [14C]mannitol apparent permeability coefficient (Papp). The Papp of dendrimers through monolayers was measured in both the apical (A)-to-basolateral (B) and B --> A directions at 4 degrees C and 37 degrees C and also in the presence and absence of ethylenediamine tetraacetic acid (EDTA) and colchicine. The cytotoxicity and permeation of dendrimers increased with both concentration and generation. The cytotoxicity of cationic dendrimers (G2, G3, G4) was greater than that of anionic dendrimers (G2.5, G3.5) but was reduced by conjugation with lauroyl chloride: the least cytotoxic conjugates were those with six attached lauroyl chains. At 37 degrees C the Papp of cationic dendrimers was higher than that of anionic dendrimers and, in general, increased with the number of attached lipid chains. Cationic dendrimers decreased TEER and significantly increased the Papp of mannitol. Modified dendrimers also reduced TEER and caused a more marked increase in the Papp of mannitol. The Papp values of dendrimers and modified dendrimers were higher in the presence of EDTA, lower in the presence of colchicine, and lower at 4 degrees C than at 37 degrees C. The properties of dendrimers may be significantly modified by surface engineering. Conjugation of cationic PAMAM dendrimers with lauroyl chloride decreased their cytotoxicity and increased their permeation through Caco-2 cell monolayers. Both PAMAM dendrimers and lauroyl-PAMAM dendrimer conjugates can cross epithelial monolayers by paracellular and transcellular pathways.

Assessment of serum leptin, pregnancy-associated plasma protein A and CRP levels as indicators of plaque vulnerability in patients with acute coronary syndrome.

PubMed

Lodh, Moushumi; Goswami, Binita; Parida, Ashok; Patra, Surajeet; Saxena, Alpana

2012-07-01

A multifactorial aetiology of coronary artery disease (CAD) has been established in the recent past. Extensive research is now underway to understand the mechanisms responsible for plaque vulnerability. The identification of a novel biomarker that will help in the assessment of plaque status is urgently needed for the purpose of patient stratification and prognostication. The aim of the present study was to evaluate leptin, pregnancy-associated plasma protein A (PAPP-A) and C-reactive protein (CRP) levels in patients with acute coronary syndrome and to assess their diagnostic efficacy in the identification of vulnerable plaques. The study group comprised 105 patients who had chest pain along with ECG changes (ST elevation, ST depression, T inversion) and raised cardiac enzyme levels. Sixty-two patients with chest pain and ECG changes but with normal cardiac enzyme profiles were included in the control group. Lipid profiles, and leptin, PAPP-A and CRP levels were assessed in these two groups. Receiver operating characteristics (ROC) curves were plotted to determine the utility of the parameters under study as markers of plaque vulnerability. Significantly higher levels of serum lipoprotein (a), leptin, PAPP-A and high-sensitivity CRP (hs-CRP) were observed in the cases than in the controls. A positive correlation was observed between CRP and PAPP-A levels as well as CRP and leptin concentrations. ROC curve analysis revealed similar efficacies of CRP and PAPP-A levels in their ability to detect unstable plaques with areas under the curve of 0.762 and 0.732, respectively. Multivariate analysis established the superiority of hs-CRP as a predictor of plaque instability. Our study highlights the utility of both CRP and PAPP-A levels as determinants of plaque instability. Our findings necessitate population-based follow-up studies to establish the superiority of either of the two biomarkers in the field of preventive cardiology.

Editors' Fall Picks

ERIC Educational Resources Information Center

Heilbrun, Margaret; McCormack, Heather; Katterjohn, Anna; Kuzyk, Raya; Roncevic, Mirela; Fox, Bette-Lee; Hoffert, Barbara

2009-01-01

"Library Journal's" review editors select fall titles readers won't want to miss--"Waiting on a Train: The Embattled Future of Passenger Rail Service" (James McCommons); "Happy" (Alex Lemon); "Free for All: Joe Papp, the Public, and the Greatest Theater Story Ever Told" (Kenneth Turan & Joseph Papp); "In My Father's Shadow: A Daughter Remembers…

Associations of pregnancy-associated plasma protein-A level with essential hypertension and hypertensive disorders in pregnancy in Chinese population: a meta-analysis of 20 research studies involving 3332 individuals

PubMed Central

Cai, Gaojun; Zhang, Bifeng; Weng, Weijin; Yang, Liping; Shi, Ganwei; Xue, Sheliang; Fu, Xingli

2015-01-01

Objective To explore the associations between serum pregnancy-associated plasma protein-A (PAPP-A) level, and essential hypertension (EH) and hypertensive disorders in pregnancy (HDP) in Chinese population. Methods Pertinent studies were independently searched in PubMed, Embase, Cochrane Library, Chinese Biomedical Database (CBM), Wanfang databases and China National Knowledge Infrastructure (CNKI). The standardised mean difference (SMD) with 95% CIs was used to estimate the size of the effect. The subgroup analyses and meta-regression analysis were performed to identify the sources of heterogeneity among studies. Sensitivity analysis was conducted to assess the stability of the results. The publication bias between studies was examined by using Begg's funnel plots and Egger's test. Results A total of 20 studies involving 1493 patients and 1839 controls were included in the current meta-analysis. The PAPP-A level was significantly higher in EH patients than in controls (SMD=1.960, 95% CI 1.305 to 2.615, p<0.001), and significant associations were observed in all subgroups. The PAPP-A level was also significantly higher in HDP patients than in healthy pregnant women (SMD=2.249; 95% CI 1.324 to 3.173, p<0.001). The positive association between PAPP-A level and the risk of HDP was consistently observed in all subgroups except the subgroup with low NOS score. Conclusions The present meta-analysis suggests that an elevated PAPP-A level may be associated with susceptibilities to EH and HDP. PMID:26416511

Multivariate analysis identifies the estradiol level at ovulation triggering as an independent predictor of the first trimester pregnancy-associated plasma protein-A level in IVF/ICSI pregnancies.

PubMed

Giorgetti, C; Vanden Meerschaut, F; De Roo, C; Saunier, O; Quarello, E; Hairion, D; Penaranda, G; Chabert-Orsini, V; De Sutter, P

2013-10-01

Can independent predictors of pregnancy-associated plasma protein-A (PAPP-A) levels be identified in a group of women who conceived following IVF/ICSI? The significantly decreased PAPP-A level in IVF and ICSI pregnancies compared with non-IVF/ICSI pregnancies was correlated strongly with the serum estradiol (E2) level at ovulation triggering. The first trimester prenatal combined screening test for fetal aneuploidies in pregnancies conceived following assisted reproduction techniques (ART) is complicated by an alteration of the maternal biomarkers free β-hCG and PAPP-A, causing a higher false-positive rate compared with pregnancies which are conceived naturally. The use of controlled ovarian stimulation prior to IVF/ICSI is suggested to be the principle reason for these alterations of biomarkers in ART pregnancies. Between January 2010 and December 2011, 1474 women who conceived naturally and 374 women who conceived following IVF (n = 89), ICSI (n = 204) or intrauterine insemination (IUI, n = 81) were included in this retrospective study. Only singleton pregnancies were eligible for this study. For all women, serum analysis was performed in the same clinical laboratory. Measurement of nuchal translucency (NT) thickness was performed by four physicians belonging to the same infertility centre. First-trimester combined screening test of aneuploidy parameters (maternal age, PAPP-A and free β-hCG, NT thickness) were compared between non-ART and ART (IVF, ICSI and IUI) singleton pregnancies. Next, a minimal threshold E2 level at ovulation triggering was suggested for IVF/ICSI pregnancies above which the PAPP-A levels were significantly decreased compared with non-ART pregnancies. Finally, a multivariate analysis was performed to reveal independent predictors of PAPP-A level in IVF/ICSI pregnancies. We showed a decrease of the multiple of the median (MoM) PAPP-A level in IVF and ICSI singleton pregnancies compared with non-ART singleton pregnancies (P < 0.001), with Mo

Relationship between first trimester aneuploidy screening test serum analytes and placenta accreta.

PubMed

Büke, Barış; Akkaya, Hatice; Demir, Sibel; Sağol, Sermet; Şimşek, Deniz; Başol, Güneş; Barutçuoğlu, Burcu

2018-01-01

The aim of this study is to determine whether there is a relationship between first trimester serum pregnancy-associated plasma protein A (PAPP-A) and free beta human chorionic gonadotropin (fβhCG) MoM values and placenta accreta in women who had placenta previa. A total of 88 patients with placenta previa who had first trimester aneuploidy screening test results were enrolled in the study. Nineteen of these patients were also diagnosed with placenta accreta. As probable markers of excessive placental invasion, serum PAPP-A and fβhCG MoM values were compared in two groups with and without placenta accreta. Patients with placenta accreta had higher statistically significant serum PAPP-A (1.20 versus 0.865, respectively, p = 0.045) and fβhCG MoM (1.42 versus 0.93, respectively, p = 0.042) values than patients without accreta. Higher first trimester serum PAPP-A and fβhCG MoM values seem to be associated with placenta accreta in women with placenta previa. Further studies are needed to use these promising additional tools for early detection of placenta accreta.

Acute manic episode is associated with an increased risk of lower limb edema.

PubMed

Hochman, Eldar; Krivoy, Amir; Shoval, Gal; Valevski, Avi; Weizman, Abraham; Fischel, Tsvi

2013-12-02

Lower limb edema (LLE) was suggested to be associated with the use of psychotropic drugs among patients suffering from severe mental illnesses; however no direct mechanism was found. Therefore, we examined the association between the occurrence of LLE and acute untreated episode leading to hospitalization. A retrospective cross-sectional study was conducted using medical charts of 2529 patients admitted to Geha Mental Health Center between 2002 and 2012. Incident cases of LLE, demographic and clinical data were retrieved. Admission clinical status was modeled as three non-overlapping groups of patients: (i) Patients with a non-affective psychosis (NAP) episode (n = 1563), (ii) patients with a manic episode (n = 366), and (iii) patients with a depressive episode (n = 600). We performed a logistic regression analysis with LLE as the dependent variable controlling for the demographic and clinical variables that may be associated with LLE. LLE was diagnosed in 3.8% (n = 95) of the study population. The rate of LLE was 3-fold higher (χ(2) = 51.9, df = 2, p<0.001) in patients admitted with a manic episode (n = 38; 10.4%) compared to patients admitted with a NAP episode (n = 41; 2.6%) and patients admitted with a depressive episode (n = 16; 2.7%). Manic episode was associated with an increased risk for LLE compared to depressive episode (OR 8.72, 95% CI: 3.53-21.52, p<0.001) or NAP episode (OR 3.96, 95% CI: 2.16-7.26, p<0.001) after controlling for relevant confounders. Acute manic episode, leading to hospitalization, is associated with an increased risk of LLE, compared to NAP or depressive episode, suggesting causal relationship between mood and fluid imbalance. Yet, future prospective studies are needed to rule out the contribution of physical agitation and lithium treatment. © 2013.

Tricuspid insufficiency after laser lead extraction.

PubMed

Rodriguez, Yasser; Mesa, Julian; Arguelles, Eric; Carrillo, Roger G

2013-08-01

The use of laser lead extraction (LLE) to remove pacemaker and implantable cardiac defibrillator leads has become more prevalent in the past decade. Though the procedure is associated with a low rate of complications, LLE still poses some risks to patients. Some reports have suggested an increase in tricuspid insufficiency (TI) associated with LLE. We present a series of patients who underwent both LLE and complete evaluation for TI with echocardiographic techniques. From August 2008 to January 2010, 173 prospective, consecutive patients underwent LLE in a single center. All patients had transesophageal echocardiograms (TEE) during the extraction. Fifty-three patients had tricuspid valve function evaluated a day before the procedure with a transthoracic echocardiogram (TTE), during the procedure with a TEE and 2 days postoperatively with a TTE. All 173 patients experienced no change in tricuspid valve function during the procedure with TEE. Of the 53 patients who underwent a complete TI evaluation, 38 were males (72%) and 15 females (38%), with a mean age of 69.45 ± 14.08. Mean ejection fraction was 35.82 ± 14.72. Three (6%) patients experienced TI after the procedure (two mild and one severe, all with tricuspid valve endocarditis); 16 (30%) patients were found to have TI before LLE that returned to normal valve function during or after the procedure. Thirty-four (64%) patients did not experience any significant change of the tricuspid valve performance after LLE. LLE was not associated with increased TI. ©2013, The Authors. Journal compilation ©2013 Wiley Periodicals, Inc.

Associations of pregnancy-associated plasma protein-A level with essential hypertension and hypertensive disorders in pregnancy in Chinese population: a meta-analysis of 20 research studies involving 3332 individuals.

PubMed

Cai, Gaojun; Zhang, Bifeng; Weng, Weijin; Yang, Liping; Shi, Ganwei; Xue, Sheliang; Fu, Xingli

2015-09-28

To explore the associations between serum pregnancy-associated plasma protein-A (PAPP-A) level, and essential hypertension (EH) and hypertensive disorders in pregnancy (HDP) in Chinese population. Pertinent studies were independently searched in PubMed, Embase, Cochrane Library, Chinese Biomedical Database (CBM), Wanfang databases and China National Knowledge Infrastructure (CNKI). The standardised mean difference (SMD) with 95% CIs was used to estimate the size of the effect. The subgroup analyses and meta-regression analysis were performed to identify the sources of heterogeneity among studies. Sensitivity analysis was conducted to assess the stability of the results. The publication bias between studies was examined by using Begg's funnel plots and Egger's test. A total of 20 studies involving 1493 patients and 1839 controls were included in the current meta-analysis. The PAPP-A level was significantly higher in EH patients than in controls (SMD=1.960, 95% CI 1.305 to 2.615, p<0.001), and significant associations were observed in all subgroups. The PAPP-A level was also significantly higher in HDP patients than in healthy pregnant women (SMD=2.249; 95% CI 1.324 to 3.173, p<0.001). The positive association between PAPP-A level and the risk of HDP was consistently observed in all subgroups except the subgroup with low NOS score. The present meta-analysis suggests that an elevated PAPP-A level may be associated with susceptibilities to EH and HDP. Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to http://group.bmj.com/group/rights-licensing/permissions.

Preparation and characterization of poly(AA co PVP)/PGS composite and its application for methylene blue adsorption.

PubMed

Yang, Cai-xia; Lei, Lei; Zhou, Peng-xin; Zhang, Zhe; Lei, Zi-qiang

2015-04-01

Poly (AA co PVP)/PGS (PAPP) composite adsorbent was prepared by radical polymerization from Acrylic acid (AA), Polyvinylpyrrolidone (PVP) and Palygorskite (PGS), using N,N-methylenebisacrylamide (MBA) as cross-linker and potassium persulfate (KPS) as initiator. The PAPP was characterized with Fourier transform infrared (FT-IR), thermogravimetric analysis (TG), scanning electron microscope (SEM) and transmission electron microscopy (TEM). PAPP was used as adsorbent for the removal of methylene blue from aqueous solutions. The influences of pH, adsorption temperature and adsorption time on the adsorption properties of the composite to the dye were also investigated. Meanwhile, the adsorption rate data and adsorption equilibrium date were analyzed based on the pseudo-first-order and pseudo-second-order kinetic model, Langmuir and Freundlich isotherm models, respectively. The results indicating that the kinetic behavior better fit with the pseudo-second-order kinetic model. The maximum equilibrium adsorption capacity (q(m)) is 1815 mg/g at 289 K. The isotherm behavior can be explained by the Langmuir isotherm models. The activation energy was also evaluated for the removal of methylene blue onto PAPP. These results demonstrate that this composite material could be used as a good adsorbent for the removal of cationic dyes from wastewater. Copyright © 2014 Elsevier Inc. All rights reserved.

Prenatal and perinatal risks for late language emergence in a population-level sample of twins at age 2.

PubMed

Taylor, Catherine L; Rice, Mabel L; Christensen, Daniel; Blair, Eve; Zubrick, Stephen R

2018-02-07

Late Language Emergence (LLE) in the first two years of life is one of the most common parental concerns about child development and reasons for seeking advice from health professionals. LLE is much more prevalent in twins (38%) than singletons (20%). In studies of language development in twins without overt disability, adverse prenatal and perinatal environments have been reported to play a lesser role in the etiology of LLE than adverse postnatal environments. However, there is a lack of population-level evidence about prenatal and perinatal risk factors for LLE in twins. This study investigated the extent to which prenatal and perinatal risk factors were associated with LLE in a population-level sample of twins at age 2 without overt disability. The sample comprised 473 twin pairs drawn from a population sample frame comprising statutory notifications of all births in Western Australia (WA), 2000-2003. Twin pairs in which either twin had a known developmental disorder or exposure to language(s) other than English were excluded. Of the 946 twins, 47.9% were male. There were 313 dizygotic and 160 monozygotic twin pairs. LLE was defined as a score at or below the gender-specific 10th percentile on the MacArthur Communicative Development Inventories: Words and Sentences (CDI-WS) (Words Produced). Bivariate and multivariable logistic regression was used to investigate risk factors associated with LLE. In the multivariable model, risk factors for LLE in order of decreasing magnitude were: Gestational diabetes had an adjusted odds ratio (aOR) of 19.5 (95% confidence interval (CI) 1.2, 313.1); prolonged TSR (aOR: 13.6 [2.0, 91.1]); multiparity (aOR: 7.6 [1.6, 37.5]), monozygosity (aOR: 6.9 [1.7, 27.9]) and fetal growth restriction (aOR: 4.6 [1.7, 12.7]). Sociodemographic risk factors (e.g., low maternal education, socioeconomic area disadvantage) were not associated with increased odds of LLE. The results suggest that adverse prenatal and perinatal environments are

[Variable selection methods combined with local linear embedding theory used for optimization of near infrared spectral quantitative models].

PubMed

Hao, Yong; Sun, Xu-Dong; Yang, Qiang

2012-12-01

Variables selection strategy combined with local linear embedding (LLE) was introduced for the analysis of complex samples by using near infrared spectroscopy (NIRS). Three methods include Monte Carlo uninformation variable elimination (MCUVE), successive projections algorithm (SPA) and MCUVE connected with SPA were used for eliminating redundancy spectral variables. Partial least squares regression (PLSR) and LLE-PLSR were used for modeling complex samples. The results shown that MCUVE can both extract effective informative variables and improve the precision of models. Compared with PLSR models, LLE-PLSR models can achieve more accurate analysis results. MCUVE combined with LLE-PLSR is an effective modeling method for NIRS quantitative analysis.

Paracellular transport of avidin saturated or not with biotinylated cobalamin through Caco-2 cell epithelium monolayer.

PubMed

Guy, M; Pons, L; Namour, F; de Nonancourt, M; Michalski, J C; Hatier, R; Guéant, J L

2001-01-01

The cationic charge of molecules may promote their uptake across epithelia, which are rich in brush border anionic sites. The transport of unsaturated avidin and avidin saturated with a biotinylated compound was investigated across Caco-2 adenocarcinoma cell with fetal enterocyte phenotype. The unsaturated avidin and avidin saturated with either biotin or a biotinyl-cobalamin conjugate (biotinyl-Cbl) were iodinated to follow their transport through the cell monolayer. Their apparent permeability coefficient (Papp) and transepithelial pathway were determined and compared to those for control radiolabeled markers [3H]-mannitol, [125I]-beta-lactoglobulin and [57Co]-cobalamin/intrinsic factor (Cbl/IF). The Papp of [125I]-avidin estimated at 2.8 x 10(-7) +/- 0.08 cm/s was close to that for mannitol that uses paracellular pathway. The binding of biotin or biotin conjugate to avidin enhanced its tetrameric conformation. The Papp for [125I]-avidin/biotin and [125I]- avidin/biotinyl-Cbl were respectively increased by 2-fold, compared to that for [125I]-avidin and 4-fold, compared to that for [125I]-beta-lactoglobulin and [54Co]-Cbl/IF. The protein was not accumulated in the cell and was found in intact form in the basolateral side, after its transport across the monolayer. Chloroquine (0.66 micromol/ml) did not significantly decrease the Papp for [125I]-avidin/biotinyl-Cbl. Conversely it decreased by 80% the Papp for Cbl/IF, that uses transepithelial pathway. Avidin (either saturated or not with biotin and biotinyl-Cbl) was able to cross the monolayer of Caco-2 cell line through a paracellular pathway. This study pointed out the interest for using this protein as a shuttle for increasing the transport rate of biotinylated compounds through fetal epithelial barriers. Copyright 2001 S. Karger AG, Basel

Placental size and the prediction of severe early-onset intrauterine growth restriction in women with low pregnancy-associated plasma protein-A.

PubMed

Proctor, L K; Toal, M; Keating, S; Chitayat, D; Okun, N; Windrim, R C; Smith, G C S; Kingdom, J C P

2009-09-01

Screening studies for trisomy 21 demonstrate that low maternal serum pregnancy-associated plasma protein-A (PAPP-A) at 11-13 weeks' gestation is associated with stillbirth, intrauterine growth restriction (IUGR) and pre-eclampsia in chromosomally normal fetuses. However, the strength of these associations is too weak to justify screening for these placental insufficiency syndromes. Our objective was to evaluate placental size and uterine artery (UtA) Doppler imaging as second-stage screening tests for women with low PAPP-A. We prospectively studied 90 normal singleton pregnancies with first-trimester PAPP-A PAPP-A at high risk of IUGR, extreme preterm delivery and stillbirth. These additional screening tests may directly improve perinatal outcomes in women with low PAPP-A.

First trimester combined screening biochemistry in detection of congenital heart defects.

PubMed

Alanen, Julia; Korpimaki, Teemu; Kouru, Heikki; Sairanen, Mikko; Leskinen, Markku; Gissler, Mika; Ryynanen, Markku; Nevalainen, Jaana

2018-04-22

To evaluate the performance of first trimester biochemical markers, pregnancy-associated plasma protein-A (PAPP-A), free beta human chorionic gonadotropin (fβ-hCG), and nuchal translucency (NT) in detection of severe congenital heart defects (CHDs). During the study period from 1 January 2008 to 31 December 2011, biochemical markers and NT were measured in 31,144 women as part of voluntary first trimester screening program for Down's syndrome in Northern Finland. Data for 71 severe CHD cases and 762 controls were obtained from the hospital records and from the National Medical Birth Register, which records the birth of all liveborn and stillborn infants, and from the National Register of Congenital Malformations that receives information about all the CHD cases diagnosed in Finland. Both PAPP-A and fβ-hCG multiple of median (MoM) values were decreased in all severe CHDs: 0.71 and 0.69 in ventricular septal defects (VSDs), 0.58 and 0.88 in tetralogy of Fallot cases (TOFs), 0.82 and 0.89 in hypoplastic left heart syndromes (HLHSs), and 0.88 and 0.96 in multiple defects, respectively. NT was increased in all study groups except of VSD group. ROC AUC was 0.72 for VSD when combining prior risk with PAPP-A and fβ-hCG. Adding NT did not improve the detection rate. With normal NT but decreased (<0.5 MoM) PAPP-A and fβ-hCG odds ratios for VSD and HLHS were 19.5 and 25.6, respectively. Maternal serum biochemistry improves the detection of CHDs compared to NT measurement only. In cases with normal NT measurement but low concentrations of both PAPP-A and fβ-hCG, an alert for possible CHD, especially VSD, could be given with thorough examination of fetal heart in later ultrasound scans.

Microdialysis as a New Technique for Extracting Phenolic Compounds from Extra Virgin Olive Oil.

PubMed

Bazzu, Gianfranco; Molinu, Maria Giovanna; Dore, Antonio; Serra, Pier Andrea

2017-03-01

The amount and composition of the phenolic components play a major role in determining the quality of olive oil. The traditional liquid-liquid extraction (LLE) method requires a time-consuming sample preparation to obtain the "phenolic profile" of extra virgin olive oil (EVOO). This study aimed to develop a microdialysis extraction (MDE) as an alternative to the LLE method to evaluate the phenolic components of EVOO. To this purpose, a microdialysis device and dialysis procedure were developed. "Dynamic-oil" microdialysis was performed using an extracting solution (80:20 methanol/water) flow rate of 2 μL min -1 and a constant EVOO stream of 4 μL min -1 . The results indicated a strong positive correlation between MDE and the LLE method, providing a very similar phenolic profile obtained with traditional LLE. In conclusion, the MDE approach, easier and quicker in comparison to LLE, provided a reliable procedure to determine the phenolic components used as a marker of the quality and traceability of EVOO.

Evaluation of risk for late language emergence after in utero antiretroviral drug exposure in HIV-exposed uninfected infants.

PubMed

Rice, Mabel L; Zeldow, Bret; Siberry, George K; Purswani, Murli; Malee, Kathleen; Hoffman, Howard J; Frederick, Toni; Buchanan, Ashley; Sirois, Patricia A; Allison, Susannah M; Williams, Paige L

2013-10-01

Combination antiretroviral (cARV) regimens are recommended for pregnant women with HIV to prevent perinatal HIV transmission. Safety is a concern for infants who were HIV-exposed but uninfected, particularly for neurodevelopmental problems, such as language delays. We studied late language emergence (LLE) in HIV-exposed but uninfected children enrolled in a US-based prospective cohort study. LLE was defined as a caregiver-reported score ≤10th percentile in any of 4 domains of the MacArthur-Bates Communicative Development Inventory for 1-year olds and as ≥1 standard deviation below age-specific norms for the Ages and Stages Questionnaire for 2-year olds. Logistic regression models were used to evaluate associations of in utero cARV exposure with LLE, adjusting for infant, maternal and environmental characteristics. 1129 language assessments were conducted among 792 1- and 2-year-old children (50% male, 62% black and 37% Hispanic). Overall, 86% had in utero exposure to cARV and 83% to protease inhibitors. LLE was identified in 26% of 1-year olds and 23% of 2-year olds, with higher rates among boys. In adjusted models, LLE was not associated with maternal cARV or ARV drug classes in either age group. Among cARV-exposed 1-year olds, increased odds of LLE was observed for those exposed to atazanavir (adjusted odds ratio = 1.83, 95% confidence interval: 1.10-3.04), particularly after the first trimester (adjusted odds ratio = 3.56, P = 0.001), compared with atazanavir-unexposed infants. No associations of individual ARV drugs with LLE were observed among 2-year olds. In utero cARV exposure showed little association with LLE, except for a higher risk of language delay observed in 1-year-old infants with atazanavir exposure.

First trimester maternal lipid levels and serum markers of small- and large-for-gestational age infants.

PubMed

Parlakgumus, Huriye Ayse; Aytac, Pinar Caglar; Kalaycı, Hakan; Tarim, Ebru

2014-01-01

To investigate if first trimester lipids, sonographic parameters and serum markers are related to small- and large-for-gestational age (SGA, LGA) infants. This study was conducted at Baskent University Adana Research Center between December 2009 and July 2011 and enrolled 433 women. Blood samples were drawn to measure fasting blood glucose, serum triglycerides, cholesterol, very low-density lipoprotein, low-density lipoprotein, high-density lipoprotein, fβ-hCG and pregnancy associated protein-A (PAPP-A) at the first trimester. Crown rump length and nuchal translucency were measured as suggested by the fetal medicine foundation. LGA group was significantly taller (p = 0.016) and SGA group had significantly greater BMI (0.025). SGA fetuses were born at a significantly earlier gestational age (p = 0.001). Univariate analysis revealed that LGA group had significantly lower cholesterol (p = 0.038) and LDL levels (p = 0.041). PAPP-A was significantly lower in SGA Group compared with LGA Group (0.027). After controlling for age, parity, height, pre-pregnant BMI, weight gain during pregnancy and fasting blood sugar, none of the lipids, serum markers or sonographic parameters was related to LGA. PAPP-A was the only parameter significantly associated with SGA after multivariate analysis (p = 0.008). PAPP-A was significantly associated with SGA after controlling for confounders.

Pregnancy-associated plasma protein A gene polymorphism in pregnant women with preeclampsia and intrauterine growth restriction.

PubMed

Ozkan, Sultan; Sanhal, Cem Yasar; Yeniel, Ozgur; Arslan Ates, Esra; Ergenoglu, Mete; Bınbır, Birol; Onay, Huseyin; Ozkınay, Ferda; Sagol, Sermet

2015-10-01

Preeclampsia (PE) and intrauterine growth restriction (IUGR) are still among the most commonly researched titles in perinatology. To shed light on their etiology, new prevention and treatment strategies are the major targets of studies. In this study, we aimed to investigate the relation between gene polymorphism of one of the products of trophoblasts, pregnancy-associated plasma protein A (PAPP-A) and PE/IUGR.A total of 147 women (IUGR, n = 61; PE, n = 47; IUGR + PE, n = 37; eclampsia, n = 2) were compared with 103 controls with respect to the sequencing of exon 14 of the PAPP-A gene to detect (rs7020782) polymorphism. Genotypes "AA" and "CC" were given in the event of A or C allele homozygosity and "AC" in A and C allele heterozygosity. Our findings revealed that the rate of AA, CC homozygotes, and AC heterozygotes did not differ between groups. Moreover, there was no difference in the distribution of PAPP-A genotypes among the patients with IUGR, PE, IUGR + PE, or eclampsia. Finally, birth weight, rate of the presence of proteinuria, and total protein excretion on 24-hour urine were similar in the subgroups of AA, AC, and CC genotypes in the study group. Our study demonstrated no association between PAPP-A gene rs7020782 polymorphism and PE/IUGR. Copyright © 2015. Published by Elsevier Taiwan.

Maternal serum free-beta-chorionic gonadotrophin, pregnancy-associated plasma protein-A and fetal nuchal translucency thickness at 10-13(+6) weeks in relation to co-variables in pregnant Saudi women.

PubMed

Ardawi, Mohammed-Salleh M; Nasrat, Hasan A; Rouzi, Abdulrahim A; Qari, Mohammed H; Al-Qahtani, Mohammed H; Abuzenadah, Adel M

2007-04-01

To establish normative values and distribution parameters of first-trimester screening markers, namely, fetal nuchal translucency (NT), maternal serum free beta-human chorionic gonadotrophin (beta-hCG) and pregnancy-associated plasma protein-A (PAPP-A), at 10 to 13(+6) weeks of gestation in Saudi women and to evaluate the effect of co-variables including maternal body weight, gravidity, parity, fetal gender, twin pregnancy, smoking and ethnicity on these markers. A cohort of Saudi women (first cohort n = 1616) with singleton pregnancies prospectively participated in the present study, and fetal NT together with maternal serum free beta-hCG and PAPP-A were determined at 10 to 13(+6) weeks of gestation. The distribution of gestational age-independent multiples of the median (MoM) of the parameters was defined and normative values were established, and correction for maternal body weight was made accordingly. The influence of various co-variables was examined using the data collected from the first and the second (n = 1849) cohorts of women and 62 twin pregnancies, and compared with other studies. All markers exhibited log-normally distributed MoMs. Gestational age-independent normative values were established. Maternal body weight was corrected, particularly for maternal free beta-hCG and PAPP-A using standard methods. Fetal NT showed a negative relationship with increasing gravidity (r = -0.296) or parity (r = -0.311), whereas both free beta-hCG and PAPP-A exhibited a significant positive relationship. There was a significant increase in the MoM of free beta-hCG in female fetuses. Smoking decreased MoM values of free beta-hCG (by 14.6%; P < 0.01) and PAPP-A (by 18.8%; P < 0.001). Twin pregnancy showed significant increases in MoM values of free beta-hCG (by 1.87-fold) and PAPP-A (by 2.24-fold), with no significant changes in fetal NT MoM values. Fetal NT MoM values were lower in Africans and Asians but higher in Orientals, as compared to Saudi women (P < 0.05; in

Understanding the Link Between Pregnancy and Breast Cancer

DTIC Science & Technology

2014-06-01

injected in the mammary glands of nude mice females and 2 groups were generated virgin group and the pregnant group, in which a male was added for mating...to modulate the effect of collagen. A key mediator of involution is the insulin -like growth factor binding protein 5 (IGFBP-5) 6-9. IGFBP-5 is...expressing PAPP-A were used. We found that rIGFBP-5 is resistant to cleavage by PAPP-A in the absence of collagen (Fig. 2f). Upon addition of

Spatial and gender scenario of literate life expectancy at birth in India.

PubMed

Chattopadhyay, Aparajita; Sinha, Kumar Chiman

2010-10-01

Measuring human quality of life is academically challenging. The human development index (HDI) substantially captures the overall country level status on human welfare. However, this index has some drawbacks. Therefore, Lutz composed a simple index in 1995 combining life expectancy and literacy, called literate life expectancy (LLE). LLE can be calculated for subpopulations depending on availability of data. This article captures the LLE in major states in India and the gender differences in LLE at rural and urban levels. The authors have tried to highlight the social development scenario in India and its major states by using this pure social indicator that intentionally does not use any economic measurement. The state scenario comprehensively depicts gender differentials in social development, and it calls for implementing development measures more seriously in states like Haryana, Bihar, Rajasthan, Madhya Pradesh, and Uttar Pradesh to reduce the gender gap. Being highly correlated with the HDI, the LLE index proves to be a very clear and simple comprehensive measure of social development for different subpopulations.

Locally Linear Embedding of Local Orthogonal Least Squares Images for Face Recognition

NASA Astrophysics Data System (ADS)

Hafizhelmi Kamaru Zaman, Fadhlan

2018-03-01

Dimensionality reduction is very important in face recognition since it ensures that high-dimensionality data can be mapped to lower dimensional space without losing salient and integral facial information. Locally Linear Embedding (LLE) has been previously used to serve this purpose, however, the process of acquiring LLE features requires high computation and resources. To overcome this limitation, we propose a locally-applied Local Orthogonal Least Squares (LOLS) model can be used as initial feature extraction before the application of LLE. By construction of least squares regression under orthogonal constraints we can preserve more discriminant information in the local subspace of facial features while reducing the overall features into a more compact form that we called LOLS images. LLE can then be applied on the LOLS images to maps its representation into a global coordinate system of much lower dimensionality. Several experiments carried out using publicly available face datasets such as AR, ORL, YaleB, and FERET under Single Sample Per Person (SSPP) constraint demonstrates that our proposed method can reduce the time required to compute LLE features while delivering better accuracy when compared to when either LLE or OLS alone is used. Comparison against several other feature extraction methods and more recent feature-learning method such as state-of-the-art Convolutional Neural Networks (CNN) also reveal the superiority of the proposed method under SSPP constraint.

Intestinal absorption of forsythoside A in in situ single-pass intestinal perfusion and in vitro Caco-2 cell models

PubMed Central

Zhou, Wei; Di, Liu-qing; Wang, Juan; Shan, Jin-jun; Liu, Shi-jia; Ju, Wen-zheng; Cai, Bao-chang

2012-01-01

Aim: To investigate the mechanisms underlying the intestinal absorption of the major bioactive component forsythoside A (FTA) extracted from Forsythiae fructus. Methods: An in vitro Caco-2 cell model and a single-pass intestinal perfusion in situ model in SD rats were used. Results: In the in vitro Caco-2 cell model, the mean apparent permeability value (Papp-value) was 4.15×10-7 cm/s in the apical-to-basolateral (AP-BL) direction. At the concentrations of 2.6–10.4 μg/mL, the efflux ratio of FTA in the bi-directional transport experiments was approximately 1.00. After the transport, >96% of the apically loaded FTA was retained on the apical side, while >97% of the basolaterally loaded FTA was retained on the basolateral side. The Papp-values of FTA were inversely correlated with the transepithelial electrical resistance. The paracellular permeability enhancers sodium caprate and EDTA, the P-gp inhibitor verapamil and the multidrug resistance related protein (MRP) inhibitors cyclosporine and MK571 could concentration-dependently increase the Papp-values, while the uptake (OATP) transporter inhibitors diclofenac sodium and indomethacin could concentration-dependently decrease the Papp-values. The intake transporter SGLT1 inhibitor mannitol did not cause significant change in the Papp-values. In the in situ intestinal perfusion model, both the absorption rate constant (Ka) and the effective permeability (Peff-values) following perfusion of FTA 2.6, 5.2 and 10.4 μg/mL via the duodenum, jejunum and ileum had no significant difference, although the values were slightly higher for the duodenum as compared to those in the jejunum and ileum. The low, medium and high concentrations of verapamil caused the largest increase in the Peff-values for duodenum, jejunum and ileum, respectively. Sodium caprate, EDTA and cyclosporine resulted in concentration-dependent increase in the Peff-values. Diclofenac sodium and indomethacin caused concentration-dependent decrease in the

Preventive effects of lignan extract from flax hulls on experimentally induced benign prostate hyperplasia.

PubMed

Bisson, Jean-François; Hidalgo, Sophie; Simons, Rudy; Verbruggen, Marian

2014-06-01

Consumption of diet rich in lignans may decrease the risk of some chronic hormonal conditions such as benign prostatic hyperplasia (BPH). This study investigated whether a lignan-rich extract from flaxseed hulls, LinumLife EXTRA (LLE), could prevent BPH using the testosterone propionate (TP)-induced BPH rat model. Male Wistar-Unilever rats were randomly divided into four groups of 12 rats each: a negative control group fed with control diet and receiving daily subcutaneous injections of corn oil without TP, and three groups fed with control diet (positive control), diet containing 0.5% LLE (LLE 0.5) or 1.0% LLE (LLE 1.0) and receiving daily subcutaneous injections of TP in corn oil. Treatments with diets started 2 weeks before the induction of BPH and were carried out for 5 consecutive weeks. The influence of TP and LLE on body weight (BW), food and water consumptions, and enterolactone (ENL) levels in serum and urine of rats was examined at the end of the 5-week treatment period. TP significantly diminished the mean body weight gain (MBWG) of positive control rats and their food and water consumptions while LLE reduced significantly this MBWG reduction in a dose-dependent manner. The lignan-rich extract significantly inhibited TP-induced prostate size ratio (prostate weight/rat BW) increase in comparison with positive controls (P<.001). This effect was dose dependent. Higher serum and urine levels of ENL correlated well with the dose of extract provided to rats. It was concluded that the lignan-rich flaxseed hull extract prevented the TP-induced BPH indicating it might be beneficial in the prevention of BPH.

Thiolene and SIFEL-based Microfluidic Platforms for Liquid-Liquid Extraction

PubMed Central

Goyal, Sachit; Desai, Amit V.; Lewis, Robert W.; Ranganathan, David R.; Li, Hairong; Zeng, Dexing; Reichert, David E.; Kenis, Paul J.A.

2014-01-01

Microfluidic platforms provide several advantages for liquid-liquid extraction (LLE) processes over conventional methods, for example with respect to lower consumption of solvents and enhanced extraction efficiencies due to the inherent shorter diffusional distances. Here, we report the development of polymer-based parallel-flow microfluidic platforms for LLE. To date, parallel-flow microfluidic platforms have predominantly been made out of silicon or glass due to their compatibility with most organic solvents used for LLE. Fabrication of silicon and glass-based LLE platforms typically requires extensive use of photolithography, plasma or laser-based etching, high temperature (anodic) bonding, and/or wet etching with KOH or HF solutions. In contrast, polymeric microfluidic platforms can be fabricated using less involved processes, typically photolithography in combination with replica molding, hot embossing, and/or bonding at much lower temperatures. Here we report the fabrication and testing of microfluidic LLE platforms comprised of thiolene or a perfluoropolyether-based material, SIFEL, where the choice of materials was mainly guided by the need for solvent compatibility and fabrication amenability. Suitable designs for polymer-based LLE platforms that maximize extraction efficiencies within the constraints of the fabrication methods and feasible operational conditions were obtained using analytical modeling. To optimize the performance of the polymer-based LLE platforms, we systematically studied the effect of surface functionalization and of microstructures on the stability of the liquid-liquid interface and on the ability to separate the phases. As demonstrative examples, we report (i) a thiolene-based platform to determine the lipophilicity of caffeine, and (ii) a SIFEL-based platform to extract radioactive copper from an acidic aqueous solution. PMID:25246730

Screening of pharmacokinetic properties of fifty dihydropyrimidin(thi)one derivatives using a combo of in vitro and in silico assays.

PubMed

Matias, Mariana; Fortuna, Ana; Bicker, Joana; Silvestre, Samuel; Falcão, Amílcar; Alves, Gilberto

2017-11-15

The heterocycles dihydropyrimidin(thi)ones have been under intensive pharmacological research, but their pharmacokinetic properties remain almost unknown. Herein, fifty dihydropyrimidin(thi)ones were submitted to in vitro screening tests using parallel artificial membrane permeability assays (PAMPA) to evaluate their apparent permeability (Papp) through intestinal membrane and blood-brain barrier models, and cell-based assays to assess their interference on the efflux transporter P-glycoprotein (P-gp). Moreover, a set of kinetic and toxicological parameters was also estimated employing a new computational tool, the pkCSM. The in vitro results suggested that 82% of the test compounds have good intestinal permeability (Papp>1.1×10 -6 cm/s), and 66% of these are also expected to exhibit good permeability through blood-brain barrier (Papp>2.0×10 -6 cm/s); these findings are consistent with a high transport rate by passive transcellular pathway. In both PAMPA models, thiourea derivatives presented higher Papp values than the respective urea analogues, which were further corroborated by in silico predictions. The in vitro results also suggested a low extent of plasma protein binding for all compounds (Papp<1.0×10 -5 cm/s), and these findings were also supported by in silico data (unbound fraction ranging from 0.13 to 0.59). In addition, although approximately half of the compounds did not modulate P-gp at the tested concentrations (10 and 50μM), nine of them presented a trend to induce P-gp and particularly the chlorinated compounds exhibited a marked P-gp inhibition at 50μM. Furthermore, the in silico predictions suggested that half of the compounds have hepatotoxic potential. Overall, within this group of compounds, the thiourea derivatives containing an unsubstituted or a monosubstituted (NO 2 , CH 3 , OCH 3 ) phenyl ring attached to the position 4 of the dihydropyrimidine ring represented the most promising structures and should be considered in the subsequent

Comparison of methods for determination of volatile organic compounds in drinking water.

PubMed

Golfinopoulos, S K; Lekkas, T D; Nikolaou, A D

2001-10-01

Comparison of four methods including liquid-liquid extraction (LLE), direct aqueous injection (DAI), purge and trap (PAT) and head space (HS) were carried out in this work for determination of volatile organic compounds (VOCs) including trihalomethanes (THMs) in drinking water. This comparison is made especially to show the advantages and disadvantages and specifically the different detection limits (DL) that can be obtained for a given type of analysis. LLE is applicable only for determination of the THMs concentrations, while DAI, PAT, HS methods with different DL each of them are applicable for all VOCs, with PAT to be the most sensitive. Sampling apparatus and procedure for all these methods except of PAT are very simple and easy, but possible disadvantages for LLE and DAI are the low sensitivity and especially the detection only of THMs with LLE.

A new method for drug transport studies on pig nasal mucosa using a horizontal Ussing chamber.

PubMed

Osth, Karin; Gråsjö, Johan; Björk, Erik

2002-05-01

The horizontal Ussing chamber method described here allows performance of transport studies on pig nasal respiratory mucosa under conditions simulating reality in that it mimics the air-mucosa interface. The transport of testosterone and mannitol through pig nasal mucosa in the horizontal Ussing chamber was investigated using both liquid and air mucosal interfaces. There were no significant differences in either the bioelectrical parameters (transmucosal electrical resistance, R, potential difference, PD, and short circuit current, I(sc)) or the apparent permeability (P(app)) of the mucosa to testosterone or mannitol between the liquid and air interface experiments. The histological study showed that the epithelial cell layer tolerates exposure to the air interface well. The P(app) equation was developed to correct for substance binding to the wall of the receiver chamber. The mean values +/- SD of R, PD, and I(sc) for the mucosae in the study were 75.0 +/- 28.0 Omegacm(2), (-4.53) +/- 3.46 mV and 58.6 +/- 28.8 microA/cm(2), respectively. The corrected P(app) for testosterone with and without the mucosal air interface were 9.82. 10(-6) +/- 11.41. 10(-6) cm/s and 32.24. 10(-6) +/- 31.12. 10(-6) cm/s, respectively. The P(app) values for mannitol with and without the air interface were 2.26. 10(-6) +/- 1.42. 10(-6) cm/s and 3.12. 10(-6) +/- 1.72. 10(-6) cm/s, respectively. Copyright 2002 Wiley-Liss, Inc. and the American Pharmaceutical Association

Amelioration of azoxymethane induced-carcinogenesis by reducing oxidative stress in rat colon by natural extracts

PubMed Central

2014-01-01

Background Azoxymethane (AOM) is a potent carcinogenic agent commonly used to induce colon cancer in rats; the cytotoxicity of AOM is considered to mediate oxidative stress. This study investigated the chemopreventive effect of three natural extracts [pomegranate peel extract (PomPE), papaya peel extract (PapPE) and seaweed extract (SE)] against AOM-induced oxidative stress and carcinogenesis in rat colon. Methods Eighty Sprague–Dawley rats (aged 4 weeks) were randomly divided into 8 groups (10 rats/group). Control group was fed a basal diet; AOM-treated group was fed a basal diet and received AOM intraperitonial injections for two weeks at a dose of 15 mg/kg bodyweight, whereas the other six groups were received oral supplementation of PomPE, PapPE or SE, in the presence or absence of AOM injection. All animals were continuously fed ad-libitum until aged 16 weeks, then all rats were sacrificed and the colon tissues were examined microscopically for pathological changes and aberrant crypt foci (ACF) development, genotoxicity (induced micronuclei (MN) cells enumeration), and glutathione and lipid peroxidation. Results Our results showed that AOM-induced ACF development and pathological changes in the colonic mucosal tissues, increased bone marrow MN cells and oxidative stress (glutathione depletion, lipid peroxidation) in rat colonic cells. The concomitant treatment of AOM with PomPE, PapPE or SE significantly ameliorated the cytotoxic effects of AOM. Conclusions The results of this study provide in-vivo evidence that PomPE, PapPE and SE reduced the AOM-induced colon cancer in rats, through their potent anti-oxidant activities. PMID:24533833

Micellar versus hydro-organic mobile phases for retention-hydrophobicity relationship studies with ionizable diuretics and an anionic surfactant.

PubMed

Ruiz-Angel, M J; Carda-Broch, S; García-Alvarez-Coque, M C; Berthod, A

2004-03-19

Logarithm of retention factors (log k) of a group of 14 ionizable diuretics were correlated with the molecular (log P o/w) and apparent (log P(app)) octanol-water partition coefficients. The compounds were chromatographed using aqueous-organic (reversed-phase liquid chromatography, RPLC) and micellar-organic mobile phases (micellar liquid chromatography, MLC) with the anionic surfactant sodium dodecyl sulfate (SDS), in the pH range 3-7, and a conventional octadecylsilane column. Acetonitrile was used as the organic modifier in both modes. The quality of the correlations obtained for log P(app) at varying ionization degree confirms that this correction is required in the aqueous-organic mixtures. The correlation is less improved with SDS micellar media because the acid-base equilibriums are shifted towards higher pH values for acidic compounds. In micellar chromatography, an electrostatic interaction with charged solutes is added to hydrophobic forces; consequently, different correlations should be established for neutral and acidic compounds, and for basic compounds. Correlations between log k and the isocratic descriptors log k(w), log k(wm) (extrapolated retention to pure water in the aqueous-organic and micellar-organic systems, respectively), and psi0 (extrapolated mobile phase composition giving a k = 1 retention factor or twice the dead time), and between these descriptors and log P(app) were also satisfactory, although poorer than those between log k and log P(app) due to the extrapolation. The study shows that, in the particular case of the ionizable diuretics studied, classical RPLC gives better results than MLC with SDS in the retention hydrophobicity correlations.

Comparative evaluation of the efficiency of low-cost adsorbents and ligninolytic fungi to remove a combination of xenoestrogens and pesticides from a landfill leachate and abate its phytotoxicity.

PubMed

Loffredo, Elisabetta; Castellana, Giancarlo

2015-01-01

In this study, two widely available low-cost adsorbents, almond shells and a green compost, and two ligninolytic fungi, Pleurotus ostreatus and Stereum hirsutum, were used to remove organic contaminants from a landfill leachate (LLe) and abate its phytotoxicity. The methodology adopted was based on the occurrence of two simultaneous processes, such as adsorption and bioremoval. The leachate was artificially contaminated with a mixture of the xenoestrogens bisphenol A (BPA), ethynilestadiol (EE2) and 4-n-nonylphenol (NP), the herbicide linuron and the insecticide dimethoate at concentrations of 10, 1, 1, 10 and 10 mg L(-1), respectively. Three adsorption substrates were prepared: potato dextrose agar alone or the same incorporating each adsorbent. The substrates were either not inoculated or inoculated with each fungus, separately, before to be superimposed on LLe. After 2 months, the residual amount of each contaminant, the electrical conductivity, the pH and the content of total phenols were measured in treated LLe. Germination assays using lettuce, ryegrass and radish were performed to evaluate LLe phytotoxicity. The combination substrate+P. ostreatus showed the best results with average removals of 88, 96, 99, 58 and 46% for BPA, EE2, NP, linuron and dimethoate, respectively. The same treatment considerably reduced the phenol content in LLe compared to no treatment. The combination substrate+S. hirsutum produced average removals of 39, 71, 100, 61 and 32% for BPA, EE2, NP, linuron and dimethoate, respectively. Also uninoculated substrates showed relevant adsorption capacities towards the five contaminants. Most treatments significantly reduced LLe phytotoxicity, especially on lettuce. The best results were obtained with the treatment compost+S. hirsutum, which produced root and shoot lengths and seedling biomass of lettuce, respectively, 2.3, 3.3, and 1.9 times those measured in untreated LLe. In general, germination results were negatively correlated with LLe

Poor permeability and absorption affect the activity of four alkaloids from Coptis.

PubMed

Cui, Han-Ming; Zhang, Qiu-Yan; Wang, Jia-Long; Chen, Jian-Long; Zhang, Yu-Ling; Tong, Xiao-Lin

2015-11-01

Coptidis rhizoma (Coptis) and its alkaloids exert various pharmacological functions in cells and tissues; however, the oral absorption of these alkaloids requires further elucidation. The present study aimed to examine the mechanism underlying the poor absorption of alkaloids, including berberine (BER), coptisine (COP), palmatine (PAL) and jatrorrhizine (JAT). An ultra‑performance liquid chromatography (UPLC) method was validated for the determination of BER, COP, PAL and JAT in the above experimental medium. In addition, the apparent oil‑water partition coefficient (Po/w); apparent permeability coefficient (Papp), determined using a parallel artificial membrane permeability assay (PAMPA) plate; membrane retention coefficient (R %); and effect of P‑glycoprotein (P‑gp) inhibitor on the Papp of the four alkaloids were investigated. The intestinal absorption rate constant (Ka) and absorption percentage (A %) of the four alkaloids were also determined. The results of the present study demonstrated that the Po/w of the four alkaloids in 0.1 mol·l‑1 HCl medium was significantly higher (P<0.01), compared with those of the alkaloids in phosphate buffer (pH 7.4). The Papp of BER was 1.0‑1.2x10‑6 cm·s‑1, determined using a PAMPA plate, and the Papp of BER, COP, PAL and JAT decreased sequentially. The concentrations of the four alkaloids on the apical‑to‑basolateral (AP‑BL) surface and the basolateral‑to‑apical (BL‑AP) surface increased in a linear manner, with increasing concentrations between 10 and 100 µmol. In addition, the transportation of BER on the BL‑AP surface was significantly faster (P<0.01), compared with that on the AP‑BL surface and, following the addition of verpamil (a P‑gp inhibitor), the Papp (AP‑BL) of the four alkaloids increased, whereas the Papp (BL‑AP) was significantly decreased (P<0.01). The rat intestinal perfusion experiment demonstrated that the four alkaloids were poorly absorbed; however, the Ka of BER

Late language emergence in 24-month-old twins: heritable and increased risk for late language emergence in twins.

PubMed

Rice, Mabel L; Zubrick, Stephen R; Taylor, Catherine L; Gayán, Javier; Bontempo, Daniel E

2014-06-01

This study investigated the etiology of late language emergence (LLE) in 24-month-old twins, considering possible twinning, zygosity, gender, and heritability effects for vocabulary and grammar phenotypes. A population-based sample of 473 twin pairs participated. Multilevel modeling estimated means and variances of vocabulary and grammar phenotypes, controlling for familiality. Heritability was estimated with DeFries-Fulker regression and variance components models to determine effects of heritability, shared environment, and nonshared environment. Twins had lower average language scores than norms for single-born children, with lower average performance for monozygotic than dizygotic twins and for boys than girls, although gender and zygosity did not interact. Gender did not predict LLE. Significant heritability was detected for vocabulary (0.26) and grammar phenotypes (0.52 and 0.43 for boys and girls, respectively) in the full sample and in the sample selected for LLE (0.42 and 0.44). LLE and the appearance of Word Combinations were also significantly heritable (0.22-0.23). The findings revealed an increased likelihood of LLE in twin toddlers compared with single-born children that is modulated by zygosity and gender differences. Heritability estimates are consistent with previous research for vocabulary and add further suggestion of heritable differences in early grammar acquisition.

A Study of Care Work in Welfare Facilities for the Elderly, Using Non Linear Analysis of Finger Plethysmograms

NASA Astrophysics Data System (ADS)

Hirohashi, Yoko; Oyama-Higa, Mayumi; Lee, Sangjae

2011-06-01

The fingertip pulse waves of a number of staff working in a daycare center for the elderly and a special nursing home for the elderly were measured several times throughout the day for a period of one or two days, and the chaotic information gained was analyzed using a non linear analysis method. As a result, a relation between the staff's length of career and the change of Largest Lyapunov Exponent (LLE) of the fingertip pulse waves that synchronized with the mental revitalization degrees and the tension of the sympathetic nerve was evident. The LLE of the staff with short careers dramatically changed and also took a long time to settle down again. In addition, staff LLE changed greatly after sessions of bathing assistance and watching residents with dementia. LLE measurements showed drops in some staff after a period of rest, but this was not the case for other staff. It can be concluded that the LLE is related to the length of the staff member's career and what is actually done during working hours and rest periods. A high level of sympathetic nerve was seen in almost all of the care workers. On this basis, the authors propose that improvements are needed in the content of the care work.

PubMed

Hachenberg, Thomas; Kols, Kerstin

2018-04-01

Schlichtungsstellen für Arzthaftpflichtfragen bieten Patienten, Ärzten und Versicherern eine Möglichkeit, Arzthaftungsstreitigkeiten außergerichtlich zu klären. In der Rubrik „Fälle der Schlichtungsstelle“ stellen wir abgeschlossene Fälle aus der Schlichtungsstelle für Arzthaftpflichtfragen der norddeutschen Ärztekammern vor.

1999 Summer Research Program for High School Juniors at the University of Rochester's Laboratory for Laser Energetics

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

None

2002-10-09

oak-B202--During the summer of 1999, 12 students from Rochester-area high schools participated in the Laboratory for Laser Energetics' Summer High School Research Program. The goal of this program is to excite a group of high school students about careers in the areas of science and technology by exposing them to research in a state-of-the-art environment. Too often, students are exposed to ''research'' only through classroom laboratories that have prescribed procedures and predictable results. In LLE's summer program, the students experience all of the trials, tribulations, and rewards of scientific research. By participating in research in a real environment, the studentsmore » often become more enthusiastic about careers in science and technology. In addition, LLE gains from the contributions of the many highly talented students who are attracted to the program. The students spent most of their time working on their individual research projects with members of LLE's technical staff. The projects were related to current research activities at LLE and covered a broad range of areas of interest including laser modeling, diagnostic development, chemistry, liquid crystal devices, and opacity data visualization. The students, their high schools, their LLE supervisors and their project titles are listed in the table. Their written reports are collected in this volume. The students attended weekly seminars on technical topics associated with LLE's research. Topics this year included lasers, fusion, holography, optical materials, global warming, measurement errors, and scientific ethics. The students also received safety training, learned how to give scientific presentations, and were introduced to LLE's resources, especially the computational facilities. The program culminated with the High School Student Summer Research Symposium on 25 August at which the students presented the results of their research to an audience that included parents, teachers, and members of

The Insulin-Like Growth Factor System in the Long-Lived Naked Mole-Rat

PubMed Central

Brohus, Malene; Gorbunova, Vera; Faulkes, Chris G.; Overgaard, Michael T.; Conover, Cheryl A.

2015-01-01

Naked mole-rats (Heterocephalus glaber) (NMRs) are the longest living rodents known. They show negligible senescence, and are resistant to cancers and certain damaging effects associated with aging. The insulin-like growth factors (IGFs) have pluripotent actions, influencing growth processes in virtually every system of the body. They are established contributors to the aging process, confirmed by the demonstration that decreased IGF signaling results in life-extending effects in a variety of species. The IGFs are likewise involved in progression of cancers by mediating survival signals in malignant cells. This report presents a full characterization of the IGF system in the NMR: ligands, receptors, IGF binding proteins (IGFBPs), and IGFBP proteases. A particular emphasis was placed on the IGFBP protease, pregnancy-associated plasma protein-A (PAPP-A), shown to be an important lifespan modulator in mice. Comparisons of IGF-related genes in the NMR with human and murine sequences indicated no major differences in essential parts of the IGF system, including PAPP-A. The protease was shown to possess an intact active site despite the report of a contradictory genome sequence. Furthermore, PAPP-A was expressed and translated in NMRs cells and retained IGF-dependent proteolytic activity towards IGFBP-4 and IGF-independent activity towards IGFBP-5. However, experimental data suggest differential regulatory mechanisms for PAPP-A expression in NMRs than those described in humans and mice. This overall description of the IGF system in the NMR represents an initial step towards elucidating the complex molecular mechanisms underlying longevity, and how these animals have evolved to ensure a delayed and healthy aging process. PMID:26694858

Identifying mild and severe preeclampsia in asymptomatic pregnant women by levels of cell-free fetal DNA.

PubMed

Jakobsen, Tanja Roien; Clausen, Frederik Banch; Rode, Line; Dziegiel, Morten Hanefeld; Tabor, Ann

2013-09-01

The objective was to investigate whether women who develop preeclampsia can be identified in a routine analysis when determining fetal RHD status at 25 weeks' gestation in combination with PAPP-A levels at the first-trimester combined risk assessment for Trisomy 21. D- women participating in the routine antenatal RHD screening program in the capital region of Denmark were retrospectively studied. We used a standard dilution curve to quantify the amounts of cell-free fetal DNA (cffDNA) and divided women into groups according to cffDNA levels. PAPP-A was measured at 11 to 14 weeks. Information about pregnancy outcome and complications was obtained from the National Fetal Medicine Database, medical charts, and discharge letters. The odds ratio (OR) of developing severe preeclampsia given a cffDNA level above the 90th percentile compared to cffDNA below the 90th percentile was 8.1 (95% confidence interval [CI], 2.6-25.5). The OR of developing mild preeclampsia given a cffDNA level below the 5th percentile compared to cffDNA levels above the 5th percentile was 3.6 (95% CI, 1.1-11.7). PAPP-A levels below the 5th percentile were associated with mild preeclampsia, but adding it to the analysis did not increase the detection rate (DR). Women with cffDNA levels below the 5th percentile and above the 90th percentile quantified at 25 weeks' gestation are at increased risk of developing preeclampsia. Adding PAPP-A levels to the analysis did not increase the DR of preeclampsia. © 2013 American Association of Blood Banks.

[Study on intestinal absorption of formononetin in Millettia nitita var. hirsutissima in rats].

PubMed

Liu, Ya-Li; Xiong, Xian-Bing; Su, Dan; Song, Yong-Gui; Zhang, Ling; Yang, Shi-Lin

2013-10-01

To use the single-pass intestine perfusion (SPIP) model and HPLC to determine the concentration of formononetin, the effect of quality concentrations of formononetin, different intestinal segments and P-glycoprotein inhibitor on intestinal absorption of formononetin, in order to observe the intestinal absorption mechanism of formononetin from Millettia nitita var. hirsutissima in rats. The experimental results showed that the qulaity concentration of formononetin in the perfusate had no significant effect on the absorption rate constant (K(a)) and the apparent absorption coefficient (P(app)); K(a) and P(app) of formononetin in duodenum, jejunum and ileum showed no significant difference. However, K(a) was significantly higher than that in colon (P < 0.05), with significant difference between that in intestinum tenue and colon. P-glycoprotein inhibitor verapamil showed significant difference in K(a) and P(app) in intestinal segments (P < 0.05). This indicated that the absorption mechanism of formononein in rat intestinal tracts passive diffusion, without any saturated absorption. Formononein is absorbed well in all intestines. Their absorption windows were mainly concentrated in the intestinum tenue, without specific absorption sites. Formononein may be the substrate of P-glycoprotein.

The influence of parity and gravidity on first trimester markers of chromosomal abnormality.

PubMed

Spencer, K; Ong, C Y; Liao, A W; Nicolaides, K H

2000-10-01

We have studied changes in first trimester fetal nuchal translucency (NT) and maternal serum free beta-hCG and PAPP-A with gravidity and parity in 3252 singleton pregnancies unaffected by chromosomal abnormality or major pregnancy complications. We have shown that gravidity and parity is associated with a small but progressive decrease in fetal NT and a small but progressive increase in free beta-hCG and PAPP-A. None of these small changes with increasing gravidity or parity are statistically significant and hence correction for these variables is not necessary when considering first trimester screening for chromosomal abnormalities. Copyright 2000 John Wiley & Sons, Ltd.

Adverse Pregnancy Outcomes after Abnormal First Trimester Screening for Aneuploidy

PubMed Central

Goetzl, Laura

2010-01-01

Women with abnormal first trimester screening but with a normal karyotype are at risk for adverse pregnancy outcomes. A nuchal translucency >3.5mm is associated with an increased risk of subsequent pregnancy loss, fetal infection, fetal heart abnormalities and other structural abnormalities. Abnormal first trimester analytes are also associated with adverse pregnancy outcomes but the predictive value is less impressive. As a single marker, PAPP-A <1st%ile has a good predictive value for subsequent fetal growth restriction. Women with PAPP-A<5th%ile should undergo subsequent risk assessment with routine MSAFP screening with the possible addition of uterine artery PI assessment in the midtrimester. PMID:20638576

Principles of Stagewise Separation Process Calculations: A Simple Algebraic Approach Using Solvent Extraction.

ERIC Educational Resources Information Center

Crittenden, Barry D.

1991-01-01

A simple liquid-liquid equilibrium (LLE) system involving a constant partition coefficient based on solute ratios is used to develop an algebraic understanding of multistage contacting in a first-year separation processes course. This algebraic approach to the LLE system is shown to be operable for the introduction of graphical techniques…

Development and validation of a LC-MS/MS method for assessment of an anti-inflammatory indolinone derivative by in vitro blood-brain barrier models.

PubMed

Jähne, Evelyn A; Eigenmann, Daniela E; Culot, Maxime; Cecchelli, Roméo; Walter, Fruzsina R; Deli, Mária A; Tremmel, Robin; Fricker, Gert; Smiesko, Martin; Hamburger, Matthias; Oufir, Mouhssin

2014-09-01

The compound (E,Z)-3-(4-hydroxy-3,5-dimethoxybenzylidene)indolin-2-one (indolinone) was identified from lipophilic woad extracts (Isatis tinctoria L., Brassicaceae) as a compound possessing potent histamine release inhibitory and anti-inflammatory properties [1]. To further evaluate the potential of indolinone in terms of crossing the blood-brain barrier (BBB), we screened the compound in several in vitro cell-based human and animal BBB models. Therefore, we developed a quantitative LC-MS/MS method for the compound in modified Ringer HEPES buffer (RHB) and validated it according to FDA and EMA guidelines [2,3]. The calibration curve of indolinone in the range between 30.0 and 3000ng/ml was quadratic, and the limit of quantification was 30.0ng/ml. Dilution of samples up to 100-fold did not affect precision and accuracy. The carry-over was within acceptance criteria. Indolinone proved to be stable in RHB for 3h at room temperature (RT), and for three successive freeze/thaw cycles. The processed samples could be stored in the autosampler at 10°C for at least 28h. Moreover, indolinone was stable for at least 16 days in RHB when stored below -65°C. This validation study demonstrates that our method is specific, selective, precise, accurate, and capable to produce reliable results. In the immortalized human BBB mono-culture model, the apparent permeability coefficient from apical to basolateral (PappA→B), and the Papp from basolateral to apical (PappB→A) were 19.2±0.485×10(-6)cm/s and 21.7±0.326×10(-6)cm/s, respectively. For the primary rat/bovine BBB co-culture model a PappA→B of 27.1±1.67×10(-6)cm/s was determined. In the primary rat BBB triple co-culture model, the PappA→B and the PappB→A were 56.2±3.63×10(-6)cm/s and 34.6±1.41×10(-6)cm/s, respectively. The data obtained with the different models showed good correlation and were indicative of a high BBB permeation potential of indolinone confirmed by in silico prediction calculations. P

Becoming an L2 Learner (Again): How a Brief Language Learning Experience Sparked Connections with SLA Theory

ERIC Educational Resources Information Center

Forman, Ross

2015-01-01

A brief "language learning experience" (LLE) in Thai was integrated into a second language development course as part of postgraduate TESOL study at an Australian university. Sixty primary and secondary teachers from a range of schools evaluated the impact of the LLE by means of a questionnaire; the teachers proved highly affirming of…

Evaluation of tricuspid valve regurgitation following laser lead extraction†.

PubMed

Pecha, Simon; Castro, Liesa; Gosau, Nils; Linder, Matthias; Vogler, Julia; Willems, Stephan; Reichenspurner, Hermann; Hakmi, Samer

2017-06-01

The objective of this study was to examine the effect of laser lead extraction (LLE) on the development of post-procedural tricuspid regurgitation (TR). Some reports have suggested an increase in TR associated with LLE. We present a series of patients who underwent both, LLE and complete echocardiographic evaluation for TR. A single centre analysis of consecutive patients referred for LLE between January 2012 and August 2015. One hundred and three patients had tricuspid valve function evaluated before the procedure with a transthoracic echocardiography (TTE), during the procedure using transoesophageal echocardiography and postoperatively using a TTE. TR was graded from 0 (none) to 4 (severe). We treated 235 leads in 103 patients, including 118 ventricular leads. Seventy-seven were male (74.8%) and 26 female (25.2%), with a mean age of 65.6 ± 15.4 years. Mean time from initial lead implantation was 98.0 ± 67.3 months. Twenty-one patients (20.4%) had ejection fraction below 30%. No intra-procedural worsening of tricuspid valve function was seen with TEE in any of the patients. Ten patients (9.7%) were found to have TR before LLE that returned to normal valve function after the procedure. Two patients (1.9%) experienced mild TR after the procedure (both with tricuspid valve endocarditis). Ninety-one patients (88.3%) did not experience any significant change of the tricuspid valve function after LLE. Transthoracic and transoesophageal echocardiography findings showed that laser lead extraction was not associated with a significant increase in the incidence of tricuspid valve regurgitation. © The Author 2017. Published by Oxford University Press on behalf of the European Association for Cardio-Thoracic Surgery. All rights reserved.

Gas pressure assisted microliquid-liquid extraction coupled online to direct infusion mass spectrometry: a new automated screening platform for bioanalysis.

PubMed

Raterink, Robert-Jan; Witkam, Yoeri; Vreeken, Rob J; Ramautar, Rawi; Hankemeier, Thomas

2014-10-21

In the field of bioanalysis, there is an increasing demand for miniaturized, automated, robust sample pretreatment procedures that can be easily connected to direct-infusion mass spectrometry (DI-MS) in order to allow the high-throughput screening of drugs and/or their metabolites in complex body fluids like plasma. Liquid-Liquid extraction (LLE) is a common sample pretreatment technique often used for complex aqueous samples in bioanalysis. Despite significant developments that have been made in automated and miniaturized LLE procedures, fully automated LLE techniques allowing high-throughput bioanalytical studies on small-volume samples using direct infusion mass spectrometry, have not been matured yet. Here, we introduce a new fully automated micro-LLE technique based on gas-pressure assisted mixing followed by passive phase separation, coupled online to nanoelectrospray-DI-MS. Our method was characterized by varying the gas flow and its duration through the solvent mixture. For evaluation of the analytical performance, four drugs were spiked to human plasma, resulting in highly acceptable precision (RSD down to 9%) and linearity (R(2) ranging from 0.990 to 0.998). We demonstrate that our new method does not only allow the reliable extraction of analytes from small sample volumes of a few microliters in an automated and high-throughput manner, but also performs comparable or better than conventional offline LLE, in which the handling of small volumes remains challenging. Finally, we demonstrate the applicability of our method for drug screening on dried blood spots showing excellent linearity (R(2) of 0.998) and precision (RSD of 9%). In conclusion, we present the proof of principe of a new high-throughput screening platform for bioanalysis based on a new automated microLLE method, coupled online to a commercially available nano-ESI-DI-MS.

The Systematics of Light Lithophile Elements (Li, Be, B) in Lunar Picritic Glasses

NASA Astrophysics Data System (ADS)

Shearer, C. K.; Layne, G. D.; Papike, J. J.

1993-07-01

Lunar picritic glasses are thought to be the product of either partial melting of the deep lunar mantle followed by rapid ascent [1,2] or polybaric partial melting initiated in the deep lunar mantle [3]. The near primary compositions of these volcanic glasses provide us with a unique perspective for evaluating mare basaltic magmatism and the characteristics and evolution of the lunar mantle. Because of their obvious importance in deciphering the evolution of the Earth-Moon system, we have initiated an extensive trace element study of these picritic glasses using ion microprobe techniques. Here, we report the initial results of light lithophile element (LLE) analyses of these glasses. This is the first reported study of LLE in lunar basalts. The LLE have only recently received attention in terrestrial basaltic systems [4-6]. Their correlations with other more routinely analyzed trace elements (Li:Yb or V, Be:Nd, B:K) in a variety of terrestrial mantle environments have yielded several important insights into mantle magmatism [4-6]. Ion microprobe analyses of the glasses were conducted using a Cameca 4f ion microprobe operated on the UNM campus. The light lithophile elements were analyzed under the following conditions: 10-kV O- primary beam, 8-nA primary beam current, 10-15-micrometer beam diameter, sample voltage offset of -70 +- 25 V, and a 150-micrometer secondary ion image field with a 33-micrometer field aperature inserted. Counting times included background (2 seconds), 30Si (2 seconds), 7Li (2 seconds), 9Be (4 seconds), and 11B (8 seconds). Each analysis involved 30 to 40 counting cycles. These counting times resulted in precision for Li of better than 1.2% and for B and Be of better than 2.2%. Standards for Li, Be, and B in basaltic glass matrices were kindly provided by J. Ryan [4-6]. Calibration curves (LLE/30Si x wt% SiO2 vs. LLE concentration) were originally defined by a minimum of five standards for each element and are linear for the concentration

Sample preparation combined with electroanalysis to improve simultaneous determination of antibiotics in animal derived food samples.

PubMed

da Silva, Wesley Pereira; de Oliveira, Luiz Henrique; Santos, André Luiz Dos; Ferreira, Valdir Souza; Trindade, Magno Aparecido Gonçalves

2018-06-01

A procedure based on liquid-liquid extraction (LLE) and phase separation using magnetically stirred salt-induced high-temperature liquid-liquid extraction (PS-MSSI-HT-LLE) was developed to extract and pre-concentrate ciprofloxacin (CIPRO) and enrofloxacin (ENRO) from animal food samples before electroanalysis. Firstly, simple LLE was used to extract the fluoroquinolones (FQs) from animal food samples, in which dilution was performed to reduce interference effects to below a tolerable threshold. Then, adapted PS-MSSI-HT-LLE protocols allowed re-extraction and further pre-concentration of target analytes in the diluted acid samples for simultaneous electrochemical quantification at low concentration levels. To improve the peak separation, in simultaneous detection, a baseline-corrected second-order derivative approach was processed. These approaches allowed quantification of target FQs from animal food samples spiked at levels of 0.80 to 2.00 µmol L -1 in chicken meat, with recovery values always higher than 80.5%, as well as in milk samples spiked at 4.00 µmol L -1 , with recovery values close to 70.0%. Copyright © 2018 Elsevier Ltd. All rights reserved.

First-trimester markers of aneuploidy in women positive for HIV.

PubMed

Savvidou, M D; Samuel, I; Syngelaki, A; Poulton, M; Nicolaides, K H

2011-06-01

To investigate whether the sonographic and maternal serum biochemical markers used in first-trimester screening for chromosomal abnormalities are altered in pregnancies affected by maternal HIV infection. Nested case-control study. Routine antenatal visit in a teaching hospital. Ninety HIV-positive and 450 HIV-negative pregnant women. Findings from first-trimester antenatal visit for calculation of the risk for chromosomal abnormalities were compared between HIV-positive (treated and untreated) and HIV-negative women. First-trimester maternal serum free β human chorionic gonadotrophin (free β-hCG) pregnancy-associated plasma protein-A (PAPP-A) and fetal nuchal translucency thickness (NT), were compared. There were no statistically significant differences between the HIV-positive and HIV-negative women in the median maternal levels of free β-hCG, PAPP-A and fetal NT. However, within the HIV-positive group those receiving antiretroviral treatment (n = 41) had a significantly lower median multiple of the median (MoM) for free β-hCG (0.74, interquartile range [IQR] 0.45-1.32 MoM) than HIV-positive women on no treatment (1.03, IQR 0.76-1.85 MoM; P = 0.006) and HIV-negative women (1.0, IQR 0.68-1.47 MoM; P = 0.003). There was no correlation between the level of free β-hCG or PAPP-A and maternal viral load or CD4(+) count. Maternal levels of free β-hCG in treated HIV-positive pregnant women were lower compared with those in non-treated HIV-positive and HIV-negative women, whereas the PAPP-A levels and fetal NT remained unaltered. © 2010 The Authors Journal compilation © RCOG 2010 BJOG An International Journal of Obstetrics and Gynaecology.

Screening for chromosomal anomalies in the first trimester: does repeat maternal serum screening improve detection rates?

PubMed

Spencer, Kevin; Cuckle, Howard S

2002-10-01

To assess the within person biological variability of first trimester maternal serum biochemical markers of trisomy 21 across the 10-14 week gestational period. To evaluate whether repeat sampling and testing of free beta-hCG and PAPP-A during this period would result in an improved detection rate. Women presenting at the first trimester OSCAR clinic have blood collected prior to ultrasound dating and nuchal translucency measurement. All samples are analysed for free beta-hCG and PAPP-A before an accurate estimate of gestation is available. In 10% of cases the gestation is prior to the minimum time for NT measurement (11 weeks) and these women are rebooked for a repeat visit to the clinic at the appropriate time. Our fetal database was interrogated to obtain cases in which two maternal blood samples had been collected and analysed in the 10-14 week period. Using data from the marker correlations and statistical modelling, the impact of repeat testing on detection rate for trisomy 21 at a fixed 5% false positive rate, was assessed. 261 pairs of data were available for analysis collected over a 3 year period. The correlation between free beta-hCG in sample 1 and sample 2 was 0.890 and that for PAPP-A was 0.827. The average within person biological variation for free beta-hCG was 21% and 32% for PAPP-A. The increase in detection rate when using both sets of marker data was 3.5% when using serum biochemistry and maternal age, and 1.3% when using nuchal translucency, serum biochemistry and maternal age. Repeat sampling and testing of maternal serum biochemical markers is unlikely to substantially improve first trimester screening performance. Copyright 2002 John Wiley & Sons, Ltd.

Insulin- like Growth Factor-Binding Protein Action in Bone Tissue: A Key Role for Pregnancy- Associated Plasma Protein-A.

PubMed

Beattie, James; Al-Khafaji, Hasanain; Noer, Pernille R; Alkharobi, Hanaa Esa; Alhodhodi, Aishah; Meade, Josephine; El-Gendy, Reem; Oxvig, Claus

2018-01-01

The insulin-like growth factor (IGF) axis is required for the differentiation, development, and maintenance of bone tissue. Accordingly, dysregulation of this axis is associated with various skeletal pathologies including growth abnormalities and compromised bone structure. It is becoming increasingly apparent that the action of the IGF axis must be viewed holistically taking into account not just the actions of the growth factors and receptors, but also the influence of soluble high affinity IGF binding proteins (IGFBPs).There is a recognition that IGFBPs exert IGF-dependent and IGF-independent effects in bone and other tissues and that an understanding of the mechanisms of action of IGFBPs and their regulation in the pericellular environment impact critically on tissue physiology. In this respect, a group of IGFBP proteinases (which may be considered as ancillary members of the IGF axis) play a crucial role in regulating IGFBP function. In this model, cleavage of IGFBPs by specific proteinases into fragments with lower affinity for growth factor(s) regulates the partition of IGFs between IGFBPs and cell surface IGF receptors. In this review, we examine the importance of IGFBP function in bone tissue with special emphasis on the role of pregnancy associated plasma protein-A (PAPP-A). We examine the function of PAPP-A primarily as an IGFBP-4 proteinase and present evidence that PAPP-A induced cleavage of IGFBP-4 is potentially a key regulatory step in bone metabolism. We also highlight some recent findings with regard to IGFBP-2 and IGFBP-5 (also PAPP-A substrates) function in bone tissue and briefly discuss the actions of the other three IGFBPs (-1, -3, and -6) in this tissue. Although our main focus will be in bone we will allude to IGFBP activity in other cells and tissues where appropriate.

A simple liquid extraction protocol for overcoming the ion suppression of triacylglycerols by phospholipids in liquid chromatography mass spectrometry studies.

PubMed

Araujo, Pedro; Tilahun, Ephrem; Breivik, Joar Fjørtoft; Abdulkader, Bashir M; Frøyland, Livar; Zeng, Yingxu

2016-02-01

It is well-known that triacylglycerol (TAG) ions are suppressed by phospholipid (PL) ions in regiospecific analysis of TAG by mass spectrometry (MS). Hence, it is essential to remove the PL during sample preparation prior to MS analysis. The present article proposes a cost-effective liquid-liquid extraction (LLE) method to remove PL from TAG in different kinds of biological samples by using methanol, hexane and water. High performance thin layer chromatography confirmed the lack of PL in krill oil and salmon liver samples, submitted to the proposed LLE protocol, and liquid chromatography tandem MS confirmed that the identified TAG ions were highly enhanced after implementing the LLE procedure. Copyright © 2015 Elsevier B.V. All rights reserved.

Use of plasma proteins as solubilizing agents in in vitro permeability experiments: correction for unbound drug concentration using the reciprocal permeability approach.

PubMed

Katneni, Kasiram; Charman, Susan A; Porter, Christopher J H

2008-01-01

The purpose of the present study was to explore the applicability of the reciprocal permeability approach to correct for changes in thermodynamic activity when in vitro permeability data are generated in the presence of plasma proteins. Diazepam (DIA), digoxin (DIG), and propranolol (PRO) permeability was assessed in the presence of bovine serum albumin (BSA) and bovine alpha-1-acid glycoprotein (AAG). The reciprocal permeability approach was subsequently employed to calculate the true permeability coefficient (Papp(corr)) and the operational protein association constant (nK(a)). For BSA binding, good agreement was observed between the Papp(corr) values and Papp values obtained in the absence of protein. For PRO and AAG, where binding affinity was high, deviation in the reciprocal permeability plots was evident suggesting ligand depletion at low drug/high protein concentrations. Bidirectional DIG permeability data in the presence of either BSA or AAG indicated that neither protein had an effect on the efflux transporters involved in DIG permeability. The data suggest that plasma proteins can be utilized in permeability experiments with no adverse effects on transporter function and that the reciprocal permeability approach can be used to correct permeability data for changes in unbound drug concentration. c) 2007 Wiley-Liss, Inc.

[Traditional Chinese medicine pairs (III)--effect of extract of Ginseng Radix et Rhizoma and Puerariae Lobatae Radix on intestinal absorption in rats].

PubMed

Chen, Yi-hang; Li, Meng-xuan; Meng, Zhao-qing; Yang, Jiao-jiao; Huang, Wen-zhe; Wang, Zhen-zhong; Wang, Yue-sheng; Xiao, Wei

2015-08-01

This study focused on the intestinal absorption of traditional Chinese medicines (TCM) to reveal the scientific connotation of the compatibility of TCM pairs. The single pass intestinal perfusion (SPIP) was used in rats to compare the absorption of single extracts from Puerariae Lobatae Radix, single extracts from Ginseng Radix et Rhizoma, combined extracts from Puerariae Lobatae Radix and Ginseng Radix et Rhizoma and Puerariae Lobatae Radix and Ginseng Radix et Rhizoma mixture in rats. The content of puerarin, ginsenoside Rg1, ginsenoside Re and ginsenoside Rb1 in liquid were tested by HPLC. The speed constant (Ka) and apparent permeability coefficients (Papp) were calculated and compared. Specifically, the order of puerarin Ka and Papp values from high to low was Ginseng Radix et Rhizoma and Puerariae Lobatae Radix mixture > single extracts from Puerariae Lobatae Radix > combined extracts from Ginseng Radix et Rhizoma and Puerariae Lobatae Radix; the order of ginsenosides Ka and Papp values from high to low was Ginseng Radix et Rhizoma and Puerariae Lobatae Radix mixture > single extracts from Ginseng Radix et Rhizoma > combined extracts from Ginseng Radix et Rhizoma and Puerariae Lobatae Radix. The combined administration of Ginseng Radix et Rhizoma and Puerariae Lobatae Radix may improve the absorption in the intestinal tract.

Locally linear embedding: dimension reduction of massive protostellar spectra

NASA Astrophysics Data System (ADS)

Ward, J. L.; Lumsden, S. L.

2016-09-01

We present the results of the application of locally linear embedding (LLE) to reduce the dimensionality of dereddened and continuum subtracted near-infrared spectra using a combination of models and real spectra of massive protostars selected from the Red MSX Source survey data base. A brief comparison is also made with two other dimension reduction techniques; principal component analysis (PCA) and Isomap using the same set of spectra as well as a more advanced form of LLE, Hessian locally linear embedding. We find that whilst LLE certainly has its limitations, it significantly outperforms both PCA and Isomap in classification of spectra based on the presence/absence of emission lines and provides a valuable tool for classification and analysis of large spectral data sets.

Cost effectiveness, the economic considerations of prenatal screening strategies for trisomy 21 in the Czech Republic.

PubMed

Dhaifalah, I; Májek, O

2012-02-01

To perform an incremental cost-effectiveness analysis for screening of trisomy 21 (Down syndrome) in the Czech Republic through a decision tree model designed to evaluate the costs and potential risks involved in using different strategies of screening. METHODS AND DATA ANALYSIS: Using decision-analysis modelling, we compared the cost-effectiveness of nine possible screening strategies for trisomy 21: 1. maternal age > or = 35 in first trimester, 2. maternal age > or = 35 in second trimester, 3. second trimester triple test (AFP, hCG, mu E3), 4. nuchal translucency measurement, 5. first trimester serum test (PAPP-A, fbeta-hCG), 6. first trimester combined (nuchal translucency, PAPP-A, fbeta-hCG) not in OSCAR manner, 7. first trimester combined (nuchal translucency, PAPP-A, fbeta-hCG) in OSCAR manner, 8. first trimester combined (nuchal translucency, nasal bone, PAPP-A, fbeta-hCG) not in OSCAR manner, 9. first trimester combined (nuchal translucency, nasal bone, PAPP-A, fbeta-hCG) in OSCAR manner. The analysis is performed from a health care payer perspective using relevant cost and outcomes related to each screening strategy in a cohort of 118,135 pregnant women presenting around 12 weeks of pregnancy in the Czech Republic. Using a computer spreadsheet Excel (Microsoft Corporation, Redmond, Wash) the following outcomes: overall cost-effectiveness, trisomy 21 cases detected, trisomy 21 live birth prevented and euploid losses from invasive procedures were obtained. The incremental cost-effectiveness ratios were also calculated by a comparison of strategy nine and strategy three (the current practice in the Czech Republic). Under the baseline assumptions, the model favors strategy nine as the most cost-effective trisomy 21 screening strategy. This strategy was the least expensive strategy per trisomy 21 cases averted. Although all the other strategies cost less, they all had lower trisomy 21 detection rates and higher numbers of procedure-related losses (except for

Comparison of Electron Imaging Modes for Dimensional Measurements in the Scanning Electron Microscope.

PubMed

Postek, Michael T; Vladár, András E; Villarrubia, John S; Muto, Atsushi

2016-08-01

Dimensional measurements from secondary electron (SE) images were compared with those from backscattered electron (BSE) and low-loss electron (LLE) images. With the commonly used 50% threshold criterion, the lines consistently appeared larger in the SE images. As the images were acquired simultaneously by an instrument with the capability to operate detectors for both signals at the same time, the differences cannot be explained by the assumption that contamination or drift between images affected the SE, BSE, or LLE images differently. Simulations with JMONSEL, an electron microscope simulator, indicate that the nanometer-scale differences observed on this sample can be explained by the different convolution effects of a beam with finite size on signals with different symmetry (the SE signal's characteristic peak versus the BSE or LLE signal's characteristic step). This effect is too small to explain the >100 nm discrepancies that were observed in earlier work on different samples. Additional modeling indicates that those discrepancies can be explained by the much larger sidewall angles of the earlier samples, coupled with the different response of SE versus BSE/LLE profiles to such wall angles.

Delivery of paclitaxel across cellular barriers using a dendrimer-based nanocarrier.

PubMed

Teow, Huey Minn; Zhou, Zhengyuan; Najlah, Mohammad; Yusof, Siti R; Abbott, N Joan; D'Emanuele, Antony

2013-01-30

The aim of this study was to investigate the ability of a third-generation (G3) polyamidoamine (PAMAM) dendrimer-based carrier to enhance the permeability of paclitaxel (pac) and to overcome cellular barriers. G3 dendrimers were surface modified with lauryl chains (L) and conjugated with paclitaxel (pac) via a glutaric anhydride (glu) linker, followed by labeling with FITC. Biological evaluation of the dendrimer and conjugates was conducted using the human colon adenocarcinoma cell line (Caco-2) and primary cultured porcine brain endothelial cells (PBECs). LDH assay was used to evaluate the cytotoxicity of the dendrimer and conjugates. Cytotoxicity studies showed that the conjugation of lauryl chains and paclitaxel on G3 dendrimer significantly (p<0.05) increased the cytotoxicity against both cell types. Permeability studies of dendrimer-drug conjugates demonstrated an increase in the apparent permeability coefficient (P(app)) in both apical to basolateral A→B and basolateral to apical B→A directions across both cell monolayers compared to unmodified G3 and free drug. The B→A P(app) of paclitaxel was significantly (p<0.05) higher than the A→B P(app), indicating active function of P-gp efflux transporter system in both cell models. L6-G3-glu-pac conjugate had approximately 12-fold greater permeability across both cell monolayers than that of paclitaxel alone. Copyright © 2012 Elsevier B.V. All rights reserved.

One level up: abnormal proteolytic regulation of IGF activity plays a role in human pathophysiology.

PubMed

Argente, Jesús; Chowen, Julie A; Pérez-Jurado, Luis A; Frystyk, Jan; Oxvig, Claus

2017-10-01

The discovery of a mutation in a specific gene can be very important for determining the pathophysiology underlying the disease of a patient and may also help to decide the best treatment protocol on an individual basis. However, sometimes the discovery of mutations in new proteins advances our comprehension in a more widespread manner. The growth hormone (GH)/insulin-like growth factor (IGF)-1 axis is fundamental for systemic growth, but is also involved in many other important processes. Our understanding of this system in physiology and pathophysiology has advanced throughout the years with each discovery of mutations in members of this axis. This review focuses on the most recent discovery: mutations in the metalloproteinase pregnancy-associated plasma protein-A2 (PAPP-A2), one of the proteases involved in liberating IGF-1 from the complexes in which it circulates, in patients with delayed growth failure. We also discuss the advances in the stanniocalcins (STC1 and STC2), proteins that modulate PAPP-A2, as well as PAPP-A. These new advances not only bring us one step closer to understanding the strict spatial and temporal control of this axis in systemic growth and maturation, but also highlight possible therapeutic targets when this system goes awry. © 2017 The Authors. Published under the terms of the CC BY 4.0 license.

Bioaccessibility, Intestinal Permeability and Plasma Stability of Isorhamnetin Glycosides from Opuntia ficus-indica (L.).

PubMed

Antunes-Ricardo, Marilena; Rodríguez-Rodríguez, César; Gutiérrez-Uribe, Janet A; Cepeda-Cañedo, Eduardo; Serna-Saldívar, Sergio O

2017-08-22

Isorhamnetin glycosides are representative compounds of Opuntia ficus-indica that possess different biological activities. There is slight information about the changes in bioaccessibility induced by the glycosylation pattern of flavonoids, particularly for isorhamnetin. In this study, the bioaccessibility and permeability of isorhamnetin glycosides extracted from O. ficus-indica were contrasted with an isorhamnetin standard. Also, the plasma stability of these isorhamnetin glycosides after intravenous administration in rats was evaluated. Recoveries of isorhamnetin after oral and gastric digestion were lower than that observed for its glycosides. After intestinal digestion, isorhamnetin glycosides recoveries were reduced to less than 81.0%. The apparent permeability coefficient from apical (AP) to basolateral (BL) direction (Papp (AP-BL) ) of isorhamnetin was 2.6 to 4.6-fold higher than those obtained for its glycosides. Isorhamnetin diglycosides showed higher Papp (AP-BL) values than triglycosides. Sugar substituents affected the Papp (AP-BL) of the triglycosides. Isorhamnetin glycosides were better retained in the circulatory system than the aglycone. After intravenous dose of the isorhamnetin standard, the elimination half-life was 0.64 h but increased to 1.08 h when the O. ficus-indica extract was administered. These results suggest that isorhamnetin glycosides naturally found in O. ficus-indica could be a controlled delivery system to maintain a constant plasmatic concentration of this important flavonoid to exert its biological effects in vivo.

Effect of ethnicity on first trimester biomarkers for combined trisomy 21 screening: results from a multicenter study in six Asian countries.

PubMed

Manotaya, Saknan; Zitzler, Juergen; Li, Xiaotian; Wibowo, Noroyono; Pham, Thi Mai; Kang, Myung Seo; Lee, Chien-Nan

2015-08-01

To assess differences between first trimester trisomy 21 screening markers free beta chain of the human chorionic gonadotrophin (βhCG) and pregnancy-associated plasma protein A (PAPP-A) in pregnant women of six different Asian countries (China, Indonesia, Korea, Taiwan, Thailand, and Vietnam) and compare serum levels with those in women of European countries. Median and multiple of median (MoM) values of free βhCG and PAPP-A were determined in more than 3000 pregnant women from the Asian countries during their first trimester of pregnancy. Differences in MoM values between a European reference group from a previous multicenter evaluation and the Asian population were evaluated. Two different types of population correction factors for T21 risk estimation were assessed. An at least 10% difference of median MoMs between European and Asian PAPP-A values was found to be statistically significant (p < 0.0001). The specificity of the screening did not show a big difference in individual countries, when using the country-specific correction factor compared with the overall Asian correction factor (<1.4%). The use of a correction factor is recommended based on the differences in European and Asian MoM values. Developing country-specific medians in larger study populations can help identify clinical relevant differences and give the opportunity to explore a more accurate risk calculation. © 2015 John Wiley & Sons, Ltd.

Bioaccessibility, Intestinal Permeability and Plasma Stability of Isorhamnetin Glycosides from Opuntia ficus-indica (L.)

PubMed Central

Antunes-Ricardo, Marilena; Rodríguez-Rodríguez, César; Cepeda-Cañedo, Eduardo

2017-01-01

Isorhamnetin glycosides are representative compounds of Opuntia ficus-indica that possess different biological activities. There is slight information about the changes in bioaccessibility induced by the glycosylation pattern of flavonoids, particularly for isorhamnetin. In this study, the bioaccessibility and permeability of isorhamnetin glycosides extracted from O. ficus-indica were contrasted with an isorhamnetin standard. Also, the plasma stability of these isorhamnetin glycosides after intravenous administration in rats was evaluated. Recoveries of isorhamnetin after oral and gastric digestion were lower than that observed for its glycosides. After intestinal digestion, isorhamnetin glycosides recoveries were reduced to less than 81.0%. The apparent permeability coefficient from apical (AP) to basolateral (BL) direction (Papp(AP-BL)) of isorhamnetin was 2.6 to 4.6-fold higher than those obtained for its glycosides. Isorhamnetin diglycosides showed higher Papp(AP-BL) values than triglycosides. Sugar substituents affected the Papp(AP-BL) of the triglycosides. Isorhamnetin glycosides were better retained in the circulatory system than the aglycone. After intravenous dose of the isorhamnetin standard, the elimination half-life was 0.64 h but increased to 1.08 h when the O. ficus-indica extract was administered. These results suggest that isorhamnetin glycosides naturally found in O. ficus-indica could be a controlled delivery system to maintain a constant plasmatic concentration of this important flavonoid to exert its biological effects in vivo. PMID:28829356

Co-variables in first trimester maternal serum screening.

PubMed

de Graaf, I M; Cuckle, H S; Pajkrt, E; Leschot, N J; Bleker, O P; van Lith, J M

2000-03-01

The objective of this study was to determined the influence of maternal weight, maternal smoking habits, gravidity, parity and fetal gender on the level of maternal serum marker used in first trimester screening for Down syndrome. A total of 2449 singleton unaffected pregnancies from two centres were studied. Maternal serum free beta-human chorionic gonadotrophin (hCG) and alpha-fetoprotein (AFP) concentrations had been measured in all pregnancies, and pregnancy associated plasma protein (PAPP)-A levels had been measured in 924. All results were expressed as multiples of the gestation specific median (MoM) values after regression, using each centre's own medians. Information on maternal weight was available in 2259 pregnancies, on self-reported current cigarette smoking in 1364 (of whom 117 (8.6%) were smokers), on gravidity in 1371, parity in 1303 and fetal gender in 253. All three markers showed a statistically significant negative association with maternal weight (p<0.0005) and in the subsequent analyses MoM values were weight adjusted using standard methods. The median PAPP-A level in smokers was 0.81 MoM, a significant reduction (p<0.005); free beta-hCG was also reduced (median 0.89 MoM) but not significantly (p=0.17), and AFP was unaltered. The median AFP level in primagravidas was highly significantly greater than that in gravid women (p<0.0005). In PAPP-A the reverse effect was seen but it did not reach statistical significance (p=0.15) and there was no effect for free beta-hCG. Results of a similar magnitude and direction were found for parity. The median level of free beta-hCG was higher (p=0.0005), and the median AFP lower in female pregnancies. Maternal weight and, for PAPP-A, maternal smoking are important first trimester screening co-variables. Gravidity, parity and fetal gender also seem to influence one or more first trimester markers. Copyright 2000 John Wiley & Sons, Ltd.

Using redescription mining to relate clinical and biological characteristics of cognitively impaired and Alzheimer's disease patients.

PubMed

Mihelčić, Matej; Šimić, Goran; Babić Leko, Mirjana; Lavrač, Nada; Džeroski, Sašo; Šmuc, Tomislav

2017-01-01

Based on a set of subjects and a collection of attributes obtained from the Alzheimer's Disease Neuroimaging Initiative database, we used redescription mining to find interpretable rules revealing associations between those determinants that provide insights about the Alzheimer's disease (AD). We extended the CLUS-RM redescription mining algorithm to a constraint-based redescription mining (CBRM) setting, which enables several modes of targeted exploration of specific, user-constrained associations. Redescription mining enabled finding specific constructs of clinical and biological attributes that describe many groups of subjects of different size, homogeneity and levels of cognitive impairment. We confirmed some previously known findings. However, in some instances, as with the attributes: testosterone, ciliary neurotrophic factor, brain natriuretic peptide, Fas ligand, the imaging attribute Spatial Pattern of Abnormalities for Recognition of Early AD, as well as the levels of leptin and angiopoietin-2 in plasma, we corroborated previously debatable findings or provided additional information about these variables and their association with AD pathogenesis. Moreover, applying redescription mining on ADNI data resulted with the discovery of one largely unknown attribute: the Pregnancy-Associated Protein-A (PAPP-A), which we found highly associated with cognitive impairment in AD. Statistically significant correlations (p ≤ 0.01) were found between PAPP-A and clinical tests: Alzheimer's Disease Assessment Scale, Clinical Dementia Rating Sum of Boxes, Mini Mental State Examination, etc. The high importance of this finding lies in the fact that PAPP-A is a metalloproteinase, known to cleave insulin-like growth factor binding proteins. Since it also shares similar substrates with A Disintegrin and the Metalloproteinase family of enzymes that act as α-secretase to physiologically cleave amyloid precursor protein (APP) in the non-amyloidogenic pathway, it could be

Genomic association for sexual precocity in beef heifers using pre-selection of genes and haplotype reconstruction

PubMed Central

Barbero, Marina M. D.; Oliveira, Henrique N.; de Camargo, Gregório M. F.; Fernandes Júnior, Gerardo A.; Aspilcueta-Borquis, Rusbel R.; Souza, Fabio R. P.; Boligon, Arione A.; Melo, Thaise P.; Regatieri, Inaê C.; Feitosa, Fabieli L. B.; Fonseca, Larissa F. S.; Magalhães, Ana F. B.; Costa, Raphael B.; Albuquerque, Lucia G.

2018-01-01

Reproductive traits are of the utmost importance for any livestock farming, but are difficult to measure and to interpret since they are influenced by various factors. The objective of this study was to detect associations between known polymorphisms in candidate genes related to sexual precocity in Nellore heifers, which could be used in breeding programs. Records of 1,689 precocious and non-precocious heifers from farms participating in the Conexão Delta G breeding program were analyzed. A subset of single nucleotide polymorphisms (SNP) located in the region of the candidate genes at a distance of up to 5 kb from the boundaries of each gene, were selected from the panel of 777,000 SNPs of the High-Density Bovine SNP BeadChip. Linear mixed models were used for statistical analysis of early heifer pregnancy, relating the trait with isolated SNPs or with haplotype groups. The model included the contemporary group (year and month of birth) as fixed effect and parent of the animal (sire effect) as random effect. The fastPHASE® and GenomeStudio® were used for reconstruction of the haplotypes and for analysis of linkage disequilibrium based on r2 statistics. A total of 125 candidate genes and 2,024 SNPs forming haplotypes were analyzed. Statistical analysis after Bonferroni correction showed that nine haplotypes exerted a significant effect (p<0.05) on sexual precocity. Four of these haplotypes were located in the Pregnancy-associated plasma protein-A2 gene (PAPP-A2), two in the Estrogen-related receptor gamma gene (ESRRG), and one each in the Pregnancy-associated plasma protein-A gene (PAPP-A), Kell blood group complex subunit-related family (XKR4) and mannose-binding lectin genes (MBL-1) genes. Although the present results indicate that the PAPP-A2, PAPP-A, XKR4, MBL-1 and ESRRG genes influence sexual precocity in Nellore heifers, further studies are needed to evaluate their possible use in breeding programs. PMID:29293544

Using redescription mining to relate clinical and biological characteristics of cognitively impaired and Alzheimer’s disease patients

PubMed Central

Mihelčić, Matej; Šimić, Goran; Babić Leko, Mirjana; Lavrač, Nada; Džeroski, Sašo; Šmuc, Tomislav

2017-01-01

Based on a set of subjects and a collection of attributes obtained from the Alzheimer’s Disease Neuroimaging Initiative database, we used redescription mining to find interpretable rules revealing associations between those determinants that provide insights about the Alzheimer’s disease (AD). We extended the CLUS-RM redescription mining algorithm to a constraint-based redescription mining (CBRM) setting, which enables several modes of targeted exploration of specific, user-constrained associations. Redescription mining enabled finding specific constructs of clinical and biological attributes that describe many groups of subjects of different size, homogeneity and levels of cognitive impairment. We confirmed some previously known findings. However, in some instances, as with the attributes: testosterone, ciliary neurotrophic factor, brain natriuretic peptide, Fas ligand, the imaging attribute Spatial Pattern of Abnormalities for Recognition of Early AD, as well as the levels of leptin and angiopoietin-2 in plasma, we corroborated previously debatable findings or provided additional information about these variables and their association with AD pathogenesis. Moreover, applying redescription mining on ADNI data resulted with the discovery of one largely unknown attribute: the Pregnancy-Associated Protein-A (PAPP-A), which we found highly associated with cognitive impairment in AD. Statistically significant correlations (p ≤ 0.01) were found between PAPP-A and clinical tests: Alzheimer’s Disease Assessment Scale, Clinical Dementia Rating Sum of Boxes, Mini Mental State Examination, etc. The high importance of this finding lies in the fact that PAPP-A is a metalloproteinase, known to cleave insulin-like growth factor binding proteins. Since it also shares similar substrates with A Disintegrin and the Metalloproteinase family of enzymes that act as α-secretase to physiologically cleave amyloid precursor protein (APP) in the non-amyloidogenic pathway, it could

Genomic association for sexual precocity in beef heifers using pre-selection of genes and haplotype reconstruction.

PubMed

Takada, Luciana; Barbero, Marina M D; Oliveira, Henrique N; de Camargo, Gregório M F; Fernandes Júnior, Gerardo A; Aspilcueta-Borquis, Rusbel R; Souza, Fabio R P; Boligon, Arione A; Melo, Thaise P; Regatieri, Inaê C; Feitosa, Fabieli L B; Fonseca, Larissa F S; Magalhães, Ana F B; Costa, Raphael B; Albuquerque, Lucia G

2018-01-01

Reproductive traits are of the utmost importance for any livestock farming, but are difficult to measure and to interpret since they are influenced by various factors. The objective of this study was to detect associations between known polymorphisms in candidate genes related to sexual precocity in Nellore heifers, which could be used in breeding programs. Records of 1,689 precocious and non-precocious heifers from farms participating in the Conexão Delta G breeding program were analyzed. A subset of single nucleotide polymorphisms (SNP) located in the region of the candidate genes at a distance of up to 5 kb from the boundaries of each gene, were selected from the panel of 777,000 SNPs of the High-Density Bovine SNP BeadChip. Linear mixed models were used for statistical analysis of early heifer pregnancy, relating the trait with isolated SNPs or with haplotype groups. The model included the contemporary group (year and month of birth) as fixed effect and parent of the animal (sire effect) as random effect. The fastPHASE® and GenomeStudio® were used for reconstruction of the haplotypes and for analysis of linkage disequilibrium based on r2 statistics. A total of 125 candidate genes and 2,024 SNPs forming haplotypes were analyzed. Statistical analysis after Bonferroni correction showed that nine haplotypes exerted a significant effect (p<0.05) on sexual precocity. Four of these haplotypes were located in the Pregnancy-associated plasma protein-A2 gene (PAPP-A2), two in the Estrogen-related receptor gamma gene (ESRRG), and one each in the Pregnancy-associated plasma protein-A gene (PAPP-A), Kell blood group complex subunit-related family (XKR4) and mannose-binding lectin genes (MBL-1) genes. Although the present results indicate that the PAPP-A2, PAPP-A, XKR4, MBL-1 and ESRRG genes influence sexual precocity in Nellore heifers, further studies are needed to evaluate their possible use in breeding programs.

A new mechanism for increasing the oral bioavailability of scutellarin with Cremophor EL: Activation of MRP3 with concurrent inhibition of MRP2 and BCRP.

PubMed

Xiao, Lu; Yi, Tao; Chen, Min; Lam, Christopher Wai Kei; Zhou, Hua

2016-10-10

Efflux transporters are extensively distributed and expressed in the intestinal epithelium and contribute to the low oral bioavailability of flavonoids and flavonoid glucuronides by pumping these compounds back into intestinal lumen. Our previous study has shown the inhibitory effect of Cremophor EL, a non-ionic surfactant, on efflux transporter multidrug resistance-associated protein (MRP) 2. In the current study, by using membranes overexpressing several common ATP-binding cassette (ABC) transporters including P-glycoprotein (P-gp), MRP1, MRP2, MRP3 and breast cancer resistance protein (BCRP), scutellarin, a poorly water-soluble flavonoid, was identified as the substrate of MPR2, MRP3 and BCRP. The effects of Cremophor EL on the transmembrane transportation of scutellarin by MRP2, BCRP, and MRP3 were investigated with inside-out Sf9 vesicles. Results showed that at nontoxic concentrations, Cremophor EL enhanced the transportation of scutellarin by MRP3 and inhibited the efflux transportation of scutellarin by MRP2 and BCRP concurrently. The relations between Cremophor EL and these transporters were explored using MDCK II-MRP2, MDCK II-BCRP, and MDCK II-MRP3 cell models. Compared with the control group, 5μg/ml Cremophor EL decreased the Papp(BL-AP) of scutellarin in MDCK II-MRP2 cell monolayers by >4 fold (from 13.57±0.76×10(-7) to 2.90±0.14×10(-7)cm/s), and the Papp(BL-AP) in MDCK II-BCRP cell monolayers decreased from 9.12±0.15×10(-7) to 6.34±0.08×10(-7)cm/s. On MDCK II-MRP3 cell monolayers, 5μg/ml Cremophor EL increased the Papp(AP-BL) of scutellarin by 3.5 fold (from 7.88±0.43×10(-7) to 2.79±1.61×10(-6)cm/s), and caused an over 5-fold increase in Papp(AP-BL)/Papp(BL-AP). These findings suggested that Cremophor EL possesses the potent ability of inhibiting MRP2 and BCRP, as well as activating MRP3 effectively. In vivo pharmacokinetic research in rats further confirmed the improvement of oral absorption of scutellarin by Cremophor EL. In summary

Bearing Fault Diagnosis Based on Statistical Locally Linear Embedding

PubMed Central

Wang, Xiang; Zheng, Yuan; Zhao, Zhenzhou; Wang, Jinping

2015-01-01

Fault diagnosis is essentially a kind of pattern recognition. The measured signal samples usually distribute on nonlinear low-dimensional manifolds embedded in the high-dimensional signal space, so how to implement feature extraction, dimensionality reduction and improve recognition performance is a crucial task. In this paper a novel machinery fault diagnosis approach based on a statistical locally linear embedding (S-LLE) algorithm which is an extension of LLE by exploiting the fault class label information is proposed. The fault diagnosis approach first extracts the intrinsic manifold features from the high-dimensional feature vectors which are obtained from vibration signals that feature extraction by time-domain, frequency-domain and empirical mode decomposition (EMD), and then translates the complex mode space into a salient low-dimensional feature space by the manifold learning algorithm S-LLE, which outperforms other feature reduction methods such as PCA, LDA and LLE. Finally in the feature reduction space pattern classification and fault diagnosis by classifier are carried out easily and rapidly. Rolling bearing fault signals are used to validate the proposed fault diagnosis approach. The results indicate that the proposed approach obviously improves the classification performance of fault pattern recognition and outperforms the other traditional approaches. PMID:26153771

Chronic low back pain after lumbosacral fracture due to sagittal and frontal vertebral imbalance.

PubMed

Boyoud-Garnier, L; Boudissa, M; Ruatti, S; Kerschbaumer, G; Grobost, P; Tonetti, J

2017-06-01

Over time, some patients with unilateral or bilateral lumbosacral injuries experience chronic low back pain. We studied the sagittal and frontal balance in a population with these injuries to determine whether mismatch in the pelvic and lumbar angles are associated with chronic low back pain. Patients with posterior pelvic ring fractures (Tile C1, C2, C3 and A3.3) that had healed were included. Foreign patients and those with an associated spinal or acetabular fracture or nonunion were excluded. The review consisted of subjective questionnaires, a clinical examination, and standing A/P and lateral stereoradiographic views. The pelvic tilt (PT), sacral slope (SS), pelvic incidence (PI), measured lumbar lordosis (LLm), T9 sagittal offset, leg discrepancy (LD) and lateral curvature (LC). The expected lumbar lordosis (LLe) was calculated using the formula LLe=PI+9°. We defined lumbopelvic mismatch (LPM) as the difference between LLm and LLe being equal or greater than 25% of LLe. Fifteen patients were reviewed after an average follow-up of 8.8 years [5.4-15]. There were four Tile C1, five Tile C2, five Tile C3 and one Tile A3.3 fracture. Ten of the 15 patients had low back pain. The mean angles were: LLm 49.6° and LLe 71.9° (P=0.002), PT 21.3°, SS 44.1°, PI 62.9° in patients with low back pain and LLm 57.4° and LLe 63.2° (P=0.55), PT 13°, SS 43.1°, PI 54.2° in those without. LPM was present in 9 patients, 8 of who had low back pain (P=0.02). Six patients, all of whom had low back pain, had a mean LC of 7.5° [4.5-23] (P=0.02). The mean LD was 0.77cm. The findings of this small study suggest that patients who experience low back pain after their posterior arch of the pelvic ring fracture has healed, have a lumbopelvic mismatch. Early treatment of these patients should aim to reestablish the anatomy of the pelvic base relative to the frontal and sagittal balance. IV. Copyright © 2017 Elsevier Masson SAS. All rights reserved.

The Sixth Omega Laser Facility Users Group Workshop

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

Petrasso, R. D.

A capacity gathering of over 100 researchers from 25 universities and laboratories met at the Laboratory for Laser Energetics (LLE) for the Sixth Omega Laser Facility Users Group (OLUG) workshop. The purpose of the 2.5-day workshop was to facilitate communications and exchanges among individual OMEGA users, and between users and the LLE management; to present ongoing and proposed research; to encourage research opportunities and collaborations that could be undertaken at the Omega Laser Facility and in a complementary fashion at other facilities [such as the National Ignition Facility (NIF) or the Laboratoire pour l’Utilisation des Lasers Intenses (LULI)]; to providemore » an opportunity for students, postdoctoral fellows, and young researchers to present their research in an informal setting; and to provide feedback from the users to LLE management about ways to improve and keep the facility and future experimental campaigns at the cutting edge.« less

The Fifth Omega Laser Facility Users Group Workshop

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

Petrasso, R. D.

A capacity gathering of over 100 researchers from 25 universities and laboratories met at the Laboratory for Laser Energetics (LLE) for the Fifth Omega Laser Facility Users Group (OLUG) workshop. The purpose of the 2.5-day workshop was to facilitate communications and exchanges among individual Omega users and between users and the LLE management; to present ongoing and proposed research; to encourage research opportunities and collaborations that could be undertaken at the Omega Laser Facility and in a complementary fashion at other facilities [such as the National Ignition Facility (NIF) or the Laboratoire pour l’Utilisation des Lasers Intenses (LULI)]; to providemore » an opportunity for students, postdoctoral fellows, and young researchers to present their research in an informal setting; and to provide feedback to LLE management from the users about ways to improve the facility and future experimental campaigns.« less

Lyapunov exponent and criticality in the Hamiltonian mean field model

NASA Astrophysics Data System (ADS)

Filho, L. H. Miranda; Amato, M. A.; Rocha Filho, T. M.

2018-03-01

We investigate the dependence of the largest Lyapunov exponent (LLE) of an N-particle self-gravitating ring model at equilibrium with respect to the number of particles and its dependence on energy. This model has a continuous phase-transition from a ferromagnetic to homogeneous phase, and we numerically confirm with large scale simulations the existence of a critical exponent associated to the LLE, although at variance with the theoretical estimate. The existence of strong chaos in the magnetized state evidenced by a positive Lyapunov exponent is explained by the coupling of individual particle oscillations to the diffusive motion of the center of mass of the system and also results in a change of the scaling of the LLE with the number of particles. We also discuss thoroughly for the model the validity and limits of the approximations made by a geometrical model for their analytic estimate.

Chaotic characteristics enhanced by impeller of perturbed six-bent-bladed turbine in stirred tank

NASA Astrophysics Data System (ADS)

Luan, Deyu; Zhang, Shengfeng; Lu, Jianping; Zhang, Xiaoguang

The fundamental way of improving the mixing efficiency is to induce the chaotic flow in a stirred vessel. The impeller form plays an important role for changing the structure of flow field and realizing chaotic mixing. Based on the velocity time series acquired by the experiment of particle image velocimetry (PIV), with the software Matlab, the macro-instability (MI), largest Lyapunov exponent (LLE), and Kolmogorov entropy in the water stirred tank is investigated respectively with the impeller of perturbed six-bent-bladed turbine (6PBT). The results show that the MI characteristics are obvious and two peak values of MI frequency are observed at the speed N = 60 rpm. With the increasing speed (more than 100 rpm), the peak characteristics of MI frequency disappear and a multi-scale wavelet structure of characterizing the chaotic flow field appears. Moreover, under the speed N = 60 rpm, the LLE is less than 0 and Kolmogorov entropy is 0, which means that the flow field is in the periodic moving state. As the speed is increased to more than 100 rpm, the LLE and Kolmogorov entropy are all more than 0, which indicates that the flow field goes into the chaotic mixing. When the speed reaches up to about 210 rpm, both of the LLE and Kolmogorov entropy achieve the optimum values, which will result in an excellent chaos with the highest mixing efficient. So it is feasible that the MI frequency, the LLE and the Kolmogorov entropy can be used to analyze the flow field characteristics in a stirred tank. The research results promote the understanding of the chaotic mixing mechanism and provide a theoretical reference for the development of new type impeller.

Three Months of Progressive High-Load Versus Traditional Low-Load Strength Training Among Patients With Rotator Cuff Tendinopathy: Primary Results From the Double-Blind Randomized Controlled RoCTEx Trial

PubMed Central

Ingwersen, Kim Gordon; Jensen, Steen Lund; Sørensen, Lilli; Jørgensen, Hans Ri; Christensen, Robin; Søgaard, Karen; Juul-Kristensen, Birgit

2017-01-01

Background: Progressive high-load exercise (PHLE) has led to positive clinical results in patients with patellar and Achilles tendinopathy. However, its effects on rotator cuff tendinopathy still need to be investigated. Purpose: To assess the clinical effects of PHLE versus low-load exercise (LLE) among patients with rotator cuff tendinopathy. Study Design: Randomized controlled trial; Level of evidence, 1. Methods: Patients with rotator cuff tendinopathy were recruited and randomized to 12 weeks of PHLE or LLE, stratified for concomitant administration of corticosteroid injection. The primary outcome measure was change from baseline to 12 weeks in the Disabilities of the Arm, Shoulder, and Hand (DASH) questionnaire, assessed in the intention-to-treat population. Results: A total of 100 patients were randomized to PHLE (n = 49) or LLE (n = 51). Mean changes in the DASH questionnaire were 7.11 points (95% CI, 3.07-11.16) and 8.39 points (95% CI, 4.35-12.44) in the PHLE and LLE groups, respectively; this corresponded to a statistically nonsignificant adjusted mean group difference of −1.37 points (95% CI, −6.72 to 3.99; P = .61). Similar nonsignificant results were seen for pain, range of motion, and strength. However, a significant interaction effect was found between the 2 groups and concomitant corticosteroid use (P = .028), with the largest positive change in DASH in favor of PHLE for the group receiving concomitant corticosteroid. Conclusion: The study results showed no superior benefit from PHLE over traditional LLE among patients with rotator cuff tendinopathy. Further investigation of the possible interaction between exercise type and corticosteroid injection is needed to establish optimal and potentially synergistic combinations of these 2 factors. Registration: NCT01984203 (ClinicalTrials.gov identifier): Rotator Cuff Tendinopathy Exercise Trial (RoCTEx). PMID:28875153

Three Months of Progressive High-Load Versus Traditional Low-Load Strength Training Among Patients With Rotator Cuff Tendinopathy: Primary Results From the Double-Blind Randomized Controlled RoCTEx Trial.

PubMed

Ingwersen, Kim Gordon; Jensen, Steen Lund; Sørensen, Lilli; Jørgensen, Hans Ri; Christensen, Robin; Søgaard, Karen; Juul-Kristensen, Birgit

2017-08-01

Progressive high-load exercise (PHLE) has led to positive clinical results in patients with patellar and Achilles tendinopathy. However, its effects on rotator cuff tendinopathy still need to be investigated. To assess the clinical effects of PHLE versus low-load exercise (LLE) among patients with rotator cuff tendinopathy. Randomized controlled trial; Level of evidence, 1. Patients with rotator cuff tendinopathy were recruited and randomized to 12 weeks of PHLE or LLE, stratified for concomitant administration of corticosteroid injection. The primary outcome measure was change from baseline to 12 weeks in the Disabilities of the Arm, Shoulder, and Hand (DASH) questionnaire, assessed in the intention-to-treat population. A total of 100 patients were randomized to PHLE (n = 49) or LLE (n = 51). Mean changes in the DASH questionnaire were 7.11 points (95% CI, 3.07-11.16) and 8.39 points (95% CI, 4.35-12.44) in the PHLE and LLE groups, respectively; this corresponded to a statistically nonsignificant adjusted mean group difference of -1.37 points (95% CI, -6.72 to 3.99; P = .61). Similar nonsignificant results were seen for pain, range of motion, and strength. However, a significant interaction effect was found between the 2 groups and concomitant corticosteroid use ( P = .028), with the largest positive change in DASH in favor of PHLE for the group receiving concomitant corticosteroid. The study results showed no superior benefit from PHLE over traditional LLE among patients with rotator cuff tendinopathy. Further investigation of the possible interaction between exercise type and corticosteroid injection is needed to establish optimal and potentially synergistic combinations of these 2 factors. NCT01984203 (ClinicalTrials.gov identifier): Rotator Cuff Tendinopathy Exercise Trial (RoCTEx).

Early prediction of hypertension during pregnancy in a low-resource setting.

PubMed

Kumar, Manisha; Gupta, Usha; Bhattacharjee, Jayashree; Singh, Ritu; Singh, Shalini; Goel, Manish; Sharma, Karuna; Rehman, Mujeeb U

2016-02-01

To evaluate the role of maternal factors, biomarkers, and uterine-artery Doppler in the prediction of hypertension during pregnancy. A prospective cohort study was performed between December 2012 and November 2014. All singleton pregnancies between 11 weeks and 13 weeks, 6 days of pregnancy were included. Patients had their body mass index (BMI, calculated as weight in kilograms divided by the square of height in meters), mean arterial pressure, uterine-artery Doppler pulsatility index, and pregnancy-associated plasma protein A (PAPP-A) and free β-human chorionic gonadotropin levels recorded. Any patients diagnosed with hypertension during follow-up were assigned to the case cohort; all other patients were assigned to the control group. Hypertension during pregnancy was observed in 198 (9.7%) of 2042 patients that attended follow-up. The mean BMI, mean arterial pressure, uterine-artery Doppler pulsatility index, and the PAPP-A level at study enrollment were all significantly correlated with the later development of hypertension (P<0.001 for all variables). The combined sensitivity, specificity, positive predictive value, and negative predictive value of using the investigated parameters to predict hypertension was 76%, 80%, 31%, and 93%, respectively. Patient BMI, mean arterial pressure, PAPP-A, and pulsatility index were found to be effective predictors of hypertension during pregnancy. Combining these predictors may be beneficial in selecting individuals for close monitoring and early intervention during pregnancy. Copyright © 2015 International Federation of Gynecology and Obstetrics. Published by Elsevier Ireland Ltd. All rights reserved.

Extensive Evaluation of the Conductor-like Screening Model for Real Solvents Method in Predicting Liquid-Liquid Equilibria in Ternary Systems of Ionic Liquids with Molecular Compounds.

PubMed

Paduszyński, Kamil

2018-04-12

A conductor-like screening model for real solvents (COSMO-RS) is nowadays one of the most popular and commonly applied tools for the estimation of thermodynamic properties of complex fluids. The goal of this work is to provide a comprehensive review and analysis of the performance of this approach in calculating liquid-liquid equilibrium (LLE) phase diagrams in ternary systems composed of ionic liquid and two molecular compounds belonging to diverse families of chemicals (alkanes, aromatics, S/N-compounds, alcohols, ketones, ethers, carboxylic acid, esters, and water). The predictions are presented for extensive experimental database, including 930 LLE data sets and more than 9000 data points (LLE tie lines) reported for 779 unique ternary mixtures. An impact of the type of molecular binary subsystem on the accuracy of predictions is demonstrated and discussed on the basis of representative examples. The model's capability of capturing qualitative trends in the LLE distribution ratio and selectivity is also checked for a number of structural effects. Comparative analysis of two levels of quantum chemical theory (BP-TZVP-COSMO vs BP-TZVPD-FINE) for the input molecular data for COSMO-RS is presented. Finally, some general recommendations for the applicability of the model are indicated based on the analysis of the global performance as well as on the results obtained for systems relevant from the point of view of important separation problems.

Low tritium partial pressure permeation system for mass transport measurement in lead lithium eutectic

DOE PAGES

Pawelko, R. J.; Shimada, M.; Katayama, K.; ...

2015-11-28

This paper describes a new experimental system designed to investigate tritium mass transfer properties in materials important to fusion technology. Experimental activities were carried out at the Safety and Tritium Applied Research (STAR) facility located at the Idaho National Laboratory (INL). The tritium permeation measurement system was developed as part of the Japan/US TITAN collaboration to investigate tritium mass transfer properties in liquid lead lithium eutectic (LLE) alloy. The experimental system is configured to measure tritium mass transfer properties at low tritium partial pressures. Initial tritium permeation scoping tests were conducted on a 1 mm thick α-Fe plate to determinemore » operating parameters and to validate the experimental technique. A second series of permeation tests was then conducted with the α-Fe plate covered with an approximately 8.5 mm layer of liquid lead lithium eutectic alloy (α-Fe/LLE). We present preliminary tritium permeation data for α-Fe and α-Fe/LLE at temperatures between 400 and 600°C and at tritium partial pressures between 1.7E-3 and 2.5 Pa in helium. Preliminary results for the α-Fe plate and α-Fe/LLE indicate that the data spans a transition region between the diffusion-limited regime and the surface-limited regime. In conclusion, additional data is required to determine the existence and range of a surface-limited regime.« less

[Diverse sustainability--sustainable diversity].

PubMed

Schmeling-Kludas, Christoph; Koch-Gromus, Uwe

2011-08-01

In spite of its plenitude, the scientific works of the important German psychologist Ernst August Dölle (1898-1972) are little adapted till today, mostly they are being reduced to his studies about dichotomy and duplicity. But based on his diaries of the year 1968, the authors can verify without doubt, that Dölle far ahead of his time, carried on research about sustainability and diversity. He was the first scientist worldwide to connect these two concepts. Georg Thieme Verlag KG Stuttgart · New York.

Environmental and cultural correlates of physical activity parenting practices among Latino parents with preschool-aged children

USDA-ARS?s Scientific Manuscript database

Parents can influence their children's physical activity (PA) through parenting practices (PP). Correlates of PA-PP have not been investigated. This study therefore aimed to examine the independent contributions of (1) socio-demographic, (2) cultural, (3) parent perceived-environmental, and (4) obje...

Investigation of transport mechanism of exendin-4 across Madin Darby canine kidney cell monolayers.

PubMed

Wang, Mengshu; Sun, Bingxue; Feng, Jiao; Zhang, Haihong; Liu, Bin; Li, Chun; Chen, Yan; Zhang, Yong; Kong, Wei

2012-01-01

The purpose of this study was to investigate the transport mechanism of exendin-4 using Madin Darby canine kidney (MDCK) cell monolayer as an in vitro model of the human intestinal barrier. The roles of active and passive mechanisms of exendin-4 in the cell models were well studied and the corresponding contributions of the transcelluar and paracellular pathway to exendin-4 transport were also evaluated. Moreover, the apparent permeability coefficient (P(app)) values of exendin-4 were determined in the presence of chitosan, sodium decanoate and ethylenediaminetetraacetic acid (EDTA) to further confirm the relative transport mechanism and to evaluate their potential utility in future formulation design. The results revealed the low transport capacity of exendin-4 (P(app), 0.10±0.06×10(-6) cm/s). And exendin-4 transport across the cell models was time and concentration-dependence, direction and energy-independence, and similar to the passive transport marker. Drug efflux and active transport were not observed. In the presence of absorption enhancers, the P(app) value significantly increased up to 2.2-11.9 folds without apparent cytotoxicity, which is comparable to that of the paracellular transport marker. And the order of enhancement was to the effect of chitosan>EDTA>sodium decanoate, and the order of safety was sodium decanoate≈chitosan>EDTA. These findings demonstrated that exendin-4 transport across MDCK cell monolayer mainly by passive paracellular pathway, which agrees with the result of confocal laser scanning microscopy. And these absorption enhancers can be used as potential safe ingredients to improve oral efficacy of exendin-4.

Evaluation of biochemical markers combined with uterine artery Doppler parameters in fetuses with growth restriction: a case-control study.

PubMed

Zamarian, Ana Cristina Perez; Araujo Júnior, Edward; Daher, Sílvia; Rolo, Liliam Cristine; Moron, Antonio Fernandes; Nardozza, Luciano Marcondes Machado

2016-10-01

Assessing the biochemical markers levels and the uterine artery Doppler (UtA) parameters in fetuses with growth restriction (FGR). Prospective case-control study included 66 patients with diagnosis of FGR and 64 healthy pregnancies at 24-41 weeks of gestation. For both groups, maternal circulating concentrations of biochemical factors of soluble fms-like tyrosine kinase-1 (sFlt-1), soluble endoglin(sEng), adiponectin, A disintegrin and metalloproteinases (ADAM-12), pregnancy-associated plasma protein-A (PAPP-A), angiopoietin-2 (ANGI-2), vascular endothelial growth factor (VEGF) and transforming growth factor-β (TGF-β) were assayed by ELISA and UtA by Doppler were performed. ANOVA, Mann-Whitney tests and Pearson correlation coefficient were applied to compare the biochemical factors, UtA Doppler and EFW Z-score between the groups. Concentrations of sFlt-1, sEng, PAPP-A were significantly higher in FGR than controls (p < 0.0001, p = 0.02 and p = 0.03, respectively), but concentration of ANGI-2 (p < 0.0001) was significantly lower in FGR than controls and ADAM-12 levels had a tendency to be lower in the FGR, though not statistically significant (p = 0.059). Increased sEng concentrations were correlated with abnormal UtA Doppler in FGR. Fetal growth restriction fetuses showed increased serum levels of sFlt-1, sEng and PAPP-A with levels of ANGI-2 decreased and a positive association between elevated concentrations of sEng and changing impedance of UtA Doppler were observed.

Transport and metabolism of MitoQ10, a mitochondria-targeted antioxidant, in Caco-2 cell monolayers.

PubMed

Li, Yan; Fawcett, J Paul; Zhang, Hu; Tucker, Ian G

2007-04-01

Mitoquinone (MitoQ(10) mesylate) is a mitochondria-targeted antioxidant formulated for oral administration in the treatment of neurodegenerative diseases. We have investigated the absorption and metabolism of MitoQ(10) in Caco-2 cell monolayers. The intracellular accumulation of MitoQ(10) was 18-41% of the total amount of MitoQ(10) added. Some of the intracellular MitoQ(10) was reduced to mitoquinol and subsequently metabolized to glucuronide and sulfate conjugates. Transport of MitoQ(10) was polarized with the apparent permeability (P(app)) from basolateral (BL) to apical (AP) (P(appBL-->AP)) being >2.5-fold the P(app) from apical to basolateral (P(appAP-->BL)). In the presence of 4% bovine serum albumin on the basolateral side, the P(appAP-->BL) value increased 7-fold compared with control. The P(appBL-->AP) value decreased by 26, 31 and 61% in the presence of verapamil 100 microM, ciclosporin 10 and 30 microM, respectively, whereas the P(appAP-->BL) value increased 71% in the presence of ciclosporin 30 microM. Apical efflux of mitoquinol sulfate and mitoquinol glucuronide conjugates was significantly decreased by ciclosporin 30 microM and the breast cancer receptor protein (BCRP) inhibitor, reserpine 25 microM, respectively. These results suggested that the bioavailability of MitoQ(10) may be limited by intracellular metabolism and the action of P-glycoprotein and BCRP. However, the dramatic increase in absorptive P(app) in the presence of bovine serum albumin on the receiver side suggests these barrier functions may be less significant in-vivo.

Fabrication of coated bovine serum albumin (BSA)-epigallocatechin gallate (EGCG) nanoparticles and their transport across monolayers of human intestinal epithelial Caco-2 cells.

PubMed

Li, Zheng; Ha, Jungheun; Zou, Tao; Gu, Liwei

2014-06-01

The bovine serum albumin (BSA)-epigallocatechin gallate (EGCG) nanoparticles were fabricated using a desolvation method, and coated with poly-ε-lysine or chitosan. BSA-EGCG nanoparticles (BEN), poly-ε-lysine coated BSA-EGCG nanoparticles (PBEN), and chitosan coated BSA-EGCG nanoparticles (CBEN) had a spherical morphology and a size of 186, 259, and 300 nm, respectively. The loading efficiency of EGCG in these nanoparticles was 32.3%, 35.4%, and 32.7%, whereas the loading capacity was 18.9%, 17.0%, and 16.0% (w/w), respectively. Poly-ε-lysine or chitosan coating prevented the aggregation of nanoparticles at pH 4.5-5.0. However, they caused particle aggregation at pH 6.5-7.0. BEN had negative zeta-potentials between pH 4.5 and 6.0. Poly-ε-lysine or chitosan coating changed the zeta-potentials to positive. The release study of EGCG from the nanoparticles in the simulated gastric or intestinal fluid with or without digestive enzymes showed that poly-ε-lysine and chitosan coatings delayed EGCG release from the nanoparticles. Poly-ε-lysine or chitosan coating improved the stability of EGCG during storage at 60 °C compared with EGCG in the uncoated particles. EGCG in BEN, PBEN, and CBEN had a decreasing apparent permeability coefficient (Papp) on Caco-2 monolayers, whereas pure EGCG showed relatively stable Papp during the incubation over time. EGCG in CBEN showed significantly higher Papp, suggesting that chitosan coated BSA-EGCG nanoparticles may improve the absorption of EGCG.

Bioactivity of food peptides: biological response of rats to bovine milk whey peptides following acute exercise

PubMed Central

Moura, Carolina Soares; Lollo, Pablo Christiano Barboza; Morato, Priscila Neder; Risso, Eder Muller; Amaya-Farfan, Jaime

2017-01-01

ABSTRACT Background: Several physiologically beneficial effects of consuming a whey protein hydrolysate (WPH) have been attributed to the greater availability of bioactive peptides. Aims: The aim was to investigate the effect of four branched-chain amino acid- (BCAA-)containing dipeptides, present in WPH, on immune modulation, stimulation of HSP expression, muscle protein synthesis, glycogen content, satiety signals and the impact of these peptides on the plasma free amino acid profiles. Methods: The animals were divided in groups: control (rest, without gavage), vehicle (water), L-isoleucyl-L-leucine (lle-Leu), L-leucyl-L-isoleucine (Leu-lle), L-valyl-Lleucine (Val-Leu), L-leucyl-L-valine (Leu-Val) and WPH. All animals were submitted to acute exercise, except for control. Results: lle-Leu stimulated immune response, hepatic and muscle glycogen and HSP60 expression, whereas Leu-Val enhanced HSP90 expression. All dipeptides reduced glucagon-like peptide-1 and glucose-dependent insulinotropic polypeptide, no changes were observed on leptin. All peptides inhibited NF-kB expression. The plasma amino acid time-course showed peptide-specific and isomer-specific metabolic features, including increases of the BCAAs. Conclusion: The data indicate that lle-Leu was effective to attenuate immune-suppression exercise-induced, promoted glycogen content and stimulated anti-stress effect (HSP). Furthermore, Leu-Val increased HSP90, p-4EBP1, p-mTOR and p-AMPK expression. The data suggest the involvement of these peptides in various beneficial functions of WPH consumption. PMID:28326005

Risk equivalent of exposure versus dose of radiation

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

Bond, V.P.

This report describes a risk analysis study of low-dose irradiation and the resulting biological effects on a cell. The author describes fundamental differences between the effects of high-level exposure (HLE) and low-level exposure (LLE). He stresses that the concept of absorbed dose to an organ is not a dose but a level of effect produced by a particular number of particles. He discusses the confusion between a linear-proportional representation of dose limits and a threshold-curvilinear representation, suggesting that a LLE is a composite of both systems. (TEM)

Optimizing Ligand Efficiency of Selective Androgen Receptor Modulators (SARMs)

PubMed Central

2015-01-01

A series of selective androgen receptor modulators (SARMs) containing the 1-(trifluoromethyl)benzyl alcohol core have been optimized for androgen receptor (AR) potency and drug-like properties. We have taken advantage of the lipophilic ligand efficiency (LLE) parameter as a guide to interpret the effect of structural changes on AR activity. Over the course of optimization efforts the LLE increased over 3 log units leading to a SARM 43 with nanomolar potency, good aqueous kinetic solubility (>700 μM), and high oral bioavailability in rats (83%). PMID:26819671

Transepithelial transport of rosuvastatin and effect of ursolic acid on its transport in Caco-2 monolayers.

PubMed

Hua, Wen Jin; Fang, Hu Jin; Hua, Wei Xiao

2012-09-01

The aim of this study was to determine transepithelial transport characteristics of rosuvastatin and effect of ursolic acid (P-gp potential inhibitor) and ko143 (ABC transporters selective inhibitor) on its transport in Caco-2 monolayers. A reliable Caco-2 cell monolayers model was established. The TEER value was used to inspect integrity of cell model. Apparent permeability coefficients (Papp(BL-AP) and Papp(AP-BL)) were used to analyze transepithelial transport of rosuvastatin. Uptake of rosuvastatin was time- and concentration-dependent in Caco-2 cell. The ko143 but not ursolic acid had effect on the uptake of rosuvastatin in Caco-2 cell monolayer model and affected apparent permeability coefficient and apparent permeability of rosuvastatin. Active transport and passive diffusion absorption existed in transepithelial transport of rosuvastatin in Caco-2 cell model. Ursolic acid had no effect on transport of rosuvastatin in Caco-2 cell monolayer. The result indicated that ursolic acid may not cause effect on intestinal absorption of rosuvastatin.

Molecular mechanisms of the naringin low uptake by intestinal Caco-2 cells.

PubMed

Tourniaire, Franck; Hassan, Meryl; André, Marc; Ghiringhelli, Odette; Alquier, Christian; Amiot, Marie-Josèphe

2005-10-01

Naringin, the main flavanone of grapefruit, was reported to display numerous biological effects: antioxidant, hypocholesteremic, anti-atherogenic and favoring drug absorption. Naringin absorption mechanisms were studied in Caco-2 cells (TC7 clone). We investigated the possible involvement of several membrane transporters implicated in polyphenolic compounds intestinal transport (sodium-dependent glucose transporter 1, monocarboxylate transporter, multidrug-associated resistance proteins 1 and 2, and P-glycoprotein). Naringin was poorly absorbed by Caco-2 cells, according to its low value of apparent permeability coefficient (P(app) = 8.1 +/- 0.9 x 10(-8) cm/s). In the presence of verapamil, a specific inhibitor of P-glycoprotein, cellular uptake was increased by almost threefold after 5 min, and P(app) was doubled after 30 min. Our results indicated the involvement of P-glycoprotein, an ATP-driven efflux pump, capable of transporting naringin from the Caco-2 cell to the apical side. This phenomenon could explain, at least in part, the low absorption of this flavanone at the upper intestinal level.

Characteristic Extraction of Mental Disease Patients by Nonlinear Analysis of Plethysmograms

NASA Astrophysics Data System (ADS)

Hu, Yuyu; Wang, Wenbiao; Suzuki, Takashi; Oyama-Higa, Mayumi

2011-06-01

We measured the pulse waves of 196 mentally ill patients and 113 healthy students. Using heartbeat changes, we calculated the values of their sympathetic nerves, parasympathetic nerves, and autonomic nerve balance. In addition, we calculated the largest Lyapunov exponents (LLE) by non-linear analysis of plethysmograms. Values were analyzed by group. The results revealed a significant relationship between LLE and the autonomic nerve balance. The sympathetic nerve values in the patient group were significantly higher than those in the student group, whereas the LLE values were significantly lower. Furthermore, we illustrated the dynamic change in the results for single participants over several testing times. The measurement of pulse waves is easy and economical and does not put a strain on the subject. Additionally, these values can provide information that is more accurate than medical examination obtained from an interview. Our study contributed to the existing methodology in this field, and future data collection and measurement will be carried out. We hope that our study will be useful for neurologists and psychotherapists in their detection and treatment of mental illness.

Sustainable efficient way for opioid peptide LVV-h7 preparation from enzymatic proteolysis in a microfluidic-based reaction-extraction process with solvent recycling.

PubMed

Elagli, Adil; Belhacene, Kalim; Dhulster, Pascal; Froidevaux, Renato

2016-05-01

LVV-h7 (LVVYPWTQFR) is a bioactive peptide that can be obtained from blood as waste of food industry, more precisely from hemoglobin hydrolysis by pepsin. This opioid peptide belongs to the hemorphins family and have strong physiological effects that bring its use in pharmaceutics and various therapeutic treatments attractive, in particular for substituting its costly chemically synthetized analogous. Hemoglobin hydrolysis by pepsin generates a huge variety of peptides among whose LVV-h7 can be purified by liquid-liquid extraction (LLE). Herein, selective preparation of this peptide is proposed by a microfluidic-based continuous reaction-separation process. Hemoglobin hydrolysis in microreactor was firstly coupled to LVV-h7 LLE in octan-1-ol and then coupled to LVV-h7 back LLE in acidic water. This continuous process allowed to prepare pure LVV-h7, as confirmed by liquid chromatography and mass spectrometry. The microfluidic circuit also allowed octan-1-ol recycling in a closed loop, making this method more sustainable than similar biphasic batch process. Copyright © 2016 Elsevier B.V. All rights reserved.

Mapping High Dimensional Sparse Customer Requirements into Product Configurations

NASA Astrophysics Data System (ADS)

Jiao, Yao; Yang, Yu; Zhang, Hongshan

2017-10-01

Mapping customer requirements into product configurations is a crucial step for product design, while, customers express their needs ambiguously and locally due to the lack of domain knowledge. Thus the data mining process of customer requirements might result in fragmental information with high dimensional sparsity, leading the mapping procedure risk uncertainty and complexity. The Expert Judgment is widely applied against that background since there is no formal requirements for systematic or structural data. However, there are concerns on the repeatability and bias for Expert Judgment. In this study, an integrated method by adjusted Local Linear Embedding (LLE) and Naïve Bayes (NB) classifier is proposed to map high dimensional sparse customer requirements to product configurations. The integrated method adjusts classical LLE to preprocess high dimensional sparse dataset to satisfy the prerequisite of NB for classifying different customer requirements to corresponding product configurations. Compared with Expert Judgment, the adjusted LLE with NB performs much better in a real-world Tablet PC design case both in accuracy and robustness.

Unfälle mit Kleintransportern

NASA Astrophysics Data System (ADS)

Tschirschwitz, Christian

Auf einer außerörtlichen Bundesstraße geriet ein mit vier Personen besetzter Pkw Toyota Corolla aus letztlich nicht vollständig geklärten Gründen ins Schleudern. Nachdem sich das Fahrzeug beträchtlich entgegen dem Uhrzeigersinn ausgedreht hatte, prallte ein entgegenkommender Kleintransporter VW T4 frontal an die rechte Flanke des Toyota. Der Transporter wurde gedreht, ausgehoben und durch einen Pkw Ford Escort unterfahren. Alle Fahrzeuge kamen in Kollisionsortnähe zum Endstand. Die vier Toyota-Insassen wurden getötet. Aus den anderen Fahrzeugen wurden sechs Personen überwiegend schwer verletzt. Unbeteiligte Zeugen waren nicht vorhanden.

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

Shvydky, Alex

This volume of LLE Review, covering October–December 2011, features “Crossed-Beam Energy Transfer in Direct-Drive Implosions” by I. V. Igumenshchev, W. Seka, D. H. Edgell, D. T. Michel, D. H. Froula, R. S. Craxton, R. Follett, J. H. Kelly, T. Z. Kosc, J. F. Myatt, T. C. Sangster, A. Shvydky, S. Skupsky, and C. Stoeckl (LLE); V. N. Goncharov and A. V. Maximov (LLE and Department of Mechanical Engineering, U. of Rochester); L. Divol and P. Michel (LLNL); and R. L. McCrory and D. D. Meyerhofer (LLE and Departments of Mechanical Engineering and Physics, U. of Rochester). In this article (p.more » 1), direct-drive–implosion experiments on the OMEGA laser [T. R. Boehly et al., Opt. Commun. 133, 495 (1995)] have shown discrepancies between simulations of the scattered (non-absorbed) light levels and measured ones that indicates the presence of a mechanism that reduces laser coupling efficiency by 10% to 20%. The authors attribute this degradation in laser coupling to crossed-beam energy transfer (CBET)— which is electromagnetically seeded—low-gain stimulated Brillouin scattering. CBET scatters energy from the central portion of the incoming light beam to outgoing light, reducing the laser absorption and hydrodynamic efficiency of implosions. One-dimensional hydrodynamic simulations including CBET show good agreement with all observables in implosion experiments on OMEGA. Three strategies to mitigate CBET and improve laser coupling are considered: the use of narrow beams, multicolor lasers, and higher-Z ablators. Experiments on OMEGA using narrow beams have demonstrated improvements in implosion performance.« less

University of Rochester, Laboratory for Laser Energetics

NASA Astrophysics Data System (ADS)

1987-01-01

In FY86 the Laboratory has produced a list of accomplishments in which it takes pride. LLE has met every laser-fusion program milestone to date in a program of research for direct-drive ultraviolet laser fusion originally formulated in 1981. LLE scientists authored or co-authored 135 scientific papers during 1985 to 1986. The collaborative experiments with NRL, LANL, and LLNL have led to a number of important ICF results. The cryogenic target system developed by KMS Fusion for LLE will be used in future high-density experiments on OMEGA to demonstrate the compression of thermonuclear fuel to 100 to 200 times that of solid (20 to 40 g/cm) in a test of the direct-drive concept, as noted in the National Academy of Sciences' report. The excellence of the advanced technology efforts at LLE is illustrated by the establishment of the Ultrafast Science Center by the Department of Defense through the Air Force Office of Scientific Research. Research in the Center will concentrate on bridging the gap between high-speed electronics and ultrafast optics by providing education, research, and development in areas critical to future communications and high-speed computer systems. The Laboratory for Laser Energetics continues its pioneering work on the interaction of intense radiation with matter. This includes inertial-fusion and advanced optical and optical electronics research; training people in the technology and applications of high-power, short-pulse lasers; and interacting with the scientific community, business, industry, and government to promote the growth of laser technology.

Prospective Changes in Infertile Patients using Nonlinear Analysis

NASA Astrophysics Data System (ADS)

Takahashi, Yuko; Tomiyama, Tatsuhiro; Matsubayashi, Hidehiko; Tsukamoto, Asami; Oyama-Higa, Mayumi

2011-06-01

We measured pulse waves in 22 infertile women from the beginning of in vitro fertilization-embryo transfer (IVF-ET) through to pregnancy testing. The largest Lyapunov exponent (LLE) and autonomic nerve balance in the pregnancy group were significantly lower than that in the non-pregnancy group. In this study, we measured plethysmograms of four women who became pregnant and 18 who did not, ten times from each. We calculated LLE and a value for the autonomic nerve balance; from this analysis, we conclude that a mental state that allows for the possibility of becoming pregnant is necessary for a successful pregnancy.

Dual-axis reflective continuous-wave terahertz confocal scanning polarization imaging and image fusion

NASA Astrophysics Data System (ADS)

Zhou, Yi; Li, Qi

2017-01-01

A dual-axis reflective continuous-wave terahertz (THz) confocal scanning polarization imaging system was adopted. THz polarization imaging experiments on gaps on film and metallic letters "BeLLE" were carried out. Imaging results indicate that the THz polarization imaging is sensitive to the tilted gap or wide flat gap, suggesting the THz polarization imaging is able to detect edges and stains. An image fusion method based on the digital image processing was proposed to ameliorate the imaging quality of metallic letters "BeLLE." Objective and subjective evaluation both prove that this method can improve the imaging quality.

Transport of ginkgolides with different lipophilicities based on an hCMEC/D3 cell monolayer as a blood-brain barrier cell model.

PubMed

Ma, Shuwei; Liu, Xingyan; Xu, Qingrun; Zhang, Xiantao

2014-10-02

In this report, the transport of ginkgolides with different lipophilicities was investigated using an hCMEC/D3 cell monolayer as a blood-brain barrier (BBB) cell model in vitro in an attempt to explain ginkgolide transport path mediated by lipophilicity. The log P values of ginkgolides were determined by measuring the distribution of the molecule between oil and water. Additionally, the cytotoxicity of ginkgolides on hCMEC/D3 cells was assayed with the MTT method. Ginkgolide contents were determined with an ultra performance liquid chromatograph equipped with an evaporative light scattering detector (ULPC-ELSD) method. Apparent permeability coefficients (Papp) and efflux ratios (PappBL→AP/PappAP→BL) were then calculated to describe the transport characteristics of ginkgolide. The transport of ginkgolide A, ginkgolide B, ginkgolide C, and ginkgolide J across the hCMEC/D3 cell monolayer was non-directional. Additionally, ginkgolide C transport on the cell monolayer was time- and concentration-dependent in the paracellular pathway controlled by cytochalasin D (a tight junction modulator). The transport of ginkgolide N, ginkgolide L, and ginkgolide K across the cell monolayer displayed clear directionality at low ginkgolide concentrations. This behavior indicated that the transport of ginkgolide N, ginkgolide L, and ginkgolide K was influenced by the transcellular pathway containing an efflux protein accompanied by the paracellular pathway for passive diffusion. Additionally, the transport of ginkgolide K was increased significantly by co-culturing with a P-gp inhibitor. These findings provide important information for elucidating ginkgolide transport pathways and may be beneficial for the design of ginkgolide molecules with high neuroprotective effects. Copyright © 2014 Elsevier Inc. All rights reserved.

pH Dependent but not P-gp Dependent Bidirectional Transport Study of S-propranolol: The Importance of Passive Diffusion.

PubMed

Zheng, Yi; Benet, Leslie Z; Okochi, Hideaki; Chen, Xijing

2015-08-01

Recent controversial publications, citing studies purporting to show that P-gp mediates the transport of propranolol, proposed that passive biological membrane transport is negligible. Based on the BDDCS, the extensively metabolized-highly permeable-highly soluble BDDCS class 1 drug, propranolol, shows a high passive permeability at concentrations unrestricted by solubility that can overwhelm any potential transporter effects. Here we reinvestigate the effects of passive diffusion and carrier-mediated transport on S-propranolol. Bidirectional permeability and inhibition of efflux transport studies were carried out in MDCK, MDCK-MDR1 and Caco-2 cell lines at different concentrations. Transcellular permeability studies were conducted at different apical pHs in the rat jejunum Ussing chamber model and PAMPA system. S-propranolol exhibited efflux ratios lower than 1 in MDCK, MDCK-MDR1 and Caco-2 cells. No significant differences of Papp, B->A in the presence and absence of the efflux inhibitor GG918 were observed. However, an efflux ratio of 3.63 was found at apical pH 6.5 with significant decrease in Papp, A->B and increase in Papp, B->A compared to apical pH 7.4 in Caco-2 cell lines. The pH dependent permeability was confirmed in the Ussing chamber model. S-propranolol flux was unchanged during inhibition by verapamil and rifampin. Furthermore, pH dependent permeability was also observed in the PAMPA system. S-propranolol does not exhibit active transport as proposed previously. The "false" positive efflux ratio can be explained by the pH partition theory. As expected, passive diffusion, but not active transport, plays the primary role in the permeability of the BDDCS class 1 drug propranolol.

First trimesters Pregnancy-Associated Plasma Protein-A levels value to Predict Gestational diabetes Mellitus: A systematic review and meta-analysis of the literature.

PubMed

Talasaz, Zahra Hadizadeh; Sadeghi, Ramin; Askari, Fariba; Dadgar, Salmeh; Vatanchi, Atiyeh

2018-04-01

Detecting pregnant women at risk of diabetes in first months can help them by early intervention for delaying or preventing onset of GDM. In this study, we aimed to assess the Predictive value of first trimester Pregnancy related plasma protein-A (PAPP-A) levels for detecting Gestational diabetes Mellitus (GDM). This systematic review and meta-analysis was conducted through probing in databases. PubMed, Scopus, Medline and Google scholar citations were searched to find the published papers from 1974 to 2017. Studies were considered eligible if they were cohorts, case-control studies, reported GDM result, not other types, conducted on singleton pregnancy, measured Serum pregnancy associated plasma protein A in the first trimester and evaluated the relation of first trimester pregnancy associated plasma protein-A and GDM. Two reviewers independently assessed the quality with Newcastle-Ottawa and extracted data in the Pre-defined checklist. Analysis of the data was carried out by "Comprehensive Meta-analysis Version 2 (CAM)" and Metadisc software. 17 articles have our inclusion criteria and were considered in our systematic review, 5 studies included in Meta-analysis. Meta-analysis of these articles showed that the predictive value of PAPP-A for GDM has 55% sensitivity (53-58), 90% (89-90) specificity, LR + 2.48 (0.83-7.36) and LR - 0.70 (0.45-1.09) with 95% confidence intervals. In our study PAPP-A has low predictive accuracy overall, but it may be useful when combined with other tests, and this is an active part for future research. One limitation of our study is significant heterogeneity because of different adjusted variables and varied diagnostic criteria. Copyright © 2018. Published by Elsevier B.V.

Transport of decursin and decursinol angelate across Caco-2 and MDR-MDCK cell monolayers: in vitro models for intestinal and blood-brain barrier permeability.

PubMed

Madgula, Vamsi L; Avula, Bharathi; Reddy V L, Niranjan; Khan, Ikhlas A; Khan, Shabana I

2007-04-01

Decursin (DE) and decursinol angelate (DA) were isolated from the roots of Angelica gigas (Apiaceae) and purified by HPLC. DE and DA have been reported to exhibit significant neuropharmacological activities, but their intestinal transport and permeability in terms of CNS penetration across the blood-brain barrier (BBB) are unknown. This study was undertaken to evaluate the IN VITRO intestinal and BBB transport of DE and DA using Caco-2 and MDR-MDCK cell monolayer models, respectively. The bidirectional transport of DE and DA across Caco-2 and MDR-MDCK monolayers was examined for 2 hours. Integrity of the monolayer was determined by TEER value and by monitoring the transport of Lucifer yellow (Ly) across the monolayers. Quantitation of DE and DA was performed by HPLC. DE and DA exhibited bidirectional transport with a Papp value in the range of 9.0-12.0x10(-6) cm/sec and 7.2-11.7x10(-6) cm/sec in Caco-2 and MDR-MDCK monolayers, respectively. The TEER values were in the range of 410-440 and 1170-1230 ohm cm2 for Caco-2 and MDR-MDCK monolayers, respectively. Ly measurement, the fluorescent marker of passive paracellular diffusion, resulted in Papp values of 2.5-5.0x10(-6) in Caco-2 and 6.0-8.0x10(-6) cm/sec in MDR-MDCK monolayers, confirming that the monolayer integrity was intact at the end of the experiment. Caco-2:human colonic adenocarcinoma DA:decursinol angelate DE:decursin Ly:Lucifer yellow MDCK:Madin-Darby canine kidney MDR:multidrug resistant Papp:apparent permeability TEER:transepithelial electrical resistance.

Optimized conditions for MDCK permeability and turbidimetric solubility studies using compounds representative of BCS classes I-IV.

PubMed

Taub, Mitchell E; Kristensen, Lisbeth; Frokjaer, Sven

2002-05-01

The solubility enhancing effects of various excipients, including their compatibility with in vitro permeability (P(app)) systems, was investigated using drugs representative of Biopharmaceutics Classification System (BCS) classes I-IV. Turbidimetric solubility determination using nephelometry and transport experiments using MDCK Strain I cell monolayers were employed. The highest usable concentration of each excipient [dimethyl sulfoxide (DMSO), ethanol, hydroxypropyl-beta-cyclodextrin (HPCD), and sodium taurocholate] was determined by monitoring apical (AP) to basolateral (BL) [14C]mannitol apparent permeability (P(app)) and the transepithelial electrical resistance (TEER) in transport experiments done at pH 6.0 and 7.4. The excipients were used in conjunction with compounds demonstrating relatively low aqueous solubility (amphotericin B, danazol, mefenamic acid, and phenytoin) in order to obtain a drug concentration >50 microM in the donor compartment. The addition of at least one of the selected excipients enhanced the solubility of the inherently poorly soluble compounds to >50 microM as determined via turbidimetric evaluation at pH 6.0 and 7.4. Ethanol and DMSO were found to be generally disruptive to the MDCK monolayer and were not nearly as useful as HPCD and sodium taurocholate. Sodium taurocholate (5 mM) was compatible with MDCK monolayers under all conditions investigated. Additionally, a novel in vitro system aimed at more accurately simulating in vivo conditions, i.e., a pH gradient (6.0 AP/7.4 BL), sodium taurocholate (5 mM, AP), and bovine serum albumin (0.25%, BL), was shown to generate more reliable P(app) values for compounds that are poorly soluble and/or highly protein bound.

Determination of permeability coefficients of ophthalmic drugs through different layers of porcine, rabbit and bovine eyes.

PubMed

Loch, Christian; Zakelj, Simon; Kristl, Albin; Nagel, Stefan; Guthoff, Rudolf; Weitschies, Werner; Seidlitz, Anne

2012-08-30

To treat ophthalmic diseases like glaucoma or inflammatory disorders topically applied ophthalmic formulations such as eye drops are usually used. In addition, novel ophthalmic implants releasing drug substances locally into different parts of the eye are available today. In the work presented here, the permeability coefficients of selected drugs (ciprofloxacin hydrochloride, lidocaine hydrochloride, timolol maleate) for ophthalmic tissues were determined using side-by-side diffusion chambers (so-called Ussing chambers). Sclera, conjunctiva, cornea, choroidea-retina-complex and a complex of conjunctiva-sclera-choroidea-retina were excised from fresh porcine, rabbit and bovine eyes. In the porcine eye tissues the highest P(app) values were obtained for conjunctiva with the exception of lidocaine. Therefore, it can be estimated that a certain amount of drug diffuses or is transported through conjunctiva after application. The P(app) values for sclera were also higher than those for cornea and even more, the surface area of sclera which is available for drug absorption is much larger than that of cornea when applying an implant. The obtained permeability coefficients for sclera and conjunctiva indicate that the administration of periocular implants can be an alternative to topically applied formulations. The complexes of the tissues were a significantly (p<0.01) stronger barrier to the investigated substances than the separated tissues. Distinct differences in permeability coefficients between the investigated animal tissues were observed. Overall the highest P(app) values for all mounted tissues were obtained with the rabbit, followed by porcine and bovine eyes. Because of these distinct interspecies differences one must be very careful when selecting the proper animal model for the permeability experiments. Copyright © 2012 Elsevier B.V. All rights reserved.

77 FR 12361 - Qualification of Drivers; Exemption Applications; Vision

Federal Register 2010, 2011, 2012, 2013, 2014

2012-02-29

.... FOR FURTHER INFORMATION CONTACT: Elaine M. Papp, Chief, Medical Programs Division, 202-366-4001, U.S... INFORMATION: Background Under 49 U.S.C. 31136(e) and 31315, FMCSA may grant an exemption from the Federal.... The list published in this notice summarizes the Agency's recent denials as required under 49 U.S.C...

Was the Risk from Nursing-Home Evacuation after the Fukushima Accident Higher than the Radiation Risk?

PubMed

Murakami, Michio; Ono, Kyoko; Tsubokura, Masaharu; Nomura, Shuhei; Oikawa, Tomoyoshi; Oka, Tosihiro; Kami, Masahiro; Oki, Taikan

2015-01-01

After the 2011 accident at the Fukushima Daiichi nuclear power plant, nursing-home residents and staff were evacuated voluntarily from damaged areas to avoid radiation exposure. Unfortunately, the evacuation resulted in increased mortalities among nursing home residents. We assessed the risk trade-off between evacuation and radiation for 191 residents and 184 staff at three nursing homes by using the same detriment indicator, namely loss of life expectancy (LLE), under four scenarios, i.e. "rapid evacuation (in accordance with the actual situation; i.e. evacuation on 22 March)," "deliberate evacuation (i.e. evacuation on 20 June)," "20-mSv exposure," and "100-mSv exposure." The LLE from evacuation-related mortality among nursing home residents was assessed with survival probability data from nursing homes in the city of Minamisoma and the city of Soma. The LLE from radiation mortality was calculated from the estimated age-specific mortality rates from leukemia and all solid cancers based on the additional effective doses and the survival probabilities. The total LLE of residents due to evacuation-related risks in rapid evacuation was 11,000 persons-d-much higher than the total LLEs of residents and staff due to radiation in the other scenarios (27, 1100, and 5800 persons-d for deliberate evacuation, 20 mSv-exposure, and 100 mSv-exposure, respectively). The latitude for reducing evacuation risks among nursing home residents is surprisingly large. Evacuation regulation and planning should therefore be well balanced with the trade-offs against radiation risks. This is the first quantitative assessment of the risk trade-off between radiation exposure and evacuation after a nuclear power plant accident.

Strahlungsfeldbedingungen bei der Ionisationsdosimetrie

NASA Astrophysics Data System (ADS)

Krieger, Hanno

Bei der Dosimetrie von Photonenstrahlungen mit luftgefüllten Ionisationskammern werden in diesem Kapitel zwei Grenzfälle unterschieden. Der eine Fall ist die Bedingung des so genannten Sekundärelektronengleichwichts im Kammervolumen. In diesem Fall bestimmen ausschließlich die Photonen im Messvolumen die dosimetrische Anzeige. Der zweite Grenzfall ist gegeben, wenn das Luftvolumen und die Kammer das Strahlungsfeld im Phantom so wenig stören, dass der Sekundärelektronenfluss unverändert bleibt. Diese Bedingungen nennt man BRAGG-GRAY-Bedingungen. Beide Grenzfälle sind in der Praxis nur näherungsweise zu verwirklichen. Abweichungen müssen durch entsprechende Korrekturen oder Kalibrierungen berücksichtigt werden.

pH dependent but not P-gp dependent bidirectional transport study of S-propranolol: the importance of passive diffusion

PubMed Central

Zheng, Yi; Benet, Leslie Z.; Okochi, Hideaki; Chen, Xijing

2016-01-01

Purpose Recent controversial publications, citing studies purporting to show that P-gp mediates the transport of propranolol, proposed that passive biological membrane transport is negligible. Based on the BDDCS, the extensively metabolized-highly permeable-highly soluble BDDCS class 1 drug, propranolol, shows a high passive permeability at concentrations unrestricted by solubility that can overwhelm any potential transporter effects. Here we reinvestigate the effects of passive diffusion and carrier-mediated transport on S-propranolol. Methods Bidirectional permeability and inhibition of efflux transport studies were carried out in MDCK, MDCK-MDR1 and Caco-2 cell lines at different concentrations. Transcellular permeability studies were conducted at different apical pHs in the rat jejunum Ussing chamber model and PAMPA system. Results S-propranolol exhibited efflux ratios lower than 1 in MDCK, MDCK-MDR1 and Caco-2 cells. No significant differences of Papp, B->A in the presence and absence of the efflux inhibitor GG918 were observed. However, an efflux ratio of 3.63 was found at apical pH 6.5 with significant decrease in Papp, A->B and increase in Papp, B->A compared to apical pH 7.4 in Caco-2 cell lines. The pH dependent permeability was confirmed in the Ussing chamber model. S-propranolol flux was unchanged during inhibition by verapamil and rifampin. Furthermore, pH dependent permeability was also observed in the PAMPA system. Conclusions S-propranolol does not exhibit active transport as proposed previously. The "false" positive efflux ratio can be explained by the pH partition theory. As expected, passive diffusion, but not active transport, plays the primary role in the permeability of the BDDCS class 1 drug propranolol. PMID:25690341

Counting and behavior of an individual fluorescent molecule without hydrodynamic flow, immobilization, or photon count statistics.

PubMed

Földes-Papp, Zeno; Baumann, Gerd; Demel, Ulrike; Tilz, Gernot P

2004-04-01

Many theoretical models of molecular interactions, biochemical and chemical reactions are described on the single-molecule level, although our knowledge about the biochemical/chemical structure and dynamics primarily originates from the investigation of many-molecule systems. At present, there are four experimental platforms to observe the movement and the behavior of single fluorescent molecules: wide-field epi-illumination, near-field optical scanning, and laser scanning confocal and multiphoton microscopy. The platforms are combined with analytical methods such as fluorescence resonance energy transfer (FRET), fluorescence auto-or two-color cross-correlation spectroscopy (FCS), fluorescence polarizing anisotropy, fluorescence quenching and fluorescence lifetime measurements. The original contribution focuses on counting and characterization of freely diffusing single molecules in a single-phase like a solution or a membrane without hydrodynamic flow, immobilization or burst size analysis of intensity traces. This can be achieved, for example, by Fluorescence auto- or two-color cross-Correlation Spectroscopy as demonstrated in this original article. Three criteria (Földes-Papp (2002) Pteridines, 13, 73-82; Földes-Papp et al. (2004a) J. Immunol. Meth., 286, 1-11; Földes-Papp et al. (2004b) J. Immunol. Meth., 286, 13-20) are discussed for performing continuous measurements with one and the same single (individual) molecule, freely diffusing in a solution or a membrane, from sub-milliseconds up to severals hours. The 'algorithms' developed for single-molecule fluorescence detection are called the 'selfsame single-fluorescent-molecule regime'. An interesting application of the results found is in the field of immunology. The application of the theory to experimental results shows that the theory is consistent with the experiments. The exposition of the novel ideas on Single (Solution)-Phase Single-Molecule Fluorescence auto- or two-color cross

In vitro and in vivo assessment of cellular permeability and pharmacodynamics of S-nitrosylated Captopril, a nitric oxide donor

PubMed Central

Jia, Lee; Wong, Hong

2001-01-01

The present studies were aimed at testing the hypothesis that S-nitrosylated captopril (CapNO), a novel crystalline nitric oxide (NO) donor, readily permeates both in vitro and in vivo endothelial monolayers, resulting in its pharmacodynamic effects. CapNO and Captopril (Cap) were added to apical side of endothelial monolayers formed on microporous membranes, and the permeated drugs were collected from basolateral side and detected by a HPLC method. The permeability coefficient (Papp; cm sec−1) of CapNO across the endothelial monolayers was 6.0×10−5, higher than that of Cap (3.13×10−5), indicating the enhancement effect of the attached NO group in CapNO on cellular permeability. The Papp of CapNO and Cap across Caco-2 cells were 3.15×10−5 and 1.53×10−5, respectively. The low Papp of CapNO to Caco-2 cells may be attributed to the high membrane resistance of Caco-2 cells. A bolus injection of CapNO to epicardial coronary artery of chronically-instrumented awake dogs caused significant increases in coronary blood flow and coronary diameters dose-dependently without significant changes in aortic pressure. In contrast, the equimolar doses of Cap did not produce haemodynamic responses. Intravenous CapNO caused an instant increase in the regional cerebral blood flow determined by H2-clearance, whereas the equimolar doses of Cap did not enhance the cerebral blood flow. These results conclude that the NO group, an active component of CapNO, enhances both in vitro and in vivo endothelial permeability to the entire compound, resulting in instant increases in blood flow and vascular diameters. In contrast, the equimolar Cap does not have the instant vascular effects. PMID:11739246

In vitro and in vivo assessment of cellular permeability and pharmacodynamics of S-nitrosylated captopril, a nitric oxide donor.

PubMed

Jia, L; Wong, H

2001-12-01

1. The present studies were aimed at testing the hypothesis that S-nitrosylated captopril (CapNO), a novel crystalline nitric oxide (NO) donor, readily permeates both in vitro and in vivo endothelial monolayers, resulting in its pharmacodynamic effects. 2. CapNO and Captopril (Cap) were added to apical side of endothelial monolayers formed on microporous membranes, and the permeated drugs were collected from basolateral side and detected by a HPLC method. The permeability coefficient (P(app); cm sec(-1)) of CapNO across the endothelial monolayers was 6.0 x 10(-5), higher than that of Cap (3.13 x 10(-5)), indicating the enhancement effect of the attached NO group in CapNO on cellular permeability. The P(app) of CapNO and Cap across Caco-2 cells were 3.15 x 10(-5) and 1.53 x 10(-5), respectively. The low P(app) of CapNO to Caco-2 cells may be attributed to the high membrane resistance of Caco-2 cells. 3. A bolus injection of CapNO to epicardial coronary artery of chronically-instrumented awake dogs caused significant increases in coronary blood flow and coronary diameters dose-dependently without significant changes in aortic pressure. In contrast, the equimolar doses of Cap did not produce haemodynamic responses. 4. Intravenous CapNO caused an instant increase in the regional cerebral blood flow determined by H(2)-clearance, whereas the equimolar doses of Cap did not enhance the cerebral blood flow. 5. These results conclude that the NO group, an active component of CapNO, enhances both in vitro and in vivo endothelial permeability to the entire compound, resulting in instant increases in blood flow and vascular diameters. In contrast, the equimolar Cap does not have the instant vascular effects.

Biopharmaceutic Risk Assessment of Brand and Generic Lamotrigine Tablets.

PubMed

Vaithianathan, Soundarya; Raman, Siddarth; Jiang, Wenlei; Ting, Tricia Y; Kane, Maureen A; Polli, James E

2015-07-06

The therapeutic equivalence of generic and brand name antiepileptic drugs has been questioned by neurologists and the epilepsy community. A potential contributor to such concerns is pharmaceutical quality. The objective was to assess the biopharmaceutic risk of brand name Lamictal 100 mg tablets and generic lamotrigine 100 mg tablets from several manufacturers. Lamotrigine was characterized in terms of the Biopharmaceutics Classification System (BCS), including aqueous solubility and Caco-2 permeability. A panel of pharmaceutical quality tests was also performed on three batches of Lamictal, three batches of Teva generic, and one batch of each of four other generics: appearance, identity, assay, impurity, uniformity of dosage units, disintegration, dissolution, friability, and loss on drying. These market surveillance results indicate that all brand name and generic lamotrigine 100 mg tablets passed all tests and showed acceptable pharmaceutical quality and low biopharmaceutic risk. Lamotrigine was classified as a BCS class IIb drug, exhibiting pH-dependent aqueous solubility and dissolution. At pH 1.2 and 4.5, lamotrigine exhibited high solubility, whereas lamotrigine exhibited low solubility at pH 6.8, including non-sink dissolution. Lamotrigine showed high Caco-2 permeability. The apparent permeability (Papp) of lamotrigine was (73.7 ± 8.7) × 10(-6) cm/s in the apical-to-basolateral (AP-BL) direction and (41.4 ± 1.6) × 10(-6) cm/s in the BL-AP direction, which were higher than metoprolol's AP-BL Papp of (21.2 ± 0.9) × 10(-6) cm/s and BL-AP Papp of (34.6 ± 4.6) × 10(-6) cm/s. Overall, lamotrigine's favorable biopharmaceutics from a drug substance perspective and favorable quality characteristics from a tablet formulation perspective suggest that multisource lamotrigine tablets exhibit a low biopharmaceutic risk.

Analysis of Investigational Drugs in Biological Fluids. Method Development and Routine Assay. Appendix A.

DTIC Science & Technology

1997-02-13

AMINOPROPIOPHENONE IN DOG PLASMA 0 OCH 3 CH2 CH3 OCH2CHOHCH 2 OH H2 N& p-Aminopropiophenone Guaifenesin (WR 000,302) Internal Standard APPROVALS: This Analytical...40 - 80 il VOLUME: RUN TIME: 14 min (PAPP: 10.7 min; Guaifenesin (Internal Standard): 8.5 min) DETECTOR Wavelength: 316 nm SETTINGS: Absorption Range

Staff - Kenneth R. Papp | Alaska Division of Geological & Geophysical

Science.gov Websites

Alaska MAPTEACH Tsunami Inundation Mapping Energy Resources Gas Hydrates STATEMAP Program information Alaska Energy Authority, and the Curator of the Geologic Materials Center (2009-2015). Position: Division survey-wide interface for geologists to publish digital map data (DGGS) Established the Alaska Energy

State Anxiety and Nonlinear Dynamics of Heart Rate Variability in Students.

PubMed

Dimitriev, Dimitriy A; Saperova, Elena V; Dimitriev, Aleksey D

2016-01-01

Clinical and experimental research studies have demonstrated that the emotional experience of anxiety impairs heart rate variability (HRV) in humans. The present study investigated whether changes in state anxiety (SA) can also modulate nonlinear dynamics of heart rate. A group of 96 students volunteered to participate in the study. For each student, two 5-minute recordings of beat intervals (RR) were performed: one during a rest period and one just before a university examination, which was assumed to be a real-life stressor. Nonlinear analysis of HRV was performed. The Spielberger's State-Trait Anxiety Inventory was used to assess the level of SA. Before adjusting for heart rate, a Wilcoxon matched pairs test showed significant decreases in Poincaré plot measures, entropy, largest Lyapunov exponent (LLE), and pointwise correlation dimension (PD2), and an increase in the short-term fractal-like scaling exponent of detrended fluctuation analysis (α1) during the exam session, compared with the rest period. A Pearson analysis indicated significant negative correlations between the dynamics of SA and Poincaré plot axes ratio (SD1/SD2), and between changes in SA and changes in entropy measures. A strong negative correlation was found between the dynamics of SA and LLE. A significant positive correlation was found between the dynamics of SA and α1. The decreases in Poincaré plot measures (SD1, complex correlation measure), entropy measures, and LLE were still significant after adjusting for heart rate. Corrected α1 was increased during the exam session. As before, the dynamics of adjusted LLE was significantly correlated with the dynamics of SA. The qualitative increase in SA during academic examination was related to the decrease in the complexity and size of the Poincaré plot through a reduction of both the interbeat interval and its variation.

State Anxiety and Nonlinear Dynamics of Heart Rate Variability in Students

PubMed Central

Dimitriev, Aleksey D.

2016-01-01

Objectives Clinical and experimental research studies have demonstrated that the emotional experience of anxiety impairs heart rate variability (HRV) in humans. The present study investigated whether changes in state anxiety (SA) can also modulate nonlinear dynamics of heart rate. Methods A group of 96 students volunteered to participate in the study. For each student, two 5-minute recordings of beat intervals (RR) were performed: one during a rest period and one just before a university examination, which was assumed to be a real-life stressor. Nonlinear analysis of HRV was performed. The Spielberger’s State-Trait Anxiety Inventory was used to assess the level of SA. Results Before adjusting for heart rate, a Wilcoxon matched pairs test showed significant decreases in Poincaré plot measures, entropy, largest Lyapunov exponent (LLE), and pointwise correlation dimension (PD2), and an increase in the short-term fractal-like scaling exponent of detrended fluctuation analysis (α1) during the exam session, compared with the rest period. A Pearson analysis indicated significant negative correlations between the dynamics of SA and Poincaré plot axes ratio (SD1/SD2), and between changes in SA and changes in entropy measures. A strong negative correlation was found between the dynamics of SA and LLE. A significant positive correlation was found between the dynamics of SA and α1. The decreases in Poincaré plot measures (SD1, complex correlation measure), entropy measures, and LLE were still significant after adjusting for heart rate. Corrected α1 was increased during the exam session. As before, the dynamics of adjusted LLE was significantly correlated with the dynamics of SA. Conclusions The qualitative increase in SA during academic examination was related to the decrease in the complexity and size of the Poincaré plot through a reduction of both the interbeat interval and its variation. PMID:26807793

Prospective validation of first-trimester combined screening for trisomy 21.

PubMed

Kagan, K O; Etchegaray, A; Zhou, Y; Wright, D; Nicolaides, K H

2009-07-01

To examine the performance of the new algorithm in screening for trisomy 21 by a combination of maternal age, fetal nuchal translucency (NT) and maternal serum free beta-human chorionic gonadotropin (beta-hCG) and pregnancy-associated plasma protein-A (PAPP-A). This was a prospective screening study for trisomy 21 in singleton pregnancies at 11 + 0 to 13 + 6 weeks of gestation using an algorithm combining maternal age, fetal NT thickness based on the mixture model for the assessment of NT, and maternal serum free beta-hCG and PAPP-A based on a multiple regression model for the assessment of serum biochemistry. The NT measurements were performed by 60 operators who had obtained The Fetal Medicine Foundation certificate of competence in the 11-13-week scan. The study population consisted of 19 614 pregnancies with a normal karyotype or delivery of a phenotypically normal baby (euploid group) and 122 cases of trisomy 21. In the euploid fetuses the NT was above the previously defined 50(th), 95(th) and 99(th) centiles in 10 033 (51.2%), 618 (3.2%) and 123 (0.6%) cases and the respective values for trisomy 21 were 117 (95.9%), 94 (77.0%) and 57 (46.7%). The median fetal NT was within 0.1 mm of the expected in 47 (78.3%) of the 60 sonographers and within 0.2 mm in all. In the euploid fetuses the median free beta-hCG was 1.0 (range, 0.1-29.4) multiples of the median (MoM) and the median PAPP-A was 1.0 (range, 0.2-3.3) MoM. The median MoM values were 1.0 or close to 1.0 MoM for each subgroup of pregnancy characteristics, including gestations of 11, 12 and 13 weeks, maternal weight of < 60 kg, 60-80 kg and > 80 kg, different ethnic origins, cigarette smokers and non-smokers, natural conception and in vitro fertilization. For a false-positive rate of 3%, the detection rate of trisomy 21 in screening by maternal age and fetal NT was 81% (95% CI, 73-89%), by maternal age and maternal serum biochemistry it was 63% (95% CI, 56-72%) and by combined screening based on maternal age

[Preparation and applications of a supported liquid-liquid extraction column with a composite diatomite material].

PubMed

Bao, Jianmin; Ma, Zhishuang; Sun, Ying; Wang, Yongzun; Li, Youxin

2012-08-01

A rapid and special supported liquid-liquid extraction (SLE) column was developed with a composite diatomite material. The SLE column was evaluated by high performance liquid chromatography (HPLC) with acidic, neutral and alkaline compounds dissolved in water. Furthermore, some real complex samples were also analyzed by HPLC with the SLE method. The recoveries of benzoic acid (acidic), p-nitroaniline (alkaline) and 4-hydroxy-benzoic methyl ester (neutral) treated by the SLE column were 90.6%, 98.1% and 97.7%. However, the recoveries of the three compounds treated by traditional liquid-liquid extraction (LLE) method were 71.9%, 81.9% and 83.9%. The results showed that the SLE technique had higher recoveries than the traditional LLE method. The spiked recoveries of the complex samples, such as benzoic acid in Sprite and dexamethasone acetate, chlorphenamine maleate, indomethacin in bovine serum, were between 80% and 110% and the relative standard deviations (RSDs) were less than 15%. For biological specimen, the results could be accepted. Meantime, many disadvantages associated with traditional LLE method, such as emulsion formation, didn't occur using SLE column. The SLE column technique is a good sample preparation method with many advantages, such as rapid, simple, robust, easily automated, high recovery and high-throughput, which would be widely used in the future.

Quantitative determination of methamphetamine in oral fluid by liquid-liquid extraction and gas chromatography/mass spectrometry.

PubMed

Bahmanabadi, L; Akhgari, M; Jokar, F; Sadeghi, H B

2017-02-01

Methamphetamine abuse is one of the most medical and social problems many countries face. In spite of the ban on the use of methamphetamine, it is widely available in Iran's drug black market. There are many analytical methods for the detection of methamphetamine in biological specimen. Oral fluid has become a popular specimen to test for the presence of methamphetamine. The purpose of the present study was to develop a method for the extraction and detection of methamphetamine in oral fluid samples using liquid-liquid extraction (LLE) and gas chromatography/mass spectrometry (GC/MS) methods. An analytical study was designed in that blank and 50 authentic oral fluid samples were collected to be first extracted by LLE and subsequently analysed by GC/MS. The method was fully validated and showed an excellent intra- and inter-assay precision (reflex sympathetic dystrophy ˂ 10%) for external quality control samples. Recovery with LLE methods was 96%. Limit of detection and limit of quantitation were 5 and 15 ng/mL, respectively. The method showed high selectivity, no additional peak due to interfering substances in samples was observed. The introduced method was sensitive, accurate and precise enough for the extraction of methamphetamine from oral fluid samples in forensic toxicology laboratories.

LLE Review 118 (January-March 2009)

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

Bittle, W., editor

2009-08-03

This issue has the following articles: (1) Applied Plasma Spectroscopy: Laser-Fusion Experiments; (2) Relativistic Electron-Beam Transport Studies Using High-Resolution, Coherent Transition Radiation Imaging; (3) Pressure-Driven, Resistive Magnetohydrodynamic Interchange Instabilities in Laser-Produced, High-Energy-Density Plasmas; (4) Extended Model for Polymer Cholesteric Liquid Crystal Flake Reorientation and Relaxation; (5) Modeling the Effects of Microencapsulation on the Electro-Optic Behavior of Polymer Cholesteric Liquid Crystal Flakes; (6) Capillarity and Dielectrophoresis of Liquid Deuterium; and (7) A Stable Mid-IR, GaSb-Based Diode Laser Source for Cryogenic Target Layering at the OMEGA Laser Facility.

Only a minority of sex chromosome abnormalities are detected by a national prenatal screening program for Down syndrome.

PubMed

Viuff, Mette Hansen; Stochholm, Kirstine; Uldbjerg, Niels; Nielsen, Birgitte Bruun; Gravholt, Claus Højbjerg

2015-10-01

How does a national prenatal screening program for Down syndrome (DS) perform in detecting sex chromosome abnormalities (SCAs)-Turner syndrome (TS), Klinefelter syndrome, 47,XXX and 47,XYY syndromes. The SCA detection rate resulting from DS screening was below 50% for all four groups of SCAs. The detection rates of SCAs are higher in countries with DS screening. TS is associated with greater nuchal translucency (NT) and lower pregnancy-associated plasma protein-A (PAPP-A). However, specific detection rates of SCAs using prenatal DS screening have not been determined. No clear trend in PAPP-A, free beta human chorionic gonadotropin (β-hCG) and NT has been found in the remaining SCAs. Several lines of inquiry suggest that it would be advantageous for individuals with SCA to be detected early in life, leading to prevention or treatment of accompanying conditions. There is limited information about pre- and perinatal status that distinguishes SCA embryogenesis from normal fetal development. A register-based case-control study from the Danish Central Cytogenetic Register (DCCR), cross-linked with the Danish Fetal Medicine Database (DFMD), was performed from 2008 to 2012. Groups of SCAs were compared with DS and then matched with non-SCA controls to assess differences between these groups in prenatal markers and birth outcomes. We included cases with prenatal and post-natal SCA karyotypes (n = 213), DS (n = 802) and 168 056 controls. We screened 275 037 individuals examined prenatally. We retrieved information regarding maternal age, NT, β-hCG and PAPP-A, as well as details regarding maternal and newborn characteristics. The DS screening procedure detected 87 per 100 000 TS (42% of expected), 19 per 100 000 Klinefelter syndrome (13% of expected), 16 per 100 000 47,XXX (16% of cases) and 5 per 100 000 47,XYY (5% of expected) SCAs, with an overall detection rate of 27%. Compared with controls, all four SCA groups showed significantly higher NT and lower PAPP-A compared

The Framework for an Information Technology Strategic Roadmap for the United States Marine Corps: How Current Acquisitions Align to the Current Strategic Direction of the Department of Defense, Department of the Navy, and United States Marine Corps

DTIC Science & Technology

2008-06-01

PAGE INTENTIONALLY LEFT BLANK xv ACKNOWLEDGMENTS We would like to thank Mr. Clint Swett (Director, Technology Services Organization, DFAS- KC ) and...Major Jeffrey Thiry (Deputy Director, Technology Services Organization, DFAS- KC ) for their help and support. Their guidance proved invaluable in... Teo (1996) define alignment as the “coordination between the business and IS planning functions and activities”. Luftman, Papp and Brier (1999

[Effect of Radix euphorbiae pekinensis extract on bioavailability of paclitaxel after their oral co-administration].

PubMed

Li, Minghua; Peng, Li; Yang, Fuheng; Liu, Sijia; Wang, Shengqi

2015-06-01

To evaluate the effect of Radix euphorbiae pekinensis extract on the permeability and bioavailability of paclitaxel co-administered orally. Based on Ussing Chamber and in vivo experiment, the permeability and bioavailability of paclitaxel were evaluated after oral co-administration with radix euphorbiae pekinensis in rats. The contents of paclitaxel in the permeates and the blood samples were determined using HPLC and LC-MS/MS method, respectively. In Radix euphorbiae pekinensis co-administration group, the Papp of the mucosal-to-serosal (M-S) transport or serosal-to-mucosal transport (S-M) of paclitaxel in the jejunum or ileum segment differed significantly from those in verapamil co-administration group and blank control group (P<0.05), but the Papp of S-M transport in the colon showed no significant difference from that in the blank control group. In the blank group, the average absolute bioavailability (AB%) of orally administered paclitaxel was only 2.81%, compared to that of 7.63% in radix euphorbiae pekinensis group. The average AB% in verapamil group was about 1.5 times that of the blank group. Co-administration of Radix euphorbiae pekinensis extract can increase the bioavailability of orally administered paclitaxel.

Determination of the pK values of 5-aminosalicylic acid and N-acetylaminosalicylic acid and comparison of the pH dependent lipid-water partition coefficients of sulphasalazine and its metabolites.

PubMed

Allgayer, H; Sonnenbichler, J; Kruis, W; Paumgartner, G

1985-01-01

Sulphasalazine (SASP), used in the treatment of inflammatory bowel disease, is split into sulphapyridine (SP) and 5-aminosalicylic acid (5-ASA) in the colon. Lower plasma levels of SASP and 5-ASA as compared to those of SP may be due to different absorption rates from the colon because of different pK values and pH dependent lipid-water partition coefficients. In this study we determined the pK values of 5-ASA and its major metabolite, N-acetyl amino-salicylic acid (AcASA), by 13C-NMR spectroscopy and compared the pH dependent apparent benzene-water partition coefficients (Papp) of SASP, SP and 5-ASA with respect to their different plasma levels. The COOH group of 5-ASA had a pK value of 3.0, the -NH3+ group had 6.0, the -OH group 13.9; the -COOH group of AcASA had 2.7 and the -OH group 12.9; The Papp of SASP (0.042 +/- 0.004) and 5-ASA (0.059 +/- 0.01) were significantly lower than that of SP (0.092 +/- 0.03) (at pH 5.5).

Identification and quantification analysis of nonlinear dynamics properties of combustion instability in a diesel engine

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

Yang, Li-Ping, E-mail: yangliping302@hrbeu.edu.cn; Ding, Shun-Liang; Song, En-Zhe

The cycling combustion instabilities in a diesel engine have been analyzed based on chaos theory. The objective was to investigate the dynamical characteristics of combustion in diesel engine. In this study, experiments were performed under the entire operating range of a diesel engine (the engine speed was changed from 600 to 1400 rpm and the engine load rate was from 0% to 100%), and acquired real-time series of in-cylinder combustion pressure using a piezoelectric transducer installed on the cylinder head. Several methods were applied to identify and quantitatively analyze the combustion process complexity in the diesel engine including delay-coordinate embedding, recurrencemore » plot (RP), Recurrence Quantification Analysis, correlation dimension (CD), and the largest Lyapunov exponent (LLE) estimation. The results show that the combustion process exhibits some determinism. If LLE is positive, then the combustion system has a fractal dimension and CD is no more than 1.6 and within the diesel engine operating range. We have concluded that the combustion system of diesel engine is a low-dimensional chaotic system and the maximum values of CD and LLE occur at the lowest engine speed and load. This means that combustion system is more complex and sensitive to initial conditions and that poor combustion quality leads to the decrease of fuel economy and the increase of exhaust emissions.« less

A continuous mapping of sleep states through association of EEG with a mesoscale cortical model.

PubMed

Lopour, Beth A; Tasoglu, Savas; Kirsch, Heidi E; Sleigh, James W; Szeri, Andrew J

2011-04-01

Here we show that a mathematical model of the human sleep cycle can be used to obtain a detailed description of electroencephalogram (EEG) sleep stages, and we discuss how this analysis may aid in the prediction and prevention of seizures during sleep. The association between EEG data and the cortical model is found via locally linear embedding (LLE), a method of dimensionality reduction. We first show that LLE can distinguish between traditional sleep stages when applied to EEG data. It reliably separates REM and non-REM sleep and maps the EEG data to a low-dimensional output space where the sleep state changes smoothly over time. We also incorporate the concept of strongly connected components and use this as a method of automatic outlier rejection for EEG data. Then, by using LLE on a hybrid data set containing both sleep EEG and signals generated from the mesoscale cortical model, we quantify the relationship between the data and the mathematical model. This enables us to take any sample of sleep EEG data and associate it with a position among the continuous range of sleep states provided by the model; we can thus infer a trajectory of states as the subject sleeps. Lastly, we show that this method gives consistent results for various subjects over a full night of sleep and can be done in real time.

Identification and quantification analysis of nonlinear dynamics properties of combustion instability in a diesel engine.

PubMed

Yang, Li-Ping; Ding, Shun-Liang; Litak, Grzegorz; Song, En-Zhe; Ma, Xiu-Zhen

2015-01-01

The cycling combustion instabilities in a diesel engine have been analyzed based on chaos theory. The objective was to investigate the dynamical characteristics of combustion in diesel engine. In this study, experiments were performed under the entire operating range of a diesel engine (the engine speed was changed from 600 to 1400 rpm and the engine load rate was from 0% to 100%), and acquired real-time series of in-cylinder combustion pressure using a piezoelectric transducer installed on the cylinder head. Several methods were applied to identify and quantitatively analyze the combustion process complexity in the diesel engine including delay-coordinate embedding, recurrence plot (RP), Recurrence Quantification Analysis, correlation dimension (CD), and the largest Lyapunov exponent (LLE) estimation. The results show that the combustion process exhibits some determinism. If LLE is positive, then the combustion system has a fractal dimension and CD is no more than 1.6 and within the diesel engine operating range. We have concluded that the combustion system of diesel engine is a low-dimensional chaotic system and the maximum values of CD and LLE occur at the lowest engine speed and load. This means that combustion system is more complex and sensitive to initial conditions and that poor combustion quality leads to the decrease of fuel economy and the increase of exhaust emissions.

In vitro porcine blood-brain barrier model for permeability studies: pCEL-X software pKa(FLUX) method for aqueous boundary layer correction and detailed data analysis.

PubMed

Yusof, Siti R; Avdeef, Alex; Abbott, N Joan

2014-12-18

In vitro blood-brain barrier (BBB) models from primary brain endothelial cells can closely resemble the in vivo BBB, offering valuable models to assay BBB functions and to screen potential central nervous system drugs. We have recently developed an in vitro BBB model using primary porcine brain endothelial cells. The model shows expression of tight junction proteins and high transendothelial electrical resistance, evidence for a restrictive paracellular pathway. Validation studies using small drug-like compounds demonstrated functional uptake and efflux transporters, showing the suitability of the model to assay drug permeability. However, one limitation of in vitro model permeability measurement is the presence of the aqueous boundary layer (ABL) resulting from inefficient stirring during the permeability assay. The ABL can be a rate-limiting step in permeation, particularly for lipophilic compounds, causing underestimation of the permeability. If the ABL effect is ignored, the permeability measured in vitro will not reflect the permeability in vivo. To address the issue, we explored the combination of in vitro permeability measurement using our porcine model with the pKa(FLUX) method in pCEL-X software to correct for the ABL effect and allow a detailed analysis of in vitro (transendothelial) permeability data, Papp. Published Papp using porcine models generated by our group and other groups are also analyzed. From the Papp, intrinsic transcellular permeability (P0) is derived by simultaneous refinement using a weighted nonlinear regression, taking into account permeability through the ABL, paracellular permeability and filter restrictions on permeation. The in vitro P0 derived for 22 compounds (35 measurements) showed good correlation with P0 derived from in situ brain perfusion data (r(2)=0.61). The analysis also gave evidence for carrier-mediated uptake of naloxone, propranolol and vinblastine. The combination of the in vitro porcine model and the software

Influence of gravidity and foetal gender on the value of screening variables in the first trimester of pregnancy.

PubMed

Illescas, Tamara; Fernández, Cristina; Ortega, Dolores; de la Puente, Miriam; Coronado, Pluvio; Montalvo, Joaquín

2013-03-01

Combined screening for chromosome abnormalities in the first trimester of pregnancy is based on maternal age, nuchal translucency (NT) and biochemical markers (PAPP-A and free β-hCG). We sought to assess the value of the variables used in the combined screening strategy taking into account maternal gravidity and foetal gender. Between July 1999 and December 2009, a total of 21,193 singleton pregnancies were screened for aneuploidy in the first trimester, in the Hospital Clínico San Carlos (Madrid, Spain). In the original database foetal gender data were available in 4370 euploid cases, and there were 2343 women with at least two consecutive pregnancies. We conducted a retrospective assessment of ultrasound and biochemical markers taking into account foetal gender and maternal gravidity, and evaluated the effect on the performance of screening, in terms of detection rates and false positive rates. Information on pregnancy outcome was obtained from the hospital's intranet medical records or by contacting the patient by telephone postpartum. Karyotype was ascertained by amniocentesis or chorionic villus sampling, and euploid status was assumed in newborns with normal phenotype. Student's t-tests (paired or unpaired as appropriate) were applied to the data, and the Bland-Altmann method was applied in evaluating individual differences in markers between successive gestations. PAPP-A decreased significantly between the first and the second pregnancy (p<0.01). PAPP-A and free β-hCG values were significantly higher (p=0.04 and p<0.01 respectively) and NT was lower (p=0.02) in pregnancies with a female foetus. Correlations between the biochemical variables in relation to gravidity and foetal gender can introduce a bias in the calculated risk of chromosome abnormalities. Differences in NT measurements with respect to foetal gender do not seem to be of clinical importance. NT is independent of gravidity so routine use of NT compensates for the influence of these maternal

Quantitative ELISAs for serum soluble LHCGR and hCG-LHCGR complex: potential diagnostics in first trimester pregnancy screening for stillbirth, Down’s syndrome, preterm delivery and preeclampsia

PubMed Central

2012-01-01

Background Soluble LH/hCG receptor (sLHCGR) released from placental explants and transfected cells can be detected in sera from pregnant women. To determine whether sLHCGR has diagnostic potential, quantitative ELISAs were developed and tested to examine the correlation between pregnancy outcome and levels of serum sLHCGR and hCG-sLHCGR complex. Methods Anti-LHCGR poly- and monoclonal antibodies recognizing defined LHCGR epitopes, commerical anti-hCGbeta antibody, together with recombinant LHCGR and yoked hCGbeta-LHCGR standard calibrators were used to develop two ELISAs. These assays were employed to quantify serum sLHCGR and hCG-sLHCGR at first trimester human pregnancy. Results Two ELISAs were developed and validated. Unlike any known biomarker, sLHCGR and hCG-sLHCGR are unique because Down’s syndrome (DS), preeclampsia and preterm delivery are linked to both low (less than or equal to 5 pmol/mL), and high (equal to or greater than 170 pmol/mL) concentrations. At these cut-off values, serum hCG-sLHCGR together with PAPP-A detected additional DS pregnancies (21%) which were negative by free hCGbeta plus PAPP-A screening procedure. Therefore, sLHCGR/hCG-sLHCGR has an additive effect on the current primary biochemical screening of aneuploid pregnancies. More than 88% of pregnancies destined to end in fetal demise (stillbirth) exhibited very low serum hCG-sLHCGR(less than or equal to 5 pmol/mL) compared to controls (median 16.15 pmol/mL, n = 390). The frequency of high hCG-sLHCGR concentrations (equal to or greater than 170 pmol/mL) in pathological pregnancies was at least 3-6-fold higher than that of the control, suggesting possible modulation of the thyrotropic effect of hCG by sLHCGR. Conclusions Serum sLHCGR/hCG-sLHCGR together with PAPP-A, have significant potential as first trimester screening markers for predicting pathological outcomes in pregnancy. PMID:23245345

Risk assessment of mortality for all-cause, ischemic heart disease, cardiopulmonary disease, and lung cancer due to the operation of the world's largest coal-fired power plant

NASA Astrophysics Data System (ADS)

Kuo, Pei-Hsuan; Tsuang, Ben-Jei; Chen, Chien-Jen; Hu, Suh-Woan; Chiang, Chun-Ju; Tsai, Jeng-Lin; Tang, Mei-Ling; Chen, Guan-Jie; Ku, Kai-Chen

2014-10-01

Based on recent understanding of PM2.5 health-related problems from fossil-fueled power plants emission inventories collected in Taiwan, we have determined the loss of life expectancy (LLE) and the lifetime (75-year) risks for PM2.5 health-related mortalities as attributed to the operation of the world's largest coal-fired power plant; the Taichung Power Plant (TCP), with an installed nominal electrical capacity of 5780 MW in 2013. Five plausible scenarios (combinations of emission controls, fuel switch, and relocation) and two risk factors were considered. It is estimated that the lifetime (75-y) risk for all-cause mortality was 0.3%-0.6% for males and 0.2%-0.4% for females, and LLE at 84 days in 1997 for the 23 million residents of Taiwan. The risk has been reduced to one-fourth at 0.05%-0.10% for males and 0.03%-0.06% for females, and LLE at 15 days in 2007, which was mainly attributed to the installation of desulfurization and de-NOx equipment. Moreover, additional improvements can be expected if we can relocate the power plant to a downwind site on Taiwan, and convert the fuel source from coal to natural gas. The risk can be significantly reduced further to one-fiftieth at 0.001%-0.002% for males and 0.001% for females, and LLE at 0.3 days. Nonetheless, it is still an order higher than the commonly accepted elevated-cancer risk at 0.0001% (10-6), indicating that the PM2.5 health-related risk for operating such a world-class power plant is not negligible. In addition, this study finds that a better-chosen site (involving moving the plant to the leeward side of Taiwan) can reduce the risk significantly as opposed to solely transitioning the fuel source to natural gas. Note that the fuel cost of using natural gas (0.11 USD/kWh in 2013) in Taiwan is about twice the price of using coal fuel (0.05 USD/kWh in 2013).

Tests and calibration of NIF neutron time of flight detectors.

PubMed

Ali, Z A; Glebov, V Yu; Cruz, M; Duffy, T; Stoeckl, C; Roberts, S; Sangster, T C; Tommasini, R; Throop, A; Moran, M; Dauffy, L; Horsefield, C

2008-10-01

The National Ignition Facility (NIF) neutron time of flight (NTOF) diagnostic will measure neutron yield and ion temperature in all NIF campaigns in DD, DT, and THD(*) implosions. The NIF NTOF diagnostic is designed to measure neutron yield from 1x10(9) to 2x10(19). The NTOF consists of several detectors of varying sensitivity located on the NIF at about 5 and 20 m from the target. Production, testing, and calibration of the NIF NTOF detectors have begun at the Laboratory for Laser Energetics (LLE). Operational tests of the NTOF detectors were performed on several facilities including the OMEGA laser at LLE and the Titan laser at Lawrence Livermore National Laboratory. Neutron calibrations were carried out on the OMEGA laser. Results of the NTOF detector tests and calibration will be presented.

General rigid motion correction for computed tomography imaging based on locally linear embedding

NASA Astrophysics Data System (ADS)

Chen, Mianyi; He, Peng; Feng, Peng; Liu, Baodong; Yang, Qingsong; Wei, Biao; Wang, Ge

2018-02-01

The patient motion can damage the quality of computed tomography images, which are typically acquired in cone-beam geometry. The rigid patient motion is characterized by six geometric parameters and are more challenging to correct than in fan-beam geometry. We extend our previous rigid patient motion correction method based on the principle of locally linear embedding (LLE) from fan-beam to cone-beam geometry and accelerate the computational procedure with the graphics processing unit (GPU)-based all scale tomographic reconstruction Antwerp toolbox. The major merit of our method is that we need neither fiducial markers nor motion-tracking devices. The numerical and experimental studies show that the LLE-based patient motion correction is capable of calibrating the six parameters of the patient motion simultaneously, reducing patient motion artifacts significantly.

The Design and Implementation of a Data Flow Multiprocessor.

DTIC Science & Technology

1981-12-01

to thank Captain Charles Papp who taught me how to use the logic analyzer and the storage oscilloscope. Without these tools, I could never have...debugged and repaired the microprocessors. Finally, I wish to thank my thesis readers, Major Charles Lillie and Major Walt Seward, for taking valuable time...Neumann/ Babbage architecture with the a data flow architecture. The next section describes the benefits of data flow computing. The following section

Improving Non-Linear Approaches to Anomaly Detection, Class Separation, and Visualization

DTIC Science & Technology

2014-12-26

Chainlink . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 10 2.2.3 Modified Banana ...45 3.3 LLE Example for the Modified Banana Dataset. . . . . . . . . . . . . . . . . . 47 x...Figure Page 3.4 Banana Dataset RLLE and Supervised RLLE Example. . . . . . . . . . . . . . 51 3.5 DWT Decomposition [162

Late Language Emergence at 24 Months: An Epidemiological Study of Prevalence, Predictors, and Covariates

PubMed Central

Zubrick, Stephen R.; Taylor, Catherine L.; Rice, Mabel L.

2012-01-01

Purpose The primary objectives of this study were to determine the prevalence of late language emergence (LLE) and to investigate the predictive status of maternal, family, and child variables. Method This is a prospective cohort study of 1766 epidemiologically ascertained twenty-four-month singleton children. The framework was an ecological model of child development, encompassing a wide range of maternal, family, and child variables. Data were obtained using postal questionnaire. Item analyses of the 6-item Ages and Stages Questionnaire (ASQ) Communication Scale yielded a composite score encompassing comprehension as well as production items. One standard deviation below the mean yielded good separation of affected from unaffected children. Analyses of bivariate relationships with maternal, family, and child variables were carried out, followed by multivariate logistic regression to predict LLE group membership. Results 13.4% of the sample showed late language emergence via the ASQ criterion; 19.1% using a single item “combining words.” Risk for LLE at 24 months was not associated with particular strata of parental educational levels, socioeconomic resources, parental mental health, parenting practices or family functioning. Significant predictors included familial history of late language emergence, male gender and early neurobiological growth. Covariates included psychosocial indicators. Conclusion Results are congruent with models of language emergence and impairment that posit a strong role for neurobiological and genetic mechanisms of onset that operate across a wide variation in maternal and family characteristics. PMID:18055773

Direct-drive inertial confinement fusion research at the Laboratory for Laser Energetics: charting the path to thermonuclear ignition

NASA Astrophysics Data System (ADS)

McCrory, R. L.; Regan, S. P.; Loucks, S. J.; Meyerhofer, D. D.; Skupsky, S.; Betti, R.; Boehly, T. R.; Craxton, R. S.; Collins, T. J. B.; Delettrez, J. A.; Edgell, D.; Epstein, R.; Fletcher, K. A.; Freeman, C.; Frenje, J. A.; Glebov, V. Yu.; Goncharov, V. N.; Harding, D. R.; Igumenshchev, I. V.; Keck, R. L.; Kilkenny, J. D.; Knauer, J. P.; Li, C. K.; Marciante, J.; Marozas, J. A.; Marshall, F. J.; Maximov, A. V.; McKenty, P. W.; Myatt, J.; Padalino, S.; Petrasso, R. D.; Radha, P. B.; Sangster, T. C.; Séguin, F. H.; Seka, W.; Smalyuk, V. A.; Soures, J. M.; Stoeckl, C.; Yaakobi, B.; Zuegel, J. D.

2005-10-01

Significant theoretical and experimental progress continues to be made at the University of Rochester's Laboratory for Laser Energetics (LLE), charting the path to direct-drive inertial confinement fusion (ICF) ignition. Direct drive offers the potential for higher-gain implosions than x-ray drive and is a leading candidate for an inertial fusion energy power plant. LLE's direct-drive ICF ignition target designs for the National Ignition Facility (NIF) are based on hot-spot ignition. A cryogenic target with a spherical DT-ice layer, within or without a foam matrix, enclosed by a thin plastic shell, will be directly irradiated with ~1.5 MJ of laser energy. Cryogenic and plastic/foam (surrogate-cryogenic) targets that are hydrodynamically scaled from these ignition target designs are imploded on the 60-beam, 30 kJ, UV OMEGA laser system to validate the key target physics issues, including energy coupling, hydrodynamic instabilities and implosion symmetry. Prospects for direct-drive ignition on the NIF are extremely favourable, even while it is in its x-ray-drive irradiation configuration, with the development of the polar-direct-drive concept. A high-energy petawatt capability is being constructed at LLE next to the existing 60-beam OMEGA compression facility. This OMEGA EP (extended performance) laser will add two short-pulse, 2.6 kJ beams to the OMEGA laser system to backlight direct-drive ICF implosions and study fast-ignition physics with focused intensities up to 6 × 1020 W cm-2.

Method development for the analysis of organophosphate and pyrethroid insecticides at low parts per trillion levels in water.

PubMed

Wang, Dongli; Weston, Donald P; Lydy, Michael J

2009-06-15

In the current study, organophosphate and pyrethroid insecticides including diazinon, chlorpyrifos, bifenthrin, fenpropathrin, permethrin, lambda-cyhalothrin, cyfluthrin, cypermethrin, esfenvalerate and deltamethrin were analyzed in laboratory and field-collected water samples. Water samples were extracted and analyzed by gas chromatography/electron capture detector (GC/ECD) and gas chromatography/nitrogen-phosphorous detector (GC/NPD). Comparison of results from liquid-liquid extraction and subsequent normal phase solid-phase extraction cleanup (LLE-NPSPE), and reversed phase solid-phase extraction (RPSPE) showed that LLE-NPSPE was the better choice to extract trace amounts of pesticides from water. Pesticide recoveries from four spiked water samples using LLE-NPSPE ranged from 63.2 to 148.8% at four spiking concentrations. Method detection limits were 0.72-1.69 ng/L using four different water sources. The stability of the target pesticides in lake water was investigated at 4 degrees C for 1h, 1d, 4d, and 7d under three conditions: (1) water samples only; (2) with 20 mL hexane used as a keeper solvent; and (3) with acidification to pH 2 with HCl. Results showed that water storage without treatment resulted in slow degradation of some pesticides with storage time, storage using water acidification led to significant degradation and loss of diazinon and chlorpyrifos, while water storage with hexane as a keeper solvent showed good stability for all of the target pesticides over the 7d storage period.

Predicting phenolic acid absorption in Caco-2 cells: a theoretical permeability model and mechanistic study.

PubMed

Farrell, Tracy L; Poquet, Laure; Dew, Tristan P; Barber, Stuart; Williamson, Gary

2012-02-01

There is a considerable need to rationalize the membrane permeability and mechanism of transport for potential nutraceuticals. The aim of this investigation was to develop a theoretical permeability equation, based on a reported descriptive absorption model, enabling calculation of the transcellular component of absorption across Caco-2 monolayers. Published data for Caco-2 permeability of 30 drugs transported by the transcellular route were correlated with the descriptors 1-octanol/water distribution coefficient (log D, pH 7.4) and size, based on molecular mass. Nonlinear regression analysis was used to derive a set of model parameters a', β', and b' with an integrated molecular mass function. The new theoretical transcellular permeability (TTP) model obtained a good fit of the published data (R² = 0.93) and predicted reasonably well (R² = 0.86) the experimental apparent permeability coefficient (P(app)) for nine non-training set compounds reportedly transported by the transcellular route. For the first time, the TTP model was used to predict the absorption characteristics of six phenolic acids, and this original investigation was supported by in vitro Caco-2 cell mechanistic studies, which suggested that deviation of the P(app) value from the predicted transcellular permeability (P(app)(trans)) may be attributed to involvement of active uptake, efflux transporters, or paracellular flux.

Comparison of isorhamnetin absorption properties in total flavones of Hippophae rhamnoides L. with its pure form in a Caco-2 cell model mediated by multidrug resistance-associated protein.

PubMed

Xie, Yan; Duan, Jingze; Fu, Qingxue; Xia, Mengxin; Zhang, Lei; Li, Guowen; Wu, Tao; Ji, Guang

2015-06-20

Total flavones of Hippophae rhamnoides L. (TFH) are extracted from the widely distributed thorny bush Sea buckthorn (Hippophae rhamnoides L.). Isorhamnetin (IS) is one of the representative ingredients in TFH. In this study, the absorption properties of IS in TFH and its pure form were compared through transepithelial transport and cellular uptake experiments in a Caco-2 cell model. Our results show that the absorption properties of IS in TFH and its pure form were remarkably different: (1) Both PappAB and PappBA of IS in TFH were dramatically increased compared with those of IS pure form; consequently, its Pratio was 2.3-fold higher than that of IS; (2) Both the accumulation and efflux of IS in TFH were significantly enhanced compared with the single compound. One likely reason for these differences is that the multiple components in TFH significantly down regulated the mRNA expression level of MRP2, which lead to a decrease in the protein level of MRP2, based on western blotting and RT-PCR assays. This study highlights the significant differences in the absorption properties of flavonoid components in different forms and the potential multi-component interactions in TFH. Copyright © 2015 Elsevier B.V. All rights reserved.

Assessment of rate of drug release from oil vehicle using a rotating dialysis cell.

PubMed

Larsen, D H; Fredholt, K; Larsen, C

2000-09-01

The rate constants for transfer of model compounds (naproxen and lidocaine) from oily vehicle (Viscoleo) to aqueous buffer phases were determined by use of the rotating dialysis cell. Release studies were done for the partly ionized compounds at several pH values. A correlation between the overall first-order rate constant related to attainment of equilibrium, k(obs), and the pH-dependent distribution coefficient, D, determined between oil vehicle and aqueous buffer was established according to the equation: logk(obs)=-0.71 logD-0.22 (k(obs) in h(-1)). Based on this correlation it was suggested that the rate constant of a weak electrolyte at a specified D value could be considered equal to the k(obs) value for a non-electrolyte possessing a partition coefficient, P(app), the magnitude of which was equal to D. Specific rate constants k(ow) and k(wo) were calculated from the overall rate constant and the pH-dependent distribution coefficient. The rate constant representing the transport from oily vehicle to aqueous phase, k(ow), was found to be significantly influenced by the magnitude of the partition coefficient P(app) according to: logk(ow)=-0.71 logP(app)-log(P(app)+1)-0.22 (k(ow) in h(-1)).

Semi-automated 96-well liquid-liquid extraction for quantitation of drugs in biological fluids.

PubMed

Zhang, N; Hoffman, K L; Li, W; Rossi, D T

2000-02-01

A semi-automated liquid-liquid extraction (LLE) technique for biological fluid sample preparation was introduced for the quantitation of four drugs in rat plasma. All liquid transferring during the sample preparation was automated using a Tomtec Quadra 96 Model 320 liquid handling robot, which processed up to 96 samples in parallel. The samples were either in 96-deep-well plate or tube-rack format. One plate of samples can be prepared in approximately 1.5 h, and the 96-well plate is directly compatible with the autosampler of an LC/MS system. Selection of organic solvents and recoveries are discussed. Also, precision, relative error, linearity and quantitation of the semi automated LLE method are estimated for four example drugs using LC/MS/MS with a multiple reaction monitoring (MRM) approach. The applicability of this method and future directions are evaluated.

Tuning the control system of a nonlinear inverted pendulum by means of the new method of Lyapunov exponents estimation

NASA Astrophysics Data System (ADS)

Balcerzak, Marek; Dąbrowski, Artur; Pikunov, Danylo

2018-01-01

This paper presents a practical application of a new, simplified method of Lyapunov exponents estimation. The method has been applied to optimization of a real, nonlinear inverted pendulum system. Authors presented how the algorithm of the Largest Lyapunov Exponent (LLE) estimation can be applied to evaluate control systems performance. The new LLE-based control performance index has been proposed. Equations of the inverted pendulum system of the fourth order have been found. The nonlinear friction of the regulation object has been identified by means of the nonlinear least squares method. Three different friction models have been tested: linear, cubic and Coulomb model. The Differential Evolution (DE) algorithm has been used to search for the best set of parameters of the general linear regulator. This work proves that proposed method is efficient and results in faster perturbation rejection, especially when disturbances are significant.

The Pharmacology of p-Aminopropiophenone in the Detoxification of Cyanide

DTIC Science & Technology

1992-01-01

45). High purity PAPP ( melting point of 140°C) is available as a light yellow crystal commercially from Eastman Kodak (Rochester, NY, U.S.A...synthesized in 1900 from acetanilide and propionyl chloride (58). More modern methods of chemical synthesis from aniline derivatives appear in the literature...Other chemicals (i.e., acetanilide ) are known to produce methemoglobinemia as well as hemolysis (dogs) (100), but the mechanism is not thought to be due

Concentration dependent survival and neural differentiation of murine embryonic stem cells cultured on polyethylene glycol dimethacrylate hydrogels possessing a continuous concentration gradient of n-cadherin derived peptide His-Ala-Val-Asp-Lle.

PubMed

Lim, Hyun Ju; Mosley, Matthew C; Kurosu, Yuki; Smith Callahan, Laura A

2017-07-01

N-cadherin cell-cell signaling plays a key role in the structure and function of the nervous system. However, few studies have incorporated bioactive signaling from n-cadherin into tissue engineering matrices. The present study uses a continuous gradient approach in polyethylene glycol dimethacrylate hydrogels to identify concentration dependent effects of n-cadherin peptide, His-Ala-Val-Asp-Lle (HAVDI), on murine embryonic stem cell survival and neural differentiation. The n-cadherin peptide was found to affect the expression of pluripotency marker, alkaline phosphatase, in murine embryonic stem cells cultured on n-cadherin peptide containing hydrogels in a concentration dependent manner. Increasing n-cadherin peptide concentrations in the hydrogels elicited a biphasic response in neurite extension length and mRNA expression of neural differentiation marker, neuron-specific class III β-tubulin, in murine embryonic stem cells cultured on the hydrogels. High concentrations of n-cadherin peptide in the hydrogels were found to increase the expression of apoptotic marker, caspase 3/7, in murine embryonic stem cells compared to that of murine embryonic stem cell cultures on hydrogels containing lower concentrations of n-cadherin peptide. Increasing the n-cadherin peptide concentration in the hydrogels facilitated greater survival of murine embryonic stem cells exposed to increasing oxidative stress caused by hydrogen peroxide exposure. The combinatorial approach presented in this work demonstrates concentration dependent effects of n-cadherin signaling on mouse embryonic stem cell behavior, underscoring the need for the greater use of systematic approaches in tissue engineering matrix design in order to understand and optimize bioactive signaling in the matrix for tissue formation. Single cell encapsulation is common in tissue engineering matrices. This eliminates cellular access to cell-cell signaling. N-cadherin, a cell-cell signaling molecule, plays a vital role in

Proposal for Prevention or Alleviation of Protein/Lymph-Losing Enteropathy (PLE/LLE) After Fontan Circulation Treatment of Univentricular Hearts: Restoration of Lymph Balance With a "Lymphatic Right-to-Left Shunt."

PubMed

James, H; Witte, M H; Bernas, M; Barber, B

2016-09-01

In Fontan circulations created for univentricular hearts, systemic venous return is diverted to the lungs before returning to the heart. The Total Cavopulmonary Connection (TCPC) is often the preferred surgical procedure whereby a 4-way anastomosis is created with inflow from the superior vena cava (SVC) and inferior vena cava (IVC) and outflow to the right and left branches of the pulmonary artery. In this arrangement, the systemic venous pressure must be elevated sufficiently to perfuse the lungs passively without the normal boost of the right ventricle. Hence, unlike surgical corrections for other congenital heart conditions, the systemic venous pressures in a Fontan circuit must be elevated to make the circulation work. It is proposed here that the incidence of PLE/LLE is directly related to elevated venous and lymphatic pressures, which cause leakage of proteins/lymph into the gastrointestinal tract (GIT) and expulsion from the body. It is commonly held that elevated venous pressures are relatively better tolerated in the upper body, but much less so in the heptatosplanchnic circulation and the lower body. It is also well established that elevated venous pressure increases lymph formation, most of which is produced in the hepatosplanchnic region (liver and intestine). It is further argued here that the increase in lymph filling pressure arising from the higher lymph flow, in association with the backpressure exerted by elevated venous pressure at the main drainage point into the venous system, results in a substantial increase in pressure in the thoracic duct. This pressure is transmitted back to the intestinal lymphatics, causing dilatation with lacteal rupture and protein or bulk lymph leakage into the intestine. We propose in this paper a new approach, based on experimental evidence, to prevent and/or alleviate this condition by draining or redirecting the thoracic duct (or, alternatively, a more localized intestinal lymphatic vessel) into one of the

RaPToRS Sample Delivery System

NASA Astrophysics Data System (ADS)

Henchen, Robert; Shibata, Kye; Krieger, Michael; Pogozelski, Edward; Padalino, Stephen; Glebov, Vladimir; Sangster, Craig

2010-11-01

At various labs (NIF, LLE, NRL), activated material samples are used to measure reaction properties. The Rapid Pneumatic Transport of Radioactive Samples (RaPToRS) system quickly and safely moves these radioactive samples through a closed PVC tube via airflow. The carrier travels from the reaction chamber to the control and analysis station, pneumatically braking at the outlet. A reversible multiplexer routes samples from various locations near the shot chamber to the analysis station. Also, the multiplexer allows users to remotely load unactivated samples without manually approaching the reaction chamber. All elements of the system (pneumatic drivers, flow control valves, optical position sensors, multiplexers, Geiger counters, and release gates at the analysis station) can be controlled manually or automatically using a custom LabVIEW interface. A prototype is currently operating at NRL in Washington DC. Prospective facilities for Raptors systems include LLE and NIF.

Evaluating source separation of plastic waste using conjoint analysis.

PubMed

Nakatani, Jun; Aramaki, Toshiya; Hanaki, Keisuke

2008-11-01

Using conjoint analysis, we estimated the willingness to pay (WTP) of households for source separation of plastic waste and the improvement of related environmental impacts, the residents' loss of life expectancy (LLE), the landfill capacity, and the CO2 emissions. Unreliable respondents were identified and removed from the sample based on their answers to follow-up questions. It was found that the utility associated with reducing LLE and with the landfill capacity were both well expressed by logarithmic functions, but that residents were indifferent to the level of CO2 emissions even though they approved of CO2 reduction. In addition, residents derived utility from the act of separating plastic waste, irrespective of its environmental impacts; that is, they were willing to practice the separation of plastic waste at home in anticipation of its "invisible effects", such as the improvement of citizens' attitudes toward solid waste issues.

Enabling the intestinal absorption of highly polar antiviral agents: ion-pair facilitated membrane permeation of zanamivir heptyl ester and guanidino oseltamivir.

PubMed

Miller, Jonathan M; Dahan, Arik; Gupta, Deepak; Varghese, Sheeba; Amidon, Gordon L

2010-08-02

Antiviral drugs often suffer from poor intestinal permeability, preventing their delivery via the oral route. The goal of this work was to enhance the intestinal absorption of the low-permeability antiviral agents zanamivir heptyl ester (ZHE) and guanidino oseltamivir (GO) utilizing an ion-pairing approach, as a critical step toward making them oral drugs. The counterion 1-hydroxy-2-naphthoic acid (HNAP) was utilized to enhance the lipophilicity and permeability of the highly polar drugs. HNAP substantially increased the log P of the drugs by up to 3.7 log units. Binding constants (K(11(aq))) of 388 M(-1) for ZHE-HNAP and 2.91 M(-1) for GO-HNAP were obtained by applying a quasi-equilibrium transport model to double-reciprocal plots of apparent octanol-buffer distribution coefficients versus HNAP concentration. HNAP enhanced the apparent permeability (P(app)) of both compounds across Caco-2 cell monolayers in a concentration-dependent manner, as substantial P(app) (0.8-3.0 x 10(-6) cm/s) was observed in the presence of 6-24 mM HNAP, whereas no detectable transport was observed without counterion. Consistent with a quasi-equilibrium transport model, a linear relationship with slope near 1 was obtained from a log-log plot of Caco-2 P(app) versus HNAP concentration, supporting the ion-pair mechanism behind the permeability enhancement. In the rat jejunal perfusion assay, the addition of HNAP failed to increase the effective permeability (P(eff)) of GO. However, the rat jejunal permeability of ZHE was significantly enhanced by the addition of HNAP in a concentration-dependent manner, from essentially zero without HNAP to 4.0 x 10(-5) cm/s with 10 mM HNAP, matching the P(eff) of the high-permeability standard metoprolol. The success of ZHE-HNAP was explained by its >100-fold stronger K(11(aq)) versus GO-HNAP, making ZHE-HNAP less prone to dissociation and ion-exchange with competing endogenous anions and able to remain intact during membrane permeation. Overall, this

Characterization of halogenated DBPs and identification of new DBPs trihalomethanols in chlorine dioxide treated drinking water with multiple extractions.

PubMed

Han, Jiarui; Zhang, Xiangru; Liu, Jiaqi; Zhu, Xiaohu; Gong, Tingting

2017-08-01

Chlorine dioxide (ClO 2 ) is a widely used alternative disinfectant due to its high biocidal efficiency and low-level formation of trihalomethanes and haloacetic acids. A major portion of total organic halogen (TOX), a collective parameter for all halogenated DBPs, formed in ClO 2 -treated drinking water is still unknown. A commonly used pretreatment method for analyzing halogenated DBPs in drinking water is one-time liquid-liquid extraction (LLE), which may lead to a substantial loss of DBPs prior to analysis. In this study, characterization and identification of polar halogenated DBPs in a ClO 2 -treated drinking water sample were conducted by pretreating the sample with multiple extractions. Compared to one-time LLE, the combined four-time LLEs improved the recovery of TOX by 2.3 times. The developmental toxicity of the drinking water sample pretreated with the combined four-time LLEs was 1.67 times higher than that pretreated with one-time LLE. With the aid of ultra-performance liquid chromatography/electrospray ionization-triple quadrupole mass spectrometry, a new group of polar halogenated DBPs, trihalomethanols, were detected in the drinking water sample pretreated with multiple extractions; two of them, trichloromethanol and bromodichloromethanol, were identified with synthesized standard compounds. Moreover, these trihalomethanols were found to be the transformation products of trihalomethanes formed during ClO 2 disinfection. The results indicate that multiple LLEs can significantly improve extraction efficiencies of polar halogenated DBPs and is a better pretreatment method for characterizing and identifying new polar halogenated DBPs in drinking water. Copyright © 2017. Published by Elsevier B.V.

Combined first-trimester Down syndrome screening in HIV-infected women.

PubMed

Chougrani, Imène; Muller, Françoise; Marcelin, Louis; Tsatsaris, Vassilis; Abric, Judith; Luton, Dominique; Guibourdenche, Jean; Azria, Elie

2016-08-01

To determine if human immunodeficiency virus (HIV) infection or antiretroviral therapy interferes with maternal levels of free human β-chorionic gonadotrophin (hCGβ) and pregnancy-associated plasma protein-A (PAPP-A) and whether any such influence alters first-trimester Down syndrome (DS) screening in HIV-infected women. We performed a multicenter 1:2 matched case-control study comparing 84 HIV-infected women with singleton pregnancies with controls randomly selected among uninfected women, delivered and screened in the same center and matched for maternal age, geographical origin and fetal sex. Groups did not differ significantly in screening results, although case women showed a slightly lower median free hCGβ multiple of the median (MoM) (1.11 versus 1.24 MoM, p=0.32) and higher median PAPP-A MoM (1.45 versus 1.32 MoM, p=0.23) than control women. The false-positive rate was similar in the case and control groups (5% versus 6.5%, p=0.5). Biomarker levels did not differ when comparing treated and untreated patients with their respective controls, and with one another. First-trimester DS combined screening biomarker levels and calculated risk do not seem to be significantly altered by HIV infection or antiretroviral treatment. This screening strategy appears to be suitable for HIV-infected women. Copyright © 2016 Elsevier Ireland Ltd. All rights reserved.

Cationic drug pharmacokinetics in diseased livers determined by fibrosis index, hepatic protein content, microsomal activity, and nature of drug.

PubMed

Hung, Daniel Y; Chang, Ping; Cheung, Kee; McWhinney, Brett; Masci, Paul P; Weiss, Michael; Roberts, Michael S

2002-06-01

The disposition kinetics of six cationic drugs in perfused diseased and normal rat livers were determined by multiple indicator dilution and related to the drug physicochemical properties and liver histopathology. A carbon tetrachloride (CCl(4))-induced acute hepatocellular injury model had a higher fibrosis index (FI), determined by computer-assisted image analysis, than did an alcohol-induced chronic hepatocellular injury model. The alcohol-treated group had the highest hepatic alpha(1)-acid glycoprotein, microsomal protein (MP), and cytochrome P450 (P450) concentrations. Various pharmacokinetic parameters could be related to the octanol-water partition coefficient (log P(app)) of the drug as a surrogate for plasma membrane partition coefficient and affinity for MP or P450, the dependence being lower in the CCl(4)-treated group and higher in the alcohol-treated group relative to controls. Stepwise regression analysis showed that hepatic extraction ratio, permeability-surface area product, tissue-binding constant, intrinsic clearance, partition ratio of influx (k(in)) and efflux rate constant (k(out)), and k(in)/k(out) were related to physicochemical properties of drug (log P(app) or pK(a)) and liver histopathology (FI, MP, or P450). In addition, hepatocyte organelle ion trapping of cationic drugs was evident in all groups. It is concluded that fibrosis-inducing hepatic disease effects on cationic drug disposition in the liver may be predicted from drug properties and liver histopathology.

Meta-regression analysis to evaluate relationships between maternal blood levels of placentation biomarkers and low delivery weight.

PubMed

Goto, Eita

2018-05-03

Caution is required for women at increased risk of low neonatal delivery weight. To evaluate relationships between maternal placentation biomarkers and the odds of low delivery weight. Databases including PubMed/MEDLINE were searched up to May 2017 using keywords involving biomarker names and "low birthweight." English language studies providing true- and false-positive, and true- and false-negative results of low delivery weight classified by maternal blood levels of placentation biomarkers (in units of multiple of the mean [MoM]) were included. Coefficients representing changes in log odds ratio for low delivery weight per 1 MoM increase in maternal blood placentation biomarkers, and those adjusted for race, sampling period, and/or study quality were calculated. Adjusted coefficients representing changes in log odds ratio for low delivery weight per 1 MoM increase in maternal blood levels of α-fetoprotein (AFP) and β-human chorionic gonadotropin (β-hCG) were significantly greater than 0 (both P<0.001), whereas that for pregnancy-associated plasma protein A (PAPP-A) was significantly less than 0 (P=0.028). Adjusted models explained the higher proportion of between-study variance better than non-adjusted models. Elevated AFP and β-hCG, and reduced PAPP-A in maternal blood were positively associated with odds of low delivery weight. © 2018 International Federation of Gynecology and Obstetrics.

Estimating the effect of gestational age on test performance of combined first-trimester screening for Down syndrome: a preliminary study.

PubMed

van Heesch, Peter N; Struijk, Pieter C; Laudy, Jaqueline A M; Steegers, Eric A P; Wildschut, Hajo I J

2010-05-01

To establish how different methods of estimating gestational age (GA) affect reliability of first-trimester screening for Down syndrome. Retrospective single-center study of 100 women with a viable singleton pregnancy, who had first-trimester screening. We calculated multiples of the median (MoM) for maternal-serum free beta human chorionic gonadotropin (free beta-hCG) and pregnancy associated plasma protein-A (PAPP-A), derived from either last menstrual period (LMP) or ultrasound-dating scans. In women with a regular cycle, LMP-derived estimates of GA were two days longer (range -11 to 18), than crown-rump length (CRL)-derived estimates of GA whereas this discrepancy was more pronounced in women who reported to have an irregular cycle, i.e., six days (range -7 to 32). Except for PAPP-A in the regular-cycle group, all differences were significant. Consequently, risk estimates are affected by the mode of estimating GA. In fact, LMP-based estimates revealed ten "screen-positive" cases compared to five "screen-positive" cases where GA was derived from dating-scans. Provided fixed values for nuchal translucency are applied, dating-scans reduce the number of screen-positive findings on the basis of biochemical screening. We recommend implementation of guidelines for Down syndrome screening based on CRL-dependent rather than LMP-dependent parameters of GA.

Tacrolimus is a class II low-solubility high-permeability drug: the effect of P-glycoprotein efflux on regional permeability of tacrolimus in rats.

PubMed

Tamura, Shigeki; Ohike, Atsuo; Ibuki, Rinta; Amidon, Gordon L; Yamashita, Shinji

2002-03-01

The objective of this study is to investigate the role of P-glycoprotein (P-gp), a membrane efflux pump associated with multidrug resistance (MDR) and a known substrate for tacrolimus, in determining the regional intestinal permeability of tacrolimus in rats. Thus, isolated segments of rat jejunum, ileum, or colon were perfused with tacrolimus solutions containing polyethoxylated hydrogenated castor oil 60 surfactant, and with or without verapamil, a P-gp substrate used to reverse the MDR phenotype. The results indicated that the intrinsic permeability of tacrolimus in the jejunum, calculated on the basis of the concentration of non-micellized free tacrolimus, was quite high ( approximately 1.4 x 10(-4) cm/s). The apparent permeability (P(app)) in the jejunum was unaffected by the presence of verapamil; however, the P(app) in the ileum and the colon increased significantly in the presence of verapamil and were similar to the values observed in the jejunum. The results suggest that systemic absorption of tacrolimus from the gastrointestinal tract could be significantly affected by P-gp efflux mechanisms. It is also possible that differences in P-gp function at various intestinal sites in a subject or at a given intestinal site in various subjects could lead to large intra- and interindividual variability in bioavailability of tacrolimus following oral administration. Copyright 2002 Wiley-Liss, Inc. and the American Pharmaceutical Association .

New Predictive Model at 11+0 to 13+6 Gestational Weeks for Early-Onset Preeclampsia With Fetal Growth Restriction.

PubMed

Chang, Ying; Chen, Xu; Cui, Hong-Yan; Li, Xing; Xu, Ya-Ling

2017-05-01

The aim of the present study was to determine a predictive model for early-onset preeclampsia with fetal growth restriction (FGR) to be used at 11 +0 to 13 +6 gestational weeks, by combining the maternal serum level of pregnancy-associated plasma protein-A (PAPP-A), placental growth factor (PLGF), placental protein 13 (PP13), soluble endoglin (sEng), mean arterial pressure (MAP), and uterine artery Doppler. This was a retrospective cohort study of 4453 pregnant women. Uterine artery Doppler examination was conducted in the first trimester. Maternal serum PAPP-A, PLGF, PP13, and sEng were measured. Mean arterial pressure was obtained. Women were classified as with/without early-onset preeclampsia, and women with preeclampsia were classified as with/without FGR. Receiver operating characteristic analysis was performed to determine the value of the model. There were 30 and 32 pregnant women with early-onset preeclampsia with and without FGR. The diagnosis rate of early-onset preeclampsia with FGR was 67.4% using the predictive model when the false positive rate was set at 5% and 73.2% when the false positive rate was 10%. The predictive model (MAP, uterine artery Doppler measurements, and serum biomarkers) had some predictive value for the early diagnosis (11 +0 to 13 +6 gestational weeks) of early-onset preeclampsia with FGR.

Propagation Influences on Digital Transmission Systems: Problems and Solutions Held at Athens, Greece on 4-8 June 1984.

DTIC Science & Technology

1984-06-08

compared with predictions of dispersion. The predictions considerably underestimated the measured dispersion, but the inclusion of a beam hro~ adening ...41 ’ii Nl A TRANSMISSION ASYNCHRONE A FORT ETALEMENT DE SPECTRE Par- M. SCHILLIGER et C. LELOUP - MT RADIOPROFESSIONNE.LLE 46, Quai Alphonse le Gallo

Analysis of the mobile phone effect on the heart rate variability by using the largest Lyapunov exponent.

PubMed

Yılmaz, Derya; Yıldız, Metin

2010-12-01

In this study, the effects of electromagnetic fields (EMFs) emitted by GSM900 based mobile phones (MPs) on the heart rate variability (HRV) were examined by using nonlinear analysis methods. The largest Lyapunov exponent (LLE) calculation was used to evaluate the effect of MP under various real exposure conditions. Sixteen healthy young volunteers were exposed to EMFs emitted by GSM900 based MP at two levels from a very low EMF (MP at stand-by) to a higher EMF (MP at pre-ring handshaking and ringing). A blind experimental protocol was designed and utilized with consideration to the physiological and psychological factors that may affect HRV. The results showed that the LLE values increased slightly with higher EMF produced by MP (P < 0.05). This change indicates that the degree of chaos in the HRV signals increased at higher EMF compared to low level EMF. Consequently, we have concluded that high level EMF changed the complexity of cardiac system behavior, significantly.

Preliminary numerical investigation of bandwidth effects on CBET using the LPSE-CBET code

NASA Astrophysics Data System (ADS)

Bates, Jason; Myatt, Jason; Shaw, John; Weaver, James; Obenschain, Keith; Lehmberg, Robert; Obenschain, Steve

2016-10-01

Cross beam energy transfer (CBET) is a significant energy-loss mechanism for direct-drive implosions on the OMEGA laser facility. Recently, a working group that includes participants from the Laboratory for Laser Energetics (LLE) at the University of Rochester and the U.S. Naval Research Laboratory (NRL) was formed to investigate strategies for ameliorating the deleterious effects of CBET. As part of this collaboration, the wave-based code LPSE-CBET developed at LLE has been made available to researchers at NRL and is being used to study the feasibility of suppressing CBET through the enhancement of laser bandwidth by stimulated rotational Raman scattering (SRRS). In this poster, we present some preliminary results on this subject. In particular, we discuss initial efforts to evaluate mitigation levels of 4 discrete Stokes lines from SRRS in air and compare our findings with ray-based simulation results of wavelength shifted (-6Å ,0, +6Å) driver-lines on OMEGA. Work Supported by DoE/NNSA.

Theory of Random Copolymer Fractionation in Columns

NASA Astrophysics Data System (ADS)

Enders, Sabine

Random copolymers show polydispersity both with respect to molecular weight and with respect to chemical composition, where the physical and chemical properties depend on both polydispersities. For special applications, the two-dimensional distribution function must adjusted to the application purpose. The adjustment can be achieved by polymer fractionation. From the thermodynamic point of view, the distribution function can be adjusted by the successive establishment of liquid-liquid equilibria (LLE) for suitable solutions of the polymer to be fractionated. The fractionation column is divided into theoretical stages. Assuming an LLE on each theoretical stage, the polymer fractionation can be modeled using phase equilibrium thermodynamics. As examples, simulations of stepwise fractionation in one direction, cross-fractionation in two directions, and two different column fractionations (Baker-Williams fractionation and continuous polymer fractionation) have been investigated. The simulation delivers the distribution according the molecular weight and chemical composition in every obtained fraction, depending on the operative properties, and is able to optimize the fractionation effectively.

Late Language Emergence in 24-Month-Old Twins: Heritable and Increased Risk for Late Language Emergence in Twins

ERIC Educational Resources Information Center

Rice, Mabel L.; Zubrick, Stephen R.; Taylor, Catherine L.; Gayán, Javier; Bontempo, Daniel E.

2014-01-01

Purpose: This study investigated the etiology of late language emergence (LLE) in 24-month-old twins, considering possible twinning, zygosity, gender, and heritability effects for vocabulary and grammar phenotypes. Method: A population-based sample of 473 twin pairs participated. Multilevel modeling estimated means and variances of vocabulary and…

Comparison of salting-out and sugaring-out liquid-liquid extraction methods for the partition of 10-hydroxy-2-decenoic acid in royal jelly and their co-extracted protein content.

PubMed

Tu, Xijuan; Sun, Fanyi; Wu, Siyuan; Liu, Weiyi; Gao, Zhaosheng; Huang, Shaokang; Chen, Wenbin

2018-01-15

Homogeneous liquid-liquid extraction (h-LLE) has been receiving considerable attention as a sample preparation method due to its simple and fast partition of compounds with a wide range of polarities. To better understand the differences between the two h-LLE extraction approaches, salting-out assisted liquid-liquid extraction (SALLE) and sugaring-out assisted liquid-liquid extraction (SULLE), have been compared for the partition of 10-hydroxy-2-decenoic acid (10-HDA) from royal jelly, and for the co-extraction of proteins. Effects of the amount of phase partition agents and the concentration of acetonitrile (ACN) on the h-LLE were discussed. Results showed that partition efficiency of 10-HDA depends on the phase ratio in both SALLE and SULLE. Though the partition triggered by NaCl and glucose is less efficient than MgSO 4 in the 50% (v/v) ACN-water mixture, their extraction yields can be improved to be similar with that in MgSO 4 SALLE by increasing the initial concentration of ACN in the ACN-water mixture. The content of co-extracted protein was correlated with water concentration in the obtained upper phase. MgSO 4 showed the largest protein co-extraction at the low concentration of salt. Glucose exhibited a large protein co-extraction in the high phase ratio condition. Furthermore, NaCl with high initial ACN concentration is recommended because it produced high extraction yield for 10-HDA and the lowest amount of co-extracted protein. These observations would be valuable for the sample preparation of royal jelly. Copyright © 2017 Elsevier B.V. All rights reserved.

Techno-economic analysis for incorporating a liquid-liquid extraction system to remove acetic acid into a proposed commercial scale biorefinery.

PubMed

Aghazadeh, Mahdieh; Engelberth, Abigail S

2016-07-08

Mitigating the effect of fermentation inhibitors in bioethanol plants can have a great positive impact on the economy of this industry. Liquid-liquid extraction (LLE) using ethyl acetate is able to remove fermentation inhibitors-chiefly, acetic acid-from an aqueous solution used to produce bioethanol. The fermentation broth resulting from LLE has higher performance for ethanol yield and its production rate. Previous techno-economic analyses focused on second-generation biofuel production did not address the impact of removing the fermentation inhibitors on the economic performance of the biorefinery. A comprehensive analysis of applying a separation system to mitigate the fermentation inhibition effect and to provide an analysis on the economic impact of removal of acetic acid from corn stover hydrolysate on the overall revenue of the biorefinery is necessary. This study examines the pros and cons associated with implementing LLE column along with the solvent recovery system into a commercial scale bioethanol plant. Using details from the NREL-developed model of corn stover biorefinery, the capital costs associated with the equipment and the operating cost for the use of solvent were estimated and the results were compared with the profit gain due to higher ethanol production. Results indicate that the additional capital will add 1% to the total capital and manufacturing cost will increase by 5.9%. The benefit arises from the higher ethanol production rate and yield as a consequence of inhibitor extraction and results in a $0.35 per gallon reduction in the minimum ethanol selling price (MESP). © 2016 American Institute of Chemical Engineers Biotechnol. Prog., 32:971-977, 2016. © 2016 American Institute of Chemical Engineers.

Pre-conceptual design of the Z-LLE accelerator.

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

Stygar, William A.

We begin with a model of 20 LTD modules, connected in parallel. We assume each LTD module consists of 10 LTD cavities, connected in series. We assume each cavity includes 20 LTD bricks, in parallel. Each brick is assumed to have a 40-nF capacitance and a 160-nH inductance. We use for this calculation the RLC-circuit model of an LTD system that was developed by Mazarakis and colleagues.

LLE 1994 annual report, October 1993--September 1994

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

NONE

1995-01-01

This is the 1994 annual report for the University of Rochester, Laboratory for Laser Energetics. The report is presented as a series of research type reports. The titles emphasize the breadth of work carried out. They are: stability analysis of unsteady ablation fronts; characterization of laser-produced plasma density profiles using grid image refractometry; transport and sound waves in plasmas with light and heavy ions; three-halves-harmonic radiation from long-scale-length plasmas revisited; OMEGA upgrade status report; target imaging and backlighting diagnosis; effect of electron collisions on ion-acoustic waves and heat flow; particle-in-cell code simulations of the interaction of gaussian ultrashort laser pulsesmore » with targets of varying initial scale lengths; characterization of thick cryogenic fuel layers: compensation for the lens effect using convergent beam interferometry; compact, multijoule-output, Nd:Glass, large-aperture ring amplifier; atomic force microscopy observation of water-induced morphological changes in Y{sub 2}O{sub 3} monolayer coatings; observation of longitudinal acceleration of electrons born in a high-intensity laser focus; spatial intensity nonuniformities of an OMEGA beam due to nonlinear beam propagation; calculated X-ray backlighting images of mixed imploded targets; evaluation of cosmic rays for use in the monitoring of the MEDUSA scintillator-photomultiplier diagnostic array; highly efficient second-harmonic generation of ultra-intense Nd:Glass laser pulses multiple cutoff wave numbers of the ablative Rayleigh-Taylor instability; ultrafast, all-silicon light modulator; angular dependence of the stimulated Brillouin scattering in homogeneous plasma; femtosecond excited-state dynamics of a conjugated ladder polymer.« less

A spatiotemporal view of plasmid loss in biofilms and planktonic cultures.

PubMed

Madsen, Jonas Stenløkke; Burmølle, Mette; Sørensen, Søren Johannes

2013-12-01

This Commentary by Madsen, Burmølle, and Sørensen discusses the article Non-invasive in situ monitoring and quantification of TOL plasmid segregational loss within Pseudomonas putida biofilms by Ma, Katzenmeyer, and Bryers. (2013. Biotechnol Bioeng. 110(11):2949-2958. DOI: 10.1002/bit.24953). © 2013 Wiley Periodicals, Inc.

Late Language Emergence at 24 Months: An Epidemiological Study of Prevalence, Predictors, and Covariates

ERIC Educational Resources Information Center

Zubrick, Stephen R.; Taylor, Catherine L.; Rice, Mabel L.; Slegers, David W.

2007-01-01

Purpose: The primary objectives of this study were to determine the prevalence of late language emergence (LLE) and to investigate the predictive status of maternal, family, and child variables. Method: This is a prospective cohort study of 1,766 epidemiologically ascertained 24-month-old singleton children. The framework was an ecological model…

Transport properties of puerarin and effect of Radix Angelicae Dahuricae extract on the transport of puerarin in Caco-2 cell model.

PubMed

Liang, Xin-Li; Zhao, Li-Jun; Liao, Zheng-Gen; Zhao, Guo-Wei; Zhang, Jing; Chao, Yun-Chao; Yang, Ming; Yin, Rong-Li

2012-12-18

Angelicae Dahurica (Hoffm.)Benth.& Hook.f.ex Franch.&Sav combined with Pueraria labota (Willd.)Ohwi has been widely used as herb-pairs in traditional Chinese medicine (TCM) for utilization of antipyretic analgesic and anti-inflammatory drugs, and modern pharmacological studies have shown that application compatibility of the two drugs has the effects of cardiovascular disease treatment. The previous study has proved that Radix Angelicae Dahuricae extract could enhance the intestinal absorption of puerarin in Pueraria. But the underlying compatibility mechanism of the two herbs remains unknown. In this study we tried to further evaluate the improvement of Radix Angelicae Dahuricae extract on the puerarin using the Caco-2 cell model and explore the transport properties of puerarin through the above research to discuss the possible effect mechanism of Radix Angelicae Dahuricae extract on the transport of puerarin and the underlying compatibility mechanism of the two herbs. The aim of this work was to study the transport properties of puerarin in Radix Pueraria across Caco-2 cell membrane and to explore how the Radix Angelicae Dahuricae extract affected the transport of puerarin using the well-characterized, human-based intestinal Caco-2 cell model as a platform. The bidirectional transport, and the effects of time, drug concentration, pH, P-gp inhibitors (Verapamil, Cyclosporin A), MRP inhibitor (MK-571) and EDTA-Na(2) (tight junction modulator) on the absorption of puerarin were observed. Then the influence of extract of Radix Angelicae Dahuricae on the transport of puerarin was studied. Drug concentration was measured by HPLC and the apparent permeability coefficients (Papp) and apparent permeability ratio (PDR) were calculated. The results showed that the transport (Papp) of puerarin in Caco-2 cell monolayer model had time and concentration dependence, and the transport showed saturation characteristics with the time and concentration of puerarin to a certain

Protocol for the prospective validation study: 'Screening programme for pre-eclampsia' (SPREE).

PubMed

Tan, M Y; Koutoulas, L; Wright, D; Nicolaides, K H; Poon, L C Y

2017-08-01

Pre-eclampsia (PE), which affects about 2% of pregnancies, is a major cause of maternal and perinatal morbidity and mortality. Early detection of PE can improve pregnancy outcome by providing timely intervention and closer monitoring. The current guideline from the UK National Institute for Health and Care Excellence (NICE) recommends that, at the booking visit, women identified with one major risk factor or more than one moderate risk factor for PE should be advised to take low-dose aspirin daily from 12 weeks until delivery. However, performance of the current method of screening is poor and identifies only about 35% of PE. Extensive studies in the last decade have established that the best performance for early prediction of PE can be achieved by using a novel Bayes' theorem-based method that combines maternal characteristics and medical history together with measurements of mean arterial pressure (MAP), uterine artery pulsatility index (UtA-PI), serum placental growth factor (PlGF) and pregnancy-associated plasma protein-A (PAPP-A) at 11-13 weeks' gestation. This forms the 'combined test', which could be simplified to the 'mini combined test' when only maternal factors, MAP and PAPP-A are taken into consideration. We present the protocol (version 3.1, 14 November 2016) for the 'Screening programme for pre-eclampsia' (SPREE) study, a prospective multicenter cohort study that will be carried out in seven National Health Service maternity hospitals in England. Eligible pregnant women attending their routine scan at 11-13 weeks' gestation will be invited to participate in this study. Maternal characteristics and history and measurements of MAP, UtA-PI, serum PAPP-A and PlGF will be recorded according to standardized protocols. The patient-specific risk for PE will be calculated and data on pregnancy outcomes collected. We hypothesize that the first-trimester mini combined test and combined test for PE screening, using the Bayes' theorem-based method, are likely to

Evaluation of the intestinal permeability of rosemary (Rosmarinus officinalis L.) extract polyphenols and terpenoids in Caco-2 cell monolayers

PubMed Central

Arráez-Román, David; González-Álvarez, Isabel; Ibáñez, Elena; Segura-Carretero, Antonio; Bermejo, Marival; Micol, Vicente

2017-01-01

Rosemary (Rosmarinus officinalis) is grown throughout the world and is widely used as a medicinal herb and to season and preserve food. Rosemary polyphenols and terpenoids have attracted great interest due to their potential health benefits. However, complete information regarding their absorption and bioavailability in Caco-2 cell model is scarce. The permeation properties of the bioactive compounds (flavonoids, diterpenes, triterpenes and phenylpropanoids) of a rosemary extract (RE), obtained by supercritical fluid extraction, was studied in Caco-2 cell monolayer model, both in a free form or liposomed. Compounds were identified and quantitated by liquid chromatography coupled to quadrupole time-of-flight with electrospray ionization mass spectrometry analysis (HPLC-ESI-QTOF-MS), and the apparent permeability values (Papp) were determined, for the first time in the extract, for 24 compounds in both directions across cell monolayer. For some compounds, such as triterpenoids and some flavonoids, Papp values found were reported for the first time in Caco-2 cells.Our results indicate that most compounds are scarcely absorbed, and passive diffusion is suggested to be the primary mechanism of absorption. The use of liposomes to vehiculize the extract resulted in reduced permeability for most compounds. Finally, the biopharmaceutical classification (BCS) of all the compounds was achieved according to their permeability and solubility data for bioequivalence purposes. BCS study reveal that most of the RE compounds could be classified as classes III and IV (low permeability); therefore, RE itself should also be classified into this category. PMID:28234919

Retrospective study evaluating the performance of a first-trimester combined screening for trisomy 21 in an Italian unselected population

PubMed Central

Padula, Francesco; Cignini, Pietro; Giannarelli, Diana; Brizzi, Cristiana; Coco, Claudio; D’Emidio, Laura; Giorgio, Elsa; Giorlandino, Maurizio; Mangiafico, Lucia; Mastrandrea, Marialuisa; Milite, Vincenzo; Mobili, Luisa; Nanni, Cinzia; Raffio, Raffaella; Taramanni, Cinzia; Vigna, Roberto; Mesoraca, Alvaro; Bizzoco, Domenico; Gabrielli, Ivan; Di Giacomo, Gianluca; Barone, Maria Antonietta; Cima, Antonella; Giorlandino, Francesca Romana; Emili, Sabrina; Cupellaro, Marina; Giorlandino, Claudio

2014-01-01

Objectives to assess the performance of a combined first-trimester screening for trisomy 21 in an unselected Italian population referred to a specialized private center for prenatal medicine. Methods a retrospective validation of first-trimester screening algorithms [risk calculation based on maternal age and nuchal translucency (NT) alone, maternal age and serum parameters (free β-hCG and PAPP-A) alone and a combination of both] for fetal aneuploidies evaluated in an unselected Italian population at Artemisia Fetal-Maternal Medical Centre in Rome. All measurements were performed between 11+0 and 13+6 weeks of gestation, between April 2007 and December 2008. Results of 3,610 single fetuses included in the study, we had a complete follow-up on 2,984. Fourteen of 17 cases of trisomy 21 were detected when a cut-off of 1:300 was applied [detection rate (DR) 82.4%, 95% confidence interval (CI) 64.2–100; false-positive rate (FPR) 4.7%, 95% CI 3.9–5.4; false-negative rate (FNR) 17.6%, 95% CI 0–35.8%]. Conclusion in our study population the detection rate for trisomy 21, using the combined risk calculation based on maternal age, fetal NT, maternal PAPP-A and free β-hCG levels, was superior to the application of either parameter alone. The algorithm has been validated for first trimester screening in the Italian population. PMID:26266002

Forms of selenium affect its transport, uptake and glutathione peroxidase activity in the Caco-2 cell model.

PubMed

Wang, Yanbo; Fu, Linglin

2012-10-01

The experiment was designed to investigate the effect of selenium (Se) chemical forms (sodium selenite, selenium nanoparticle [nano-Se] and selenomethionine) on the transport, uptake and glutathione peroxidase (GSH-Px) activity in the Caco-2 cell model. The transport and uptake of different forms of Se (0.1 μmol l(-1)) across the Caco-2 cell monolayer were carried out in two directions (apical [AP] to basolateral [BL] and BL to AP) for 2 h, respectively, and the apparent permeability coefficient (P(app)), transport efficiency and uptake efficiency were all calculated. In the present study, the transport and uptake of three forms of Se were time-dependent both in AP to BL and BL to AP directions. By the end of 2 h, the transport efficiencies of selenomethionine and nano-Se were higher than that of sodium selenite (P<0.05). The highest uptake efficiency (P<0.05) was observed in cells treated with nano-Se and significant difference (P<0.05) was also observed between the cells incubated with sodium selenite and selenomethionine. As for the P(app), sodium selenite (P<0.05) had the lowest values compared with that of selenomethionine and nano-Se, in both AP-BL and BL-AP. However, no significant differences were observed in GSH-Px activities. These results indicated that the efficiency of Se in the Caco-2 cells varied with its chemical forms, which might be associated with the differences in Se transport and uptake.

Intestinal transport of sophocarpine across the Caco-2 cell monolayer model and quantification by LC/MS.

PubMed

Sun, Sen; Zhang, Hai; Sun, Fengfeng; Zhao, Liang; Zhong, Yanqiang; Chai, Yifeng; Zhang, Guoqing

2014-06-01

Sophocarpine is a biologically active component obtained from the foxtail-like sophora herb and seed that is often orally administered for the treatment of cancer and chronic bronchial asthma. The aim of this study was to develop a rapid and specific LC/MS method for the determination of sophocarpine and to explore its transcellular transport mechanism across the Caco-2 (the human colon adenocarcia cell lines) monolayer cell transwell model. Caco-2 cells were seeded on permeable polycarbonate membranes and incubated for 21 days. Before the experiment, the trans-epithelial electric resistance, integrity and alkaline phosphatase activity of the Caco-2 monolayers were verified and used in subsequent experiments. In the Caco-2 model constructed, many influencing factors were investigated, including time, concentration, pH and different protein inhibitors. The results suggested that sophocarpine was transported mainly by passive diffusion. The flux of sophocarpine was time- and concentration-dependent, and the pH also had an effect on its transportation. The PappBA was higher than PappAB , indicating that a polarized transport might exist for sophocarpine. MK-571 and reserpine, inhibitors of the multidrug resistance associated protein 2 and the breast cancer resistance protein, decreased the efflux of sophocarpine, while verapamil had no effect on its transport. These results revealed that sophocarpine is absorbed mainly by passive diffusion, and that a carrier-mediated mechanism is also involved in the transport of sophocarpine. Copyright © 2014 John Wiley & Sons, Ltd.

Evaluation of the intestinal permeability of rosemary (Rosmarinus officinalis L.) extract polyphenols and terpenoids in Caco-2 cell monolayers.

PubMed

Pérez-Sánchez, Almudena; Borrás-Linares, Isabel; Barrajón-Catalán, Enrique; Arráez-Román, David; González-Álvarez, Isabel; Ibáñez, Elena; Segura-Carretero, Antonio; Bermejo, Marival; Micol, Vicente

2017-01-01

Rosemary (Rosmarinus officinalis) is grown throughout the world and is widely used as a medicinal herb and to season and preserve food. Rosemary polyphenols and terpenoids have attracted great interest due to their potential health benefits. However, complete information regarding their absorption and bioavailability in Caco-2 cell model is scarce. The permeation properties of the bioactive compounds (flavonoids, diterpenes, triterpenes and phenylpropanoids) of a rosemary extract (RE), obtained by supercritical fluid extraction, was studied in Caco-2 cell monolayer model, both in a free form or liposomed. Compounds were identified and quantitated by liquid chromatography coupled to quadrupole time-of-flight with electrospray ionization mass spectrometry analysis (HPLC-ESI-QTOF-MS), and the apparent permeability values (Papp) were determined, for the first time in the extract, for 24 compounds in both directions across cell monolayer. For some compounds, such as triterpenoids and some flavonoids, Papp values found were reported for the first time in Caco-2 cells.Our results indicate that most compounds are scarcely absorbed, and passive diffusion is suggested to be the primary mechanism of absorption. The use of liposomes to vehiculize the extract resulted in reduced permeability for most compounds. Finally, the biopharmaceutical classification (BCS) of all the compounds was achieved according to their permeability and solubility data for bioequivalence purposes. BCS study reveal that most of the RE compounds could be classified as classes III and IV (low permeability); therefore, RE itself should also be classified into this category.

Effect of drug lipophilicity on in vitro release rate from oil vehicles using nicotinic acid esters as model prodrug derivatives.

PubMed

Weng Larsen, S; Engelbrecht Thomsen, A E; Rinvar, E; Friis, G J; Larsen, C

2001-03-23

The rate constants for transfer of a homologous series of nicotinic acid esters from oil vehicles to aqueous buffer phases were determined using a rotating dialysis cell. The chemical stability of butyl nicotinate has been investigated at 60 degrees C over pH range 0.5--10. Maximum stability occurs at pH 4--5 and an inflection point was seen around the pK(a). For the nicotinic acid esters, a linear correlation was established between the first-order rate constant related to attainment of equilibrium, k(obs) and the apparent partition coefficient, P(app): log k(obs)=-0.83log P(app)+0.26 (k(obs) in h(-1), n=9). For hexyl nicotinate with a true partition coefficient of 4 it was possible to determine k(obs) by decreasing pH in the aqueous release medium to 2.05. Thus, under the latter experimental conditions estimation of the relative release rates for the esters were performed. The ratio between the specific rate constant k(ow), related to the transport from oil vehicle to aqueous phase, for ethyl and hexyl nicotinate was 139. The hydrophobic substituent constant for a methylene group, pi(CH(2)), was determined for nicotinic acid esters in different oil/buffer partitioning systems to 0.54--0.58. Addition of hydroxypropyl-beta-cyclodextrin to the aqueous release medium did not enhance the transport rate of the esters from the oil phase.

First-trimester contingent screening for trisomies 21, 18 and 13 by biomarkers and maternal blood cell-free DNA testing.

PubMed

Nicolaides, K H; Syngelaki, A; Poon, L C; Gil, M M; Wright, D

2014-01-01

To examine potential performance of screening for trisomies by cell-free (cf) DNA testing in maternal blood contingent on results of first-line testing by combinations of fetal translucency thickness (NT), fetal heart rate (FHR), ductus venosus pulsatility index (DV PIV), and serum-free β-human chorionic gonadotropin (β-hCG), pregnancy-associated plasma protein-A (PAPP-A), placental growth factor (PLGF) and α-fetoprotein (AFP). Performance was estimated for firstly, screening by cfDNA in all pregnancies and secondly, cfDNA testing contingent on results of first-line testing by combinations of ultrasound and biochemical markers. In first-line screening by cfDNA testing, the detection rate for trisomy 21 and trisomies 18 or 13 would be 99 and 96%, respectively, after invasive testing in 1% of the population. In contingent screening, a detection rate of 98% for trisomy 21 and 96% for trisomy 18 or 13, at an invasive testing rate of 0.7%, can be achieved by carrying out cfDNA testing in about 35, 20 and 11% of cases identified by first-line screening with the combined test alone (age, NT, FHR, β-hCG, PAPP-A), the combined test plus PLGF and AFP and the combined test plus PLGF, AFP and DV PIV, respectively. Effective first-trimester screening for trisomies can be achieved by contingent screening incorporating biomarkers and cfDNA testing. © 2013 S. Karger AG, Basel.

Comparative evaluation of liquid-liquid extraction, solid-phase extraction and solid-phase microextraction for the gas chromatography-mass spectrometry determination of multiclass priority organic contaminants in wastewater.

PubMed

Robles-Molina, José; Gilbert-López, Bienvenida; García-Reyes, Juan F; Molina-Díaz, Antonio

2013-12-15

The European Water Framework Directive (WFD) 2000/60/EC establishes guidelines to control the pollution of surface water by sorting out a list of priority substances that involves a significant risk to or via the aquatic systems. In this article, the analytical performance of three different sample preparation methodologies for the GC-MS/MS determination of multiclass organic contaminants-including priority comprounds from the WFD-in wastewater samples using gas chromatography-mass spectrometry was evaluated. The methodologies tested were: (a) liquid-liquid extraction (LLE) with n-hexane; (b) solid-phase extraction (SPE) with C18 cartridges and elution with ethyl acetate:dichloromethane (1:1 (v/v)), and (c) headspace solid-phase microextraction (HS-SPME) using two different fibers: polyacrylate and polydimethylsiloxane/carboxen/divinilbenzene. Identification and confirmation of the selected 57 compounds included in the study (comprising polycyclic aromatic hydrocarbons (PAHs), pesticides and other contaminants) were accomplished using gas chromatography tandem mass spectrometry (GC-MS/MS) with a triple quadrupole instrument operated in the multiple reaction monitoring (MRM) mode. Three MS/MS transitions were selected for unambiguous confirmation of the target chemicals. The different advantages and pitfalls of each method were discussed. In the case of both LLE and SPE procedures, the method was validated at two different concentration levels (15 and 150 ng L(-1)) obtaining recovery rates in the range 70-120% for most of the target compounds. In terms of analyte coverage, results with HS-SPME were not satisfactory, since 14 of the compounds tested were not properly recovered and the overall performance was worse than the other two methods tested. LLE, SPE and HS-SPME (using polyacrylate fiber) procedures also showed good linearity and precision. Using any of the three methodologies tested, limits of quantitation obtained for most of the detected compounds were in

Effectiveness of tai chi as a community-based falls prevention intervention: a randomized controlled trial.

PubMed

Taylor, Denise; Hale, Leigh; Schluter, Philip; Waters, Debra L; Binns, Elizabeth E; McCracken, Hamish; McPherson, Kathryn; Wolf, Steven L

2012-05-01

To compare the effectiveness of tai chi and low-level exercise in reducing falls in older adults; to determine whether mobility, balance, and lower limb strength improved and whether higher doses of tai chi resulted in greater effect. Randomized controlled trial. Eleven sites throughout New Zealand. Six hundred eighty-four community-residing older adults (mean age 74.5; 73% female) with at least one falls risk factor. Tai chi once a week (TC1) (n = 233); tai chi twice a week (TC2) (n = 220), or a low-level exercise program control group (LLE) (n = 231) for 20 wks. Number of falls was ascertained according to monthly falls calendars. Mobility (Timed-Up-and-Go Test), balance (step test), and lower limb strength (chair stand test) were assessed. The adjusted incident rate ratio (IRR) for falls was not significantly different between the TC1 and LLE groups (IRR = 1.05, 95% confidence interval (CI) = 0.83-1.33, P = .70) or between the TC2 and LLE groups (IRR = 0.88, 95% CI = 0.68-1.16, P = .37). Adjusted multilevel mixed-effects Poisson regression showed a significant reduction in logarithmic mean fall rate of -0.050 (95% CI = -0.064 to -0.037, P < .001) per month for all groups. Multilevel fixed-effects analyses indicated improvements in balance (P < .001 right and left leg) and lower limb strength (P < .001) but not mobility (P = .54) in all groups over time, with no differences between the groups (P = .37 (right leg), P = .66 (left leg), P = .21, and P = .44, respectively). There was no difference in falls rates between the groups, with falls reducing similarly (mean falls rate reduction of 58%) over the 17-month follow-up period. Strength and balance improved similarly in all groups over time. © 2012, Copyright the Authors Journal compilation © 2012, The American Geriatrics Society.

Language Learning Experience in School Context and Metacognitive Awareness of Multilingual Children

ERIC Educational Resources Information Center

Le Pichon Vorstman, Emmanuelle; De Swart, Henriette; Ceginskas, Viktorija; Van Den Bergh, Huub

2009-01-01

What is the influence of a language learning experience (LLE) in a school context on the metacognitive development of children? To answer that question, we presented 54 multilingual preschoolers with two movie clips and examined their reactions to an exolingual situation of communication. These preschoolers were aged four and a half to six and a…

40 CFR 141.131 - Analytical requirements.

Code of Federal Regulations, 2011 CFR

2011-07-01

..., respectively. The cited methods published in either edition may be used. Copies may be obtained from the... obtained from the American Society for Testing and Materials International, 100 Barr Harbor Drive, West... 6251 B-94 SPE (acidic methanol)/GC/ECD 552.1 5 LLE (acidic methanol)/GC/ECD 552.2, 552.3 Bromate Ion...

40 CFR 141.131 - Analytical requirements.

Code of Federal Regulations, 2010 CFR

2010-07-01

..., respectively. The cited methods published in either edition may be used. Copies may be obtained from the... obtained from the American Society for Testing and Materials International, 100 Barr Harbor Drive, West... 6251 B-94 SPE (acidic methanol)/GC/ECD 552.1 5 LLE (acidic methanol)/GC/ECD 552.2, 552.3 Bromate Ion...

OMEGA: A NEW COLD X-RAY SIMULATION FACILITY FOR THE EVALUATION OF OPTICAL COATINGS

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

Fisher, J H; Newlander, C D; Fournier, K B

We report on recent progress for the development of a new cold X-ray optical test capability using the Omega Facility located at the Laboratory for Laser Energetics (LLE) at the University of Rochester. These tests were done on the 30 kJ OMEGA laser at the Laboratory for Laser Energetics (LLE) at the University of Rochester, Rochester, NY. We conducted a six-shot series called OMEGA II on 14 July 2006 in one eight-hour day (supported by the Defense Threat Reduction Agency). The initial testing was performed using simple protected gold optical coatings on fused silica substrates. PUFFTFT analyses were completed andmore » the specimen's thermal lateral stress and transverse stress conditions were calculated and interpreted. No major anomalies were detected. Comparison of the pre- and posttest reflective measurements coupled with the TFCALC analyses proved invaluable in guiding the analyses and interpreting the observed damage. The Omega facility is a high quality facility for performing evaluation of optical coatings and coupons and provides experience for the development of future National Ignition Facility (NIF) testing.« less

VizieR Online Data Catalog: GRB prompt emission fitted with the DREAM model (Ahlgren+, 2015)

NASA Astrophysics Data System (ADS)

Ahlgren, B.; Larsson, J.; Nymark, T.; Ryde, F.; Pe'Er, A.

2018-01-01

We illustrate the application of the DREAM model by fitting it to two different, bright Fermi GRBs; GRB 090618 and GRB 100724B. While GRB 090618 is well fitted by a Band function, GRB 100724B was the first example of a burst with a significant additional BB component (Guiriec et al. 2011ApJ...727L..33G). GRB 090618 is analysed using Gamma-ray Burst Monitor (GBM) data (Meegan et al. 2009ApJ...702..791M) from the NaI and BGO detectors. For GRB 100724B, we used GBM data from the NaI and BGO detectors as well as Large Area Telescope Low Energy (LAT-LLE) data. For both bursts we selected NaI detectors seeing the GRB at an off-axis angle lower than 60° and the BGO detector as being the best aligned of the two BGO detectors. The spectra were fitted in the energy ranges 8-1000 keV (NaI), 200-40000 keV (BGO) and 30-1000 MeV (LAT-LLE). (2 data files).

Quantitative determination of 5-hydroxy-N-methylpyrrolidone in urine for biological monitoring of N-methylpyrrolidone exposure.

PubMed

Ligocka, D; Lison, D; Haufroid, V

2002-10-05

The aim of this work was to validate a sensitive method for quantitative analysis of 5-hydroxy-N-methylpyrrolidone (5-HNMP) in urine. This compound has been recommended as a marker for biological monitoring of N-methylpyrrolidone (NMP) exposure. Different solvents and alternative methods of extraction including liquid-liquid extraction (LLE) on Chem Elut and solid-phase extraction (SPE) on Oasis HLB columns were tested. The most efficient extraction of 5-HNMP in urine was LLE with Chem Elut columns and dichloromethane as a solvent (consistently 22% of recovery). The urinary extracts were derivatized by bis(trimethylsilyl)trifluoroacetamide and analysed by gas chromatography-mass spectrometry (GC-MS) with tetradeutered 5-HNMP as an internal standard. The detection limit of this method is 0.017 mg/l urine with an intraassay precision of 1.6-2.6%. The proposed method of extraction is simple and reproducible. Four different m/z signal ratios of TMS-5-HNMP and tetralabelled TMS-5-HNMP have been validated and could be indifferently used in case of unexpected impurities from urine matrix. Copyright 2002 Elsevier Science B.V.

LLE Review, Volume 57. Quarterly report, October--December 1993

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

Simon, A.

During this quarter, the visible fruits of long design labors on the OMEGA Upgrade began to appear. The target mirror structure was put in place, along with the target chamber itself. The laser bay structures were also installed, and the bay is now being prepared to receive optomechanical, control, and laser assemblies. Further details are in the OMEGA Upgrade Status Report in this issue. Theory and analysis of previous experiments continued during this reporting period. Articles contained herein describe an improved theory of the ablative Rayleigh-Taylor instability; a novel proposal for characterizing plasma-density profiles by using grid image refractometry; amore » much-improved treatment of the damping of ion sound waves in a mixture of light and heavy ions; and, finally, a new interpretation of measurements of 3/2-harmonic radiation emitted from the long-scale-length plasmas created in earlier OMEGA experiments.« less

First-trimester prediction of birth weight.

PubMed

Boucoiran, Isabelle; Djemli, Anissa; Taillefer, Catherine; Rypens, Françoise; Delvin, Edgard; Audibert, François

2013-09-01

To determine whether the parameters used in first-trimester screening for aneuploidies contribute significantly to the prediction of birth weight. In this retrospective cohort study (n = 4110), nuchal translucency (NT), free β-chorionic gonadotropin (fβ-hCG), and pregnancy-associated plasma protein-A (PAPP-A) blood concentrations were measured between 11 + 0 and 13 + 6 weeks. Multiple pregnancies, chromosomal anomalies, major fetal defects, and deliveries before 24 weeks were excluded. NT (0.95 versus 0.98 multiples of the expected median [MoM], p < 0.001) and PAPP-A (0.93 versus 1.06 MoM, p = 0.005) were significantly lower in small-for-gestational-age (SGA) newborns (<10th percentile) than the unaffected group, but not fβ-hCG (0.89 versus 0.93 MoM, p = 0.113). NT was significantly higher (1.03 versus 0.98 MoM, p < 0.001) in the large-for-gestational-age (LGA) group (>90th percentile) compared with the unaffected group, and biomarkers did not differ. After controlling for gestational age, maternal weight, smoking status, ethnicity, and fetal sex, first-trimester markers contributed to the prediction of birth weight in a multiple linear model but did not significantly improved the prediction of SGA and LGA compared with maternal characteristics alone. Parameters used in first-trimester screening for aneuploidies contribute to the prediction of birth weight but their clinical utility to detect women at risk of SGA or LGA baby is limited. Thieme Medical Publishers 333 Seventh Avenue, New York, NY 10001, USA.

Effect of different types of plastic packaging films on the moisture and aflatoxin contents of pistachio nuts during storage.

PubMed

Shakerardekani, Ahmad; Karim, Roselina

2013-04-01

Pistachio nut (Pistacia vera L.) is one of the popular tree nuts in the world. Proper selection of packaging materials is necessary to prevent absorption of moisture and aflatoxin formation which will influence the overall product quality and safety. This research is undertaken to study the effect of different type of flexible packaging films on the moisture and aflatoxin contents of whole pistachio nuts during storage at ambient temperature (22-28 °C) and relative humidity of 85-100%. Five types of plastic films tested were low density polyethylene (LDPE) which serves as the control, food-grade polyvinyl chloride (PVC), nylon (LDPE/PA), polyamide/polypropylene (PA/PP) and polyethylene terephthalate (PET). The moisture content and aflatoxin content of pistachio nuts were measured using oven drying method and HPLC, respectively. Sample were analysed at 0, 2, 4, 6, 8 and 10 months during the storage period. Results showed that there was an increase in moisture content with the increase in storage time of pistachio nuts. The increase in moisture content was associated with the aflatoxin level of pistachio nuts during storage time. All the packaging materials except LDPE delayed the moisture absorption and aflatoxin formation of the product. The most suitable packaging materials for maintaining the quality and safety of pistachio nuts is PET films followed by nylon, PA/PP and PVC. The shelf-life of pistachio can be extended from 2 months (Control) to 5 months when PET is used as the packaging material.

First and second trimester markers of fetal aneuploidy in pregnant women with HIV infection.

PubMed

Spencer, Kevin

2011-01-01

To evaluate if levels of pregnancy-associated plasma protein-A (PAPP-A), free β-hCG and nuchal translucency (NT) used in first trimester aneuploidy screening and α-fetoprotein (AFP), unconjugated oestriol (UE3) and free β-hCG in the second trimester are altered in pregnancies with human immunodeficiency virus (HIV) infection. Median MoM values of biochemical markers and δ-NT in 92 women with HIV infection in the first trimester were compared with those from 912 HIV-seronegative controls. In the second trimester, biochemical marker levels were compared in 52 women with HIV infection and 378 HIV-seronegative controls. First trimester free β-hCG median MoM levels in HIV-infected pregnancies were not different to controls (0.978 vs. 0.981, p = 1.000), as were PAPP-A levels (1.190 vs. 1.102, p = 0.099) and δ-NT (0.1374 vs. 0.0445, p = 0.0631). Second trimester levels of free β-hCG were not significantly different (1.0575 vs. 0.9619, p = 0.1827), as was AFP (0.9734 vs. 0.9350, p = 0.6576), although UE3 was significantly lower (0.970 vs. 1.110, p = 0.0005). In the first trimester, marker levels are not affected by the presence of HIV infection, and risks for aneuploidy are likely to be accurate in this group. Further studies are required to evaluate if UE3 levels continue to be low in HIV-infected women since this may have an impact on screening in the second trimester. Copyright © 2010 S. Karger AG, Basel.

Clicking in shallow rivers: short-range echolocation of Irrawaddy and Ganges River dolphins in a shallow, acoustically complex habitat.

PubMed

Jensen, Frants H; Rocco, Alice; Mansur, Rubaiyat M; Smith, Brian D; Janik, Vincent M; Madsen, Peter T

2013-01-01

Toothed whales (Cetacea, odontoceti) use biosonar to navigate their environment and to find and catch prey. All studied toothed whale species have evolved highly directional, high-amplitude ultrasonic clicks suited for long-range echolocation of prey in open water. Little is known about the biosonar signals of toothed whale species inhabiting freshwater habitats such as endangered river dolphins. To address the evolutionary pressures shaping the echolocation signal parameters of non-marine toothed whales, we investigated the biosonar source parameters of Ganges river dolphins (Platanista gangetica gangetica) and Irrawaddy dolphins (Orcaella brevirostris) within the river systems of the Sundarban mangrove forest. Both Ganges and Irrawaddy dolphins produced echolocation clicks with a high repetition rate and low source level compared to marine species. Irrawaddy dolphins, inhabiting coastal and riverine habitats, produced a mean source level of 195 dB (max 203 dB) re 1 µPapp whereas Ganges river dolphins, living exclusively upriver, produced a mean source level of 184 dB (max 191) re 1 µPapp. These source levels are 1-2 orders of magnitude lower than those of similar sized marine delphinids and may reflect an adaptation to a shallow, acoustically complex freshwater habitat with high reverberation and acoustic clutter. The centroid frequency of Ganges river dolphin clicks are an octave lower than predicted from scaling, but with an estimated beamwidth comparable to that of porpoises. The unique bony maxillary crests found in the Platanista forehead may help achieve a higher directionality than expected using clicks nearly an octave lower than similar sized odontocetes.

Clicking in Shallow Rivers: Short-Range Echolocation of Irrawaddy and Ganges River Dolphins in a Shallow, Acoustically Complex Habitat

PubMed Central

Jensen, Frants H.; Rocco, Alice; Mansur, Rubaiyat M.; Smith, Brian D.; Janik, Vincent M.; Madsen, Peter T.

2013-01-01

Toothed whales (Cetacea, odontoceti) use biosonar to navigate their environment and to find and catch prey. All studied toothed whale species have evolved highly directional, high-amplitude ultrasonic clicks suited for long-range echolocation of prey in open water. Little is known about the biosonar signals of toothed whale species inhabiting freshwater habitats such as endangered river dolphins. To address the evolutionary pressures shaping the echolocation signal parameters of non-marine toothed whales, we investigated the biosonar source parameters of Ganges river dolphins (Platanista gangetica gangetica) and Irrawaddy dolphins (Orcaella brevirostris) within the river systems of the Sundarban mangrove forest. Both Ganges and Irrawaddy dolphins produced echolocation clicks with a high repetition rate and low source level compared to marine species. Irrawaddy dolphins, inhabiting coastal and riverine habitats, produced a mean source level of 195 dB (max 203 dB) re 1 µPapp whereas Ganges river dolphins, living exclusively upriver, produced a mean source level of 184 dB (max 191) re 1 µPapp. These source levels are 1–2 orders of magnitude lower than those of similar sized marine delphinids and may reflect an adaptation to a shallow, acoustically complex freshwater habitat with high reverberation and acoustic clutter. The centroid frequency of Ganges river dolphin clicks are an octave lower than predicted from scaling, but with an estimated beamwidth comparable to that of porpoises. The unique bony maxillary crests found in the Platanista forehead may help achieve a higher directionality than expected using clicks nearly an octave lower than similar sized odontocetes. PMID:23573197

Permeability of rosmarinic acid in Prunella vulgaris and ursolic acid in Salvia officinalis extracts across Caco-2 cell monolayers.

PubMed

Qiang, Zhiyi; Ye, Zhong; Hauck, Cathy; Murphy, Patricia A; McCoy, Joe-Ann; Widrlechner, Mark P; Reddy, Manju B; Hendrich, Suzanne

2011-10-11

Rosmarinic acid (RA), a caffeic acid-related compound found in high concentrations in Prunella vulgaris (self-heal), and ursolic acid (UA), a pentacyclic triterpene acid concentrated in Salvia officinalis (sage), have been traditionally used to treat inflammation in the mouth, and may also be beneficial for gastrointestinal health in general. To investigate the permeabilities of RA and UA as pure compounds and in Prunella vulgaris and Salvia officinalis ethanol extracts across human intestinal epithelial Caco-2 cell monolayers. The permeabilities and phase II biotransformation of RA and UA as pure compounds and in herbal extracts were compared using Caco-2 cells with HPLC detection. The apparent permeability coefficient (P(app)) for RA and RA in Prunella vulgaris extracts was 0.2 ± 0.05 × 10(-6)cm/s, significantly increased to 0.9 ± 0.2 × 10(-6)cm/s after β-glucuronidase/sulfatase treatment. P(app) for UA and UA in Salvia officinalis extract was 2.7 ± 0.3 × 10(-6)cm/s and 2.3 ± 0.5 × 10(-6)cm/s before and after β-glucuronidase/sulfatase treatment, respectively. Neither compound was affected in permeability by the herbal extract matrix. RA and UA in herbal extracts had similar uptake as that found using the pure compounds, which may simplify the prediction of compound efficacy, but the apparent lack of intestinal glucuronidation/sulfation of UA is likely to further enhance the bioavailability of that compound compared with RA. Copyright © 2011 Elsevier Ireland Ltd. All rights reserved.

Permeability of Rosmarinic acid in Prunella vulgaris and Ursolic acid in Salvia officinalis Extracts across Caco-2 Cell Monolayers

PubMed Central

Qiang, Zhiyi; Ye, Zhong; Hauck, Cathy; Murphy, Patricia A.; McCoy, Joe-Ann; Widrlechner, Mark P.; Reddy, Manju B.; Hendrich, Suzanne

2011-01-01

Ethnopharmacological relevance Rosmarinic acid (RA), a caffeic acid-related compound found in high concentrations in Prunella vulgaris (self-heal), and ursolic acid (UA), a pentacyclic triterpene acid concentrated in Salvia officinalis (sage), have been traditionally used to treat inflammation in the mouth, and may also be beneficial for gastrointestinal health in general. Aim of the study To investigate the permeabilities of RA and UA as pure compounds and in P. vulgaris and S. officinalis ethanol extracts across human intestinal epithelial Caco-2 cell monolayers. Materials and methods The permeabilities and Phase II biotransformation of RA and UA as pure compounds and in herbal extracts were compared using Caco-2 cells with HPLC detection. Results The apparent permeability coefficient (Papp) for RA and RA in P. vulgaris extracts was 0.2 ± 0.05 × 10−6 cm/s, significantly increased to 0.9 ± 0.2 × 10−6 cm/s after β-glucuronidase/sulfatase treatment. Papp for UA and UA in S. officinalis extract was 2.7 ± 0.3 × 10−6 cm/s and 2.3 ± 0.5 × 10−6 cm/s before and after β-glucuronidase/sulfatase treatment, respectively. Neither compound was affected in permeability by the herbal extract matrix. Conclusion RA and UA in herbal extracts had similar uptake as that found using the pure compounds, which may simplify the prediction of compound efficacy, but the apparent lack of intestinal glucuronidation/sulfation of UA is likely to further enhance the bioavailability of that compound compared with RA. PMID:21798330

Highly sensitive and label-free electrochemical detection of microRNAs based on triple signal amplification of multifunctional gold nanoparticles, enzymes and redox-cycling reaction.

PubMed

Liu, Lin; Xia, Ning; Liu, Huiping; Kang, Xiaojing; Liu, Xiaoshuan; Xue, Chan; He, Xiaoling

2014-03-15

MicroRNAs (miRNAs) are believed to be important for cancer diagnosis and prognosis, serving as reliable molecular biomarkers. In this work, we presented a label-free and highly sensitive electrochemical genosensor for miRNAs detection with the triple signal amplification of gold nanoparticles (AuNPs), alkaline phosphatase (ALP) and p-aminophenol (p-AP) redox cycling. The label-free strategy is based on the difference in the structures of RNA and DNA. Specifically, miRNAs were first captured by the pre-immobilized DNA probes on a gold electrode. Next, the cis-diol group of ribose sugar at the end of the miRNAs chain allowed 3-aminophenylboronic acid (APBA)/biotin-modified multifunctional AuNPs (denoted as APBA-biotin-AuNPs) to be attached through the formation of a boronate ester covalent bond, which facilitated the capture of streptavidin-conjugated alkaline phosphatase (SA-ALP) via the biotin-streptavidin interaction. After the addition of the 4-aminophenylphosphate (p-APP) substrate, the enzymatic conversion from p-APP to p-AP occurred. The resulting p-AP could be cycled by a chemical reducing reagent after its electro-oxidization on the electrode (known as p-AP redox cycling), thus enabling an increase in the anodic current. As a result, the current increased linearly with the miRNAs concentration over a range of 10 fM-5 pM, and a detection limit of 3 fM was achieved. We believe that this work will be valuable for the design of new types of label-free and sensitive electrochemical biosensors. © 2013 Published by Elsevier B.V.

A Novel Early Pregnancy Risk Prediction Model for Gestational Diabetes Mellitus.

PubMed

Sweeting, Arianne N; Wong, Jencia; Appelblom, Heidi; Ross, Glynis P; Kouru, Heikki; Williams, Paul F; Sairanen, Mikko; Hyett, Jon A

2018-06-13

Accurate early risk prediction for gestational diabetes mellitus (GDM) would target intervention and prevention in women at the highest risk. We evaluated novel biomarker predictors to develop a first-trimester risk prediction model in a large multiethnic cohort. Maternal clinical, aneuploidy and pre-eclampsia screening markers (PAPP-A, free hCGβ, mean arterial pressure, uterine artery pulsatility index) were measured prospectively at 11-13+6 weeks' gestation in 980 women (248 with GDM; 732 controls). Nonfasting glucose, lipids, adiponectin, leptin, lipocalin-2, and plasminogen activator inhibitor-2 were measured on banked serum. The relationship between marker multiples-of-the-median and GDM was examined with multivariate regression. Model predictive performance for early (< 24 weeks' gestation) and overall GDM diagnosis was evaluated by receiver operating characteristic curves. Glucose, triglycerides, leptin, and lipocalin-2 were higher, while adiponectin was lower, in GDM (p < 0.05). Lipocalin-2 performed best in Caucasians, and triglycerides in South Asians with GDM. Family history of diabetes, previous GDM, South/East Asian ethnicity, parity, BMI, PAPP-A, triglycerides, and lipocalin-2 were significant independent GDM predictors (all p < 0.01), achieving an area under the curve of 0.91 (95% confidence interval [CI] 0.89-0.94) overall, and 0.93 (95% CI 0.89-0.96) for early GDM, in a combined multivariate prediction model. A first-trimester risk prediction model, which incorporates novel maternal lipid markers, accurately identifies women at high risk of GDM, including early GDM. © 2018 S. Karger AG, Basel.

In vitro transport characteristics of EFdA, a novel nucleoside reverse transcriptase inhibitor using Caco-2 and MDCKII cell monolayers.

PubMed

Zhang, Wei; Parniak, Michael A; Sarafianos, Stefan G; Empey, Philip E; Rohan, Lisa C

2014-06-05

4'-Ethynyl-2-fluoro-2'-deoxyadenosine (EFdA) is a novel nucleoside reverse transcriptase inhibitor with a unique mechanism of action and highly potent activity against both wild-type and clinically relevant drug resistant HIV-1 variants. Furthermore, in vivo efficacy and safety evaluations have shown EFdA to be a promising therapeutic candidate for use in the treatment of HIV infection. However, little is known about the pharmacokinetic and biopharmaceutical properties of EFdA. In this study, we evaluated cellular EFdA transport using Caco-2 and Madin-Darby Canine Kidney II (MDCKII) in vitro cell models. Studies using Caco-2 cell monolayers showed that EFdA efflux ratios were >2.0, suggesting that active drug transport mechanisms may play a role in EFdA flux. ABCB1 transporter (PGP1) inhibition was assessed using the acetomethoxy derivate of calcein (calcein-AM) as a fluorescent probe in both wild-type MDCKII and PGP1 overexpressing MDCKII cells. Nonetheless, our data showed that EFdA is not a substrate of PGP1. Additionally, comparative bidirectional flux of EFdA and Lucifer yellow (LY, a well-known paracellular marker) was studied over a range of EFdA concentrations. In MDCKII monolayers, EFdA had an apparent permeability coefficient (Papp) (a-b) of <1×10(-6)cm/s. The Papp values significantly increased in the presence of the paracellular permeability enhancer, indicating that EFdA primarily permeates via the paracellular route. Copyright © 2014 Elsevier B.V. All rights reserved.

Preliminary Results on TID (Travelling Ionospheric Disturbances) over Ebro from TEC Data.

DTIC Science & Technology

1982-10-30

auroral zone during magnetio substOrms (Chimonas and Etnes,1970, Testud , 1970, Titheridge,1971) while several causes have been poin-ted out for the...88 62 Testud , J.. 1970 Jro.At.Terr.,A202,32087 Mutnri, .. 1971 Jus.GoPhys.esL1,6915 TOkuao,I., .Om andLle195JAmerPhs,715 0. tsui .ad .g 19J73

Language Outcomes of 7-Year-Old Children with or without a History of Late Language Emergence at 24 Months

ERIC Educational Resources Information Center

Rice, Mabel L.; Taylor, Catherine L.; Zubrick, Stephen R.

2008-01-01

Purpose: The aim of this study was to investigate the language outcomes of 7-year-old children with and without a history of late language emergence at 24 months. Method: One hundred twenty-eight children with a history of late language emergence (LLE) at 24 months and 109 children with a history of normal language emergence (NLE) at 24 months…

Extraction of benzene and cyclohexane using [BMIM][N(CN)2] and their equilibrium modeling

NASA Astrophysics Data System (ADS)

Ismail, Marhaina; Bustam, M. Azmi; Man, Zakaria

2017-12-01

The separation of aromatic compound from aliphatic mixture is one of the essential industrial processes for an economically green process. In order to determine the separation efficiency of ionic liquid (IL) as a solvent in the separation, the ternary diagram of liquid-liquid extraction (LLE) 1-butyl-3-methylimidazolium dicyanamide [BMIM][N(CN)2] with benzene and cyclohexane was studied at T=298.15 K and atmospheric pressure. The solute distribution coefficient and solvent selectivity derived from the equilibrium data were used to evaluate if the selected ionic liquid can be considered as potential solvent for the separation of benzene from cyclohexane. The experimental tie line data was correlated using non-random two liquid model (NRTL) and Margules model. It was found that the solute distribution coefficient is (0.4430-0.0776) and selectivity of [BMIM][N(CN)2] for benzene is (53.6-13.9). The ternary diagram showed that the selected IL can perform the separation of benzene and cyclohexane as it has extractive capacity and selectivity. Therefore, [BMIM][N(CN)2] can be considered as a potential extracting solvent for the LLE of benzene and cyclohexane.

IViPP: A Tool for Visualization in Particle Physics

NASA Astrophysics Data System (ADS)

Tran, Hieu; Skiba, Elizabeth; Baldwin, Doug

2011-10-01

Experiments and simulations in physics generate a lot of data; visualization is helpful to prepare that data for analysis. IViPP (Interactive Visualizations in Particle Physics) is an interactive computer program that visualizes results of particle physics simulations or experiments. IViPP can handle data from different simulators, such as SRIM or MCNP. It can display relevant geometry and measured scalar data; it can do simple selection from the visualized data. In order to be an effective visualization tool, IViPP must have a software architecture that can flexibly adapt to new data sources and display styles. It must be able to display complicated geometry and measured data with a high dynamic range. We therefore organize it in a highly modular structure, we develop libraries to describe geometry algorithmically, use rendering algorithms running on the powerful GPU to display 3-D geometry at interactive rates, and we represent scalar values in a visual form of scientific notation that shows both mantissa and exponent. This work was supported in part by the US Department of Energy through the Laboratory for Laser Energetics (LLE), with special thanks to Craig Sangster at LLE.

Optimization of squalene produced from crude palm oil waste

NASA Astrophysics Data System (ADS)

Wandira, Irda; Legowo, Evita H.; Widiputri, Diah I.

2017-01-01

Squalene is a hydrocarbon originally and still mostly extracted from shark liver oil. Due to environmental issues over shark hunting, there have been efforts to extract squalene from alternative sources, such as Palm Fatty Acid Distillate (PFAD), one of crude palm oil (CPO) wastes. Previous researches have shown that squalene can be extracted from PFAD using saponification process followed with liquid-liquid extraction process although the method had yet to be optimized in order to optimize the amount of squalene extracted from PFAD. The optimization was done by optimizing both processes of squalene extraction method: saponification and liquid-liquid extraction. The factors utilized in the saponification process optimization were KOH concentration and saponification duration while during the liquid-liquid extraction (LLE) process optimization, the factors used were the volumes of distilled water and dichloromethane. The optimum percentage of squalene content in the extract (24.08%) was achieved by saponifying the PFAD with 50%w/v KOH for 60 minutes and subjecting the saponified PFAD to LLE, utilizing 100 ml of distilled water along with 3 times addition of fresh dichloromethane, 75 ml each; those factors would be utilized in the optimum squalene extraction method.

Classification of molecular structure images by using ANN, RF, LBP, HOG, and size reduction methods for early stomach cancer detection

NASA Astrophysics Data System (ADS)

Aytaç Korkmaz, Sevcan; Binol, Hamidullah

2018-03-01

Patients who die from stomach cancer are still present. Early diagnosis is crucial in reducing the mortality rate of cancer patients. Therefore, computer aided methods have been developed for early detection in this article. Stomach cancer images were obtained from Fırat University Medical Faculty Pathology Department. The Local Binary Patterns (LBP) and Histogram of Oriented Gradients (HOG) features of these images are calculated. At the same time, Sammon mapping, Stochastic Neighbor Embedding (SNE), Isomap, Classical multidimensional scaling (MDS), Local Linear Embedding (LLE), Linear Discriminant Analysis (LDA), t-Distributed Stochastic Neighbor Embedding (t-SNE), and Laplacian Eigenmaps methods are used for dimensional the reduction of the features. The high dimension of these features has been reduced to lower dimensions using dimensional reduction methods. Artificial neural networks (ANN) and Random Forest (RF) classifiers were used to classify stomach cancer images with these new lower feature sizes. New medical systems have developed to measure the effects of these dimensions by obtaining features in different dimensional with dimensional reduction methods. When all the methods developed are compared, it has been found that the best accuracy results are obtained with LBP_MDS_ANN and LBP_LLE_ANN methods.

Effectiveness of Liquid-Liquid Extraction, Solid Phase Extraction, and Headspace Technique for Determination of Some Volatile Water-Soluble Compounds of Rose Aromatic Water

PubMed Central

2017-01-01

Steam distillation is used to isolate scent of rose flowers. Rose aromatic water is commonly used in European cuisine and aromatherapy besides its use in cosmetic industry for its lovely scent. In this study, three different sampling techniques, liquid-liquid extraction (LLE), headspace technique (HS), and solid phase extraction (SPE), were compared for the analysis of volatile water-soluble compounds in commercial rose aromatic water. Some volatile water-soluble compounds of rose aromatic water were also analyzed by gas chromatography mass spectrometry (GCMS). In any case, it was concluded that one of the solid phase extraction methods led to higher recoveries for 2-phenylethyl alcohol (PEA) in the rose aromatic water than the liquid-liquid extraction and headspace technique. Liquid-liquid extraction method provided higher recovery ratios for citronellol, nerol, and geraniol than others. Ideal linear correlation coefficient values were observed by GCMS for quantitative analysis of volatile compounds (r2 ≥ 0.999). Optimized methods showed acceptable repeatability (RSDs < 5%) and excellent recovery (>95%). For compounds such as α-pinene, linalool, β-caryophyllene, α-humulene, methyl eugenol, and eugenol, the best recovery values were obtained with LLE and SPE. PMID:28791049

Parallel screening of drug-like natural compounds using Caco-2 cell permeability QSAR model with applicability domain, lipophilic ligand efficiency index and shape property: A case study of HIV-1 reverse transcriptase inhibitors

NASA Astrophysics Data System (ADS)

Patel, Rikin D.; Kumar, Sivakumar Prasanth; Patel, Chirag N.; Shankar, Shetty Shilpa; Pandya, Himanshu A.; Solanki, Hitesh A.

2017-10-01

The traditional drug design strategy centrally focuses on optimizing binding affinity with the receptor target and evaluates pharmacokinetic properties at a later stage which causes high rate of attrition in clinical trials. Alternatively, parallel screening allows evaluation of these properties and affinity simultaneously. In a case study to identify leads from natural compounds with experimental HIV-1 reverse transcriptase (RT) inhibition, we integrated various computational approaches including Caco-2 cell permeability QSAR model with applicability domain (AD) to recognize drug-like natural compounds, molecular docking to study HIV-1 RT interactions and shape similarity analysis with known crystal inhibitors having characteristic butterfly-like model. Further, the lipophilic properties of the compounds refined from the process with best scores were examined using lipophilic ligand efficiency (LLE) index. Seven natural compound hits viz. baicalien, (+)-calanolide A, mniopetal F, fagaronine chloride, 3,5,8-trihydroxy-4-quinolone methyl ether derivative, nitidine chloride and palmatine, were prioritized based on LLE score which demonstrated Caco-2 well absorption labeling, encompassment in AD structural coverage, better receptor affinity, shape adaptation and permissible AlogP value. We showed that this integrative approach is successful in lead exploration of natural compounds targeted against HIV-1 RT enzyme.

Optimisation of olive oil phenol extraction conditions using a high-power probe ultrasonication.

PubMed

Jerman Klen, T; Mozetič Vodopivec, B

2012-10-15

A new method of ultrasound probe assisted liquid-liquid extraction (US-LLE) combined with a freeze-based fat precipitation clean-up and HPLC-DAD-FLD-MS detection is described for extra virgin olive oil (EVOO) phenol analysis. Three extraction variables (solvent type; 100%, 80%, 50% methanol, sonication time; 5, 10, 20 min, extraction steps; 1-5) and two clean-up methods (n-hexane washing vs. low temperature fat precipitation) were studied and optimised with aim to maximise extracts' phenol recoveries. A three-step extraction of 10 min with pure methanol (5 mL) resulted in the highest phenol content of freeze-based defatted extracts (667 μg GAE g(-1)) from 10 g of EVOO, providing much higher efficiency (up to 68%) and repeatability (up to 51%) vs. its non-sonicated counterpart (LLE-agitation) and n-hexane washing. In addition, the overall method provided high linearity (r(2)≥0.97), precision (RSD: 0.4-9.3%) and sensitivity with LODs/LOQs ranging from 0.03 to 0.16 μg g(-1) and 0.10-0.51 μg g(-1) of EVOO, respectively. Copyright © 2012 Elsevier Ltd. All rights reserved.

Determining the Most Vital Arcs Within a Multi-Mode Communication Network Using Set-Based Measures

DTIC Science & Technology

2015-03-26

Disruption • llE"GreedyDisruption F’ ig u r c8 . A b..-o r grap h d isplayin g tho avcragcch augc in v;• lnc at cnchdcgrccor d is r u l>- t io n w h...Force Institute of Technology Graduate School of Engineering and Management (AFIT/ENS) 2950 Hobson Way WPAFB OH 45433-7765 AFIT-ENS-MS-15-M-131

SU-E-J-261: Statistical Analysis and Chaotic Dynamics of Respiratory Signal of Patients in BodyFix

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

Michalski, D; Huq, M; Bednarz, G

Purpose: To quantify respiratory signal of patients in BodyFix undergoing 4DCT scan with and without immobilization cover. Methods: 20 pairs of respiratory tracks recorded with RPM system during 4DCT scan were analyzed. Descriptive statistic was applied to selected parameters of exhale-inhale decomposition. Standardized signals were used with the delay method to build orbits in embedded space. Nonlinear behavior was tested with surrogate data. Sample entropy SE, Lempel-Ziv complexity LZC and the largest Lyapunov exponents LLE were compared. Results: Statistical tests show difference between scans for inspiration time and its variability, which is bigger for scans without cover. The same ismore » for variability of the end of exhalation and inhalation. Other parameters fail to show the difference. For both scans respiratory signals show determinism and nonlinear stationarity. Statistical test on surrogate data reveals their nonlinearity. LLEs show signals chaotic nature and its correlation with breathing period and its embedding delay time. SE, LZC and LLE measure respiratory signal complexity. Nonlinear characteristics do not differ between scans. Conclusion: Contrary to expectation cover applied to patients in BodyFix appears to have limited effect on signal parameters. Analysis based on trajectories of delay vectors shows respiratory system nonlinear character and its sensitive dependence on initial conditions. Reproducibility of respiratory signal can be evaluated with measures of signal complexity and its predictability window. Longer respiratory period is conducive for signal reproducibility as shown by these gauges. Statistical independence of the exhale and inhale times is also supported by the magnitude of LLE. The nonlinear parameters seem more appropriate to gauge respiratory signal complexity since its deterministic chaotic nature. It contrasts with measures based on harmonic analysis that are blind for nonlinear features. Dynamics of breathing, so

Determination of six iodotrihalomethanes in drinking water in Korea.

PubMed

Woo, Bomi; Park, Ju-Hyun; Kim, Seungki; Lee, Jeongae; Choi, Jong-Ho; Pyo, Heesoo

2018-06-02

Trihalomethanes (THMs) are chemicals regulated by Environmental Protection Agency's first drinking water regulation issued after the passage of the Safe Drinking Water Act. Among THMs, iodotrihalomethanes (I-THMs) are produced by treating water containing iodides ion with chlorine or ozone. I-THMs are more carcinogenic and biotoxic than chlorinated or brominated THMs. The purpose of this study was to analyze of I-THMs in drinking water using the liquid-liquid extraction (LLE) method with various extraction solvents. The calibration curves ranged from 0.01 to 20 ng/mL and the correlation coefficient showed a good linearity of 0.99 or more. The method detection limit ranged from 0.01 to 0.10 ng/mL. The accuracy of the LLE method ranged from 99.43 to 112.40%, and its precision ranged from 1.10 to 10.36%. Good recoveries (71.35-118.60%) were obtained for spiked drinking water samples, demonstrating that the LLE method is suitable for the analysis of drinking water samples. Dichloroiodomethane, bromochloroiodomethane, and dibromoiodomethane were identified in drinking water collected from 70 places of water purification plants in Korea. The samples were classified by disinfection systems, regions, seasons, and water sources. The concentration of I-THMs in pre-/postchlorination facilities owing to excess chlorine usage was higher than in ozonization/postchlorination facilities. Moreover, the concentrations of I-THMs were high in the coastal region, because of the large amount of halide ions from the sea. There was no seasonal difference; however, the concentration of I-THMs in pre-/postchlorination facilities increased in spring and summer. The concentration of I-THMs in water sources was high in samples from the Geum River and the Yeongsan and Sumjin River. The concentration and detection frequency of I-THMs in Han River and Nakdong River were high in the coastal region, because of numerous pre-/postchlorination facilities and the abundance of halide ions from the

Summer 2017 Microfluidics Research Report

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

Mcculloch, Quinn

Liquid-liquid Extraction (LLE), also known as solvent extraction, represents a large subset of chemistry where one or more solutes are transferred across an interface between two immiscible liquids. This type of chemistry is used in industrial scale processes to purify solvents, refine ore, process petroleum, treat wastewater, and much more. Although LLE has been successfully employed at the macroscale, where many liters/kgs of species are processed at large flow rates, LLE stands to benefit from lab-on-a-chip technology, where reactions take place quickly and efficiently at the microscale. A device, called a screen contactor, has been invented at Los Alamos Nationalmore » Laboratory (LANL) to perform solvent extraction at the microscale. This invention has been submitted to LANL’s Feynman Center for Innovation, and has been filed for provisional patent under U.S. Patent Application No. 62/483,107 1. The screen contactor consists of a housing that contains two different screen materials, flametreated stainless steel and polyether ether ketone (PEEK) thermoplastic, that are uniquely wetted by either an aqueous or an organic liquid phase, respectively. Liquids in this device flow longitudinally through the screens. The fine pore size of the screens (tens of microns) provide large capillary/adhesional forces while maintaining small hydraulic pressure drops. These physical characteristics are paramount to efficient microscale liquid phase separation. To demonstrate mass transfer using the screen contactor, a well-known chemical system 2 consisting of water and n-decane as solvents and trimethylamine (TEA) as a solute was selected. TEA is basic in water so its concentration can easily be quantified using a digital pH meter and an experimentally determined base dissociation constant. Characterization of this solvent system and its behavior in the screen contactor have been the focus of my research activities this summer. In the following sections, I have detailed

Square-wave voltammetry assays for glycoproteins on nanoporous gold

PubMed Central

Pandey, Binod; Bhattarai, Jay K.; Pornsuriyasak, Papapida; Fujikawa, Kohki; Catania, Rosa; Demchenko, Alexei V.; Stine, Keith J.

2014-01-01

Electrochemical enzyme-linked lectinsorbent assays (ELLA) were developed using nanoporous gold (NPG) as a solid support for protein immobilization and as an electrode for the electrochemical determination of the product of the reaction between alkaline phosphatase (ALP) and p-aminophenyl phosphate (p-APP), which is p-aminophenol (p-AP). Glycoproteins or concanavalin A (Con A) and ALP conjugates were covalently immobilized onto lipoic acid self-assembled monolayers on NPG. The binding of Con A – ALP (or soybean agglutinin – ALP) conjugate to glycoproteins covalently immobilized on NPG and subsequent incubation with p-APP substrate was found to result in square-wave voltammograms whose peak difference current varied with the identity of the glycoprotein. NPG presenting covalently bound glycoproteins was used as the basis for a competitive electrochemical assay for glycoproteins in solution (transferrin and IgG). A kinetic ELLA based on steric hindrance of the enzyme-substrate reaction and hence reduced enzymatic reaction rate after glycoprotein binding is demonstrated using immobilized Con A–ALP conjugates. Using the immobilized Con A-ALP conjugate, the binding affinity of immunoglobulin G (IgG) was found to be 105 nM, and that for transferrin was found to be 650 nM. Minimal interference was observed in the presence of 5 mg mL−1 BSA as a model serum protein in both the kinetic and competitive ELLA. Inhibition studies were performed with methyl D-mannoside for the binding of TSF and IgG to Con A-ALP; IC50 values were found to be 90 μM and 286 μM, respectively. Surface coverages of proteins were estimated using solution depletion and the BCA protein concentration assay. PMID:24611035

The constituents of Cibotium barometz and their permeability in the human Caco-2 monolayer cell model.

PubMed

Wu, Qi; Yang, Xiu-Wei

2009-09-25

Cibotium barometz (L.) J. Sm. (Dicksoniaceae) has been traditionally used as anti-inflammatory and anodyne. To investigate the constituents in the rhizomes of Cibotium barometz, and evaluate their permeability in the human Caco-2 model. The rhizomes extracts of Cibotium barometz were isolated by chromatographic techniques. Structures of isolated compounds were identified by spectroscopic methods. The permeability of the main constituents was evaluated using human Caco-2 cell monolayer as a model system. Three unusual sesquiterpenes having 1-indanone nucleus (1, 3 and 4) and an unusual orthoester spiropyranosyl derivative of protocatechuic acid (2) were isolated from the rhizomes of Cibotium barometz. Among these, the bilateral permeation of 1, 3 and 4 in Caco-2 model was examined. The apparent permeability coefficients (P(app)) of 1 was identical with those of propranolol, which is often used as reference standard of high permeability. The P(app) values of 3 and 4 were in agreement with those of atenolol, which is often used as reference standard of poor permeability. The permeation rates of 1, 3 and 4 increased linearly as a function of time up to 180 min and with the concentration within the test range of 25-200 microM. This is the first report on the presence of compounds 2 and 3 in this plant and 4 was a new compound. Compound 1 is assigned for a well-absorbed, and 2 and 3 are assigned for the poorly absorbed compounds in human intestine. A passive diffusion mechanism for transport of 1, 3 and 4 in Caco-2 model was proposed. The results provided some useful information for predicting the oral bioavailability of 1, 3 and 4.

Long Range Spoil Disposal Study. Part III. Sub-Study 2. Nature, Source, and Cause of Shoal. Appendix A,

DTIC Science & Technology

1973-12-01

MAP OF DELI N TOWN FM, ENGLISHTOWN, WOODBURY ak ADJACENT MERCHANTVILLE CLAY, NONMARINE SEDIMENTS SUCH AS MAGOTHY , RARITAN, LN PATAPSCO, PATUXENT LN...Tr and Patuxent Magothy 39 - 61 - Merchantville 21 - 55 24 Woodbury 29 - 41 30 Englishtown 38 - 35 27 Marshalltown 28 42 12 18 Wenonah 40 - 28 32 77...FORMATIONS V * (INCLUDES RARITAN, PATAPCO, \\~ .c PATUXENT, MAGOTHY . MERCHANTVI LLE, WOODBURY, ENGLISHTOWN, MARSHALL- TOWN, WENONAM, MOUNT LAUREL, NAVESINK a

Development of X-Ray Laser Media. Measurement of Gain and Development of Cavity Resonators for Wavelengths near 130 Angstroms. Volume 3.

DTIC Science & Technology

1983-02-01

ray microscope (Kirkpatrick and Baez, 1948). At present such systems use single layer coatings illminated at very glancing angles. Ikltilayer coatings...might be useful as a means of operating such a system at an increased angle of incidence to the surface (this would reduce the geometrical aberrations...of the focussing elements); however our analysis of the LLE system indicates that one will have to accept a trade-off between collection aperture

The Decision to Not Invade Baghdad (Persian Gulf War)

DTIC Science & Technology

2007-04-12

LAWRENCE K. MONTGOMERY, JR. United States Army National Guard Se ni or Se rv ic e Co lle ge DISTRIBUTION STATEMENT A: Approved for Public Release...Distribution is Unlimited. USAWC CLASS OF 2007 REPORT DOCUMENTATION PAGE Form Approved OMB No. 0704-0188 Public reporting burden for this collection of...information is estimated to average 1 hour per response, including the time for reviewing instructions, searching existing data sources, gathering and

Gender impact on first trimester markers in Down syndrome screening.

PubMed

Larsen, Severin Olesen; Wøjdemann, Karen R; Shalmi, Anne-Cathrine; Sundberg, Karin; Christiansen, Michael; Tabor, Ann

2002-12-01

The influence of fetal gender on the level in the first trimester of the serological markers alpha-fetoprotein (AFP), pregnancy-associated plasma protein-A (PAPP-A) and free beta human chorionic gonadotropin (betahCG) and on nuchal translucency is described for 2637 singleton pregnancies with normal outcome. Mean log MoM values for pregnancies with female and male fetuses were calculated using regression of log marker values on gestational age expressed as crown rump length and on maternal weight. A pronounced gender impact was found for free betahCG, being 16% higher for female than for male fetuses. Copyright 2002 John Wiley & Sons, Ltd.

LLE review, volume 73. Quarterly report, October 1997--December 1997

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

NONE

1998-04-01

This progress report contains discussion on the following topics: A high-bandwidth electrical-waveform generator based on aperture-coupled striplines for OMEGA pulse-shaping applications; sweep deflection circuit development using computer-aided circuit design for the OMEGA multichannel streak camera; D-{sup 3}He protons as a diagnostic for target {rho}R; growth rates of the ablative Rayleigh-Taylor instability in inertial confinement fusion; three-dimensional analysis of the power transfer between crossed laser beams; characterization of freestanding polymer films for application in 351-nm, high-peak-power laser systems; subsurface damage in microgrinding optical glasses; bound-abrasive polishers for optical glass; and color gamut of cholesteric liquid crystal films and flakes by standardmore » colorimetry.« less

Anticipated improvement in laser beam uniformity using distributed phase plates with quasirandom patterns

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

Epstein, R.; Skupsky, S.

1990-08-01

The uniformity of focused laser beams, that has been modified with randomly phased distributed phase plates (C. B. Burckhardt, Appl. Opt. {bold 9}, 695 (1970); Kato and Mima, Appl. Phys. B {bold 29}, 186 (1982); Kato {ital et} {ital al}., Phys. Rev. Lett. {bold 53}, 1057 (1984); LLE Rev. {bold 33}, 1 (1987)), can be improved further by constructing patterns of phase elements which minimize phase correlations over small separations. Long-wavelength nonuniformities in the intensity distribution, which are relatively difficult to overcome in the target by thermal smoothing and in the laser by, e.g., spectral dispersion (Skupsky {ital et} {italmore » al}., J. Appl. Phys. {bold 66}, 3456 (1989); LLE Rev. {bold 36}, 158 (1989); {bold 37}, 29 (1989); {bold 37}, 40 (1989)), result largely from short-range phase correlations between phase plate elements. To reduce the long-wavelength structure, we have constructed phase patterns with smaller short-range correlations than would occur randomly. Calculations show that long-wavelength nonuniformities in single-beam intensity patterns can be reduced with these masks when the intrinsic phase error of the beam falls below certain limits. We show the effect of this improvement on uniformity for spherical irradiation by a multibeam system.« less

Method development aspects for the quantitation of pharmaceutical compounds in human plasma with a matrix-assisted laser desorption/ionization source in the multiple reaction monitoring mode.

PubMed

Kovarik, Peter; Grivet, Chantal; Bourgogne, Emmanuel; Hopfgartner, Gérard

2007-01-01

The present work investigates various method development aspects for the quantitative analysis of pharmaceutical compounds in human plasma using matrix-assisted laser desorption/ionization and multiple reaction monitoring (MALDI-MRM). Talinolol was selected as a model analyte. Liquid-liquid extraction (LLE) and protein precipitation were evaluated regarding sensitivity and throughput for the MALDI-MRM technique and its applicability without and with chromatographic separation. Compared to classical electrospray liquid chromatography/mass spectrometry (LC/ESI-MS) method development, with MALDI-MRM the tuning of the analyte in single MS mode is more challenging due to interfering matrix background ions. An approach is proposed using background subtraction. With LLE and using a 200 microL human plasma aliquot acceptable precision and accuracy could be obtained in the range of 1 to 1000 ng/mL without any LC separation. Approximately 3 s were required for one analysis. A full calibration curve and its quality control samples (20 samples) can be analyzed within 1 min. Combining LC with the MALDI analysis allowed improving the linearity down to 50 pg/mL, while reducing the throughput potential only by two-fold. Matrix effects are still a significant issue with MALDI but can be monitored in a similar way to that used for LC/ESI-MS analysis.

Evaluation of Limb Load Asymmetry Using Two New Mathematical Models

PubMed Central

Kumar, Senthil NS; Omar, Baharudin; Joseph, Leonard H.; Htwe, Ohnmar; Jagannathan, K.; Hamdan, Nor M Y; Rajalakshmi, D.

2015-01-01

Quantitative measurement of limb loading is important in orthopedic and neurological rehabilitation. In current practice, mathematical models such as Symmetry index (SI), Symmetry ratio (SR), and Symmetry angle (SA) are used to quantify limb loading asymmetry. Literatures have identified certain limitations with the above mathematical models. Hence this study presents two new mathematical models Modified symmetry index (MSI) and Limb loading error (LLE) that would address these limitations. Furthermore, the current mathematical models were compared against the new model with the goal of achieving a better model. This study uses hypothetical data to simulate an algorithmic preliminary computational measure to perform with all numerical possibilities of even and uneven limb loading that can occur in human legs. Descriptive statistics are used to interpret the limb loading patterns: symmetry, asymmetry and maximum asymmetry. The five mathematical models were similar in analyzing symmetry between limbs. However, for asymmetry and maximum asymmetry data, the SA and SR values do not give any meaningful interpretation, and SI gives an inflated value. The MSI and LLE are direct, easy to interpret and identify the loading patterns with the side of asymmetry. The new models are notable as they quantify the amount and side of asymmetry under different loading patterns. PMID:25716372

Equilibrium study for ternary mixtures of biodiesel

NASA Astrophysics Data System (ADS)

Doungsri, S.; Sookkumnerd, T.; Wongkoblap, A.; Nuchitprasittichai, A.

2017-11-01

The liquid-liquid equilibrium (LLE) data for the ternary mixtures of methanol + fatty acid methyl ester (FAME) + palm oil and FAME + palm oil + glycerol at various temperatures from 35 to 55°C, the tie lines and binodial curves were also investigated and plotted in the equilibrium curve. The experimental results showed that the binodial curves of methanol + FAME + palm oil depended significantly with temperature while the binodial curves of FAME + palm oil + glycerol illustrated insignificant change with temperatures. The interaction parameters between liquid pair obtained for NRTL (Nonrandom Two-Liquid) and UNIQUAC (Universal Quasi-Chemical Theory) models from the experimental data were also investigated. It was found that the correlated parameters of UNIQUAC model for system of FAME + palm oil + glycerol, denoted as a13 and a31, were 580.42K and -123.69K, respectively, while those for system of methanol + FAME + palm oil, denoted as a42 and a24, were 71.48 K and 965.57K, respectively. The ternary LLE data reported here would be beneficial for engineers and scientists to use for prediction of yield and purity of biodiesel for the production. The UNIQUAC model agreed well with the experimental data of ternary mixtures of biodiesel.

Performance Characterization of RaPToRS Systems

NASA Astrophysics Data System (ADS)

Shibata, K.; Krieger, M.; Fallica, J.; Henchen, R.; Pogozelski, E.; Padalino, S.; SUNY Geneseo Collaboration; LaboratoryLaser Energetics at University of Rochester Collaboration

2011-10-01

The Rapid Pneumatic Transport of Radioactive Samples (RaPToRS) system can quickly and efficiently move radioactive materials from their activation site to a counting station. Facilities such as the NIF and LLE are considering these systems while NRL is currently using one. The system is essentially a 10 cm diameter pneumatic tube with a cylindrical sample carrier. The performance of the system depends on many factors, including the mass of the carrier, length of the tube, angle and difference in height of the tube's endpoints, the carrier's physical design, and the number, type, and distribution of blowers attached to the tube. These factors have been systematically examined to develop the fastest and most reliable system. The most significant factors are the mass and the vertical travel of the carrier. When the carrier mass is low, moving air supports the carrier in the tube, resulting in low friction. The terminal velocity ranges from 13.5 to 2.5 m/s for masses varying from 1 kg to 3 kg. Using a single 1100 W blower, the initial force exerted on the carrier was 11.3 N. This work was supported in part by the US Department of Energy through the LLE.

A Rapid Method for the Quantitative Determination of 34 Pesticides in Nonalcoholic Carbonated Beverages Using Liquid-Liquid Extraction Coupled to Dispersive Solid-Phase Cleanup Followed by Gas Chromatography with Tandem Mass Spectrometry.

PubMed

Rai, Satyajeet; Gullapalli, Madhuri Devi; Srivastava, Anshuman; Shaik, Hussain; Siddiqui, Mohammed Haris; Mudiam, Mohana Krishna Reddy

2017-05-01

An economical, rapid, and sensitive multiresidue method using liquid-liquid extraction (LLE) coupled with dispersive SPE (dSPE) cleanup was developed for the quantitative determination of 34 multiclass multiresidue (MCMR) pesticides (14 organochlorines, eight organophosphates, 10 synthetic pyrethroids, and two herbicides) in nonalcoholic carbonated beverages (cola, orange, lemon-lime, and citra) using GC with tandem MS. The procedure mainly involved LLE by dichloromethane and dSPE cleanup in the presence of magnesium sulfate, primary secondary amine, and C18. The RSD of the developed method was found to be less than 14%. The LOD and LOQ values for all the analyzed pesticides were found in the ranges of 0.001-0.027 μg/L and 0.004-0.088 μg/L, respectively. The LOQ levels of the pesticides analyzed were found to be well below the recommended limit by the European Union (0.1 μg/L in water). The mean recoveries of pesticides in different nonalcoholic carbonated beverages (cola, orange, lemon-lime, and citra) were found to be in the range of 79-111%, with RSDs less than 11%. The validation data prove that the method can be acceptable to regulatory agencies for the routine analysis of MCMR pesticides in nonalcoholic carbonated beverages.

Oral pharmacokinetics of baicalin, wogonoside, oroxylin A 7-O-β-d-glucuronide and their aglycones from an aqueous extract of Scutellariae Radix in the rat.

PubMed

Cai, Yu; Li, Sai; Li, Ting; Zhou, Ruina; Wai, Alfred Tai-Seng; Yan, Ru

2016-07-15

well as a poorer intestinal permeability of baicalein (Papp×10(-6)cm/s) should account for the lower systemic exposures of BG and baicalein. Faster microbial hydrolysis of WG, high intestinal permeability (Papp×10(-5)cm/s) and less hepatic glucuronidation of wogonin explain the relatively high systemic exposure of wogonin. Sole microbial deglycosylation of OG, high intestinal permeability (Papp×10(-5)cm/s) and extensive hepatic glucuronidation of oroxylin A supported the highest systemic exposure of OG. Taken together, the oral kinetics of six flavonoid glucuronides and aglycones in the SR extract were simultaneously obtained. Microbial conversion, intestinal epithelial permeability and hepatic glucuronidation are determinant factors for their systemic exposures. Copyright © 2015 Elsevier B.V. All rights reserved.

Identification, optimisation and in vivo evaluation of oxadiazole DGAT-1 inhibitors for the treatment of obesity and diabetes.

PubMed

McCoull, William; Addie, Matthew S; Birch, Alan M; Birtles, Susan; Buckett, Linda K; Butlin, Roger J; Bowker, Suzanne S; Boyd, Scott; Chapman, Stephen; Davies, Robert D M; Donald, Craig S; Green, Clive P; Jenner, Chloe; Kemmitt, Paul D; Leach, Andrew G; Moody, Graeme C; Gutierrez, Pablo Morentin; Newcombe, Nicholas J; Nowak, Thorsten; Packer, Martin J; Plowright, Alleyn T; Revill, John; Schofield, Paul; Sheldon, Chris; Stokes, Steve; Turnbull, Andrew V; Wang, Steven J Y; Whalley, David P; Wood, J Matthew

2012-06-15

A novel series of DGAT-1 inhibitors was discovered from an oxadiazole amide high throughput screening (HTS) hit. Optimisation of potency and ligand lipophilicity efficiency (LLE) resulted in a carboxylic acid containing clinical candidate 53 (AZD3988), which demonstrated excellent DGAT-1 potency (0.6 nM), good pharmacokinetics and pre-clinical in vivo efficacy that could be rationalised through a PK/PD relationship. Copyright © 2012 Elsevier Ltd. All rights reserved.

Soviet Development of Gyrotrons

DTIC Science & Technology

1986-05-01

Relationship Type of Device Remarks V, - Vc, anomalous Doppler Capable of 100 percent efficiency, CRM but more cumbersome than Cheren- kov devices V...authors; and discusses inlividual Soviet reseaLc- groups, the basic organizational units responAiLle for the CRM and gyrotron research and development. The...maintained a cCnEistEnt iecord of significant achievements; it has managed to overcome the systenic yeaxness of the Soviet R&C systeg in teimg atle to

JPRS Report, East Asia Southeast Asia

DTIC Science & Technology

1987-07-31

New Dell « yesterday. "We will have rallies, civil disobedi- ence . . . everything to oppose the army rule," Mr Reddy told reporters after two...21 Jun 87 p 14 [Article by David Jenkins] [Text] hr ~gu~",^llE Indonesian Ambassador to Australia, Major-General August Marpaung, leaves this...appointment (1964-68) spanned Presi- dent Soekanio’s ill-considered Confron- tation of Malaysia and the difficult early years of the New Order

Implications of failure to achieve a result from prenatal maternal serum cell-free DNA testing: a historical cohort study.

PubMed

Chan, N; Smet, M-E; Sandow, R; da Silva Costa, F; McLennan, A

2017-11-01

To investigate the pregnancy outcomes in a cohort of women who failed to obtain a result in non-invasive prenatal testing (NIPT). Historical cohort study. A multicentre private practice in Sydney, Australia. Women who failed to obtain a result from NIPT (n = 131). The maternal characteristics, antenatal investigations and pregnancy outcomes for these women were compared with those who obtained a result at the same practice and to the general Australian obstetric population. Antenatal investigations: pregnancy-associated plasma protein-A (PAPP-A), free β-human chorionic gonadotrophin (β-hCG), placental growth factor (PlGF), uterine artery pulsatility index (PI), mean arterial pressure (MAP). Pregnancy outcomes: chromosomal abnormality, pre-eclampsia, gestational diabetes, small-for-gestational-age (SGA), preterm delivery. Only 1.1% of NIPT samples failed to return a result. This cohort was significantly older and had significantly increased weight compared with the general Australian obstetric population. Pregnancy outcomes were available for 94% of the cohort. There were significantly higher rates of chromosomal aneuploidies (6.5% versus 0.2%, P < 0.0001), pre-eclampsia (11% versus 1.5%, P < 0.0001) and gestational diabetes (23% versus 7.5%, P < 0.0001) compared with the general obstetric population. Rates of preterm delivery and SGA were elevated but did not reach significance. Antenatal investigations demonstrated decreased PAPP-A MoM (0.75 versus 1.14, P < 0.0001), decreased free β-hCG (0.71 versus 1.01, P < 0.0001) and increased uterine artery PI (1.79 versus 1.65, P = 0.02). Women who fail to obtain a result from NIPT are at increased risk of adverse pregnancy outcomes, in particular chromosomal aneuploidy, gestational diabetes and pre-eclampsia. None received. Women who fail to obtain a result from cell-free DNA NIPT are at increased risk of adverse pregnancy outcomes. © 2017 Royal College of Obstetricians and Gynaecologists.

Mitosis-specific phosphorylation of amyloid precursor protein at Threonine 668 leads to its altered processing and association with centrosomes

PubMed Central

2011-01-01

Background Atypical expression of cell cycle regulatory proteins has been implicated in Alzheimer's disease (AD), but the molecular mechanisms by which they induce neurodegeneration are not well understood. We examined transgenic mice expressing human amyloid precursor protein (APP) and presenilin 1 (PS1) for changes in cell cycle regulatory proteins to determine whether there is a correlation between cell cycle activation and pathology development in AD. Results Our studies in the AD transgenic mice show significantly higher levels of cyclin E, cyclin D1, E2F1, and P-cdc2 in the cells in the vicinity of the plaques where maximum levels of Threonine 668 (Thr668)-phosphorylated APP accumulation was observed. This suggests that the cell cycle regulatory proteins might be influencing plaque pathology by affecting APP phosphorylation. Using neuroglioma cells overexpressing APP we demonstrate that phosphorylation of APP at Thr668 is mitosis-specific. Cells undergoing mitosis show altered cellular distribution and localization of P-APP at the centrosomes. Also, Thr668 phosphorylation in mitosis correlates with increased processing of APP to generate Aβ and the C-terminal fragment of APP, which is prevented by pharmacological inhibitors of the G1/S transition. Conclusions The data presented here suggests that cell cycle-dependent phosphorylation of APP may affect its normal cellular function. For example, association of P-APP with the centrosome may affect spindle assembly and cell cycle progression, further contributing to the development of pathology in AD. The experiments with G1/S inhibitors suggest that cell cycle inhibition may impede the development of Alzheimer's pathology by suppressing modification of βAPP, and thus may represent a novel approach to AD treatment. Finally, the cell cycle regulated phosphorylation and processing of APP into Aβ and the C-terminal fragment suggest that these proteins may have a normal function during mitosis. PMID:22112898

Between pregnancy biological variability of first trimester markers of Down syndrome and the implications for screening in subsequent pregnancies: an issue revisited.

PubMed

Spencer, Kevin

2002-10-01

To assess the level of correlation of first trimester biochemical and biophysical markers of Down syndrome between different pregnancies in the same individual. To assess the impact that between pregnancy biological variability has on the likelihood that women who are at increased risk in a first pregnancy being also at increased risk in a subsequent pregnancy. During a three period women attending the OSCAR clinic at Harold Wood Hospital have had the opportunity to have first trimester screening for Down syndrome and other aneuploidies using the maternal serum biochemical markers free beta-human chorionic gonadotrophin (hCG) and pregnancy associated plasma protein-A (PAPP-A) in conjunction with fetal nuchal translucency (NT) thickness and maternal age. Of the 111,105 women undergoing such screening, the computer records were examined for women who had more than one pregnancy. The results from 1002 women with two normal singleton pregnancies were available for analysis. Marker correlations (as MoM) were established between the pregnancies and the proportion of women likely to be at increased risk in each pregnancy estimated, as was the likelihood of women being at increased risk in both pregnancies. For fetal NT there was no correlation between NT MoM in the first and second pregnancy (r = 0.0959, p > 0.10). For maternal serum free beta-hCG MoM a significant correlation was found (r = 0.3976, p < 0.001), as was also found for PAPP-A MoM (r = 0.4371, p < 0.001). The implication for such between pregnancy marker association is that women who have an increased risk of Down syndrome in one pregnancy are two or three times more likely to repeat this event in their next pregnancy. This information may be useful in counselling women when undergoing first trimester screening in a subsequent pregnancy. Copyright 2002 John Wiley & Sons, Ltd.

Comparison of MDCK-MDR1 and Caco-2 cell based permeability assays for anti-malarial drug screening and drug investigations.

PubMed

Jin, Xiannu; Luong, Thu-Lan; Reese, Necole; Gaona, Heather; Collazo-Velez, Vanessa; Vuong, Chau; Potter, Brittney; Sousa, Jason C; Olmeda, Raul; Li, Qigui; Xie, Lisa; Zhang, Jing; Zhang, Ping; Reichard, Greg; Melendez, Victor; Marcsisin, Sean R; Pybus, Brandon S

2014-01-01

Malaria is a major health concern and affects over 300million people a year. Accordingly, there is an urgent need for new efficacious anti-malarial drugs. A major challenge in developing new anti-malarial drugs is to design active molecules that have preferable drug-like characteristics. These "drug-like" characteristics include physiochemical properties that affect drug absorption, distribution, metabolism, and excretion (ADME). Compounds with poor ADME profiles will likely fail in vivo due to poor pharmacokinetics and/or other drug delivery related issues. There have been numerous assays developed in order to pre-screen compounds that would likely fail in further development due to poor absorption properties including PAMPA, Caco-2, and MDCK permeability assays. The use of cell-based permeability assays such as Caco-2 and MDCK serve as surrogate indicators of drug absorption and transport, with the two approaches often used interchangeably. We sought to evaluate both approaches in support of anti-malarial drug development. Accordingly, a comparison of both assays was conducted utilizing apparent permeability coefficient (Papp) values determined from liquid chromatography/tandem mass spectrometry (LC-MS) analyses. Both Caco-2 and MDCK permeability assays produced similar Papp results for potential anti-malarial compounds with low and medium permeability. Differences were observed for compounds with high permeability and compounds that were P-gp substrates. Additionally, the utility of MDCK-MDR1 permeability measurements was demonstrated in probing the role of P-glycoprotein transport in Primaquine-Chloroquine drug-drug interactions in comparison with in vivo pharmacokinetic changes. This study provides an in-depth comparison of the Caco-2 and MDCK-MDR1 cell based permeability assays and illustrates the utility of cell-based permeability assays in anti-malarial drug screening/development in regard to understanding transporter mediated changes in drug absorption

Emigration dynamics in the Arab region. IOM / UNFPA workshop, 7-8 October 1996, Geneva, Switzerland.

PubMed

Appleyard, R

1996-01-01

This paper describes the four research monographs on emigration that were presented at the December 1995 Regional Workshop in the Arab Region. The workshop was an exchange of views and discussion of policy implications of emigration. Monographs were presented by Dr. Mayar Farrag on emigration in Egypt, Professor Nadji Safir on migration in the Maghreb, Dr. Setenay Shami on emigration dynamics in Jordan, and Dr. Lynn Evans on behalf of Dr. Ivy Papps on migration in Gulf Cooperation Council (GCC) countries. Dr. Farrag identified three periods of migration. During the mid-1960s to the mid-1970s, migrants were officially encouraged by Egypt to fill education positions. During the 1970s, many migrants left for the oil-producing countries on a temporary basis. Since the mid-1980s, the influences on Egyptian migration have been the economic recession and oil prices in the Gulf states, the completion of infrastructure projects in most Gulf states, and the replacement of foreign labor with nationals. Dr. Farrag recommended improving the migrants' skills in English and technology in order to maintain a dominant flow of temporary migrants to the Gulf region. Professor Safir reported that persons from the Maghreb region (Tunisia, Algeria, and Morocco) migrated to France before independence and subsequently to West Germany and the Benelux countries. Algeria had the highest migration potential, and Morocco had the highest migration. Morocco had established networks in destination countries, high population growth rates, and high unemployment. Maghreb countries are receiving migrants from the south. Professor Safir recommended regional integration. Dr. Shami separated step migration from stepwise migration, which complicates push-pull theories. Dr. Papps argued that use of foreign labor may not be the best option for development, and that sending countries should be more aware of skill needs in GCC countries.

Electrochemical immunoassay for vitellogenin based on sequential injection using antigen-immobilized magnetic microbeads.

PubMed

Hirakawa, Koji; Katayama, Masaaki; Soh, Nobuaki; Nakano, Koji; Imato, Toshihiko

2006-01-01

A rapid and sensitive immunoassay for the determination of vitellogenin (Vg) is described. The method involves a sequential injection analysis (SIA) system equipped with an amperometric detector and a neodymium magnet. Magnetic beads, onto which an antigen (Vg) was immobilized, were used as a solid support in an immunoassay. The introduction, trapping and release of magnetic beads in an immunoreaction cell were controlled by means of the neodymium magnet and by adjusting the flow of the carrier solution. The immunoassay was based on an indirect competitive immunoreaction of an alkaline phosphatase (ALP) labeled anti-Vg monoclonal antibody between the fraction of Vg immobilized on the magnetic beads and Vg in the sample solution. The immobilization of Vg on the beads involved coupling an amino group moiety of Vg with the magnetic beads after activation of a carboxylate moiety on the surface of magnetic beads that had been coated with a polylactate film. The Vg-immobilized magnetic beads were introduced and trapped in the immunoreaction cell equipped with the neodymium magnet; a Vg sample solution containing an ALP labeled anti-Vg antibody at a constant concentration and a p-aminophenyl phosphate (PAPP) solution were sequentially introduced into the immunoreaction cell. The product of the enzyme reaction of PAPP with ALP on the antibody, paminophenol, was transported to an amperometric detector, the applied voltage of which was set at +0.2 V vs. an Ag/AgCl reference electrode. A sigmoid calibration curve was obtained when the logarithm of the concentration of Vg was plotted against the peak current of the amperometric detector using various concentrations of standard Vg sample solutions (0-500 ppb). The time required for the analysis is less than 15 min.

Impact of passive permeability and gut efflux transport on the oral bioavailability of novel series of piperidine-based renin inhibitors in rodents.

PubMed

Lévesque, Jean-François; Bleasby, Kelly; Chefson, Amandine; Chen, Austin; Dubé, Daniel; Ducharme, Yves; Fournier, Pierre-André; Gagné, Sébastien; Gallant, Michel; Grimm, Erich; Hafey, Michael; Han, Yongxin; Houle, Robert; Lacombe, Patrick; Laliberté, Sébastien; MacDonald, Dwight; Mackay, Bruce; Papp, Robert; Tschirret-Guth, Richard

2011-09-15

An oral bioavailability issue encountered during the course of lead optimization in the renin program is described herein. The low F(po) of pyridone analogs was shown to be caused by a combination of poor passive permeability and gut efflux transport. Substitution of pyridone ring for a more lipophilic moiety (logD>1.7) had minimal effect on rMdr1a transport but led to increased passive permeability (P(app)>10 × 10(-6) cm/s), which contributed to overwhelm gut transporters and increase rat F(po). LogD and in vitro passive permeability determination were found to be key in guiding SAR and improve oral exposure of renin inhibitors. Copyright © 2011 Elsevier Ltd. All rights reserved.

Nonlinear dynamics analysis of the human balance control subjected to physical and sensory perturbations.

PubMed

Ashtiani, Mohammed N; Mahmood-Reza, Azghani

2017-01-01

Postural control after applying perturbation involves neural and muscular efforts to limit the center of mass (CoM) motion. Linear dynamical approaches may not unveil all complexities of body efforts. This study was aimed at determining two nonlinear dynamics parameters (fractal dimension (FD) and largest Lyapunov exponent (LLE)) in addition to the linear standing metrics of balance in perturbed stance. Sixteen healthy young males were subjected to sudden rotations of the standing platform. The vision and cognition during the standing were also interfered. Motion capturing was used to measure the lower limb joints and the CoM displacements. The CoM path length as a linear parameter was increased by elimination of vision (p<0.01) and adding a cognitive load (p<0.01). The CoM nonlinear metric FD was decreased due to the cognitive loads (p<0.001). The visual interference increased the FD of all joints when the task included the cognitive loads (p<0.01). The slightly positive LLE values showed weakly-chaotic behavior of the whole body. The local joint rotations indicated higher LLEs. Results indicated weakly chaotic response of the whole body. Increase in the task difficulty by adding sensory interference had difference effects on parameters. Linear and nonlinear metrics of the perturbed stance showed that a combination of them may properly represent the body behavior.

Social Interventions to Prevent Heat-Related Mortality in the Older Adult in Rome, Italy: A Quasi-Experimental Study

PubMed Central

Inzerilli, Maria Chiara; Palombi, Leonardo; Madaro, Olga; Betti, Daniela; Marazzi, Maria Cristina

2018-01-01

This study focuses on the impact of a program aimed at reducing heat-related mortality among older adults residing in central Rome by counteracting social isolation. The mortality of citizens over the age of 75 living in three Urban Areas (UAs) located in central Rome is compared with that of the residents of four adjacent UAs during the summer of 2015. The data, broken down by UA, were provided by the Statistical Office of the Municipality of Rome, which gathers them on a routine basis. During the summer of 2015, 167 deaths were recorded in those UAs in which the Long Live the Elderly (LLE) program was active and 169 in those in which it was not, implying cumulative mortality rates of 25‰ (SD ± 1.4; Cl 95%: 23–29) and 29‰ (SD ± 6.7; Cl 95%: 17–43), respectively. Relative to the summer of 2014, the increase of deaths during the summer of 2015 was greater in UAs in which the LLE program had not been implemented (+97.3% vs. +48.8%). In conclusion, the paper shows the impact of a community-based active monitoring program, focused on strengthening individual relationship networks and the social capital of the community, on mortality in those over 75 during heat waves. PMID:29641436

The Dortmund Data Bank: A computerized system for retrieval, correlation, and prediction of thermodynamic properties of mixtures

NASA Astrophysics Data System (ADS)

Onken, U.; Rarey-Nies, J.; Gmehling, J.

1989-05-01

The Dortmund Data Bank (DDB) was started in 1973 with the intention to employ the vast store of vapor-liquid equilibrium (VLE) data from the literature for the development of models for the prediction of VLE. From the beginning, the structure of the DDB has been organized in such a way that it was possible to take advantage of the full potential of electronic computers. With the experience gained in fitting and processing VLE data, we extended the DDB system to other types of mixture properties, i.e., liquid-liquid equilibria (LLE), gas solubilities (GLE), activity coefficients at infinite dilution γ∞, heats of mixing ( h E), and excess heat capacities. Besides the files for mixture properties, the DDB contains pure-component data and program packages for various applications. New experimental data are checked for consistency before they are stored. For data retrieval user-specified search masks can be used. The data files are available via an online data service and through the Dechema Chemistry Data Series. For the purpose of data correlation and model testing, parameter fitting is performed with an optimization routine (Nelder-Mead). In the past years the DDB system has been successfully employed for the development of prediction methods for VLE, LLE, GLE, γ∞, and h E (UNIFAC, mod. UNIFAC, etc.).

Speciation of organotin compounds in urine by GC-MIP-AED and GC-MS after ethylation and liquid-liquid extraction.

PubMed

Zachariadis, G A; Rosenberg, E

2009-04-15

A method for the determination of organotin compounds in urine samples based on liquid-liquid extraction (LLE) in hexane and gas chromatographic separation was developed and optimized. Seven organotin species, namely monobutyltin (MBT), dibutyltin (DBT), tributyltin (TBT), tetrabutyltin (TeBT), monophenyltin (MPhT), diphenyltin (DPhT) and triphenyltin (TPhT), were in situ derivatized by sodium tetraethylborate (NaBEt(4)) to form ethylated less polar derivatives directly in the urine matrix. The critical parameters which have a significant effect on the yield of the successive liquid-liquid extraction procedure were examined, by using standard solutions of tetrabutyltin in hexane. The method was optimized for use in direct analysis of undiluted human urine samples and ways to overcome practical problems such as foam formation during extraction, due to various constituents of urine are discussed. After thorough optimization of the extraction procedure, all examined species could be determined after 3 min of simultaneous derivatization and extraction at room temperature and 5 min phase separation by centrifugation. Gas chromatography with a microwave-induced plasma atomic emission detector (MIP-AED) as element specific detector was employed for quantitative measurements, while a quadrupole mass spectrometric detector (MS) was used as molecular specific detector. The detection limits were between 0.42 and 0.67 microg L(-1) (as Sn) for the quantitative LLE-GC-MIP-AED method and the precision between 4.2% and 11.7%, respectively.

Efficacy of recombinant protein vaccines for protection against Nocardia seriolae infection in the largemouth bass Micropterus salmoides.

PubMed

Ho, Ping-Yueh; Chen, Yao-Chung; Maekawa, Shun; Hu, Hsiang-Hui; Tsai, An-Wei; Chang, Yung-Fu; Wang, Pei-Chi; Chen, Shih-Chu

2018-07-01

A reverse vaccinology-based survey of potent antigens associated with fish nocardiosis was conducted using the largemouth bass, Micropterus salmoides, with an aim to develop subunit vaccines. The antigens selected from the virulent strain Nocardia seriolae 961113 include the gene products of NGL2579 (GAPDH), NGL5701 (MMP), NGL4377 (OCTase), NGL4486 (ABC transporter), NGL3372 (LLE), NGL3388 (GHf10), NGL6627 (Antigen-85), NGL6696 (Esterase), and NGL6936 (CBP). These antigens were heterologously expressed in E. coli BL21 (DE3) for recombinant protein production. Then fish were vaccinated was these antigens, boosted at 2 weeks, and challenged with N. seriolae at 6 weeks after vaccination. The relative protection survival assay revealed high and significant protection efficacies of 94.45, 50.00, and 44.45 in fish that received the NGL3388 (GHf10), NGL6936 (CBP), and NGL3372 (LLE) vaccines, respectively. There were no apparent relationships or differences in tissue lesions among the administered vaccines. The serum titers against the bacterial preparations were higher for all vaccinated groups than for the control group at 4 weeks after immunization. However, no significant difference in serum titer was found at 6 weeks after immunization. The results of this study demonstrate that subunit vaccines against fish nocardiosis have differential effects, but are highly promising for nocardial prophylaxis. Copyright © 2018 Elsevier Ltd. All rights reserved.

Analysis of fentanyl in urine by DLLME-GC-MS.

PubMed

Gardner, Michael A; Sampsel, Sheena; Jenkins, Werner W; Owens, Janel E

2015-03-01

Fentanyl is a synthetic narcotic anesthetic ∼80-100 times more potent than morphine. Owing to the potential for its abuse, the drug may be included in a forensic toxicology work-up, which requires fast, precise and accurate measurements. Here, the stability of fentanyl was assessed when stored at three different temperatures (-20, 4 and 25°C) in synthetic urine. Stability at those three temperatures was demonstrated over 12 weeks upon analysis by gas chromatography-mass spectrometry with a deuterated internal standard (fentanyl-D5) utilizing three different extraction techniques: liquid-liquid extraction (LLE), solid-phase extraction and dispersed liquid-liquid microextraction (DLLME). The DLLME method was then optimized before use in the analysis of fentanyl in urine samples obtained from autopsy cases at the El Paso County Coroner's Office. Accuracy of the DLLME method was assessed by completing spike and recovery studies at three different fortification levels (10, 100 and 250 ng/mL) with excellent recovery (89.9-102.6%). The excellent comparability between DLLME and LLE is demonstrated (Bland-Altman difference plot with a mean difference of 4.9 ng/mL) and the use of this methodology in the analysis of forensically relevant samples is discussed. © The Author 2014. Published by Oxford University Press. All rights reserved. For Permissions, please email: journals.permissions@oup.com.

Infrared Optical Properties of Bipropellant Cryocontaminants

DTIC Science & Technology

1979-08-01

9 1.402~19 1.39105~ k 0.018800 0.U20900 0.022700 0 .025200 .0.027700 0.030~00 0 .033?00 O.03? 3UV 0 . 0 ~ 0 4 0 0 0.04~300 0.0~?/00...I152 TI-5-0- 1148 TD ;6 l l ~ l-1 ~--~ ll4O Tl-Yff- 1136 TI󈧦 113~ -I-I-3D- 117.8 -l-l-E6- 1124 1T22 1120 ] 1 1 8 1116 1114 1112

Design of a Film-Cooled Entraining Diffuser.

DTIC Science & Technology

1980-04-01

AD-A783 951 DEFENCE RESEARCH ESTABLISHMENT SUFFIELD RALSTON (ALBERTA) FIG 20/4 NL3 DESIGN OF A FILM-COOLED ENTRAINING DIFFUSER. 1U) APR 80 S B MURRAY...S.B. Murray C PCN 27C01 April 1980 80 4 29 004 DEFENCE RESEARCH ESTABLISHMENT SUFFIELD: RALSTON: ALBERTA WARNING rht ... , i. to - °aton is per lle...ulje(f to -ogoltio • IIl proprieh’~ra~r ind wtent it hh , i j l - UNCLASS I FI ED Li m DEFENCE RESEARCH ESTABLISHMENT SUFFIELD RALSTON ALBERTA

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

Functional Description for the Department of the Army Movements Management System. Redesign Phase 1. (DAMMS-R1). Volume 3.

DTIC Science & Technology

1987-12-31

Maintan -.ountry-TbI e CARDINALiii 134; HL~.,N-L.". 1); bL t i 11L h I...MEMO: FCityCd-Memo SOURCE IS: ’TMAS DAlA MODEL’ ATTRIBUTE IS: MEDIA ’DISK’ SEC-CLASS ’UNCLASSIFIED’ volatility ’DYNAMIC’I UPDATE- METHOD ’INTERACTIVE...8217 ATTRIBUTE IS: MEDIA ’DISK’ SEC-CLASS ’UNCLASSIFIED’ volatility ’STATTO’ UPDATE- METHOD ’INTERACTIVE’ UPDATE-FREQUENCY ’AS PER CHANGE’ Tt.LLE-FORM ’COMMAND’

The risk equivalent of an exposure to-, versus a dose of radiation

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

Bond, V.P.

The long-term potential carcinogenic effects of low-level exposure (LLE) are addressed. The principal point discussed is linear, no-threshold dose-response curve. That the linear no-threshold, or proportional relationship is widely used is seen in the way in which the values for cancer risk coefficients are expressed - in terms of new cases, per million persons exposed, per year, per unit exposure or dose. This implies that the underlying relationship is proportional, i.e., ''linear, without threshold''. 12 refs., 9 figs., 1 tab.

Effects of Solar Ultraviolet Radiation on Biogeochemical Dynamics in Aquatic Environments: Report of a Workshop Held in Woods Hole, Massachusetts on 23-26 October 1989

DTIC Science & Technology

1990-01-01

V’V for aqluatic organismls call be calclltteli wit Ii kmlowle’lle oIi 11151’ fatcto(rs. HIowI’ver , ai ke ,N un cert ainty remains in tile choice of...of the rapid rate of oxidation of Fe(II) at such pH and, possibly more importantly, the tendency of reduced iron to remain sorbed to particuiate iron...surface-located metal-organic complexes appears the most reasonable explanation for the ability of light to enhance colloid dissolution, much remains

Phase Equilibrium Investigation on 2-Phenylethanol in Binary and Ternary Systems: Influence of High Pressure on Density and Solid-Liquid Phase Equilibrium.

PubMed

Domańska, Urszula; Królikowski, Marek; Wlazło, Michał; Więckowski, Mikołaj

2018-05-30

Ionic liquids (ILs) are important new solvents proposed for applications in different separation processes. Herein, an idea of possible use of high pressure in a general strategy of production of 2-phenylethanol (PEA) is discussed. In this work, we present the influence of pressure on the density in binary systems of {1-hexyl-1-methylpyrrolidynium bis{(trifluoromethyl)sulfonyl}imide, [HMPYR][NTf 2 ], or 1-dodecyl-3-methylimidazolium bis{(trifluoromethyl)sulfonyl}imide, [DoMIM][NTf 2 ] + PEA} in a wide range of temperatures (298.15-348.15 K) and pressures (0.1-40 MPa). The densities at ambient and high pressures are measured to present the physicochemical properties of the ILs used in the process of separation of PEA from aqueous phase. The Tait equation was used for the correlation of density of one-component and two-component systems as a function of mole fraction, temperature, and pressure. The influence of pressure is not significant. These systems exhibit mainly negative molar excess volumes, V E . The solid-liquid phase equilibrium (SLE) of [DoMIM][NTf 2 ] in PEA at atmospheric pressure was measured and compared to the SLE high-pressure results. Additionally, the ternary liquid-liquid phase equilibrium (LLE) at ambient pressure in the {[DoMIM][NTf 2 ] (1) + PEA (2) + water (3)} at temperature T = 308.15 K was investigated. The solubility of water in the [DoMIM][NTf 2 ] is quite high in comparison with that measured by us earlier for ILs ( x 3 = 0.403) at T = 308.15 K, which results in not very successful average selectivity of extraction of PEA from the aqueous phase. The [DoMIM][NTf 2 ] has shown strong interaction with PEA without the immiscibility region. The ternary system revealed Treybal's type phase equilibrium in which two partially miscible binaries ([DoMIM][NTf 2 ] + water) and (PEA + water) exist. From the results of LLE in the ternary system, the selectivity and the solute distribution ratio of separation of water/PEA were calculated and compared

First trimester serum tests for Down's syndrome screening.

PubMed

Alldred, S Kate; Takwoingi, Yemisi; Guo, Boliang; Pennant, Mary; Deeks, Jonathan J; Neilson, James P; Alfirevic, Zarko

2015-11-30

Med 'related articles'. We did not apply a diagnostic test search filter. We also searched reference lists and published review articles.   We included studies in which all women from a given population had one or more index test(s) compared to a reference standard (either chromosomal verification or macroscopic postnatal inspection). Both consecutive series and diagnostic case-control study designs were included. Randomised trials where individuals were randomised to different screening strategies and all verified using a reference standard were also eligible for inclusion. Studies in which test strategies were compared head-to-head either in the same women, or between randomised groups were identified for inclusion in separate comparisons of test strategies. We excluded studies if they included less than five Down's syndrome cases, or more than 20% of participants were not followed up. We extracted data as test positive or test negative results for Down's and non-Down's pregnancies allowing estimation of detection rates (sensitivity) and false positive rates (1-specificity). We performed quality assessment according to QUADAS (Quality Assessment of Diagnostic Accuracy Studies) criteria. We used hierarchical summary ROC meta-analytical methods or random-effects logistic regression methods to analyse test performance and compare test accuracy as appropriate. Analyses of studies allowing direct and indirect comparisons between tests were undertaken. We included 56 studies (reported in 68 publications) involving 204,759 pregnancies (including 2113 with Down's syndrome). Studies were generally of good quality, although differential verification was common with invasive testing of only high-risk pregnancies. We evaluated 78 test combinations formed from combinations of 18 different tests, with or without maternal age; ADAM12 (a disintegrin and metalloprotease), AFP (alpha-fetoprotein), inhibin, PAPP-A (pregnancy-associated plasma protein A, ITA (invasive trophoblast antigen

Kombinierte Hoch-/Niedrig-Dosis-Therapie mit systemischen Glukokor-tikoiden bei schweren Verlaufsformen der Alopecia areata im Kindesalter.

PubMed

Jahn-Bassler, Karin; Bauer, Wolfgang Michael; Karlhofer, Franz; Vossen, Matthias G; Stingl, Georg

2017-01-01

Schwere Verlaufsformen der Alopecia areata (AA) im Kindesalter sind aufgrund limitierter Optionen therapeutisch herausfordernd. Systemische, hochdosierte Glukokortikoide weisen die schnellste Ansprechrate auf, nach dem Absetzen kommt es allerdings zu Rezidiven. Eine längerfristige Hochdosis-Anwendung ist aufgrund der zu erwartenden Nebenwirkungen nicht empfehlenswert. Eine dauerhafte Steroiderhaltungstherapie unterhalb der Cushing-Schwellen-Dosis nach Bolustherapie könnte die Krankheitsaktivität ohne Nebenwirkungen längerfristig unterdrücken. Im Rahmen einer offenen Anwendungsbeobachtung wurden 13 Kinder mit schweren Formen der AA in diese Studie eingeschlossen. Bei sieben Kindern lag eine AA totalis/universalis vor, bei sechs eine multifokale AA mit Befall von mehr als 50 % der Kopfhaut. Das Therapieregime sah eine initiale Prednisolon-Dosierung von 2 mg/kg Körpergeweicht (KG) vor und wurde innerhalb von neun Wochen auf eine Erhaltungsdosierung unter der individuellen Cushing-Schwelle reduziert. Der Nachbeobachtungszeitraum betrug ein bis drei Jahre. Wir beobachteten in 62 % aller Fälle ein komplettes Nachwachsen der Haare. Die mittlere Dauer bis zum Ansprechen lag bei 6,6 Wochen und konnte mit der Erhaltungstherapie über den gesamten Beobachtungszeitraum aufrechterhalten werden. An Nebenwirkungen wurden ausschließlich eine Gewichtszunahme (1-3 kg) bei allen Behandelten sowie eine milde Steroidakne in 23 % der Fälle beobachtet. Die kombinierte Hoch-/Niedrig-Dosis-Therapie mit systemischen Glukokortikoiden mittels Prednisolon zeigte eine hohe, dauerhafte Ansprechrate ohne signifikante Nebenwirkungen. © 2017 Deutsche Dermatologische Gesellschaft (DDG). Published by John Wiley & Sons Ltd.

Multiview Locally Linear Embedding for Effective Medical Image Retrieval

PubMed Central

Shen, Hualei; Tao, Dacheng; Ma, Dianfu

2013-01-01

Content-based medical image retrieval continues to gain attention for its potential to assist radiological image interpretation and decision making. Many approaches have been proposed to improve the performance of medical image retrieval system, among which visual features such as SIFT, LBP, and intensity histogram play a critical role. Typically, these features are concatenated into a long vector to represent medical images, and thus traditional dimension reduction techniques such as locally linear embedding (LLE), principal component analysis (PCA), or laplacian eigenmaps (LE) can be employed to reduce the “curse of dimensionality”. Though these approaches show promising performance for medical image retrieval, the feature-concatenating method ignores the fact that different features have distinct physical meanings. In this paper, we propose a new method called multiview locally linear embedding (MLLE) for medical image retrieval. Following the patch alignment framework, MLLE preserves the geometric structure of the local patch in each feature space according to the LLE criterion. To explore complementary properties among a range of features, MLLE assigns different weights to local patches from different feature spaces. Finally, MLLE employs global coordinate alignment and alternating optimization techniques to learn a smooth low-dimensional embedding from different features. To justify the effectiveness of MLLE for medical image retrieval, we compare it with conventional spectral embedding methods. We conduct experiments on a subset of the IRMA medical image data set. Evaluation results show that MLLE outperforms state-of-the-art dimension reduction methods. PMID:24349277

Simultaneous determination of dextromethorphan, dextrorphan, and guaifenesin in human plasma using semi-automated liquid/liquid extraction and gradient liquid chromatography tandem mass spectrometry.

PubMed

Eichhold, Thomas H; McCauley-Myers, David L; Khambe, Deepa A; Thompson, Gary A; Hoke, Steven H

2007-01-17

A method for the simultaneous determination of dextromethorphan (DEX), dextrorphan (DET), and guaifenesin (GG) in human plasma was developed, validated, and applied to determine plasma concentrations of these compounds in samples from six clinical pharmacokinetic (PK) studies. Semi-automated liquid handling systems were used to perform the majority of the sample manipulation including liquid/liquid extraction (LLE) of the analytes from human plasma. Stable-isotope-labeled analogues were utilized as internal standards (ISTDs) for each analyte to facilitate accurate and precise quantification. Extracts were analyzed using gradient liquid chromatography coupled with tandem mass spectrometry (LC-MS/MS). Use of semi-automated LLE with LC-MS/MS proved to be a very rugged and reliable approach for analysis of more than 6200 clinical study samples. The lower limit of quantification was validated at 0.010, 0.010, and 1.0 ng/mL of plasma for DEX, DET, and GG, respectively. Accuracy and precision of quality control (QC) samples for all three analytes met FDA Guidance criteria of +/-15% for average QC accuracy with coefficients of variation less than 15%. Data from the thorough evaluation of the method during development, validation, and application are presented to characterize selectivity, linearity, over-range sample analysis, accuracy, precision, autosampler carry-over, ruggedness, extraction efficiency, ionization suppression, and stability. Pharmacokinetic data are also provided to illustrate improvements in systemic drug and metabolite concentration-time profiles that were achieved by formulation optimization.

Technische Systeme für den Herzersatz und die Herzunterstützung

NASA Astrophysics Data System (ADS)

Schöb, Reto; Loree, Howard M.

Herzkrankheiten verursachen allein in den Vereinigten Staaten jährlich mehr als 700’000 Todesfälle. Ungefähr 3 Millionen Patienten in den U.S.A. leiden gemäss der American Heart Association (AHA) und dem National Heart, Lung and Blood Institute (NHLBI) an kongestivem Herzversagen (Congestive Heart Failure, CHF), welches eine chronische, sehr entkräftende und degenerative Krankheit ist: Das Herz ist dabei unfähig, hinreichend Blut zu den Organen des Körpers zu pumpen. Über 400’000 Fälle von CHF werden jedes Jahr diagnostiziert. Ähnliche Zahlen werden für Europa und Japan zusammen geschätzt. Basierend auf Daten vom AHA und NHLBI beträgt die fünfjährige Überlebensrate für CHF-Patienten lediglich etwa 50% [1]. 70’000-120’000 dieser Patienten könnten von einer Herzverpflanzung profitieren. 1999 wurden in den USA aber nur 2185 Herztransplantationen durchgeführt während die Warteliste über 4000 Patienten beträgt [2]. Ein akuter Mangel an Spenderherzen und die enormen Kosten (250’000-400’000 USD pro Patient) sind die begrenzenden Faktoren für Herztransplantationen [3]. Dies bedeutet, dass eine riesige Anzahl von Patienten durch ein zuverlässiges und verschleissfreies, nichtthrombotisches, total implantierbares, künstliches Herz gerettet werden könnten. Bis heute jedoch kein derartiges Implantat kommerziell verfügbar.

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

Pierson, Stephen A.; Nacham, Omprakash; Clark, Kevin D.

Magnetic ionic liquids (MILs) are distinguished from traditional ionic liquids (ILs) by the incorporation of a paramagnetic component within their chemical structure. Hydrophobic MILs are novel solvents that can be used in many applications, including liquid–liquid extraction (LLE) and catalysis. Low viscosity and low water solubility are essential features that determine their feasibility in LLE. Here, we synthesized extremely hydrophobic MILs by using transition and rare earth metal hexafluoroacetylacetonate chelated anions paired with the trihexyl(tetradecyl)phosphonium ([P 66614 +]) cation. Hydrophobic MILs exhibiting water solubilities less than 0.01% (v/v) were synthesized in a rapid two-step procedure. Furthermore, the viscosities of themore » MILs are among some of the lowest ever reported for hydrophobic MILs (276.5–927.9 centipoise (cP) at 23.7 °C) dramatically improving the ease of handling these liquids. For the first time, the magnetic properties of MILs possessing hexafluoroacetylacetonate chelated metal anions synthesized in this study are reported using a superconducting quantum interference device (SQUID) magnetometer. We also achieved an effective magnetic moments (μ eff) as high as 9.7 and 7.7 Bohr magnetons (μ B) by incorporating high spin dysprosium and gadolinium ions, respectively, into the anion component of the MIL. The low viscosity, high hydrophobicity, and large magnetic susceptibility of these MILs make them highly attractive and promising solvents for separations and purification, liquid electrochromic materials, catalytic studies, as well as microfluidic applications.« less

Detecting a wide range of environmental contaminants in human blood samples--combining QuEChERS with LC-MS and GC-MS methods.

PubMed

Plassmann, Merle M; Schmidt, Magdalena; Brack, Werner; Krauss, Martin

2015-09-01

Exposure to environmental pollution and consumer products may result in an uptake of chemicals into human tissues. Several studies have reported the presence of diverse environmental contaminants in human blood samples. However, previously developed multi-target methods for the analysis of human blood include a fairly limited amount of compounds stemming from one or two related compound groups. Thus, the sample preparation method QuEChERS (quick easy cheap effective rugged and safe) was tested for the extraction of 64 analytes covering a broad compound domain followed by detection using liquid and gas chromatography coupled to mass spectrometry (LC- and GC-MS). Forty-seven analytes showed absolute recoveries above 70% in the first QuEChERS step, being a simple liquid-liquid extraction (LLE) using acetonitrile and salt. The second QuEChERS step, being a dispersive solid phase extraction, did not result in an overall improvement of recoveries or removal of background signals. Using solely the LLE step, eight analytes could subsequently be detected in human blood samples from the German Environmental Specimen Bank. Using a LC-multiple reaction monitoring (MRM) method with a triple quadrupole instrument, better recoveries were achieved than with an older LC-high-resolution (HR) MS full scan orbitrap instrument, which required a higher concentration factor of the extracts. However, the application of HRMS full scan methods could be used for the detection of additional compounds retrospectively.

Quantification of maltol in Korean ginseng (Panax ginseng) products by high-performance liquid chromatography-diode array detector

PubMed Central

Jeong, Hyun Cheol; Hong, Hee-Do; Kim, Young-Chan; Rhee, Young Kyoung; Choi, Sang Yoon; Kim, Kyung-Tack; Kim, Sung Soo; Lee, Young-Chul; Cho, Chang-Won

2015-01-01

Background: Maltol, as a type of phenolic compounds, is produced by the browning reaction during the high-temperature treatment of ginseng. Thus, maltol can be used as a marker for the quality control of various ginseng products manufactured by high-temperature treatment including red ginseng. For the quantification of maltol in Korean ginseng products, an effective high-performance liquid chromatography-diode array detector (HPLC-DAD) method was developed. Materials and Methods: The HPLC-DAD method for maltol quantification coupled with a liquid-liquid extraction (LLE) method was developed and validated in terms of linearity, precision, and accuracy. An HPLC separation was performed on a C18 column. Results: The LLE methods and HPLC running conditions for maltol quantification were optimized. The calibration curve of the maltol exhibited good linearity (R2 = 1.00). The limit of detection value of maltol was 0.26 μg/mL, and the limit of quantification value was 0.79 μg/mL. The relative standard deviations (RSDs) of the data of the intra- and inter-day experiments were <1.27% and 0.61%, respectively. The results of the recovery test were 101.35–101.75% with an RSD value of 0.21–1.65%. The developed method was applied successfully to quantify the maltol in three ginseng products manufactured by different methods. Conclusion: The results of validation demonstrated that the proposed HPLC-DAD method was useful for the quantification of maltol in various ginseng products. PMID:26246746

Catechin concentrates of garden tea leaves (Camellia sinensis L.): extraction/isolation and evaluation of chemical composition.

PubMed

Gadkari, Pravin Vasantrao; Kadimi, Udaya Sankar; Balaraman, Manohar

2014-11-01

Solid-liquid (SLE) and liquid-liquid (LLE) extraction techniques were applied to extract catechins and caffeine from quick mechanically expelled tea leaf juice (QMETLJ) and freeze-dried (FD)-QMETLJ of Camellia sinensis L. The concentrates obtained were analyzed for total polyphenol content and antioxidant activity (DPPH(•) inhibition, FRAP and phosphomolybdenum assay). Catechins were identified and quantified using HPLC. Overall, 95% (v/v) ethanol was the best solvent system for extracting total polyphenols (355.26 ± 23.68 to 457.89 ± 28.94 g GAE kg(-1) extractable solid yield (ESY)) and antioxidants (DPPH(•) inhibition, 16.97 ± 0.52 to 20.83 ± 3.11%; FRAP, 4.15 ± 0.32 to 6.38 ± 0.57 mmol TE g(-1) ESY; Mo(V) reduction, 2.47 ± 0.19 to 3.84 ± 0.39 mmol AAE g(-1) ESY) from FD-QMETLJ. Similarly, in LLE, ethyl acetate showed the best results for recovering polyphenols (960.52 ± 7.89 g GAE kg(-1) ESY) and antioxidants (DPPH(•) inhibition, 42.39 ± 0.91%; FRAP, 11.39 ± 0.83 mmol TE g(-1) ESY; Mo(V) reduction, 6.71 ± 1.14 mmol AAE g(-1) ESY) from QMETLJ. It was found that 95% ethanol can be used to increase the total polyphenols and antioxidants in extracts from FD-QMETLJ, while ethyl acetate can be effectively employed for concentrating catechins from QMETLJ. © 2014 Society of Chemical Industry.

Career Anchors: Understanding Differences Among Demographic Groups at the Naval Postgraduate School

DTIC Science & Technology

2001-12-01

r C ha lle ng e C re at iv ity Id eo lo gy Id en tit y W ill in gn es s...to L ea ve C ar ee r Sa tis fa ct io n Technical 1.00 0.14 0.01 -0.10 -0.08 -0.08 -0.10 0.17 0.10 0.12 -0.04 Security 1.00 0.18 0.31 0.10...Technological Changes in Office Jobs.” Changing Nature of Work: 173-208. San Francisco: Jossey-Bass. 6. Deci, E . L. with R . Flaste.

Fort Sill Oklahoma/Post Field. Revised Uniform Summary of Surface Weather Observations

DTIC Science & Technology

1975-06-23

TEMPERATURE DEPRESSIO (F) TOTAL TOTAL (F) 0 t .2 3-4 5 6 7 - ,9 I 1 1 1 .1 516 17 -18119 -20 21 22 23 -2412S.26 27 -2 9 3, 1i ’’WB ~ ub e ub~ we.. 2/ 1...Temp WET BULB TEMPERATURE DEPRESSIO (F) TOTAL _ TOTAL F)/ 03 1 .2 3C 4, 0 1-1 I3- 5, 6 1 .1 9-20 2 2_3- 5-." 26 27 -28 D.B W .2 0 31b We B lle on 90

Elucidation of Transport Mechanism of Paeoniflorin and the Influence of Ligustilide, Senkyunolide I and Senkyunolide A on Paeoniflorin Transport through Mdck-Mdr1 Cells as Blood-Brain Barrier in Vitro Model.

PubMed

Hu, Peng-Yi; Liu, Dan; Zheng, Qin; Wu, Qing; Tang, Yu; Yang, Ming

2016-03-02

The objectives of the present investigation were to: (1) elucidate the transport mechanism of paeoniflorin (PF) across MDCK-MDR1 monolayers; and (2) evaluate the effect of ligustilide (LIG), senkyunolide I (SENI) and senkyunolide A (SENA) on the transport of PF through blood-brain barrier so as to explore the enhancement mechanism. Transport studies of PF were performed in both directions, from apical to basolateral side (A→B) and from basolateral to apical sides (B→A). Drug concentrations were analyzed by LC-MS/MS. PF showed relatively poor absorption in MDCK-MDR1 cells, apparent permeability coefficients (Papp) ranging from 0.587 × 10(-6) to 0.705 × 10(-6) cm/s. In vitro experiments showed that the transport of PF in both directions was concentration dependent and not saturable. The B→A/A→B permeability ER of PF was more than 2 in the MDCK-MDR1 cells, which indicated that the transport mechanism of PF might be passive diffusion as the dominating process with the active transportation mediated mechanism involved. The increased Papp of PF in A→B direction by EDTA-Na₂ suggested that PF was absorbed via the paracellular route. The P-gp inhibitor verapamil could significantly increase the transport of PF in A→B direction, and ER decreased from 2.210 to 0.690, which indicated that PF was P-gp substance. The transport of PF in A→B direction significantly increased when co-administrated with increasing concentrations of LIG, SENI and SENA. An increased cellular accumulation of Rho 123 and Western blot analysis indicated that LIG, SENI and SENA had increased the transport of PF in the BBB models attribute to down-regulate P-gp expression. A decrease in transepithelial electrical resistance (TEER) during the permeation experiment can be explained by the modulation and opening of the tight junctions caused by the permeation enhancer LIG, SENI and SENA.

S-protected thiolated chitosan for oral delivery of hydrophilic macromolecules: evaluation of permeation enhancing and efflux pump inhibitory properties.

PubMed

Dünnhaupt, Sarah; Barthelmes, Jan; Rahmat, Deni; Leithner, Katharina; Thurner, Clemens C; Friedl, Heike; Bernkop-Schnürch, Andreas

2012-05-07

The objective of this study was the investigation of permeation enhancing and P-glycoprotein (P-gp) inhibition effects of a novel thiolated chitosan, the so-named S-protected thiolated chitosan. Mediated by a carbodiimide, increasing amounts of thioglycolic acid (TGA) were covalently bound to chitosan (CS) in the first step of modification. In the second step, these thiol groups of thiolated chitosan were protected by disulfide bond formation with the thiolated aromatic residue 6-mercaptonicotinamide (6-MNA). Mucoadhesive properties of all conjugates were evaluated in vitro on porcine intestinal mucosa based on tensile strength investigations. Permeation enhancing effects were evaluated ex vivo using rat intestinal mucosa and in vitro via Caco-2 cells using the hydrophilic macromolecule FD(4) as the model drug. Caco-2 cells were further used to show P-gp inhibition effects by using Rho-123 as P-gp substrate. Apparent permeability coefficients (P(app)) were calculated and compared to values obtained from each buffer control. Three different thiolated chitosans were generated in the first step of modification, which displayed increasing amounts of covalently attached free thiol groups on the polymer backbone. In the second modification step, more than 50% of these free thiol groups were covalently linked with 6-MNA. Within 3 h of permeation studies on excised rat intestine, P(app) values of all S-protected chitosans were at least 1.3-fold higher compared to those of corresponding thiomers and more than twice as high as that of unmodified chitosan. Additional permeation studies on Caco-2 cells confirmed these results. Because of the chemical modification and higher amount of reactive thiol groups, all S-protected thiolated chitosans exhibit at least 1.4-fold pronounced P-gp inhibition effects in contrast to their corresponding thiomers. These features approve S-protected thiolated chitosan as a promising excipient for various drug delivery systems providing improved

Transdermal delivery of curcumin via microemulsion.

PubMed

Sintov, Amnon C

2015-03-15

The objective of this study was to evaluate the transdermal delivery potential of a new curcumin-containing microemulsion system. Three series of experiments were carried out to comprehend the system characteristics: (a) examining the influence of water content on curcumin permeation, (b) studying the effect of curcumin loading on its permeability, and (c) assessing the contribution of the vesicular nature of the microemulsion on permeability. The skin permeability of curcumin from microemulsions, which contained 5%, 10%, and 20% of water content (1% curcumin), was measured in vitro using excised rat skin. It has been shown that the permeability coefficient of CUR in a formulation containing 10% aqueous phase (ME-10) was twofold higher than the values obtained for formulations with 5% and 20% water (Papp=0.116 × 10(-3)± 0.052 × 10(-3)vs. 0.043 × 10(-3)± 0.022 × 10(-3) and 0.047 × 10(-3)± 0.025 × 10(-3)cm/h, respectively. A reasonable explanation for this phenomenon may be the reduction of both droplet size and droplets' concentration in the microemulsion as the aqueous phase decreased from 20% to 5%. It has also been shown that a linear correlation exists between the decrease in droplet size and the increase of curcumin loading in the microemulsion. In addition, it has been demonstrated that a micellar system, S/O-mix, and a plain solution of curcumin resulted in a significantly lower curcumin permeation relative to that presented by the microemulsion, Papp=0.018 × 10(-3)± 0.011 × 10(-3), 0.005 × 10(-3)± 0.002 × 10(-3), and 0.002 × 10(-3)± 0.000 × 10(-3)cm/h, respectively, vs. 0.110 × 10(-3)± 0.021 × 10(-3)cm/h for the microemulsion. The enhancement ratio (ER=Jss-ME/Jss-solution) of CUR permeated via 1% loaded microemulsion was 55. Copyright © 2015 Elsevier B.V. All rights reserved.

Cell-free fetal DNA screening in the USA: a cost analysis of screening strategies.

PubMed

Evans, M I; Sonek, J D; Hallahan, T W; Krantz, D A

2015-01-01

To determine whether implementation of primary cell-free fetal DNA (cffDNA) screening would be cost-effective in the USA and to evaluate potential lower-cost alternatives. Three strategies to screen for trisomy 21 were evaluated using decision tree analysis: 1) a primary strategy in which cffDNA screening was offered to all patients, 2) a contingent strategy in which cffDNA screening was offered only to patients who were high risk on traditional first-trimester screening and 3) a hybrid strategy in which cffDNA screening was offered to all patients ≥ 35 years of age and only to patients < 35 years who were high risk after first-trimester screening. Four traditional screening protocols were evaluated, each assessing nuchal translucency (NT) and pregnancy-associated plasma protein-A (PAPP-A) along with either free or total beta-human chorionic gonadotropin (β-hCG), with or without nasal bone (NB) assessment. Utilizing a primary cffDNA screening strategy, the cost per patient was 1017 US$. With a traditional screening protocol using free β-hCG, PAPP-A and NT assessment as part of a hybrid screening strategy, a contingent strategy with a 1/300 cut-off and a contingent strategy with a 1/1000 cut-off, the cost per patient was 474, 430 and 409 US$, respectively. Findings were similar using the other traditional screening protocols. Marginal cost per viable case detected for the primary screening strategy as compared to the other strategies was 3-16 times greater than the cost of care for a missed case. Primary cffDNA screening is not currently a cost-effective strategy. The contingent strategy was the lowest-cost alternative, especially with a risk cut-off of 1/1000. The hybrid strategy, although less costly than primary cffDNA screening, was more costly than the contingent strategy. Copyright © 2014 ISUOG. Published by John Wiley & Sons Ltd.

Fixed-dose combination orally disintegrating tablets to treat cardiovascular disease: formulation, in vitro characterization and physiologically based pharmacokinetic modeling to assess bioavailability

PubMed Central

Dennison, Thomas J; Smith, Julian C; Badhan, Raj K; Mohammed, Afzal R

2017-01-01

Cardiovascular disease (CVD) is the leading cause of death among men and women worldwide. In CVD, hypertension and dyslipidemia commonly coexist and are managed through coadministration of amlodipine and atorvastatin, respectively. The case for fixed-dose combination (FDC) oral dosage forms and orally disintegrating tablet (ODT) technology to enhance outcomes and compliance is strong. This work follows the development and characterization of single and FDC ODTs containing amlodipine and atorvastatin, followed by bioequivalence comparison between these single and FDC formulations, using in vitro dissolution and Caco-2 apparent permeability (Papp) and in silico physiologically based pharmacokinetic modeling approaches. ODTs containing amlodipine (5 mg) and atorvastatin (10 mg) either alone or in combination rapidly disintegrated (<30 s) while displaying a radial crushing strength in excess of 100 N and friability ≤1%. In vitro dissolution test was performed in fasted and fed-state simulated intestinal fluid (FeSSIF) and analyzed using high-performance liquid chromatography. Dissolution profiles for single and FDC ODTs were compared using US FDA recommended difference (f1) and similarity (f2) factor testing for bioequivalence. In all cases, there was no difference in active pharmaceutical ingredient dissolution between single or FDC ODTs, with the exception of amlodipine in FeSSIF. Pharmacokinetic clinical trial simulations were conducted using Simcyp (Version 14), incorporating Papp and dissolution data. Simulated clinical trials in healthy volunteers showed no difference in bioavailability based on pharmacokinetic parameters between single and combination doses with either active pharmaceutical ingredient. An increase in Cmax and AUC for atorvastatin in fed subjects was attributed to extended transit along the gut lumen and reduced atorvastatin metabolism due to lower CYP3A4 expression at more distal small intestine absorption sites. The results demonstrated

Accuracy of Down syndrome risks produced in a first-trimester screening programme incorporating fetal nuchal translucency thickness and maternal serum biochemistry.

PubMed

Spencer, Kevin

2002-03-01

Over the past three years approximately 12 000 women have been screened in the first trimester through our OSCAR programme, which utilizes fetal NT and maternal serum free beta-hCG and PAPP-A. During this time 30 cases of Down syndrome were identified either prenatally or postnatally. Using an established procedure the accuracy of predicted risk for Down syndrome was assessed in a population of 30 cases of Down syndrome and 11 758 unaffected pregnancies. The correlation between predicted risk and prevalence of Down syndrome was very high (r=0.9995). It is concluded that risks produced by the Fetal Medicine Foundation combined risk algorithm agree very closely with Down syndrome prevalence and can be used with confidence when counselling women of their risk. Copyright 2002 John Wiley & Sons, Ltd.

Effectiveness of Program Visualization: A Case Study with the ViLLE Tool

ERIC Educational Resources Information Center

Rajala, Teemu; Laakso, Mikko-Jussi; Kaila, Erkki; Salakoski, Tapio

2008-01-01

Program visualization is one of the various methods developed over the years to aid novices with their difficulties in learning to program. It consists of different graphical--often animated--and textual objects, visualizing the execution of programs. The aim of program visualization is to enhance students' understanding of different areas of…

Liquid chromatography-negative ion atmospheric pressure photoionization tandem mass spectrometry for the determination of brominated flame retardants in environmental water and industrial effluents.

PubMed

Bacaloni, Alessandro; Callipo, Luciano; Corradini, Eleonora; Giansanti, Piero; Gubbiotti, Riccardo; Samperi, Roberto; Laganà, Aldo

2009-09-04

We describe the development of a liquid chromatography with negative-ion atmospheric pressure photoionization tandem mass spectrometric (LC/NI-APPI/MS/MS) method for the simultaneous determination of tetrabromobisphenol A (TBBP-A) and five polybrominated diphenyl ethers (BDE-47, BDE-99, BDE-100, BDE-153 and BDE-154) in water. A mobile phase methanol/acetone/water was used, where acetone acts also as dopant. NI-APPI produced precursor ions corresponding to [M-H](-) for TBBP-A, [M-Br+O](-), and [M-2Br+O](-) for the BDE congeners studied. Each compound was quantified operating in multiple reaction monitoring mode. Linearity was observed in the range 0.025-10 ng injected for all compounds. Coefficients of determination R(2) ranged from 0.9934 to 0.9982. BDEs were poorly retained by solid-phase extraction (SPE) from river water and sewage treatment plant effluent, thus liquid-liquid extraction (LLE) by n-hexane should be used for these samples. The recoveries of TBBP-A and PBDEs from tap water (SPE), river water and industrial wastewater (LLE) were in the range of 81-88%, 78-92%, and 43-99%, respectively, with relative standard deviations below 17%. The limits of detection, based on signal-to-noise ratio of 3, ranged from 0.004 to 0.1 ng injected, and method quantification limits were 0.2-3.3 ng L(-1) but BDE47 (20.3 ng L(-1)). Only TBBP-A was found in a treated industrial sewage at 4 ng L(-1), while BDE-99 and BDE-100 were detected on suspended solids.

Reduction of time-averaged irradiation speckle nonuniformity in laser-driven plasmas due to target ablation

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

Epstein, R.

1997-09-01

In inertial confinement fusion (ICF) experiments, irradiation uniformity is improved by passing laser beams through distributed phase plates (DPPs), which produce focused intensity profiles with well-controlled, reproducible envelopes modulated by fine random speckle. [C. B. Burckhardt, Appl. Opt. {bold 9}, 695 (1970); Y. Kato and K. Mima, Appl. Phys. B {bold 29}, 186 (1982); Y. Kato {ital et al.}, Phys. Rev. Lett. {bold 53}, 1057 (1984); Laboratory for Laser Energetics LLE Review 33, NTIS Document No. DOE/DP/40200-65, 1987 (unpublished), p. 1; Laboratory for Laser Energetics LLE Review 63, NTIS Document No. DOE/SF/19460-91, 1995 (unpublished), p. 1.] A uniformly ablating plasmamore » atmosphere acts to reduce the contribution of the speckle to the time-averaged irradiation nonuniformity by causing the intensity distribution to move relative to the absorption layer of the plasma. This occurs most directly as the absorption layer in the plasma moves with the ablation-driven flow, but it is shown that the effect of the accumulating ablated plasma on the phase of the laser light also makes a quantitatively significant contribution. Analytical results are obtained using the paraxial approximation applied to the beam propagation, and a simple statistical model is assumed for the properties of DPPs. The reduction in the time-averaged spatial spectrum of the speckle due to these effects is shown to be quantitatively significant within time intervals characteristic of atmospheric hydrodynamics under typical ICF irradiation intensities. {copyright} {ital 1997 American Institute of Physics.}« less

Study of 3-Ethylamino-but-2-enoic acid phenylamide as a new ligand for preconcentration of lanthanides from aqueous media by liquid-liquid extraction prior to ICP-MS analysis.

PubMed

Varbanova, Evelina K; Angelov, Plamen A; Stefanova, Violeta M

2016-11-01

In the present work the potential of a new ligand 3-Ethylamino-but-2-enoic acid phenylamide (representing the class of enaminones) for selective preconcentration of lanthanides (La, Ce, Eu, Gd and Er) from aqueous medium is examined. Liquid-liquid extraction parameters, such as pH of the water phase, type and volume of organic solvent, quantity of ligand and reaction time are optimized on model solutions. Recovery of lanthanides by re-extraction with nitric acid makes the LLE procedure compatible with Inductively Coupled Plasma Mass Spectrometry. Spectral and non-spectral interferences are studied. Two isotopes per element are measured (with exception of La) for dynamic evaluation of the potential risk of spectral interference in variable real samples. The selectivity of complex formation reaction towards concomitant alkali and alkali-earth elements eliminates the interferences from sample matrix. Subjecting the standards to the optimized extraction procedure in combination with Re as internal standard is recommended as calibration strategy. The accuracy of developed method is approved by analysis of CRM Bush branches and leaves (NCS DC 73348) and recovery of spiked water and plant samples. The method's limits of detection for both studied objects are in the ranges from 0.2 ((158)Gd) to 3.7 ((139)La) ngl(-1) and 0.02 ((158)Gd) to 0.37((139)La) ngg(-1) for waters and plants respectively. The studied compound is an effective new ligand for preconcentration/separation of lanthanides from aqueous medium by LLE and subsequent determination by ICP-MS. Copyright © 2016 Elsevier B.V. All rights reserved.

Determination of ten monohydroxylated polycyclic aromatic hydrocarbons by liquid-liquid extraction and liquid chromatography/tandem mass spectrometry.

PubMed

Fan, Ruifang; Ramage, Robert; Wang, Dongli; Zhou, Junqiang; She, Jianwen

2012-05-15

The aim of this study is to develop and validate an analytical method for the quantitation of ten urinary monohydroxylated polycyclic aromatic hydrocarbons (OH-PAHs) through high pressure liquid chromatography/tandem mass spectrometry (HPLC/MS/MS). After enzymatic deconjugation, urine samples were extracted by liquid-liquid extraction (LLE) and OH-PAHs were analyzed by HPLC/MS/MS operated in negative electrospray ionization (ESI) and multiple reaction monitoring (MRM) mode. LLE was conducted with the solvent mixture of pentane and toluene, which reduced the matrix interferences and enhanced the method sensitivity significantly. Deuterated and (13)C-labeled analogs are used as internal standards. Calibration curves of all target analytes shows favorable linearity within the concentration range of 5.9-15,000.0 ng/L for different OH-PAHs with the regression coefficients above 0.993. The limits of detection (LODs) in pooled urine ranged from 1.72 to 17.47 ng/L, which were much lower than those obtained by a gas chromatography/high resolution mass spectrometry (GC/HRMS) method. The method shows satisfactory accuracy and precision when analyzing three different levels of OH-PAHs spiked in pooled urine. Except for 1-hydroxynaphthalene, recoveries of other OH-PAHs were in the range of 100 ± 20% with a variation coefficient of less than 13%. The measurement of OH-PAHs from a QC sample of the Centers for Disease Control and Prevention (CDC) generated results close to the values measured by CDC. This method has been successfully employed in the California Biomonitoring Program. Published by Elsevier B.V.

Detection and quantification of ionophore antibiotics in runoff, soil and poultry litter.

PubMed

Sun, Peizhe; Barmaz, Delphine; Cabrera, Miguel L; Pavlostathis, Spyros G; Huang, Ching-Hua

2013-10-18

Ionophore antibiotics (IPAs) are widely used as coccidiostats in poultry and other livestock industries to promote growth and prevent infections. Because most of the ingested IPAs are excreted in poultry litter, which is primarily applied as grassland fertilizer, a significant amount of IPAs can be released into the litter-soil-water environment. A robust analytical method has been developed to quantify IPAs (monensin (MON), salinomycin (SAL) and narasin (NAR)) in complex environmental compartments including surface runoff, soil and poultry litter, with success to minimize matrix interference. The method for water samples involves solid-phase extraction (SPE) followed by liquid-liquid extraction (LLE) post-clean up steps. The method for solid samples involves bi-solvent LLE. IPAs were detected by HPLC-MS, with optimized parameters to achieve the highest sensitivity. Nigericin (NIG), an IPA not used in livestock industry, is successfully applied and validated as a surrogate standard. The method recoveries were at 92-95% and 81-85% in runoff samples from unfertilized and litter-fertilized fields, respectively. For solids, the method recoveries were at 93-99% in soils, and 79-83% in poultry litter samples. SAL was detected at up to 22mg/kg and MON and NAR at up to 4mg/kg in broiler litter from different farms. Up to 183μg/kg of MON was detected in litter-fertilized soils. All three IPAs were detected in the rainfall runoff from litter-fertilized lands at concentrations up to 9μg/L. Copyright © 2013 Elsevier B.V. All rights reserved.

Relativistic Electron Beams, Forward Thomson Scattering, and ``Raman'' Scattering

NASA Astrophysics Data System (ADS)

Simon, A.

1999-11-01

Experiments at LLE (see abstract by D. Hicks at this meeting) show that surprisingly high potentials (+0.5 to 2.0 MV) develop in plasmas irradiated by high-energy lasers. The highly conducting plasma will be a near equipotential and should attract return-current electrons in a radial beam-like distribution, especially in the outer low-density regions. This will initiate the BOT instability, creating large plasma waves with phase velocities close to c. Coherent Thomson scattering of the interaction beam from these waves must occur primarily in the forward direction. This will appear to be ``backward SRS'' upon reflection from a critical surface. We will show that the resulting spectrum is fairly broad and at short wavelengths. Collisional absorption of the scattered EM wave limits the reflectivity to low values (depending on the density scale length). Thus, a distinct difference exists between the spectrum for thick targets (nc surface present) and thin targets (gasbags, etc., from which primarily a narrow absolute-SRS backward emission occurs, at the peak density). The thick-target, reflected-wave angular distribution will be concentrated in the backward direction. The corresponding plasma-wave k-vector will be a fraction of k_0. The variation of the spectrum with potential and angle will be discussed. Comparison will be made with recent results at LLE and LLNL. This work was supported by the U.S. Department of Energy Office of Inertial Confinement Fusion under Cooperative Agreement No. DE-FC03-92SF19460, UR, and NYSERDA.

Report on the B-Fields at NIF Workshop Held at LLNL October 12-13, 2015

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

Fournier, K. B.; Moody, J. D.

2015-12-13

A national ICF laboratory workshop on requirements for a magnetized target capability on NIF was held by NIF at LLNL on October 12 and 13, attended by experts from LLNL, SNL, LLE, LANL, GA, and NRL. Advocates for indirect drive (LLNL), magnetic (Z) drive (SNL), polar direct drive (LLE), and basic science needing applied B (many institutions) presented and discussed requirements for the magnetized target capabilities they would like to see. 30T capability was most frequently requested. A phased operation increasing the field in steps experimentally can be envisioned. The NIF management will take the inputs from the scientific communitymore » represented at the workshop and recommend pulse-powered magnet parameters for NIF that best meet the collective user requests. In parallel, LLNL will continue investigating magnets for future generations that might be powered by compact laser-B-field generators (Moody, Fujioka, Santos, Woolsey, Pollock). The NIF facility engineers will start to analyze compatibility of the recommended pulsed magnet parameters (size, field, rise time, materials) with NIF chamber constraints, diagnostic access, and final optics protection against debris in FY16. The objective of this assessment will be to develop a schedule for achieving an initial Bfield capability. Based on an initial assessment, room temperature magnetized gas capsules will be fielded on NIF first. Magnetized cryo-ice-layered targets will take longer (more compatibility issues). Magnetized wetted foam DT targets (Olson) may have somewhat fewer compatibility issues making them a more likely choice for the first cryo-ice-layered target fielded with applied Bz.« less

Grundlegende Steuerungsverfahren im heterogenen Logistiknetz mit Kanban

NASA Astrophysics Data System (ADS)

Dickmann, Eva; Dickmann, Philipp; Lödding, Hermann; Möller, Niklas; Rücker, Thomas; Schneider, Herfried M.; Zäh, Michael F.

In vielen Unternehmen werden heterogene (verschiedene) Steuerungen in einem abgestimmten Konzept kombiniert. Je nach Anwendungsfall und Rahmenbedingungen werden Kombinationen allgemein bekannter Steuerungen oder Steuerungsvarianten gemischt eingesetzt, um eine optimale Steuerung für unterschiedliche Fälle zu erreichen. Hierbei stehen neben den bekannten und weit verbreiteten Methoden, wie Material Requirements Planning (MRP) oder Kanban, auch weniger bekannte oder neue Methoden zur Auswahl, wie die Produktionssteuerung mit dezentraler, bestandsorientierter Fertigungsregelung (DBF). Kanban ist ein simples und effizientes Steuerungskonzept, das in der klassischen Form für spezifische einfache Anwendungsfälle umsetzbar ist. Hochentwickelte Steuerungsalgorithmen können helfen, komplexe Abläufe optimal abzubilden. Mit einer grundlegenden Vereinfachung der Abläufe kann allerdings in vielen Fällen ein wesentlich stärkerer und umfassender Verbesserungseffekt erzielt werden. Die wesentliche Fragestellung sollte folglich lauten: Warum ist der Ablauf nicht mit einer einfachen Steuerung wie Kanban abzubilden? Um die Vorteile des Konzepts auch in untypischen Bereichen anwenden zu können, sind jedoch verschiedene Varianten oder Kanban-ähnliche Steuerungsmethoden entstanden. Darüber hinaus sind in der Praxis hybride Steuerungen im Einsatz, welche so kombiniert werden, dass die Zusammensetzung anspruchsvolle Eigenschaftsbilder noch exakt abbildet. In der Praxis basieren die Steuerungsentscheidungen nur zu einem kleinen Teil auf den eigentlichen Steuerungsalgorithmen, wie sie uns das MRP-System zur Verfügung stellt. Moderne Steuerungswelten" schließen alle relevanten Informationsquellen in eine heterogene Entscheidungsmatrix mit ein. Letztlich zählt nicht, ob die Entscheidung auf den Informationen aus dem MRP-System oder auf Softfacts basierend getroffen wurde, sondern nur, ob die Entscheidung erfolgreich war.

Light Emitting Diodes for Fiber Optic Communications.

DTIC Science & Technology

1981-03-31

asC.3~~ in.(c)- above and do- (1) pcait by volu.3 of dicst.iLle =zto.- Pazo 10 .61Edd, tcxcopt colvonts used cha-l bo: * ( a ) Methyl. alcohbl I7or 04...AD £101 480 LASER DIODE LABS INC NEW BRUNSWICK NJ / 1 / L I GT EMITTING DIODES FOR FIBER OPTIC COWMICATIONS.Cul AR, at A GENNARO DAARO-76-C-813 NA 1...PRArrcmA. P . 1"UNISPE-D TO DDC CONTAINE A II&~-’llryBE v., R OF :AO , MflG DO 9W CORADCOM U S ARMY COMMUNICATIONS RESEARCH 9 DEVELOPMENT COMMAND

Probleme aus der Physik

NASA Astrophysics Data System (ADS)

Vogel, Helmut

Das beliebte Arbeitsbuch "Probleme aus der Physik" bietet nun auch zur 17. Auflage von Gerthsen Vogel "Physik" (ISBN 3-540-56638-4) mit über 1150 gelösten Aufgaben aus der Physik und ihren Anwendungen in Technik, Astrophysik, Geound Biowissenschaften eine Fülle an Material zum Üben und Weiterlernen, zur Prüfungsvorbereitung und zum Selbststudium. Neu hinzugekommen ist ein Kapitel zur nichtlinearen Dynamik. Aufgaben aller Schwierigkeitsgrade machen "Probleme aus der Physik" unentbehrlich für Studenten der Physik im Haupt- und Nebenfach; Schüler der Leistungskurse Physik finden hier eine hervorragende Ergänzung.

One-step liquid-liquid extraction of cocaine from urine samples for gas chromatographic analysis.

PubMed

Farina, Marcelo; Yonamine, Maurício; Silva, Ovandir A

2002-07-17

An improved technique for cocaine extraction from urine samples for gas chromatographic (GC) analysis is described. Employing a simple liquid-liquid extraction (LLE) of cocaine with a mixture of ethyl ether:isopropanol (9:1) the method presents a mean recovery of 74.49%. Limit of detection (LOD) and limit of quantification (LOQ) were 5 and 20 ng/ml, respectively. The method is highly precise (coefficient of variation (CV) <8%) and linear from 20 to 2000 ng/ml. It can he applied to detect the presence of cocaine in urine as a marker of its recent use in drug abuse treatment protocols.

An Examination of Cleaning and Gas Freeing Costs of Oil Tankers in Government Service

DTIC Science & Technology

1994-03-01

showing age and wear as exhibited by pervasive rust and peeling of tank coatings. (The author observed at least two different color coatings in...quality and environmental directives. MSC Sealift Class tankers, in particular, are showing their age as evidenced by the declining material condition of...acII5 gs aIIc se e.lleSais4% a a t soo • s a s* f *b Ill lb.a a 4 Ioll IC * I°assl aO~ at 1.1.o Mo eill, a, 44. ft sall ages e gg@i sae $"ef ispe Oe? s

Geographic List of Prime Contract Awards. Oct 1992-Sep 1993. (Addison, Alabama-Yell County, Arkansas). Part 1

DTIC Science & Technology

1994-03-01

LL. LLj. to 00 co 9 L LL a.. OLG. LLL. . LL.LA.I ND 1 40£’ I) W Ia o Go LA.. W OHP IV 4~ Oru IY 0i’ 00 4) NNN 4~ 0) 0£O ) O V a o G CV)) M£’ IT ( Mm...1I000 0 000 0000000 0 000 000 0000 M N L. 1 00 110 0000oo 000000000 00o 0000 C0000 W0000000 LUJ Ka I 00W KaRL L A.. MEM M~nE)E mmmmmm LL.E M .E()E m MM

Probabilistic Structural Analysis Methods (PSAM) for select space propulsion system components

NASA Technical Reports Server (NTRS)

1991-01-01

The fourth year of technical developments on the Numerical Evaluation of Stochastic Structures Under Stress (NESSUS) system for Probabilistic Structural Analysis Methods is summarized. The effort focused on the continued expansion of the Probabilistic Finite Element Method (PFEM) code, the implementation of the Probabilistic Boundary Element Method (PBEM), and the implementation of the Probabilistic Approximate Methods (PAppM) code. The principal focus for the PFEM code is the addition of a multilevel structural dynamics capability. The strategy includes probabilistic loads, treatment of material, geometry uncertainty, and full probabilistic variables. Enhancements are included for the Fast Probability Integration (FPI) algorithms and the addition of Monte Carlo simulation as an alternate. Work on the expert system and boundary element developments continues. The enhanced capability in the computer codes is validated by applications to a turbine blade and to an oxidizer duct.

Propylene glycol-linked amino acid/dipeptide diester prodrugs of oleanolic acid for PepT1-mediated transport: synthesis, intestinal permeability, and pharmacokinetics.

PubMed

Cao, Feng; Gao, Yahan; Wang, Meng; Fang, Lei; Ping, Qineng

2013-04-01

In our previous studies, ethylene glycol-linked amino acid diester prodrugs of oleanolic acid (OA), a Biopharmaceutics Classification System (BCS) class IV drug, designed to target peptide transporter 1 (PepT1) have been synthesized and evaluated. Unlike ethylene glycol, propylene glycol is of very low toxicity in vivo. In this study, propylene glycol was used as a linker to further compare the effect of the type of linker on the stability, permeability, affinity, and bioavailability of the prodrugs of OA. Seven diester prodrugs with amino acid/dipeptide promoieties containing L-Val ester (7a), L-Phe ester (7b), L-Ile ester (7c), D-Val-L-Val ester (9a), L-Val-L-Val ester (9b), L-Ala-L-Val ester (9c), and L-Ala-L-Ile ester (9d) were designed and successfully synthesized. In situ rat single-pass intestinal perfusion (SPIP) model was performed to screen the effective permeability (P(eff)) of the prodrugs. P(eff) of 7a, 7b, 7c, 9a, 9b, 9c, and 9d (6.7-fold, 2.4-fold, 1.24-fold, 1.22-fold, 4.15-fold, 2.2-fold, and 1.4-fold, respectively) in 2-(N-morpholino)ethanesulfonic acid buffer (MES) with pH 6.0 showed significant increase compared to that of OA (p < 0.01). In hydroxyethyl piperazine ethanesulfonic acid buffer (HEPES) of pH 7.4, except for 7c, 9a, and 9d, P(eff) of the other prodrugs containing 7a (5.2-fold), 7b (2.0-fold), 9b (3.1-fold), and 9c (1.7-fold) exhibited significantly higher values than that of OA (p < 0.01). In inhibition studies with glycyl-sarcosine (Gly-Sar, a typical substrate of PepT1), P(eff) of 7a (5.2-fold), 7b (2.0-fold), 9b (3.1-fold), and 9c (2.3-fold) had significantly reduced values (p < 0.01). Compared to the apparent permeability coefficient (P(app)) of OA with Caco-2 cell monolayer, significant enhancement of the P(app) of 7a (5.27-fold), 9b (3.31-fold), 9a (2.26-fold), 7b (2.10-fold), 7c (2.03-fold), 9c (1.87-fold), and 9d (1.39-fold) was also observed (p < 0.01). Inhibition studies with Gly-Sar (1 mM) showed that P(app) of 7a, 9b, and

Zeitlicher Verlauf der avaskulären Nekrose des Hüftkopfes bei Patienten mit Pemphigus vulgaris.

PubMed

Balighi, Kamran; Daneshpazhooh, Maryam; Aghazadeh, Nessa; Saeidi, Vahide; Shahpouri, Farzam; Hejazi, Pardis; Chams-Davatchi, Cheyda

2016-10-01

Pemphigus vulgaris (PV) wird in der Regel mit systemischen Corticosteroiden und Immunsuppressiva behandelt. Avaskuläre Nekrose (AVN) des Hüftkopfes ist eine gut bekannte schwerere Komplikation einer Corticosteroid-Therapie. Die Charakteristika dieser schweren Komplikation bei PV sind nach wie vor unbekannt. Nicht kontrollierte, retrospektive Untersuchung aller PV-bedingten AVN-Fälle, die in einer iranischen Klinik für bullöse Autoimmunerkrankungen zwischen 1985 und 2013 diagnostiziert wurden. Anhand der Krankenakten von 2321 untersuchten PV-Patienten wurden 45 Fälle (1,93 %) von femoraler AVN identifiziert. Dreißig davon waren Männer. Das mittlere Alter bei der Diagnose der AVN betrug 47,4 ± 14,2 Jahre. Der mittlere Zeitraum zwischen der Diagnose des PV und dem Einsetzen der AVN lag bei 25,3 ± 18,3 Monaten. Mit Ausnahme von acht Fällen (17,8 %) setzte die AVN bei der Mehrheit der Patienten innerhalb von drei Jahren nach Diagnose des PV ein. Die mittlere kumulative Dosis von Prednisolon bei Patienten mit AVN betrug 13.115,8 ± 7041,1 mg. Zwischen der Prednisolon-Gesamtdosis und dem Zeitraum bis zum Einsetzen der AVN bestand eine starke Korrelation (p = 0,001). Bei Patienten mit Alendronateinnahme in der Vorgeschichte war dieser Zeitraum signifikant kürzer (p = 0,01). Die AVN ist eine schwere Komplikation einer Corticosteroid-Behandlung bei Patienten mit PV. Sie wird bei 2 % der Patienten beobachtet und tritt vor allem in den ersten drei Behandlungsjahren auf. Bei Patienten, die höhere Dosen von Prednisolon erhalten, setzt die AVN tendenziell früher ein. © 2016 Deutsche Dermatologische Gesellschaft (DDG). Published by John Wiley & Sons Ltd.

Isolation of atropine and scopolamine from plant material using liquid-liquid extraction and EXtrelut® columns.

PubMed

Śramska, Paula; Maciejka, Artur; Topolewska, Anna; Stepnowski, Piotr; Haliński, Łukasz P

2017-02-01

Tropane alkaloids are toxic secondary metabolites produced by Solanaceae plants. Among them, plants from Datura genus produce significant amounts of scopolamine and hyoscyamine; the latter undergoes racemization to atropine during isolation. Because of their biological importance, toxic properties and commonly reported food and animal feed contamination by different Datura sp. organs, there is a constant need for reliable methods for the analysis of tropane alkaloids in many matrices. In the current study, three extraction and sample-clean up procedures for the determination of scopolamine and atropine in plant material were compared in terms of their effectiveness and repeatability. Standard liquid-liquid extraction (LLE) and EXtrelut ® NT 3 columns were used for the sample clean-up. Combined ultrasound-assisted extraction and 24h static extraction using ethyl acetate, followed by multiple LLE steps was found the most effective separation method among tested. However, absolute extraction recovery was relatively low and reached 45-67% for atropine and 52-73% for scopolamine, depending on the compound concentration. The same method was also the most effective one for the isolation of target compounds from Datura stramonium leaves. EXtrelut ® columns, on the other hand, displayed relatively low effectiveness in isolating atropine and scopolamine from such a complex matrix and hence could not be recommended. The most effective method was also applied to the extraction of alkaloids from roots and stems of D. stramonium. Quantitative analyses were performed using validated method based on gas chromatography with flame ionization detector (GC-FID). Based on the results, the importance of the proper selection of internal standards in the analysis of tropane alkaloids was stressed out. Copyright © 2016 Elsevier B.V. All rights reserved.

Identification of temporal variations in mental workload using locally-linear-embedding-based EEG feature reduction and support-vector-machine-based clustering and classification techniques.

PubMed

Yin, Zhong; Zhang, Jianhua

2014-07-01

Identifying the abnormal changes of mental workload (MWL) over time is quite crucial for preventing the accidents due to cognitive overload and inattention of human operators in safety-critical human-machine systems. It is known that various neuroimaging technologies can be used to identify the MWL variations. In order to classify MWL into a few discrete levels using representative MWL indicators and small-sized training samples, a novel EEG-based approach by combining locally linear embedding (LLE), support vector clustering (SVC) and support vector data description (SVDD) techniques is proposed and evaluated by using the experimentally measured data. The MWL indicators from different cortical regions are first elicited by using the LLE technique. Then, the SVC approach is used to find the clusters of these MWL indicators and thereby to detect MWL variations. It is shown that the clusters can be interpreted as the binary class MWL. Furthermore, a trained binary SVDD classifier is shown to be capable of detecting slight variations of those indicators. By combining the two schemes, a SVC-SVDD framework is proposed, where the clear-cut (smaller) cluster is detected by SVC first and then a subsequent SVDD model is utilized to divide the overlapped (larger) cluster into two classes. Finally, three-class MWL levels (low, normal and high) can be identified automatically. The experimental data analysis results are compared with those of several existing methods. It has been demonstrated that the proposed framework can lead to acceptable computational accuracy and has the advantages of both unsupervised and supervised training strategies. Copyright © 2014 Elsevier Ireland Ltd. All rights reserved.

Integrated Fast-Ignition Core-Heating Experiments on OMEGA

NASA Astrophysics Data System (ADS)

Theobald, W.

2010-11-01

Integrated fast-ignition core-heating experiments are carried out at the Omega Laser Facility. Plastic (CD) shell targets with a re-entrant gold cone are compressed with a ˜20-kJ, UV low-adiabat laser pulse. A 1-kJ, 10-ps pulse from OMEGA EP generates fast electrons in the hollow cone that are transported into the compressed core. The experiments demonstrate a significant enhancement of the neutron yield. The neutron-yield enhancement caused by the high-intensity pulse is 1.5 x 10^7, which is more than 150% of the implosion yield. For the first time, measurements of the breakout time of the compression-induced shock wave through the cone were performed for the same targets as used in the integrated experiments. The shock breakout was measured to be ˜100 ps after peak neutron production. The experiments demonstrate that the cone tip is intact at the time when the short-pulse laser interacts with the cone. This work was supported by the U.S. Department of Energy Office of Inertial Confinement Fusion under Cooperative Agreement Nos. DE-FC52-08NA28302, DE-FC02-04ER54789, and DE-FG02-05ER54839. [4pt] In collaboration with A. A. Solodov, K. S. Anderson, R. Betti (LLE/FSC); C. Stoeckl, T.R. Boehly, R.S. Craxton, J.A. Delettrez, V.Yu. Glebov, J.P. Knauer, F.J. Marshall, K.L. Marshall, D.D. Meyerhofer,^ P.M. Nilson, T.C. Sangster, W. Seka (LLE); F.N. Beg (UCSD), H. Habara (ILE), P.K. Patel (LLNL), R.B. Stephens (GA); J.A. Frenje, N. Sinenian (PSFC/MIT).

A modified approach for isolation of essential oil from fruit of Amorpha fruticosa Linn using microwave-assisted hydrodistillation concatenated liquid-liquid extraction.

PubMed

Chen, Fengli; Jia, Jia; Zhang, Qiang; Gu, Huiyan; Yang, Lei

2017-11-17

In this work, a modified technique was developed to separate essential oil from the fruit of Amorpha fruticosa using microwave-assisted hydrodistillation concatenated liquid-liquid extraction (MHD-LLE). The new apparatus consists of two series-wound separation columns for separating essential oil, one is the conventional oil-water separation column, and the other is the extraction column of components from hydrosol using an organic solvent. Therefore, the apparatus can simultaneously collect the essential oil separated on the top of hydrosol and the components extracted from hydrosol using an organic solvent. Based on the yield of essential oil in the first and second separation columns, the effects of parameters were investigated by single factor experiments and Box-Behnken design. Under the optimum conditions (2mL ethyl ether as the extraction solvent in the second separation column, 12mL/g liquid-solid ratio, 4.0min homogenate time, 35min microwave irradiation time and 540W microwave irradiation power), satisfactory yields for the essential oil in the first separation column (10.31±0.33g/kg) and second separation column (0.82±0.03g/kg) were obtained. Compared with traditional methods, the developed method gave a higher yield of essential oil in a shorter time. In addition, GC-MS analysis of the essential oil indicated significant differences of the relative contents of individual volatile components in the essential oils obtained in the two separation columns. Therefore, the MHD-LLE technique developed here is a good alternative for the isolation of essential oil from A. fruticosa fruit as well as other herbs. Copyright © 2017 Elsevier B.V. All rights reserved.

High Incidence and Levels of Ochratoxin A in Wines Sourced from the United States.

PubMed

De Jesus, Christopher Lawrence; Bartley, Amanda; Welch, Aaron Z; Berry, John P

2017-12-21

Ochratoxin A (OTA) is one of the most prevalent mycotoxin contaminants of food crops. Among the agricultural products consequently contaminated by OTA is wine. In the present study, a sample of wines sourced from the United States was assessed for OTA. Wines were primarily analyzed by high-performance liquid chromatography with fluorescence detection (HPLC-FD) coupled to a liquid-liquid extraction (LLE) technique which was developed and validated as a simplified sample preparation approach. More than 85% of the wines evaluated were found to contain OTA, at levels above the limit-of-detection (LOD = 0.1 µg L -1 ), and 76% were above the limit-of-quantitation (LOQ = 0.3 µg L -1 ) for the LLE/HPLC-FD method. More than two-thirds of the wines above the LOQ were found to exceed 1 µg L -1 . Complementary analysis by HPLC coupled to tandem mass spectrometry (HPLC-MS/MS) confirmed OTA in 74% of the OTA-positive wines (i.e., >LOQ by HPLC-FD). Overall, both the occurrence and measured levels of OTA were generally high, specifically relative to previous assessments of OTA in wine, and two of the wines were above the only current (European Union) regulatory limit of two parts-per-billion (ppb, ~2 µg L -1 ). Possible trends with respect to geographical region and/or growing climate are noted. As the first assessment of U.S. wines in more than a decade, the overall high occurrence and levels of OTA in wine, and possible geographic and climatic trends, point to a need for regular surveillance of wines, as well as investigation of the relevant contributors to OTA occurrence toward mitigating contamination and exposure risks.

A novel dual-valve sequential injection manifold (DV-SIA) for automated liquid-liquid extraction. Application for the determination of picric acid.

PubMed

Skrlíková, Jana; Andruch, Vasil; Sklenárová, Hana; Chocholous, Petr; Solich, Petr; Balogh, Ioseph S

2010-05-07

A novel dual-valve sequential injection system (DV-SIA) for online liquid-liquid extraction which resolves the main problems of LLE utilization in SIA has been designed. The main idea behind this new design was to construct an SIA system by connecting two independent units, one for aqueous-organic mixture flow and the second specifically for organic phase flow. As a result, the DV-SIA manifold consists of an Extraction unit and a Detection unit. Processing a mixture of aqueous-organic phase in the Extraction unit and a separated organic phase in the Detection unit solves the problems associated with the change of phases having different affinities to the walls of the Teflon tubing used in the SI-system. The developed manifold is a simple, user-friendly and universal system built entirely from commercially available components. The system can be used for a variety of samples and organic solvents and is simple enough to be easily handled by operators less familiar with flow systems. The efficiency of the DV-SIA system is demonstrated by the extraction of picric acid in the form of an ion associate with 2-[2-(4-methoxy-phenylamino)-vinyl]-1,3,3-trimethyl-3H-indolium reagent, with subsequent spectrophotometric detection. The suggested DV-SIA concept can be expected to stimulate new experiments in analytical laboratories and can be applied to the elaboration of procedures for the determination of other compounds extractable by organic solvents. It could thus form a basis for the design of simple, single-purpose commercial instruments used in LLE procedures. 2010 Elsevier B.V. All rights reserved.

Performance of third-trimester ultrasound for prediction of small-for-gestational-age neonates and evaluation of contingency screening policies.

PubMed

Souka, A P; Papastefanou, I; Pilalis, A; Michalitsi, V; Kassanos, D

2012-05-01

To assess the performance of third-trimester fetal biometry and fetal Doppler studies for the prediction of small-for-gestational-age (SGA) neonates, and to explore contingency strategies using a first-trimester prediction model based on maternal and fetal parameters and third-trimester ultrasound. This was an observational cross-sectional study of uncomplicated singleton pregnancies. Risk assessment for chromosomal abnormality was carried out in 4702 pregnancies using a combination of ultrasound markers (fetal nuchal translucency thickness (NT) and nasal bone assessment) and biochemistry (free beta-human chorionic gonadotropin (β-hCG) and pregnancy-associated plasma protein-A (PAPP-A)) at 11 to 13 + 6 weeks. Maternal demographic characteristics and method of conception were recorded. Third-trimester (30-34 weeks) fetal biometry (biparietal diameter (BPD), head circumference (HC), abdominal circumference (AC) and femur length (FL)) and umbilical artery (UA) and middle cerebral artery Doppler studies were performed routinely in a subgroup (n = 2310). Reference ranges for birth weight were constructed using the cohort of 4702 women, and neonates were classified as small (SGA, ≤ 5th centile) or appropriate (AGA) for gestational age. First-trimester, third-trimester and integrated first- and third-trimester prediction models for SGA were constructed using regression analysis and three different contingency strategies of rescanning in the third trimester were investigated. According to the areas under the receiver-operating characteristics curves (AUCs), AC (AUC = 0.85) and ultrasound-estimated fetal weight (EFW, AUC = 0.87) were equally good predictors of SGA. The model was marginally improved by the addition of UA Doppler, smoking status and first-trimester indices (free β-hCG and PAPP-A multiples of the median) (combined model, AUC = 0.88), but the difference was not statistically significant. A contingency strategy of rescanning 50% of the population in the

In vitro solubility, dissolution and permeability studies combined with semi-mechanistic modeling to investigate the intestinal absorption of desvenlafaxine from an immediate- and extended release formulation.

PubMed

Franek, F; Jarlfors, A; Larsen, F; Holm, P; Steffansen, B

2015-09-18

Desvenlafaxine is a biopharmaceutics classification system (BCS) class 1 (high solubility, high permeability) and biopharmaceutical drug disposition classification system (BDDCS) class 3, (high solubility, poor metabolism; implying low permeability) compound. Thus the rate-limiting step for desvenlafaxine absorption (i.e. intestinal dissolution or permeation) is not fully clarified. The aim of this study was to investigate whether dissolution and/or intestinal permeability rate-limit desvenlafaxine absorption from an immediate-release formulation (IRF) and Pristiq(®), an extended release formulation (ERF). Semi-mechanistic models of desvenlafaxine were built (using SimCyp(®)) by combining in vitro data on dissolution and permeation (mechanistic part of model) with clinical data (obtained from literature) on distribution and clearance (non-mechanistic part of model). The model predictions of desvenlafaxine pharmacokinetics after IRF and ERF administration were compared with published clinical data from 14 trials. Desvenlafaxine in vivo dissolution from the IRF and ERF was predicted from in vitro solubility studies and biorelevant dissolution studies (using the USP3 dissolution apparatus), respectively. Desvenlafaxine apparent permeability (Papp) at varying apical pH was investigated using the Caco-2 cell line and extrapolated to effective intestinal permeability (Peff) in human duodenum, jejunum, ileum and colon. Desvenlafaxine pKa-values and octanol-water partition coefficients (Do:w) were determined experimentally. Due to predicted rapid dissolution after IRF administration, desvenlafaxine was predicted to be available for permeation in the duodenum. Desvenlafaxine Do:w and Papp increased approximately 13-fold when increasing apical pH from 5.5 to 7.4. Desvenlafaxine Peff thus increased with pH down the small intestine. Consequently, desvenlafaxine absorption from an IRF appears rate-limited by low Peff in the upper small intestine, which "delays" the predicted

First-Trimester Maternal Serum Amino Acids and Acylcarnitines Are Significant Predictors of Gestational Diabetes

PubMed Central

Nevalainen, Jaana; Sairanen, Mikko; Appelblom, Heidi; Gissler, Mika; Timonen, Susanna; Ryynänen, Markku

2016-01-01

BACKGROUND: Current screening methods for gestational diabetes mellitus (GDM) are insufficient in detecting the risk of GDM in the first trimester of the pregnancy. Recent metabolomic studies have detected altered amino acid and acylcarnitine concentrations in type 2 diabetes (T2D). Because of the similarities between T2D and GDM, the determination of these metabolites may be useful in early screening for GDM. AIM: To evaluate the association between GDM and first-trimester maternal serum concentrations of ten amino acids and 31 acylcarnitines. METHODS: This retrospective case-control study included data from pregnant women screened at Oulu University Hospital between 1.1.2008 and 31.12.2011. A total of 31,146 women participated voluntarily in a first-trimester combined screening (for chromosomal abnormalities). The study population included 69 women who developed GDM during pregnancy and 295 women without diabetes before or after pregnancy. The serum concentrations of ten amino acids and 31 acylcarnitines were analyzed from frozen serum samples taken in the first-trimester screening. Multiple of median (MoM) values were compared between the two groups. RESULTS: In the GDM group, serum levels of arginine were significantly higher (1.13 MoM vs. 0.97 MoM), and those of glycine (0.93 MoM vs. 1.03 MoM) and 3-hydroxy-isovalerylcarnitine (0.86 MoM vs. 1.03 MoM) significantly lower compared to the control group (all p < 0.01). In each case, arginine, glycine, and 3-hydroxy-isovaleryl-carnitine would have detected 46%, 32%, and 39% of GDM cases, with a false-positive rate of 20%. Combining these three metabolites with the first-trimester serum marker pregnancy-associated plasma protein A (PAPP-A) and prior risk (age, BMI, and smoking) achieved a detection rate of 72%. CONCLUSION: There are significant differences in the serum levels of arginine, glycine, and 3-hydroxy-isovalerylcarnitine between controls and women who subsequently develop GDM. These differences were

Phosphor-Penetration Color Cathode-Ray Tube.

DTIC Science & Technology

1979-06-01

radii of curvature and with differing optical transmission. The face- plate chosen for this program has a 40-inch inside radius and a light- transmission...DIFFERENCE WHEN V3 V2I SMALL AREAMIESH -TO- SCREEN GEOMIETRY FIGURE 13 Ri =40 INCHES A .50 INCHES R 2= 60 INCHES H771 7.0 INCHES * Vs I V4 ~ VST V4 2...APMIY COIL"UNTCATIONS R&D CO*MtAND 001 DOVER, NJ 07801 000 FORT MONMOUTH, NJ 07703 1 DRDCO-COM-RO 711 METALS AND CERAMICS INF CENTER I USMC- LNO BATE LLE I ATFE-LO-EC SOS KING AVENUE 001 COLUMBUS, OHi 43201 4

A Very Simple Method to Calculate the (Positive) Largest Lyapunov Exponent Using Interval Extensions

NASA Astrophysics Data System (ADS)

Mendes, Eduardo M. A. M.; Nepomuceno, Erivelton G.

2016-12-01

In this letter, a very simple method to calculate the positive Largest Lyapunov Exponent (LLE) based on the concept of interval extensions and using the original equations of motion is presented. The exponent is estimated from the slope of the line derived from the lower bound error when considering two interval extensions of the original system. It is shown that the algorithm is robust, fast and easy to implement and can be considered as alternative to other algorithms available in the literature. The method has been successfully tested in five well-known systems: Logistic, Hénon, Lorenz and Rössler equations and the Mackey-Glass system.

Smart Water Conservation System for Irrigated Landscape

DTIC Science & Technology

2016-05-01

Ir ri ga tio n Sy st em s Ir ri... ire d fo r i rr ig at io n. Le ss w at er u se d re su lts in re du ce d en er gy us ag e. C on tro lle r c ol le ct s a nd e va lu at es re...al -ti m e se ns or d at a to de te rm in e w he n it is n ec es sa ry to ir rig at e an d ho w m uc h w at er to a pp ly b as ed

DNA extraction on bio-chip: history and preeminence over conventional and solid-phase extraction methods.

PubMed

Ayoib, Adilah; Hashim, Uda; Gopinath, Subash C B; Md Arshad, M K

2017-11-01

This review covers a developmental progression on early to modern taxonomy at cellular level following the advent of electron microscopy and the advancement in deoxyribonucleic acid (DNA) extraction for expatiation of biological classification at DNA level. Here, we discuss the fundamental values of conventional chemical methods of DNA extraction using liquid/liquid extraction (LLE) followed by development of solid-phase extraction (SPE) methods, as well as recent advances in microfluidics device-based system for DNA extraction on-chip. We also discuss the importance of DNA extraction as well as the advantages over conventional chemical methods, and how Lab-on-a-Chip (LOC) system plays a crucial role for the future achievements.

Prenatal diagnosis and molecular cytogenetic characterization of de novo pure partial trisomy 6p associated with microcephaly, craniosynostosis and abnormal maternal serum biochemistry.

PubMed

Chen, Chih-Ping; Chen, Ming; Chen, Chen-Yu; Chern, Schu-Rern; Wu, Peih-Shan; Chang, Shun-Ping; Kuo, Yu-Ling; Chen, Wen-Lin; Pan, Chen-Wen; Wang, Wayseen

2014-02-25

We present prenatal diagnosis and molecular cytogenetic characterization of de novo pure trisomy 6p22.3 → p25.3 encompassing BMP6 in a fetus associated with microcephaly and craniosynostosis on prenatal ultrasound, abnormal maternal serum biochemistry of a low PAPP-A level in the first-trimester combined test, and a karyotype of 46,XX,der(22)t(6;22)(p22.3;p13)dn. The present case demonstrates the usefulness of rapid prenatal identification of the origin of the extra chromosome material on the short arm of an acrocentric chromosome by spectral karyotyping, fluorescence in situ hybridization and array comparative genomic hybridization. We review the phenotypic abnormality of craniosynostosis in previously reported patients with partial trisomy 6p. We discuss the genotype-phenotype correlation of the involved gene of BMP6 in this case. Copyright © 2013 Elsevier B.V. All rights reserved.

An illustrated key to the genera and subgenera of the Alysiini (Hymenoptera, Braconidae, Alysiinae), with three genera new for China

PubMed Central

Zhu, Jia-Chen; van Achterberg, Cornelis; Chen, Xue-Xin

2017-01-01

Abstract An illustrated key to the genera and subgenera of the Alysiini (Hymenoptera, Braconidae, Alysiinae) from China is presented. Three genera new for China are reported: Adelurola Strand, 1924, Anisocyrta Foerster, 1863, and Pentapleura Foerster, 1863. The total for China is 26 genera of Alysiini and an additional seven subgenera (excluding the nominal subgenera, which are included in the total of genera). The known Chinese species are listed under each genus and the biology is summarised. Separatatus sinicus (Zheng, Chen & Yang, 2012) and Grammospila eurys (Chen & Wu, 1994) are new combinations. Regetus Papp, 1999, and Adelphenaldis Fischer, 2003, are new synonyms of Eusynaldis Zaykov & Fischer, 1982. In addition, Eusynaldis Zaykov & Fischer and Synaldis Foerster, 1863, are treated as subgenera of Aspilota Foerster, 1863, and Dinotrema Foerster, 1863, respectively. An aberrant species of Separatatus Chen & Wu, 1994, S. parallelus sp. n., is described from Yunnan and Hainan. PMID:29308029

Identification of Dynamic Patterns of Speech-Evoked Auditory Brainstem Response Based on Ensemble Empirical Mode Decomposition and Nonlinear Time Series Analysis Methods

NASA Astrophysics Data System (ADS)

Mozaffarilegha, Marjan; Esteki, Ali; Ahadi, Mohsen; Nazeri, Ahmadreza

The speech-evoked auditory brainstem response (sABR) shows how complex sounds such as speech and music are processed in the auditory system. Speech-ABR could be used to evaluate particular impairments and improvements in auditory processing system. Many researchers used linear approaches for characterizing different components of sABR signal, whereas nonlinear techniques are not applied so commonly. The primary aim of the present study is to examine the underlying dynamics of normal sABR signals. The secondary goal is to evaluate whether some chaotic features exist in this signal. We have presented a methodology for determining various components of sABR signals, by performing Ensemble Empirical Mode Decomposition (EEMD) to get the intrinsic mode functions (IMFs). Then, composite multiscale entropy (CMSE), the largest Lyapunov exponent (LLE) and deterministic nonlinear prediction are computed for each extracted IMF. EEMD decomposes sABR signal into five modes and a residue. The CMSE results of sABR signals obtained from 40 healthy people showed that 1st, and 2nd IMFs were similar to the white noise, IMF-3 with synthetic chaotic time series and 4th, and 5th IMFs with sine waveform. LLE analysis showed positive values for 3rd IMFs. Moreover, 1st, and 2nd IMFs showed overlaps with surrogate data and 3rd, 4th and 5th IMFs showed no overlap with corresponding surrogate data. Results showed the presence of noisy, chaotic and deterministic components in the signal which respectively corresponded to 1st, and 2nd IMFs, IMF-3, and 4th and 5th IMFs. While these findings provide supportive evidence of the chaos conjecture for the 3rd IMF, they do not confirm any such claims. However, they provide a first step towards an understanding of nonlinear behavior of auditory system dynamics in brainstem level.

Characterization and determination of naphthenic acids species in oil sands process-affected water and groundwater from oil sands development area of Alberta, Canada.

PubMed

Huang, Rongfu; Chen, Yuan; Meshref, Mohamed N A; Chelme-Ayala, Pamela; Dong, Shimiao; Ibrahim, Mohamed D; Wang, Chengjin; Klamerth, Nikolaus; Hughes, Sarah A; Headley, John V; Peru, Kerry M; Brown, Christine; Mahaffey, Ashley; Gamal El-Din, Mohamed

2018-01-01

This work reports the monitoring and assessment of naphthenic acids (NAs) in oil sands process-affected water (OSPW), Pleistocene channel aquifer groundwater (PLCA), and oil sands basal aquifer groundwater (OSBA) from an active oil sands development in Alberta, Canada, using ultra performance liquid chromatography time-of-flight mass spectrometry (UPLC-TOF-MS) analysis with internal standard (ISTD) and external standard (ESTD) calibration methods and Fourier transform ion cyclotron resonance mass spectrometry (FTICR-MS) for compositional analysis. PLCA was collected at 45-51 m depth and OSBA was collected at 67-144 m depth. Results of O x -NA concentrations follow an order as OSPW > OSBA > PLCA, indicating that occurrences of NAs in OSBA were likely related to natural bitumen deposits instead of OSPW. Liquid-liquid extraction (LLE) was applied to avoid the matrix effect for the ESTD method. Reduced LLE efficiency accounted for the divergence of the ISTD and ESTD calibrated results for oxidized NAs. Principle component analysis results of O 2 and O 4 species could be employed for differentiation of water types, while classical NAs with C13-15 and Z (-4)-(-6) and aromatic O 2 -NAs with C16-18 and Z (-14)-(-16) could be measured as marker compounds to characterize water sources and potential temporal variations of samples, respectively. FTICR-MS results revealed that compositions of NA species varied greatly among OSPW, PLCA, and OSBA, because of NA transfer and transformation processes. This work contributed to the understanding of the concentration and composition of NAs in various types of water, and provided a useful combination of analytical and statistical tools for monitoring studies, in support of future safe discharge of treated OSPW. Copyright © 2017 Elsevier Ltd. All rights reserved.

Liquid-liquid extraction of strongly protein bound BMS-299897 from human plasma and cerebrospinal fluid, followed by high-performance liquid chromatography/tandem mass spectrometry.

PubMed

Xue, Y J; Pursley, Janice; Arnold, Mark

2007-04-11

BMS-299897 is a gamma-secretase inhibitor that is being developed for the treatment of Alzheimer's disease. Liquid-liquid extraction (LLE), chromatographic/tandem mass spectrometry (LC/MS/MS) methods have been developed and validated for the quantitation of BMS-299897 in human plasma and cerebrospinal fluid (CSF). Both methods utilized (13)C6-BMS-299897, the stable label isotope analog, as the internal standard. For the human plasma extraction method, two incubation steps were required after the addition of 5 mM ammonium acetate and the internal standard in acetonitrile to release the analyte bound to proteins prior to LLE with toluene. For the human CSF extraction method, after the addition of 0.5 N HCl and the internal standard, CSF samples were extracted with toluene and no incubation was required. The organic layers obtained from both extraction methods were removed and evaporated to dryness. The residues were reconstituted and injected into the LC/MS/MS system. Chromatographic separation was achieved isocratically on a MetaChem C18 Hypersil BDS column (2.0 mm x 50 mm, 3 microm). The mobile phase contained 10 mM ammonium acetate pH 5 and acetonitrile. Detection was by negative ion electrospray tandem mass spectrometry. The standard curves ranged from 1 to 1000 ng/ml for human plasma and 0.25-100 ng/ml for human CSF. Both standard curves were fitted to a 1/x weighted quadratic regression model. For both methods, the intra-assay precision was within 8.2% CV, the inter-assay precision was within 5.4% CV, and assay accuracy was within +/-7.4% of the nominal values. The validation and sample analysis results demonstrated that both methods had acceptable precision and accuracy across the calibration ranges.

Studies of Magnetic Reconnection in Colliding Laser-Produced Plasmas

NASA Astrophysics Data System (ADS)

Rosenberg, Michael

2013-10-01

Novel images of magnetic fields and measurements of electron and ion temperatures have been obtained in the magnetic reconnection region of high- β, laser-produced plasmas. Experiments using laser-irradiated foils produce expanding, hemispherical plasma plumes carrying MG Biermann-battery magnetic fields, which can be driven to interact and reconnect. Thomson-scattering measurements of electron and ion temperatures in the interaction region of two colliding, magnetized plasmas show no thermal enhancement due to reconnection, as expected for β ~ 8 plasmas. Two different proton radiography techniques used to image the magnetic field structures show deformation, pileup, and annihilation of magnetic flux. High-resolution images reveal unambiguously reconnection-induced jets emerging from the interaction region and show instabilities in the expanding plasma plumes and supersonic, hydrodynamic jets due to the plasma collision. Quantitative magnetic flux data show that reconnection in experiments with asymmetry in the scale size, density, temperature, and plasma flow across the reconnection region occurs less efficiently than in similar, symmetric experiments. This result is attributed to disruption of the Hall mechanism mediating collisionless reconnection. The collision of plasmas carrying parallel magnetic fields has also been probed, illustrating the deformation of magnetic field structures in high-energy-density plasmas in the absence of reconnection. These experiments are particularly relevant to high- β reconnection environments, such as the magnetopause. This work was performed in collaboration with C. Li, F. Séguin, A. Zylstra, H. Rinderknecht, H. Sio, J. Frenje, and R. Petrasso (MIT), I. Igumenshchev, V. Glebov, C. Stoeckl, and D. Froula (LLE), J. Ross and R. Town (LLNL), W. Fox (UNH), and A. Nikroo (GA), and was supported in part by the NLUF, FSC/UR, U.S. DOE, LLNL, and LLE.

Characterization of N-palmitoylated human growth hormone by in situ liquid-liquid extraction and MALDI tandem mass spectrometry.

PubMed

Sachon, Emmanuelle; Nielsen, Per Franklin; Jensen, Ole Nørregaard

2007-06-01

Acylation is a common post-translational modification found in secreted proteins and membrane-associated proteins, including signal transducing and regulatory proteins. Acylation is also explored in the pharmaceutical and biotechnology industry to increase the stability and lifetime of protein-based products. The presence of acyl moieties in proteins and peptides affects the physico-chemical properties of these species, thereby modulating protein stability, function, localization and molecular interactions. Characterization of protein acylation is a challenging analytical task, which includes the precise definition of the acylation sites in proteins and determination of the identity and molecular heterogeneity of the acyl moiety at each individual site. In this study, we generated a chemically modified human growth hormone (hGH) by incorporation of a palmitoyl moiety on the N(epsilon) group of a lysine residue. Monoacylation of the hGH protein was confirmed by determination of the intact molecular weight by mass spectrometry. Detailed analysis of protein acylation was achieved by analysis of peptides derived from hGH by protease treatment. However, peptide mass mapping by MALDI MS using trypsin and AspN proteases and standard sample preparation methods did not reveal any palmitoylated peptides. In contrast, in situ liquid-liquid extraction (LLE) performed directly on the MALDI MS metal target enabled detection of acylated peptide candidates by MALDI MS and demonstrated that hGH was N-palmitoylated at multiple lysine residues. MALDI MS and MS/MS analysis of the modified peptides mapped the N-palmitoylation sites to Lys158, Lys172 and Lys140 or Lys145. This study demonstrates the utility of LLE/MALDI MS/MS for mapping and characterization of acylation sites in proteins and peptides and the importance of optimizing sample preparation methods for mass spectrometry-based determination of substoichiometric, multi-site protein modifications.

Simultaneous determination of trace rare-earth elements in simulated water samples using ICP-OES with TODGA extraction/back-extraction.

PubMed

Li, FuKai; Gong, AiJun; Qiu, LiNa; Zhang, WeiWei; Li, JingRui; Liu, Yu; Liu, YuNing; Yuan, HuiTing

2017-01-01

The determination of trace rare-earth elements (REEs) can be used for the assessment of environmental pollution, and is of great significance to the study of toxicity and toxicology in animals and plants. N, N, N', N'-tetraoctyl diglycolamide (TODGA) is an environmental friendly extractant that is highly selective to REEs. In this study, an analytical method was developed for the simultaneous determination of 16 trace REEs in simulated water samples by inductively coupled plasma optical emission spectroscopy (ICP-OES). With this method, TODGA was used as the extractant to perform the liquid-liquid extraction (LLE) sample pretreatment procedure. All 16 REEs were extracted from a 3 M nitric acid medium into an organic phase by a 0.025 M TODGA petroleum ether solution. A 0.03 M ethylenediaminetetraacetic acid disodium salt (EDTA) solution was used for back-extraction to strip the REEs from the organic phase into the aqueous phase. The aqueous phase was concentrated using a vacuum rotary evaporator and the concentration of the 16 REEs was detected by ICP-OES. Under the optimum experimental conditions, the limits of detection (3σ, n = 7) for the REEs ranged from 0.0405 ng mL-1 (Nd) to 0.5038 ng mL-1 (Ho). The relative standard deviations (c = 100 ng mL-1, n = 7) were from 0.5% (Eu) to 4.0% (Tm) with a linear range of 4-1000 ng mL-1 (R2 > 0.999). The recoveries of 16 REEs ranged from 95% to 106%. The LLE-ICP-OES method established in this study has the advantages of simple operation, low detection limits, fast analysis speed and the ability to simultaneously determine 16 REEs, thereby acting as a viable alternative for the simultaneous detection of trace amounts of REEs in water samples.

Hysteresis-induced bifurcation and chaos in a magneto-rheological suspension system under external excitation

NASA Astrophysics Data System (ADS)

Hailong, Zhang; Enrong, Wang; Fuhong, Min; Ning, Zhang

2016-03-01

The magneto-rheological damper (MRD) is a promising device used in vehicle semi-active suspension systems, for its continuous adjustable damping output. However, the innate nonlinear hysteresis characteristic of MRD may cause the nonlinear behaviors. In this work, a two-degree-of-freedom (2-DOF) MR suspension system was established first, by employing the modified Bouc-Wen force-velocity (F-v) hysteretic model. The nonlinear dynamic response of the system was investigated under the external excitation of single-frequency harmonic and bandwidth-limited stochastic road surface. The largest Lyapunov exponent (LLE) was used to detect the chaotic area of the frequency and amplitude of harmonic excitation, and the bifurcation diagrams, time histories, phase portraits, and power spectrum density (PSD) diagrams were used to reveal the dynamic evolution process in detail. Moreover, the LLE and Kolmogorov entropy (K entropy) were used to identify whether the system response was random or chaotic under stochastic road surface. The results demonstrated that the complex dynamical behaviors occur under different external excitation conditions. The oscillating mechanism of alternating periodic oscillations, quasi-periodic oscillations, and chaotic oscillations was observed in detail. The chaotic regions revealed that chaotic motions may appear in conditions of mid-low frequency and large amplitude, as well as small amplitude and all frequency. The obtained parameter regions where the chaotic motions may appear are useful for design of structural parameters of the vibration isolation, and the optimization of control strategy for MR suspension system. Projects supported by the National Natural Science Foundation of China (Grant Nos. 51475246, 51277098, and 51075215), the Research Innovation Program for College Graduates of Jiangsu Province China (Grant No. KYLX15 0725), and the Natural Science Foundation of Jiangsu Province of China (Grant No. BK20131402).

Automated High-Throughput Permethylation for Glycosylation Analysis of Biologics Using MALDI-TOF-MS.

PubMed

Shubhakar, Archana; Kozak, Radoslaw P; Reiding, Karli R; Royle, Louise; Spencer, Daniel I R; Fernandes, Daryl L; Wuhrer, Manfred

2016-09-06

Monitoring glycoprotein therapeutics for changes in glycosylation throughout the drug's life cycle is vital, as glycans significantly modulate the stability, biological activity, serum half-life, safety, and immunogenicity. Biopharma companies are increasingly adopting Quality by Design (QbD) frameworks for measuring, optimizing, and controlling drug glycosylation. Permethylation of glycans prior to analysis by matrix-assisted laser desorption/ionization time-of-flight mass spectrometry (MALDI-TOF-MS) is a valuable tool for glycan characterization and for screening of large numbers of samples in QbD drug realization. However, the existing protocols for manual permethylation and liquid-liquid extraction (LLE) steps are labor intensive and are thus not practical for high-throughput (HT) studies. Here we present a glycan permethylation protocol, based on 96-well microplates, that has been developed into a kit suitable for HT work. The workflow is largely automated using a liquid handling robot and includes N-glycan release, enrichment of N-glycans, permethylation, and LLE. The kit has been validated according to industry analytical performance guidelines and applied to characterize biopharmaceutical samples, including IgG4 monoclonal antibodies (mAbs) and recombinant human erythropoietin (rhEPO). The HT permethylation enabled glycan characterization and relative quantitation with minimal side reactions: the MALDI-TOF-MS profiles obtained were in good agreement with hydrophilic liquid interaction chromatography (HILIC) and ultrahigh performance liquid chromatography (UHPLC) data. Automated permethylation and extraction of 96 glycan samples was achieved in less than 5 h and automated data acquisition on MALDI-TOF-MS took on average less than 1 min per sample. This automated and HT glycan preparation and permethylation showed to be convenient, fast, and reliable and can be applied for drug glycan profiling and clinical glycan biomarker studies.

Time series analyses of breathing patterns of lung cancer patients using nonlinear dynamical system theory.

PubMed

Tewatia, D K; Tolakanahalli, R P; Paliwal, B R; Tomé, W A

2011-04-07

The underlying requirements for successful implementation of any efficient tumour motion management strategy are regularity and reproducibility of a patient's breathing pattern. The physiological act of breathing is controlled by multiple nonlinear feedback and feed-forward couplings. It would therefore be appropriate to analyse the breathing pattern of lung cancer patients in the light of nonlinear dynamical system theory. The purpose of this paper is to analyse the one-dimensional respiratory time series of lung cancer patients based on nonlinear dynamics and delay coordinate state space embedding. It is very important to select a suitable pair of embedding dimension 'm' and time delay 'τ' when performing a state space reconstruction. Appropriate time delay and embedding dimension were obtained using well-established methods, namely mutual information and the false nearest neighbour method, respectively. Establishing stationarity and determinism in a given scalar time series is a prerequisite to demonstrating that the nonlinear dynamical system that gave rise to the scalar time series exhibits a sensitive dependence on initial conditions, i.e. is chaotic. Hence, once an appropriate state space embedding of the dynamical system has been reconstructed, we show that the time series of the nonlinear dynamical systems under study are both stationary and deterministic in nature. Once both criteria are established, we proceed to calculate the largest Lyapunov exponent (LLE), which is an invariant quantity under time delay embedding. The LLE for all 16 patients is positive, which along with stationarity and determinism establishes the fact that the time series of a lung cancer patient's breathing pattern is not random or irregular, but rather it is deterministic in nature albeit chaotic. These results indicate that chaotic characteristics exist in the respiratory waveform and techniques based on state space dynamics should be employed for tumour motion management.

Simultaneous determination of trace rare-earth elements in simulated water samples using ICP-OES with TODGA extraction/back-extraction

PubMed Central

Li, FuKai; Qiu, LiNa; Zhang, WeiWei; Li, JingRui; Liu, Yu; Liu, YuNing; Yuan, HuiTing

2017-01-01

The determination of trace rare-earth elements (REEs) can be used for the assessment of environmental pollution, and is of great significance to the study of toxicity and toxicology in animals and plants. N, N, N′, N′-tetraoctyl diglycolamide (TODGA) is an environmental friendly extractant that is highly selective to REEs. In this study, an analytical method was developed for the simultaneous determination of 16 trace REEs in simulated water samples by inductively coupled plasma optical emission spectroscopy (ICP-OES). With this method, TODGA was used as the extractant to perform the liquid-liquid extraction (LLE) sample pretreatment procedure. All 16 REEs were extracted from a 3 M nitric acid medium into an organic phase by a 0.025 M TODGA petroleum ether solution. A 0.03 M ethylenediaminetetraacetic acid disodium salt (EDTA) solution was used for back-extraction to strip the REEs from the organic phase into the aqueous phase. The aqueous phase was concentrated using a vacuum rotary evaporator and the concentration of the 16 REEs was detected by ICP-OES. Under the optimum experimental conditions, the limits of detection (3σ, n = 7) for the REEs ranged from 0.0405 ng mL-1 (Nd) to 0.5038 ng mL-1 (Ho). The relative standard deviations (c = 100 ng mL-1, n = 7) were from 0.5% (Eu) to 4.0% (Tm) with a linear range of 4–1000 ng mL-1 (R2 > 0.999). The recoveries of 16 REEs ranged from 95% to 106%. The LLE-ICP-OES method established in this study has the advantages of simple operation, low detection limits, fast analysis speed and the ability to simultaneously determine 16 REEs, thereby acting as a viable alternative for the simultaneous detection of trace amounts of REEs in water samples. PMID:28945788

Mutational analysis of AGXT gene in Libyan children with primary hyperoxaluria type 1 at Tripoli Children Hospital.

PubMed

Rhuma, Naziha R; Fituri, Omar A; Sabei, Laila T

2018-01-01

Primary hyperoxaluria type 1 (PH1) is an inborn error of glyoxylate metabolism. It results from genetic mutation of the AGXT gene. The study objective was to verify the clinical and epidemiological patterns of PH1 in Libyan children at Tripoli Children Hospital confirmed by AGXT gene mutation. A descriptive case series study of 53 children with PH1 diagnosed between 1994 and 2015 was carried out in the Nephrology Unit at Tripoli Children Hospital. Diagnosis of PH1 was based on the clinical presentation (renal stones or nephrocalcinosis), positive family history of PH1, and high 24 h urinary oxalate. Sampling for AGXT gene mutation was collected from April 2012 to December. 2015. Among the 53 children included, males composed of 62.3% of patients. Their age at presentation ranged between two months and 20 years with a mean age of 55.4 ± 48 months. The parents of 81.1% of these patients had positive consanguinity. Forty (75.5%) patients were from South West (mountain area), and 16 (40%) of them were from Yefrin. The most common mutation found in this study was c.731T>C (p.lle244thr) seen in 32 (71%) of children, and interestingly, among these patients, 87.1% were homozygous in gene typing, 86.2% had positive history of consanguinity, 71.4% were from South West (mountain area), 96.6% had family history of PH1, and 20% presented with impaired renal function. The patients with this mutation were younger at presentation than that with other genes, and it was more prevalent among boys (61.3%). Thus, the most common gene mutation found in Libyan children with PH1 was c.731T>C (p.lle244thr) and this is more likely due to the strong genetic pooling caused by the high consanguinity rate which requires an extensive genetic counseling.

[Prenatal risk calculation: comparison between Fast Screen pre I plus software and ViewPoint software. Evaluation of the risk calculation algorithms].

PubMed

Morin, Jean-François; Botton, Eléonore; Jacquemard, François; Richard-Gireme, Anouk

2013-01-01

The Fetal medicine foundation (FMF) has developed a new algorithm called Prenatal Risk Calculation (PRC) to evaluate Down syndrome screening based on free hCGβ, PAPP-A and nuchal translucency. The peculiarity of this algorithm is to use the degree of extremeness (DoE) instead of the multiple of the median (MoM). The biologists measuring maternal seric markers on Kryptor™ machines (Thermo Fisher Scientific) use Fast Screen pre I plus software for the prenatal risk calculation. This software integrates the PRC algorithm. Our study evaluates the data of 2.092 patient files of which 19 show a fœtal abnormality. These files have been first evaluated with the ViewPoint software based on MoM. The link between DoE and MoM has been analyzed and the different calculated risks compared. The study shows that Fast Screen pre I plus software gives the same risk results as ViewPoint software, but yields significantly fewer false positive results.

Likely effects of construction of Scroby Sands offshore wind farm on a mixed population of harbour Phoca vitulina and grey Halichoerus grypus seals.

PubMed

Skeate, Eleanor R; Perrow, Martin R; Gilroy, James J

2012-04-01

Scroby Sands offshore wind farm was built close to a haul-out and breeding site for harbour seal, a species of conservation concern. An aerial survey programme conducted during a five-year period spanning wind farm construction, revealed a significant post-construction decline in haul-out counts. Multivariate model selection suggested that the decline was not related to the environmental factors considered, nor did it mirror wider population trends. Although cause and effect could not be unequivocally established, the theoretical basis of hearing in pinnipeds and previous studies suggested that extreme noise (to 257 dB re 1 μ Pa(pp) @ 1m) generated by pile-driving of turbine bases led to displacement of seals. A lack of full recovery of harbour seal during the study was also linked to their sensitivity to vessel activity and/or rapid colonisation of competing grey seal. Any impact of offshore wind farm development upon pinnipeds would be much reduced without pile-driving. Copyright © 2012 Elsevier Ltd. All rights reserved.

Pre-Deployment Handbook Papua New Guinea

DTIC Science & Technology

2014-03-01

ai M or eh ea d W ea m Ku pi an o A ng or am Te le fo m in Ta la se a G lo uc es te r...rit ai n B ou ga in vi lle C ho is eu l S an ta Y sa be l W oo dl ar k P oc kl in gt on R ee f D ’E nt re ca st ea ux Is la nd s Lo ui si ad e A...rc hi pe la go B is m a rc k A rc h ip e la g o Ta sk ul K ar ka r Lo ng K iw ai U

Waterborne Commerce of the United States, Calendar Year 1982. Part 2. Waterways and Harbors, Gulf Coast, Mississippi River System and Antilles.

DTIC Science & Technology

1984-07-01

PRACTICABLE. THE COPY FURNISHED TO DTIC CONTAINED A SIGNIFICANT NUMBER OF PAGES WHICH DO NOT REPRODUCE LEGIBLY. ". * e ...CW July 1984 % 13. NUMBER OF PAGES• % ~~Forrestal Bldg, Stop 391 , RR E "’-虗 O Tn314 IS..nDECA IA T1ON/DDCNRAD4 1NG -% .M IOR.IN(; G ENpC3Y NAME...joK C) 1 -z $1N CL i5 - C0 -’ IN~ 0 0 Lj -f z 2 10 2 4b. La I \\ ~ E LsJ . ~’ %Q~f %V7 ~, z - %.at 0 - . V Q iJ A E / I 41 r-- 11 ;,4. 4 LLE 0c 01 q CLI

Measuring spatial distributions of nuclear burn in ICF implosions at OMEGA and the NIF using proton emission imaging

NASA Astrophysics Data System (ADS)

Seguin, Fredrick; Rinderknecht, H. G.; Zylstra, A.; Sio, H.; Frenje, J.; Li, C. K.; Petrasso, R.; Rosenberg, M.; Marshall, F. J.; Sangster, T. C.; McKenty, P.; Craxton, S.; Rygg, J. R.; Le Pape, S.; Smalyuk, V.; Amendt, P. A.; Wilks, S. C.; MacKinnon, A.; Hoffman, N. M.

2015-11-01

Fusion reactions in ICF implosions of D3He-filled capsules produce 14.7-MeV D3He protons and 3-MeV DD protons. Spatial distributions of the D3He and DD reactions are studied with a penumbral imaging camera that utilizes a CR-39-based imaging detector to detect the protons. Up to three orthogonal cameras have been used simultaneously at OMEGA to study the 3-D structure of asymmetric implosions, and two orthogonal cameras have now been used to study an exploding-pusher implosion at the NIF. Recent data from OMEGA and from the NIF will be shown. This work was supported in part by NLUF, US DOE, and LLE.

Magnetoseed - Vasculäres Tissue Engineering

NASA Astrophysics Data System (ADS)

Perea Saavedra, Héctor; Methe, Heiko; Wintermantel, Erich

Gegenwärtig sind kardiovaskuläre Erkrankungen, allen voran die Arteriosklerose koronarer und zerebraler Gefäße, Ursache für 38% aller Todesfälle in Nordamerika und häufigste Todesursache europäischer Männer < 65 Jahre und zweithäufigste Todesursache bei Frauen [4]. Es wird prognostiziert, dass innerhalb der nächsten 10-15 Jahre kardiovaskuläre Erkrankungen und deren Komplikationen weltweit die häufigste Todesursache stellen werden. Dies ist zum einen Folge der ansteigenden Prävalenz kardiovaskulärer Erkrankungen in Osteuropa und zunehmend auch in den Entwicklungsländern, zum anderen Folge der kontinuierlich ansteigenden Inzidenz von Übergewicht und Diabetes mellitus in den westlichen Ländern.

Evaluation of 7 serum biomarkers and uterine artery Doppler ultrasound for first-trimester prediction of preeclampsia: a systematic review.

PubMed

Kuc, Sylwia; Wortelboer, Esther J; van Rijn, Bas B; Franx, Arie; Visser, Gerard H A; Schielen, Peter C J I

2011-04-01

Preeclampsia (PE) affects 1% to 2% of pregnant women and is a leading cause of maternal and perinatal morbidity and mortality worldwide. The clinical syndrome of PE arises in the second half of pregnancy. However, many underlying factors including defective placentation may already be apparent in the first and early second trimester in many patients. In clinical practice, there is currently no reliable screening method in the first trimester of pregnancy with sufficient accuracy to identify women at high risk to develop PE. Early identification of high-risk pregnancy may facilitate the development of new strategies for antenatal surveillance or prevention and thus improve maternal and perinatal outcome. The aim of this systematic review was to study the literature on the predictive potential of first-trimester serum markers and of uterine artery Doppler velocity waveform assessment (Ut-A Doppler). Literature on the 7 most studied serum markers (ADAM12, fβ-hCG, Inhibin A, Activin A, PP13, PlGF, and PAPP-A) and Ut-A Doppler was primarily selected. In the selected literature, a combination of these markers was analyzed, and where relevant, the value of maternal characteristics was added. Measurements of serum markers and Ut-A Doppler were performed between week 8 + 0 and 14 + 0 GA. Low levels of PP13, PlGF, and PAPP-A and elevated level of Inhibin A have been found to be significantly associated with the development of PE later in pregnancy. The detection rates of single markers, fixed at 10% false-positive rate, in the prediction of early-onset PE were relatively low, and ranged from 22% to 83%. Detection rates for combinations of multiple markers varied between 38% and 100%. Therefore, a combination of multiple markers yields high detection rates and is promising to identify patients at high risk of developing PE. However, large scale prospective studies are required to evaluate the power of this integrated approach in clinical practice. Obstetricians and

The Magnetic Recoil Spectrometer for time-resolved neutron measurements (MRSt) at the NIF

NASA Astrophysics Data System (ADS)

Parker, C. E.; Frenje, J. A.; Wink, C. W.; Gatu Johnson, M.; Lahmann, B.; Li, C. K.; Seguin, F. H.; Petrasso, R. D.; Hilsabeck, T. J.; Kilkenny, J. D.; Bionta, R.; Casey, D. T.; Khater, H. Y.; Forrest, C. J.; Glebov, V. Yu.; Sorce, C.; Hares, J. D.; Siegmund, O. H. W.

2017-10-01

The next-generation Magnetic Recoil Spectrometer, called MRSt, will provide time-resolved measurements of the DT-neutron spectrum. These measurements will provide critical information about the time evolution of the fuel assembly, hot-spot formation, and nuclear burn in Inertial Confinement Fusion (ICF) implosions at the National Ignition Facility (NIF). The neutron spectrum in the energy range 12-16 MeV will be measured with high accuracy ( 5%), unprecedented energy resolution ( 100 keV) and, for the first time ever, time resolution ( 20 ps). An overview of the physics motivation, conceptual design for meeting these performance requirements, and the status of the offline tests for critical components will be presented. This work was supported in part by the U.S. DOE, LLNL, and LLE.

Application of gas chromatography to analysis of spirit-based alcoholic beverages.

PubMed

Wiśniewska, Paulina; Śliwińska, Magdalena; Dymerski, Tomasz; Wardencki, Waldemar; Namieśnik, Jacek

2015-01-01

Spirit-based beverages are alcoholic drinks; their production processes are dependent on the type and origin of raw materials. The composition of this complex matrix is difficult to analyze, and scientists commonly choose gas chromatography techniques for this reason. With a wide selection of extraction methods and detectors it is possible to provide qualitative and quantitative analysis for many chemical compounds with various functional groups. This article describes different types of gas chromatography techniques and their most commonly used associated extraction techniques (e.g., LLE, SPME, SPE, SFE, and SBME) and detectors (MS, TOFMS, FID, ECD, NPD, AED, O or EPD). Additionally, brief characteristics of internationally popular spirit-based beverages and application of gas chromatography to the analysis of selected alcoholic drinks are presented.

Neutron-induced reactions in the hohlraum to study reaction in flight neutrons

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

Boswell, M. S.; Elliott, S. R.; Tybo, J.

2013-04-19

We are currently developing the physics necessary to measure the Reaction In Flight (RIF) neutron flux from a NIF capsule. A measurement of the RIF neutron flux from a NIF capsule could be used to deduce the stopping power in the cold fuel of the NIF capsule. A foil irradiated at the Omega laser at LLE was counted at the LANL low-background counting facility at WIPP. The estimated production rate of {sup 195}Au was just below our experimental sensitivity. We have made several improvements to our counting facility in recent months. These improvements are designed to increase our sensitivity, andmore » include installing two new low-background detectors, and taking steps to reduce noise in the signals.« less

Spill Assessment Model (SAM) Procedure for Manual Field Calculations.

DTIC Science & Technology

1980-04-01

34or ~ d 0 <OJ -i~ < 1I/6 z L) C.) 9. I- a. c cu cj El 0 0. 0. 0 0 ~~1~ 3 ci h -z L - 00,0o c 0. Ci) 0 #. .2 a) 13 i __ ______4-- (± 3d ) Hld3(Q 00 o 0 0 r...release rate since for the purpose of expected use it was assumed that inadequate in- formation would be available to accurately characterize a...Io:ot:.n1311 Madten.tepecificHas ofVWpels): S. HEALTH AZARDS Aqar I3 12,,tHit aoV~otrri A5lle~ t1es ,feWP6O 3eutrns: .1 9 Laten I-atdy1p,1 F I en: 0 1k

Ex Vivo and In Situ Evaluation of 'Dispelling-Wind' Chinese Medicine Herb-Drugs on Intestinal Absorption of Chlorogenic Acid.

PubMed

Zhai, Lixiang; Shi, Jun; Xu, Weitong; Heinrich, Michael; Wang, Jianying; Deng, Wenji

2015-12-01

This study aims to investigate the additive or synergistic effects and mechanism of intestinal absorption of extracts from two commonly used 'dispelling-wind' TCM botanical drugs [roots of Angelica dahurica (Hoffm.) Benth. & Hook. f. ex Franch. & Sav. (RAD) and Saposhnikovia divaricata (Turcz.) Schischk. (RSD)] using chlorogenic acid as a marker substance. Ex vivo everted intestinal sac and in situ single pass perfusion methods using rats were employed to investigate the effects of two TCM botanical drugs extracts on the intestinal absorption of chlorogenic acid. Both the extracts of RAD and RSD showed synergistic properties on the intestinal absorption of chlorogenic acid. The verapamil (a P-gp inhibitor) and intestinal dysbacteriosis model induced by norfloxacin increased the P(app) and K(a) of intestinal absorption of chlorogenic acid. These synergistic effects on intestinal absorption in a rat model can be correlated with the inhibition of P-gp and regulation of gut microbiota. This experimental approach has helped to better understand changes in the absorption of chlorogenic acid under different conditions. Copyright © 2015 John Wiley & Sons, Ltd.

Transepithelial Transport of PAMAM Dendrimers across Isolated Rat Jejunal Mucosae in Ussing Chambers

PubMed Central

2015-01-01

Oral delivery remains a challenge for poorly permeable hydrophilic macromolecules. Poly(amido amine) (PAMAM) dendrimers have shown potential for their possible oral delivery. Transepithelial transport of carboxyl-terminated G3.5 and amine-terminated G4 PAMAM dendrimers was assessed using isolated rat jejunal mucosae mounted in Ussing chambers. The 1 mM FITC-labeled dendrimers were added to the apical side of mucosae. Apparent permeability coefficients (Papp) from the apical to the basolateral side were significantly increased for FITC when conjugated to G3.5 PAMAM dendrimer compared to FITC alone. Minimal signs of toxicity were observed when mucosae were exposed to both dendrimers with respect to transepithelial electrical resistance changes, carbachol-induced short circuit current stimulation, and histological changes. [14C]-mannitol fluxes were not altered in the presence of 1 mM dendrimers, suggesting that the paracellular pathway was not affected at this concentration in this model. These results give insight into the mechanism of PAMAM dendrimer transepithelial rat jejunal transport, as well as toxicological considerations important for oral drug delivery. PMID:24992090

Transepithelial transport of PAMAM dendrimers across isolated rat jejunal mucosae in ussing chambers.

PubMed

Hubbard, Dallin; Ghandehari, Hamidreza; Brayden, David J

2014-08-11

Oral delivery remains a challenge for poorly permeable hydrophilic macromolecules. Poly(amido amine) (PAMAM) dendrimers have shown potential for their possible oral delivery. Transepithelial transport of carboxyl-terminated G3.5 and amine-terminated G4 PAMAM dendrimers was assessed using isolated rat jejunal mucosae mounted in Ussing chambers. The 1 mM FITC-labeled dendrimers were added to the apical side of mucosae. Apparent permeability coefficients (Papp) from the apical to the basolateral side were significantly increased for FITC when conjugated to G3.5 PAMAM dendrimer compared to FITC alone. Minimal signs of toxicity were observed when mucosae were exposed to both dendrimers with respect to transepithelial electrical resistance changes, carbachol-induced short circuit current stimulation, and histological changes. [(14)C]-mannitol fluxes were not altered in the presence of 1 mM dendrimers, suggesting that the paracellular pathway was not affected at this concentration in this model. These results give insight into the mechanism of PAMAM dendrimer transepithelial rat jejunal transport, as well as toxicological considerations important for oral drug delivery.

Prediction of intestinal absorption and metabolism of pharmacologically active flavones and flavanones.

PubMed

Serra, H; Mendes, T; Bronze, M R; Simplício, Ana Luísa

2008-04-01

Three glycosilated flavonoids (diosmin, hesperidin and naringin) and respective aglycones were characterized in terms of their apparent ionisation constants and bidirectional permeability using the cellular model Caco-2 as well as the artificial membrane model PAMPA. Ionisation curves were established by capillary electrophoresis. It was confirmed that significant amounts of the aglycones are ionised at physiological pH whereas the glycosides are in the neutral form. Permeation was not detected for the glycosides in either the apical-to-basolateral or basolateral-to-apical directions confirming the need for metabolism before absorption through the intestinal membrane. The aglycones permeated in both directions with apparent permeabilities (P(app)) in the range of 1-8x10(-5) cm/s. The results from both in vitro methods correlated providing some evidence of passive transport; however, the hypothesis of active transport cannot be excluded particularly in the case of diosmetin. Metabolism of the aglycones was detected with the cell model, more extensively when loading in the apical side. Some of the metabolites were identified as glucuronide conjugates by enzymatic hydrolysis.

Rare and low-frequency coding variants alter human adult height

PubMed Central

Marouli, Eirini; Graff, Mariaelisa; Medina-Gomez, Carolina; Lo, Ken Sin; Wood, Andrew R; Kjaer, Troels R; Fine, Rebecca S; Lu, Yingchang; Schurmann, Claudia; Highland, Heather M; Rüeger, Sina; Thorleifsson, Gudmar; Justice, Anne E; Lamparter, David; Stirrups, Kathleen E; Turcot, Valérie; Young, Kristin L; Winkler, Thomas W; Esko, Tõnu; Karaderi, Tugce; Locke, Adam E; Masca, Nicholas GD; Ng, Maggie CY; Mudgal, Poorva; Rivas, Manuel A; Vedantam, Sailaja; Mahajan, Anubha; Guo, Xiuqing; Abecasis, Goncalo; Aben, Katja K; Adair, Linda S; Alam, Dewan S; Albrecht, Eva; Allin, Kristine H; Allison, Matthew; Amouyel, Philippe; Appel, Emil V; Arveiler, Dominique; Asselbergs, Folkert W; Auer, Paul L; Balkau, Beverley; Banas, Bernhard; Bang, Lia E; Benn, Marianne; Bergmann, Sven; Bielak, Lawrence F; Blüher, Matthias; Boeing, Heiner; Boerwinkle, Eric; Böger, Carsten A; Bonnycastle, Lori L; Bork-Jensen, Jette; Bots, Michiel L; Bottinger, Erwin P; Bowden, Donald W; Brandslund, Ivan; Breen, Gerome; Brilliant, Murray H; Broer, Linda; Burt, Amber A; Butterworth, Adam S; Carey, David J; Caulfield, Mark J; Chambers, John C; Chasman, Daniel I; Chen, Yii-Der Ida; Chowdhury, Rajiv; Christensen, Cramer; Chu, Audrey Y; Cocca, Massimiliano; Collins, Francis S; Cook, James P; Corley, Janie; Galbany, Jordi Corominas; Cox, Amanda J; Cuellar-Partida, Gabriel; Danesh, John; Davies, Gail; de Bakker, Paul IW; de Borst, Gert J.; de Denus, Simon; de Groot, Mark CH; de Mutsert, Renée; Deary, Ian J; Dedoussis, George; Demerath, Ellen W; den Hollander, Anneke I; Dennis, Joe G; Di Angelantonio, Emanuele; Drenos, Fotios; Du, Mengmeng; Dunning, Alison M; Easton, Douglas F; Ebeling, Tapani; Edwards, Todd L; Ellinor, Patrick T; Elliott, Paul; Evangelou, Evangelos; Farmaki, Aliki-Eleni; Faul, Jessica D; Feitosa, Mary F; Feng, Shuang; Ferrannini, Ele; Ferrario, Marco M; Ferrieres, Jean; Florez, Jose C; Ford, Ian; Fornage, Myriam; Franks, Paul W; Frikke-Schmidt, Ruth; Galesloot, Tessel E; Gan, Wei; Gandin, Ilaria; Gasparini, Paolo; Giedraitis, Vilmantas; Giri, Ayush; Girotto, Giorgia; Gordon, Scott D; Gordon-Larsen, Penny; Gorski, Mathias; Grarup, Niels; Grove, Megan L.; Gudnason, Vilmundur; Gustafsson, Stefan; Hansen, Torben; Harris, Kathleen Mullan; Harris, Tamara B; Hattersley, Andrew T; Hayward, Caroline; He, Liang; Heid, Iris M; Heikkilä, Kauko; Helgeland, Øyvind; Hernesniemi, Jussi; Hewitt, Alex W; Hocking, Lynne J; Hollensted, Mette; Holmen, Oddgeir L; Hovingh, G. Kees; Howson, Joanna MM; Hoyng, Carel B; Huang, Paul L; Hveem, Kristian; Ikram, M. Arfan; Ingelsson, Erik; Jackson, Anne U; Jansson, Jan-Håkan; Jarvik, Gail P; Jensen, Gorm B; Jhun, Min A; Jia, Yucheng; Jiang, Xuejuan; Johansson, Stefan; Jørgensen, Marit E; Jørgensen, Torben; Jousilahti, Pekka; Jukema, J Wouter; Kahali, Bratati; Kahn, René S; Kähönen, Mika; Kamstrup, Pia R; Kanoni, Stavroula; Kaprio, Jaakko; Karaleftheri, Maria; Kardia, Sharon LR; Karpe, Fredrik; Kee, Frank; Keeman, Renske; Kiemeney, Lambertus A; Kitajima, Hidetoshi; Kluivers, Kirsten B; Kocher, Thomas; Komulainen, Pirjo; Kontto, Jukka; Kooner, Jaspal S; Kooperberg, Charles; Kovacs, Peter; Kriebel, Jennifer; Kuivaniemi, Helena; Küry, Sébastien; Kuusisto, Johanna; La Bianca, Martina; Laakso, Markku; Lakka, Timo A; Lange, Ethan M; Lange, Leslie A; Langefeld, Carl D; Langenberg, Claudia; Larson, Eric B; Lee, I-Te; Lehtimäki, Terho; Lewis, Cora E; Li, Huaixing; Li, Jin; Li-Gao, Ruifang; Lin, Honghuang; Lin, Li-An; Lin, Xu; Lind, Lars; Lindström, Jaana; Linneberg, Allan; Liu, Yeheng; Liu, Yongmei; Lophatananon, Artitaya; Luan, Jian'an; Lubitz, Steven A; Lyytikäinen, Leo-Pekka; Mackey, David A; Madden, Pamela AF; Manning, Alisa K; Männistö, Satu; Marenne, Gaëlle; Marten, Jonathan; Martin, Nicholas G; Mazul, Angela L; Meidtner, Karina; Metspalu, Andres; Mitchell, Paul; Mohlke, Karen L; Mook-Kanamori, Dennis O; Morgan, Anna; Morris, Andrew D; Morris, Andrew P; Müller-Nurasyid, Martina; Munroe, Patricia B; Nalls, Mike A; Nauck, Matthias; Nelson, Christopher P; Neville, Matt; Nielsen, Sune F; Nikus, Kjell; Njølstad, Pål R; Nordestgaard, Børge G; Ntalla, Ioanna; O'Connel, Jeffrey R; Oksa, Heikki; Loohuis, Loes M Olde; Ophoff, Roel A; Owen, Katharine R; Packard, Chris J; Padmanabhan, Sandosh; Palmer, Colin NA; Pasterkamp, Gerard; Patel, Aniruddh P; Pattie, Alison; Pedersen, Oluf; Peissig, Peggy L; Peloso, Gina M; Pennell, Craig E; Perola, Markus; Perry, James A; Perry, John R.B.; Person, Thomas N; Pirie, Ailith; Polasek, Ozren; Posthuma, Danielle; Raitakari, Olli T; Rasheed, Asif; Rauramaa, Rainer; Reilly, Dermot F; Reiner, Alex P; Renström, Frida; Ridker, Paul M; Rioux, John D; Robertson, Neil; Robino, Antonietta; Rolandsson, Olov; Rudan, Igor; Ruth, Katherine S; Saleheen, Danish; Salomaa, Veikko; Samani, Nilesh J; Sandow, Kevin; Sapkota, Yadav; Sattar, Naveed; Schmidt, Marjanka K; Schreiner, Pamela J; Schulze, Matthias B; Scott, Robert A; Segura-Lepe, Marcelo P; Shah, Svati; Sim, Xueling; Sivapalaratnam, Suthesh; Small, Kerrin S; Smith, Albert Vernon; Smith, Jennifer A; Southam, Lorraine; Spector, Timothy D; Speliotes, Elizabeth K; Starr, John M; Steinthorsdottir, Valgerdur; Stringham, Heather M; Stumvoll, Michael; Surendran, Praveen; Hart, Leen M ‘t; Tansey, Katherine E; Tardif, Jean-Claude; Taylor, Kent D; Teumer, Alexander; Thompson, Deborah J; Thorsteinsdottir, Unnur; Thuesen, Betina H; Tönjes, Anke; Tromp, Gerard; Trompet, Stella; Tsafantakis, Emmanouil; Tuomilehto, Jaakko; Tybjaerg-Hansen, Anne; Tyrer, Jonathan P; Uher, Rudolf; Uitterlinden, André G; Ulivi, Sheila; van der Laan, Sander W; Van Der Leij, Andries R; van Duijn, Cornelia M; van Schoor, Natasja M; van Setten, Jessica; Varbo, Anette; Varga, Tibor V; Varma, Rohit; Edwards, Digna R Velez; Vermeulen, Sita H; Vestergaard, Henrik; Vitart, Veronique; Vogt, Thomas F; Vozzi, Diego; Walker, Mark; Wang, Feijie; Wang, Carol A; Wang, Shuai; Wang, Yiqin; Wareham, Nicholas J; Warren, Helen R; Wessel, Jennifer; Willems, Sara M; Wilson, James G; Witte, Daniel R; Woods, Michael O; Wu, Ying; Yaghootkar, Hanieh; Yao, Jie; Yao, Pang; Yerges-Armstrong, Laura M; Young, Robin; Zeggini, Eleftheria; Zhan, Xiaowei; Zhang, Weihua; Zhao, Jing Hua; Zhao, Wei; Zhao, Wei; Zheng, He; Zhou, Wei; Rotter, Jerome I; Boehnke, Michael; Kathiresan, Sekar; McCarthy, Mark I; Willer, Cristen J; Stefansson, Kari; Borecki, Ingrid B; Liu, Dajiang J; North, Kari E; Heard-Costa, Nancy L; Pers, Tune H; Lindgren, Cecilia M; Oxvig, Claus; Kutalik, Zoltán; Rivadeneira, Fernando; Loos, Ruth JF; Frayling, Timothy M; Hirschhorn, Joel N; Deloukas, Panos; Lettre, Guillaume

2016-01-01

Summary Height is a highly heritable, classic polygenic trait with ∼700 common associated variants identified so far through genome-wide association studies. Here, we report 83 height-associated coding variants with lower minor allele frequencies (range of 0.1-4.8%) and effects of up to 2 cm/allele (e.g. in IHH, STC2, AR and CRISPLD2), >10 times the average effect of common variants. In functional follow-up studies, rare height-increasing alleles of STC2 (+1-2 cm/allele) compromised proteolytic inhibition of PAPP-A and increased cleavage of IGFBP-4 in vitro, resulting in higher bioavailability of insulin-like growth factors. These 83 height-associated variants overlap genes mutated in monogenic growth disorders and highlight new biological candidates (e.g. ADAMTS3, IL11RA, NOX4) and pathways (e.g. proteoglycan/glycosaminoglycan synthesis) involved in growth. Our results demonstrate that sufficiently large sample sizes can uncover rare and low-frequency variants of moderate to large effect associated with polygenic human phenotypes, and that these variants implicate relevant genes and pathways. PMID:28146470

De Novo Design and Experimental Characterization of Ultrashort Self-Associating Peptides

PubMed Central

Xue, Bo; Robinson, Robert C.; Hauser, Charlotte A. E.; Floudas, Christodoulos A.

2014-01-01

Self-association is a common phenomenon in biology and one that can have positive and negative impacts, from the construction of the architectural cytoskeleton of cells to the formation of fibrils in amyloid diseases. Understanding the nature and mechanisms of self-association is important for modulating these systems and in creating biologically-inspired materials. Here, we present a two-stage de novo peptide design framework that can generate novel self-associating peptide systems. The first stage uses a simulated multimeric template structure as input into the optimization-based Sequence Selection to generate low potential energy sequences. The second stage is a computational validation procedure that calculates Fold Specificity and/or Approximate Association Affinity (K*association) based on metrics that we have devised for multimeric systems. This framework was applied to the design of self-associating tripeptides using the known self-associating tripeptide, Ac-IVD, as a structural template. Six computationally predicted tripeptides (Ac-LVE, Ac-YYD, Ac-LLE, Ac-YLD, Ac-MYD, Ac-VIE) were chosen for experimental validation in order to illustrate the self-association outcomes predicted by the three metrics. Self-association and electron microscopy studies revealed that Ac-LLE formed bead-like microstructures, Ac-LVE and Ac-YYD formed fibrillar aggregates, Ac-VIE and Ac-MYD formed hydrogels, and Ac-YLD crystallized under ambient conditions. An X-ray crystallographic study was carried out on a single crystal of Ac-YLD, which revealed that each molecule adopts a β-strand conformation that stack together to form parallel β-sheets. As an additional validation of the approach, the hydrogel-forming sequences of Ac-MYD and Ac-VIE were shuffled. The shuffled sequences were computationally predicted to have lower K*association values and were experimentally verified to not form hydrogels. This illustrates the robustness of the framework in predicting self

Efficacy of head space solid-phase microextraction coupled to gas chromatography-mass spectrometry method for determination of the trace extracellular hydrocarbons of cyanobacteria.

PubMed

Guan, Wenna; Zhu, Tao; Wang, Yuejie; Zhang, Zhongyi; Jin, Zhao; Wang, Cong; Bai, Fali

2016-09-01

Hydrocarbons are widespread in cyanobacteria, and the biochemical synthetic pathways were recently identified. Intracellular fatty alka(e)nes of cyanobacteria have been detected by liquid-liquid extraction (LLE) coupled to gas chromatography-mass spectrometry (GC/MS). However, whether fatty alka(e)nes can be released to cyanobacterial culture media remains to be clarified. This work develops a sensitive method for analyzing the trace level of extracellular hydrocarbons in cyanobacterial culture media by head space solid-phase microextraction (HS-SPME) coupled to GC/MS. Headspace (HS) extraction mode using polydimethylsiloxane fiber to extract for 30min at 50°C was employed as the optimal extraction conditions. Five cyanobacterial fatty alka(e)nes analogs including pentadecene (C15:1), pentadecane (C15:0), heptadecene (C17:1), heptadecane (C17:0), nonadecane (C19:0) were analyzed, and the data obtained from HS-SPME-GC/MS method were quantified using internal standard peak area comparisons. Limits of detection (LOD), limits of quantitation (LOQ), linear dynamic range, precisions (RSD) and recovery for the analysis of extracellular fatty alka(e)nes of cyanobacteria by HS-SPME-GC/MS were evaluated. The LODs limits of detection (S/N = 3) varied from 10 to 21 ng L-1. The correlation coefficients (r) of the calibration curves ranged from 0.9873 to 0.9977 with a linearity from 0.1 to 50 μg L-1. The RSD values were ranging from 7.8 to 14.0% and from 4.0 to 8.8% at 1.0 μg L-1 and 10.0 μg L-1 standard solutions, respectively. Comparative analysis of extracellular fatty alka(e)nes in the culture media of model cyanobacteria Synechocystis sp. PCC 6803 demonstrated that sensitivity of HS-SPME-GC/MS method was significantly higher than LLE method. Finally, we found that heptadecane can be released into the culture media of Synechocystis sp. PCC 6803 at the later growth period. Copyright © 2016 Elsevier B.V. All rights reserved.

Level of Education as a Risk Factor for Extensive Prevalence of Cervical Intervertebral Disc Degenerative Changes and Chronic Neck Pain.

PubMed

Markotić, Vedran; Zubac, Damir; Miljko, Miro; Šimić, Goran; Zalihić, Amra; Bogdan, Gojko; Radančević, Dorijan; Šimić, Ana Dugandžić; Mašković, Josip

2017-09-01

The aim of this study was to document the prevalence of degenerative intervertebral disc changes in the patients who previously reported symptoms of neck pain and to determine the influence of education level on degenerative intervertebral disc changes and subsequent chronic neck pain. One hundred and twelve patients were randomly selected from the University Hospital in Mostar, Bosna and Herzegovina, (aged 48.5±12.7 years) and submitted to magnetic resonance imaging (MRI) of the cervical spine. MRI of 3.0 T (Siemens, Skyrim, Erlangen, Germany) was used to obtain cervical spine images. Patients were separated into two groups based on their education level: low education level (LLE) and high education level (HLE). Pfirrmann classification was used to document intervertebral disc degeneration, while self-reported chronic neck pain was evaluated using the previously validated Oswestry questionnaire. The entire logistic regression model containing all predictors was statistically significant, (χ 2 (3)=12.2, p=0.02), and was able to distinguish between respondents who had chronic neck pain and vice versa. The model explained between 10.0% (Cox-Snell R 2 ) and 13.8% (Nagelkerke R 2 ) of common variance with Pfirrmann classification, and it had the strength to discriminate and correctly classify 69.6% of patients. The probability of a patient being classified in the high or low group of degenerative disc changes according to the Pfirrmann scale was associated with the education level (Wald test: 5.5, p=0.02). Based on the Pfirrmann assessment scale, the HLE group was significantly different from the LLE group in the degree of degenerative changes of the cervical intervertebral discs (U=1,077.5, p=0.001). A moderate level of intervertebral disc degenerative changes (grade II and III) was equally matched among all patients, while the overall results suggest a higher level of education as a risk factor leading to cervical disc degenerative changes, regardless of age

Quantitative studies of kinetic effects in direct- and indirect-drive Inertial Confinement Fusion implosions

NASA Astrophysics Data System (ADS)

Rinderknecht, Hans

2013-10-01

A comprehensive set of experiments using shock-driven implosions has been conducted to quantitatively study kinetic effects by exploring deviations from hydrodynamic behavior in plasmas relevant to inertial confinement fusion (ICF). Two types of targets were imploded at OMEGA to create ~10 keV, ~1022 cm-3 plasmas with conditions comparable to the incipient hotspot in ignition designs: thin-glass targets filled with mixtures of D2 and 3He gas; and thin deuterated-plastic shells filled with 3He. In the thin-glass experiments, the gas pressure was varied from 1 to 25 atm to scan the ion-mean-free path in the plasma at shock burn. The observed nuclear yields and temperatures deviated more strongly from hydrodynamic predictions as the ion-mean-free path increased to the order of the plasma size. This result provides the first direct experimental evidence how kinetic effects impact yields and ion temperature. The ratio of D to 3He was also varied while maintaining the fuel mass density. As the D fraction was reduced, the DD and D3He fusion products displayed an anomalous yield reduction. Separation of the D and 3He ion species across the strong (Mach ~10) shock-front will be discussed as the likely cause of this result. Finally, thin-CD shells filled with 3He produced significantly more D3He-protons when imploded than is explained by hydrodynamic mix models. This result suggests a kinetic form of mix dominates at the strongly-shocked shell-gas interface. This work was performed in collaboration with C. Li, M. Rosenberg, A. Zylstra, H. Sio, M. Gatu Johnson, F. Séguin, J. Frenje, and R. Petrasso (MIT), V. Glebov, C. Stoeckl, J. Delettrez, and C. Sangster (LLE), J. Pino, P. Amendt, C. Bellei, and S. Wilks (LLNL), G. Kagan, N. Hoffmann and K. Molvig (LANL), and A. Nikroo (GA) and was supported in part by the NLUF, FSC/UR, U.S. DOE, LLNL and LLE.

Rapid analysis of pharmaceuticals and personal care products in fish plasma micro-aliquots using liquid chromatography tandem mass spectrometry.

PubMed

Chen, Fangfang; Gong, Zhiyuan; Kelly, Barry C

2015-02-27

A sensitive analytical method based on liquid-liquid extraction (LLE) and liquid chromatography tandem mass spectrometry (LC-MS/MS) was developed for rapid analysis of 11 pharmaceuticals and personal care products (PPCPs) in fish plasma micro-aliquots (∼20μL). Target PPCPs included, bisphenol A, carbamazepine, diclofenac, fluoxetine, gemfibrozil, ibuprofen, naproxen, risperidone, sertraline, simvastatin and triclosan. A relatively quicker and cheaper LLE procedure exhibited comparable analyte recoveries with solid-phase extraction. Rapid separation and analysis of target compounds in fish plasma extracts was achieved by employing a high efficiency C-18 HPLC column (Agilent Poroshell 120 SB-C18, 2.1mm×50mm, 2.7μm) and fast polarity switching, enabling effective monitoring of positive and negative ions in a single 9min run. With the exception of bisphenol A, which exhibited relatively high background contamination, method detection limits of individual PPCPs ranged between 0.15 and 0.69pg/μL, while method quantification limits were between 0.05 and 2.3pg/μL. Mean matrix effect (ME) values ranged between 65 and 156% for the various target analytes. Isotope dilution quantification using isotopically labelled internal surrogates was utilized to correct for signal suppression or enhancement and analyte losses during sample preparation. The method was evaluated by analysis of 20μL plasma micro-aliquots collected from zebrafish (Danio rerio) from a laboratory bioaccumulation study, which included control group fish (no exposure), as well as fish exposed to environmentally relevant concentrations of PPCPs. Using the developed LC-MS/MS based method, concentrations of the studied PPCPs were consistently detected in the low pg/μL (ppb) range. The method may be useful for investigations requiring fast, reliable concentration measurements of PPCPs in fish plasma. In particular, the method may be applicable for in situ contaminant biomonitoring, as well as

Rapid and automated analysis of aflatoxin M1 in milk and dairy products by online solid phase extraction coupled to ultra-high-pressure-liquid-chromatography tandem mass spectrometry.

PubMed

Campone, Luca; Piccinelli, Anna Lisa; Celano, Rita; Pagano, Imma; Russo, Mariateresa; Rastrelli, Luca

2016-01-08

This study reports a fast and automated analytical procedure for the analysis of aflatoxin M1 (AFM1) in milk and dairy products. The method is based on the simultaneous protein precipitation and AFM1 extraction, by salt-induced liquid-liquid extraction (SI-LLE), followed by an online solid-phase extraction (online SPE) coupled to ultra-high-pressure-liquid chromatography-tandem mass spectrometry (UHPLC-MS/MS) analysis to the automatic pre-concentration, clean up and sensitive and selective determination of AFM1. The main parameters affecting the extraction efficiency and accuracy of the analytical method were studied in detail. In the optimal conditions, acetonitrile and NaCl were used as extraction/denaturant solvent and salting-out agent in SI-LLE, respectively. After centrifugation, the organic phase (acetonitrile) was diluted with water (1:9 v/v) and purified (1mL) by online C18 cartridge coupled with an UHPLC column. Finally, selected reaction monitoring (SRM) acquisition mode was applied to the detection of AFM1. Validation studies were carried out on different dairy products (whole and skimmed cow milk, yogurt, goat milk, and powder infant formula), providing method quantification limits about 25 times lower than AFM1 maximum levels permitted by EU regulation 1881/2006 in milk and dairy products for direct human consumption. Recoveries (86-102%) and repeatability (RSD<3, n=6) meet the performance criteria required by EU regulation N. 401/2006 for the determination of the levels of mycotoxins in foodstuffs. Moreover, no matrix effects were observed in the different milk and dairy products studied. The proposed method improves the performance of AFM1 analysis in milk samples as AFM1 determination is performed with a degree of accuracy higher than the conventional methods. Other advantages are the reduction of sample preparation procedure, time and cost of the analysis, enabling high sample throughput that meet the current concerns of food safety and the public

A manifold learning approach to target detection in high-resolution hyperspectral imagery

NASA Astrophysics Data System (ADS)

Ziemann, Amanda K.

Imagery collected from airborne platforms and satellites provide an important medium for remotely analyzing the content in a scene. In particular, the ability to detect a specific material within a scene is of high importance to both civilian and defense applications. This may include identifying "targets" such as vehicles, buildings, or boats. Sensors that process hyperspectral images provide the high-dimensional spectral information necessary to perform such analyses. However, for a d-dimensional hyperspectral image, it is typical for the data to inherently occupy an m-dimensional space, with m << d. In the remote sensing community, this has led to a recent increase in the use of manifold learning, which aims to characterize the embedded lower-dimensional, non-linear manifold upon which the hyperspectral data inherently lie. Classic hyperspectral data models include statistical, linear subspace, and linear mixture models, but these can place restrictive assumptions on the distribution of the data; this is particularly true when implementing traditional target detection approaches, and the limitations of these models are well-documented. With manifold learning based approaches, the only assumption is that the data reside on an underlying manifold that can be discretely modeled by a graph. The research presented here focuses on the use of graph theory and manifold learning in hyperspectral imagery. Early work explored various graph-building techniques with application to the background model of the Topological Anomaly Detection (TAD) algorithm, which is a graph theory based approach to anomaly detection. This led towards a focus on target detection, and in the development of a specific graph-based model of the data and subsequent dimensionality reduction using manifold learning. An adaptive graph is built on the data, and then used to implement an adaptive version of locally linear embedding (LLE). We artificially induce a target manifold and incorporate it into

Expeditious method to determine uranium in the process control samples of chemical plant separating (233)U from thoria irradiated in power reactors.

PubMed

Kedari, C S; Kharwandikar, B K; Banerjee, K

2016-11-01

Analysis of U in the samples containing a significant proportion of (232)U and high concentration of Th is of great concern. Transmutation of Th in the nuclear power reactor produces a notable quantity of (232)U (half life 68.9 years) along with fissile isotope (233)U. The decay series of (232)U is initiated with (228)Th (half life 1.9 year) and it is followed by several short lived α emitting progenies, (224)Ra, (220)Rn, (216)Po, (212)Bi and (212)Po. Even at the smallest contamination of (228)Th in the sample, a very high pulse rate of α emission is obtained, which is to be counted for the radiometric determination of [U]. A commercially available anionic type of extractant Alamine®336 is used to obtain the selective extraction of U from other alpha active elements and fission products present in the sample. Experimental conditions of liquid-liquid extraction (LLE) are optimized for obtaining maximum decontamination and recovery of U in the organic phase. The effect of some interfering ionic impurities in the sample on the process of separation is investigated. Depending on the level of the concentration of U in the samples, spectrophotometry or radiometry methods are adopted for its determination after separation by LLE. Under optimized experimental conditions, i.e. 5.5M HCl in the aqueous phase and 0.27M Alamin®336 in the organic phase, the recovery of U is about 100%, the decontamination factor with respect to Th is >2000 and the extraction of fission products like (90)Sr, (144)Ce and (134,137)Cs is negligible. The detection limit for [U] using α radiometry is 10mg/L, even in presence of >100g/L of Th in the sample. Accuracy and precision for the determination of U is also assessed. Reproducibility of results is within 5%. This method shows very good agreement with the results obtained by mass spectrometry. Copyright © 2016 Elsevier B.V. All rights reserved.

Studies on Five Senses Treatment

NASA Astrophysics Data System (ADS)

Sato, Sadaka; Miao, Tiejun; Oyama-Higa, Mayumi

2011-06-01

This study proposed a therapy from complementary and alternative medicine to treat mental disorder by through interactions of five senses between therapist and patient. In this method sounding a certain six voices play an important role in healing and recovery. First, we studied effects of speaking using scalp- EEG measurement. Chaos analysis of EEG showed a largely enhanced largest Lyapunov exponent (LLE) during the speaking. In addition, EEG power spectrum showed an increase over most frequencies. Second, we performed case studies on mental disorder using the therapy. Running power spectrum of EEG of patients indicated decreasing power at end of treatment, implying five senses therapy induced relaxed and lowered energy in central neural system. The results agreed with patient's reports that there were considerable decline in anxiety and improvements in mood.

Satellitenbewegung, band III: Natiirliche und gesteuerte bewegung.

NASA Astrophysics Data System (ADS)

Jochim, E. F.

2014-12-01

Im dritten Band der Satellitenbewegung werden in fortlaufender Nummerierung einige für Untersuchungen der Bewegung der künstlichen Satelliten wichtige Grundlagen der Astrodynamik mit ausführlichen mathematischen Formelsystemen behandelt. Dazu zählen die unterschiedlichen Aspekte der Bewegung der natürlichen Himmelskörper, die Steuerung und Kontrolle von künstlichen Objekten, und insbesondere die für eine Satellitenbahnanalyse wichtigen physikalischen Beeinflussungen einer Satellitenbewegung. Mathematisch entscheidend ist die Wahl geeigneter Bahnparameter, die ein bestimmtes Bewegungsproblem widerspruchsfrei und singularitätenfrei zu behandeln gestatten. Für die Behandlung routinemäßiger Aufgabenstellungen der Satellitenbewegung, in erster Linie einer präzisen Bahnbestimmung und Bahnverbesserung, kann auf eine Fülle von lehrbuchartigen Monographien verwiesen werden, so dass diese Problematik in der vorliegenden Arbeit nur angedeutet werden soll.

Exploration of kinetic and multiple-ion-fluids effects in D3He and T3He gas-filled ICF implosions using multiple nuclear reaction histories

NASA Astrophysics Data System (ADS)

Sio, Hong; Rinderknecht, Hans; Rosenberg, Michael; Zylstra, Alex; Séguin, Fredrick; Gatu Johnson, Maria; Li, Chikang; Petrasso, Richard; Hoffman, Nelson; Kagan, Krigory; Molvig, Kim; Amendt, Peter; Bellei, Claudio; Wilks, Scott; Stoeckl, Christian; Glebov, Vladimir; Betti, Riccardo; Sangster, Thomas; Katz, Joseph

2014-10-01

To explore kinetic and multi-ion-fluid effects in D3He and T3He gas-filled shock-driven implosions, multiple nuclear reaction histories were measured using the upgraded Particle Temporal Diagnostic (PTD) on OMEGA. For D3He gas-filled implosions, the relative timing of the DD and D3He reaction histories were measured with 20 ps precision. For T3He gas-filled implosions (with 1-2% deuterium), the relative timing of the DT and D3He reaction histories were measured with 10 ps precision. The observed differences between the reaction histories on these two OMEGA experiments are contrasted to 1-D single-ion hydro simulations for different gas-fill pressure and gas mixture. This work is supported in part by the U.S. DOE, LLNL, LLE, and NNSA SSGF.

A Review of Feature Extraction Software for Microarray Gene Expression Data

PubMed Central

Tan, Ching Siang; Ting, Wai Soon; Mohamad, Mohd Saberi; Chan, Weng Howe; Deris, Safaai; Ali Shah, Zuraini

2014-01-01

When gene expression data are too large to be processed, they are transformed into a reduced representation set of genes. Transforming large-scale gene expression data into a set of genes is called feature extraction. If the genes extracted are carefully chosen, this gene set can extract the relevant information from the large-scale gene expression data, allowing further analysis by using this reduced representation instead of the full size data. In this paper, we review numerous software applications that can be used for feature extraction. The software reviewed is mainly for Principal Component Analysis (PCA), Independent Component Analysis (ICA), Partial Least Squares (PLS), and Local Linear Embedding (LLE). A summary and sources of the software are provided in the last section for each feature extraction method. PMID:25250315

Nuchal translucency measurement, free β-hCG and PAPP-A concentrations in IVF/ICSI pregnancies: systematic review and meta-analysis.

PubMed

Cavoretto, Paolo; Giorgione, Veronica; Cipriani, Sonia; Viganò, Paola; Candiani, Massimo; Inversetti, Annalisa; Ricci, Elena; Parazzini, Fabio

2017-06-01

So far, data on the effect of assisted reproductive technologies (ART) on the components of first trimester combined screening for Down syndrome are still controversial. A systematic search of the literature was performed in order to identify the effect of ART, particularly in vitro fertilization (IVF) and intracytoplasmic sperm injection (ICSI) with fresh embryo transfer, on the nuchal translucency, free beta-human chorionic gonadotrophin and pregnancy-associated plasma protein-A measurements. Moreover, a meta-analysis and a descriptive graphical representation of the ratios between ART and spontaneous pregnancies (controls) values of median of the multiple of median (m 0 MoM) were performed. Free beta-human chorionic gonadotrophin test showed slightly higher values in the ICSI group than controls (RR = 1.09, 95%CI: 1.03-1.16) but not in the IVF group (RR = 1.03, 95%CI: 0.94-1.12). Pregnancy-associated plasma protein-A values for IVF/ICSI, IVF and ICSI showed lower values in comparison with controls (RR, 95%CI 0.85, 0.80-0.90; 0.82, 0.74-0.89 and 0.83, 0.79-0.86, respectively). The nuchal translucency measurement did not show any statistical differences between study groups (IVF and ICSI) and controls (RR = 1.00, 95%CI: 0.94-1.08 and RR = 1.01, 95%CI: 0.97-1.05, respectively). These results may be due to alterations in the placentation of ART pregnancies. Differentiating further subgroups of ART pregnancies may explain the differences in biomarker concentrations, in prenatal behavior and in obstetric outcomes between ART and spontaneous pregnancies. © 2017 John Wiley & Sons, Ltd. © 2017 John Wiley & Sons, Ltd.

OS087. Maternal characteristics, mean arterial pressure and PLGF in early prediction of preeclampsia.

PubMed

Kuc, S; Koster, M P; Franx, A; Schielen, P C; Visser, G H

2012-07-01

In a previous study, we described the predictive value of first-trimester pregnancy-associated plasma protein-A (PAPP-A), free beta-subunit of human chorionic gonadotrophin (fb-hCG), Placental Growth Factor (PlGF) and A Desintegrin And Metalloproteinase 12 (ADAM12) for early onset preeclampsia (delivery <34 weeks) [1]. The objective of the current study was to obtain the predictive value of these serum makers, for both early onset PE (EOPE) and late onset PE (LOPE), combined with maternal characteristics and first-trimester maternal mean arterial blood pressure (MAP). This was a nested case-control study, using stored first-trimester maternal serum from 167 women who subsequently developed PE, and 500 uncomplicated singleton pregnancies which resulted in a live birth =>37 weeks. Maternal characteristics (i.e. medical records, parity, weight, length) MAP and pregnancy outcome (i.e. gestational age at delivery, birthweight, fetal sex) were collected for each individual and used to calculate prior risks for PE in a multiple logistic regression model. MAP values and marker levels of PAPP-A, fb-hCG, PlGF and ADAM12 were expressed as multiples of the gestation-specific normal median (MoMs). Subsequently, MoMs were log-transformed and compared between PE and controls using Student's t-tests. Posterior risks were calculated using different combinations of variables;(1) maternal characteristics, serum markers, and MAP separately (2) maternal characteristics combined with serum markers or MAP (3) maternal characteristics combined with serum markers and MAP. The model-predicted detection rates (DR) for fixed 10% false-positive rates were obtained for EOPE and LOPE with or without intra-uterine growth restriction (IUGR,birth weight <10th centile). The maternal characteristics: maternal age, weight, length, smoking status and nulliparity were discriminative between PE and control groups and therefore incorporated in the multiple logistic regression model. MoM MAP was

Augmented bioavailability of felodipine through an α-linolenic acid-based microemulsion.

PubMed

Singh, Mahendra; Kanoujia, Jovita; Parashar, Poonam; Arya, Malti; Tripathi, Chandra B; Sinha, V R; Saraf, Shailendra K; Saraf, Shubhini A

2018-02-01

The oral bioavailability of felodipine, a dihydropyridine calcium channel antagonist, is about 15%. This may be due to poor water solubility, and a lower intestinal permeability than a BCS class I drug, and hepatic first-pass metabolism of the drug. Many drugs are unpopular due to solubility issues. The goal of this study was to develop and optimize a felodipine-containing microemulsion to improve the intestinal permeability and bioavailability of the drug. The felodipine microemulsions were developed with the selected components, i.e., α-linolenic acid as the oil phase, Tween 80 as a surfactant, and isopropyl alcohol as co-surfactant using Box-Behnken design and characterized for in vitro release and particle size. The optimized felodipine-loaded microemulsion was investigated for physicochemical interaction, surface morphology, intestinal permeability, rheology, cytotoxicity, cellular uptake, pharmacodynamic (electrocardiogram and heart rate variability), and pharmacokinetic studies to explore its suitability as a promising oral drug delivery system for the treatment of hypertension. The optimized felodipine-loaded microemulsion showed significantly higher (P < 0.05) apparent permeability coefficients (Papp) at 7.918 × 10 -5  cm/s after 1 h, when compared with conventional formulations that are marketed tablet, drug oily solution, and drug emulsion, which showed a maximum Papp of 3.013, 4.428, and 5.335 × 10 -5  cm/s, respectively. The optimized felodipine-loaded microemulsion showed biocompatibility and no cytotoxicity. Cellular uptake studies confirmed payload delivery to a cellular site on the J774.A1 cell line. The rheology study of the optimized felodipine-loaded microemulsion revealed Newtonian-type flow behavior and discontinuous microemulsion formation. In pharmacodynamic studies, significant differences in parameters were observed between the optimized felodipine-loaded microemulsion and marketed formulation. The optimized felodipine

Bifurcation and Firing Patterns of the Pancreatic β-Cell

NASA Astrophysics Data System (ADS)

Wang, Jing; Liu, Shenquan; Liu, Xuanliang; Zeng, Yanjun

Using a model of individual isolated pancreatic β-cells, we investigated bifurcation diagrams of interspike intervals (ISIs) and largest Lyapunov exponents (LLE), which clearly demonstrated a wide range of transitions between different firing patterns. The numerical simulation results revealed the effect of different time constants and ion channels on the neuronal discharge rhythm. Furthermore, an individual cell exhibited tonic spiking, square-wave bursting, and tapered bursting. Additionally, several bifurcation phenomena can be observed in this paper, such as period-doubling, period-adding, inverse period-doubling and inverse period-adding scenarios. In addition, we researched the mechanisms underlying two kinds of bursting (tapered and square-wave bursting) by use of fast-slow dynamics analysis. Finally, we analyzed the codimension-two bifurcation of the fast subsystem and studied cusp bifurcation, generalized Hopf (or Bautin) bifurcation and Bogdanov-Takens bifurcation.

Double-shell target fabrication workshop-2016 report

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

Wang, Y. Morris; Oertel, John; Farrell, Michael

On June 30, 2016, over 40 representatives from Lawrence Livermore National Laboratory (LLNL), Los Alamos National Laboratory (LANL), General Atomics (GA), Laboratory for Laser Energetics (LLE), Schafer Corporation, and NNSA headquarter attended a double-shell (DS) target fabrication workshop at Livermore, California. Pushered-single-shell (PSS) and DS metalgas platforms potentially have a large impact on programmatic applications. The goal of this focused workshop is to bring together target fabrication scientists, physicists, and designers to brainstorm future PSS and DS target fabrication needs and strategies. This one-day workshop intends to give an overall view of historical information, recent approaches, and future research activitiesmore » at each participating organization. Five topical areas have been discussed that are vital to the success of future DS target fabrications, including inner metal shells, foam spheres, outer ablators, fill tube assembly, and metrology.« less

Method of analysis and quality-assurance practices by the U. S. Geological Survey Organic Geochemistry Research Group; determination of four selected mosquito insecticides and a synergist in water using liquid-liquid extraction and gas chrom

USGS Publications Warehouse

Zimmerman, L.R.; Strahan, A.P.; Thurman, E.M.

2001-01-01

A method of analysis and quality-assurance practices were developed for the determination of four mosquito insecticides (malathion, metho-prene, phenothrin, and resmethrin) and one synergist (piperonyl butoxide) in water. The analytical method uses liquid-liquid extraction (LLE) and gas chromatography/mass spectrometry (GC/MS). Good precision and accuracy were demonstrated in reagent water, urban surface water, and ground water. The mean accuracies as percentages of the true compound concentrations from water samples spiked at 10 and 50 nanograms per liter ranged from 68 to 171 percent, with standard deviations in concentrations of 27 nanograms per liter or less. The method detection limit for all compounds was 5.9 nanograms per liter or less for 247-milliliter samples. This method is valuable for acquiring information about the fate and transport of these mosquito insecticides and one synergist in water.

Individualized correction for maternal weight in calculating the risk of chromosomal abnormalities with first-trimester screening data.

PubMed

Merz, E; Thode, C; Eiben, B; Faber, R; Hackelöer, B J; Huesgen, G; Pruggmaier, M; Wellek, S

2011-02-01

In the algorithm developed by the Fetal Medicine Foundation (FMF) Germany designed to evaluate the findings of routine first-trimester screening, the false-positive rate (FPR) was determined for the entire study group without stratification by maternal weight. Based on the data received from the continuous audit we were able to identify an increase in the FPR for the weight-related subgroups of patients, particularly for patients with extremely high body weights. The aim of this study was to demonstrate that the variability of the FPR can be reduced through adjusting the concentrations of free β-HCG and PAPP-A measured in the maternal serum by means of a nonlinear regression function modeling the dependence of these values on maternal weight. The database used to establish a version of the algorithm enabling control of the FPR over the whole range of maternal weight consisted of n = 123 546 pregnancies resulting in the birth of a child without chromosomal anomalies. The group with positive outcomes covered n = 500 cases of trisomy 21 and n = 159 trisomies 13 or 18. The dependency of the serum parameters free β-HCG and PAPP-A on maternal weight was analyzed in the sample of negative outcomes by means of nonlinear regression. The fitted regression curve was of exponential form with negative slope. Using this model, all individual measurements were corrected through multiplication with a factor obtained as the ratio of the concentration level predicted by the model to belong to the average maternal body weight of 68.2 kg, over the ordinate of that point on the regression curve which belongs to the weight actually measured. Subsequently, the totality of all values of free β-HCG and PAPP-A corrected for deviation from average weight were used as input data for carrying out the construction of diagnostic discrimination rules described in our recent paper for a database to which no corrections for over- or under-weight had been applied. This entailed in particular the

Rare and low-frequency coding variants alter human adult height.

PubMed

Marouli, Eirini; Graff, Mariaelisa; Medina-Gomez, Carolina; Lo, Ken Sin; Wood, Andrew R; Kjaer, Troels R; Fine, Rebecca S; Lu, Yingchang; Schurmann, Claudia; Highland, Heather M; Rüeger, Sina; Thorleifsson, Gudmar; Justice, Anne E; Lamparter, David; Stirrups, Kathleen E; Turcot, Valérie; Young, Kristin L; Winkler, Thomas W; Esko, Tõnu; Karaderi, Tugce; Locke, Adam E; Masca, Nicholas G D; Ng, Maggie C Y; Mudgal, Poorva; Rivas, Manuel A; Vedantam, Sailaja; Mahajan, Anubha; Guo, Xiuqing; Abecasis, Goncalo; Aben, Katja K; Adair, Linda S; Alam, Dewan S; Albrecht, Eva; Allin, Kristine H; Allison, Matthew; Amouyel, Philippe; Appel, Emil V; Arveiler, Dominique; Asselbergs, Folkert W; Auer, Paul L; Balkau, Beverley; Banas, Bernhard; Bang, Lia E; Benn, Marianne; Bergmann, Sven; Bielak, Lawrence F; Blüher, Matthias; Boeing, Heiner; Boerwinkle, Eric; Böger, Carsten A; Bonnycastle, Lori L; Bork-Jensen, Jette; Bots, Michiel L; Bottinger, Erwin P; Bowden, Donald W; Brandslund, Ivan; Breen, Gerome; Brilliant, Murray H; Broer, Linda; Burt, Amber A; Butterworth, Adam S; Carey, David J; Caulfield, Mark J; Chambers, John C; Chasman, Daniel I; Chen, Yii-Der Ida; Chowdhury, Rajiv; Christensen, Cramer; Chu, Audrey Y; Cocca, Massimiliano; Collins, Francis S; Cook, James P; Corley, Janie; Galbany, Jordi Corominas; Cox, Amanda J; Cuellar-Partida, Gabriel; Danesh, John; Davies, Gail; de Bakker, Paul I W; de Borst, Gert J; de Denus, Simon; de Groot, Mark C H; de Mutsert, Renée; Deary, Ian J; Dedoussis, George; Demerath, Ellen W; den Hollander, Anneke I; Dennis, Joe G; Di Angelantonio, Emanuele; Drenos, Fotios; Du, Mengmeng; Dunning, Alison M; Easton, Douglas F; Ebeling, Tapani; Edwards, Todd L; Ellinor, Patrick T; Elliott, Paul; Evangelou, Evangelos; Farmaki, Aliki-Eleni; Faul, Jessica D; Feitosa, Mary F; Feng, Shuang; Ferrannini, Ele; Ferrario, Marco M; Ferrieres, Jean; Florez, Jose C; Ford, Ian; Fornage, Myriam; Franks, Paul W; Frikke-Schmidt, Ruth; Galesloot, Tessel E; Gan, Wei; Gandin, Ilaria; Gasparini, Paolo; Giedraitis, Vilmantas; Giri, Ayush; Girotto, Giorgia; Gordon, Scott D; Gordon-Larsen, Penny; Gorski, Mathias; Grarup, Niels; Grove, Megan L; Gudnason, Vilmundur; Gustafsson, Stefan; Hansen, Torben; Harris, Kathleen Mullan; Harris, Tamara B; Hattersley, Andrew T; Hayward, Caroline; He, Liang; Heid, Iris M; Heikkilä, Kauko; Helgeland, Øyvind; Hernesniemi, Jussi; Hewitt, Alex W; Hocking, Lynne J; Hollensted, Mette; Holmen, Oddgeir L; Hovingh, G Kees; Howson, Joanna M M; Hoyng, Carel B; Huang, Paul L; Hveem, Kristian; Ikram, M Arfan; Ingelsson, Erik; Jackson, Anne U; Jansson, Jan-Håkan; Jarvik, Gail P; Jensen, Gorm B; Jhun, Min A; Jia, Yucheng; Jiang, Xuejuan; Johansson, Stefan; Jørgensen, Marit E; Jørgensen, Torben; Jousilahti, Pekka; Jukema, J Wouter; Kahali, Bratati; Kahn, René S; Kähönen, Mika; Kamstrup, Pia R; Kanoni, Stavroula; Kaprio, Jaakko; Karaleftheri, Maria; Kardia, Sharon L R; Karpe, Fredrik; Kee, Frank; Keeman, Renske; Kiemeney, Lambertus A; Kitajima, Hidetoshi; Kluivers, Kirsten B; Kocher, Thomas; Komulainen, Pirjo; Kontto, Jukka; Kooner, Jaspal S; Kooperberg, Charles; Kovacs, Peter; Kriebel, Jennifer; Kuivaniemi, Helena; Küry, Sébastien; Kuusisto, Johanna; La Bianca, Martina; Laakso, Markku; Lakka, Timo A; Lange, Ethan M; Lange, Leslie A; Langefeld, Carl D; Langenberg, Claudia; Larson, Eric B; Lee, I-Te; Lehtimäki, Terho; Lewis, Cora E; Li, Huaixing; Li, Jin; Li-Gao, Ruifang; Lin, Honghuang; Lin, Li-An; Lin, Xu; Lind, Lars; Lindström, Jaana; Linneberg, Allan; Liu, Yeheng; Liu, Yongmei; Lophatananon, Artitaya; Luan, Jian'an; Lubitz, Steven A; Lyytikäinen, Leo-Pekka; Mackey, David A; Madden, Pamela A F; Manning, Alisa K; Männistö, Satu; Marenne, Gaëlle; Marten, Jonathan; Martin, Nicholas G; Mazul, Angela L; Meidtner, Karina; Metspalu, Andres; Mitchell, Paul; Mohlke, Karen L; Mook-Kanamori, Dennis O; Morgan, Anna; Morris, Andrew D; Morris, Andrew P; Müller-Nurasyid, Martina; Munroe, Patricia B; Nalls, Mike A; Nauck, Matthias; Nelson, Christopher P; Neville, Matt; Nielsen, Sune F; Nikus, Kjell; Njølstad, Pål R; Nordestgaard, Børge G; Ntalla, Ioanna; O'Connel, Jeffrey R; Oksa, Heikki; Loohuis, Loes M Olde; Ophoff, Roel A; Owen, Katharine R; Packard, Chris J; Padmanabhan, Sandosh; Palmer, Colin N A; Pasterkamp, Gerard; Patel, Aniruddh P; Pattie, Alison; Pedersen, Oluf; Peissig, Peggy L; Peloso, Gina M; Pennell, Craig E; Perola, Markus; Perry, James A; Perry, John R B; Person, Thomas N; Pirie, Ailith; Polasek, Ozren; Posthuma, Danielle; Raitakari, Olli T; Rasheed, Asif; Rauramaa, Rainer; Reilly, Dermot F; Reiner, Alex P; Renström, Frida; Ridker, Paul M; Rioux, John D; Robertson, Neil; Robino, Antonietta; Rolandsson, Olov; Rudan, Igor; Ruth, Katherine S; Saleheen, Danish; Salomaa, Veikko; Samani, Nilesh J; Sandow, Kevin; Sapkota, Yadav; Sattar, Naveed; Schmidt, Marjanka K; Schreiner, Pamela J; Schulze, Matthias B; Scott, Robert A; Segura-Lepe, Marcelo P; Shah, Svati; Sim, Xueling; Sivapalaratnam, Suthesh; Small, Kerrin S; Smith, Albert Vernon; Smith, Jennifer A; Southam, Lorraine; Spector, Timothy D; Speliotes, Elizabeth K; Starr, John M; Steinthorsdottir, Valgerdur; Stringham, Heather M; Stumvoll, Michael; Surendran, Praveen; 't Hart, Leen M; Tansey, Katherine E; Tardif, Jean-Claude; Taylor, Kent D; Teumer, Alexander; Thompson, Deborah J; Thorsteinsdottir, Unnur; Thuesen, Betina H; Tönjes, Anke; Tromp, Gerard; Trompet, Stella; Tsafantakis, Emmanouil; Tuomilehto, Jaakko; Tybjaerg-Hansen, Anne; Tyrer, Jonathan P; Uher, Rudolf; Uitterlinden, André G; Ulivi, Sheila; van der Laan, Sander W; Van Der Leij, Andries R; van Duijn, Cornelia M; van Schoor, Natasja M; van Setten, Jessica; Varbo, Anette; Varga, Tibor V; Varma, Rohit; Edwards, Digna R Velez; Vermeulen, Sita H; Vestergaard, Henrik; Vitart, Veronique; Vogt, Thomas F; Vozzi, Diego; Walker, Mark; Wang, Feijie; Wang, Carol A; Wang, Shuai; Wang, Yiqin; Wareham, Nicholas J; Warren, Helen R; Wessel, Jennifer; Willems, Sara M; Wilson, James G; Witte, Daniel R; Woods, Michael O; Wu, Ying; Yaghootkar, Hanieh; Yao, Jie; Yao, Pang; Yerges-Armstrong, Laura M; Young, Robin; Zeggini, Eleftheria; Zhan, Xiaowei; Zhang, Weihua; Zhao, Jing Hua; Zhao, Wei; Zhao, Wei; Zheng, He; Zhou, Wei; Rotter, Jerome I; Boehnke, Michael; Kathiresan, Sekar; McCarthy, Mark I; Willer, Cristen J; Stefansson, Kari; Borecki, Ingrid B; Liu, Dajiang J; North, Kari E; Heard-Costa, Nancy L; Pers, Tune H; Lindgren, Cecilia M; Oxvig, Claus; Kutalik, Zoltán; Rivadeneira, Fernando; Loos, Ruth J F; Frayling, Timothy M; Hirschhorn, Joel N; Deloukas, Panos; Lettre, Guillaume

2017-02-09

Height is a highly heritable, classic polygenic trait with approximately 700 common associated variants identified through genome-wide association studies so far. Here, we report 83 height-associated coding variants with lower minor-allele frequencies (in the range of 0.1-4.8%) and effects of up to 2 centimetres per allele (such as those in IHH, STC2, AR and CRISPLD2), greater than ten times the average effect of common variants. In functional follow-up studies, rare height-increasing alleles of STC2 (giving an increase of 1-2 centimetres per allele) compromised proteolytic inhibition of PAPP-A and increased cleavage of IGFBP-4 in vitro, resulting in higher bioavailability of insulin-like growth factors. These 83 height-associated variants overlap genes that are mutated in monogenic growth disorders and highlight new biological candidates (such as ADAMTS3, IL11RA and NOX4) and pathways (such as proteoglycan and glycosaminoglycan synthesis) involved in growth. Our results demonstrate that sufficiently large sample sizes can uncover rare and low-frequency variants of moderate-to-large effect associated with polygenic human phenotypes, and that these variants implicate relevant genes and pathways.

Protein profiling of preeclampsia placental tissues.

PubMed

Shu, Chang; Liu, Zitao; Cui, Lifeng; Wei, Chengguo; Wang, Shuwen; Tang, Jian Jenny; Cui, Miao; Lian, Guodong; Li, Wei; Liu, Xiufen; Xu, Hongmei; Jiang, Jing; Lee, Peng; Zhang, David Y; He, Jin; Ye, Fei

2014-01-01

Preeclampsia is a multi-system disorder involved in pregnancy without an effective treatment except delivery. The precise pathogenesis of this complicated disorder is still not completely understood. The objective of this study is to evaluate the alterations of protein expression and phosphorylations that are important in regulating placental cell function in preterm and term preeclampsia. Using the Protein Pathway Array, 38 proteins in placental tissues were found to be differentially expressed between preterm preeclampsia and gestational age matched control, while 25 proteins were found to be expressed differentially between term preeclampsia and matched controls. Among these proteins, 16 proteins and their associated signaling pathways overlapped between preterm and term preeclampsia, suggesting the common pathogenesis of two subsets of disease. On the other hand, many proteins are uniquely altered in either preterm or term preeclampsia and correlated with severity of clinical symptoms and outcomes, therefore, providing molecular basis for these two subsets of preeclampsia. Furthermore, the expression levels of some of these proteins correlated with neonatal small for gestational age (PAI-1 and PAPP-A) and adverse outcomes (Flt-1) in women with preterm preeclampsia. These proteins could potentially be used as candidate biomarkers for predicting outcomes of preeclampsia.

Review of the East Palaearctic and North Oriental Psyttalia Walker, with the description of three new species (Hymenoptera, Braconidae, Opiinae).

PubMed

Wu, Qiong; van Achterberg, Cornelis; Tan, Jiang-Li; Chen, Xue-Xin

2016-01-01

The East Palaearctic and North Oriental species of the genus Psyttalia Walker (Hymenoptera, Braconidae, Opiinae) are reviewed. Three new species are described and illustrated: Psyttalia latinervis Wu & van Achterberg, sp. n . and Psyttalia majocellata Wu & van Achterberg, sp. n . from China, and Psyttalia spectabilis van Achterberg, sp. n. from Japan. Coeloreuteus formosanus Watanabe, 1934, Opius (Lissosema) proclivis Papp, 1981, Opius (Psyttalia) subcyclogaster Tobias, 1998, Opius (Psyttalia) darasunicus Tobias, 1998, Opius (Psyttalia) cyclogastroides Tobias, 1998, Psyttalia extensa Weng & Chen, 2001, and Rhogadopsis longicaudifera Li & van Achterberg, 2013, are new synonyms of Psyttalia cyclogaster (Thomson, 1895); Opius (Psyttalia) ophthalmicus Tobias, 1977, and Opius (Psyttalia) brevitemporalis Tobias, 1998, of Psyttalia carinata (Thomson, 1895) and both Opius (Psyttalia) vacuus Tobias, 1998, and Opius (Lissosema) longurius Chen & Weng, 1995, of Rhogadopsis mediocarinata (Fischer, 1963). Phaedrotoma daghestanicum (Telenga, 1950), Rhogadopsis mediocarinata (Fischer, 1963) and Rhogadopsis mystica (Fischer, 1963) are new combinations. New records are Psyttalia carinata (Thomson, 1895) from The Netherlands and Norway, and Psyttalia cyclogaster (Thomson, 1895) from Japan. A lectotype is designated for Psyttalia carinata (Thomson, 1895) and Psyttalia cyclogaster (Thomson, 1895). A key to the East Palaearctic and North Oriental species of the genus Psyttalia Walker is included.

Review of the East Palaearctic and North Oriental Psyttalia Walker, with the description of three new species (Hymenoptera, Braconidae, Opiinae)

PubMed Central

Wu, Qiong; van Achterberg, Cornelis; Tan, Jiang-Li; Chen, Xue-Xin

2016-01-01

Abstract The East Palaearctic and North Oriental species of the genus Psyttalia Walker (Hymenoptera, Braconidae, Opiinae) are reviewed. Three new species are described and illustrated: Psyttalia latinervis Wu & van Achterberg, sp. n. and Psyttalia majocellata Wu & van Achterberg, sp. n. from China, and Psyttalia spectabilis van Achterberg, sp. n. from Japan. Coeloreuteus formosanus Watanabe, 1934, Opius (Lissosema) proclivis Papp, 1981, Opius (Psyttalia) subcyclogaster Tobias, 1998, Opius (Psyttalia) darasunicus Tobias, 1998, Opius (Psyttalia) cyclogastroides Tobias, 1998, Psyttalia extensa Weng & Chen, 2001, and Rhogadopsis longicaudifera Li & van Achterberg, 2013, are new synonyms of Psyttalia cyclogaster (Thomson, 1895); Opius (Psyttalia) ophthalmicus Tobias, 1977, and Opius (Psyttalia) brevitemporalis Tobias, 1998, of Psyttalia carinata (Thomson, 1895) and both Opius (Psyttalia) vacuus Tobias, 1998, and Opius (Lissosema) longurius Chen & Weng, 1995, of Rhogadopsis mediocarinata (Fischer, 1963). Phaedrotoma daghestanicum (Telenga, 1950), Rhogadopsis mediocarinata (Fischer, 1963) and Rhogadopsis mystica (Fischer, 1963) are new combinations. New records are Psyttalia carinata (Thomson, 1895) from The Netherlands and Norway, and Psyttalia cyclogaster (Thomson, 1895) from Japan. A lectotype is designated for Psyttalia carinata (Thomson, 1895) and Psyttalia cyclogaster (Thomson, 1895). A key to the East Palaearctic and North Oriental species of the genus Psyttalia Walker is included. PMID:27920599

Multiphase, multicomponent phase behavior prediction

NASA Astrophysics Data System (ADS)

Dadmohammadi, Younas

Accurate prediction of phase behavior of fluid mixtures in the chemical industry is essential for designing and operating a multitude of processes. Reliable generalized predictions of phase equilibrium properties, such as pressure, temperature, and phase compositions offer an attractive alternative to costly and time consuming experimental measurements. The main purpose of this work was to assess the efficacy of recently generalized activity coefficient models based on binary experimental data to (a) predict binary and ternary vapor-liquid equilibrium systems, and (b) characterize liquid-liquid equilibrium systems. These studies were completed using a diverse binary VLE database consisting of 916 binary and 86 ternary systems involving 140 compounds belonging to 31 chemical classes. Specifically the following tasks were undertaken: First, a comprehensive assessment of the two common approaches (gamma-phi (gamma-ϕ) and phi-phi (ϕ-ϕ)) used for determining the phase behavior of vapor-liquid equilibrium systems is presented. Both the representation and predictive capabilities of these two approaches were examined, as delineated form internal and external consistency tests of 916 binary systems. For the purpose, the universal quasi-chemical (UNIQUAC) model and the Peng-Robinson (PR) equation of state (EOS) were used in this assessment. Second, the efficacy of recently developed generalized UNIQUAC and the nonrandom two-liquid (NRTL) for predicting multicomponent VLE systems were investigated. Third, the abilities of recently modified NRTL model (mNRTL2 and mNRTL1) to characterize liquid-liquid equilibria (LLE) phase conditions and attributes, including phase stability, miscibility, and consolute point coordinates, were assessed. The results of this work indicate that the ϕ-ϕ approach represents the binary VLE systems considered within three times the error of the gamma-ϕ approach. A similar trend was observed for the for the generalized model predictions using

A randomized controlled pilot trial comparing the impact of access to clinical endocrinology video demonstrations with access to usual revision resources on medical student performance of clinical endocrinology skills

PubMed Central

2013-01-01

Background Demonstrating competence in clinical skills is key to course completion for medical students. Methods of providing clinical instruction that foster immediate learning and potentially serve as longer-term repositories for on-demand revision, such as online videos demonstrating competent performance of clinical skills, are increasingly being used. However, their impact on learning has been little studied. The aim of this study was to determine the value of adjunctive on-demand video-based training for clinical skills acquisition by medical students in endocrinology. Methods Following an endocrinology clinical tutorial program, 2nd year medical students in the pre-assessment revision period were recruited and randomized to either a set of bespoke on-line clinical skills training videos (TV), or to revision as usual (RAU). The skills demonstrated on video were history taking in diabetes mellitus (DMH), examination for diabetes lower limb complications (LLE), and examination for signs of thyroid disease (TE). Students were assessed on these clinical skills in an observed structured clinical examination two weeks after randomization. Assessors were blinded to student randomization status. Results For both diabetes related clinical skills assessment tasks, students in the TV group performed significantly better than those in the RAU group. There were no between group differences in thyroid examination performance. For the LLE, 91.7% (n = 11/12) of students randomized to the video were rated globally as competent at the skill compared with 40% (n = 4/10) of students not randomized to the video (p = 0.024). For the DMH, 83.3% (n = 10/12) of students randomized to the video were rated globally as competent at the skill compared with 20% (n = 2/10) of students not randomized to the video (p = 0.007). Conclusion Exposure to high quality videos demonstrating clinical skills can significantly improve medical student skill performance in an

A randomized controlled pilot trial comparing the impact of access to clinical endocrinology video demonstrations with access to usual revision resources on medical student performance of clinical endocrinology skills.

PubMed

Hibbert, Emily J; Lambert, Tim; Carter, John N; Learoyd, Diana L; Twigg, Stephen; Clarke, Stephen

2013-10-03

Demonstrating competence in clinical skills is key to course completion for medical students. Methods of providing clinical instruction that foster immediate learning and potentially serve as longer-term repositories for on-demand revision, such as online videos demonstrating competent performance of clinical skills, are increasingly being used. However, their impact on learning has been little studied. The aim of this study was to determine the value of adjunctive on-demand video-based training for clinical skills acquisition by medical students in endocrinology. Following an endocrinology clinical tutorial program, 2nd year medical students in the pre-assessment revision period were recruited and randomized to either a set of bespoke on-line clinical skills training videos (TV), or to revision as usual (RAU). The skills demonstrated on video were history taking in diabetes mellitus (DMH), examination for diabetes lower limb complications (LLE), and examination for signs of thyroid disease (TE). Students were assessed on these clinical skills in an observed structured clinical examination two weeks after randomization. Assessors were blinded to student randomization status. For both diabetes related clinical skills assessment tasks, students in the TV group performed significantly better than those in the RAU group. There were no between group differences in thyroid examination performance. For the LLE, 91.7% (n = 11/12) of students randomized to the video were rated globally as competent at the skill compared with 40% (n = 4/10) of students not randomized to the video (p = 0.024). For the DMH, 83.3% (n = 10/12) of students randomized to the video were rated globally as competent at the skill compared with 20% (n = 2/10) of students not randomized to the video (p = 0.007). Exposure to high quality videos demonstrating clinical skills can significantly improve medical student skill performance in an observed structured clinical examination of these skills, when

Computation of liquid-liquid equilibria and phase stabilities: implications for RH-dependent gas/particle partitioning of organic-inorganic aerosols

NASA Astrophysics Data System (ADS)

Zuend, A.; Marcolli, C.; Peter, T.; Seinfeld, J. H.

2010-08-01

Semivolatile organic and inorganic aerosol species partition between the gas and aerosol particle phases to maintain thermodynamic equilibrium. Liquid-liquid phase separation into an organic-rich and an aqueous electrolyte phase can occur in the aerosol as a result of the salting-out effect. Such liquid-liquid equilibria (LLE) affect the gas/particle partitioning of the different semivolatile compounds and might significantly alter both particle mass and composition as compared to a one-phase particle. We present a new liquid-liquid equilibrium and gas/particle partitioning model, using as a basis the group-contribution model AIOMFAC (Zuend et al., 2008). This model allows the reliable computation of the liquid-liquid coexistence curve (binodal), corresponding tie-lines, the limit of stability/metastability (spinodal), and further thermodynamic properties of multicomponent systems. Calculations for ternary and multicomponent alcohol/polyol-water-salt mixtures suggest that LLE are a prevalent feature of organic-inorganic aerosol systems. A six-component polyol-water-ammonium sulphate system is used to simulate effects of relative humidity (RH) and the presence of liquid-liquid phase separation on the gas/particle partitioning. RH, salt concentration, and hydrophilicity (water-solubility) are identified as key features in defining the region of a miscibility gap and govern the extent to which compound partitioning is affected by changes in RH. The model predicts that liquid-liquid phase separation can lead to either an increase or decrease in total particulate mass, depending on the overall composition of a system and the particle water content, which is related to the hydrophilicity of the different organic and inorganic compounds. Neglecting non-ideality and liquid-liquid phase separations by assuming an ideal mixture leads to an overestimation of the total particulate mass by up to 30% for the composition and RH range considered in the six-component system

Computation of liquid-liquid equilibria and phase stabilities: implications for RH-dependent gas/particle partitioning of organic-inorganic aerosols

NASA Astrophysics Data System (ADS)

Zuend, A.; Marcolli, C.; Peter, T.; Seinfeld, J. H.

2010-05-01

Semivolatile organic and inorganic aerosol species partition between the gas and aerosol particle phases to maintain thermodynamic equilibrium. Liquid-liquid phase separation into an organic-rich and an aqueous electrolyte phase can occur in the aerosol as a result of the salting-out effect. Such liquid-liquid equilibria (LLE) affect the gas/particle partitioning of the different semivolatile compounds and might significantly alter both particle mass and composition as compared to a one-phase particle. We present a new liquid-liquid equilibrium and gas/particle partitioning model, using as a basis the group-contribution model AIOMFAC (Zuend et al., 2008). This model allows the reliable computation of the liquid-liquid coexistence curve (binodal), corresponding tie-lines, the limit of stability/metastability (spinodal), and further thermodynamic properties of the phase diagram. Calculations for ternary and multicomponent alcohol/polyol-water-salt mixtures suggest that LLE are a prevalent feature of organic-inorganic aerosol systems. A six-component polyol-water-ammonium sulphate system is used to simulate effects of relative humidity (RH) and the presence of liquid-liquid phase separation on the gas/particle partitioning. RH, salt concentration, and hydrophilicity (water-solubility) are identified as key features in defining the region of a miscibility gap and govern the extent to which compound partitioning is affected by changes in RH. The model predicts that liquid-liquid phase separation can lead to either an increase or decrease in total particulate mass, depending on the overall composition of a system and the particle water content, which is related to the hydrophilicity of the different organic and inorganic compounds. Neglecting non-ideality and liquid-liquid phase separations by assuming an ideal mixture leads to an overestimation of the total particulate mass by up to 30% for the composition and RH range considered in the six-component system simulation

Downstream processing of antibodies: single-stage versus multi-stage aqueous two-phase extraction.

PubMed

Rosa, P A J; Azevedo, A M; Ferreira, I F; Sommerfeld, S; Bäcker, W; Aires-Barros, M R

2009-12-11

Single-stage and multi-stage strategies have been evaluated and compared for the purification of human antibodies using liquid-liquid extraction in aqueous two-phase systems (ATPSs) composed of polyethylene glycol 3350 (PEG 3350), dextran, and triethylene glycol diglutaric acid (TEG-COOH). The performance of single-stage extraction systems was firstly investigated by studying the effect of pH, TEG-COOH concentration and volume ratio on the partitioning of the different components of a Chinese hamster ovary (CHO) cells supernatant. It was observed that lower pH values and high TEG-COOH concentrations favoured the selective extraction of human immunoglobulin G (IgG) to the PEG-rich phase. Higher recovery yields, purities and percentage of contaminants removal were always achieved in the presence of the ligand, TEG-COOH. The extraction of IgG could be enhanced using higher volume ratios, however with a significant decrease in both purity and percentage of contaminants removal. The best single-stage extraction conditions were achieved for an ATPS containing 1.3% (w/w) TEG-COOH with a volume ratio of 2.2, which allowed the recovery of 96% of IgG in the PEG-rich phase with a final IgG concentration of 0.21mg/mL, a protein purity of 87% and a total purity of 43%. In order to enhance simultaneously both recovery yield and purity, a four stage cross-current operation was simulated and the corresponding liquid-liquid equilibrium (LLE) data determined. A predicted optimised scheme of a counter-current multi-stage aqueous two-phase extraction was hence described. IgG can be purified in the PEG-rich top phase with a final recovery yield of 95%, a final concentration of 1.04mg/mL and a protein purity of 93%, if a PEG/dextran ATPS containing 1.3% (w/w) TEG-COOH, 5 stages and volume ratio of 0.4 are used. Moreover, according to the LLE data of all CHO cells supernatant components, it was possible to observe that most of the cells supernatant contaminants can be removed during this

Design of a Neutron Temporal Diagnostic for measuring DD or DT burn histories at the NIF

NASA Astrophysics Data System (ADS)

Lahmann, B.; Frenje, J. A.; Sio, H.; Petrasso, R. D.; Bradley, D. K.; Le Pape, S.; MacKinnon, A. J.; Isumi, N.; Macphee, A.; Zayas, C.; Spears, B. K.; Hermann, H.; Hilsabeck, T. J.; Kilkenny, J. D.

2015-11-01

The DD or DT burn history in Inertial Confinement Fusion (ICF) implosions provides essential information about implosion performance and helps to constrain numerical modeling. The capability of measuring this burn history is thus important for the NIF in its pursuit of ignition. Currently, the Gamma Reaction History (GRH) diagnostic is the only system capable of measuring the burn history for DT implosions with yields greater than ~ 1e14. To complement GRH, a new NIF Neutron Temporal Diagnostic (NTD) is being designed for measuring the DD or DT burn history with yields greater than ~ 1e10. A traditional scintillator-based design and a pulse-dilation-based design are being considered. Using MCNPX simulations, both designs have been optimized, validated and contrasted for various types of implosions at the NIF. This work was supported in part by the U.S. DOE, LLNL and LLE.

Analysis of the VP2 protein gene of canine parvovirus strains from affected dogs in Japan.

PubMed

Soma, Takehisa; Taharaguchi, Satoshi; Ohinata, Tsuyoshi; Ishii, Hiroshi; Hara, Motonobu

2013-04-01

To clarify the evolution of canine parvovirus 2 (CPV-2) that has recently been epidemic in Japan, VP2 gene sequences at positions 3556-4166 were analyzed in 107 CPV-2 strains obtained from rectal swabs of diarrheic dogs from 2009 to 2011. CPV-2b (95 strains) was more frequently detected than CPV-2a (nine strains), while CPV-2c was not detected. Remaining three strains were identified as the original type CPV-2, which should be derived from vaccines. These findings are similar to the previous results involving Japanese strains, suggesting there has been no great change in the recent CPV-2 epidemic in Japan. This epidemic is the same as that in Taiwan. Furthermore, a 324-lle mutant, which has been reported in Korean and Chinese strains, was detected in 66.7% of CPV-2a strains. Copyright © 2012 Elsevier Ltd. All rights reserved.

US Army Aeromedical Research Laboratory Annual Progress Report, FY 1981.

DTIC Science & Technology

1981-10-01

PROGRAM ELEMENT. PROJECT. TASK US Army Aeromedical Research Laboratory AREA 6 WORK UNIT NUMBERS PO Box 577 Fort Rucker, Alabama 36362 Listed on each DD...d J F I’ 0 l I I I I ;11 11 it Ili di fi li I t t o tim!L’ 151 niii tt 11 ,0 lo 1’ I I J rt 1,( K 1 soo m~r mOo I r I) o r t AIi t tO hi1t Lle I’I tu...I I, I ’ 11 t hit f:1iU :IJ . ] i ;)1T11C 1t 11i1 hs boo par kcW ind ulitac~u ho 1,1-i c " t I a It Cs rt I U I o v’! : a rd anId oxo c t cc ha at in

Aroma Characterization and Safety Assessment of a Beverage Fermented by Trametes versicolor.

PubMed

Zhang, Yanyan; Fraatz, Marco Alexander; Müller, Julia; Schmitz, Hans-Joachim; Birk, Florian; Schrenk, Dieter; Zorn, Holger

2015-08-12

A cereal-based beverage was developed by fermentation of wort with the basidiomycete Trametes versicolor. The beverage possessed a fruity, fresh, and slightly floral aroma. The volatiles of the beverage were isolated by liquid-liquid extraction (LLE) and additionally by headspace solid phase microextraction (HS-SPME). The aroma compounds were analyzed by a gas chromatography system equipped with a tandem mass spectrometer and an olfactory detection port (GC-MS/MS-O) followed by aroma (extract) dilution analysis. Thirty-four different odor impressions were perceived, and 27 corresponding compounds were identified. Fifteen key odorants with flavor dilution (FD) factors ranging from 8 to 128 were quantitated, and their respective odor activity values (OAVs) were calculated. Six key odorants were synthesized de novo by T. versicolor. Furthermore, quantitative changes during the fermentation process were analyzed. To prepare for the market introduction of the beverage, a comprehensive safety assessment was performed.

Identification of one polymorphism from the PAPP-A2 gene associated to fertility in Romosinuano beef heifers raised under a subtropical environment

USDA-ARS?s Scientific Manuscript database

The objective of this study was to identify single nucleotide polymorphisms (SNP) associated to fertility in female cows raised under a subtropical environment. Re-sequencing of 9 genes associated to GH-IGF endocrine pathway located in bovine chromosome 5, identified 75 SNP useful for associative ge...

Evolution of Magnetized Liner Inertial Fusion (MagLIF) Targets

DOE PAGES

Fooks, J. A.; Carlson, L. C.; Fitzsimmons, P.; ...

2017-12-19

Here, the magnetized liner inertial fusion (MagLIF) experimental campaign conducted at the University of Rochester’s Laboratory for Laser Energetics (LLE) has evolved significantly since its start in 2014. Scientific requirements and OMEGA EP system technology both have progressed, resulting in necessary and available updates to the target design. These include, but are not limited to: optimizing target dimensions and aspect ratios to maximize survival at desired pressures; coating target components to enhance physics diagnosis; precision-machining diagnostic windows along the axis of the target; improving fiducial placement reproducibility and reducing subsequent assembly time by 50%; and implementing gas-pressure transducers on themore » targets. In addition, target fabrication techniques have changed and improved, allowing for simpler target reproducibility and decreased assembly time. To date, eleven variations of targets have been fabricated, with successful target fielding ranging from 1 to 20atm internal pressure and a maximum survivability of 33atm.« less

Models for the Aerosols of the Lower Atmosphere and the Effects of Humidity Variations on their Optical Properties

DTIC Science & Technology

1979-09-20

PSi NEN.4 0 0i Si -t .4 It 4D NN 16*. * 4 . M% 0 NU% .Ir. N ’ .0 41% a E D 0. P.4 0 .. 4 ’A a4 4% 9 4 44 P 4s C’ r) Ai N U% IAN 40 U’ 0u4 i’ Ný .4 .4...1128101 1 1901 9 AI I I goo-I 1 4M-I SC*Ti*Lle PARAM1ETE .ff@ 1.66911*66 1*9911-01 1090619-01 .0407 .7773 sole 90119-1-1 809011-11 1.4761-01 all...2.9.1H-02 1.9611-01 1.6631-01 .666 .23 .3.75 2.5071-0? 1.103S-01 9..774E-02 . 65292 .12 4.0 23.9-19.0511-0 6.4p9E-%32 *.24#4 .66 1.0 1931-02 1.2.01S-03

Liquid-liquid extraction/headspace/gas chromatographic/mass spectrometric determination of benzene, toluene, ethylbenzene, (o-, m- and p-)xylene and styrene in olive oil using surfactant-coated carbon nanotubes as extractant.

PubMed

Carrillo-Carrión, Carolina; Lucena, Rafael; Cárdenas, Soledad; Valcárcel, Miguel

2007-11-09

BTEX-S compounds are widely distributed in the environment and can be present in different foodstuffs, including olive oil. Taking into account the risks of the exposure to these compounds, analytical methods for their determination in different matrices are mandatory. In this paper, the use of surfactant-coated multiwalled carbon nanotubes as additive in liquid-liquid extraction is applied for the determination of single-ring aromatic compounds in olive oil samples. After sample treatment, the aqueous extracts are subsequently analyzed by headspace/gas chromatography/mass spectrometry allowing the determination of BTEX-S within ca. 15 min. Each stage of the proposed LLE/HS/GC/MS configuration involves a selectivity enhancement avoiding the interference of other compounds of the sample matrix. Limits of detection were in the range 0.25 ng mL(-1) (obtained for ethylbenzene) and 0.43 ng mL(-1) (for benzene). The repeatability of the proposed method expressed as RSD varied between 1.9% (styrene) and 3.3% (benzene) (n=11).

Using Rutherford Backscattering Spectroscopy to Characterize Targets for MTW

NASA Astrophysics Data System (ADS)

Brown, Gunnar; Stockler, Barak; Ward, Ryan; Freeman, Charlie; Padalino, Stephen; Stillman, Collin; Ivancic, Steven; Reagan, S. P.; Sangster, T. C.

2017-10-01

A study is underway to determine the composition and thickness of targets used at the Multiterawatt (MTW) laser facility at the Laboratory for Laser Energetics (LLE) using Rutherford backscattering spectroscopy (RBS). In RBS, an ion beam is incident on a sample and the scattered ions are detected with a surface barrier detector. The resulting energy spectra of the scattered ions can be analyzed to determine important parameters of the target including elemental composition and thickness. Proton, helium and deuterium beams from the 1.7 MV Pelletron accelerator at SUNY Geneseo have been used to characterize several different targets for MTW, including CH and aluminum foils of varying thickness. RBS spectra were also obtained for a cylindrical iron buried-layer target with aluminum dopant which was mounted on a silicon carbide stalk. The computer program SIMNRA is used to analyze the spectra. This work was funded in part by a Grant from the DOE through the Laboratory for Laser Energetics.

Measuring radial profiles of nuclear burn in ICF implosions at OMEGA and the NIF using proton emission imaging

NASA Astrophysics Data System (ADS)

Seguin, F. H.; Rinderknecht, H. G.; Rosenberg, M.; Zylstra, A.; Frenje, J.; Li, C. K.; Petrasso, R.; Marshall, F. J.; Sangster, T. C.; Hoffman, N. M.; Amendt, P. A.; Bellei, C.; Le Pape, S.; Wilks, S. C.

2014-10-01

Fusion reactions in ICF implosions of D3He-filled capsules produce 14.7-MeV D3He protons and 3-MeV DD protons. Measurements of the spatial distributions of the D3He and DD reactions are studied with a penumbral imaging system that utilizes a CR-39-based imaging detector to simultaneously record separate penumbral images of the two types of protons. Measured burn profiles are useful for studying implosion physics and provide a critical test for benchmarking simulations. Recent implosions at OMEGA of CD capsules containing 3He gas fill and SiO2 capsules containing low-pressure D3He gas were expected to have hollow D3He burn profiles (in the 3He-filled capsule, due to fuel-shell mix), but penumbral imaging showed that the reactions were centrally peaked due to enhanced ion diffusion. The imaging technique is to be implemented soon on the NIF. This work was supported in part by NLUF, DOE, and LLE.

Word Frequency Analysis. MOS: 57H. Skill Levels 1 & 2.

DTIC Science & Technology

1981-05-01

8217 . -4 1a’ _________ Palms 1t. FLL& T - VI;:.P - -- S LtrTZE5 I Lu" I rprz l * 4 2lE p:Zn.uAwn PLCU4LLE 14 Piz;* I P RTICULAR 4 PZR1S 7 J _________ 2...I’ I VIn 1 fIV 7 IaIIA!’I TIP 2 1-111 L LAlT P i;10! S II*,s , 11- 1 L Ii1! p UIIIc tInlG Z :𔃻 S -W (INSf4 2 IZ 1111tE~ ;l ,’I I z a5T p Oil ’(1$I1...p --G 6 RIGGING- I~ V~. 1 5EL~ .1 50:L I SF AFY~~3!.rS_7I; 7 SAFETY I----c- 7 -- ss1 ’_F T_-------- 1 HPPI 7A! I1CEUE SCP .~LaG 3 SHUTWI ~ SC’~J’!LI

100J Pulsed Laser Shock Driver for Dynamic Compression Research

NASA Astrophysics Data System (ADS)

Wang, X.; Sethian, J.; Bromage, J.; Fochs, S.; Broege, D.; Zuegel, J.; Roides, R.; Cuffney, R.; Brent, G.; Zweiback, J.; Currier, Z.; D'Amico, K.; Hawreliak, J.; Zhang, J.; Rigg, P. A.; Gupta, Y. M.

2017-06-01

Logos Technologies and the Laboratory for Laser Energetics (LLE, University of Rochester) - in partnership with Washington State University - have designed, built and deployed a one of a kind 100J pulsed UV (351 nm) laser system to perform real-time, x-ray diffraction and imaging experiments in laser-driven compression experiments at the Dynamic Compression Sector (DCS) at the Advanced Photon Source, Argonne National Laboratory. The laser complements the other dynamic compression drivers at DCS. The laser system features beam smoothing for 2-d spatially uniform loading of samples and four, highly reproducible, temporal profiles (total pulse duration: 5-15 ns) to accommodate a wide variety of scientific needs. Other pulse shapes can be achieved as the experimental needs evolve. Timing of the laser pulse is highly precise (<200 ps) to allow accurate synchronization of the x-rays with the dynamic compression event. Details of the laser system, its operating parameters, and representative results will be presented. Work supported by DOE/NNSA.

Evolution of Magnetized Liner Inertial Fusion (MagLIF) Targets

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

Fooks, J. A.; Carlson, L. C.; Fitzsimmons, P.

Here, the magnetized liner inertial fusion (MagLIF) experimental campaign conducted at the University of Rochester’s Laboratory for Laser Energetics (LLE) has evolved significantly since its start in 2014. Scientific requirements and OMEGA EP system technology both have progressed, resulting in necessary and available updates to the target design. These include, but are not limited to: optimizing target dimensions and aspect ratios to maximize survival at desired pressures; coating target components to enhance physics diagnosis; precision-machining diagnostic windows along the axis of the target; improving fiducial placement reproducibility and reducing subsequent assembly time by 50%; and implementing gas-pressure transducers on themore » targets. In addition, target fabrication techniques have changed and improved, allowing for simpler target reproducibility and decreased assembly time. To date, eleven variations of targets have been fabricated, with successful target fielding ranging from 1 to 20atm internal pressure and a maximum survivability of 33atm.« less

Determination of itopride in human plasma by liquid chromatography coupled to tandem mass spectrometric detection: application to a bioequivalence study.

PubMed

Lee, Heon-Woo; Seo, Ji-Hyung; Choi, Seung-Ki; Lee, Kyung-Tae

2007-01-30

A simple method using a one-step liquid-liquid extraction (LLE) with butyl acetate followed by high-performance liquid chromatography (HPLC) with positive ion electrospray ionization tandem mass spectrometric (ESI-MS/MS) detection was developed for the determination of itopride in human plasma, using sulpiride as an internal standard (IS). Acquisition was performed in multiple reaction monitoring (MRM) mode, by monitoring the transitions: m/z 359.5>166.1 for itopride and m/z 342.3>111.6 for IS, respectively. Analytes were chromatographed on an YMC C18 reverse-phase chromatographic column by isocratic elution with 1 mM ammonium acetate buffer-methanol (20: 80, v/v; pH 4.0 adjusted with acetic acid). Results were linear (r2=0.9999) over the studied range (0.5-1000 ng mL(-1)) with a total analysis time per run of 2 min for LC-MS/MS. The developed method was validated and successfully applied to bioequivalence studies of itopride hydrochloride in healthy male volunteers.

Fluorescein transport properties across artificial lipid membranes, Caco-2 cell monolayers and rat jejunum.

PubMed

Berginc, Katja; Zakelj, Simon; Levstik, Lea; Ursic, Darko; Kristl, Albin

2007-05-01

Membrane transport characteristics of a paracellular permeability marker fluorescein were evaluated using artificial membrane, Caco-2 cell monolayers and rat jejunum, all mounted in side-by-side diffusion cells. Modified Ringer buffers with varied pH values were applied as incubation salines on both sides of artificial membrane, cell culture monolayers or rat jejunum. Passive transport according to pH partition theory was determined using all three permeability models. In addition to that, active transport of fluorescein in the M-S (mucosal-to-serosal) direction through rat jejunum was observed. The highest M-S P(app) values regarding the active transport through the rat jejunum were observed in incubation saline with pH 6.5. Fluorescein transport through the rat jejunum was inhibited by DIDS (4,4'-diisothiocyanatostilbene-2,2'-disulfonic acid) and alpha-CHC (alpha-cyano-4-hydroxycinnamic acid). Thus, we assume that two pH-dependent influx transporters could be involved in the fluorescein membrane transport through the intestinal (jejunal) epithelium. One is very likely an MCT (monocarboxylic acid cotransporter) isoform, inhibited by specific MCT inhibitor alpha-CHC, while the involvement of the second one with overlapping substrate/inhibitor specificities (most probably a member of the organic anion-transporting polypeptide family, inhibited at least partially by DIDS) could not be excluded.

Intestinal Permeability and Cellular Antioxidant Activity of Phenolic Compounds from Mango (Mangifera indica cv. Ataulfo) Peels.

PubMed

Pacheco-Ordaz, Ramón; Antunes-Ricardo, Marilena; Gutiérrez-Uribe, Janet A; González-Aguilar, Gustavo A

2018-02-08

Mango ( Mangifera indica cv. Ataulfo) peel contains bound phenolics that may be released by alkaline or acid hydrolysis and may be converted into less complex molecules. Free phenolics from mango cv. Ataulfo peel were obtained using a methanolic extraction, and their cellular antioxidant activity (CAA) and permeability were compared to those obtained for bound phenolics released by alkaline or acid hydrolysis. Gallic acid was found as a simple phenolic acid after alkaline hydrolysis along with mangiferin isomers and quercetin as aglycone and glycosides. Only gallic acid, ethyl gallate, mangiferin, and quercetin were identified in the acid fraction. The acid and alkaline fractions showed the highest CAA (60.5% and 51.5%) when tested at 125 µg/mL. The value of the apparent permeability coefficient (Papp) across the Caco-2/HT-29 monolayer of gallic acid from the alkaline fraction was higher (2.61 × 10 -6 cm/s) than in the other fractions and similar to that obtained when tested pure (2.48 × 10 -6 cm/s). In conclusion, mango peels contain bound phenolic compounds that, after their release, have permeability similar to pure compounds and exert an important CAA. This finding can be applied in the development of nutraceuticals using this important by-product from the mango processing industry.

Transport of surface engineered polyamidoamine (PAMAM) dendrimers across IPEC-J2 cell monolayers.

PubMed

Pisal, Dipak S; Yellepeddi, Venkata K; Kumar, Ajay; Palakurthi, Srinath

2008-11-01

The aim of our study was to prepare arginine-and ornithine-conjugated Polyamidoamine (PAMAM) dendrimers and study their permeability across IPEC-J2 cell monolayers, a new intestinal cell line model for drug absorption studies. Arginine and ornithine were conjugated to the amine terminals of the PAMAM(G4) dendrimers by Fmoc synthesis. The apical-to-basolateral (AB) and basolateral-to-apical (BA) apparent permeability coefficients (P(app)) for the PAMAM dendrimers increased by conjugating the dendrimers with both of these polyamines. The enhancement in permeability was dependent on the dendrimer concentration and duration of incubation. Correlation between monolayer permeability and the decrease in transepithelial electrical resistance (TEER) with the PAMAM dendrimers and the polyamine-conjugated dendrimers suggests that paracellular transport is one of the mechanisms of transport across the epithelial cells. Cytotoxicity of these surface-modified dendrimers was evaluated in IPEC-J2 cells by MTT (methylthiazoletetrazolium) assay. Arginine-conjugated dendrimers were insignificantly more toxic than PAMAM dendrimer as well as ornithine-conjugated dendrimers. Though investigations on the possible involvement of other transport mechanisms are in progress, results of the present study suggest the potential of dendrimer-polyamine conjugates as the carriers for antigen/drug delivery through the oral mucosa.

The permeability characteristics and interaction of the main components from Zhizi Bopi decoction in the MDCK cell model.

PubMed

Qian, Zhengyue; Huang, Cheng; Shen, Chenlin; Meng, Xiaoming; Chen, Zhaolin; Hu, Tingting; Li, Yangyang; Li, Jun

2016-08-01

1. Although emerging evidence indicates the therapeutic effects of Zhizi Bopi Decoction, the extent to which essential ingredients are absorbed and the possible synergistic actions are poorly understood. 2. In this study, MDCK cell model was used to determine the bi-directional permeability and interaction between the main components (geniposide, berberine and glycyrrhizic acid) of Zhizi Bopi Decoction. 3. The transport of the active ingredients was concentration-dependent in both directions. Moreover, the Papp (AP-BL) values of berberine and glycyrrhizic acid were significantly reduced when co-incubation with an ATP inhibitor. Additionally, uptake of berberine, glycyrrhizic acid were clearly inhibited by the inhibitors of P-glycoprotein and MRP2, indicating that P-gp and MRP2 may be involved in the transport of berberine and glycyrrhizic acid, respectively. However, it was found that geniposide may be purely passive diffusion. Furthermore, the combined incubation of geniposide with berberine and glycyrrhizic acid had a powerful sorbefacient effect than use of a single drug alone which may be regulated by tight junctions. 4. In summary, our study provides useful information for pharmacological applications of Zhizi Bopi Decoction and offers new insights into this ancient decoction for further researches, especially in drug synergism.

A mechanism enhancing macromolecule transport through paracellular spaces induced by Poly-L-Arginine: Poly-L-Arginine induces the internalization of tight junction proteins via clathrin-mediated endocytosis.

PubMed

Yamaki, Tsutomu; Kamiya, Yusuke; Ohtake, Kazuo; Uchida, Masaki; Seki, Toshinobu; Ueda, Hideo; Kobayashi, Jun; Morimoto, Yasunori; Natsume, Hideshi

2014-09-01

Poly-L-arginine (PLA) enhances the paracellular permeability of the Caco-2 cell monolayer to hydrophilic macromolecules by disappearance of tight junction (TJ) proteins from cell-cell junctions. However, the mechanism of the disappearance of TJ proteins in response to PLA has been unclear. In this study, we investigated the mechanism of disappearance of TJ proteins from cell-cell junctions after the application of PLA to Caco-2 cell monolayers. The membrane conductance (Gt), FITC-dextran (FD-4) permeability, and localization of TJ proteins were examined after the treatment of Caco-2 cell monolayers with PLA in the presence of various endocytosis inhibitors. In addition, the localization of endosome marker proteins was also observed. Clathrin-mediated endocytosis inhibitors suppressed the increase in Gt and Papp of FD-4 induced by PLA, and also significantly suppressed the disappearance of TJ proteins induced by PLA. Furthermore, occludin, one of the TJ proteins, colocalized with early endosome and recycling endosomes after the internalization of occludin induced by PLA, and then was recycled to the cell-cell junctions. PLA induced the transient internalization of TJ proteins in cell-cell junctions via clathrin-mediated endocytosis, subsequently increasing the permeability of the Caco-2 cell monolayer to FD-4 via a paracellular route.

Evaluation of the use of partition coefficients and molecular surface properties as predictors of drug absorption: a provisional biopharmaceutical classification of the list of national essential medicines of Pakistan

PubMed Central

Shawahna, R.; Rahman, NU.

2011-01-01

Background and the purpose of the study Partition coefficients (log D and log P) and molecular surface area (PSA) are potential predictors of the intestinal permeability of drugs. The aim of this investigation was to evaluate and compare these intestinal permeability indicators. Methods Aqueous solubility data were obtained from literature or calculated using ACD/Labs and ALOGPS. Permeability data were predicted based on log P, log D at pH 6.0 (log D6.0), and PSA. Results Metoprolol's log P, log D6.0, and a PSA of <65 Å correctly predicted 55.9%, 50.8% and 54.2% of permeability classes, respectively. Labetalol's log P, log D6.0 and PSA correctly predicted 54.2%, 64.4% and 61% of permeability classes, respectively. Log D6.0 correlated well (81%) with Caco-2 permeability (Papp). Of the list of national essential medicines, 135 orally administered drugs were classified into biopharmaceutical classification system (BCS). Of these, 57 (42.2%), 28 (20.7%), 44 (32.6%), and 6 (4.4%) were class I, II, III and IV respectively. Conclusion Log D6.0 showed better prediction capability than log P. Metoprolol as permeability internal standard was more conservative than labetalol. PMID:22615645

Enhanced oral delivery of docetaxel using thiolated chitosan nanoparticles: preparation, in vitro and in vivo studies.

PubMed

Saremi, Shahrooz; Dinarvand, Rassoul; Kebriaeezadeh, Abbas; Ostad, Seyed Nasser; Atyabi, Fatemeh

2013-01-01

The aim of this study was to evaluate a nanoparticulate system with mucoadhesion properties composed of a core of polymethyl methacrylate surrounded by a shell of thiolated chitosan (Ch-GSH-pMMA) for enhancing oral bioavailability of docetaxel (DTX), an anticancer drug. DTX-loaded nanoparticles were prepared by emulsion polymerization method using cerium ammonium nitrate as an initiator. Physicochemical properties of the nanoparticles such as particle size, size distribution, morphology, drug loading, and entrapment efficiency were characterized. The pharmacokinetic study was carried out in vivo using wistar rats. The half-life of DTX-loaded NPs was about 9 times longer than oral DTX used as positive control. The oral bioavailability of DTX was increased to 68.9% for DTX-loaded nanoparticles compared to 6.5% for positive control. The nanoparticles showed stronger effect on the reduction of the transepithelial electrical resistance (TEER) of Caco-2 cell monolayer by opening the tight junctions. According to apparent permeability coefficient (P(app)) results, the DTX-loaded NPs showed more specific permeation across the Caco-2 cell monolayer in comparison to the DTX. In conclusion, the nanoparticles prepared in this study showed promising results for the development of an oral drug delivery system for anticancer drugs.

Placental Dysfunction Underlies Increased Risk of Fetal Growth Restriction and Stillbirth in Advanced Maternal Age Women.

PubMed

Lean, Samantha C; Heazell, Alexander E P; Dilworth, Mark R; Mills, Tracey A; Jones, Rebecca L

2017-08-29

Pregnancies in women of advanced maternal age (AMA) are susceptible to fetal growth restriction (FGR) and stillbirth. We hypothesised that maternal ageing is associated with utero-placental dysfunction, predisposing to adverse fetal outcomes. Women of AMA (≥35 years) and young controls (20-30 years) with uncomplicated pregnancies were studied. Placentas from AMA women exhibited increased syncytial nuclear aggregates and decreased proliferation, and had increased amino acid transporter activity. Chorionic plate and myometrial artery relaxation was increased compared to controls. AMA was associated with lower maternal serum PAPP-A and sFlt and a higher PlGF:sFlt ratio. AMA mice (38-41 weeks) at E17.5 had fewer pups, more late fetal deaths, reduced fetal weight, increased placental weight and reduced fetal:placental weight ratio compared to 8-12 week controls. Maternofetal clearance of 14 C-MeAIB and 3 H-taurine was reduced and uterine arteries showed increased relaxation. These studies identify reduced placental efficiency and altered placental function with AMA in women, with evidence of placental adaptations in normal pregnancies. The AMA mouse model complements the human studies, demonstrating high rates of adverse fetal outcomes and commonalities in placental phenotype. These findings highlight placental dysfunction as a potential mechanism for susceptibility to FGR and stillbirth with AMA.

Management of abnormal serum markers in the absence of aneuploidy or neural tube defects

PubMed Central

Schnettler, William T.; Hacker, Michele R.; Barber, Rachel E.; Rana, Sarosh

2013-01-01

Objective Few guidelines address the management of pregnancies complicated by abnormal maternal serum analytes (MSAs) in the absence of aneuploidy or neural tube defects (NTDs). Our objective was to gather preliminary data regarding current opinions and management strategies among perinatologists in the US. Methods This survey of Maternal Fetal Medicine (MFM) physicians and fellows used a secure electronic web-based data capture tool. Results A total of 545 potential participants were contacted, and 136 (25%) responded. The majority were experienced academic physicians with robust practices. Nearly all (97.7%) respondents reported a belief in an association between abnormal MSAs and adverse pregnancy outcomes other than aneuploidy or NTDs. Plasma protein A (PAPP-A) and α-fetoprotein (AFP) were most often chosen as markers demonstrating a strong association with adverse outcomes. Most (86.9%) respondents acknowledged that abnormal MSAs influenced their counseling approach, and the majority (80.1%) offered additional ultrasound examinations. Nearly half started at 28 weeks and almost one-third at 32 weeks. Respondents acknowledging a relevant protocol in their hospital or practice were more likely to offer additional antenatal testing (p = 0.01). Conclusions Although most perinatologists were in agreement regarding the association of MSAs with adverse pregnancy outcomes, a lack of consensus exists regarding management strategies. PMID:22372385

Protein Profiling of Preeclampsia Placental Tissues

PubMed Central

Shu, Chang; Liu, Zitao; Cui, Lifeng; Wei, Chengguo; Wang, Shuwen; Tang, Jian Jenny; Cui, Miao; Lian, Guodong; Li, Wei; Liu, Xiufen; Xu, Hongmei; Jiang, Jing; Lee, Peng; Zhang, David Y.

2014-01-01

Preeclampsia is a multi-system disorder involved in pregnancy without an effective treatment except delivery. The precise pathogenesis of this complicated disorder is still not completely understood. The objective of this study is to evaluate the alterations of protein expression and phosphorylations that are important in regulating placental cell function in preterm and term preeclampsia. Using the Protein Pathway Array, 38 proteins in placental tissues were found to be differentially expressed between preterm preeclampsia and gestational age matched control, while 25 proteins were found to be expressed differentially between term preeclampsia and matched controls. Among these proteins, 16 proteins and their associated signaling pathways overlapped between preterm and term preeclampsia, suggesting the common pathogenesis of two subsets of disease. On the other hand, many proteins are uniquely altered in either preterm or term preeclampsia and correlated with severity of clinical symptoms and outcomes, therefore, providing molecular basis for these two subsets of preeclampsia. Furthermore, the expression levels of some of these proteins correlated with neonatal small for gestational age (PAI-1 and PAPP-A) and adverse outcomes (Flt-1) in women with preterm preeclampsia. These proteins could potentially be used as candidate biomarkers for predicting outcomes of preeclampsia. PMID:25392996

Impact of flows on ion temperatures inferred from neutron spectra in asymmetrically driven OMEGA DT implosions

NASA Astrophysics Data System (ADS)

Gatu Johnson, M.; Frenje, J. A.; Seguin, F. H.; Petrasso, R. D.; Aappelbe, B.; Chittenden, J.; Walsh, C.; Knauer, J. P.; Glebov, V. Yu.; Forrest, C.; Marshall, F.; Michel, T.; Stoeckl, C.; Sangster, T. C.; Zylstra, A.

2016-10-01

Ion temperatures (Tion) in Inertial Confinement Fusion (ICF) experiments have traditionally been inferred from the broadening of primary neutron spectra. Directional motion (flow) of the fuel at burn, expected to arise due to asymmetries imposed by engineering features (such as stalks, fill tubes, tents, or capsule imperfections) or drive non-uniformity, also impacts broadening and may lead to artificially inflated ``Tion'' values. Flow due to low-mode asymmetries is expected to give rise to line-of-sight variations in measured Tion, as observed in OMEGA cryogenic DT implosions but not in similar experiments at the NIF. In this presentation we report on an OMEGA experiment with intentionally asymmetric drive, designed to test the ability to accurately predict and measure line-of-sight differences in apparent Tion due to low-mode asymmetry-seeded flows. The results provide insight into the complexity of hot-spot dynamics, which is a problem that must be mastered to achieve ICF ignition. This work was supported in part by LLE, the U.S. DoE (NNSA, NLUF) and LLNL.

Calibration of a Thomson parabola ion spectrometer and Fujifilm imaging plate detectors for protons, deuterons, and alpha particles.

PubMed

Freeman, C G; Fiksel, G; Stoeckl, C; Sinenian, N; Canfield, M J; Graeper, G B; Lombardo, A T; Stillman, C R; Padalino, S J; Mileham, C; Sangster, T C; Frenje, J A

2011-07-01

A Thomson parabola ion spectrometer has been designed for use at the Multiterawatt (MTW) laser facility at the Laboratory for Laser Energetics (LLE) at the University of Rochester. This device uses parallel electric and magnetic fields to deflect particles of a given mass-to-charge ratio onto parabolic curves on the detector plane. Once calibrated, the position of the ions on the detector plane can be used to determine the particle energy. The position dispersion of both the electric and magnetic fields of the Thomson parabola was measured using monoenergetic proton and alpha particle beams from the SUNY Geneseo 1.7 MV tandem Pelletron accelerator. The sensitivity of Fujifilm BAS-TR imaging plates, used as a detector in the Thomson parabola, was also measured as a function of the incident particle energy over the range from 0.6 MeV to 3.4 MeV for protons and deuterons and from 0.9 MeV to 5.4 MeV for alpha particles. The device was used to measure the energy spectrum of laser-produced protons at MTW.

Characterizing Neutron Diagnostics on the nTOF Line at SUNY Geneseo

NASA Astrophysics Data System (ADS)

Harrison, Hannah; Seppala, Hannah; Visca, Hannah; Wakwella, Praveen; Fletcher, Kurt; Padalino, Stephen; Forrest, Chad; Regan, Sean; Sangster, Craig

2016-10-01

Charged particle beams from SUNY Geneseo's 1.7 MV Tandem Pelletron Accelerator induce nuclear reactions that emit neutrons ranging from 0.5 to 17.9 MeV via 2H(d,n)3He and 11B(d,n)12C. This adjustable neutron source can be used to calibrate ICF and HEDP neutron scintillators for ICF diagnostics. However, gamma rays and muons, which are often present during an accelerator-based calibration, are difficult to differentiate from neutron signals in scintillators. To mitigate this problem, a new neutron time-of-flight (nTOF) line has been constructed. The nTOF timing is measured using the associated particle technique. A charged particle produced by the nuclear reaction serves as a start signal, while its associated neutron is the stop signal. Each reaction is analyzed event-by-event to determine whether the scintillator signal was generated by a neutron, gamma or muon. Using this nTOF technique, the neutron response for different scintillation detectors can be determined. Funded in part by a LLE contract through the DOE.

"One-pot" ethyl chloroformate derivatization and liquid-liquid extraction of reduced glutathione in erythrocyte and its quantitative GC-MS analysis.

PubMed

Manca, Alessandra; Alladio, Eugenio; Massarenti, Paola; Puccinelli, M Paola; De Francesco, Antonella; Del Grosso, Erika; Mengozzi, Giulio; Pazzi, Marco; Vincenti, Marco

2017-12-01

A simple "one-pot" derivatization and liquid-liquid extraction (LLE) procedure was developed for GC-MS analysis of reduced glutathione (GSH) analysis in erythrocytes. The metabolite was extracted by 5% (w/v) TCA, the supernatant treated with ECF and ethanol-pyridine media, the derivative separated and detected by gas chromatography-mass spectrometry using a short non-polar capillary GC column at a high column-head pressure. Total analysis time was 11min. The process was optimized by a Design of Experiment. The method was validated showing a good linearity over the 25.4-813.4μM concentration range, providing satisfactory results in terms of intra-day and inter-day precision as well as an optimal accuracy. The new method was evaluated in a pilot study involving patients with severe protein malnutrition. Comparison of this group with a group of healthy subjects revealed significantly lower GSH concentrations in erythrocytes in the former, thus proving that the described GC-MS method could be employed for fast and simple GSH analysis in clinical studies. Copyright © 2017 Elsevier B.V. All rights reserved.

CBET Experiments with Wavelength Shifting at the Nike Laser

NASA Astrophysics Data System (ADS)

Weaver, James; McKenty, P.; Bates, J.; Myatt, J.; Shaw, J.; Obenschain, K.; Oh, J.; Kehne, D.; Obenschain, S.; Lehmberg, R. H.; Tsung, F.; Schmitt, A. J.; Serlin, V.

2016-10-01

Studies conducted at NRL during 2015 searched for cross-beam energy transport (CBET) in small-scale plastic targets with strong gradients in planar, cylindrical, and spherical geometries. The targets were irradiated by two widely separated beam arrays in a geometry similar to polar direct drive. Data from these shots will be presented that show a lack of a clear CBET signature even with wavelength shifting of one set of beams. This poster will discuss the next campaign being planned, in part, with modelling codes developed at LLE. The next experiments will use a target configuration optimized to create stronger SBS growth. The primary path under consideration is to increase scale lengths 5-10x over the previous study by using exploding foils or low density foams. In addition to simulations, the presentation will also discuss improvements to the diagnostic suite and laser operations; for example, a new set of etalons will be available for the next campaign that should double the range of wavelength shifting between the two beam arrays. Work supported by DoE/NNSA.

Prime Contract Awards Alphabetically by Contractor, by State or Country, and Place. Part 9. (H and H Meat Products, Inc.-Iannucci and Son Con.)

DTIC Science & Technology

1989-01-01

8217 Cl - 4 enC )() COOIn-Mi I -4N(r4 N(\\J C C NN N lc04-. >N I 40(00 000 0 (NJ>om -4N(04L) 1 00 CIoOC ’o >0 0 I 20 0 0 Q n4 00 0 L ooQC IM 4(-4 C4 o a oI...1- Q( a ɘ ə a < LA-L-L) < 00(u0N D 0( W1 I’N D (D (DN 41 If 4( c I lle W M.-(--4.1000 U).- 4(D LA- LADO LA4 ( (0C 01.᝴ L -4 - 14-4 I-4 -4 -- of...Mooɜ IftVci 0I oU1 n107,I nL nI nI CaN InC) LALLAALL L -4 1.1Q(0 O C1(1Cim 1000 -00 1 f (D(0 f1 ENc nu nI nu )t nL)I r nI nu O L A L A L A L 10 C -i

High-throughput method for the determination of residues of β-lactam antibiotics in bovine milk by LC-MS/MS.

PubMed

Jank, Louise; Martins, Magda Targa; Arsand, Juliana Bazzan; Hoff, Rodrigo Barcellos; Barreto, Fabiano; Pizzolato, Tânia Mara

2015-01-01

This study describes the development and validation procedures for scope extension of a method for the determination of β-lactam antibiotic residues (ampicillin, amoxicillin, penicillin G, penicillin V, oxacillin, cloxacillin, dicloxacillin, nafcillin, ceftiofur, cefquinome, cefoperazone, cephapirine, cefalexin and cephalonium) in bovine milk. Sample preparation was performed by liquid-liquid extraction (LLE) followed by two clean-up steps, including low temperature purification (LTP) and a solid phase dispersion clean-up. Extracts were analysed using a liquid chromatography-electrospray-tandem mass spectrometry system (LC-ESI-MS/MS). Chromatographic separation was performed in a C18 column, using methanol and water (both with 0.1% of formic acid) as mobile phase. Method validation was performed according to the criteria of Commission Decision 2002/657/EC. Main validation parameters such as linearity, limit of detection, decision limit (CCα), detection capability (CCβ), accuracy, and repeatability were determined and were shown to be adequate. The method was applied to real samples (more than 250) and two milk samples had levels above maximum residues limits (MRLs) for cloxacillin - CLX and cefapirin - CFAP.

Monolithic methacrylate packed 96-tips for high throughput bioanalysis.

PubMed

Altun, Zeki; Skoglund, Christina; Abdel-Rehim, Mohamed

2010-04-16

In the pharmaceutical industry the growing number of samples to be analyzed requires high throughput and fully automated analytical techniques. Commonly used sample-preparation methods are solid-phase extraction (SPE), liquid-liquid extraction (LLE) and protein precipitation. In this paper we will discus a new sample-preparation technique based on SPE for high throughput drug extraction developed and used by our group. This new sample-preparation method is based on monolithic methacrylate polymer as packing sorbent for 96-tip robotic device. Using this device a 96-well plate could be handled in 2-4min. The key aspect of the monolithic phase is that monolithic material can offer both good binding capacity and low back-pressure properties compared to e.g. silica phases. The present paper presents the successful application of monolithic 96-tips and LC-MS/MS by the sample preparation of busulphan, rescovitine, metoprolol, pindolol and local anaesthetics from human plasma samples and cyklophosphamid from mice blood samples. Copyright 2009 Elsevier B.V. All rights reserved.

Long Scalelength Plasmas for LPI Studies at the Nike Laser

NASA Astrophysics Data System (ADS)

Weaver, J. L.; Oh, J.; Bates, J. W.; Schmitt, A. J.; Kehne, D. M.; Wolford, M. F.; Obenschain, S. P.; Serlin, V.; Lehmberg, R. H.; Follett, R. K.; Shaw, J. G.; Myatt, J. F.; McKenty, P. W.; Wei, M. S.; Reynolds, H.; Williams, J.; Tsung, F.

2017-10-01

Studies of laser plasma instabilities (LPI) at the Nike laser have mainly used short pulses, small focal spots, and solid plastic (CH) targets that have yielded maximum gradient scalelengths below 200 microns. The current experimental effort aims to produce larger volume plasmas with 5-10x reduction in the density and velocity gradients as a platform for SBS, SRS, and TPD studies. The next campaign will concentrate on the effects of wavelength shifting and bandwidth changes on CBET in low density (5-10 mg/cm3) CH foam targets. This poster will discuss the development of this new LPI target platform based on modelling with the LPSE code developed at LLE. The presentation will also discuss alternative target schemes (e.g. exploding foils) and improvements to the LPI diagnostic suite and laser operations; for example, a new set of etalons will be available for the next campaign that should double the range of available wavelength shifting. Upgrades to the scattered light spectrometers in general use for LPI studies will also be presented. Work supported by DoE/NNSA.

Liquid to liquid extraction and liquid chromatography-tandem mass spectrometry determination of hainanmycin in feed.

PubMed

Wang, Ze Ping; Shen, Jian Zhong; Linhardt, Robert J; Jiang, Hui; Cheng, Lin Li

2017-03-01

Hainanmycin is a new veterinary polyether antibiotic and has few sensitive analytical method in present days. In this study, a liquid chromatography-tandem mass spectrometry (LC-MS/MS) relying on multiple reaction monitoring (MRM) detection was developed for analysis of hainanmycin in animal feed. Feed samples were extracted with ethyl acetate and purified by two steps of liquid-liquid extraction (LLE) to get rid of water solvable matrix and lipids one by one. The final simple was analyzed by LC-MS/MS. The LC mobile phase was composed of 0.1% aqueous formic acid and 0.1% formic acidified acetonitrile by gradient elution. Average recoveries ranged from 74.22% to 87.85%, as determined by spiking with 2.0 (LOQ) ∼2500μgkg -1 of hainanmycin. The inter-day and intra-day coefficient of variation was 9.21% to 11.77% and 7.67% to 13.49%, respectively. The limit of detection (LOD) and the limit of quantitation (LOQ) were 0.36μgkg -1 and 2.0μgkg -1 , respectively. Copyright © 2016. Published by Elsevier B.V.

A Retrieval System for Radioactive Target Materials at the NIF

NASA Astrophysics Data System (ADS)

Krieger, M.; Shibata, K.; Fallica, J.; Henchen, R.; Pogozelski, E.; Padalino, S.; Sangster, T. C.; Suny Collaboration; Laboratory Collaboration

2011-10-01

Currently, solid radioactive material collection from the NIF target chamber is performed via the DIM. The retrieval process takes several hours to complete. To decrease this time for short lived radioisotopes, the Target Materials Retrieval System (TMRS) is being designed to move a radioactive sample from the target chamber to the counting station in less than 50 seconds, using a closed-loop helium filled RaPToRS system. The TMRS consists of three components: the retrieval apparatus, RaPToRS and the counting station. Starting at 0.5 meters from TCC, the sample will move from the vacuum chamber, travel through 60 meters of 10 centimeter diameter RaPToRS tubes, reaching speeds of 10 m/s. The sample will then arrive at the counting station, where it be robotically placed in front of a gamma ray detector. The use of helium will decrease background gamma radiation produced by activated N2 normally found in a pressurized air system. This work was supported in part by the US Department of Energy through the LLE.

Nonadditive entropy Sq and nonextensive statistical mechanics: Applications in geophysics and elsewhere

NASA Astrophysics Data System (ADS)

Tsallis, Constantino

2012-06-01

The celebrated Boltzmann-Gibbs (BG) entropy, S BG = -kΣi p i ln p i, and associated statistical mechanics are essentially based on hypotheses such as ergodicity, i.e., when ensemble averages coincide with time averages. This dynamical simplification occurs in classical systems (and quantum counterparts) whose microscopic evolution is governed by a positive largest Lyapunov exponent (LLE). Under such circumstances, relevant microscopic variables behave, from the probabilistic viewpoint, as (nearly) independent. Many phenomena exist, however, in natural, artificial and social systems (geophysics, astrophysics, biophysics, economics, and others) that violate ergodicity. To cover a (possibly) wide class of such systems, a generalization (nonextensive statistical mechanics) of the BG theory was proposed in 1988. This theory is based on nonadditive entropies such as S_q = kfrac{{1 - sumnolimits_i {p_i^q } }} {{q - 1}}left( {S_1 = S_{BG} } right). Here we comment some central aspects of this theory, and briefly review typical predictions, verifications and applications in geophysics and elsewhere, as illustrated through theoretical, experimental, observational, and computational results.

Using secondary nuclear products for inferring the fuel areal density, convergence, and electron temperatures of deuterium filled implosions on the NIF

NASA Astrophysics Data System (ADS)

Lahmann, B.; Frenje, J. A.; Gatu Johnson, M.; Sio, H.; Kabadi, N. V.; Sutcliffe, G.; Seguin, F. H.; Li, C. K.; Petrasso, R. D.; Hartouni, E. P.; Rinderknecht, H. G.; Sayre, D. B.; Yeamans, C. B.; Khan, S. F.; Kyrala, G. A.; Lepape, S.; Berzak-Hopkins, L.; Meezan, N.; Bionta, R.; Ma, T.

2016-10-01

In deuterium-filled inertial confinement fusion implosions, 0.82 MeV 3He and 1.01 MeV T born from the primary DD reaction branches can undergo fusion reactions with the thermal deuterium plasma to create secondary D3He protons and DT neutrons respectively. In regimes of moderate fuel areal density (ρR 5 - 100 mg/cm2) the ratio of both of these secondary yields to the primary yield can be used to infer the fuel ρR, convergence, and an electron temperature (Te) simultaneously. This technique has been used on a myriad of deuterium filled implosion experiments on the NIF using the nuclear time of flight (NTOF) diagnostics to measure the secondary DT neutrons and CR-39 based wedge range filters (WRFs) to measure the secondary D3He protons. Additionally, a comparative study is conducted between the nuclear inferred convergence and x-ray inferred convergence obtained on these experiments. This work was supported in part by LLE, the U.S. DoE (NNSA, NLUF) and LLNL.

Studies of ion kinetic effects in OMEGA shock-driven implosions using fusion burn imaging

NASA Astrophysics Data System (ADS)

Rosenberg, M. J.; Seguin, F. H.; Rinderknecht, H. G.; Sio, H.; Zylstra, A. B.; Gatu Johnson, M.; Frenje, J. A.; Li, C. K.; Petrasso, R. D.; Amendt, P. A.; Wilks, S. C.; Zimmerman, G.; Hoffman, N. M.; Kagan, G.; Molvig, K.; Glebov, V. Yu.; Stoeckl, C.; Marshall, F. J.; Seka, W.; Delettrez, J. A.; Sangster, T. C.; Betti, R.; Meyerhofer, D. D.; Atzeni, S.; Nikroo, A.

2014-10-01

Ion kinetic effects have been inferred in a series of shock-driven implosions at OMEGA from an increasing yield discrepancy between observations and hydrodynamic simulations as the ion-ion mean free path increases. To more precisely identify the nature and impact of ion kinetic effects, spatial burn profile measurements of DD and D3He reactions in these D3He-filled shock-driven implosions are presented and contrasted to both purely hydrodynamic models and models that include ion kinetic effects. It is shown that in implosions where the ion mean free path is equal to or greater than the size of the fuel region, purely hydrodynamic models fail to capture the observed burn profiles, while a model that includes ion diffusion is able to recover the observed burn profile shape. These results further elucidate the ion kinetic mechanisms that are present under long mean-free-path conditions after shock convergence in both shock-driven and ablatively-driven implosions. This work was supported in part by the U.S. DOE, NLUF, LLE, and LLNL.

First quantitative measurements of charged-particle stopping and its dependence on electron temperature and density in Inertial-Confinement-Fusion plasmas

NASA Astrophysics Data System (ADS)

Frenje, J.; Li, C. K.; Séguin, F.; Zylstra, A.; Rinderknecht, H.; Petrasso, R.; Delettrez, J.; Glebov, V.; Sangster, T.

2013-10-01

We report on the first quantitative measurements of charged-particle stopping in Inertial-Confinement-Fusion (ICF) plasmas at various conditions. In these experiments, four charged fusion products from the DD and D3He reactions in D3He gas-filled filled implosions were used to determine the stopping power of ICF plasmas at electron temperatures (Te) , ion temperatures (Ti) , and areal densities (ρR) in the range of 0.6-4.0 keV, 3-14 keV and 2-10 mg/cm2, respectively. The resulting data, in the form of measured energy downshift of the charged fusion products, clearly indicate that the stopping-power function depends strongly on Te. It was also observed that the stopping-power function change in characteristics for higher-density implosions in which ions and electrons equilibrate faster, resulting in higher Te relative to Ti and higher ρR s. These results will be modelled by Landau-Spitzer theory and contrasted to different stopping-power models. This work was partially supported by the US DOE, NLUF, LLE, and GA.

Ether bond effects in quaternary ammonium and phosphonium ionic liquid-propanol solutions

NASA Astrophysics Data System (ADS)

Kishimura, Hiroaki; Kohki, Erica; Nakada, Ayumu; Tamatani, Kentaro; Abe, Hiroshi

2018-03-01

The liquid-liquid equilibria (LLE) of quaternary ammonium and phosphonium ionic liquid (IL)-propanol solutions were examined. The ILs contained cations with or without ether bonds; the anion in all the ILs was bis(trifluoromethanesulfonyl)imide (TFSI-). The cations without ether groups are tributylmethyl ammonium (N4441+), triethylpentyl phosphonium (P2225+), triethyloctyl phosphonium (P2228+), and tributylmethyl phosphonium (P4441+). The cations containing ether groups are N,N-diethyl-N-methyl-N-(2-methoxyethyl) ammonium, (N122(2O1)+), triethyl(methoxymethyl) phosphonium (P222(1O1)+), and triethyl(2-methoxyethyl) phosphonium, (P222(2O1)+). Propanol isomer effect was observed to affect the LLEs, reflecting the geometrical factors and hydrophobicities of 1-propanol and 2-propanol. According to Raman spectroscopy, the TFSI- anion conformers in the mixtures were altered in the presence of ether bonds in the cations. The universal quasichemical (UNIQUAC) interaction parameters are consistent with significant factors affecting IL-propanol solutions, such as the type of cation (ammonium or phosphonium), ether bonds, TFSI- conformers, and propanol isomer effects.

Preparation of penta-O-galloyl-β-D-glucose from tannic acid and plasma pharmacokinetic analyses by liquid-liquid extraction and reverse-phase HPLC.

PubMed

Li, Li; Shaik, Ahmad Ali; Zhang, Jinhui; Nhkata, Katai; Wang, Lei; Zhang, Yong; Xing, Chengguo; Kim, Sung-Hoon; Lü, Junxuan

2011-02-20

The gallotannin penta-O-galloyl-beta-D-glucose (PGG) has many biological activities including in vivo anti-cancer efficacy. We present in this paper a scaled-up protocol for its preparation in high purity from tannic acid by acidic methanolysis with typical yield of 15%. We also describe a method for the analysis of PGG in mouse plasma by HPLC and its application in preliminary pharmacokinetic studies. A liquid-liquid extraction (LLE) protocol was optimized for the extraction of PGG from mouse plasma. The extraction efficiency for PGG at 1 μg/mL in mouse plasma was 70.0±1.3% (n=5). The limit of detection (LOD) for PGG was approximately 0.2 μg/mL. Preliminary pharmacokinetic parameters of PGG following a single i.p. injection with 5% ethanol/saline vehicle in mice were established. The peak plasma PGG concentrations (C(max)) were approximately 3-4 μM at a dose of 0.5 mg per mouse (∼20 mg/kg) at 2 h post-injection (T(max)). Copyright © 2010 Elsevier B.V. All rights reserved.

Validation of a Laser-Ray Package in an Eulerian Code

NASA Astrophysics Data System (ADS)

Bradley, Paul; Hall, Mike; McKenty, Patrick; Collins, Tim; Keller, David

2014-10-01

A laser-ray absorption package was recently installed in the RAGE code by the Laboratory for Laser Energetics (LLE). In this presentation, we describe our use of this package to implode Omega 60 beam symmetric direct drive capsules. The capsules have outer diameters of about 860 microns, CH plastic shell thicknesses between 8 and 32 microns, DD or DT gas fills between 5 and 20 atmospheres, and a 1 ns square pulse of 23 to 27 kJ. These capsule implosions were previously modeled with a calibrated energy source in the outer layer of the capsule, where we matched bang time and burn ion temperature well, but the simulated yields were two to three times higher than the data. We will run simulations with laser ray energy deposition to the experiments and the results to the yield and spectroscopic data. Work performed by Los Alamos National Laboratory under Contract DE-AC52-06NA25396 for the National Nuclear Security Administration of the U.S. Department of Energy.

Turbulent Dynamo Amplification of Magnetic Fields in Laser-Produced Plasmas: Simulations and Experiments

NASA Astrophysics Data System (ADS)

Tzeferacos, P.; Rigby, A.; Bott, A.; Bell, A.; Bingham, R.; Casner, A.; Cattaneo, F.; Churazov, E.; Forest, C.; Katz, J.; Koenig, M.; Li, C.-K.; Meinecke, J.; Petrasso, R.; Park, H.-S.; Remington, B.; Ross, J.; Ryutov, D.; Ryu, D.; Reville, B.; Miniati, F.; Schekochihin, A.; Froula, D.; Lamb, D.; Gregori, G.

2017-10-01

The universe is permeated by magnetic fields, with strengths ranging from a femtogauss in the voids between the filaments of galaxy clusters to several teragauss in black holes and neutron stars. The standard model for cosmological magnetic fields is the nonlinear amplification of seed fields via turbulent dynamo. We have conceived experiments to demonstrate and study the turbulent dynamo mechanism in the laboratory. Here, we describe the design of these experiments through large-scale 3D FLASH simulations on the Mira supercomputer at ANL, and the laser-driven experiments we conducted with the OMEGA laser at LLE. Our results indicate that turbulence is capable of rapidly amplifying seed fields to near equipartition with the turbulent fluid motions. This work was supported in part from the ERC (FP7/2007-2013, No. 256973 and 247039), and the U.S. DOE, Contract No. B591485 to LLNL, FWP 57789 to ANL, Grant No. DE-NA0002724 and DE-SC0016566 to the University of Chicago, and DE-AC02-06CH11357 to ANL.

The Mini Orange Spectrometer (MOS) for Stellar and Big-Bang Nucleosynthesis studies at OMEGA and the National Ignition Facility

NASA Astrophysics Data System (ADS)

Sutcliffe, G. D.; Frenje, J. A.; Gatu Johnson, M.; Li, C. K.; Parker, C.; Simpson, R.; Sio, H.; Seguin, F. H.; Petrasso, R. D.; Zylstra, A.

2017-10-01

A compact and highly efficient Mini Orange Spectrometer (MOS) is being designed for measurements of energy spectra of protons and alphas in the range of 1-12 MeV in experiments at the OMEGA laser facility and the National Ignition Facility (NIF). The MOS will extend charged-particle spectrometry at these laser facilities to lower energies (<5 MeV) and lower yields (<5×108) than current instrumentation allows. This new spectrometer will enable studies of low-probability stellar nucleosynthesis reactions, including the 3He+3He reaction that is part of the solar proton-proton chain. Its unique capabilities will also be exploited in other basic science experiments, including studies of stopping power in ICF-relevant plasmas, astrophysical shocks and kinetic physics. The MOS design achieves high efficiency by maximizing the solid angle of particle acceptance. The optimization of the MOS design uses simulated magnetic fields and particle tracing. Performance requirements of the MOS system, including desired detection efficiencies and energy resolution, are discussed. This work was supported in part by the U.S. DoE, LLNL, and LLE.

Effect of solvent polarity levels on separation of xanthone and coumarin from Calophyllum inophyllum leaves extract

NASA Astrophysics Data System (ADS)

Susanto, D. F.; Hapsari, S.; Trilutfiani, Z.; Borhet, A.; Aparamarta, H. W.; Widjaja, A.; Gunawan, S.

2018-03-01

Calophyllum inophyllum has various benefits that can be utilized from root, stem, leaf, until seed. C. inophyllum leaves contain many bioactive compounds, such as xanthone and coumarin which are useful as antioxidant, and inhibitors of enzyme activity from HIV virus. The aim of this research was to investigate the effect of solvent polarity levels on the separation of xanthone and coumarin compounds contained in the crude extract of C. inophyllum leaves. Crude leaves extract was obtained by percolation method. Moreover, Liquid Liquid Extraction (LLE) was used for separating xanthone and coumarin compounds. It was performed by methanol (polar solvent) and hexane (non-polar solvent) with solvent ratio of 1. Methanol concentration in water used were 20%, 50%, 80%, and 100%. Each fraction obtained was tested qualitatively using Thin Layer Chromatography (TLC) and quantitatively using Gas Chromatography (GC) to analyze xanthone and coumarin. The best separation result was obtained by using 50% methanol. In this results, coumarin and xanthones were separated in methanol fraction (81.18% recovery) and in hexane fraction (81.91% recovery), respectively.

Stability of catechins in green tea nutraceutical products: application of solid phase extraction-thin layer chromatography densitometry.

PubMed

Abd-Elsalam, Heba-Alla H; Al-Ghobashy, Medhat A; Zaazaa, Hala E; Ibrahim, Mohamed A

2014-08-01

Epigallocatechin gallate (EGCG) is a powerful antioxidant and commonly used nutraceutical. Accelerated stability of EGCG in tablet formulations was investigated. LLE and SPE were employed for sample clean-up and enrichment of EGCG over caffeine. Samples were analysed after spiking with fixed concentration of gallic acid (GA), in order to verify reproducibility of analysis. A TLC-densitometric assay was developed and validated for determination of % loss EGCG. EGCG, GA and caffeine were resolved with Rf values 0.54, 0.69 and 0.80, respectively. LC-MS/MS was used to verify identity and purity of the EGCG band. Determination was carried out over a concentration range of 0.50-5.00μg/band and 0.20-2.40μg/band for GA and caffeine, respectively. Results showed significant reduction in EGCG content after one, three and six months: 24.00%, 28.00% and 52.00% respectively. Results continue to demonstrate that stability of nutraceutical products should be investigated in-depth using industry-oriented protocols before granting marketing authorisation. Copyright © 2014 Elsevier Ltd. All rights reserved.

Oleic acid derivative of polyethylenimine-functionalized proliposomes for enhancing oral bioavailability of extract of Ginkgo biloba.

PubMed

Zheng, Bin; Yang, Shuang; Fan, Chunyu; Bi, Ye; Du, Lin; Zhao, Lingzhi; Lee, Robert J; Teng, Lesheng; Teng, Lirong; Xie, Jing

2016-05-01

The present systematic study focused to investigate the oleic acid derivative of branched polyethylenimine (bPEI-OA)-functionalized proliposomes for improving the oral delivery of extract of Ginkgo biloba (GbE). The GbE proliposomes were prepared by a spray drying method at varying ratios of egg yolk phosphatidylcholine and cholesterol, and the optimized formulation was tailored with bPEI-OA to obtain bPEI-OA-functionalized proliposomes. The formulations were characterized for particle size, zeta potential, and entrapment efficiency. The release of GbE from proliposomes exhibited a sustained release. And the release rate was regulated by changing the amount of bPEI-OA on the proliposomes. The physical state characterization studies showed some interactions between GbE and other materials, such as hydrogen bonds and van der Waals forces during the process of preparation of proliposomes. The in situ single-pass perfusion and oral bioavailability studies were performed in rats. The significant increase in absorption constant (Ka) and apparent permeability coefficient (Papp) from bPEI-OA-functionalized proliposomes indicated the importance of positive charge for effective uptake across the gastrointestinal tract. The oral bioavailability of bPEI-OA-functionalized proliposomes was remarkable enhanced in comparison with control and conventional proliposomes. The bPEI-OA-functionalized proliposomes showed great potential of improving oral absorption of GbE as a suitable carrier.

Predictive factors for intrauterine growth restriction

PubMed Central

Albu, AR; Anca, AF; Horhoianu, VV; Horhoianu, IA

2014-01-01

Abstract Reduced fetal growth is seen in about 10% of the pregnancies but only a minority has a pathological background and is known as intrauterine growth restriction or fetal growth restriction (IUGR / FGR). Increased fetal and neonatal mortality and morbidity as well as adult pathologic conditions are often associated to IUGR. Risk factors for IUGR are easy to assess but have poor predictive value. For the diagnostic purpose, biochemical serum markers, ultrasound and Doppler study of uterine and spiral arteries, placental volume and vascularization, first trimester growth pattern are object of assessment today. Modern evaluations propose combined algorithms using these strategies, all with the goal of a better prediction of risk pregnancies. Abbreviations: SGA = small for gestational age; IUGR = intrauterine growth restriction; FGR = fetal growth restriction; IUFD = intrauterine fetal demise; HIV = human immunodeficiency virus; PAPP-A = pregnancy associated plasmatic protein A; β-hCG = beta human chorionic gonadotropin; MoM = multiple of median; ADAM-12 = A-disintegrin and metalloprotease 12; PP-13 = placental protein 13; VEGF = vascular endothelial growth factor; PlGF = placental growth factor; sFlt-1 = soluble fms-like tyrosine kinase-1; UAD = uterine arteries Doppler ultrasound; RI = resistence index; PI = pulsatility index; VOCAL = Virtual Organ Computer–Aided Analysis software; VI = vascularization index; FI = flow index; VFI = vascularization flow index; PQ = placental quotient PMID:25408721

Chitosan-modified porous silicon microparticles for enhanced permeability of insulin across intestinal cell monolayers.

PubMed

Shrestha, Neha; Shahbazi, Mohammad-Ali; Araújo, Francisca; Zhang, Hongbo; Mäkilä, Ermei M; Kauppila, Jussi; Sarmento, Bruno; Salonen, Jarno J; Hirvonen, Jouni T; Santos, Hélder A

2014-08-01

Porous silicon (PSi) based particulate systems are emerging as an important drug delivery system due to its advantageous properties such as biocompatibility, biodegradability and ability to tailor the particles' physicochemical properties. Here, annealed thermally hydrocarbonized PSi (AnnTHCPSi) and undecylenic acid modified AnnTHCPSi (AnnUnTHCPSi) microparticles were developed as a PSi-based platform for oral delivery of insulin. Chitosan (CS) was used to modify the AnnUnTHCPSi microparticles to enhance the intestinal permeation of insulin. Surface modification with CS led to significant increase in the interaction of PSi microparticles with Caco-2/HT-29 cell co-culture monolayers. Compared to pure insulin, the CS-conjugated microparticles significantly improved the permeation of insulin across the Caco-2/HT-29 cell monolayers, with ca. 20-fold increase in the amount of insulin permeated and ca. 7-fold increase in the apparent permeability (P(app)) value. Moreover, among all the investigated particles, the CS-conjugated microparticles also showed the highest amount of insulin associated with the mucus layer and the intestinal Caco-2 cells and mucus secreting HT-29 cells. Our results demonstrate that CS-conjugated AnnUnTHCPSi microparticles can efficiently enhance the insulin absorption across intestinal cells, and thus, they are promising microsystems for the oral delivery of proteins and peptides across the intestinal cell membrane. Copyright © 2014 Elsevier Ltd. All rights reserved.

In Vitro Plasma Stability, Permeability and Solubility of Mercaptoacetamide Histone Deacetylase Inhibitors

PubMed Central

Konsoula, Roula; Jung, Mira

2008-01-01

Histone deacetylase inhibitors (HDACIs) are emerging as a new class of therapeutic agents with potent antitumor activities in a broad spectrum of human cancers. In this study, the in vitro plasma stability, permeability, solubility, and lipophilicity (logD) of two mercaptoacetamide-based HDACIs (coded as W2 and S2) were evaluated and compared to Vorinostat (SAHA). The results demonstrated that the compounds manifested high solubility in HCl (pH 1.2) but lower in PBS (pH 7.4) than SAHA. Moreover, mercaptoacetamide-based HDACIs exhibited higher lipophilicity values compared to SAHA. The permeability of these compounds was evaluated using the Caco-2 cell monolayer as a model of the intestinal mucosa. The Caco-2 studies revealed that the compounds S2 and W2 are highly permeable with apparent permeability coefficients (Papp) in the apical to basolateral direction of 7.33 × 10−6 and 15.0 × 10−6 cm/s, respectively. The in vitro stability was determined in human, mouse, porcine and rat plasma. Data showed that the compound W2 is more stable in human and rat plasma and the S2 is more stable in all plasma species than SAHA. Taken together, these results indicate that the mercaptoacetamide-based HDACIs possess favorable solubility, lipophilicity, permeability and plasma stability features. PMID:18562136

A systematic review of first trimester biochemical and molecular predictive tests for preeclampsia.

PubMed

Abdi, Fatemeh; Aghaie, Zohreh; Rahnemaie, Fatemeh Sadat; Alimoradi, Zainab

2018-04-16

Preeclampsia is a multisystem disorder affecting 5%-8% of pregnant women. Considering the ongoing debate over the predicting value of some commercial first trimester tests, the aim of this study was to compare the existing first trimester screening tests for preeclampsia. In this systematic review, relevant articles published during 2000-2017 were extracted from PubMed, Science Direct, Scopus, Cochrane Library, ISI Web of Science, and ProQuest databases. After thorough evaluation of the 412 potentially eligible papers, only 26 papers were selected based on the inclusion criteria. From a total of 412 retrieved studies, 28 papers were found eligible. Most studies had case-control or nested case-control designs. A total of 15164 pregnant women were evaluated in the reviewed studies. Various tests were applied in the first trimester of pregnancy to predict the development of preeclampsia. The most commonly used biomarkers were uterine artery pulsatility index, pregnancy-associated plasma protein A (PAPP-A), adiponectin, human chorionic gonadotropin (hCG) hormone and inhibin-A. Other tests were used in only one or two studies. Based on this review, a combination of markers should be evaluated for the identification of high risk women. Novel methods measuring multiple markers will hopefully facilitate the development of clinically effective screening programs in the future. Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.org.

[Ambulatory blood pressure monitoring for hypertension diagnosis?

PubMed

Gijón Conde, T; Banegas, J R

2017-01-01

The early and accurate diagnosis of hypertension is essential given its importance in the development of cardiovascular disease. The boundaries between normal blood pressure (BP) and hypertension are arbitrary and based on the benefits of treating exceeding those of not treating. Conventional BP measurement at the clinic only offers information of a particular time and presents multiple biases dependent on inherent variability of BP and measurement technique itself. Multiple studies have demonstrated the prognosis superiority in the development of cardiovascular disease of ambulatory blood pressure monitoring (ABPM), allows detection of white coat hypertension, avoiding overdiagnosis and overtreatment, and the detection of patients with masked hypertension who are at risk of underdetection and undertreatment. ABPM also assess nightime BP and circadian variability, providing additional prognostic value. ABPM is recognized in the diagnosis of hypertension in 2011 British NICE Guidelines, very argued at the 2013 European Society of Hypertension guidelines, and recommended in the US Preventive Services Task Force in 2015, 2016 Canadian Guidelines and the 2016 Spanish Program of Preventive Activities and Health Promotion (PAPPS). Its generalization is likely to be only a matter of time. Copyright © 2017 Sociedad Española de Hipertension-Liga Española para la Lucha de la Hipertensión Arterial (SEH-LELHA). Publicado por Elsevier España, S.L.U. All rights reserved.

Intestinal Permeability and Cellular Antioxidant Activity of Phenolic Compounds from Mango (Mangifera indica cv. Ataulfo) Peels

PubMed Central

Pacheco-Ordaz, Ramón; González-Aguilar, Gustavo A.

2018-01-01

Mango (Mangifera indica cv. Ataulfo) peel contains bound phenolics that may be released by alkaline or acid hydrolysis and may be converted into less complex molecules. Free phenolics from mango cv. Ataulfo peel were obtained using a methanolic extraction, and their cellular antioxidant activity (CAA) and permeability were compared to those obtained for bound phenolics released by alkaline or acid hydrolysis. Gallic acid was found as a simple phenolic acid after alkaline hydrolysis along with mangiferin isomers and quercetin as aglycone and glycosides. Only gallic acid, ethyl gallate, mangiferin, and quercetin were identified in the acid fraction. The acid and alkaline fractions showed the highest CAA (60.5% and 51.5%) when tested at 125 µg/mL. The value of the apparent permeability coefficient (Papp) across the Caco-2/HT-29 monolayer of gallic acid from the alkaline fraction was higher (2.61 × 10−6 cm/s) than in the other fractions and similar to that obtained when tested pure (2.48 × 10−6 cm/s). In conclusion, mango peels contain bound phenolic compounds that, after their release, have permeability similar to pure compounds and exert an important CAA. This finding can be applied in the development of nutraceuticals using this important by-product from the mango processing industry. PMID:29419800