Variability in protein binding of teicoplanin and achievement of therapeutic drug monitoring targets in critically ill patients: lessons from the DALI Study.

PubMed

Roberts, J A; Stove, V; De Waele, J J; Sipinkoski, B; McWhinney, B; Ungerer, J P J; Akova, M; Bassetti, M; Dimopoulos, G; Kaukonen, K-M; Koulenti, D; Martin, C; Montravers, P; Rello, J; Rhodes, A; Starr, T; Wallis, S C; Lipman, J

2014-05-01

The aims of this study were to describe the variability in protein binding of teicoplanin in critically ill patients as well as the number of patients achieving therapeutic target concentrations. This report is part of the multinational pharmacokinetic DALI Study. Patients were sampled on a single day, with blood samples taken both at the midpoint and the end of the dosing interval. Total and unbound teicoplanin concentrations were assayed using validated chromatographic methods. The lower therapeutic range of teicoplanin was defined as total trough concentrations from 10 to 20 mg/L and the higher range as 10-30 mg/L. Thirteen critically ill patients were available for analysis. The following are the median (interquartile range) total and free concentrations (mg/L): midpoint, total 13.6 (11.2-26.0) and free 1.5 (0.7-2.5); trough, total 11.9 (10.2-22.7) and free 1.8 (0.6-2.6). The percentage free teicoplanin for the mid-dose and trough time points was 6.9% (4.5-15.6%) and 8.2% (5.5-16.4%), respectively. The correlation between total and free antibiotic concentrations was moderate for both the midpoint (ρ = 0.79, P = 0.0021) and trough (ρ = 0.63, P = 0.027). Only 42% and 58% of patients were in the lower and higher therapeutic ranges, respectively. In conclusion, use of standard dosing for teicoplanin leads to inappropriate concentrations in a high proportion of critically ill patients. Variability in teicoplanin protein binding is very high, placing significant doubt on the validity of total concentrations for therapeutic drug monitoring in critically ill patients. Copyright © 2014 Elsevier B.V. and the International Society of Chemotherapy. All rights reserved.

Cell-targeted platinum nanoparticles and nanoparticle clusters.

PubMed

Papst, Stefanie; Brimble, Margaret A; Evans, Clive W; Verdon, Daniel J; Feisst, Vaughan; Dunbar, P Rod; Tilley, Richard D; Williams, David E

2015-06-21

Herein, we report the facile preparation of cell-targeted platinum nanoparticles (PtNPs), through the design of peptides that, as a single molecule added in small concentration during the synthesis, control the size of PtNP clusters during their growth, stabilise the PtNPs in aqueous suspension and enable the functionalisation of the PtNPs with a versatile range of cell-targeting ligands. Water-soluble PtNPs targeted respectively at blood group antigens and at integrin receptors are demonstrated.

Active Stand-off Detection of Gas Leaks Using a Short Range Hard-target Backscatter Differential Optical Absorption System Based on a Quantum Cascade Laser Transmitter

NASA Astrophysics Data System (ADS)

Diaz, Adrian; Thomas, Benjamin; Castillo, Paulo; Gross, Barry; Moshary, Fred

2016-06-01

Fugitive gas emissions from agricultural or industrial plants and gas pipelines are an important environmental concern as they can contribute to the global increase of greenhouse gas concentration. Moreover, they are also a security and safety concern because of possible risk of fire/explosion or toxicity. This study presents gas concentration measurements using a quantum cascade laser open path system (QCLOPS). The system retrieves the pathaveraged concentration of N2O and CH4 by collecting the backscattered light from a scattering target. The gas concentration measurements have a high temporal resolution (68 ms) and are achieved at sufficient range (up to 40 m, ~ 130 feet) with a detection limit of 2.6 ppm CH4 and 0.4 ppm for N2O. Given these characteristics, this system is promising for mobile/multidirectional remote detection and evaluation of gas leaks. The instrument is monostatic with a tunable QCL emitting at ~ 7.7 μm wavelength range. The backscattered radiation is collected by a Newtonian telescope and focused on an infrared light detector. Puffs of N2O and CH4 are released along the optical path to simulate a gas leak. The measured absorption spectrum is obtained using the thermal intra-pulse frequency chirped DFB QCL and is analyzed to obtain path averaged gas concentrations.

Dosing of Milrinone in Preterm Neonates to Prevent Postligation Cardiac Syndrome: Simulation Study Suggests Need for Bolus Infusion.

PubMed

Hallik, Maarja; Tasa, Tõnis; Starkopf, Joel; Metsvaht, Tuuli

2017-01-01

Milrinone has been suggested as a possible first-line therapy for preterm neonates to prevent postligation cardiac syndrome (PLCS) through decreasing systemic vascular resistance and increasing cardiac contractility. The optimal dosing regimen, however, is not known. To model the dosing of milrinone in preterm infants for prevention of PLCS after surgical closure of patent ductus arteriosus (PDA). Milrinone time-concentration profiles were simulated for 1,000 subjects using the volume of distribution and clearance estimates based on one compartmental population pharmacokinetic model by Paradisis et al. [Arch Dis Child Fetal Neonatal Ed 2007;92:F204-F209]. Dose optimization was based on retrospectively collected demographic data from neonates undergoing PDA ligation in Estonian PICUs between 2012 and 2014 and existing pharmacodynamic data. The target plasma concentration was set at 150-200 ng/ml. The simulation study used demographic data from 31 neonates who underwent PDA ligation. The median postnatal age was 13 days (range: 3-29) and weight was 760 g (range: 500-2,351). With continuous infusion of milrinone 0.33 μg/kg/min, the proportion of subjects within the desired concentration range was 0% by 3 h, 36% by 6 h, and 61% by 8 h; 99% of subjects exceeded the range by 18 h. The maximum proportion of total simulated concentrations in the target range was attained with a bolus infusion of 0.73 μg/kg/min for 3 h followed by a 0.16-μg/kg/min maintenance infusion. Mathematical simulations suggest that in preterm neonates the plasma time-concentration profile of milrinone can be optimized with a slow loading dose followed by maintenance infusion. © 2016 S. Karger AG, Basel.

Epithelial cell biocompatibility of silica nanospheres for contrast-enhanced ultrasound molecular imaging

NASA Astrophysics Data System (ADS)

Chiriacò, Fernanda; Conversano, Francesco; Soloperto, Giulia; Casciaro, Ernesto; Ragusa, Andrea; Sbenaglia, Enzo Antonio; Dipaola, Lucia; Casciaro, Sergio

2013-07-01

Nanosized particles are receiving increasing attention as future contrast agents (CAs) for ultrasound (US) molecular imaging, possibly decorated on its surface with biological recognition agents for targeted delivery and deposition of therapeutics. In particular, silica nanospheres (SiNSs) have been demonstrated to be feasible in terms of contrast enhancement on conventional US systems. In this work, we evaluated the cytotoxicity of SiNSs on breast cancer (MCF-7) and HeLa (cervical cancer) cells employing NSs with sizes ranging from 160 to 330 nm and concentration range of 1.5-5 mg/mL. Cell viability was evaluated in terms of size, dose and time dependence, performing the MTT reduction assay with coated and uncoated SiNSs. Whereas uncoated SiNSs caused a variable significant decrease in cell viability on both cell lines mainly depending on size and exposure time, PEGylated SiNSs (SiNSs-PEG) exhibit a high level of biocompatibility. In fact, after 72-h incubation, viability of both cell types was above the cutoff value of 70 % at concentration up to 5 mg/mL. We also investigated the acoustical behavior of coated and uncoated SiNSs within conventional diagnostic US fields in order to determine a suitable configuration, in terms of particle size and concentration, for their employment as targetable CAs. Our results indicate that the employment of SiNSs with diameters around 240 nm assures the most effective contrast enhancement even at the lowest tested concentration, coupled with the possibility of targeting all tumor tissues, being the SiNSs still in a size range where reticuloendothelial system trapping effect is relatively low.

Overcoming non-specific binding to measure the active concentration and kinetics of serum anti-HLA antibodies by surface plasmon resonance.

PubMed

Visentin, Jonathan; Couzi, Lionel; Dromer, Claire; Neau-Cransac, Martine; Guidicelli, Gwendaline; Veniard, Vincent; Coniat, Karine Nubret-le; Merville, Pierre; Di Primo, Carmelo; Taupin, Jean-Luc

2018-06-07

Human leukocyte antigen (HLA) donor-specific antibodies are key serum biomarkers for assessing the outcome of transplanted patients. Measuring their active concentration, i.e. the fraction that really interacts with donor HLA, and their affinity could help deciphering their pathogenicity. Surface plasmon resonance (SPR) is recognized as the gold-standard for measuring binding kinetics but also active concentrations, without calibration curves. SPR-based biosensors often suffer from non-specific binding (NSB) occurring with the sensor chip surface and the immobilized targets, especially for complex media such as human serum. In this work we show that several serum treatments such as dialysis or IgG purification reduce NSB but insufficiently for SPR applications. We then demonstrate that the NSB contribution to the SPR signal can be eliminated to determine precisely and reliably the active concentration and the affinity of anti-HLA antibodies from patients' sera. This was achieved even at concentrations close to the limit of quantification of the method, in the 0.5-1 nM range. The robustness of the assay was demonstrated by using a wide range of artificially generated NSB and by varying the density of the targets captured onto the surface. The assay is of general interest and can be used with molecules generating strong NSB, as far as a non-cognate target structurally close to the target can be captured on the same flow cell, in a different binding cycle. Compared with current fluorescence-based methods that are semi-quantitative, we expect this SPR-based assay to help better understanding anti-HLA antibodies pathogenicity and improving organ recipients' management. Copyright © 2018 Elsevier B.V. All rights reserved.

On Chip Protein Pre-Concentration for Enhancing the Sensitivity of Porous Silicon Biosensors.

PubMed

Arshavsky-Graham, Sofia; Massad-Ivanir, Naama; Paratore, Federico; Scheper, Thomas; Bercovici, Moran; Segal, Ester

2017-12-22

Porous silicon (PSi) nanomaterials have been widely studied as label-free optical biosensors for protein detection. However, these biosensors' performance, specifically in terms of their sensitivity (which is typically in the micromolar range), is insufficient for many applications. Herein, we present a proof-of-concept application of the electrokinetic isotachophoresis (ITP) technique for real-time preconcentration of a target protein on a PSi biosensor. With ITP, a highly concentrated target zone is delivered to the sensing area, where the protein target is captured by immobilized aptamers. The detection of the binding events is conducted in a label-free manner by reflective interferometric Fourier transformation spectroscopy (RIFTS). Up to 1000-fold enhancement in local concentration of the protein target and the biosensor's sensitivity are achieved, with a measured limit of detection of 7.5 nM. Furthermore, the assay is successfully performed in complex media, such as bacteria lysate samples, while the selectivity of the biosensor is retained. The presented assay could be further utilized for other protein targets, and to promote the development of clinically useful PSi biosensors.

Occurrence of fibrates and their metabolites in source and drinking water in Shanghai and Zhejiang, China.

PubMed

Ido, Akiko; Hiromori, Youhei; Meng, Liping; Usuda, Haruki; Nagase, Hisamitsu; Yang, Min; Hu, Jianying; Nakanishi, Tsuyoshi

2017-04-12

Fibrates, which are widely used lipidaemic-modulating drugs, are emerging environmental pollutants. However, fibrate concentrations in the environment have not been thoroughly surveyed. Here, we determined concentrations of the most commonly used fibrates and their metabolites in source water and drinking water samples from ten drinking water treatment plants in Shanghai and Zhejiang, China, using solid-phase extraction and liquid chromatography-tandem mass spectrometry. All the target compounds were detected in at least some of the source water samples, at concentrations ranging from 0.04 ng/L (fenofibrate) to 1.53 ng/L (gemfibrozil). All the compounds except fenofibrate were also detected in at least some of the drinking water samples, at recoveries ranging from 35.5% to 91.7%, suggesting that these compounds are poorly removed by typical drinking water treatment processes. In a peroxisome proliferator-activated receptor α agonistic activity assay, the target compounds showed no significant activity at nanogram per litre concentrations; therefore, our results suggest that the fibrate concentrations in drinking water in Shanghai and Zhejiang, China do not significantly affect human health. However, because of the increasing westernization of the Chinese diet, fibrate use may increase, and thus monitoring fibrate concentrations in aquatic environments and drinking water in China will become increasingly important.

Occurrence of fibrates and their metabolites in source and drinking water in Shanghai and Zhejiang, China

PubMed Central

Ido, Akiko; Hiromori, Youhei; Meng, Liping; Usuda, Haruki; Nagase, Hisamitsu; Yang, Min; Hu, Jianying; Nakanishi, Tsuyoshi

2017-01-01

Fibrates, which are widely used lipidaemic-modulating drugs, are emerging environmental pollutants. However, fibrate concentrations in the environment have not been thoroughly surveyed. Here, we determined concentrations of the most commonly used fibrates and their metabolites in source water and drinking water samples from ten drinking water treatment plants in Shanghai and Zhejiang, China, using solid-phase extraction and liquid chromatography–tandem mass spectrometry. All the target compounds were detected in at least some of the source water samples, at concentrations ranging from 0.04 ng/L (fenofibrate) to 1.53 ng/L (gemfibrozil). All the compounds except fenofibrate were also detected in at least some of the drinking water samples, at recoveries ranging from 35.5% to 91.7%, suggesting that these compounds are poorly removed by typical drinking water treatment processes. In a peroxisome proliferator-activated receptor α agonistic activity assay, the target compounds showed no significant activity at nanogram per litre concentrations; therefore, our results suggest that the fibrate concentrations in drinking water in Shanghai and Zhejiang, China do not significantly affect human health. However, because of the increasing westernization of the Chinese diet, fibrate use may increase, and thus monitoring fibrate concentrations in aquatic environments and drinking water in China will become increasingly important. PMID:28401920

Occurrence of fibrates and their metabolites in source and drinking water in Shanghai and Zhejiang, China

NASA Astrophysics Data System (ADS)

Ido, Akiko; Hiromori, Youhei; Meng, Liping; Usuda, Haruki; Nagase, Hisamitsu; Yang, Min; Hu, Jianying; Nakanishi, Tsuyoshi

2017-04-01

Fibrates, which are widely used lipidaemic-modulating drugs, are emerging environmental pollutants. However, fibrate concentrations in the environment have not been thoroughly surveyed. Here, we determined concentrations of the most commonly used fibrates and their metabolites in source water and drinking water samples from ten drinking water treatment plants in Shanghai and Zhejiang, China, using solid-phase extraction and liquid chromatography-tandem mass spectrometry. All the target compounds were detected in at least some of the source water samples, at concentrations ranging from 0.04 ng/L (fenofibrate) to 1.53 ng/L (gemfibrozil). All the compounds except fenofibrate were also detected in at least some of the drinking water samples, at recoveries ranging from 35.5% to 91.7%, suggesting that these compounds are poorly removed by typical drinking water treatment processes. In a peroxisome proliferator-activated receptor α agonistic activity assay, the target compounds showed no significant activity at nanogram per litre concentrations; therefore, our results suggest that the fibrate concentrations in drinking water in Shanghai and Zhejiang, China do not significantly affect human health. However, because of the increasing westernization of the Chinese diet, fibrate use may increase, and thus monitoring fibrate concentrations in aquatic environments and drinking water in China will become increasingly important.

Toxicological relevance of pharmaceuticals in drinking water.

PubMed

Bruce, Gretchen M; Pleus, Richard C; Snyder, Shane A

2010-07-15

Interest in the public health significance of trace levels of pharmaceuticals in potable water is increasing, particularly with regard to the effects of long-term, low-dose exposures. To assess health risks and establish target concentrations for water treatment, human health risk-based screening levels for 15 pharmaceutically active ingredients and four metabolites were compared to concentrations detected at 19 drinking water treatment plants across the United States. Compounds were selected based on rate of use, likelihood of occurrence, and potential for toxicity. Screening levels were established based on animal toxicity data and adverse effects at therapeutic doses, focusing largely on reproductive and developmental toxicity and carcinogenicity. Calculated drinking water equivalent levels (DWELs) ranged from 0.49 microg/L (risperidone) to 20,000 microg/L (naproxen). None of the 10 detected compounds exceeded their DWEL. Ratios of DWELs to maximum detected concentrations ranged from 110 (phenytoin) to 6,000,000 (sulfamethoxazole). Based on this evaluation, adverse health effects from targeted pharmaceuticals occurring in U.S. drinking water are not expected.

AUC-Guided Vancomycin Dosing in Adolescent Patients With Suspected Sepsis.

PubMed

Lanke, Shankar; Yu, Tian; Rower, Joseph E; Balch, Alfred H; Korgenski, E Kent; Sherwin, Catherine M

2017-01-01

Vancomycin is a first-line treatment for β-lactam-resistant Gram-positive bacterial infections. Understanding the pharmacokinetic (PK) and pharmacodynamic (PD) characteristics of vancomycin in an adolescent population is of clinical importance in this often overlooked pediatric population. This retrospective study investigated vancomycin PK-PD in an adolescent cohort (12 to 18 years of age) of 463 patients (57% male, 81% white) admitted to the Intermountain Healthcare System between January 2006 and December 2013. Population PK modeling was performed in NONMEM 7.3. Vancomycin PK was well described with a 1-compartment model that identified both body weight (WT) and creatinine clearance (CRCL) as covariates significantly impacting vancomycin disposition. The model was then utilized to determine dosing strategies that achieved the targeted area under the 24-hour time curve vs minimum inhibitory concentration (AUC 0-24 /MIC) ratio of ≥400. Additionally, these data were correlated with minimum steady-state concentrations (C ss,min ) to find an acceptable target trough concentration range in adolescents. This analysis demonstrated that C ss,min ranging from 10 to 12.5 mg/L were highly predictive of achieving an AUC 0-24 /MIC ≥400 when the MIC was ≤1 mg/L. These results suggest that the target trough concentration for adolescents may be lower than that for adults. © 2016, The American College of Clinical Pharmacology.

Composition variations in pulsed-laser-deposited Y-Ba-Cu-O thin films as a function of deposition parameters

NASA Technical Reports Server (NTRS)

Foote, M. C.; Jones, B. B.; Hunt, B. D.; Barner, J. B.; Vasquez, R. P.; Bajuk, L. J.

1992-01-01

The composition of pulsed-ultraviolet-laser-deposited Y-Ba-Cu-O films was examined as a function of position across the substrate, laser fluence, laser spot size, substrate temperature, target conditioning, oxygen pressure and target-substrate distance. Laser fluence, laser spot size, and substrate temperature were found to have little effect on composition within the range investigated. Ablation from a fresh target surface results in films enriched in copper and barium, both of which decrease in concentration until a steady state condition is achieved. Oxygen pressure and target-substrate distance have a significant effect on film composition. In vacuum, copper and barium are slightly concentrated at the center of deposition. With the introduction of an oxygen background pressure, scattering results in copper and barium depletion in the deposition center, an effect which increases with increasing target-substrate distance. A balancing of these two effects results in stoichiometric deposition.

Accurate determination of reference materials and natural isolates by means of quantitative (1)h NMR spectroscopy.

PubMed

Frank, Oliver; Kreissl, Johanna Karoline; Daschner, Andreas; Hofmann, Thomas

2014-03-26

A fast and precise proton nuclear magnetic resonance (qHNMR) method for the quantitative determination of low molecular weight target molecules in reference materials and natural isolates has been validated using ERETIC 2 (Electronic REference To access In vivo Concentrations) based on the PULCON (PULse length based CONcentration determination) methodology and compared to the gravimetric results. Using an Avance III NMR spectrometer (400 MHz) equipped with a broad band observe (BBO) probe, the qHNMR method was validated by determining its linearity, range, precision, and accuracy as well as robustness and limit of quantitation. The linearity of the method was assessed by measuring samples of l-tyrosine, caffeine, or benzoic acid in a concentration range between 0.3 and 16.5 mmol/L (r(2) ≥ 0.99), whereas the interday and intraday precisions were found to be ≤2%. The recovery of a range of reference compounds was ≥98.5%, thus demonstrating the qHNMR method as a precise tool for the rapid quantitation (~15 min) of food-related target compounds in reference materials and natural isolates such as nucleotides, polyphenols, or cyclic peptides.

Using Cl/Br ratios and other indicators to assess potential impacts on groundwater quality from septic systems: A review and examples from principal aquifers in the United States

USGS Publications Warehouse

Katz, B.G.; Eberts, S.M.; Kauffman, L.J.

2011-01-01

A detailed review was made of chemical indicators used to identify impacts from septic tanks on groundwater quality. Potential impacts from septic tank leachate on groundwater quality were assessed using the mass ratio of chloride-bromide (Cl/Br), concentrations of selected chemical constituents, and ancillary information (land use, census data, well depth, soil characteristics) for wells in principal aquifers of the United States. Chemical data were evaluated from 1848 domestic wells in 19 aquifers, 121 public-supply wells in 6 aquifers, and associated monitoring wells in four aquifers and their overlying hydrogeologic units. Based on previously reported Cl/Br ratios, statistical comparisons between targeted wells (where Cl/Br ratios range from 400 to 1100 and Cl concentrations range from 20 to 100 mg/L) and non-targeted wells indicated that shallow targeted monitoring and domestic wells (0.5. mg/L) shallow groundwater from target domestic wells, relative to non-target wells (1.5. mg/L), corresponded to significantly higher potassium, boron, chloride, dissolved organic carbon, and sulfate concentrations, which may also indicate the influence of septic-tank effluent. Impacts on groundwater quality from septic systems were most evident for the Eastern Glacial Deposits aquifer and the Northern High Plains aquifer that were associated with the number of housing units using septic tanks, high permeability of overlying sediments, mostly oxic conditions, and shallow wells. Overall, little or no influence from septic systems were found for water samples from the deeper public-supply wells.The Cl/Br ratio is a useful first-level screening tool for assessing possible septic tank influence in water from shallow wells (<20 m) with the range of 400-1100. The use of this ratio would be enhanced with information on other chloride sources, temporal variability of chloride and bromide concentrations in shallow groundwater, knowledge of septic-system age and maintenance, and the use of multiple tracers (combination of additional chemical and microbiological indicators). ?? 2010.

A Unique Photon Bombardment System for Space Applications

NASA Technical Reports Server (NTRS)

Klein, E. J.

1993-01-01

The innovative Electromagnetic Radiation Collection and Concentration System (EMRCCS) described is the foundation for the development of a multiplicity of space and terrestrial system formats. The system capability allows its use in the visual, infrared, and ultraviolet ranges of the spectrum for EM collection, concentration, source/receptor tracking, and targeting. The nonimaging modular optical system uses a physically static position aperture for EM radiation collection. Folded optics provide the concentration of the radiation and source autotracking. The collected and concentrated electromagnetic radiation is utilized in many applications, e.g., solar spectrum in thermal and associative photon bombardment applications for hazardous waste management, water purification, metal hardening, hydrogen generation, photovoltaics, etc., in both space and terrestrial segment utilization. Additionally, at the high end of the concentration capability range, i.e., 60,000+, a solar-pulsed laser system is possible.

Effects of extraneous odors on canine detection

NASA Astrophysics Data System (ADS)

Waggoner, L. Paul; Jones, Meredith H.; Williams, Marc; Johnston, J. M.; Edge, Cindy C.; Petrousky, James A.

1998-12-01

Dogs are often required to detect target substances under challenging conditions. One of these challenges is to detect contraband in the presence of extraneous odors, whether they are part of the ambient environment or placed there for the purpose of evading detection. This paper presents the results of two studies evaluating the ability of dogs to detect target substances in the presence of varying concentrations of extraneous odors. The studies were conducted under behavioral laboratory conditions, providing good control over vapor sources and a clear basis for evaluation of detection responses. Dogs were trained to sample an air stream consisting of the extraneous odor only or the extraneous odor plus the target odor and then press the appropriate lever to earn food. The results are described in terns of the ability of dogs to detect target odors in the presence of a wide range of concentrations of the extraneous odors.

Genesis Silicon Carbide Concentrator Target 60003 Preliminary Ellipsometry Mapping Results

NASA Technical Reports Server (NTRS)

Calaway, M. J.; Rodriquez, M. C.; Stansbery, E. K.

2007-01-01

The Genesis concentrator was custom designed to focus solar wind ions primarily for terrestrial isotopic analysis of O-17/O-16 and O-18/O-16 to +/-1%, N-15/N-14 to +/-1%, and secondarily to conduct elemental and isotopic analysis of Li, Be, and B. The circular 6.2 cm diameter concentrator target holder was comprised of four quadrants of highly pure semiconductor materials that included one amorphous diamond-like carbon, one C-13 diamond, and two silicon carbide (SiC). The amorphous diamond-like carbon quadrant was fractured upon impact at Utah Test and Training Range (UTTR), but the remaining three quadrants survived fully intact and all four quadrants hold an important collection of solar wind. The quadrants were removed from the target holder at NASA Johnso n Space Center Genesis Curation Laboratory in April 2005, and have been housed in stainless steel containers under continual nitrogen purge since time of disintegration. In preparation for allocation of a silicon carbide target for oxygen isotope analyses at UCLA, the two SiC targets were photographed for preliminary inspection of macro particle contamination from the hard non-nominal landing as well as characterized by spectroscopic ellipsometry to evaluate thin film contamination. This report is focused on Genesis SiC target sample number 60003.

A rapid method for detection of genetically modified organisms based on magnetic separation and surface-enhanced Raman scattering.

PubMed

Guven, Burcu; Boyacı, İsmail Hakkı; Tamer, Ugur; Çalık, Pınar

2012-01-07

In this study, a new method combining magnetic separation (MS) and surface-enhanced Raman scattering (SERS) was developed to detect genetically modified organisms (GMOs). An oligonucleotide probe which is specific for 35 S DNA target was immobilized onto gold coated magnetic nanospheres to form oligonucleotide-coated nanoparticles. A self assembled monolayer was formed on gold nanorods using 5,5'-dithiobis (2-nitrobenzoic acid) (DTNB) and the second probe of the 35 S DNA target was immobilized on the activated nanorod surfaces. Probes on the nanoparticles were hybridized with the target oligonucleotide. Optimization parameters for hybridization were investigated by high performance liquid chromatography. Optimum hybridization parameters were determined as: 4 μM probe concentration, 20 min immobilization time, 30 min hybridization time, 55 °C hybridization temperature, 750 mM buffer salt concentration and pH: 7.4. Quantification of the target concentration was performed via SERS spectra of DTNB on the nanorods. The correlation between the target concentration and the SERS signal was found to be linear within the range of 25-100 nM. The analyses were performed with only one hybridization step in 40 min. Real sample analysis was conducted using Bt-176 maize sample. The results showed that the developed MS-SERS assay is capable of detecting GMOs in a rapid and selective manner. This journal is © The Royal Society of Chemistry 2012

A flow-proteometric platform for analyzing protein concentration (FAP): Proof of concept for quantification of PD-L1 protein in cells and tissues.

PubMed

Chou, Chao-Kai; Huang, Po-Jung; Tsou, Pei-Hsiang; Wei, Yongkun; Lee, Heng-Huan; Wang, Ying-Nai; Liu, Yen-Liang; Shi, Colin; Yeh, Hsin-Chih; Kameoka, Jun; Hung, Mien-Chie

2018-05-29

Protein expression level is critically related to the cell physiological function. However, current methodologies such as Western blot (WB) and Immunohistochemistry (IHC) in analyzing the protein level are rather semi-quantitative and without the information of actual protein concentration. We have developed a microfluidic technique termed a "flow-proteometric platform for analyzing protein concentration (FAP)" that can measure the concentration of a target protein in cells or tissues without the requirement of a calibration standard, e.g., the purified target molecules. To validate our method, we tested a number of control samples with known target protein concentrations and showed that the FAP measurement resulted in concentrations that well matched the actual concentrations in the control samples (coefficient of determination [R 2 ], 0.998), demonstrating a dynamic range of concentrations from 0.13 to 130 pM of a detection for 2 min. We successfully determined a biomarker protein (for predicting the treatment response of cancer immune check-point therapy) PD-L1 concentration in cancer cell lines (HeLa PD-L1 and MDA-MB-231) and breast cancer patient tumor tissues without any prior process of sample purification and standard line construction. Therefore, FAP is a simple, faster, and reliable method to measure the protein concentration in cells and tissues, which can support the conventional methods such as WB and IHC to determine the actual protein level. Copyright © 2018 Elsevier B.V. All rights reserved.

Active standoff detection of CH4 and N2O leaks using hard-target backscattered light using an open-path quantum cascade laser sensor

NASA Astrophysics Data System (ADS)

Diaz, Adrian; Thomas, Benjamin; Castillo, Paulo; Gross, Barry; Moshary, Fred

2016-05-01

Fugitive gas emissions from agricultural or industrial plants and gas pipelines are an important environmental concern as they contribute to the global increase of greenhouse gas concentrations. Moreover, they are also a security and safety concern because of possible risk of fire/explosion or toxicity. This study presents standoff detection of CH4 and N2O leaks using a quantum cascade laser open-path system that retrieves path-averaged concentrations by collecting the backscattered light from a remote hard target. It is a true standoff system and differs from other open-path systems that are deployed as point samplers or long-path transmission systems that use retroreflectors. The measured absorption spectra are obtained using a thermal intra-pulse frequency chirped DFB quantum cascade laser at ~7.7 µm wavelength range with ~200 ns pulse width. Making fast time resolved observations, the system simultaneously realizes high spectral resolution and range to the target, resulting in path-averaged concentration retrieval. The system performs measurements at high speed ~15 Hz and sufficient range (up to 45 m, ~148 feet) achieving an uncertainty of 3.1 % and normalized sensitivity of 3.3 ppm m Hz-1/2 for N2O and 9.3 % and normalized sensitivity of 30 ppm m Hz-1/2 for CH4 with a 0.31 mW average power QCL. Given these characteristics, this system is promising for mobile or multidirectional search and remote detection of gas leaks.

Dosing algorithm to target a predefined AUC in patients with primary central nervous system lymphoma receiving high dose methotrexate.

PubMed

Joerger, Markus; Ferreri, Andrés J M; Krähenbühl, Stephan; Schellens, Jan H M; Cerny, Thomas; Zucca, Emanuele; Huitema, Alwin D R

2012-02-01

There is no consensus regarding optimal dosing of high dose methotrexate (HDMTX) in patients with primary CNS lymphoma. Our aim was to develop a convenient dosing algorithm to target AUC(MTX) in the range between 1000 and 1100 µmol l(-1) h. A population covariate model from a pooled dataset of 131 patients receiving HDMTX was used to simulate concentration-time curves of 10,000 patients and test the efficacy of a dosing algorithm based on 24 h MTX plasma concentrations to target the prespecified AUC(MTX) . These data simulations included interindividual, interoccasion and residual unidentified variability. Patients received a total of four simulated cycles of HDMTX and adjusted MTX dosages were given for cycles two to four. The dosing algorithm proposes MTX dose adaptations ranging from +75% in patients with MTX C(24) < 0.5 µmol l(-1) up to -35% in patients with MTX C(24) > 12 µmol l(-1). The proposed dosing algorithm resulted in a marked improvement of the proportion of patients within the AUC(MTX) target between 1000 and 1100 µmol l(-1) h (11% with standard MTX dose, 35% with the adjusted dose) and a marked reduction of the interindividual variability of MTX exposure. A simple and practical dosing algorithm for HDMTX has been developed based on MTX 24 h plasma concentrations, and its potential efficacy in improving the proportion of patients within a prespecified target AUC(MTX) and reducing the interindividual variability of MTX exposure has been shown by data simulations. The clinical benefit of this dosing algorithm should be assessed in patients with primary central nervous system lymphoma (PCNSL). © 2011 The Authors. British Journal of Clinical Pharmacology © 2011 The British Pharmacological Society.

Determination of polyfluoroalkyl phosphoric acid diesters, perfluoroalkyl phosphonic acids, perfluoroalkyl phosphinic acids, perfluoroalkyl carboxylic acids, and perfluoroalkane sulfonic acids in lake trout from the Great Lakes region.

PubMed

Guo, Rui; Reiner, Eric J; Bhavsar, Satyendra P; Helm, Paul A; Mabury, Scott A; Braekevelt, Eric; Tittlemier, Sheryl A

2012-11-01

A comprehensive method to extract perfluoroalkyl carboxylic acids, perfluoroalkane sulfonic acids, perfluoroalkyl phosphonic acids, perfluoroalkyl phosphinic acids, and polyfluoroalkyl phosphoric acid diesters simultaneously from fish samples has been developed. The recoveries of target compounds ranged from 78 % to 121 %. The new method was used to analyze lake trout (Salvelinus namaycush) from the Great Lakes region. The results showed that the total perfluoroalkane sulfonate concentrations ranged from 0.1 to 145 ng/g (wet weight) with perfluorooctane sulfonate (PFOS) as the dominant contaminant. Concentrations in fish between lakes were in the order of Lakes Ontario ≈ Erie > Huron > Superior ≈ Nipigon. The total perfluoroalkyl carboxylic acid concentrations ranged from 0.2 to 18.2 ng/g wet weight. The aggregate mean perfluorooctanoic acid (PFOA) concentration in fish across all lakes was 0.045 ± 0.023 ng/g. Mean concentrations of PFOA were not significantly different (p > 0.1) among the five lakes. Perfluoroalkyl phosphinic acids were detected in lake trout from Lake Ontario, Lake Erie, and Lake Huron with concentration ranging from non-detect (ND) to 0.032 ng/g. Polyfluoroalkyl phosphoric acid diesters were detected only in lake trout from Lake Huron, at levels similar to perfluorooctanoic acid.

Investigation of high pressure steaming (HPS) as a thermal treatment for lipid extraction from Chlorella vulgaris.

PubMed

Aguirre, Ana-Maria; Bassi, Amarjeet

2014-07-01

Biofuels from algae are considered a technically viable energy source that overcomes several of the problems present in previous generations of biofuels. In this research high pressure steaming (HPS) was studied as a hydrothermal pre-treatment for extraction of lipids from Chlorella vulgaris, and analysis by response surface methodology allowed finding operational points in terms of target temperature and algae concentration for high lipid and glucose yields. Within the range covered by these experiments the best conditions for high bio-crude yield are temperatures higher than 174°C and low biomass concentrations (<5 g/L). For high glucose yield there are two suitable operational ranges, either low temperatures (<105°C) and low biomass concentrations (<4 g/L); or low temperatures (<105°C) and high biomass concentrations (<110 g/L). High pressure steaming is a good hydrothermal treatment for lipid recovery and does not significantly change the fatty acids profile for the range of temperatures studied. Copyright © 2014 Elsevier Ltd. All rights reserved.

A new ELISA for the quantification of equine procalcitonin in plasma as potential inflammation biomarker in horses.

PubMed

Rieger, Martin; Kochleus, Christian; Teschner, Dana; Rascher, Daniela; Barton, Ann Kristin; Geerlof, Arie; Kremmer, Elisabeth; Schmid, Michael; Hartmann, Anton; Gehlen, Heidrun

2014-09-01

In human medicine, procalcitonin (PCT) is a very common and well-established biomarker for sepsis. Even though sepsis is also a leading cause of death in foals and adult horses, up to now, no data about the role of equine PCT in septic horses has been available. Based on monoclonal antibodies targeted against human PCT, we report here the development of a sandwich ELISA for the quantification of equine PCT in equine plasma samples. The ELISA was characterized for intra- and interassay variance and a working range from 25 to 1,000 ng mL(-1) was defined as within this range; both intra- and interassay variances were below 15 %. The target recovery ranged between 73 and 106 %. The ELISA was used to determine the equine PCT concentration in 24 healthy and 5 septic horses to show the potential for clinical evaluation of equine PCT. Significantly different (P = 0.0006) mean equine PCT concentrations were found for the healthy control group and the sepsis group (47 and 8,450 ng mL(-1)).

Characterization of volume holographic optical elements recorded in Bayfol HX photopolymer for solar photovoltaic applications.

PubMed

Marín-Sáez, Julia; Atencia, Jesús; Chemisana, Daniel; Collados, María-Victoria

2016-03-21

Volume Holographic Optical Elements (HOEs) present interesting characteristics for photovoltaic applications as they can select spectrum for concentrating the target bandwidth and avoiding non-desired wavelengths, which can cause the decrease of the performance on the cell, for instance by overheating it. Volume HOEs have been recorded on Bayfol HX photopolymer to test the suitability of this material for solar concentrating photovoltaic systems. The HOEs were recorded at 532 nm and provided a dynamic range, reaching close to 100% efficiency at 800 nm. The diffracted spectrum had a FWHM of 230 nm when illuminating at Bragg angle. These characteristics prove HOEs recorded on Bayfol HX photopolymer are suitable for concentrating solar light onto photovoltaic cells sensitive to that wavelength range.

Diagnostic nanoparticle targeting of the EGF-receptor in complex biological conditions using single-domain antibodies.

PubMed

Zarschler, K; Prapainop, K; Mahon, E; Rocks, L; Bramini, M; Kelly, P M; Stephan, H; Dawson, K A

2014-06-07

For effective localization of functionalized nanoparticles at diseased tissues such as solid tumours or metastases through biorecognition, appropriate targeting vectors directed against selected tumour biomarkers are a key prerequisite. The diversity of such vector molecules ranges from proteins, including antibodies and fragments thereof, through aptamers and glycans to short peptides and small molecules. Here, we analyse the specific nanoparticle targeting capabilities of two previously suggested peptides (D4 and GE11) and a small camelid single-domain antibody (sdAb), representing potential recognition agents for the epidermal growth factor receptor (EGFR). We investigate specificity by way of receptor RNA silencing techniques and look at increasing complexity in vitro by introducing increasing concentrations of human or bovine serum. Peptides D4 and GE11 proved problematic to employ and conjugation resulted in non-receptor specific uptake into cells. Our results show that sdAb-functionalized particles can effectively target the EGFR, even in more complex bovine and human serum conditions where targeting specificity is largely conserved for increasing serum concentration. In human serum however, an inhibition of overall nanoparticle uptake is observed with increasing protein concentration. For highly affine targeting ligands such as sdAbs, targeting a receptor such as EGFR with low serum competitor abundance, receptor recognition function can still be partially realised in complex conditions. Here, we stress the value of evaluating the targeting efficiency of nanoparticle constructs in realistic biological milieu, prior to more extensive in vivo studies.

Cucurbitacin E as a new inhibitor of cofilin phosphorylation in human leukemia U937 cells.

PubMed

Nakashima, Souichi; Matsuda, Hisashi; Kurume, Ai; Oda, Yoshimi; Nakamura, Seikou; Yamashita, Masayuki; Yoshikawa, Masayuki

2010-05-01

Cucurbitane-type triterpenes, cucurbitacins B and E, were reported to exhibit cytotoxic effects in several cell lines mediated by JAK/STAT3 signaling. However, neither compound inhibited phosphorylation of STAT3 in human leukemia (U937) cells at low concentrations. We therefore synthesized a biotin-linked cucurbitacin E to isolate target proteins based on affinity for the molecule. As a result, cofilin, which regulates the depolymerization of actin, was isolated and suggested to be a target. Cucurbitacins E and I inhibited the phosphorylation of cofilin in a concentration-dependent manner, and their effective concentrations having the same range as the concentrations at which they had cytotoxic effects in U937 cells. In addition, the fibrous-/globular-actin ratio was decreased after treatment with cucurbitacin E in HT1080 cells. These findings suggested that the inhibition of cofilin's phosphorylation increased the severing activity of cofilin, and then the depolymerization of actin was enhanced after treatment with cucurbitacin E at lower concentrations. 2010 Elsevier Ltd. All rights reserved.

Software for Dosage Individualization of Voriconazole for Immunocompromised Patients

PubMed Central

VanGuilder, Michael; Donnelly, J. Peter; Blijlevens, Nicole M. A.; Brüggemann, Roger J. M.; Jelliffe, Roger W.; Neely, Michael N.

2013-01-01

The efficacy of voriconazole is potentially compromised by considerable pharmacokinetic variability. There are increasing insights into voriconazole concentrations that are safe and effective for treatment of invasive fungal infections. Therapeutic drug monitoring is increasingly advocated. Software to aid in the individualization of dosing would be an extremely useful clinical tool. We developed software to enable the individualization of voriconazole dosing to attain predefined serum concentration targets. The process of individualized voriconazole therapy was based on concepts of Bayesian stochastic adaptive control. Multiple-model dosage design with feedback control was used to calculate dosages that achieved desired concentration targets with maximum precision. The performance of the software program was assessed using the data from 10 recipients of an allogeneic hematopoietic stem cell transplant (HSCT) receiving intravenous (i.v.) voriconazole. The program was able to model the plasma concentrations with a high level of precision, despite the wide range of concentration trajectories and interindividual pharmacokinetic variability. The voriconazole concentrations predicted after the last dosages were largely concordant with those actually measured. Simulations provided an illustration of the way in which the software can be used to adjust dosages of patients falling outside desired concentration targets. This software appears to be an extremely useful tool to further optimize voriconazole therapy and aid in therapeutic drug monitoring. Further prospective studies are now required to define the utility of the controller in daily clinical practice. PMID:23380734

Rapid detection of multiple class pharmaceuticals in both municipal wastewater and sludge with ultra high performance liquid chromatography tandem mass spectrometry.

PubMed

Yuan, Xiangjuan; Qiang, Zhimin; Ben, Weiwei; Zhu, Bing; Liu, Junxin

2014-09-01

This work described the development, optimization and validation of an analytical method for rapid detection of multiple-class pharmaceuticals in both municipal wastewater and sludge samples based on ultrasonic solvent extraction, solid-phase extraction, and ultra high performance liquid chromatography-tandem mass spectrometry quantification. The results indicated that the developed method could effectively extract all the target pharmaceuticals (25) in a single process and analyze them within 24min. The recoveries of the target pharmaceuticals were in the range of 69%-131% for wastewater and 54%-130% for sludge at different spiked concentration levels. The method quantification limits in wastewater and sludge ranged from 0.02 to 0.73ng/L and from 0.02 to 1.00μg/kg, respectively. Subsequently, this method was validated and applied for residual pharmaceutical analysis in a wastewater treatment plant located in Beijing, China. All the target pharmaceuticals were detected in the influent samples with concentrations varying from 0.09ng/L (tiamulin) to 15.24μg/L (caffeine); meanwhile, up to 23 pharmaceuticals were detected in sludge samples with concentrations varying from 60ng/kg (sulfamethizole) to 8.55mg/kg (ofloxacin). The developed method demonstrated its selectivity, sensitivity, and reliability for detecting multiple-class pharmaceuticals in complex matrices such as municipal wastewater and sludge. Copyright © 2014. Published by Elsevier B.V.

Expanded Target-Chemical Analysis Reveals Extensive Mixed-Organic-Contaminant Exposure in U.S. Streams.

PubMed

Bradley, Paul M; Journey, Celeste A; Romanok, Kristin M; Barber, Larry B; Buxton, Herbert T; Foreman, William T; Furlong, Edward T; Glassmeyer, Susan T; Hladik, Michelle L; Iwanowicz, Luke R; Jones, Daniel K; Kolpin, Dana W; Kuivila, Kathryn M; Loftin, Keith A; Mills, Marc A; Meyer, Michael T; Orlando, James L; Reilly, Timothy J; Smalling, Kelly L; Villeneuve, Daniel L

2017-05-02

Surface water from 38 streams nationwide was assessed using 14 target-organic methods (719 compounds). Designed-bioactive anthropogenic contaminants (biocides, pharmaceuticals) comprised 57% of 406 organics detected at least once. The 10 most-frequently detected anthropogenic-organics included eight pesticides (desulfinylfipronil, AMPA, chlorpyrifos, dieldrin, metolachlor, atrazine, CIAT, glyphosate) and two pharmaceuticals (caffeine, metformin) with detection frequencies ranging 66-84% of all sites. Detected contaminant concentrations varied from less than 1 ng L -1 to greater than 10 μg L -1 , with 77 and 278 having median detected concentrations greater than 100 ng L -1 and 10 ng L -1 , respectively. Cumulative detections and concentrations ranged 4-161 compounds (median 70) and 8.5-102 847 ng L -1 , respectively, and correlated significantly with wastewater discharge, watershed development, and toxic release inventory metrics. Log 10 concentrations of widely monitored HHCB, triclosan, and carbamazepine explained 71-82% of the variability in the total number of compounds detected (linear regression; p-values: < 0.001-0.012), providing a statistical inference tool for unmonitored contaminants. Due to multiple modes of action, high bioactivity, biorecalcitrance, and direct environment application (pesticides), designed-bioactive organics (median 41 per site at μg L -1 cumulative concentrations) in developed watersheds present aquatic health concerns, given their acknowledged potential for sublethal effects to sensitive species and lifecycle stages at low ng L -1 .

Establishing human heart chromium, cobalt and vanadium concentrations by inductively coupled plasma mass spectrometry.

PubMed

Day, Patrick L; Eckdahl, Steven J; Maleszewski, Joseph J; Wright, Thomas C; Murray, David L

2017-05-01

Chromium, cobalt, and vanadium are used in metallic joint prosthesis. Case studies have associated elevated heart tissue cobalt concentrations with myocardial injury. To document the long term heart metal ion concentrations, a validated inductively coupled plasma mass spectroscopy (ICP-MS) method was needed. The method utilized a closed-vessel microwave digestion system to digest the samples. An ICP-MS method utilizing Universal Cell Technology was used to determine our target analyte concentrations. Accuracy was verified using reference materials. Precision, sensitivity, recovery and linearity studies were performed. This method was used to establish a reference range for a non-implant containing cohort of 80 autopsy human heart tissues RESULTS: This method demonstrated an analytic measurement range of 0.5-100ng/mL for each element. Accuracy was within ±10% of target value for each element. Within-run precision for each element was below 20% CV. The chromium, vanadium and cobalt concentrations (mean±SD) were 0.1523±0.2157μg/g, 0.0094±0.0211μg/g and 0.1039±0.1305μg/g respectively in 80 non-implant containing human heart tissue samples. This method provides acceptable recovery of the chromium, cobalt and vanadium in heart tissue; allowing assessment of the effects of metallic joint prosthesis on myocardial health. Copyright © 2017 Elsevier GmbH. All rights reserved.

Expanded target-chemical analysis reveals extensive mixed-organic-contaminant exposure in USA streams

USGS Publications Warehouse

Bradley, Paul M.; Journey, Celeste A.; Romanok, Kristin; Barber, Larry B.; Buxton, Herbert T.; Foreman, William T.; Furlong, Edward T.; Glassmeyer, Susan T.; Hladik, Michelle L.; Iwanowicz, Luke R.; Jones, Daniel K.; Kolpin, Dana W.; Kuivila, Kathryn M.; Loftin, Keith A.; Mills, Marc A.; Meyer, Michael T.; Orlando, James L.; Reilly, Timothy J.; Smalling, Kelly L.; Villeneuve, Daniel L.

2017-01-01

Surface water from 38 streams nationwide was assessed using 14 target-organic methods (719 compounds). Designed-bioactive anthropogenic contaminants (biocides, pharmaceuticals) comprised 57% of 406 organics detected at least once. The 10 most-frequently detected anthropogenic-organics included eight pesticides (desulfinylfipronil, AMPA, chlorpyrifos, dieldrin, metolachlor, atrazine, CIAT, glyphosate) and two pharmaceuticals (caffeine, metformin) with detection frequencies ranging 66–84% of all sites. Detected contaminant concentrations varied from less than 1 ng L–1 to greater than 10 μg L–1, with 77 and 278 having median detected concentrations greater than 100 ng L–1 and 10 ng L–1, respectively. Cumulative detections and concentrations ranged 4–161 compounds (median 70) and 8.5–102 847 ng L–1, respectively, and correlated significantly with wastewater discharge, watershed development, and toxic release inventory metrics. Log10 concentrations of widely monitored HHCB, triclosan, and carbamazepine explained 71–82% of the variability in the total number of compounds detected (linear regression; p-values: < 0.001–0.012), providing a statistical inference tool for unmonitored contaminants. Due to multiple modes of action, high bioactivity, biorecalcitrance, and direct environment application (pesticides), designed-bioactive organics (median 41 per site at μg L–1 cumulative concentrations) in developed watersheds present aquatic health concerns, given their acknowledged potential for sublethal effects to sensitive species and lifecycle stages at low ng L–1.

Differentiating high priority pathway-based toxicity from non ...

EPA Pesticide Factsheets

The ToxCast chemical screening approach enables the rapid assessment of large numbers of chemicals for biological effects, primarily at the molecular level. Adverse outcome pathways (AOPs) offer a means to link biomolecular effects with potential adverse outcomes at the level of the individual or population, thus enhancing the utility of the ToxCast effort for hazard assessment. Thus, efforts are underway to develop AOPs relevant to the pathway perturbations detected in ToxCast assays. However, activity (?‘hits’) determined for chemical-assay pairs may reflect target-specific activity relevant to a molecular initiating event of an AOP, or more generalized cell stress and cytotoxicity-mediated effects. Previous work identified a ?‘cytotoxic burst’ phenomenon wherein large numbers of assays begin to respond at or near concentrations that elicit cytotoxicity. The concentration range at which the “burst” occurs is definable, statistically. Consequently, in order to focus AOP development on the ToxCast assay targetswhich are most sensitive and relevant to pathway-specific effects, we conducted a meta-analysis to identify which assays were frequently responding at concentrations well below the cytotoxic burst. Assays were ranked by the fraction of chemical hits below the burst concentration range compared to the number of chemicals tested, resulting in a preliminary list of potentially important, target-specific assays. After eliminating cytotoxicity a

Application of High-Throughput In Vitro Assays for Risk-Based ...

EPA Pesticide Factsheets

Multiple drivers shape the types of human-health assessments performed on chemicals by U.S. EPA resulting in chemical assessments are “fit-for-purpose” ranging from prioritization for further testing to full risk assessments. Layered on top of the diverse assessment needs are the resource intensive nature of traditional toxicological studies used to test chemicals and the lack of toxicity information on many chemicals. To address these challenges, the Agency initiated the ToxCast program to screen thousands of chemicals across hundreds of high-throughput screening assays in concentrations-response format. One of the findings of the project has been that the majority of chemicals interact with multiple biological targets within a narrow concentration range and the extent of interactions increases rapidly near the concentration causing cytotoxicity. This means that application of high-throughput in vitro assays to chemical assessments will need to identify both the relative selectivity at chemicals interact with biological targets and the concentration at which these interactions perturb signaling pathways. The integrated analyses will be used to both define a point-of-departure for comparison with human exposure estimates and identify which chemicals may benefit from further studies in a mode-of-action or adverse outcome pathway framework. The application of new technologies in a risk-based, tiered manner provides flexibility in matching throughput and cos

20150325 - Application of High-Throughput In Vitro Assays for ...

EPA Pesticide Factsheets

Multiple drivers shape the types of human-health assessments performed on chemicals by U.S. EPA resulting in chemical assessments are “fit-for-purpose” ranging from prioritization for further testing to full risk assessments. Layered on top of the diverse assessment needs are the resource intensive nature of traditional toxicological studies used to test chemicals and the lack of toxicity information on many chemicals. To address these challenges, the Agency initiated the ToxCast program to screen thousands of chemicals across hundreds of high-throughput screening assays in concentrations-response format. One of the findings of the project has been that the majority of chemicals interact with multiple biological targets within a narrow concentration range and the extent of interactions increases rapidly near the concentration causing cytotoxicity. This means that application of high-throughput in vitro assays to chemical assessments will need to identify both the relative selectivity at chemicals interact with biological targets and the concentration at which these interactions perturb signaling pathways. The integrated analyses will be used to both define a point-of-departure for comparison with human exposure estimates and identify which chemicals may benefit from further studies in a mode-of-action or adverse outcome pathway framework. The application of new technologies in a risk-based, tiered manner provides flexibility in matching throughput and cos

Study of the adsorption of sodium dodecyl sulfate (SDS) at the air/water interface: targeting the sulfate headgroup using vibrational sum frequency spectroscopy.

PubMed

Johnson, C Magnus; Tyrode, Eric

2005-07-07

The surface sensitive technique vibrational sum frequency spectroscopy (VSFS), has been used to study the adsorption behaviour of SDS to the liquid/vapour interface of aqueous solutions, specifically targeting the sulfate headgroup stretches. In the spectral region extending from 980 to 1850 cm(-1), only the vibrations due to the SO(3) group were detectable. The fitted amplitudes for the symmetric SO(3) stretch observed at 1070 cm(-1) for the polarization combinations ssp and ppp, were seen to follow the adsorption isotherm calculated from surface tension measurements. The orientation of the sulfate headgroup in the concentration range spanning from 1.0 mM to above the critical micellar concentration (c.m.c.) was observed to remain constant within experimental error, with the pseudo-C(3) axis close to the surface normal. Furthermore, the effect of increasing amounts of sodium chloride at SDS concentrations above c.m.c. was also studied, showing an increase of approximately 12% in the fitted amplitude for the symmetric SO(3) stretch when increasing the ionic strength from 0 to 300 mM NaCl. Interestingly, the orientation of the SDS headgroup was also observed to remain constant within this concentration range and identical to the case without NaCl.

[Effect of propofol at different effect-site concentrations on approximate entropy of transient evoked otoacoustic emission signals in adults].

PubMed

Zhang, Xin-jian; Gu, Miao-ning; Xiao, Jin-fang

2009-01-01

To study the effect of propofol at different effect-site concentrations on approximate entropy (ApEn) of transient evoked otoacoustic emission (TEOAE) signals in adults and investigate the possibility of using ApEn for monitoring anesthesia depth. Fifteen ASA class I or II patients (aged 18-49 years with normal hearing) undergoing elective surgery under general anesthesia were enrolled in this study. Anesthesia was maintained with target-controlled infusion of propofol. With the effect-site concentrations of 1, 2, 3 and 4 microg/ml, TEOAE signals were monitored and recorded before and after anesthesia. ApEn of TEOAE in 4 frequency ranges (0-2, 1-3, 2.5-4.5, and 4-6 kHz) were calculated using MATLAB software. The ApEn of TEOAE in different frequency ranges showed no significant differences at the same effect-site concentration of propofol, or at different effect-site concentrations in the same frequency range (P>0.05). Anesthesia with propofol at different effect-site concentrations does not obviously affect ApEn of TEOAE signals in adults, and ApEn can not be used as the indicator for evaluating the depth of anesthesia.

Analytically Sensitive Protein Detection in Microtiter Plates by Proximity Ligation with Rolling Circle Amplification.

PubMed

Ebai, Tonge; Souza de Oliveira, Felipe Marques; Löf, Liza; Wik, Lotta; Schweiger, Caroline; Larsson, Anders; Keilholtz, Ulrich; Haybaeck, Johannes; Landegren, Ulf; Kamali-Moghaddam, Masood

2017-09-01

Detecting proteins at low concentrations in plasma is crucial for early diagnosis. Current techniques in clinical routine, such as sandwich ELISA, provide sensitive protein detection because of a dependence on target recognition by pairs of antibodies, but detection of still lower protein concentrations is often called for. Proximity ligation assay with rolling circle amplification (PLARCA) is a modified proximity ligation assay (PLA) for analytically specific and sensitive protein detection via binding of target proteins by 3 antibodies, and signal amplification via rolling circle amplification (RCA) in microtiter wells, easily adapted to instrumentation in use in hospitals. Proteins captured by immobilized antibodies were detected using a pair of oligonucleotide-conjugated antibodies. Upon target recognition these PLA probes guided oligonucleotide ligation, followed by amplification via RCA of circular DNA strands that formed in the reaction. The RCA products were detected by horseradish peroxidase-labeled oligonucleotides to generate colorimetric reaction products with readout in an absorbance microplate reader. We compared detection of interleukin (IL)-4, IL-6, IL-8, p53, and growth differentiation factor 15 (GDF-15) by PLARCA and conventional sandwich ELISA or immuno-RCA. PLARCA detected lower concentrations of proteins and exhibited a broader dynamic range compared to ELISA and iRCA using the same antibodies. IL-4 and IL-6 were detected in clinical samples at femtomolar concentrations, considerably lower than for ELISA. PLARCA offers detection of lower protein levels and increased dynamic ranges compared to ELISA. The PLARCA procedure may be adapted to routine instrumentation available in hospitals and research laboratories. © 2017 American Association for Clinical Chemistry.

Combination of Competitive Quantitative PCR and Constant-Denaturant Capillary Electrophoresis for High-Resolution Detection and Enumeration of Microbial Cells

PubMed Central

Lim, Eelin L.; Tomita, Aoy V.; Thilly, William G.; Polz, Martin F.

2001-01-01

A novel quantitative PCR (QPCR) approach, which combines competitive PCR with constant-denaturant capillary electrophoresis (CDCE), was adapted for enumerating microbial cells in environmental samples using the marine nanoflagellate Cafeteria roenbergensis as a model organism. Competitive PCR has been used successfully for quantification of DNA in environmental samples. However, this technique is labor intensive, and its accuracy is dependent on an internal competitor, which must possess the same amplification efficiency as the target yet can be easily discriminated from the target DNA. The use of CDCE circumvented these problems, as its high resolution permitted the use of an internal competitor which differed from the target DNA fragment by a single base and thus ensured that both sequences could be amplified with equal efficiency. The sensitivity of CDCE also enabled specific and precise detection of sequences over a broad range of concentrations. The combined competitive QPCR and CDCE approach accurately enumerated C. roenbergensis cells in eutrophic, coastal seawater at abundances ranging from approximately 10 to 104 cells ml−1. The QPCR cell estimates were confirmed by fluorescent in situ hybridization counts, but estimates of samples with <50 cells ml−1 by QPCR were less variable. This novel approach extends the usefulness of competitive QPCR by demonstrating its ability to reliably enumerate microorganisms at a range of environmentally relevant cell concentrations in complex aquatic samples. PMID:11525983

Geochemical evidence for a brooks range mineral belt, Alaska

USGS Publications Warehouse

Marsh, S.P.; Cathrall, J.B.

1981-01-01

Geochemical studies in the central Brooks Range, Alaska, delineate a regional, structurally controlled mineral belt in east-west-trending metamorphic rocks and adjacent metasedimentary rocks. The mineral belt extends eastward from the Ambler River quadrangle to the Chandalar and Philip Smith quadrangles, Alaska, from 147?? to 156??W. longitude, a distance of more than 375 km, and spans a width from 67?? to 69??N. latitude, a distance of more than 222 km. Within this belt are several occurrences of copper and molybdenum mineralization associated with meta-igneous, metasedimentary, and metavolcanic rocks; the geochemical study delineates target areas for additional occurrences. A total of 4677 stream-sediment and 2286 panned-concentrate samples were collected in the central Brooks Range, Alaska, from 1975 to 1979. The -80 mesh ( 2.86) nonmagnetic fraction of the panned concentrates from stream sediment were analyzed by semiquantitative spectrographic methods. Two geochemical suites were recognized in this investigation; a base-metal suite of copper-lead-zinc and a molybdenum suite of molybdenum-tin-tungsten. These suites suggest several types of mineralization within the metamorphic belt. Anomalies in molybdenum with associated Cu and W suggest a potential porphyry molybdenum system associated with meta-igneous rocks. This regional study indicates that areas of metaigneous rocks in the central metamorphic belt are target areas for potential mineralized porphyry systems and that areas of metavolcanic rocks are target areas for potential massive sulfide mineralization. ?? 1981.

Sensitive detection of unlabeled oligonucleotides using a paired surface plasma waves biosensor.

PubMed

Li, Ying-Chang; Chiou, Chiuan-Chian; Luo, Ji-Dung; Chen, Wei-Ju; Su, Li-Chen; Chang, Ying-Feng; Chang, Yu-Sun; Lai, Chao-Sung; Lee, Cheng-Chung; Chou, Chien

2012-05-15

Detection of unlabeled oligonucleotides using surface plasmon resonance (SPR) is difficult because of the oligonucleotides' relatively lower molecular weight compared with proteins. In this paper, we describe a method for detecting unlabeled oligonucleotides at low concentration using a paired surface plasma waves biosensor (PSPWB). The biosensor uses a sensor chip with an immobilized probe to detect a target oligonucleotide via sequence-specific hybridization. PSPWB measures the demodulated amplitude of the heterodyne signal in real time. In the meantime, the ratio of the amplitudes between the detected output signal and reference can reduce the excess noise from the laser intensity fluctuation. Also, the common-path propagation of p and s waves cancels the common phase noise induced by temperature variation. Thus, a high signal-to-noise ratio (SNR) of the heterodyne signal is detected. The sequence specificity of oligonucleotide hybridization ensures that the platform is precisely discriminating between target and non-target oligonucleotides. Under optimized experimental conditions, the detected heterodyne signal increases linearly with the logarithm of the concentration of target oligonucleotide over the range 0.5-500 pM. The detection limit is 0.5 pM in this experiment. In addition, the non-target oligonucleotide at concentrations of 10 pM and 10nM generated signals only slightly higher than background, indicating the high selectivity and specificity of this method. Different length of perfectly matched oligonucleotide targets at 10-mer, 15-mer and 20-mer were identified at the concentration of 150 pM. Copyright © 2012 Elsevier B.V. All rights reserved.

Evaluation of the adverse event profile and pharmacodynamics of toceranib phosphate administered to dogs with solid tumors at doses below the maximum tolerated dose

PubMed Central

2013-01-01

Background The receptor kinase inhibitor toceranib phosphate (Palladia) was approved for use in dogs in 2009 using a dose of 3.25 mg/kg administered every other day. Preliminary data suggests that lower doses of toeceranib may be associated with a reduced adverse event profile while maintaining sufficient drug exposure to provide biologic activity. The purpose of this study was to determine the Cmax of toceranib in dogs with solid tumors receiving 2.5-2.75 mg/kg every other day and to document the adverse events associated with this dose rate. Secondary objectives included determination of plasma VEGF concentrations in treated dogs and response to therapy. Results Dogs with solid tumors were administered toceranib at an intended target dose ranging from 2.5-2.75 mg/kg every other day and plasma samples were obtained for analysis of toceranib and VEGF plasma concentrations on days 0, 7, 14 and 30 of the study at 6 and 8 hours post drug administration. Additionally, plasma samples were obtained at 0, 1, 2, 6, 8, and 12 hours from dogs on day 30 for confirmation of Cmax. Response to therapy was assessed using standard RECIST criteria and adverse events were characterized using the VCOG-CTCAE. Toceranib administered at doses between 2.4-2.9 mg/kg every other day resulted in an average 6–8 hr plasma concentration ranging from 100–120 ng/ml, well above the 40 ng/ml concentration associated with target inhibition. Plasma VEGF concentrations increased significantly over the 30 day treatment period indicating that VEGFR2 inhibition was likely achieved in the majority of dogs. The lower doses of toceranib used in this study were associated with a substantially reduced adverse event profile compared to the established label dose of 3.25 mg/kg EOD. Conclusions Doses of toceranib ranging from 2.4-2.9 mg/kg every other day provide drug exposure considered sufficient for target inhibition while resulting in an adverse event profile substantially reduced from that associated with the label dose of toceranib. This lower dose range of toceranib should be considered for future use in dogs with cancer. PMID:24079884

Determination of endocrine disrupting compounds and their metabolites in fish bile.

PubMed

Ros, Oihana; Izaguirre, Jon Kepa; Olivares, Maitane; Bizarro, Cristina; Ortiz-Zarragoitia, Maren; Cajaraville, Miren Pilar; Etxebarria, Nestor; Prieto, Ailette; Vallejo, Asier

2015-12-01

This work describes a new methodology for the simultaneous determination of a large variety of emerging and persistent organic compounds and some of their metabolites in fish bile samples. The target compounds were musk fragrances, alkyl phenols, hormones, pesticides, phthalate esters and bisphenol-A, all of them with a known endocrine disrupting effect. To achieve the determination these three steps were optimized: i) an enzymatic hydrolysis of the metabolites to render the unconjugated compounds; ii) the solid phase extraction of the target analytes (Plexa cartridges 200-mg); and, iii) a clean-up of the extracts (Florisil cartridges 1-g). The samples were analyzed by gas-chromatography-mass spectrometry (GC-MS), though the polar fraction required a previous derivatization with O-bis (trimethylsilyl) trifluoroacetamide. Good apparent recoveries (63-122%), repeatability (<20%) and limits of detection (LODs) ranging between 0.04 and 459 ng/mL were obtained. This method was applied to the analysis of the target analytes in bile samples of thicklip grey mullets (Chelon labrosus) from five different populations of the Basque Coast (South East Bay of Biscay) during the period of May-June 2012. The target analytes were found at concentrations ranging from

Multiresidue determination and potential risks of emerging pesticides in aquatic products from Northeast China by LC-MS/MS.

PubMed

Fu, Lei; Lu, Xianbo; Tan, Jun; Wang, Longxing; Chen, Jiping

2018-01-01

A simple method for determining 33 pesticides with a wide polarity range (logK ow 0.6-4.5) in aquatic products was developed based on LC-MS/MS. The target analytes included three types of widely used pesticides: insecticides, fungicides and herbicides. Based on the optimization of ultrasonic assisted extraction and GPC clean-up procedures, the matrix effect, extraction recoveries and LOD were improved distinctively. LOQ of this method was below 0.5ng/g for all pesticides, which is superior to values in the literature, and the matrix effect was reduced effectively (-14.7% to 7.5%). The method was successfully applied to investigate the pesticide residue levels of twenty-five samples including seven common kinds of fishes from Northeast China. The results showed that all targeted pesticides were present in the fish samples; however, their levels were low, except for atrazine, linuron, ethoprophos, tetrachlorvinphos, acetochlor and fenthion. Atrazine and linuron caught our attention because the concentrations of atrazine in fish samples from Liaoning province were in the range of 0.5-8ng/g (w/w) with mean concentration of 2.3ng/g, which were far above those of other pesticides. The levels of linuron were in the range of 0.6-6ng/g (mean concentration 2.8ng/g), which were the highest among all targeted pesticides in the Inner Mongolia. This is the first systematic investigation on the characteristics and levels of these pesticides in aquatic products from northeast China. Considering their toxicity and bioaccumulation, the potential risk of atrazine and linuron from consuming aquatic products should be paid more attention. Copyright © 2017. Published by Elsevier B.V.

Accounting for pharmacokinetic differences in dual-tracer receptor density imaging

PubMed Central

Tichauer, K M; Diop, M; Elliott, J T; Samkoe, K S; Hasan, T; St. Lawrence, K; Pogue, B W

2014-01-01

Dual-tracer molecular imaging is a powerful approach to quantify receptor expression in a wide range of tissues by using an untargeted tracer to account for any nonspecific uptake of a molecular-targeted tracer. This approach has previously required the pharmacokinetics of the receptor-targeted and untargeted tracers to be identical, requiring careful selection of an ideal untargeted tracer for any given targeted tracer. In this study, methodology capable of correcting for tracer differences in arterial input functions, as well as binding-independent delivery and retention, is derived and evaluated in a mouse U251 glioma xenograft model using an Affibody tracer targeted to epidermal growth factor receptor (EGFR), a cell membrane receptor overexpressed in many cancers. Simulations demonstrated that blood, and to a lesser extent vascular-permeability, pharmacokinetic differences between targeted and untargeted tracers could be quantified by deconvolving the uptakes of the two tracers in a region of interest devoid of targeted tracer binding, and therefore corrected for, by convolving the uptake of the untargeted tracer in all regions of interest by the product of the deconvolution. Using fluorescently labelled, EGFR-targeted and untargeted Affibodies (known to have different blood clearance rates), the average tumor concentration of EGFR in 4 mice was estimated using dual-tracer kinetic modelling to be 3.9 ± 2.4 nM compared to an expected concentration of 2.0 ± 0.4 nM. However, with deconvolution correction a more equivalent EGFR concentration of 2.0 ± 0.4 nM was measured. PMID:24743262

Differential Absorption Lidar (DIAL) Measurements of Landfill Methane Emissions

NASA Astrophysics Data System (ADS)

Innocenti, Fabrizio; Robinson, Rod; Gardiner, Tom; Finlayson, Andrew; Connor, Andy

2017-04-01

DIFFERENTIAL ABSORPTION LIDAR (DIAL) MEASURMENTS OF LANDFILL METHANE EMISSIONS F. INNOCENTI *, R.A. ROBINSON *, T.D. GARDINER, A. FINLAYSON *, A. CONNOR* * National Physical Laboratory (NPL), Hampton Road, Teddington, Middlesex, TW11 0LW, United Kingdom Methane is one of the most important gaseous hydrocarbon species for both industrial and environmental reasons. Understanding and quantifying methane emissions to atmosphere is an important element of climate change research. Range-resolved infrared Differential Absorption Lidar (DIAL) measurements provide the means to map and quantify a wide range of different methane sources. DIAL is a powerful technique that can be used to track and quantify plumes emitted from area emission sources such as landfill sites, waste water treatment plants and petrochemical plants. By using lidar (light detection and ranging), the DIAL technique is able to make remote range-resolved single-ended measurements of the actual distribution of target gases in the atmosphere, with no disruption to normal site operational activities. DIAL provides 3D mapping of emission concentrations and quantification of emission rates for a wide range of target gases such as methane. The NPL DIAL laser source is operated alternately at two similar wavelengths. One of these, termed the "on-resonant wavelength", is chosen to be at a wavelength which is absorbed by the target species. The other, the "off-resonant wavelength", is chosen to be at a nearby wavelength which is not absorbed significantly by the target species. The two wavelengths are chosen to be close, so that the atmospheric scattering properties are the same for both wavelengths. They are also chosen so that any differential absorption due to other atmospheric species are minimised. Any measured difference in the returned signals is therefore due to absorption by the target gas. In the typical DIAL measurement configuration the mobile DIAL facility is positioned downwind of the area being investigated. The DIAL laser beam is then scanned in a vertical plane and the distribution of the target gas in the measurement plane is mapped. By combining this information with the wind conditions, the technique provides a direct measure of the emission rate of the target gas and its spatial distribution rather than the path-averaged concentration given by most other optical remote sensing methods. This means that localised, high concentration plumes can be discriminated from broad, low concentration plumes, and that emissions from different sources within an area can be spatially separated and independently quantified. As an example, the localised emission from an engine stack or flare can be separated from the diffuse emission from a capped area. Horizontal scans just above the surface can also be performed and they are generally used to identify emission hot-spots. Over the last decade the NPL DIAL system has carried out landfill emission surveys at over thirty sites in the UK, France and the USA measuring the total site and area-specific emissions from e.g. active areas, capped areas and engine stacks. This history of emissions measurements made with DIAL at landfill sites is testament to the maturity of the technique that can be deployed as reference tool by the waste industry. The DIAL data can be used by the site operators to validate emissions estimates and by the regulators to revise and update the emission inventories.

Evaluation of plasma diazepam and nordiazepam concentrations following administration of diazepam intravenously or via suppository per rectum in dogs.

PubMed

Probst, Curtis W; Thomas, William B; Moyers, Tamberlyn D; Martin, Tomas; Cox, Sherry

2013-04-01

To evaluate the pharmacokinetics of diazepam administered per rectum via compounded (ie, not commercially available) suppositories and determine whether a dose of 2 mg/kg in this formulation would result in plasma concentrations shown to be effective for control of status epilepticus or cluster seizures (ie, 150 to 300 ng/mL) in dogs within a clinically useful interval (10 to 15 minutes). 6 healthy mixed-breed dogs. Dogs were randomly assigned to 2 groups of 3 dogs each in a crossover-design study. Diazepam (2 mg/kg) was administered IV or via suppository per rectum, and blood samples were collected at predetermined time points. Following a 6- or 7-day washout period, each group received the alternate treatment. Plasma concentrations of diazepam and nordiazepam were analyzed via reversed phase high-performance liquid chromatography. Plasma concentrations of diazepam and nordiazepam exceeded the targeted range ≤ 3 minutes after IV administration in all dogs. After suppository administration, targeted concentrations of diazepam were not detected in any dogs, and targeted concentrations of nordiazepam were detected after 90 minutes (n = 2 dogs) or 120 minutes (3) or were not achieved (1). On the basis of these results, administration of 2 mg of diazepam/kg via the compounded suppositories used in the present study cannot be recommended for emergency treatment of seizures in dogs.

Duplexed sandwich immunoassays on a fiber-optic microarray.

PubMed

Rissin, David M; Walt, David R

2006-03-30

In this paper, we describe a duplexed imaging optical fiber array-based immunoassay for immunoglobulin A (IgA) and lactoferrin. To fabricate the individually addressable array, microspheres were functionalized with highly specific monoclonal antibodies. The microspheres were loaded in microwells etched into the distal face of an imaging optical fiber bundle. Two microsphere-based sandwich immunoassays were developed to simultaneously detect IgA and lactoferrin, two innate immune system proteins found in human saliva. Individual microspheres could be interrogated for the simultaneous measurement of both proteins. The working concentration range for IgA detection was between 700 pM and 100 nM, while the working concentration range for lactoferrin was between 385 pM and 10 nM. The cross-reactivity between detection antibodies and their non-specific targets was relatively low in comparison to the signal generated by the specific binding with their targets. These results suggest that the degree of multiplexing on this fiber-optic array platform can be increased beyond a duplex.

Targeted analysis of 116 drugs in hair by UHPLC-MS/MS and its application to forensic cases.

PubMed

Wang, Xin; Johansen, Sys Stybe; Nielsen, Marie Katrine Klose; Linnet, Kristian

2017-08-01

A multi-target method that can detect a broad range of drugs in human hair, such as hypnotics, anxiolytics, analgesics, benzodiazepines, antihistamines, antidepressants, antipsychotics, and anticonvulsants, was developed based on ultra-high-performance liquid chromatography-tandem mass spectrometry (UHPLC-MS/MS). The drugs were extracted from 10 mg of washed hair by incubation for 18 h in a 25:25:50 (v/v/v) mixture of methanol/acetonitrile/2 mM ammonium formate (8% acetonitrile, pH 5.3). For 51% of the basic drugs, the lower limits of quantification (LLOQs) were in the range of 0.05-0.5 pg/mg, and the majority (98%) were ≤ 5 pg/mg. Linearity ranged from LLOQs to 100-500 pg/mg for all the basic drugs. For acid and neutral drugs, the LLOQs ranged from 0.4 to 500 pg/mg, and linearity ranged from LLOQs to 80-40 000 pg/mg. According to published reports on concentrations attained in single dose control studies, the present method is sensitive enough to detect single-dose drug exposure for many of the drugs. The accuracy was within 75-125% for the majority of drugs. Good precision was observed (relative standard deviations [RSD%] < 25%) for most of the compounds, including the prepared quality control (QC) hair samples. The method was applied to forensic cases and concentrations of rarely reported drugs in hair in 25 post-mortem forensic cases were presented. Hair concentrations of amisulpride, gabapentin, mianserin, mepyramine, orphenadrine, and xylometazoline have not been previously reported. Copyright © 2016 John Wiley & Sons, Ltd. Copyright © 2016 John Wiley & Sons, Ltd.

Silicon and Titanium Correlation in Selected Rocks at Gale Crater, Mars

NASA Image and Video Library

2015-12-17

The yellow triangles on this graph indicate concentrations of the elements titanium and silicon in selected rock targets with high silica content analyzed by the Alpha Particle X-ray Spectrometer (APXS) instrument on NASA's Curiosity rover in Mars' Gale Crater. The pattern shows a correlation between enriched silicon content and enriched titanium content. Titanium is difficult to mobilize in weathering environments, and this correlation suggests that both titanium and silicon remain as the residue of acidic weathering. Ongoing research aims to distinguish between that possible explanation for silicon enrichment and an alternative of mobilized silicon being added to the site (see PIA20275). As a general comparison with these selected high-silica targets in Gale Crater, the gray dots in the graph show the range of titanium and silicon concentrations in all Martian targets analyzed by APXS instruments on three Mars rovers at three different areas of Mars. http://photojournal.jpl.nasa.gov/catalog/PIA20274

In vivo potency revisited - Keep the target in sight.

PubMed

Gabrielsson, Johan; Peletier, Lambertus A; Hjorth, Stephan

2018-04-01

Potency is a central parameter in pharmacological and biochemical sciences, as well as in drug discovery and development endeavors. It is however typically defined in terms only of ligand to target binding affinity also in in vivo experimentation, thus in a manner analogous to in in vitro studies. As in vivo potency is in fact a conglomerate of events involving ligand, target, and target-ligand complex processes, overlooking some of the fundamental differences between in vivo and in vitro may result in serious mispredictions of in vivo efficacious dose and exposure. The analysis presented in this paper compares potency measures derived from three model situations. Model A represents the closed in vitro system, defining target binding of a ligand when total target and ligand concentrations remain static and constant. Model B describes an open in vivo system with ligand input and clearance (Cl (L) ), adding in parallel to the turnover (k syn , k deg ) of the target. Model C further adds to the open in vivo system in Model B also the elimination of the target-ligand complex (k e(RL) ) via a first-order process. We formulate corresponding equations of the equilibrium (steady-state) relationships between target and ligand, and complex and ligand for each of the three model systems and graphically illustrate the resulting simulations. These equilibrium relationships demonstrate the relative impact of target and target-ligand complex turnover, and are easier to interpret than the more commonly used ligand-, target- and complex concentration-time courses. A new potency expression, labeled L 50 , is then derived. L 50 is the ligand concentration at half-maximal target and complex concentrations and is an amalgamation of target turnover, target-ligand binding and complex elimination parameters estimated from concentration-time data. L 50 is then compared to the dissociation constant K d (target-ligand binding affinity), the conventional Black & Leff potency estimate EC 50 , and the derived Michaelis-Menten parameter K m (target-ligand binding and complex removal) across a set of literature data. It is evident from a comparison between parameters derived from in vitro vs. in vivo experiments that L 50 can be either numerically greater or smaller than the K d (or K m ) parameter, primarily depending on the ratio of k deg -to-k e(RL) . Contrasting the limit values of target R and target-ligand complex RL for ligand concentrations approaching infinity demonstrates that the outcome of the three models differs to a great extent. Based on the analysis we propose that a better understanding of in vivo pharmacological potency requires simultaneous assessment of the impact of its underlying determinants in the open system setting. We propose that L 50 will be a useful parameter guiding predictions of the effective concentration range, for translational purposes, and assessment of in vivo target occupancy/suppression by ligand, since it also encompasses target turnover - in turn also subject to influence by pathophysiology and drug treatment. Different compounds may have similar binding affinity for a target in vitro (same K d ), but vastly different potencies in vivo. L 50 points to what parameters need to be taken into account, and particularly that closed-system (in vitro) parameters should not be first choice when ranking compounds in vivo (open system). Copyright © 2017 Elsevier Inc. All rights reserved.

Accounting for pharmacokinetic differences in dual-tracer receptor density imaging.

PubMed

Tichauer, K M; Diop, M; Elliott, J T; Samkoe, K S; Hasan, T; St Lawrence, K; Pogue, B W

2014-05-21

Dual-tracer molecular imaging is a powerful approach to quantify receptor expression in a wide range of tissues by using an untargeted tracer to account for any nonspecific uptake of a molecular-targeted tracer. This approach has previously required the pharmacokinetics of the receptor-targeted and untargeted tracers to be identical, requiring careful selection of an ideal untargeted tracer for any given targeted tracer. In this study, methodology capable of correcting for tracer differences in arterial input functions, as well as binding-independent delivery and retention, is derived and evaluated in a mouse U251 glioma xenograft model using an Affibody tracer targeted to epidermal growth factor receptor (EGFR), a cell membrane receptor overexpressed in many cancers. Simulations demonstrated that blood, and to a lesser extent vascular-permeability, pharmacokinetic differences between targeted and untargeted tracers could be quantified by deconvolving the uptakes of the two tracers in a region of interest devoid of targeted tracer binding, and therefore corrected for, by convolving the uptake of the untargeted tracer in all regions of interest by the product of the deconvolution. Using fluorescently labeled, EGFR-targeted and untargeted Affibodies (known to have different blood clearance rates), the average tumor concentration of EGFR in four mice was estimated using dual-tracer kinetic modeling to be 3.9 ± 2.4 nM compared to an expected concentration of 2.0 ± 0.4 nM. However, with deconvolution correction a more equivalent EGFR concentration of 2.0 ± 0.4 nM was measured.

Highly Specific and Wide Range NO2 Sensor with Color Readout.

PubMed

Fàbrega, Cristian; Fernández, Luis; Monereo, Oriol; Pons-Balagué, Alba; Xuriguera, Elena; Casals, Olga; Waag, Andreas; Prades, Joan Daniel

2017-11-22

We present a simple and inexpensive method to implement a Griess-Saltzman-type reaction that combines the advantages of the liquid phase method (high specificity and fast response time) with the benefits of a solid implementation (easy to handle). We demonstrate that the measurements can be carried out using conventional RGB sensors; circumventing all the limitations around the measurement of the samples with spectrometers. We also present a method to optimize the measurement protocol and target a specific range of NO 2 concentrations. We demonstrate that it is possible to measure the concentration of NO 2 from 50 ppb to 300 ppm with high specificity and without modifying the Griess-Saltzman reagent.

Hospital protocols for targeted glycemic control: Development, implementation, and models for cost justification.

PubMed

Magee, Michelle F

2007-05-15

Evolving elements of best practices for providing targeted glycemic control in the hospital setting, clinical performance measurement, basal-bolus plus correction-dose insulin regimens, components of standardized subcutaneous (s.c.) insulin order sets, and strategies for implementation and cost justification of glycemic control initiatives are discussed. Best practices for targeted glycemic control should address accurate documentation of hyperglycemia, initial patient assessment, management plan, target blood glucose range, blood glucose monitoring frequency, maintenance of glycemic control, criteria for glucose management consultations, and standardized insulin order sets and protocols. Establishing clinical performance measures, including desirable processes and outcomes, can help ensure the success of targeted hospital glycemic control initiatives. The basal-bolus plus correction-dose regimen for insulin administration will be used to mimic the normal physiologic pattern of endogenous insulin secretion. Standardized insulin order sets and protocols are being used to minimize the risk of error in insulin therapy. Components of standardized s.c. insulin order sets include specification of the hyperglycemia diagnosis, finger stick blood glucose monitoring frequency and timing, target blood glucose concentration range, cutoff values for excessively high or low blood glucose concentrations that warrant alerting the physician, basal and prandial or nutritional (i.e., bolus) insulin, correction doses, hypoglycemia treatment, and perioperative or procedural dosage adjustments. The endorsement of hospital administrators and key physician and nursing leaders is needed for glycemic control initiatives. Initiatives may be cost justified on the basis of the billings for clinical diabetes management services and/or the return- on-investment accrued to reductions in hospital length of stay, readmissions, and accurate documentation and coding of unrecognized or uncontrolled diabetes, and diabetes complications. Standardized insulin order sets and protocols may minimize risk of insulin errors. The endorsement of these protocols by administrators, physicians, nurses, and pharmacists is also needed for success.

Cure of tuberculosis despite serum concentrations of antituberculosis drugs below published reference ranges.

PubMed

Meloni, Monica; Corti, Natascia; Müller, Daniel; Henning, Lars; Gutteck, Ursula; von Braun, Amrei; Weber, Rainer; Fehr, Jan

2015-01-01

Therapeutic target serum concentrations of first-line antituberculosis drugs have not been well defined in clinical studies in tuberculosis (TB) patients. We retrospectively investigated the estimated maximum serum concentrations (eC max) of antituberculosis drugs and clinical outcome of TB patients with therapeutic drug monitoring performed between 2010-2012 at our institution, and follow-up until March 2014. The eC max was defined as the highest serum concentration during a sampling period (2, 4 and 6 hours after drug ingestion). We compared the results with published eC max values, and categorised them as either "within reference range", "low eC max", or "very low eC max".Low/very low eC max-levels were defined as follows: isoniazid 2-3/<2 mg/l, rifampicin 4-8/<4 mg/l, rifabutin 0.2-0.3/<0.2 mg/l, ethambutol 1-2/<0.1 mg/l and pyrazinamide <20 mg/l. Concentrations of antituberculosis drugs in 175 serum samples of 17 patients with TB were analysed. In 12 (71%) patients, multiple therapeutic drug monitoring samples were collected over time, in 5 (29%) patients only one sample was available for therapeutic drug monitoring. Overall, 94% of all patients had at least one low antituberculosis drug concentration. Overall, 64% of all eC max levels were classified as "low" or "very low". The eC max was below the relevant reference range in 80% of isoniazid, 95% of rifampicin, 30% of pyrazinamide, and 30% of ethambutol measurements. All but one patient were cured of tuberculosis. Although many antituberculosis drug serum concentrations were below the widely used reference ranges, 16 of 17 patients were cured of tuberculosis. These results challenge the use of the published reference ranges for therapeutic drug monitoring.

Investigation of the High Mobility IGZO Thin Films by Using Co-Sputtering Method

PubMed Central

Hsu, Chao-Ming; Tzou, Wen-Cheng; Yang, Cheng-Fu; Liou, Yu-Jhen

2015-01-01

High transmittance ratio in visible range, low resistivity, and high mobility of IGZO thin films were prepared at room temperature for 30 min by co-sputtering of Zn2Ga2O5 (Ga2O3 + 2 ZnO, GZO) ceramic and In2O3 ceramic at the same time. The deposition power of pure In2O3 ceramic target was fixed at 100 W and the deposition power of GZO ceramic target was changed from 80 W to 140 W. We chose to investigate the deposition power of GZO ceramic target on the properties of IGZO thin films. From the SEM observations, all of the deposited IGZO thin films showed a very smooth and featureless surface. From the measurements of XRD patterns, only the amorphous structure was observed. We aimed to show that the deposition power of GZO ceramic target had large effect on the Eg values, Hall mobility, carrier concentration, and resistivity of IGZO thin films. Secondary ion mass spectrometry (SIMS) analysis in the thicknesses’ profile of IGZO thin films found that In and Ga elements were uniform distribution and Zn element were non-uniform distribution. The SIMS analysis results also showed the concentrations of Ga and Zn elements increased and the concentrations of In element was almost unchanged with increasing deposition power.

Overcoming biofluid protein complexity during targeted mass spectrometry detection and quantification of protein biomarkers by MRM cubed (MRM3).

PubMed

Jeudy, Jeremy; Salvador, Arnaud; Simon, Romain; Jaffuel, Aurore; Fonbonne, Catherine; Léonard, Jean-François; Gautier, Jean-Charles; Pasquier, Olivier; Lemoine, Jerome

2014-02-01

Targeted mass spectrometry in the so-called multiple reaction monitoring mode (MRM) is certainly a promising way for the precise, accurate, and multiplexed measurement of proteins and their genetic or posttranslationally modified isoforms. MRM carried out on a low-resolution triple quadrupole instrument faces a lack of specificity when addressing the quantification of weakly concentrated proteins. In this case, extensive sample fractionation or immunoenrichment alleviates signal contamination by interferences, but in turn decreases assay performance and throughput. Recently, MRM(3) was introduced as an alternative to MRM to improve the limit of quantification of weakly concentrated protein biomarkers. In the present work, we compare MRM and MRM(3) modes for the detection of biomarkers in plasma and urine. Calibration curves drawn with MRM and MRM(3) showed a similar range of linearity (R(2) > 0.99 for both methods) with protein concentrations above 1 μg/mL in plasma and a few nanogram per milliliter in urine. In contrast, optimized MRM(3) methods improve the limits of quantification by a factor of 2 to 4 depending on the targeted peptide. This gain arises from the additional MS(3) fragmentation step, which significantly removes or decreases interfering signals within the targeted transition channels.

Evaluation of a 12-week targeted vitamin D supplementation regimen in patients with active inflammatory bowel disease.

PubMed

Garg, Mayur; Rosella, Ourania; Rosella, Gennaro; Wu, Yunqiu; Lubel, John S; Gibson, Peter R

2017-06-15

Vitamin D at serum 25(OH)D concentrations above 100 nmol/L is associated with disease remission in patients with IBD, suggesting targeted dosing might be anti-inflammatory. This study aimed to assess the effectiveness, safety and predictors of a 12-week regimen of vitamin D supplementation to achieve such a target in patients with active disease. In a pilot study, patients with active colitis and a serum 25(OH)D concentration <75 nmol/L were prescribed oral liquid vitamin D supplementation over 12 weeks using a specific protocol with dose adjusted 4-weekly to aim for a target level of 100-125 nmol/L. Five patients each with Crohn's colitis or ulcerative colitis (UC) had mean 25(OH)D concentration 52 (range 27-73 nmol/L). Five reached the targeted level and four 89-95 nmol/L. One withdrew after 4 weeks (88 nmol/L). Target dose was met only in those with BMI <30 kg/m 2 and total dose inversely correlated with initial serum 25(OH)D. One patient had developed a high level at 8 weeks (146 nmol/L) and another new hypercalciuria. There were no serious adverse events attributable to the therapy. Clinical disease activity consistently declined, but faecal calprotectin and circulating markers of inflammation did not. A specified oral vitamin D regimen successfully and safely achieved target or near-target levels, improved symptom-based activity scores, but did not alter objective measures of intestinal or systemic inflammation. A modified version of this dose-escalating regimen would be suitable for a randomised placebo-controlled trial, but does require regular safety monitoring. Copyright © 2017 Elsevier Ltd and European Society for Clinical Nutrition and Metabolism. All rights reserved.

Efficacy of a dose range of simulated sunlight exposures in raising vitamin D status in South Asian adults: implications for targeted guidance on sun exposure.

PubMed

Farrar, Mark D; Webb, Ann R; Kift, Richard; Durkin, Marie T; Allan, Donald; Herbert, Annie; Berry, Jacqueline L; Rhodes, Lesley E

2013-06-01

Vitamin D is essential for bone health, and cutaneous synthesis is an important source. South Asians cannot attain adequate amounts of vitamin D by following general recommendations on summer sunlight exposure at northerly latitudes, and increased exposure may be appropriate for improving their vitamin D status. We examined the efficacy of a dose range of simulated summer sunlight exposures in raising vitamin D status in UK adults of South Asian ethnicity. In a dose-response study, healthy adults of South Asian ethnicity (n = 60; 20-60 y old) received 1 of 6 ultraviolet exposures ranging from 0.65 to 3.9 standard erythema doses (SEDs), which were equivalent to 15-90 min unshaded noontime summer sunlight at 53.5°N (Manchester, United Kingdom), 3 times/wk for 6 wk, while wearing casual clothes that revealed a 35% skin area. Serum 25-hydroxyvitamin D [25(OH)D] was measured weekly, and dietary vitamin D was estimated. At baseline, all completing participants (n = 51) were vitamin D insufficient [25(OH)D concentrations <20 ng/mL], and a high proportion of participants were deficient [35% of subjects had 25(OH)D concentrations <5 ng/mL, and 90% of subjects had 25(OH)D concentrations <10 ng/mL, which are concentrations at which osteomalacia and rickets occur). The 25(OH)D concentration rose significantly in all dose groups. Postcourse, all participants achieved 25(OH)D concentrations ≥5 ng/mL, whereas only 6 subjects attained 25(OH)D concentrations ≥20 ng/mL. Participants who received exposures ≥1.95 SEDs (equivalent to 45 min unshaded sunlight; n = 33) attained a mean (±SD) 25(OH)D concentration of 15.7 ± 5 ng/mL (mean rise: 8.7 ± 5.7 ng/mL; 95% CI: 6.8, 10.6 ng/mL; P < 0.001), and 94% of subjects achieved concentrations >10 ng/mL. Targeted guidance on sunlight exposure could usefully enhance vitamin D status to avoid deficiency [25(OH)D concentration >10 ng/mL] in South Asians living at latitudes distant from the equator. This trial was registered at the ISRCTN Register (www.isrctn.org) as 07565297.

Favipiravir pharmacokinetics in Ebola-Infected patients of the JIKI trial reveals concentrations lower than targeted

PubMed Central

Nguyen, Thi Huyen Tram; Anglaret, Xavier; Madelain, Vincent; Taburet, Anne-Marie; Baize, Sylvain; Pastorino, Boris; Rodallec, Anne; Piorkowski, Géraldine; Conde, Mamoudou N.; Bore, Joseph Akoi; Carbonnelle, Caroline; Jacquot, Frédéric; Raoul, Hervé; Malvy, Denis; Mentré, France

2017-01-01

Background In 2014–2015, we assessed favipiravir tolerance and efficacy in patients with Ebola virus (EBOV) disease (EVD) in Guinea (JIKI trial). Because the drug had never been used before for this indication and that high concentrations of the drugs were needed to achieve antiviral efficacy against EBOV, a pharmacokinetic model had been used to propose relevant dosing regimen. Here we report the favipiravir plasma concentrations that were achieved in participants in the JIKI trial and put them in perspective with the model-based targeted concentrations. Methods and findings Pre-dose drug concentrations were collected at Day-2 and Day-4 of treatment in 66 patients of the JIKI trial and compared to those predicted by the model taking into account patient’s individual characteristics. At Day-2, the observed concentrations were slightly lower than the model predictions adjusted for patient’s characteristics (median value of 46.1 versus 54.3 μg/mL for observed and predicted concentrations, respectively, p = 0.012). However, the concentrations dropped at Day-4, which was not anticipated by the model (median values of 25.9 and 64.4 μg/mL for observed and predicted concentrations, respectively, p<10−6). There was no significant relationship between favipiravir concentrations and EBOV viral kinetics or mortality. Conclusions Favipiravir plasma concentrations in the JIKI trial failed to achieve the target exposure defined before the trial. Furthermore, the drug concentration experienced an unanticipated drop between Day-2 and Day-4. The origin of this drop could be due to severe sepsis conditions and/or to intrinsic properties of favipiravir metabolism. Dose-ranging studies should be performed in healthy volunteers to assess the concentrations and the tolerance that could be achieved with high doses. Trial registration ClinicalTrials.gov NCT02329054 PMID:28231247

Does contemporary vancomycin dosing achieve therapeutic targets in a heterogeneous clinical cohort of critically ill patients? Data from the multinational DALI study

PubMed Central

2014-01-01

Introduction The objective of this study was to describe the pharmacokinetics of vancomycin in ICU patients and to examine whether contemporary antibiotic dosing results in concentrations that have been associated with favourable response. Methods The Defining Antibiotic Levels in Intensive Care (DALI) study was a prospective, multicentre pharmacokinetic point-prevalence study. Antibiotic dosing was as per the treating clinician either by intermittent bolus or continuous infusion. Target trough concentration was defined as ≥15 mg/L and target pharmacodynamic index was defined as an area under the concentration-time curve over a 24-hour period divided by the minimum inhibitory concentration of the suspected bacteria (AUC0–24/MIC ratio) >400 (assuming MIC ≤1 mg/L). Results Data of 42 patients from 26 ICUs were eligible for analysis. A total of 24 patients received vancomycin by continuous infusion (57%). Daily dosage of vancomycin was 27 mg/kg (interquartile range (IQR) 18 to 32), and not different between patients receiving intermittent or continuous infusion. Trough concentrations were highly variable (median 27, IQR 8 to 23 mg/L). Target trough concentrations were achieved in 57% of patients, but more frequently in patients receiving continuous infusion (71% versus 39%; P = 0.038). Also the target AUC0–24/MIC ratio was reached more frequently in patients receiving continuous infusion (88% versus 50%; P = 0.008). Multivariable logistic regression analysis with adjustment by the propensity score could not confirm continuous infusion as an independent predictor of an AUC0–24/MIC >400 (odds ratio (OR) 1.65, 95% confidence interval (CI) 0.2 to 12.0) or a Cmin ≥15 mg/L (OR 1.8, 95% CI 0.4 to 8.5). Conclusions This study demonstrated large interindividual variability in vancomycin pharmacokinetic and pharmacodynamic target attainment in ICU patients. These data suggests that a re-evaluation of current vancomycin dosing recommendations in critically ill patients is needed to more rapidly and consistently achieve sufficient vancomycin exposure. PMID:24887569

Factors Contributing to the Off-Target Transport of Pyrethroid Insecticides From Urban Surfaces

PubMed Central

Jorgenson, Brant C.; Wissel-Tyson, Christopher; Young, Thomas M.

2013-01-01

Pyrethroid insecticides used in an urban and suburban context have been found in urban creek sediments and associated with toxicity in aquatic bioassays. The objectives of this study were to evaluate the main factors contributing to the off-target transport of pyrethroid insecticides from surfaces typical of residential landscapes. Controlled rainfall simulations over concrete, bare soil, and turf plots treated individually with pyrethroid insecticides in a suspension concentrate, an emulsifiable concentrate, or a granule formulation were conducted at different rainfall intensities and different product set-time intervals. Pyrethroid mass washoff varied by several orders of magnitude between experimental treatments. Suspension concentrate product application to concrete yielded significantly greater washoff than any other treatment; granule product application to turf yielded the least washoff. Fractional losses at 10 L of runoff ranged from 25.9% to 0.011% of pyrethroid mass applied and 10 L nominal mass losses ranged from 3,970 to 0.18 μg. Mass washoff depended principally on formulation and surface type combination and to a lesser degree set-time interval and rainfall intensity. Treatment effects were analyzed by ANOVA on main factors of formulation, surface type, and set time. Factor effects were not purely additive; a significant interaction between formulation and surface type was noted. PMID:22784034

High spatial resolution measurements of NO2 applying Topographic Target Light scattering-Differential Optical Absorption Spectroscopy (ToTaL-DOAS)

NASA Astrophysics Data System (ADS)

Frins, E.; Platt, U.; Wagner, T.

2008-06-01

Tomographic Target Light scattering - Differential Optical Absorption Spectroscopy (ToTaL-DOAS), also called Target-DOAS, is a novel experimental procedure to retrieve trace gas concentrations present in the low atmosphere. Scattered sunlight (partially or totally) reflected from natural or artificial targets of similar albedo located at different distances is analyzed to retrieve the concentration of different trace gases like NO2, SO2 and others. We report high spatial resolution measurements of NO2 mixing ratios in the city of Montevideo (Uruguay) observing three buildings as targets with a Mini-DOAS instrument. Our instrument was 146 m apart from the first building, 196 m from the second and 286 m from the third one. All three buildings are located along a main Avenue. We obtain temporal variation of NO2 mixing ratios between 30 ppb and 65 ppb (±2 ppb). Our measurements demonstrate that ToTaL-DOAS measurements can be made over very short distances. In polluted air masses, the retrieved absorption signal was found to be strong enough to allow measurements over distances in the range of several ten meters, and achieve a spatial resolution of 50 m approximately.

High spatial resolution measurements of NO2 applying Topographic Target Light scattering-Differential Optical Absorption Spectroscopy (ToTaL-DOAS)

NASA Astrophysics Data System (ADS)

Frins, E.; Platt, U.; Wagner, T.

2008-12-01

Topographic Target Light scattering - Differential Optical Absorption Spectroscopy (ToTaL-DOAS), also called Target-DOAS, is a novel experimental procedure to retrieve trace gas concentrations present in the low atmosphere. Scattered sunlight (diffuse or specular) reflected from natural or artificial targets located at different distances are analyzed to retrieve the spatial distribution of the concentration of different trace gases like NO2, SO2 and others. We report high spatial resolution measurements of NO2 mixing ratios in the city of Montevideo (Uruguay) observing three buildings as targets with a Mini-DOAS instrument. Our instrument was 146 m, 196 m, and 280 m apart from three different buildings located along a main Avenue. We obtain temporal variation of NO2 mixing ratios between 30 ppb and 65 ppb from measurements of November 2007 and mixing ratios up to 50 ppb from measurements of August and September 2008. Our measurements demonstrate that ToTaL-DOAS observations can be made over relative short distances. In polluted air masses, the retrieved absorption signal was found to be sufficiently strong to allow measurements over distances in the range of several tens of meters.

Population pharmacokinetics of rifampin in the treatment of Mycobacterium tuberculosis in Asian elephants.

PubMed

Egelund, E F; Isaza, R; Brock, A P; Alsultan, A; An, G; Peloquin, C A

2015-04-01

The objective of this study was to develop a population pharmacokinetic model for rifampin in elephants. Rifampin concentration data from three sources were pooled to provide a total of 233 oral concentrations from 37 Asian elephants. The population pharmacokinetic models were created using Monolix (version 4.2). Simulations were conducted using ModelRisk. We examined the influence of age, food, sex, and weight as model covariates. We further optimized the dosing of rifampin based upon simulations using the population pharmacokinetic model. Rifampin pharmacokinetics were best described by a one-compartment open model including first-order absorption with a lag time and first-order elimination. Body weight was a significant covariate for volume of distribution, and food intake was a significant covariate for lag time. The median Cmax of 6.07 μg/mL was below the target range of 8-24 μg/mL. Monte Carlo simulations predicted the highest treatable MIC of 0.25 μg/mL with the current initial dosing recommendation of 10 mg/kg, based upon a previously published target AUC0-24/MIC > 271 (fAUC > 41). Simulations from the population model indicate that the current dose of 10 mg/kg may be adequate for MICs up to 0.25 μg/mL. While the targeted AUC/MIC may be adequate for most MICs, the median Cmax for all elephants is below the human and elephant targeted ranges. © 2014 John Wiley & Sons Ltd.

Myocardial concentrations of fatty acids in dogs with dilated cardiomyopathy.

PubMed

Smith, Caren E; Freeman, Lisa M; Meydani, Mohsen; Rush, John E

2005-09-01

To compare myocardial concentrations of fatty acids in dogs with dilated cardiomyopathy (DCM) with concentrations in control dogs. Myocardial tissues from 7 dogs with DCM and 16 control dogs. Myocardial tissues were homogenized, and total fatty acids were extracted and converted to methyl esters. Myocardial concentrations of fatty acids were analyzed by use of gas chromatography and reported as corrected percentages. The amount of docosatetraenoic acid (C22:4 n-6) was significantly higher in myocardial samples from dogs with DCM (range, 0.223% to 0.774%; median, 0.451%), compared with the amount in samples obtained from control dogs (range, 0.166% to 0.621%; median, 0.280%). There were no significant differences between DCM and control dogs for concentrations of any other myocardial fatty acids. Although concentrations of most myocardial fatty acids did not differ significantly between dogs with DCM and control dogs, the concentration of docosatetraenoic acid was significantly higher in dogs with DCM. Additional investigation in a larger population is warranted to determine whether this is a primary or secondary effect of the underlying disease and whether alterations in fatty acids may be a target for intervention in dogs with DCM.

Vitamin D supplementation guidelines.

PubMed

Pludowski, Pawel; Holick, Michael F; Grant, William B; Konstantynowicz, Jerzy; Mascarenhas, Mario R; Haq, Afrozul; Povoroznyuk, Vladyslav; Balatska, Nataliya; Barbosa, Ana Paula; Karonova, Tatiana; Rudenka, Ema; Misiorowski, Waldemar; Zakharova, Irina; Rudenka, Alena; Łukaszkiewicz, Jacek; Marcinowska-Suchowierska, Ewa; Łaszcz, Natalia; Abramowicz, Pawel; Bhattoa, Harjit P; Wimalawansa, Sunil J

2018-01-01

Research carried out during the past two-decades extended the understanding of actions of vitamin D, from regulating calcium and phosphate absorption and bone metabolism to many pleiotropic actions in organs and tissues in the body. Most observational and ecological studies report association of higher serum 25-hydroxyvitamin D [25(OH)D] concentrations with improved outcomes for several chronic, communicable and non-communicable diseases. Consequently, numerous agencies and scientific organizations have developed recommendations for vitamin D supplementation and guidance on optimal serum 25(OH)D concentrations. The bone-centric guidelines recommend a target 25(OH)D concentration of 20ng/mL (50nmol/L), and age-dependent daily vitamin D doses of 400-800IU. The guidelines focused on pleiotropic effects of vitamin D recommend a target 25(OH)D concentration of 30ng/mL (75nmol/L), and age-, body weight-, disease-status, and ethnicity dependent vitamin D doses ranging between 400 and 2000IU/day. The wise and balanced choice of the recommendations to follow depends on one's individual health outcome concerns, age, body weight, latitude of residence, dietary and cultural habits, making the regional or nationwide guidelines more applicable in clinical practice. While natural sources of vitamin D can raise 25(OH)D concentrations, relative to dietary preferences and latitude of residence, in the context of general population, these sources are regarded ineffective to maintain the year-round 25(OH)D concentrations in the range of 30-50ng/mL (75-125nmol/L). Vitamin D self-administration related adverse effects, such as hypercalcemia and hypercalciuria are rare, and usually result from taking extremely high doses of vitamin D for a prolonged time. Copyright © 2017 Elsevier Ltd. All rights reserved.

Rapid QPCR-based assay for fecal Bacteroides spp. as a tool for assessing fecal contamination in recreational waters.

PubMed

Converse, Reagan R; Blackwood, A Denene; Kirs, Marek; Griffith, John F; Noble, Rachel T

2009-11-01

Concentrations of fecal indicator bacteria (FIB; e.g. Escherichia coli, and Enterococcus sp.) can only be used in limited ways for determining the source of fecal contamination in recreational waters because they cannot distinguish human from non-human fecal contamination. Several Bacteroides spp. have been suggested as potential alternative indicators. We have developed a rapid, culture-independent method for quantifying fecal Bacteroides spp. using quantitative PCR (QPCR) targeting the 16S rRNA gene. The assay specifically targets and quantifies the most common human Bacteroides spp. The details of the method are presented, including analyses of a wide range of fecal samples from different organisms. Specificity and performance of the QPCR assay were also tested via a laboratory experiment where human sewage and gull guano were inoculated into a range of environmental water samples. Concentrations of fecal Bacteroides spp., total Enterococcus sp., Enterococcus faecium, Enterococcus faecalis, and Enterococcus casseliflavus were measured using QPCR, and total Enterococcus sp. and E. coli were quantified by membrane filtration (MF). Samples spiked with gull guano were highly concentrated with total Enterococcus sp., E. coli, E. faecalis, and E. casseliflavus, demonstrating that these indicators are prominent in animal feces. On the other hand, fecal Bacteroides spp. concentrations were high in samples containing sewage and were relatively low in samples spiked with gull guano. Sensitivity and specificity results suggest that the rapid fecal Bacteroides spp. QPCR assay may be a useful tool to effectively predict the presence and concentration of human-specific fecal pollution.

The occurrence and distribution of a group of organic micropollutants in Mexico City's water sources.

PubMed

Félix-Cañedo, Thania E; Durán-Álvarez, Juan C; Jiménez-Cisneros, Blanca

2013-06-01

The occurrence and distribution of a group of 17 organic micropollutants in surface and groundwater sources from Mexico City was determined. Water samples were taken from 7 wells, 4 dams and 15 tanks where surface and groundwater are mixed and stored before distribution. Results evidenced the occurrence of seven of the target compounds in groundwater: salicylic acid, diclofenac, di-2-ethylhexylphthalate (DEHP), butylbenzylphthalate (BBP), triclosan, bisphenol A (BPA) and 4-nonylphenol (4-NP). In surface water, 11 target pollutants were detected: same found in groundwater as well as naproxen, ibuprofen, ketoprofen and gemfibrozil. In groundwater, concentration ranges of salicylic acid, 4-NP and DEHP, the most frequently found compounds, were 1-464, 1-47 and 19-232 ng/L, respectively; while in surface water, these ranges were 29-309, 89-655 and 75-2,282 ng/L, respectively. Eleven target compounds were detected in mixed water. Concentrations in mixed water were higher than those determined in groundwater but lower than the detected in surface water. Different to that found in ground and surface water, the pesticide 2,4-D was found in mixed water, indicating that some pollutants can reach areas where they are not originally present in the local water sources. Concentration of the organic micropollutants found in this study showed similar to lower to those reported in water sources from developed countries. This study provides information that enriches the state of the art on the occurrence of organic micropollutants in water sources worldwide, notably in megacities of developing countries. Copyright © 2013 Elsevier B.V. All rights reserved.

Water-quality and physical characteristics of streams in the Treyburn development area of Falls Lake watershed, North Carolina, 1994–98

USGS Publications Warehouse

Oblinger, C.J.; Cuffney, T.F.; Meador, M.R.; Garrett, R.G.

2002-01-01

Treyburn is a 5,400-acre planned, mixed-use development in the upper Neuse River Basin of North Carolina. The development, which began in 1986, is located in the Falls Lake watershed near three water-supply reservoirs-Lake Michie to the north, Falls Lake to the southeast, and Little River Reservoir to the west. A study began in 1988 to determine the water-quality characteristics of surface waters in and around the Treyburn development area.Data to characterize water quality at five different sites were collected from July 1994 through September 1998. Data from a previous study are available for some sites for the period 1988–93. The sites were selected to characterize water quality and quantity in and near the Treyburn development and included an undeveloped basin, a relatively small basin containing single-family residences and a golf course, a basin downstream from the western part of the development with some industrial land use, and two basins unaffected by the development where agricultural land is being converted to urban and forested land use.Suspended-sediment concentrations ranged from less than 1 to 581 milligrams per liter and were fairly uniform among the five sites. Median suspended-sediment concentrations ranged from 12 to 21 milligrams per liter. Few concentrations of metals and trace elements, except aluminum, iron, and manganese, exceeded the laboratory reporting levels or water-quality criteria. At one site, concentrations of silver exceeded both the action level and the reporting level; copper was detected at each site and exceeded the action level of 7 micrograms per liter at one site.The lowest range and median concentrations of total organic nitrogen, nitrate, ammonia, total phosphorus, and orthophosphorus occurred in the relatively undisturbed, forested site. The maximum concentration of organic nitrogen (1.97 milligrams per liter) occurred at one of the sites unaffected by the Treyburn development where agricultural land is being converted to urban land use. At all sites, ammonia concentrations ranged from less than 0.02 to 0.36 milligram per liter, and median concentrations were near the reporting level. Nitrate concentrations ranged from less than 0.05 to 0.80 milligram per liter.Phosphorus concentrations at all of the Treyburn study sites were low compared to phosphorus concentrations that typically exceed 0.1 milligram per liter at sites sampled nationally for the U.S. Geological Survey National Water-Quality Assessment Program, including the Albemarle-Pamlico study area in North Carolina. Total phosphorus concentrations ranged from less than 0.01 to 0.87 milligram per liter, and orthophosphorus concentrations ranged from less than 0.01 to 0.76 milligram per liter as phosphorus. The maximum concentrations of total phosphorus and orthophosphorus occurred at the Treyburn residential and golf-course site, likely as a result of the fertilizer applications associated with these two types of land use.Of the 119 different pesticides tested, 11 were detected in concentrations that exceeded the laboratory reporting levels, though in very low concentrations. Water samples from the residential and golf-course site contained the greatest number of pesticides (10). Five of six samples collected at this site had detectable concentrations of simazine, atrazine, and pendimethalin-all herbicides used to control weeds in crops or turf.Channel geometry was assessed at eight sites in the study area in February 1997. These sites were separated into three groups based on mean bank angle and mean channel width-to-depth ratios. Channel gradient ranged from 0.04 to 1.63 percent, and mean cross sectional area ranged from 31 to 1,227 square feet.Three macroinvertebrate samples were collected from each of 10 sites. These three samples were from areas designated as richest targeted habitats, depositional targeted habitats, and qualitative multitargeted habitats. Over 230 taxa were identified fromthese 10 sites. The North Carolina Biotic Indices ranged from 4.98 (excellent) to 6.82 (fair). River sites tended to have higher total taxa richness (91-108) than did the small, intermittent streams (49–84) or the midsize Mountain Creek (85). Intermittent streams represent fairly hostile environments for most aquatic organisms. Samples from richest targeted habitats typically were more than twice as rich as samples from depositional targeted habitats and represented from 50 to 75 percent of the taxa found at each site (mean of 62 percent). The industrial site lacked many of the mayfly taxa that were present at the undeveloped site. Mayflies are very sensitive to metals contamination, and their absence may indicate a possible problem. The supporting chemical information is not available for the industrial site, and additional study would be necessary to substantiate this possibility. The two sites with residential and golf-course land use tended to support more different types of sensitive invertebrates (that is, mayflies, stoneflies, and caddis flies) than did the forested/residential site, though the abundances of these taxa were very similar. Land-use effects were not evident based on a comparison among these sites.Indirect gradient analysis was used to determine patterns in the distribution of invertebrates and to examine the relations between these patterns and physical and chemical site characteristics determined in this study. This analysis supports the contention that the dominant factors accounting for the distribution of benthic invertebrates are associated with natural factors, such as basin size, rather than land use.Constituent loads at five study sites were calculated for nutrients, suspended sediment, and total organic carbon. The median annual total nitrogen yield ranged from 0.635 to 1.63 tons per square mile. The median annual phosphorus yield ranged from 0.046 to 0.619 ton per square mile, and the median annual orthophosphate yield ranged from 0.022 to 0.379 ton per square mile. Orthophosphate accounted for more than half of the phosphorus yield at the residential and golf-course site.The maximum suspended-sediment yield was 422 tons per square mile, and the minimum yield was 32 tons per square mile. The suspended-sediment yield at one of the sites unaffected by the Treyburn development where agricultural was being converted to urban land use was high compared to other forested basins in the Piedmont of North Carolina.Total organic carbon data sufficient for estimating loads were available at three of the five sites. Of these three sites, the undeveloped site had substantially more organic carbon yield than the other two sites.The only significant water-quality trend (alpha=0.05) was a downward trend for total nitrogen and organic nitrogen at the undeveloped site. The trend slope was small, only 0.019 milligram per liter as nitrogen or less than 9 percent of the median organic nitrogen concentration. No trend was observed for nitrite plus nitrate or for ammonia, indicating that the downward trend in total nitrogen was due only to organic nitrogen.

Determination of Depleted Uranium in Environmental Bio-monitor Samples and Soil from Target sites in Western Balkan Region

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

Sahoo, Sarata K.; Enomoto, Hiroko; Tokonami, Shinji

2008-08-07

Lichen and Moss are widely used to assess the atmospheric pollution by heavy metals and radionuclides. In this paper, we report results of uranium and its isotope ratios using mass spectrometric measurements (followed by chemical separation procedure) for mosses, lichens and soil samples from a depleted uranium (DU) target site in western Balkan region. Samples were collected in 2003 from Han Pijesak (Republika Srpska in Bosnia and Hercegovina). Inductively coupled plasma mass spectrometry (ICP-MS) measurements show the presence of high concentration of uranium in some samples. Concentration of uranium in moss samples ranged from 5.2-755.43 Bq/Kg. We have determined {supmore » 235}U/{sup 238}U isotope ratio using thermal ionization mass spectrometry (TIMS) from the samples with high uranium content and the ratios are in the range of 0.002097-0.002380. TIMS measurement confirms presence of DU in some samples. However, we have not noticed any traces of DU in samples containing lesser amount of uranium or from any samples from the living environment of same area.« less

Targeting polyamine metabolism for cancer therapy and prevention

PubMed Central

Murray-Stewart, Tracy R.; Woster, Patrick M.; Casero, Robert A.

2017-01-01

The chemically simple, biologically complex eukaryotic polyamines, spermidine and spermine, are positively charged alkylamines involved in many crucial cellular processes. Along with their diamine precursor putrescine, their normally high intracellular concentrations require fine attenuation by multiple regulatory mechanisms to keep these essential molecules within strict physiologic ranges. Since the metabolism of and requirement for polyamines are frequently dysregulated in neoplastic disease, the metabolic pathway and functions of polyamines provide rational drug targets; however, these targets have been difficult to exploit for chemotherapy. It is the goal of this article to review the latest findings in the field that demonstrate the potential utility of targeting the metabolism and function of polyamines as strategies for both chemotherapy and, possibly more importantly, chemoprevention. PMID:27679855

Simultaneous determination of four trace level endocrine disrupting compounds in environmental samples by solid-phase microextraction coupled with HPLC.

PubMed

Wang, Lingling; Zhang, Zhenzhen; Xu, Xu; Zhang, Danfeng; Wang, Fang; Zhang, Lei

2015-09-01

A simple, rapid, sensitive and effective method for the simultaneous determination of four endocrine disrupting compounds (EDCs) (bisphenol A (BPA), bisphenol F (BPF), bisphenol AF (BPAF) and bisphenol AP (BPAP)) in environment water samples based on solid-phase microextraction (SPME) coupled with high performance liquid chromatography (HPLC) was developed. Multi-wall carbon nanotubes (MWCNTs) adsorbents showed a good affinity to the target analytes. These compounds were rapidly extracted within 10 min. Various experimental parameters that could affect the extraction efficiencies had been investigated in detail. Under the optimum conditions, the enrichment factors of the method for the target EDCs were found to be 500. Satisfactory precision and accuracy of the method were obtained in a low concentration range of 2.0-500.0 ng mL(-1). The method detection limits were in the range of 0.10-0.30 ng mL(-1). The high pre-concentration rate and efficiency of the method ensure its successful application in extraction of trace EDCs from large volumes of environmental water samples. The extraction recoveries in real samples ranged from 85.3% to 102.5% with the relative standard deviations (n=5) less than 3.74%. Copyright © 2015 Elsevier B.V. All rights reserved.

Organochlorine pesticides (OCPs) and polychlorinated biphenyls (PCBs) in sediments from the Gulf of Batabanó, Cuba.

PubMed

Alonso-Hernandez, C M; Mesa-Albernas, M; Tolosa, I

2014-01-01

The spatial distribution of various organochlorinated compounds, e.g. PCBs, DDTs, HCB and HCHs, were investigated in sediments of the Gulf of Batabanó, Cuba. Among the target organochlorine compounds measured, ΣDDT isomers were the predominant contaminant with concentrations ranging from 0.019 to 1.27 ng g(-1)dry wt. Lindane was present at very low concentrations in the range n.d. to 0.05 ng g(-1), while PCBs and other organochlorine pesticide residues, such as HCB, Heptaclor, Aldrin and Mirex were lower than detection limits (∼0.010 ng g(-1)). According to established sediment quality guidelines, the OCPs concentrations encountered in the surface sediments are probably not having an adverse effect on sediment dwelling organisms. Compared to concentrations reported in coastal environments from other parts of the world, PCBs and OCs concentrations in surface sediments of Batabanó Gulf were low and similar to the reported for remote and pristine environments. These results contribute to the sparse regional database for organochlorinated compounds in the Caribbean marine environment. Copyright © 2013. Published by Elsevier Ltd.

Pharmaceuticals and consumer products in four wastewater treatment plants in urban and suburb areas of Shanghai.

PubMed

Sui, Qian; Wang, Dan; Zhao, Wentao; Huang, Jun; Yu, Gang; Cao, Xuqi; Qiu, Zhaofu; Lu, Shuguang

2015-04-01

Ten pharmaceuticals and two consumer products were investigated in four wastewater treatment plants (WWTPs) in Shanghai, China. The concentrations of target compounds in the wastewater influents ranged from below the limit of quantification (LOQ) to 9340 ng/L, with the frequency of detection of 31-100%, and the removal efficiencies were observed to be -82 to 100% in the four WWTPs. Concentrations of most target compounds (i.e. diclofenac, caffeine, metoprolol, sulpiride) in the wastewater influents were around three to eight times higher in urban WWTPs than in suburb ones, probably due to the different population served and lifestyles. Mean concentrations of target compounds in the wastewater influent generally decreased by 5-76% after rainfall due to the dilution of raw sewage by rainwater, which infiltrated into the sewer system. In the WWTPs located in the suburb area, the increased flow of wastewater influent led to a shortened hydraulic retention time (HRT) and decreased removal efficiencies of some compounds. On the contrary, the influence of rainfall was not significant on the removal efficiencies of investigated compounds in urban WWTPs, probably due to the almost unchanged influent flow, good removal performance, or bypass system employed.

Sub-lethal effects of the neurotoxic pyrethroid insecticide Fastac 50EC on the general motor and locomotor activities of the non-targeted beneficial carabid beetle Platynus assimilis (Coleoptera: Carabidae).

PubMed

Tooming, Ene; Merivee, Enno; Must, Anne; Sibul, Ivar; Williams, Ingrid

2014-06-01

Sub-lethal effects of pesticides on behavioural endpoints are poorly studied in carabids (Coleoptera: Carabidae) though changes in behaviour caused by chemical stress may affect populations of these non-targeted beneficial insects. General motor activity and locomotion are inherent in many behavioural patterns, and changes in these activities that result from xenobiotic influence mirror an integrated response of the insect to pesticides. Influence of pyrethroid insecticides over a wide range of sub-lethal doses on the motor activities of carabids still remains unclear. Video tracking of Platynus assimilis showed that brief exposure to alpha-cypermethrin at sub-lethal concentrations ranged from 0.01 to 100 mg L(-1) caused initial short-term (< 2 h) locomotor hyperactivity followed by a long-term (>24 h) locomotor hypo-activity. In addition, significant short- and long-term concentration and time-dependent changes occurred in general motor activity patterns and rates. Conspicuous changes in motor activity of Platynus assimilis beetles treated at alpha-cypermethrin concentrations up to 75,000-fold lower than maximum field recommended concentration (MFRC) suggest that many, basic fitness-related behaviours might be severely injured as well. These changes may negatively affect carabid populations in agro-ecosystems. Long-term hypo-activity could directly contribute to decreased trap captures of carabids frequently observed after insecticide application in the field. © 2013 Society of Chemical Industry.

Comparison of three point-of-care blood glucose meters for use in adult and juvenile alpacas.

PubMed

Tennent-Brown, Brett S; Koenig, Amie; Williamson, Lisa H; Boston, Raymond C

2011-08-01

To compare the performance of 3 point-of-care glucose meters in adult and juvenile alpacas with that of a laboratory-based analyzer. Evaluation study. 35 adult alpacas and 21 juvenile alpacas. Whole blood samples obtained via jugular venipuncture were tested with all 3 point-of-care glucose meters; plasma samples were also tested with 1 of those meters. Glucose concentrations determined by use of the point-of-care meters were compared with results from the laboratory-based analyzer. Plasma glucose concentrations determined by use of the laboratory-based analyzer ranged from 36 to 693 mg/dL. Over the entire range of glucose concentrations tested, the Lin concordance correlation coefficient (agreement) was significant and excellent for all comparisons. Concordance decreased for 1 glucometer when testing whole blood samples over a narrower range of glucose concentrations (50 to 200 mg/dL). Bias was typically small (< 10 mg/dL) for 3 of the 4 comparisons but considerable for 1 meter with the use of whole blood. The limits of agreement were wide for all comparisons over the entire range of glucose concentrations tested but decreased to within acceptable limits when the narrower glucose range (50 to 200 mg/dL) was analyzed for 3 of the comparisons. For samples with a PCV < 25%, bias and the limits of agreement were greater for one of the meters tested. Discrepancies between point-of-care glucose meters and reference techniques can be considerable in alpacas, emphasizing the importance of assessing individual meter performance in a target population.

Magnetic catechin-dextran conjugate as targeted therapeutic for pancreatic tumour cells.

PubMed

Vittorio, Orazio; Voliani, Valerio; Faraci, Paolo; Karmakar, Biswajit; Iemma, Francesca; Hampel, Silke; Kavallaris, Maria; Cirillo, Giuseppe

2014-06-01

Catechin-dextran conjugates have recently attracted a lot of attention due to their anticancer activity against a range of cancer cells. Magnetic nanoparticles have the ability to concentrate therapeutically important drugs due to their magnetic-spatial control and provide opportunities for targeted drug delivery. Enhancement of the anticancer efficiency of catechin-dextran conjugate by functionalisation with magnetic iron oxide nanoparticles. Modification of the coating shell of commercial magnetic nanoparticles (Endorem) composed of dextran with the catechin-dextran conjugate. Catechin-dextran conjugated with Endorem (Endo-Cat) increased the intracellular concentration of the drug and it induced apoptosis in 98% of pancreatic tumour cells placed under magnetic field. The conjugation of catechin-dextran with Endorem enhances the anticancer activity of this drug and provides a new strategy for targeted drug delivery on tumour cells driven by magnetic field. The ability to spatially control the delivery of the catechin-dextran by magnetic field makes it a promising agent for further application in cancer therapy.

Isotope-dilution gas chromatography-mass spectrometry coupled with injection-port butylation for the determination of 4-t-octylphenol, 4-nonylphenols and bisphenol A in human urine.

PubMed

Chung, Shuang-Hung; Ding, Wang-Hsien

2018-02-05

An analytical method that utilizes isotope-dilution gas chromatography-mass spectrometry (ID-GC-MS) coupled with injection-port butylation was developed. The method was validated, and confirmed to be able to determine the presence of three commonly detected endocrine-disrupting chemicals (EDCs: 4-tert-octylphenol (4-t-OP), 4-nonylphenols (4-NPs) and bisphenol A (BPA)) in human urine with high precision and accuracy. After sample preparation by solid-phase extraction, the extract was introduced into GC-MS via injection-port butylation. The butylated target analytes were identified and quantified by using ion-trap mass spectrometry operating in the selected-ion-storage mode, and employing the measurement of peak area ratios of the butylated target analytes and labeled-analogues in the samples and calibration standards. The labeled-analogues were also used to correct the variations associated with the analysis and matrix effect. The limits of quantitation (LOQs) ranged from 0.1 to 0.3ng/mL. High precisions for both intra- and inter-day analysis ranged from 1 to 6%, and excellent accuracy (mean recovery) ranged from 92 to 105% on two concentration levels. In human urine, the total concentrations of three selected EDCs varied from 1.28 to 7.14ng/mL. 4-NPs were detected within all collected samples. The developed method allows accurate analysis of trace-level of EDCs in urine, and these target EDCs could act as useful biomarkers to assess exposure in biomonitoring studies and programs. Copyright © 2017 Elsevier B.V. All rights reserved.

Quantification of DNA using the luminescent oxygen channeling assay.

PubMed

Patel, R; Pollner, R; de Keczer, S; Pease, J; Pirio, M; DeChene, N; Dafforn, A; Rose, S

2000-09-01

Simplified and cost-effective methods for the detection and quantification of nucleic acid targets are still a challenge in molecular diagnostics. Luminescent oxygen channeling assay (LOCI(TM)) latex particles can be conjugated to synthetic oligodeoxynucleotides and hybridized, via linking probes, to different DNA targets. These oligomer-conjugated LOCI particles survive thermocycling in a PCR reaction and allow quantified detection of DNA targets in both real-time and endpoint formats. The endpoint DNA quantification format utilized two sensitizer bead types that are sensitive to separate illumination wavelengths. These two bead types were uniquely annealed to target or control amplicons, and separate illuminations generated time-resolved chemiluminescence, which distinguished the two amplicon types. In the endpoint method, ratios of the two signals allowed determination of the target DNA concentration over a three-log range. The real-time format allowed quantification of the DNA target over a six-log range with a linear relationship between threshold cycle and log of the number of DNA targets. This is the first report of the use of an oligomer-labeled latex particle assay capable of producing DNA quantification and sequence-specific chemiluminescent signals in a homogeneous format. It is also the first report of the generation of two signals from a LOCI assay. The methods described here have been shown to be easily adaptable to new DNA targets because of the generic nature of the oligomer-labeled LOCI particles.

Reflective measurement of water concentration using millimeter wave illumination

NASA Astrophysics Data System (ADS)

Sung, Shijun; Bennett, David; Taylor, Zachary; Bajwa, Neha; Tewari, Priyamvada; Maccabi, Ashkan; Culjat, Martin; Singh, Rahul; Grundfest, Warren

2011-04-01

THz and millimeter wave technology have shown the potential to become a valuable medical imaging tool because of its sensitivity to water and safe, non-ionizing photon energy. Using the high dielectric constant of water in these frequency bands, reflectionmode THz sensing systems can be employed to measure water content in a target with high sensitivity. This phenomenology may lead to the development of clinical systems to measure the hydration state of biological targets. Such measurements may be useful in fast and convenient diagnosis of conditions whose symptoms can be characterized by changes in water concentration such as skin burns, dehydration, or chemical exposure. To explore millimeter wave sensitivity to hydration, a reflectometry system is constructed to make water concentration measurements at 100 GHz, and the minimum detectable water concentration difference is measured. This system employs a 100 GHz Gunn diode source and Golay cell detector to perform point reflectivity measurements of a wetted polypropylene towel as it dries on a mass balance. A noise limited, minimum detectable concentration difference of less than 0.5% by mass can be detected in water concentrations ranging from 70% to 80%. This sensitivity is sufficient to detect hydration changes caused by many diseases and pathologies and may be useful in the future as a diagnostic tool for the assessment of burns and other surface pathologies.

Current-use flame retardants in the water of Lake Michigan tributaries

USGS Publications Warehouse

Guo, Jiehong; Romanak, Kevin; Westenbroek, Stephen M.; Hites, Ronald A.; Venier, Marta

2017-01-01

In this study, we measured the concentrations of 65 flame retardants in water samples from five Lake Michigan tributaries. These flame retardants included organophosphate esters (OPEs), brominated flame retardants (BFRs), and Dechlorane-related compounds. A total of 59 samples, including both the particulate and the dissolved phases, were collected from the Grand, Kalamazoo, Saint Joseph, and Lower Fox rivers and from the Indiana Harbor and Ship Canal (IHSC) in 2015. OPEs were the most abundant among the targeted compounds with geometric mean concentrations ranging from 20 to 54 ng/L; OPE concentrations were comparable among the five tributaries. BFR concentrations were about 1 ng/L, and the most-abundant compounds were bis(2-ethylhexyl) tetrabromophthalate, 2-ethylhexyl 2,3,4,5-tetrabromobenzoate, and decabromodiphenyl ether. The highest BFR concentrations were measured in either the IHSC or the Saint Joseph River. The dechlorane-related compounds were detected at low concentrations (<1 pg/L). The fraction of target compounds in the particulate phase relative to the dissolved phase varied by chemical and tended to increase with their octanol–water partition coefficient. The chemical loading from all the five tributaries into Lake Michigan were <10 kg/year for the BFRs and about 500 kg/year for the OPEs.

Near-infrared diode laser absorption sensor for rapid measurements of temperature and water vapor in a shock tube

NASA Astrophysics Data System (ADS)

Li, H.; Farooq, A.; Jeffries, J. B.; Hanson, R. K.

2007-11-01

A fast-response (100 kHz) tunable diode laser absorption sensor is developed for measurements of temperature and H2O concentration in shock tubes, e.g. for studies of combustion chemistry. Gas temperature is determined from the ratio of fixed-wavelength laser absorption of two H2O transitions near 7185.60 cm-1 and 7154.35 cm-1, which are selected using design rules for the target temperature range of 1000-2000 K and pressure range of 1-2 atm. Wavelength modulation spectroscopy is employed with second-harmonic detection (WMS-2f) to improve the sensor sensitivity and accuracy. Normalization of the second-harmonic signal by the first-harmonic signal is used to remove the need for calibration and minimize interference from emission, scattering, beam steering, and window fouling. The laser modulation depth for each H2O transition is optimized to maximize the WMS-2f signal for the target test conditions. The WMS-2f sensor is first validated in mixtures of H2O and Ar in a heated cell for the temperature range of 500-1200 K (P=1 atm), yielding an accuracy of 1.9% for temperature and 1.4% for H2O concentration measurements. Shock wave tests with non-reactive H2O-Ar mixtures are then conducted to demonstrate the sensor accuracy (1.5% for temperature and 1.4% for H2O concentration) and response time at higher temperatures (1200-1700 K, P=1.3-1.6 atm).

An injection and mixing element for delivery and monitoring of inhaled nitric oxide.

PubMed

Martin, Andrew R; Jackson, Chris; Fromont, Samuel; Pont, Chloe; Katz, Ira M; Caillobotte, Georges

2016-08-30

Inhaled nitric oxide (NO) is a selective pulmonary vasodilator used primarily in the critical care setting for patients concurrently supported by invasive or noninvasive positive pressure ventilation. NO delivery devices interface with ventilator breathing circuits to inject NO in proportion with the flow of air/oxygen through the circuit, in order to maintain a constant, target concentration of inhaled NO. In the present article, a NO injection and mixing element is presented. The device borrows from the design of static elements to promote rapid mixing of injected NO-containing gas with breathing circuit gases. Bench experiments are reported to demonstrate the improved mixing afforded by the injection and mixing element, as compared with conventional breathing circuit adapters, for NO injection into breathing circuits. Computational fluid dynamics simulations are also presented to illustrate mixing patterns and nitrogen dioxide production within the element. Over the range of air flow rates and target NO concentrations investigated, mixing length, defined as the downstream distance required for NO concentration to reach within ±5 % of the target concentration, was as high as 47 cm for the conventional breathing circuit adapters, but did not exceed 7.8 cm for the injection and mixing element. The injection and mixing element has potential to improve ease of use, compatibility and safety of inhaled NO administration with mechanical ventilators and gas delivery devices.

Body burden of pesticides and wastewater-derived pollutants on freshwater invertebrates: Method development and application in the Danube River.

PubMed

Inostroza, Pedro A; Wicht, Anna-Jorina; Huber, Thomas; Nagy, Claudia; Brack, Werner; Krauss, Martin

2016-07-01

While environmental risk assessment is typically based on toxicant concentrations in water and/or sediment, awareness is increasing that internal concentrations or body burdens are the key to understand adverse effects in organisms. In order to link environmental micropollutants as causes of observed effects, there is an increasing demand for methods to analyse these chemicals in organisms. Here, a multi-target screening method based on pulverised liquid extraction (PuLE) and a modified QuEChERS approach with an additional hexane phase was developed. It is capable to extract and quantify organic micropollutants of diverse chemical classes in freshwater invertebrates. The method was tested on gammarids from the Danube River (within the Joint Danube Survey 3) and target compounds were analysed by liquid chromatography-tandem mass spectrometry (LC-MS/MS). Furthermore, a non-target screening using high resolution-tandem mass spectrometry (LC-HRMS/MS) was conducted. A total of 17 pollutants were detected and/or quantified in gammarids at low concentrations. Pesticide concentrations ranged from 0.1 to 6.52 ng g(-1) (wet weight), those of wastewater-derived pollutants from 0.1 to 2.83 ng g(-1) (wet weight). The presence of wastewater-derived pollutants was prominent at all spots sampled. Using non-target screening, we could successfully identify several chlorinated compounds. These results demonstrate for the first time the presence of pesticides and wastewater-derived pollutants in invertebrates of the Danube River. Copyright © 2016 Elsevier Ltd. All rights reserved.

EFFECTS OF TRIBUTYLTIN ON CA2+ HOMEOSTASIS AND MECHANISMS CONTROLLING CELL CYCLING IN SEA URCHIN EGGS (R823881)

EPA Science Inventory

Abstract

Tributyltin (TBT) is one of the widespread organotins in the marine environment: we have investigated its cellular targets in the eggs of the marine invertebrate sea urchin Paracentrotus lividus. TBT was used at concentrations ranging from 10^-9

Digital PCR Modeling for Maximal Sensitivity, Dynamic Range and Measurement Precision

PubMed Central

Majumdar, Nivedita; Wessel, Thomas; Marks, Jeffrey

2015-01-01

The great promise of digital PCR is the potential for unparalleled precision enabling accurate measurements for genetic quantification. A challenge associated with digital PCR experiments, when testing unknown samples, is to perform experiments at dilutions allowing the detection of one or more targets of interest at a desired level of precision. While theory states that optimal precision (Po) is achieved by targeting ~1.59 mean copies per partition (λ), and that dynamic range (R) includes the space spanning one positive (λL) to one negative (λU) result from the total number of partitions (n), these results are tempered for the practitioner seeking to construct digital PCR experiments in the laboratory. A mathematical framework is presented elucidating the relationships between precision, dynamic range, number of partitions, interrogated volume, and sensitivity in digital PCR. The impact that false reaction calls and volumetric variation have on sensitivity and precision is next considered. The resultant effects on sensitivity and precision are established via Monte Carlo simulations reflecting the real-world likelihood of encountering such scenarios in the laboratory. The simulations provide insight to the practitioner on how to adapt experimental loading concentrations to counteract any one of these conditions. The framework is augmented with a method of extending the dynamic range of digital PCR, with and without increasing n, via the use of dilutions. An example experiment demonstrating the capabilities of the framework is presented enabling detection across 3.33 logs of starting copy concentration. PMID:25806524

Human exposure to carcinogens in ambient air in Denmark, Finland and Sweden

NASA Astrophysics Data System (ADS)

Fauser, P.; Ketzel, M.; Becker, T.; Plejdrup, M. S.; Brandt, J.; Gidhagen, L.; Omstedt, G.; Skårman, T.; Bartonova, A.; Schwarze, P.; Karvosenoja, N.; Paunu, V.-V.; Kukkonen, J.; Karppinen, A.

2017-10-01

The concentrations of seventeen pollutants (particulate mass fractions PM2.5 and PM10, a range of metals, inorganic gases and organic compounds) are for the first time analyzed in a screening of the carcinogenic risk at a resolution of 1 × 1 km2 in ambient air in three Nordic countries. Modelled annual mean air concentrations in 2010 show no exceedances of the EU air quality limit, guideline or target values. The only modelled exceedance of US-EPA 1:100,000 cancer risk concentrations (0.12 ng/m3, US-EPA IRIS, 2015) occurs for B(a)P in Denmark, for approximately 80% of the Danish population. However, the EU target value threshold of 1 ng/m3 for B(a)P is not exceeded in the modelled values in any parts of Denmark. No emission data for B(a)P were available for the whole domain of the other two considered Nordic countries and important uncertainties are still related to the emissions. Long-range transport is significant for the concentrations of all of the considered pollutants, except for B(a)P that commonly originates mostly from local residential wood combustion. The ambient air concentrations of NOx, SO2, Cd, Cr and Pb also have significant contributions from national sources; 45-65% for NOx and SO2, and for the metals from 15 to 60% in urban areas and from 1 to 20% in rural areas, within the considered Nordic area. High national contributions occur especially in urban air, due to primarily road traffic, residential wood combustion, energy production and industrial point sources. It is recommended to monitor the influence from residential wood combustion more extensively, and to analyze longer time trends for long-term human exposure.

A Novel Tumor-Activated Prodrug Strategy Targeting Ferrous Iron Is Effective in Multiple Preclinical Cancer Models

PubMed Central

2016-01-01

Here we describe a new approach for tumor targeting in which augmented concentrations of Fe(II) in cancer cells and/or the tumor microenvironment triggers drug release from an Fe(II)-reactive prodrug conjugate. The 1,2,4-trioxolane scaffold developed to enable this approach can in principle be applied to a broad range of cancer therapeutics and is illustrated here with Fe(II)-targeted forms of a microtubule toxin and a duocarmycin-class DNA-alkylating agent. We show that the intrinsic reactivity/toxicity of the duocarmycin analog is masked in the conjugated form and this greatly reduced toxicity in mice. This in turn permitted elevated dosing levels, leading to higher systemic exposure and a significantly improved response in tumor xenograft models. Overall our results suggest that Fe(II)-dependent drug delivery via trioxolane conjugates could have significant utility in expanding the therapeutic index of a range of clinical and preclinical stage cancer chemotherapeutics. PMID:27936709

Highly sensitive detection of target molecules using a new fluorescence-based bead assay

NASA Astrophysics Data System (ADS)

Scheffler, Silvia; Strauß, Denis; Sauer, Markus

2007-07-01

Development of immunoassays with improved sensitivity, specificity and reliability are of major interest in modern bioanalytical research. We describe the development of a new immunomagnetic fluorescence detection (IM-FD) assay based on specific antigen/antibody interactions and on accumulation of the fluorescence signal on superparamagnetic PE beads in combination with the use of extrinsic fluorescent labels. IM-FD can be easily modified by varying the order of coatings and assay conditions. Depending on the target molecule, antibodies (ABs), entire proteins, or small protein epitopes can be used as capture molecules. The presence of target molecules is detected by fluorescence microscopy using fluorescently labeled secondary or detection antibodies. Here, we demonstrate the potential of the new assay detecting the two tumor markers IGF-I and p53 antibodies in the clinically relevant concentration range. Our data show that the fluorescence-based bead assay exhibits a large dynamic range and a high sensitivity down to the subpicomolar level.

Smart multifunctional nanoagents for in situ monitoring of small molecules with a switchable affinity towards biomedical targets

NASA Astrophysics Data System (ADS)

Shevchenko, Konstantin G.; Cherkasov, Vladimir R.; Nikitina, Irina L.; Babenyshev, Andrey V.; Nikitin, Maxim P.

2018-02-01

The great diversity of nanomaterials provides ample opportunities for constructing effective agents for biomedical applications ranging from biosensing to drug delivery. Multifunctional nanoagents that combine several features in a single particle are of special interest due to capabilities that substantially exceed those of molecular drugs. An ideal theranostic agent should simultaneously be an advanced biosensor to identify a disease and report the diagnosis and a biomedical actuator to treat the disease. While many approaches were developed to load a nanoparticle with various drugs for actuation of the diseased cells (e.g., to kill them), the nanoparticle-based approaches for the localized biosensing with real-time reporting of the marker concentration severely lag behind. Here, we show a smart in situ nanoparticle-based biosensor/actuator system that dynamically and reversibly changes its structural and optical properties in response to a small molecule marker to allow real-time monitoring of the marker concentration and adjustment of the system ability to bind its biomedical target. Using the synergistic combination of signal readout based on the localized surface plasmon resonance and an original method of fabrication of smart ON/OFF-switchable nanoagents, we demonstrate reversible responsiveness of the system to a model small molecule marker (antibiotic chloramphenicol) in a wide concentration range. The proposed approach can be used for the development of advanced multifunctional nanoagents for theranostic applications.

Pharmaceuticals and personal care products (PPCPs) and endocrine disrupting chemicals (EDCs) in stormwater canals and Bayou St. John in New Orleans, Louisiana, USA.

PubMed

Boyd, Glen R; Palmeri, Jordan M; Zhang, Shaoyuan; Grimm, Deborah A

2004-10-15

Samples were collected from two stormwater canals and a recreational urban waterway known as Bayou St. John in New Orleans, Louisiana, USA and analyzed for a range of pharmaceuticals and personal care products (PPCPs) and endocrine disrupting chemicals (EDCs). Concentrations of 7 PPCPs and EDCs were measured by a method that provides for simultaneous extraction and quantification of the following compounds: clofibric acid, naproxen, ibuprofen, fluoxetine, clorophene, triclosan, bisphenol A. The method also was used as an indicator of the occurrence of estrogenic compounds by targeting estrone and 17beta-estradiol. The two canals (Orleans and London) are used to drain a portion of the city's stormwater directly into the Mississippi River or Lake Pontchartrain. Bayou St. John is located between the two canals and supplied with water from Lake Pontchartrain. Results from the 6-month sampling period indicated the following concentration ranges for the two stormwater canals: naproxen (ND - 145 ng/l), ibuprofen (ND - 674 ng/l), triclosan (ND - 29 ng/l) and bisphenol A (1.9-158 ng/l). Concentrations of these target analytes increased with cumulative rainfall. For bayou waters, only naproxen (2.1-4.8 ng/l) and bisphenol A (0.9-44 ng/l) were detected. Estrone was detected but determined non-quantifiable for multiple sampling events at the 3 sites. None of the other target analytes (clofibric acid, fluoxetine, clorophene, and 17beta-estradiol) were detected above their method detection levels. Results of this study demonstrate the occurrence of PPCPs and EDCs in New Orleans stormwater canals and Bayou St. John. Results also demonstrate the use of this analytical technique as an indicator of non-point source sewage contamination in New Orleans stormwater canals.

Neonicotinoid Insecticide Residues in Surface Water and Soil Associated with Commercial Maize (Corn) Fields in Southwestern Ontario

PubMed Central

Schaafsma, Arthur; Limay-Rios, Victor; Baute, Tracey; Smith, Jocelyn; Xue, Yingen

2015-01-01

Neonicotinoid insecticides have come under scrutiny for their potential unintended effects on non-target organisms, particularly pollinators in agro-ecosystems. As part of a larger study of neonicotinoid residues associated with maize (corn) production, 76 water samples within or around the perimeter of 18 commercial maize fields and neighbouring apiaries were collected in 5 maize-producing counties of southwestern Ontario. Residues of clothianidin (mean = 2.28, max. = 43.60 ng/mL) and thiamethoxam (mean = 1.12, max. = 16.50 ng/mL) were detected in 100 and 98.7% of the water samples tested, respectively. The concentration of total neonicotinoid residues in water within maize fields increased six-fold during the first five weeks after planting, and returned to pre-plant levels seven weeks after planting. However, concentrations in water sampled from outside the fields were similar throughout the sampling period. Soil samples from the top 5 cm of the soil profile were also collected in these fields before and immediately following planting. The mean total neonicotinoid residue was 4.02 (range 0.07 to 20.30) ng/g, for samples taken before planting, and 9.94 (range 0.53 to 38.98) ng/g, for those taken immediately after planting. Two soil samples collected from within an conservation area contained detectable (0.03 and 0.11 ng/g) concentrations of clothianidin. Of three drifted snow samples taken, the drift stratum containing the most wind-scoured soil had 0.16 and 0.20 ng/mL mainly clothianidin in the melted snow. The concentration was at the limit of detection (0.02 ng/mL) taken across the entire vertical profile. With the exception of one sample, water samples tested had concentrations below those reported to have acute, chronic or sublethal effects to honey bees. Our results suggest that neonicotinoids may move off-target by wind erosion of contaminated soil. These results are informative to risk assessment models for other non-target species in maize agro-ecosytems. PMID:25710560

Detection of Sub-fM DNA with Target Recycling and Self-Assembly Amplification on Graphene Field-Effect Biosensors

PubMed Central

2018-01-01

All-electronic DNA biosensors based on graphene field-effect transistors (GFETs) offer the prospect of simple and cost-effective diagnostics. For GFET sensors based on complementary probe DNA, the sensitivity is limited by the binding affinity of the target oligonucleotide, in the nM range for 20 mer targets. We report a ∼20 000× improvement in sensitivity through the use of engineered hairpin probe DNA that allows for target recycling and hybridization chain reaction. This enables detection of 21 mer target DNA at sub-fM concentration and provides superior specificity against single-base mismatched oligomers. The work is based on a scalable fabrication process for biosensor arrays that is suitable for multiplexed detection. This approach overcomes the binding-affinity-dependent sensitivity of nucleic acid biosensors and offers a pathway toward multiplexed and label-free nucleic acid testing with high accuracy and selectivity. PMID:29768011

Detection of Sub-fM DNA with Target Recycling and Self-Assembly Amplification on Graphene Field-Effect Biosensors.

PubMed

Gao, Zhaoli; Xia, Han; Zauberman, Jonathan; Tomaiuolo, Maurizio; Ping, Jinglei; Zhang, Qicheng; Ducos, Pedro; Ye, Huacheng; Wang, Sheng; Yang, Xinping; Lubna, Fahmida; Luo, Zhengtang; Ren, Li; Johnson, Alan T Charlie

2018-06-13

All-electronic DNA biosensors based on graphene field-effect transistors (GFETs) offer the prospect of simple and cost-effective diagnostics. For GFET sensors based on complementary probe DNA, the sensitivity is limited by the binding affinity of the target oligonucleotide, in the nM range for 20 mer targets. We report a ∼20 000× improvement in sensitivity through the use of engineered hairpin probe DNA that allows for target recycling and hybridization chain reaction. This enables detection of 21 mer target DNA at sub-fM concentration and provides superior specificity against single-base mismatched oligomers. The work is based on a scalable fabrication process for biosensor arrays that is suitable for multiplexed detection. This approach overcomes the binding-affinity-dependent sensitivity of nucleic acid biosensors and offers a pathway toward multiplexed and label-free nucleic acid testing with high accuracy and selectivity.

Occurrence and behavior of emerging contaminants in surface water and a restored wetland.

PubMed

Matamoros, Víctor; Arias, Carlos A; Nguyen, Loc Xuan; Salvadó, Victòria; Brix, Hans

2012-08-01

Pollution mitigation is an important target for restored wetlands, and although there is much information in relation to nutrient removal, little attention has been paid to emerging contaminants. This paper reports on the occurrence and attenuation capacity of 17 emerging contaminants in a restored wetland and two rivers in North-East Denmark. The compounds belong to the groups of pharmaceuticals, fragrances, antiseptics, fire retardants, pesticides, and plasticizers. Concentrations in surface waters ranged from 2 to 1476 ng L(-1). The compounds with the highest concentrations were diclofenac, 2-methyl-4-chlorophenoxyacetic acid (MCPA), caffeine, and tris(2-chloroethyl) phosphate (TCEP). The herbicide concentrations increased after a rain-fall event, demonstrating the agricultural run-off origin of these compounds, whereas the concentration of the other emerging contaminants was rather conservative. The mitigation capacity of the restored wetland for the compounds ranged from no attenuation to 84% attenuation (19% on average). Hence, restored wetlands may be considered as a feasible alternative for mitigating emerging contaminants from river waters. Copyright © 2012 Elsevier Ltd. All rights reserved.

Beyond conventional dose-response curves: Sensorgram comparison in SPR allows single concentration activity and similarity assessment.

PubMed

Gassner, C; Karlsson, R; Lipsmeier, F; Moelleken, J

2018-05-30

Previously we have introduced two SPR-based assay principles (dual-binding assay and bridging assay), which allow the determination of two out of three possible interaction parameters for bispecific molecules within one assay setup: two individual interactions to both targets, and/or one simultaneous/overall interaction, which potentially reflects the inter-dependency of both individual binding events. However, activity and similarity are determined by comparing report points over a concentration range, which also mirrors the way data is generated by conventional ELISA-based methods So far, binding kinetics have not been specifically considered in generic approaches for activity assessment. Here, we introduce an improved slope-ratio model which, together with a sensorgram comparison based similarity assessment, allows the development of a detailed, USP-conformal ligand binding assay using only a single sample concentration. We compare this novel analysis method to the usual concentration-range approach for both SPR-based assay principles and discuss its impact on data quality and increased sample throughput. Copyright © 2018 Elsevier B.V. All rights reserved.

Cascading and Parallelising Curvilinear Inertial Focusing Systems for High Volume, Wide Size Distribution, Separation and Concentration of Particles

PubMed Central

Miller, B.; Jimenez, M.; Bridle, H.

2016-01-01

Inertial focusing is a microfluidic based separation and concentration technology that has expanded rapidly in the last few years. Throughput is high compared to other microfluidic approaches although sample volumes have typically remained in the millilitre range. Here we present a strategy for achieving rapid high volume processing with stacked and cascaded inertial focusing systems, allowing for separation and concentration of particles with a large size range, demonstrated here from 30 μm–300 μm. The system is based on curved channels, in a novel toroidal configuration and a stack of 20 devices has been shown to operate at 1 L/min. Recirculation allows for efficient removal of large particles whereas a cascading strategy enables sequential removal of particles down to a final stage where the target particle size can be concentrated. The demonstration of curved stacked channels operating in a cascaded manner allows for high throughput applications, potentially replacing filtration in applications such as environmental monitoring, industrial cleaning processes, biomedical and bioprocessing and many more. PMID:27808244

Comparative elemental analysis of fine particulate matter (PM2.5) from industrial and residential areas in Greater Cairo-Egypt by means of a multi-secondary target energy dispersive X-ray fluorescence spectrometer

NASA Astrophysics Data System (ADS)

Shaltout, Abdallah A.; Hassan, Salwa K.; Karydas, Andreas G.; Zaki, Z. I.; Mostafa, Nasser Y.; Kregsamer, Peter; Wobrauschek, Peter; Streli, Christina

2018-07-01

Fine aerosol particles with aerodynamic diameter equal or <2.5 μm (PM2.5) have been collected from industrial and residential areas of Greater Cairo, Egypt during two different seasons namely; autumn 2014 and winter 2014/2015. Energy dispersive X-ray fluorescence (EDXRF) analysis utilizing polarization geometry and three different secondary targets (CaF2, Ge, and Mo) was employed for the quantitative analysis of eighteen (18) elements in PM2.5 samples. Light elements like Na and Mg was possible to be quantified, whereas detection limits in the range of few ng m-3 were attained for the most of the detected elements. Although, the average mass concentrations of the PM2.5 collected from the residential area (27 ± 7 μg m-3) is close to the annual mean limit value, a significant number of the collected samples (33%) presented higher average mass concentrations. For the industrial location, the average mass concentration is equal to 55 ± 19 μg m-3, exceeded twofold the annual mean limit value of the European Commission. Remarkably high elemental concentrations were determined for the most of the detected elements from the industrial area samples, clearly indicating the significant influence of anthropogenic activities. The present optimized EDXRF analysis offered significantly improved analytical range and limits of detection with respect to previous similar studies, thus enhancing our knowledge and understanding on the contribution of different pollution sources.

Do centrally pre-prepared solutions achieve more reliable drug concentrations than solutions prepared on the ward?

PubMed

Dehmel, Carola; Braune, Stephan A; Kreymann, Georg; Baehr, Michael; Langebrake, Claudia; Hilgarth, Heike; Nierhaus, Axel; Dartsch, Dorothee C; Kluge, Stefan

2011-08-01

To compare the concentration conformity of infusion solutions manually prepared on intensive care units (ICU) with solutions from pharmacy-based, automated production. A prospective observational study conducted in a university hospital in Germany. Drug concentrations of 100 standardised infusion solutions manually prepared in the ICU and 100 matching solutions from automated production containing amiodarone, noradrenaline or hydrocortisone were measured by high-performance liquid chromatography analysis. Deviations from stated concentrations were calculated, and the quality of achieved concentration conformity of the two production methods was compared. Actual concentrations of 53% of the manually prepared and 16% of the machine-made solutions deviated by >5% above or below the stated concentration. A deviation of >10% was measured in 22% of the manually prepared samples and in 5% of samples from automated production. Of the manually prepared solutions, 15% deviated by >15% above or below the intended concentration. The mean concentration of the manually prepared solutions was 97.2% (SD 12.7%, range 45-129%) and of the machine-made solutions was 101.1% (SD 4.3%, range 90-114%) of the target concentration (p < 0.01). In this preliminary study, ward-based, manually prepared infusion solutions showed clinically relevant deviations in concentration conformity significantly more often than pharmacy-prepared, machine-made solutions. Centralised, automated preparation of standardised infusion solutions may be an effective means to reduce this type of medication error. Further confirmatory studies in larger settings and under conditions of routine automated production are required.

Large area silicon sheet by EFG

NASA Technical Reports Server (NTRS)

1981-01-01

The influence of parameters such as CO2 concentration, gas flow patterns, quartz in the bulk melt, melt doping level and growth speed on ribbon properties was examined for 10 cm wide ribbon. Ribbon quality is optimized for ambient CO2 in argon concentrations in the range from 1000 to 5000 ppm. Cell performance degrades at CO2 concentrations above 5000 ppm and IR interstitial oxygen levels decrease. These experiments were done primarily at a growth speed of 3.5 cm/minute. Cartridge parameters influencing the ribbon thickness were studied and thickness uniformity at 200 micrometers (8 mils) has been improved. Growth stability at the target speed of 4.0 cm/minute was improved significantly.

Fort Dix Remedial Investigation/Feasibility Study for MAG-1 Area

DTIC Science & Technology

1994-01-01

by PID headspace results or odor ), samples should be diluted to bring the target compound concentrations within the instrument calibration range...Conductivity Testing ................... 2-38 2.9 ANALYTICAL PROCEDURES FOR FIELD SCREENING SAMPLES .. 2-38 2.9.1 Volatile Organic Compounds ...ANALYSIS OF VOLATILE ORGANIC COMPOUNDS BY FIELD GAS CHROMATOGRAPHY - STANDARD OPERATING PROCEDURE APPENDIX B RDX EXPLOSIVES FIELD TEST KIT PROCEDURES

Longitudinal Urinary Protein Variability in Participants of the Space Flight Simulation Program.

PubMed

Khristenko, Nina A; Larina, Irina M; Domon, Bruno

2016-01-04

Urine is a valuable material for the diagnosis of renal pathologies and to investigate the effects of their treatment. However, the variability in protein abundance in the context of normal homeostasis remains a major challenge in urinary proteomics. In this study, the analysis of urine samples collected from healthy individuals, rigorously selected to take part in the MARS-500 spaceflight simulation program, provided a unique opportunity to estimate normal concentration ranges for an extended set of urinary proteins. In order to systematically identify and reliably quantify peptides/proteins across a large sample cohort, a targeted mass spectrometry method was developed. The performance of parallel reaction monitoring (PRM) analyses was improved by implementing tight control of the monitoring windows during LC-MS/MS runs, using an on-the-fly correction routine. Matching the experimentally obtained MS/MS spectra with reference fragmentation patterns allowed dependable peptide identifications to be made. Following optimization and evaluation, the targeted method was applied to investigate protein abundance variability in 56 urine samples, collected from six volunteers participating in the MARS-500 program. The intrapersonal protein concentration ranges were determined for each individual and showed unexpectedly high abundance variation, with an average difference of 1 order of magnitude.

Assessing Aromatic-Hydrocarbon Toxicity to Fish Early Life Stages Using Passive-Dosing Methods and Target-Lipid and Chemical-Activity Models.

PubMed

Butler, Josh D; Parkerton, Thomas F; Redman, Aaron D; Letinski, Daniel J; Cooper, Keith R

2016-08-02

Aromatic hydrocarbons (AH) are known to impair fish early life stages (ELS). However, poorly defined exposures often confound ELS-test interpretation. Passive dosing (PD) overcomes these challenges by delivering consistent, controlled exposures. The objectives of this study were to apply PD to obtain 5 d acute embryo lethality and developmental data and 30 d chronic embryo-larval survival and growth-effects data using zebrafish with different AHs; to analyze study and literature toxicity data using target-lipid (TLM) and chemical-activity (CA) models; and to extend PD to a mixture and test the assumption of AH additivity. PD maintained targeted exposures over a concentration range of 6 orders of magnitude. AH toxicity increased with log Kow up to pyrene (5.2). Pericardial edema was the most sensitive sublethal effect that often preceded embryo mortality, although some AHs did not produce developmental effects at concentrations causing mortality. Cumulative embryo-larval mortality was more sensitive than larval growth, with acute-to-chronic ratios of <10. More-hydrophobic AHs did not exhibit toxicity at aqueous saturation. The relationship and utility of the TLM-CA models for characterizing fish ELS toxicity is discussed. Application of these models indicated that concentration addition provided a conservative basis for predicting ELS effects for the mixture investigated.

High sensitivity DNA detection using gold nanoparticle functionalised polyaniline nanofibres.

PubMed

Spain, Elaine; Kojima, Robert; Kaner, Richard B; Wallace, Gordan G; O'Grady, Justin; Lacey, Katrina; Barry, Thomas; Keyes, Tia E; Forster, Robert J

2011-01-15

Polyaniline (PANI) nanofibres (PANI-NF) have been modified with chemically grown gold nanoparticles to give a nanocomposite material (PANI-NF-AuNP) and deposited on gold electrodes. Single stranded capture DNA was then bound to the gold nanoparticles and the underlying gold electrode and allowed to hybridise with a complementary target strand that is uniquely associated with the pathogen, Staphylococcus aureus (S. aureus), that causes mastitis. Significantly, cyclic voltammetry demonstrates that deposition of the gold nanoparticles increases the area available for DNA immobilisation by a factor of approximately 4. EPR reveals that the addition of the Au nanoparticles efficiently decreases the interactions between adjacent PANI chains and/or motional broadening. Finally, a second horseradish peroxidase (HRP) labelled DNA strand hybridises with the target allowing the concentration of the target DNA to be detected by monitoring the reduction of a hydroquinone mediator in solution. The sensors have a wide dynamic range, excellent ability to discriminate DNA mismatches and a high sensitivity. Semi-log plots of the pathogen DNA concentration vs. faradaic current were linear from 150×10(-12) to 1×10(-6) mol L(-1) and pM concentrations could be detected without the need for molecular, e.g., PCR or NASBA, amplification. Copyright © 2010 Elsevier B.V. All rights reserved.

Drug Concentration Thresholds Predictive of Therapy Failure and Death in Children With Tuberculosis: Bread Crumb Trails in Random Forests

PubMed Central

Swaminathan, Soumya; Pasipanodya, Jotam G.; Ramachandran, Geetha; Hemanth Kumar, A. K.; Srivastava, Shashikant; Deshpande, Devyani; Nuermberger, Eric; Gumbo, Tawanda

2016-01-01

Background. The role of drug concentrations in clinical outcomes in children with tuberculosis is unclear. Target concentrations for dose optimization are unknown. Methods. Plasma drug concentrations measured in Indian children with tuberculosis were modeled using compartmental pharmacokinetic analyses. The children were followed until end of therapy to ascertain therapy failure or death. An ensemble of artificial intelligence algorithms, including random forests, was used to identify predictors of clinical outcome from among 30 clinical, laboratory, and pharmacokinetic variables. Results. Among the 143 children with known outcomes, there was high between-child variability of isoniazid, rifampin, and pyrazinamide concentrations: 110 (77%) completed therapy, 24 (17%) failed therapy, and 9 (6%) died. The main predictors of therapy failure or death were a pyrazinamide peak concentration <38.10 mg/L and rifampin peak concentration <3.01 mg/L. The relative risk of these poor outcomes below these peak concentration thresholds was 3.64 (95% confidence interval [CI], 2.28–5.83). Isoniazid had concentration-dependent antagonism with rifampin and pyrazinamide, with an adjusted odds ratio for therapy failure of 3.00 (95% CI, 2.08–4.33) in antagonism concentration range. In regard to death alone as an outcome, the same drug concentrations, plus z scores (indicators of malnutrition), and age <3 years, were highly ranked predictors. In children <3 years old, isoniazid 0- to 24-hour area under the concentration-time curve <11.95 mg/L × hour and/or rifampin peak <3.10 mg/L were the best predictors of therapy failure, with relative risk of 3.43 (95% CI, .99–11.82). Conclusions. We have identified new antibiotic target concentrations, which are potential biomarkers associated with treatment failure and death in children with tuberculosis. PMID:27742636

LED-Absorption-QEPAS Sensor for Biogas Plants

PubMed Central

Köhring, Michael; Böttger, Stefan; Willer, Ulrike; Schade, Wolfgang

2015-01-01

A new sensor for methane and carbon dioxide concentration measurements in biogas plants is presented. LEDs in the mid infrared spectral region are implemented as low cost light source. The combination of quartz-enhanced photoacoustic spectroscopy with an absorption path leads to a sensor setup suitable for the harsh application environment. The sensor system contains an electronics unit and the two gas sensors; it was designed to work as standalone device and was tested in a biogas plant for several weeks. Gas concentration dependent measurements show a precision better than 1% in a range between 40% and 60% target gas concentration for both sensors. Concentration dependent measurements with different background gases show a considerable decrease in cross sensitivity against the major components of biogas in direct comparison to common absorption based sensors. PMID:26007746

Quantitative electrochemical metalloimmunoassay for TFF3 in urine using a paper analytical device.

PubMed

DeGregory, Paul R; Tsai, Yi-Ju; Scida, Karen; Richards, Ian; Crooks, Richard M

2016-03-07

We report a paper-based assay platform for the detection of the kidney disease marker Trefoil Factor 3 (TFF3) in human urine. The sensor is based on a quantitative metalloimmunoassay that can determine TFF3 concentrations via electrochemical detection of environmentally stable silver nanoparticle (AgNP) labels attached to magnetic microbeads via a TFF3 immunosandwich. The paper electroanalytical device incorporates two preconcentration steps that make it possible to detect concentrations of TFF3 in human urine at the low end of the target TFF3 concentration range (0.03-7.0 μg mL(-1)). Importantly, the paper device provides a level of accuracy for TFF3 determination in human urine equivalent to that of a commercial kit. The paper sensor has a dynamic range of ∼2.5 orders of magnitude, only requires a simple, one-step incubation protocol, and is fast, requiring only 10 min to complete. The cost of the materials at the prototypic laboratory scale, excluding reagents, is just US$0.42.

Applying gold nanoparticles as tumor-vascular disrupting agents during brachytherapy: estimation of endothelial dose enhancement

NASA Astrophysics Data System (ADS)

Ngwa, Wilfred; Makrigiorgos, G. Mike; Berbeco, Ross I.

2010-11-01

Tumor vascular disrupting agents (VDAs) represent a promising approach to the treatment of cancer, in view of the tumor vasculature's pivotal role in tumor survival, growth and metastasis. VDAs targeting the tumor's dysmorphic endothelial cells can cause selective and rapid occlusion of the tumor vasculature, leading to tumor cell death from ischemia and extensive hemorrhagic necrosis. In this study, the potential for applying gold nanoparticles (AuNPs) as VDAs, during brachytherapy, is examined. Analytic calculations based on the electron energy loss formula of Cole were carried out to estimate the endothelial dose enhancement caused by radiation-induced photo/Auger electrons originating from AuNPs targeting the tumor endothelium. The endothelial dose enhancement factor (EDEF), representing the ratio of the dose to the endothelium with and without gold nanoparticles was calculated for different AuNP local concentrations, and endothelial cell thicknesses. Four brachytherapy sources were investigated, I-125, Pd-103, Yb-169, as well as 50 kVp x-rays. The results reveal that, even at relatively low intra-vascular AuNP concentrations, ablative dose enhancement to tumor endothelial cells due to photo/Auger electrons from the AuNPs can be achieved. Pd-103 registered the highest EDEF values of 7.4-271.5 for local AuNP concentrations ranging from 7 to 350 mg g-1, respectively. Over the same concentration range, I-125, 50 kVp and Yb-169 yielded values of 6.4-219.9, 6.3-214.5 and 4.0-99.7, respectively. Calculations of the EDEF as a function of endothelial cell thickness showed that lower energy sources like Pd-103 reach the maximum EDEF at smaller thicknesses. The results also reveal that the highest contribution to the EDEF comes from Auger electrons, apparently due to their shorter range. Overall, the data suggest that ablative dose enhancement to tumor endothelial cells can be achieved by applying tumor vasculature-targeted AuNPs as adjuvants to brachytherapy, with lower energy sources. Such ablative magnitude dose enhancement in a relatively small endothelial volume may rapidly disrupt or cause severe biological damage to tumor endothelial cells, without increased toxicity to healthy tissues not containing AuNPs. The findings provide significant impetus for considering the application of AuNPs as VDAs during brachytherapy.

VOC source identification from personal and residential indoor, outdoor and workplace microenvironment samples in EXPOLIS-Helsinki, Finland

NASA Astrophysics Data System (ADS)

Edwards, Rufus D.; Jurvelin, J.; Koistinen, K.; Saarela, K.; Jantunen, M.

Principal component analyses (varimax rotation) were used to identify common sources of 30 target volatile organic compounds (VOCs) in residential outdoor, residential indoor and workplace microenvironment and personal 48-h exposure samples, as a component of the EXPOLIS-Helsinki study. Variability in VOC concentrations in residential outdoor microenvironments was dominated by compounds associated with long-range transport of pollutants, followed by traffic emissions, emissions from trees and product emissions. Variability in VOC concentrations in environmental tobacco smoke (ETS) free residential indoor environments was dominated by compounds associated with indoor cleaning products, followed by compounds associated with traffic emissions, long-range transport of pollutants and product emissions. Median indoor/outdoor ratios for compounds typically associated with traffic emissions and long-range transport of pollutants exceeded 1, in some cases quite considerably, indicating substantial indoor source contributions. Changes in the median indoor/outdoor ratios during different seasons reflected different seasonal ventilation patterns as increased ventilation led to dilution of those VOC compounds in the indoor environment that had indoor sources. Variability in workplace VOC concentrations was dominated by compounds associated with traffic emissions followed by product emissions, long-range transport and air fresheners. Variability in VOC concentrations in ETS free personal exposure samples was dominated by compounds associated with traffic emissions, followed by long-range transport, cleaning products and product emissions. VOC sources in personal exposure samples reflected the times spent in different microenvironments, and personal exposure samples were not adequately represented by any one microenvironment, demonstrating the need for personal exposure sampling.

Filling of a Poisson trap by a population of random intermittent searchers.

PubMed

Bressloff, Paul C; Newby, Jay M

2012-03-01

We extend the continuum theory of random intermittent search processes to the case of N independent searchers looking to deliver cargo to a single hidden target located somewhere on a semi-infinite track. Each searcher randomly switches between a stationary state and either a leftward or rightward constant velocity state. We assume that all of the particles start at one end of the track and realize sample trajectories independently generated from the same underlying stochastic process. The hidden target is treated as a partially absorbing trap in which a particle can only detect the target and deliver its cargo if it is stationary and within range of the target; the particle is removed from the system after delivering its cargo. As a further generalization of previous models, we assume that up to n successive particles can find the target and deliver its cargo. Assuming that the rate of target detection scales as 1/N, we show that there exists a well-defined mean-field limit N→∞, in which the stochastic model reduces to a deterministic system of linear reaction-hyperbolic equations for the concentrations of particles in each of the internal states. These equations decouple from the stochastic process associated with filling the target with cargo. The latter can be modeled as a Poisson process in which the time-dependent rate of filling λ(t) depends on the concentration of stationary particles within the target domain. Hence, we refer to the target as a Poisson trap. We analyze the efficiency of filling the Poisson trap with n particles in terms of the waiting time density f(n)(t). The latter is determined by the integrated Poisson rate μ(t)=∫(0)(t)λ(s)ds, which in turn depends on the solution to the reaction-hyperbolic equations. We obtain an approximate solution for the particle concentrations by reducing the system of reaction-hyperbolic equations to a scalar advection-diffusion equation using a quasisteady-state analysis. We compare our analytical results for the mean-field model with Monte Carlo simulations for finite N. We thus determine how the mean first passage time (MFPT) for filling the target depends on N and n.

Occurrence and In Vitro Bioactivity of Estrogen, Androgen, and Glucocorticoid Compounds in a Nationwide Screen of United States Stream Waters.

PubMed

Conley, Justin M; Evans, Nicola; Cardon, Mary C; Rosenblum, Laura; Iwanowicz, Luke R; Hartig, Phillip C; Schenck, Kathleen M; Bradley, Paul M; Wilson, Vickie S

2017-05-02

In vitro bioassays are sensitive, effect-based tools used to quantitatively screen for chemicals with nuclear receptor activity in environmental samples. We measured in vitro estrogen (ER), androgen (AR), and glucocorticoid receptor (GR) activity, along with a broad suite of chemical analytes, in streamwater from 35 well-characterized sites (3 reference and 32 impacted) across 24 states and Puerto Rico. ER agonism was the most frequently detected with nearly all sites (34/35) displaying activity (range, 0.054-116 ng E2Eq L -1 ). There was a strong linear relationship (r 2 = 0.917) between in vitro ER activity and concentrations of steroidal estrogens after correcting for the in vitro potency of each compound. AR agonism was detected in 5/35 samples (range, 1.6-4.8 ng DHTEq L -1 ) but concentrations of androgenic compounds were largely unable to account for the in vitro activity. Similarly, GR agonism was detected in 9/35 samples (range, 6.0-43 ng DexEq L -1 ); however, none of the recognized GR-active compounds on the target-chemical analyte list were detected. The utility of in vitro assays in water quality monitoring was evident from both the quantitative agreement between ER activity and estrogen concentrations, as well as the detection of AR and GR activity for which there were limited or no corresponding target-chemical detections to explain the bioactivity. Incorporation of in vitro bioassays as complements to chemical analyses in standard water quality monitoring efforts would allow for more complete assessment of the chemical mixtures present in many surface waters.

Occurrence and in vitro bioactivity of estrogen, androgen, and glucocorticoid compounds in a nationwide screen of United States stream waters

USGS Publications Warehouse

Conley, Justin M.; Evans, Nicola; Cardon, Mary C.; Rosenblum, Laura; Iwanowicz, Luke R.; Hartig, Phillip C.; Schenck, Kathleen M.; Bradley, Paul M.; Wilson, Vickie S.

2017-01-01

In vitro bioassays are sensitive, effect-based tools used to quantitatively screen for chemicals with nuclear receptor activity in environmental samples. We measured in vitro estrogen (ER), androgen (AR), and glucocorticoid receptor (GR) activity, along with a broad suite of chemical analytes, in streamwater from 35 well-characterized sites (3 reference and 32 impacted) across 24 states and Puerto Rico. ER agonism was the most frequently detected with nearly all sites (34/35) displaying activity (range, 0.054–116 ng E2Eq L–1). There was a strong linear relationship (r2 = 0.917) between in vitro ER activity and concentrations of steroidal estrogens after correcting for the in vitro potency of each compound. AR agonism was detected in 5/35 samples (range, 1.6–4.8 ng DHTEq L–1) but concentrations of androgenic compounds were largely unable to account for the in vitro activity. Similarly, GR agonism was detected in 9/35 samples (range, 6.0–43 ng DexEq L–1); however, none of the recognized GR-active compounds on the target-chemical analyte list were detected. The utility of in vitro assays in water quality monitoring was evident from both the quantitative agreement between ER activity and estrogen concentrations, as well as the detection of AR and GR activity for which there were limited or no corresponding target-chemical detections to explain the bioactivity. Incorporation of in vitro bioassays as complements to chemical analyses in standard water quality monitoring efforts would allow for more complete assessment of the chemical mixtures present in many surface waters.

Towards Enhanced Underwater Lidar Detection via Source Separation

NASA Astrophysics Data System (ADS)

Illig, David W.

Interest in underwater optical sensors has grown as technologies enabling autonomous underwater vehicles have been developed. Propagation of light through water is complicated by the dual challenges of absorption and scattering. While absorption can be reduced by operating in the blue-green region of the visible spectrum, reducing scattering is a more significant challenge. Collection of scattered light negatively impacts underwater optical ranging, imaging, and communications applications. This thesis concentrates on the ranging application, where scattering reduces operating range as well as range accuracy. The focus of this thesis is on the problem of backscatter, which can create a "clutter" return that may obscure submerged target(s) of interest. The main contributions of this thesis are explorations of signal processing approaches to increase the separation between the target and backscatter returns. Increasing this separation allows detection of weak targets in the presence of strong scatter, increasing both operating range and range accuracy. Simulation and experimental results will be presented for a variety of approaches as functions of water clarity and target position. This work provides several novel contributions to the underwater lidar field: 1. Quantification of temporal separation approaches: While temporal separation has been studied extensively, this work provides a quantitative assessment of the extent to which both high frequency modulation and spatial filter approaches improve the separation between target and backscatter. 2. Development and assessment of frequency separation: This work includes the first frequency-based separation approach for underwater lidar, in which the channel frequency response is measured with a wideband waveform. Transforming to the time-domain gives a channel impulse response, in which target and backscatter returns may appear in unique range bins and thus be separated. 3. Development and assessment of statistical separation: The first investigations of statistical separation approaches for underwater lidar are presented. By demonstrating that target and backscatter returns have different statistical properties, a new separation axis is opened. This work investigates and quantifies performance of three statistical separation approaches. 4. Application of detection theory to underwater lidar: While many similar applications use detection theory to assess performance, less development has occurred in the underwater lidar field. This work applies these concepts to statistical separation approaches, providing another perspective in which to assess performance. In addition, by using detection theory approaches, statistical metrics can be used to associate a level of confidence in each ranging measurement. 5. Preliminary investigation of forward scatter suppression: If backscatter is sufficiently suppressed, forward scattering becomes a performance-limiting factor. This work presents a proof-of-concept demonstration of the potential for statistical separation approaches to suppress both forward and backward scatter. These results provide a demonstration of the capability that signal processing has to improve separation between target and backscatter. Separation capability improves in the transition from temporal to frequency to statistical separation approaches, with the statistical separation approaches improving target detection sensitivity by as much as 30 dB. Ranging and detection results demonstrate the enhanced performance this would allow in ranging applications. This increased performance is an important step in moving underwater lidar capability towards the requirements of the next generation of sensors.

Formation of N-nitrosodimethylamine (NDMA) by ozonation of dyes and related compounds.

PubMed

Oya, Masami; Kosaka, Koji; Asami, Mari; Kunikane, Shoichi

2008-12-01

Formation of N-nitrosodimethylamine (NDMA) by ozonation of commercially available dyes and related compounds was investigated. Ozonation was conducted using a semi-batch type reactor, and ozone concentration in gas phase and the ozone gas flow were 10 mg L(-1) and 1.0 L min(-1), respectively. NDMA was formed by 15 min of ozonation of seven out of eight selected target compounds (0.05 mM) at pH 7. All the target compounds with N,N-dimethylamino functions were NDMA precursors in ozonation. The lowest and highest NDMA concentrations after ozonation of the target compounds were 13 ng L(-1) for N,N-dimethylformamide (DMF) and 1600 ng L(-1) for N,N-dimethyl-p-phenylenediamine (DMPD), respectively. NDMA concentrations after 15 min of ozonation of 0.05 mM methylene blue (MB) and DMPD increased with an increase in pH in its range of 6-8. The effects of coexisting compounds on NDMA concentrations after 15 min of ozonation of 0.05 mM MB and DMPD were examined at pH 7. NDMA concentrations after ozonation of MB and DMPD increased by the presence of 0.05 mM (0.7 mg L(-1) as N) nitrite (NO(2)(-)); 5000 ng L(-1) for MB and 4000 ng L(-1) for DMPD. NDMA concentration after MB ozonation decreased by the presence of 5mM tertiary butyl alcohol (TBA), a hydroxyl radical (HO.) scavenger, but that after DMPD ozonation was increased by the presence of TBA. NDMA concentrations after ozonation of MB and DMPD were not affected by the presence of 0.16 mM (5.3 mg L(-1)) hydrogen peroxide (H(2)O(2)). When 0.05 mM MB and DMPD were added to the Yodo and Tone river water samples, NDMA concentrations after 15 min of their ozonation at pH 7 increased compared with those in the case of addition to ultrapure water samples.

Alpha-synuclein is present in dental calculus but not altered in Parkinson's disease patients in comparison to controls.

PubMed

Schmid, Sabrina; Goldberg-Bockhorn, Eva; Schwarz, Silke; Rotter, Nicole; Kassubek, Jan; Del Tredici, Kelly; Pinkhardt, Elmar; Otto, Markus; Ludolph, Albert C; Oeckl, Patrick

2018-06-01

In autopsy cases staged for sporadic Parkinson's disease (PD), the neuropathology is characterized by a preclinical phase that targets the enteric nervous system of the gastrointestinal tract (GIT). Therefore, the ENS might be a source of potential (presymptomatic) PD biomarkers. In this clinically based study, we examined the alpha-synuclein (αSyn) concentration in an easily accessible protein storage medium of the GIT, dental calculus, in 21/50 patients with PD and 28/50 age- and gender-matched controls using ELISA. αSyn was detectable in dental calculus and the median concentration in the control patients was 8.6 pg/mg calculus (interquartile range 2.6-13.1 pg/mg). αSyn concentrations were significantly influenced by blood contamination and samples with a hemoglobin concentration of > 4000 ng/mL were excluded. There was no significant difference of αSyn concentrations in the dental calculus of PD patients (5.76 pg/mg, interquartile range 2.91-9.74 pg/mg) compared to those in controls (p = 0.40). The total αSyn concentration in dental calculus is not a suitable biomarker for sporadic PD. Disease-related variants such as oligomeric or phosphorylated αSyn in calculus might prove to be more specific.

Pharmacokinetics of oral gabapentin in Greyhound dogs

PubMed Central

KuKanich, Butch; Cohen, Rachael L

2009-01-01

The purpose of this study was to assess the pharmacokinetics of gabapentin in healthy Greyhound dogs after single oral doses targeted at 10 and 20 mg/kg PO. Six healthy Greyhounds were enrolled (3 males, 3 females). Blood was obtained at predetermined times for the measurement of gabapentin plasma concentrations by liquid chromatography/mass spectrometry. Pharmacokinetic parameters were determined with computer software. The actual mean (and range) doses administered were 10.2 (9.1–12.0) mg/kg and 20.5 (18.2 – 24) mg/kg for the 10 mg/kg and 20 mg/kg targeted dose groups. The mean CMAX for the 10 and 20 mg/kg groups were 8.54 and 13.22 μg/mL at 1.3 and 1.5 h, and the terminal half-lives were 3.3 and 3.4 h, respectively. The relative bioavailability of the 10 mg/kg group was 1.13 compared to the 20 mg/kg group. Gabapentin was rapidly absorbed and eliminated in dogs indicating frequent dosing is needed to maintain minimum targeted plasma concentrations. PMID:19854080

Pharmacokinetics of oral gabapentin in greyhound dogs.

PubMed

Kukanich, Butch; Cohen, Rachael L

2011-01-01

The purpose of this study was to assess the pharmacokinetics of gabapentin in healthy greyhound dogs after single oral doses targeted at 10 and 20mg/kg PO. Six healthy greyhounds were enrolled (3 males, 3 females). Blood was obtained at predetermined times for the measurement of gabapentin plasma concentrations by liquid chromatography/mass spectrometry. Pharmacokinetic parameters were determined with computer software. The actual mean (and range) doses administered were 10.2 (9.1-12.0) mg/kg and 20.5 (18.2-24) mg/kg for the 10mg/kg and 20mg/kg targeted dose groups. The mean C(MAX) for the 10 and 20mg/kg groups were 8.54 and 13.22 microg/mL at 1.3 and 1.5h, and the terminal half-lives were 3.3 and 3.4h, respectively. The relative bioavailability of the 10mg/kg group was 1.13 compared to the 20mg/kg group. Gabapentin was rapidly absorbed and eliminated in dogs, indicating that frequent dosing is needed to maintain minimum targeted plasma concentrations. 2009 Elsevier Ltd. All rights reserved.

Preparation and evaluation of enrofloxacin microspheres and tissue distribution in rats

PubMed Central

Yang, Fan; Kang, Jijun; Yang, Fang; Zhao, Zhensheng; Kong, Tao

2015-01-01

New enrofloxacin microspheres were formulated, and their physical properties, lung-targeting ability, and tissue distribution in rats were examined. The microspheres had a regular and round shape. The mean diameter was 10.06 µm, and the diameter of 89.93% of all microspheres ranged from 7.0 µm to 30.0 µm. Tissue distribution of the microspheres was evaluated along with a conventional enrofloxacin preparation after a single intravenous injection (7.5 mg of enrofloxacin/kg bw). The results showed that the elimination half-life (t1/2β) of enrofloxacin from lung was prolonged from 7.94 h for the conventional enrofloxacin to 13.28 h for the microspheres. Area under the lung concentration versus time curve from 0 h to ∞ (AUC0-∞) was increased from 11.66 h·µg/g to 508.00 h·µg/g. The peak concentration (Cmax) in lung was increased from 5.95 µg/g to 93.36 µg/g. Three lung-targeting parameters were further assessed and showed that the microspheres had remarkable lung-targeting capabilities. PMID:25643802

Preparation and evaluation of enrofloxacin microspheres and tissue distribution in rats.

PubMed

Yang, Fan; Kang, Jijun; Yang, Fang; Zhao, Zhensheng; Kong, Tao; Zeng, Zhenling

2015-01-01

New enrofloxacin microspheres were formulated, and their physical properties, lung-targeting ability, and tissue distribution in rats were examined. The microspheres had a regular and round shape. The mean diameter was 10.06 µm, and the diameter of 89.93% of all microspheres ranged from 7.0 µm to 30.0 µm. Tissue distribution of the microspheres was evaluated along with a conventional enrofloxacin preparation after a single intravenous injection (7.5 mg of enrofloxacin/kg bw). The results showed that the elimination half-life (t1/2β) of enrofloxacin from lung was prolonged from 7.94 h for the conventional enrofloxacin to 13.28 h for the microspheres. Area under the lung concentration versus time curve from 0 h to ∞ (AUC00∞) was increased from 11.66 h·µg/g to 508.00 h·µg/g. The peak concentration (Cmax) in lung was increased from 5.95 µg/g to 93.36 µg/g. Three lung-targeting parameters were further assessed and showed that the microspheres had remarkable lung-targeting capabilities.

Biodegradable Chitosan Magnetic Nanoparticle Carriers for Sub-Cellular Targeting Delivery of Artesunate for Efficient Treatment of Breast Cancer

NASA Astrophysics Data System (ADS)

Subramanian, Natesan; Abimanyu, Sugumaran; Vinoth, Jeevanesan; Sekar, Ponnusamy Chandra

2010-12-01

Artesunate is a semi-synthetic derivative of artemisinin, the active principle extracted from Artemisia annua. It possesses good anti-proliferative activity and anti-angiogenic activity with very low toxicity to normal healthy cells. The drawback of most cancer drugs is their inability to accumulate selectively in the cancerous cells. So, large quantities of doses have to be administered to get the required therapeutic concentration in the target site and it resulted in many serious side effects due to the exposure of healthy cells to higher concentrations of cytotoxic drugs. The problem may be solved by selectively and quantitatively accumulating the drug at target site using magnetic nanoparticles guided by an externally applied magnetic field. A modest attempt has been made in this present study, the artesunate magnetic nanoparticle was successfully formulated using two forms of chitosan and evaluated for its in-vitro characteristics like surface morphology, particle size and distribution, zeta potential, magnetic susceptibility, encapsulation efficiency, loading capacity and in-vitro drug release. The synthesized magnetite size was 73 nm and the size of developed magnetic nanoparticles of artesunate was in the range of 90 to 575 nm. Acetic acid soluble chitosan at low concentration exhibit highest encapsulation efficiency and drug loading whereas increase in water soluble chitosan concentration increases the encapsulation efficiency and drug loading in formulations. The developed chitosan magnetic nanoparticles of artesunate shows better release characteristics and may be screened for its in-vivo breast cancer activity.

Construction of a novel peptide nucleic acid piezoelectric gene sensor microarray detection system.

PubMed

Chen, Ming; Liu, Minghua; Yu, Lili; Cai, Guoru; Chen, Qinghai; Wu, Rong; Wang, Feng; Zhang, Bo; Jiang, Tianlun; Fu, Welling

2005-08-01

A novel 2 x 5 clamped style piezoelectric gene sensor microarray has been successfully constructed. Every crystal unit of the fabricated gene sensor can oscillate independently without interfering with each other. The bis-peptide nucleic acid (bis-PNA) probe, which can combine with target DNA or RNA sequences more effectively and specifically than a DNA probe, was designed and immobilized on the surface of the gene sensor microarray to substitute the conventional DNA probe for direct detection of the hepatitis B virus (HBV) genomic DNA. Detection conditions were then explored and optimized. Results showed that PBS buffer of pH 6.8, an ion concentration of 20 mmol/liter, and a probe concentration of 1.5 micromol/liter were optimal for the detection system. Under such optimized experimental conditions, the specificity of bis-PNA was proved much higher than that of DNA probe. The relationship between quantity of target and decrease of frequency showed a typical saturation curve when concentrations of target HBV DNA varied from 10 pg/liter to 100 microg/liter, and 10 microg/liter was the watershed, with a statistic linear regression equation of I gC = -2.7455 + 0.0691 deltaF and the correlating coefficient of 0.9923. Fortunately, this is exactly the most ordinary variant range of the HBV virus concentration in clinical hepatitis samples. So, a good technical platform is successfully constructed and it will be applied to detect HBV quantitatively in clinical samples.

The utility of ultra-performance liquid chromatography/electrospray ionisation time-of-flight mass spectrometry for multi-residue determination of pesticides in strawberry.

PubMed

Taylor, Michael J; Keenan, George A; Reid, Kirsty B; Fernández, Diana Uría

2008-09-01

The utility of ultra-performance liquid chromatography/orthogonal-acceleration time-of flight mass spectrometry (UPLC/TOFMS) for the rapid qualitative and quantitative analysis of 100 pesticides targeted in strawberry was assessed by comparing results with those obtained using a validated in-house UPLC tandem mass spectrometry (MS/MS) multi-residue method. Crude extracts from retail strawberry samples received as part of the 2007 annual UK pesticide residues in food surveillance programme were screened for the presence of pesticide residues using UPLC/TOFMS. Accurate mass measurement of positive and negative ions allowed their extraction following 'full mass range data acquisition' with negligible interference from background or co-eluting species observed during UPLC gradient separation (in a cycle time of just 6.5 min per run). Extracted ion data was used to construct calibration curves and to detect and identify any incurred residues (i.e. pesticides incorporated in or on the test material following application during cultivation, harvest and storage). Calibration using matrix-matched standards was performed over a narrow concentration range of 0.005-0.04 mg kg(-1) with determination coefficients (r2) > or =0.99 for all analytes with the exception of malathion/fenarimol/fludioxanil (r2 = 0.98), quassia/pymetrazine (r2 = 0.97) and fenthion sulfone (r2 = 0.95). Residues found in selected samples ranged from 0.025-0.28 mg kg(-1) and were in excellent agreement with results obtained using UPLC/MS/MS. Mass measurement accuracies of < or =5 ppm were achieved consistently throughout the separation, mass range and concentration range of interest thus providing the opportunity to obtain discrete elemental compositions of target ions.

RGD peptide-targeted polyethylenimine-entrapped gold nanoparticles for targeted CT imaging of an orthotopic model of human hepatocellular carcinoma

NASA Astrophysics Data System (ADS)

Zhou, Benqing; Wang, Meng; Zhou, Feifan; Song, Jun; Qu, Junle; Chen, Wei R.

2018-02-01

We report the synthesis and characterization of arginine-glycine-aspartic acid (RGD) peptide-targeted polyethylenimine (PEI)-entrapped gold nanoparticles (RGD-Au PENPs) for targeted CT imaging of hepatic carcinomas in situ. In this work, PEI sequentially modified with polyethylene glycol (PEG), and RGD linked-PEG was used as a nanoplatform to prepare AuNPs, followed by complete acetylation of PEI surface amines. We showed that the designed RGD-Au PENPs were colloidally stable and biocompatible in the given concentration range, and could be specifically taken up by αvβ3 integrin-overexpressing liver cancer cells in vitro. Furthermore, in vivo CT imaging results revealed that the particles displayed a great contrast enhancement of hepatic carcinomas region, and could target to hepatic carcinomas region in situ. With the proven biodistribution and histological examinations in vivo, the synthesized RGD-Au PENPs show a great formulation to be used as a contrast agent for targeted CT imaging of different αvβ3 integrin receptoroverexpressing tumors.

Determination of ∆-9-Tetrahydrocannabinol (THC), 11-hydroxy-THC, 11-nor-9-carboxy-THC and Cannabidiol in Human Plasma using Gas Chromatography-Tandem Mass Spectrometry.

PubMed

Andrenyak, David M; Moody, David E; Slawson, Matthew H; O'Leary, Daniel S; Haney, Margaret

2017-05-01

Two marijuana compounds of particular medical interest are delta-9-tetrahydrocannabinol (THC) and cannabidiol (CBD). A gas chromatography-tandem mass spectrometry (GC-MS-MS) method was developed to test for CBD, THC, hydroxy-THC (OH-THC) and carboxy-THC (COOH-THC) in human plasma. Calibrators (THC and OH-THC, 0.1 to 100; CBD, 0.25 to 100; COOH-THC, 0.5-500 ng/mL) and controls (0.3, 5 and 80 ng/mL, except COOH-THC at 1.5, 25 and 400 ng/mL) were prepared in blank matrix. Deuterated (d3) internal standards were added to 1-mL samples. Preparation involved acetonitrile precipitation, liquid-liquid extraction (hexane:ethyl acetate, 9:1), and MSTFA derivatization. An Agilent 7890 A GC was interfaced with an Agilent 7000 MS Triple Quadrupole. Selected reaction monitoring was employed. Blood samples were provided from a marijuana smoking study (two participants) and a CBD ingestion study (eight participants). Three analytes with the same transitions (THC, OH-THC and COOH-THC) were chromatographically separated. Matrix selectivity studies showed endogenous chromatographic peak area ratios (PAR) at the analyte retention times were <20% of the analyte limit of quantitation PAR. The intra-assay accuracy ranged from 83.5% to 118% of target and the intra-run imprecision ranged from 2.0% to 19.1%. The inter-assay accuracy ranged from 90.3% to 104% of target and the inter-run imprecision ranged from 6.5% to 12.0%. Stability was established for 25 hours at room temperature, 207 days at -20°C, after three freeze-thaw cycles and for 26 days for rederivatized processed samples. After smoking marijuana predictable concentrations of THC, OH-THC and COOH-THC were seen; low concentrations of CBD were detected at early time points. In moderate users who had not smoked for at least 9 hours before ingesting an 800 mg oral dose of CBD, the method was sensitive enough to follow residual concentrations of THC and OH-THC; sustained COOH-THC concentrations over 50 ng/mL validated its higher analytical range. © The Author 2017. Published by Oxford University Press. All rights reserved. For Permissions, please email: journals.permissions@oup.com.

Determination of ∆-9-Tetrahydrocannabinol (THC), 11-hydroxy-THC, 11-nor-9-carboxy-THC and Cannabidiol in Human Plasma using Gas Chromatography–Tandem Mass Spectrometry

PubMed Central

Andrenyak, David M.; Slawson, Matthew H.; O'Leary, Daniel S.; Haney, Margaret

2017-01-01

Abstract Two marijuana compounds of particular medical interest are delta-9-tetrahydrocannabinol (THC) and cannabidiol (CBD). A gas chromatography–tandem mass spectrometry (GC–MS-MS) method was developed to test for CBD, THC, hydroxy-THC (OH-THC) and carboxy-THC (COOH-THC) in human plasma. Calibrators (THC and OH-THC, 0.1 to 100; CBD, 0.25 to 100; COOH-THC, 0.5–500 ng/mL) and controls (0.3, 5 and 80 ng/mL, except COOH-THC at 1.5, 25 and 400 ng/mL) were prepared in blank matrix. Deuterated (d3) internal standards were added to 1-mL samples. Preparation involved acetonitrile precipitation, liquid–liquid extraction (hexane:ethyl acetate, 9:1), and MSTFA derivatization. An Agilent 7890 A GC was interfaced with an Agilent 7000 MS Triple Quadrupole. Selected reaction monitoring was employed. Blood samples were provided from a marijuana smoking study (two participants) and a CBD ingestion study (eight participants). Three analytes with the same transitions (THC, OH-THC and COOH-THC) were chromatographically separated. Matrix selectivity studies showed endogenous chromatographic peak area ratios (PAR) at the analyte retention times were <20% of the analyte limit of quantitation PAR. The intra-assay accuracy ranged from 83.5% to 118% of target and the intra-run imprecision ranged from 2.0% to 19.1%. The inter-assay accuracy ranged from 90.3% to 104% of target and the inter-run imprecision ranged from 6.5% to 12.0%. Stability was established for 25 hours at room temperature, 207 days at −20°C, after three freeze-thaw cycles and for 26 days for rederivatized processed samples. After smoking marijuana predictable concentrations of THC, OH-THC and COOH-THC were seen; low concentrations of CBD were detected at early time points. In moderate users who had not smoked for at least 9 hours before ingesting an 800 mg oral dose of CBD, the method was sensitive enough to follow residual concentrations of THC and OH-THC; sustained COOH-THC concentrations over 50 ng/mL validated its higher analytical range. PMID:28069869

Glycomacropeptide in children with phenylketonuria: does its phenylalanine content affect blood phenylalanine control?

PubMed

Daly, A; Evans, S; Chahal, S; Santra, S; MacDonald, A

2017-08-01

In phenylketonuria (PKU), there are no data available for children with respect to evaluating casein glycomacropeptide (CGMP) as an alternative to phenylalanine-free protein substitutes [Phe-free L-amino acid (AA)]. CGMP contains a residual amount of phenylalanine, which may alter blood phenylalanine control. In a prospective 6-month pilot study, we investigated the effect on blood phenylalanine control of CGMP-amino acid (CGMP-AA) protein substitute in 22 PKU subjects (13 boys, nine girls), median age (range) 11 years (6-16 years). Twelve received CGMP-AA and nine received Phe-free L-AA, (1 CGMP-AA withdrawal). Subjects partially or wholly replaced Phe-free L-AA with CGMP-AA. If blood phenylalanine exceeded the target range, the CGMP-AA dose was reduced and replaced with Phe-free L-amino acids. The control group remained on Phe-free L-AAs. Phenylalanine, tyrosine and Phe : Tyr ratio concentrations were compared with the results for the previous year. In the CGMP-AA group, there was a significant increase in blood phenylalanine concentrations (pre-study, 275 μmol L -1 ; CGMP-AA, 317 μmol L -1 ; P = 0.02), a decrease in tyrosine concentrations (pre-study, 50 μmol L -1 ; CGMP-AA, 40 μmol L -1 ; P = 0.03) and an increase in Phe : Tyr ratios (pre-study, Phe : Tyr 4.9:1; CGMP-AA, Phe : Tyr 8:1; P = 0.02). In the control group there was a non-significant fall in phenylalanine concentrations (pre-study 325μmol/L: study 280μmol/L [p = 0.9], and no significant changes for tyrosine or phe/tyr ratios [p = 0.9]. Children taking the CGMP-AA found it more acceptable to L-AA. Blood phenylalanine control declined with CGMP-AA but, by titrating the dose of CGMP-AA, blood phenylalanine control remained within target range. The additional intake of phenylalanine may have contributed to the change in blood phenylalanine concentration. CGMP-AA use requires careful monitoring in children. © 2017 The British Dietetic Association Ltd.

Gold nanoparticle-aided brachytherapy with vascular dose painting: estimation of dose enhancement to the tumor endothelial cell nucleus.

PubMed

Ngwa, Wilfred; Makrigiorgos, G Mike; Berbeco, Ross I

2012-01-01

Theoretical microdosimetry at the subcellular level is employed in this study to estimate the dose enhancement to tumor endothelial cell nuclei, caused by radiation-induced photo/Auger electrons originating from gold nanoparticles (AuNPs) targeting the tumor endothelium, during brachytherapy. A tumor vascular endothelial cell (EC) is modeled as a slab of 2 μm (thickness) × 10 μm (length) × 10 μm (width). The EC contains a nucleus of 5 μm diameter and thickness of 0.5-1 μm, corresponding to nucleus size 5%-10% of cellular volume, respectively. Analytic calculations based on the electron energy loss formula of Cole were carried out to estimate the dose enhancement to the nucleus caused by photo/Auger electrons from AuNPs attached to the exterior surface of the EC. The nucleus dose enhancement factor (nDEF), representing the ratio of the dose to the nucleus with and without the presence of gold nanoparticles was calculated for different AuNP local concentrations. The investigated concentration range considers the potential for significantly higher local concentration near the EC due to preferential accumulation of AuNP in the tumor vasculature. Four brachytherapy sources: I-125, Pd-103, Yb-169, and 50 kVp x-rays were investigated. For nucleus size of 10% of the cellular volume and AuNP concentrations ranging from 7 to 140 mg/g, brachytherapy sources Pd-103, I-125, 50 kVp, and Yb-169 yielded nDEF values of 5.6-73, 4.8-58.3, 4.7-56.6, and 3.2-25.8, respectively. Meanwhile, for nucleus size 5% of the cellular volume in the same concentration range, Pd-103, I-125, 50 kVp, and Yb-169 yielded nDEF values of 6.9-79.2, 5.1-63.2, 5.0-61.5, and 3.3-28.3, respectively. The results predict that a substantial dose boost to the nucleus of endothelial cells can be achieved by applying tumor vasculature-targeted AuNPs in combination with brachytherapy. Such vascular dose boosts could induce tumor vascular shutdown, prompting extensive tumor cell death.

Targeting radiosensitizers to DNA by attachment of an intercalating group: Nitroimidazole-linked phenanthridines

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

Cowan, D.S.; Panicucci, R.; McClelland, R.A.

The nitroimidazole-linked phenanthridine series of compounds (NLP-1, 2, and 3) were synthesized under the assumption that it should be possible to enhance the molar efficiency of 2-nitroimidazoles as hypoxic cell radiosensitizers and cytotoxins by targeting them to their likely site of action, DNA. The targeting group chosen was the phenanthridine moiety, the major component of the classical DNA intercalating compound, ethidium bromide. The sole difference between the compounds is the length of the hydrocarbon chain linking the nitroimidazole to the phenanthridine. The phenanthridine group with a three-carbon side chain, P-1, was also synthesized to allow studies on the effect ofmore » the targeting group by itself. The ability of the compounds to bind to DNA is inversely proportional to their linker chain length with binding constant values ranging from approximately 1 {times} 10(5) mol-1 for NLP-2 to 6 {times} 10(5) mol-1 for NLP-3. The NLP compounds show selective toxicity to hypoxic cells at 37 degrees C at external drug concentrations 10-40 times lower than would be required for untargeted 2-nitroimidazoles such as misonidazole in vitro. Toxicity to both hypoxic and aerobic cells is dependent on the linker chain: the shorter the chain, the greater the toxicity. In addition, the NLP compounds radiosensitize hypoxic cells at external drug concentrations as low as 0.05 mM with almost the full oxygen effect being observed at a concentration of 0.5 mM. These concentrations are 10-100 times lower than would be required for similar radiosensitization using misonidazole. Radiosensitizing ability is independent of linker chain length. The present compounds represent prototypes for further studies of the efficacy and mechanism of action of 2-nitroimidazoles targeted to DNA by linkage to an intercalating group.« less

Effects of chronic exposure to thiamethoxam on larvae of the hoverfly Eristalis tenax (Diptera, Syrphidae)

PubMed Central

Davenport, Balin; Vogiatzis, Kate

2018-01-01

There is widespread concern over the use of neonicotinoid pesticides in the agro-ecosystem, due in part to their high water solubility which can lead to widespread contamination of non-target areas including standing surface water. Most studies investigating the negative fitness consequences of neonicotinoids have focused on bees, with little research on the impact on other non-target insects. Here we examined the effect of exposure on the aquatic larval stages of the hoverfly Eristalis tenax L. (Diptera: Syrphidae) to a range of concentrations (control, 5, 15, 50, 100 and 500 ppb) of the neonicotinoid thiamethoxam; no published studies have thus far examined the effects of neonicotinoids on hoverflies. Survival was significantly lower when exposed to 500 ppb thiamethoxam, but this concentration exceeds that likely to be found in the field. We observed no effect on survival, development or any latent effects on adult activity budgets resulting from exposure to lower concentrations (up to 100 ppb). Our results suggest that E. tenax exposed as larvae to thiamethoxam are unlikely to be negatively impacted by this neonicotinoid under field conditions. PMID:29372118

Biosensing based on magnetically induced self-assembly of particles in magnetic colloids.

PubMed

Yang, Ye; Morimoto, Yoshitaka; Takamura, Tsukasa; Sandhu, Adarsh

2012-03-01

Superparamagnetic beads and nonmagnetic beads of different sizes were assembled to form a "ring-structure" in a magnetorheological (MR) fluid solution by the application of external magnetic fields. For superparamagnetic beads and non-magnetic beads functionalized with probe and target molecules, respectively, the ring-structure was maintained even after removing the external magnetic field due to biomolecular bonding. Several experiments are described, including the formation process of ring-structures with and without molecular interactions, the accelerating effect of external magnetic fields, and the effect of biotin concentration on the structures of the rings. We define the small nonmagnetic particles as "petals" because the whole structure looks like a flower. The number of remnant ring petals was a function of the concentration of target molecules in the concentration range of 0.0768 ng/ml-3.8419 ng/ml which makes this protocol a promising method for biosensing. Not only was the formation process rapid, but the resulting two-dimensional colloidal system also offers a simple method for reducing reagent consumption and waste generation.

Enhanced antioxidant activity of gold nanoparticle embedded 3,6-dihydroxyflavone: a combinational study

NASA Astrophysics Data System (ADS)

Medhe, Sharad; Bansal, Prachi; Srivastava, Man Mohan

2014-02-01

The antioxidative effect of selected dietary compounds (3,6-dihydroxyflavone, lutein and selenium methyl selenocysteine) was determined in single and combination using DPPH (2,2-diphenyl-l-picrylhydrazyl), OH (hydroxyl), H2O2 (hydrogen peroxide) and NO (nitric oxide) radical scavenging assays. Radical scavenging effect of the dietary phytochemicals individually are found to be in the order: ascorbic acid (standard) > lutein > 3,6-dihydroxyflavone > selenium methyl selenocysteine, at concentration 100 μg/ml, confirmed by all the four bioassays (p < 0.05). Among the various combinations studied, the triplet combination of 3,6-dihydroxyflavone, lutein and selenium methyl selenocysteine (1:1:1), exhibited enhancement in the target activity at same concentration level. Synthesized gold nanoparticle embedded 3,6-dihydroxyflavone further enhanced the target antioxidant activity. The combinational study including gold nanoparticle embedded 3,6-dihydroxyflavone with other native dietary nutrients showed remarkable increase in antioxidant activity at the same concentration level. The present in vitro study on combinational and nanotech enforcement of dietary phytochemicals shows the utility in the architecture of nanoparticle embedded phytoproducts having a wide range of applications in medical science.

Biosensing of DNA oxidative damage: a model of using glucose meter for non-glucose biomarker detection.

PubMed

Zhu, Xuena; Sarwar, Mehenur; Yue, Qiaoli; Chen, Chunying; Li, Chen-Zhong

2017-01-01

Non-glucose biomarker-DNA oxidative damage biomarker 8-hydroxy-2'-deoxyguanosine (8-OHdG) has been successfully detected using a smartphone-enabled glucose meter. Through a series of immune reactions and enzymatic reactions on a solid lateral flow platform, 8-OHdG concentration has been converted to a relative amount of glucose, and therefore can be detected by conventional glucose meter directly. The device was able to detect 8-OHdG concentrations in phosphate buffer saline as low as 1.73 ng mL -1 with a dynamic range of 1-200 ng mL -1 . Considering the inherent advantages of the personal glucose meter, the demonstration of this device, therefore, should provide new opportunities for the monitoring of a wide range of biomarkers and various target analytes in connection with different molecular recognition events.

Fate of Volatile Organic Compounds in Constructed Wastewater Treatment Wetlands

USGS Publications Warehouse

Keefe, S.H.; Barber, L.B.; Runkel, R.L.; Ryan, J.N.

2004-01-01

The fate of volatile organic compounds was evaluated in a wastewater-dependent constructed wetland near Phoenix, AZ, using field measurements and solute transport modeling. Numerically based volatilization rates were determined using inverse modeling techniques and hydraulic parameters established by sodium bromide tracer experiments. Theoretical volatilization rates were calculated from the two-film method incorporating physicochemical properties and environmental conditions. Additional analyses were conducted using graphically determined volatilization rates based on field measurements. Transport (with first-order removal) simulations were performed using a range of volatilization rates and were evaluated with respect to field concentrations. The inverse and two-film reactive transport simulations demonstrated excellent agreement with measured concentrations for 1,4-dichlorobenzene, tetrachloroethene, dichloromethane, and trichloromethane and fair agreement for dibromochloromethane, bromo-dichloromethane, and toluene. Wetland removal efficiencies from inlet to outlet ranged from 63% to 87% for target compounds.

Residue behavior of organochlorine pesticides during the production process of yogurt and cheese.

PubMed

Duan, Jing; Cheng, Zheng; Bi, Jiawei; Xu, Yangguang

2018-04-15

The presence of organochlorine pesticides (OCPs) in dairy products can lead to human exposure. This study investigated the behavior of OCP residues in milk during yogurt and cheese production. Gas chromatography with electron-capture detection (GC-ECD) was used to detect α-hexachlorocyclohexane (HCH), hexachlorobenzene (HCB), γ-HCH, g-chlordane, and α-chlordane in fresh milk, yogurt, and cheese. The results showed that fermentation reduced the residual concentration of OCPs in yogurt, with processing factors (PFs) ranging from 0.42 to 0.64. The reductions in residue levels during fermentation were due to the activity of the starter. The cheese making process increased the residual concentration of OCPs in cheese compared to raw milk, with PFs ranging from 2.37 to 4.93. Additionally, milk, yogurt, and cheese samples were purchased from local markets and OCP levels were analyzed. The target OCPs ranged from ND to 16.50 μg/kg in these samples. Copyright © 2017 Elsevier Ltd. All rights reserved.

Effects of neonicotinoids and fipronil on non-target invertebrates.

PubMed

Pisa, L W; Amaral-Rogers, V; Belzunces, L P; Bonmatin, J M; Downs, C A; Goulson, D; Kreutzweiser, D P; Krupke, C; Liess, M; McField, M; Morrissey, C A; Noome, D A; Settele, J; Simon-Delso, N; Stark, J D; Van der Sluijs, J P; Van Dyck, H; Wiemers, M

2015-01-01

We assessed the state of knowledge regarding the effects of large-scale pollution with neonicotinoid insecticides and fipronil on non-target invertebrate species of terrestrial, freshwater and marine environments. A large section of the assessment is dedicated to the state of knowledge on sublethal effects on honeybees (Apis mellifera) because this important pollinator is the most studied non-target invertebrate species. Lepidoptera (butterflies and moths), Lumbricidae (earthworms), Apoidae sensu lato (bumblebees, solitary bees) and the section "other invertebrates" review available studies on the other terrestrial species. The sections on freshwater and marine species are rather short as little is known so far about the impact of neonicotinoid insecticides and fipronil on the diverse invertebrate fauna of these widely exposed habitats. For terrestrial and aquatic invertebrate species, the known effects of neonicotinoid pesticides and fipronil are described ranging from organismal toxicology and behavioural effects to population-level effects. For earthworms, freshwater and marine species, the relation of findings to regulatory risk assessment is described. Neonicotinoid insecticides exhibit very high toxicity to a wide range of invertebrates, particularly insects, and field-realistic exposure is likely to result in both lethal and a broad range of important sublethal impacts. There is a major knowledge gap regarding impacts on the grand majority of invertebrates, many of which perform essential roles enabling healthy ecosystem functioning. The data on the few non-target species on which field tests have been performed are limited by major flaws in the outdated test protocols. Despite large knowledge gaps and uncertainties, enough knowledge exists to conclude that existing levels of pollution with neonicotinoids and fipronil resulting from presently authorized uses frequently exceed the lowest observed adverse effect concentrations and are thus likely to have large-scale and wide ranging negative biological and ecological impacts on a wide range of non-target invertebrates in terrestrial, aquatic, marine and benthic habitats.

Deoxynivalenol, deoxynivalenol-3-glucoside, and enniatins: the major mycotoxins found in cereal-based products on the Czech market.

PubMed

Malachova, Alexandra; Dzuman, Zbynek; Veprikova, Zdenka; Vaclavikova, Marta; Zachariasova, Milena; Hajslova, Jana

2011-12-28

Fusarium toxins, Alternaria toxins, and ergot alkaloids represent common groups of mycotoxins that can be found in cereals grown under temperate climatic conditions. Because most of them are chemically and thermally stable, these toxic fungal secondary metabolites might be transferred from grains into the final products. To get information on the commensurate contamination of various cereal-based products collected from the Czech retail market in 2010, the occurrence of "traditional" mycotoxins such as groups of A and B trichothecenes and zearalenone, less routinely determined Alternaria toxins (alternariol, alternariol monomethyl ether and altenuene), ergot alkaloids (ergosine, ergocryptine, ergocristine, and ergocornine) and "emerging" mycotoxins (enniatins A, A1, B, and B1 and beauvericin) were monitored. In a total 116 samples derived from white flour and mixed flour, breakfast cereals, snacks, and flour, only trichothecenes A and B and enniatins were found. Deoxynivalenol was detected in 75% of samples with concentrations ranging from 13 to 594 μg/kg, but its masked form, deoxynivalenol-3-β-d-glucoside, has an even higher incidence of 80% of samples, and concentrations ranging between 5 and 72 μg/kg were detected. Nivalenol was found only in three samples at levels of 30 μg/kg. For enniatins, all of the samples investigated were contaminated with at least one of four target enniatins. Enniatin A was detected in 97% of samples (concentration range of 20-2532 μg/kg) followed by enniatin B with an incidence in 91% of the samples (concentration range of 13-941 μg/kg) and enniatin B1 with an incidence of 80% in the samples tested (concentration range of 8-785 μg/kg). Enniatin A1 was found only in 44% of samples at levels ranging between 8 and 851 μg/kg.

Effect of preservative removal from fixed-combination bimatoprost/timolol on intraocular pressure lowering: a potential timolol dose–response phenomenon

PubMed Central

Shen, Jie; Bejanian, Marina

2016-01-01

Purpose Many patients with glaucoma require combination therapies to achieve target intraocular pressure (IOP) and preserve visual function. Ocular hypotensives often contain a preservative (eg, benzalkonium chloride [BAK]), but preservative-free (PF) formulations have been developed for patients with sensitivity. A Phase III study found the efficacy of bimatoprost 0.03%/timolol 0.5% (bim/tim, Ganfort®) PF to be equivalent to that of preserved bim/tim, although a trend favoring bim/tim PF was observed. As BAK is a corneal penetration enhancer, this literature review aims to explain these findings by exploring the relationship between timolol concentration and its IOP-lowering effect. Methods Systematic searches were performed in Scopus and PubMed for clinical trials published in English between 1960 and July 2014 using the keywords “timolol”, “intraocular pressure”, and the concentrations “1%, 0.5%, OR 0.25%”. Articles that directly compared IOP-lowering effects of ≥2 concentrations of timolol were identified by manual screening, and cross-checked for duplication. Results Seventeen studies that included 10–371 patients were evaluated; the majority were randomized (16/17), double-masked (14/17), and enrolled patients with open-angle glaucoma or ocular hypertension (12/17). All studies investigated timolol in preserved formulations. Timolol concentrations tested ranged from 0.008% to 1.5%. Of 13 studies comparing timolol 0.25% versus 0.5%, two found the 0.25% dose to have greater IOP-lowering effects, and three reported the opposite; eight reported similar IOP lowering. Results also indicate that timolol 0.5% may be more effective than higher concentrations. Conclusion The evidence suggests that timolol may have an inverted U-shaped dose–response curve, and that its optimal IOP-lowering concentration is between 0.25% and 0.5%. Compared with bim/tim, removal of the permeability enhancer BAK in bim/tim PF could have resulted in a lower timolol concentration at the target site, bringing the effective concentration within the 0.25%–0.5% range and enhancing the efficacy of bim/tim PF. PMID:27041984

Volatile organic compounds concentrations during the construction process in newly-built timber-frame houses: source identification and emission kinetics.

PubMed

Plaisance, H; Vignau-Laulhere, J; Mocho, P; Sauvat, N; Raulin, K; Desauziers, V

2017-05-24

Building and furniture materials are known to be major sources of volatile organic compounds (VOCs) indoors. During the construction process, an introduced material can have a more or less long-term impact on the indoor air quality according to the building characteristics. In this study, field measurements were carried out at six construction stages in three energy-efficient timber-frame houses. Data analysis focused on the ten most abundant compounds found among an initial list of fifteen target VOCs, namely formaldehyde, acetaldehyde, hexanal, toluene, m/p-xylenes, ethylbenzene, styrene, α-pinene, 3-carene and d-limonene. The chemical compositions and concentration variation patterns were recorded. The results showed a high pollution count, with m/p-xylenes and ethylbenzene concentrations ranging from 1900 to 5100 μg m -3 occurring at the time of the structural work (representing more than 88% of the sum of the target VOCs). Emission tests done on a large number of materials used in the construction revealed that this pollution is due to the emissions from the polyurethane adhesive mastic used as a sealing material. The emission kinetics of polyurethane adhesive mastic was assessed alone and also within a material assembly reconstituting a room wall. The results showed that the superposition of materials led to a slowing down of the VOC emission process from polyurethane adhesive mastic, which explains the concentration decays recorded in houses during the construction process. At the final construction stage, the concentration levels were low for all compounds (the sums of the target VOCs were between 18 and 32 μg m -3 ), with the aldehydes (formaldehyde, acetaldehyde and hexanal) now becoming the major fraction in the chemical composition in the last stages of construction (representing 50-70% of the sum of the target VOCs). This is in agreement with the fact that the sources of aldehydes are the most numerous among the materials and have rather slow emission kinetics.

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 bioaccumulation and toxicology studies employing small fishes with low blood compartment volumes. Copyright © 2015 Elsevier B.V. All rights reserved.

A broad cocktail of environmental pollutants found in eggs of three seabird species from remote colonies in Norway.

PubMed

Huber, Sandra; Warner, Nicholas A; Nygård, Torgeir; Remberger, Mikael; Harju, Mikael; Uggerud, Hilde T; Kaj, Lennart; Hanssen, Linda

2015-06-01

Eggs of 3 seabird species, common eider (Somateria mollisima), European shag (Phalacrocorax aristotelis aristotelis), and European herring gull (Larus argentatus), were surveyed for a broad range of legacy and emerging pollutants to assess chemical mixture exposure profiles of seabirds from the Norwegian marine environment. In total, 201 chemical substances were targeted for analysis ranging from metals, organotin compounds, polycyclic aromatic hydrocarbons (PAHs), polychlorinated biphenyls (PCBs) and associated metabolites, chlorinated paraffins, chlorinated and nonchlorinated organic pesticides, per- and polyfluoroalkyl substances (PFAS), dechlorane plus, octachlorostyrene, brominated flame retardants (BFRs), organophosphorous compounds, brominated and alkyl phenols, cyclic siloxanes, and phthalates. Of the chemicals targeted, 149 substances were found above the detection limits, with metals dominating the contaminant profile and comprising 60% of the total contaminant load. Polychlorinated biphenyls, pesticides, organophosphorous compounds, and PFAS were the dominant contaminant classes of organic pollutants found within the seabird species, with the highest loads occurring in herring gulls, followed by shag, and common eider. New generation pollutants (e.g., PFAS, organophosphorous compounds, and alkylphenols) were detected at similar or higher concentrations than the legacy persistent organic pollutants (POPs). Time trends of reported concentrations of legacy POPs appear to have decreased in recent decades from the Norwegian coastal environment. Concentrations of detected pollutants do not appear to have a negative effect on seabird population development within the sampling area. Additional stress caused by pollutants, however, may affect seabird health more at the individual level. © 2015 SETAC.

Evaluation of a protocol for vancomycin administration in critically patients with and without kidney dysfunction.

PubMed

Spadaro, Savino; Berselli, Angela; Fogagnolo, Alberto; Capuzzo, Maurizia; Ragazzi, Riccardo; Marangoni, Elisabetta; Bertacchini, Sara; Volta, Carlo Alberto

2015-06-27

Administration of vancomycin in critically ill patients needs close regulation. While subtherapeutical vancomycin serum concentration (VSC) is associated with increased mortality, accumulation is responsible for nephrotoxicity. Our study aimed to estimate the efficacy of a vancomycin-dosing protocol in reaching appropriate serum concentration in patients with and without kidney dysfunction. This was a retrospective study in critically ill patients treated with continuous infusion of vancomycin. Patients with creatinine clearance > 50 ml/min (Group A) were compared to those with creatinine clearance ≤ 50 ml/min (Group B). 348 patients were enrolled (210 in Group A, 138 in Group B). At first determination, patients with kidney dysfunction (Group B) had a statistically higher percentage of vancomycin in target range, while the percentage of patients with a VSC under the range was almost equal. These percentages differed at the subsequent measurements. The number of patients with low vancomycin concentration progressively decreased, except in those with augmented renal clearance; the percentage of patients with VSC over 30 mg/L was about 28 %, irrespective of the presence or absence of kidney dysfunction. Patients who reached a subtherapeutic level at the first VSC measurement had a significant correlation with in-hospital mortality. Our protocol seems to allow a rapid achievement of a target VSC particularly in patients with kidney dysfunction. In order to avoid subtherapeutical VSC, our algorithm should be implemented by the estimation of the presence of an augmented renal clearance.

Targeting the cell cycle and the PI3K pathway: a possible universal strategy to reactivate innate tumor suppressor programmes in cancer cells.

PubMed

David-Pfeuty, Thérèse; Legraverend, Michel; Ludwig, Odile; Grierson, David S

2010-04-01

Corruption of the Rb and p53 pathways occurs in virtually all human cancers. This could be because it lends oncogene-bearing cells a surfeit of Cdk activity and growth, enabling them to elaborate strategies to evade tumor-suppressive mechanisms and divide inappropriately. Targeting both Cdk activities and the PI3K pathway might be therefore a potentially universal means to palliate their deficiency in cancer cells. We showed that the killing efficacy of roscovitine and 16 other purines and potentiation of roscovitine-induced apoptosis by the PI3K inhibitor, LY294002, decreased with increasing corruption of the Rb and p53 pathways. Further, we showed that purines differing by a single substitution, which exerted little lethal effect on distant cell types in rich medium, could display widely-differing cytotoxicity profiles toward the same cell types in poor medium. Thus, closely-related compounds targeting similar Cdks may interact with different targets that could compete for their interaction with therapeutically-relevant Cdk targets. In the perspective of clinical development in association with the PI3K pathway inhibitors, it might thus be advisable to select tumor cell type-specific Cdk inhibitors on the basis of their toxicity in cell-culture-based assays performed at a limiting serum concentration sufficient to suppress their interaction with undesirable crossreacting targets whose range and concentration would depend on the cell genotype.

Method and apparatus for aligning a solar concentrator using two lasers

DOEpatents

Diver Jr., Richard Boyer

2003-07-22

A method and apparatus are provided for aligning the facets of a solar concentrator. A first laser directs a first laser beam onto a selected facet of the concentrator such that a target board positioned adjacent to the first laser at approximately one focal length behind the focal point of the concentrator is illuminated by the beam after reflection thereof off of the selected facet. A second laser, located adjacent to the vertex of the optical axis of the concentrator, is used to direct a second laser beam onto the target board at a target point thereon. By adjusting the selected facet to cause the first beam to illuminate the target point on the target board produced by the second beam, the selected facet can be brought into alignment with the target point. These steps are repeated for other selected facets of the concentrator, as necessary, to provide overall alignment of the concentrator.

Spatial and polarity precision of concentric high-definition transcranial direct current stimulation (HD-tDCS).

PubMed

Alam, Mahtab; Truong, Dennis Q; Khadka, Niranjan; Bikson, Marom

2016-06-21

Transcranial direct current stimulation (tDCS) is a non-invasive neuromodulation technique that applies low amplitude current via electrodes placed on the scalp. Rather than directly eliciting a neuronal response, tDCS is believed to modulate excitability-enhancing or suppressing neuronal activity in regions of the brain depending on the polarity of stimulation. The specificity of tDCS to any therapeutic application derives in part from how electrode configuration determines the brain regions that are stimulated. Conventional tDCS uses two relatively large pads (>25 cm(2)) whereas high-definition tDCS (HD-tDCS) uses arrays of smaller electrodes to enhance brain targeting. The 4  ×  1 concentric ring HD-tDCS (one center electrode surrounded by four returns) has been explored in application where focal targeting of cortex is desired. Here, we considered optimization of concentric ring HD-tDCS for targeting: the role of electrodes in the ring and the ring's diameter. Finite element models predicted cortical electric field generated during tDCS. High resolution MRIs were segmented into seven tissue/material masks of varying conductivities. Computer aided design (CAD) model of electrodes, gel, and sponge pads were incorporated into the segmentation. Volume meshes were generated and the Laplace equation ([Formula: see text] · (σ [Formula: see text] V)  =  0) was solved for cortical electric field, which was interpreted using physiological assumptions to correlate with stimulation and modulation. Cortical field intensity was predicted to increase with increasing ring diameter at the cost of focality while uni-directionality decreased. Additional surrounding ring electrodes increased uni-directionality while lowering cortical field intensity and increasing focality; though, this effect saturated and more than 4 surround electrode would not be justified. Using a range of concentric HD-tDCS montages, we showed that cortical region of influence can be controlled while balancing other design factors such as intensity at the target and uni-directionality. Furthermore, the evaluated concentric HD-tDCS approaches can provide categorical improvements in targeting compared to conventional tDCS. Hypothesis driven clinical trials, based on specific target engagement, would benefit by this more precise method of stimulation that could avoid potentially confounding brain regions.

Retrospective Evaluation of Milrinone Pharmacokinetics in Children With Kidney Injury.

PubMed

Gist, Katja M; Mizuno, Tomoyuki; Goldstein, Stuart L; Vinks, Alexander

2015-12-01

Milrinone is an inotropic agent with vasodilating properties used in the treatment of ventricular dysfunction. Milrinone is predominantly eliminated by the kidneys and accumulates in the setting of acute kidney injury (AKI). The purpose of this study was to evaluate milrinone pharmacokinetics in children with AKI with or without continuous renal replacement therapy (CRRT). Retrospective collection of milrinone therapeutic drug monitoring data in patients with AKI, including those requiring CRRT, through chart review from January 2008 to March 2014. Pharmacokinetic (PK) data were analyzed by Bayesian estimation using a pediatric population PK model (MW/Pharm). Clearance estimates were allometrically scaled to body weight. Data on 11 patients were available for analysis. Three patients required CRRT. Milrinone concentrations during continuous infusion varied 30-fold and ranged from 44 to 1343 ng/mL. Of the 33 samples obtained in 11 patients, 24 were outside the target range (72.7%), with 16 (48.5%) above and 8 (24.2%) below. Patients with AKI had significantly lower milrinone clearance (4.72 ± 2.26 L/h per 70 kg) compared with published data in patients without AKI. There was large between-patient variability in milrinone clearance (range: 2.91-13.6 L/h per 70 kg). Clearance in patients on CRRT ranged from 2.8 to 7.19 L/h per 70 kg. A significant correlation between milrinone clearance and estimated creatinine clearance was observed (r = 0.70, P = 0.0097). Allometrically scaled milrinone clearance was lower in the youngest patients (younger than 2 years), suggestive of ongoing renal maturation and existing AKI. Pediatric patients with AKI have significantly lower milrinone clearance compared with published data in patients without AKI. Large variability was noted in milrinone concentrations, and they were frequently outside the target range. The large between-patient variability in milrinone concentrations suggests that dosing regimens should be individualized in this population of critically ill patients. Evaluation of PK model-based milrinone dose optimization and the use of biomarkers as predictors of changes in clearance warrant further study.

Preparation of silicon target material by adding Al-B master alloy in directional solidification

NASA Astrophysics Data System (ADS)

Li, Pengting; Wang, Kai; Ren, Shiqiang; Jiang, Dachuan; Tan, Yi

2017-03-01

The silicon target material was prepared by adding Al-6B master alloy in directional solidification. The microstructure was characterized and the resistivity was studied in this work. The results showed that the purity of the silicon target material was more than 99.999% (5N). The resistivity was ranges from 0.002 to 0.030 Ω·cm along the ingot height. It was revealed that the particles of AlB2 in Al-6B master alloy would react spontaneously and generate clusters of [B] and [Al] in molten silicon at 1723 K. After directional solidification, the content of B and Al were increasing gradually with the increase of solidified fraction. The measured values of B were in good agreement with the curve of the Scheil equation below 80% of the ingot height. The mean concentration of B was about 17.20 ppmw and the mean concentration of Al was about 8.07 ppmw after directional solidification. The measured values of Al were fitting well with the curve of values which the effective segregation coefficient was 0.00378. It was observed that B co-doped Al in directional solidification polysilicon could regulate resistivity mutually. This work provides the theoretical basis and technical support for industrial production of the silicon target material.

A fluorescent glycosyl-imprinted polymer for pH and temperature regulated sensing of target glycopeptide antibiotic.

PubMed

Chen, Kuncai; He, Rong; Luo, Xiaoyan; Qin, Pengzhe; Tan, Lei; Tang, Youwen; Yang, Zhicong

2017-08-15

This paper demonstrates a new strategy for developing a fluorescent glycosyl-imprinted polymer for pH and temperature regulated sensing of target glycopeptide antibiotic. The technique provides amino modified Mn-doped ZnS QDs as fluorescent supports, 4-vinylphenylbronic acid as a covalent monomer, N-isopropyl acrylamide as a thermo-responsive monomer in combination with acrylamide as a non-covalent monomer, and glycosyl moiety of a glycopeptide antibiotic as a template to produce fluorescent molecularly imprinted polymer (FMIP) in aqueous solution. The FMIP can alter its functional moieties and structure with pH and temperature stimulation. This allows recognition of target molecules through control of pH and temperature. The fluorescence intensity of the FMIP was enhanced gradually as the concentration of telavancin increased, and showed selective recognition toward the target glycopeptide antibiotic preferentially among other antibiotics. Using the FMIP as a sensing material, good linear correlations were obtained over the concentration range of 3.0-300.0μg/L and with a low limit of detection of 1.0μg/L. The analysis results of telavancin in real samples were consistent with that obtained by liquid chromatography tandem mass spectrometry. Copyright © 2017 Elsevier B.V. All rights reserved.

Online Continuous Trace Process Analytics Using Multiplexing Gas Chromatography.

PubMed

Wunsch, Marco R; Lehnig, Rudolf; Trapp, Oliver

2017-04-04

The analysis of impurities at a trace level in chemical products, nutrition additives, and drugs is highly important to guarantee safe products suitable for consumption. However, trace analysis in the presence of a dominating component can be a challenging task because of noncompatible linear detection ranges or strong signal overlap that suppresses the signal of interest. Here, we developed a technique for quantitative analysis using multiplexing gas chromatography (mpGC) for continuous and completely automated process trace analytics exemplified for the analysis of a CO 2 stream in a production plant for detection of benzene, toluene, ethylbenzene, and the three structural isomers of xylene (BTEX) in the concentration range of 0-10 ppb. Additional minor components are methane and methanol with concentrations up to 100 ppm. The sample is injected up to 512 times according to a pseudorandom binary sequence (PRBS) with a mean frequency of 0.1 Hz into a gas chromatograph equipped with a flame ionization detector (FID). A superimposed chromatogram is recorded which is deconvoluted into an averaged chromatogram with Hadamard transformation. Novel algorithms to maintain the data acquisition rate of the detector by application of Hadamard transformation and to suppress correlation noise induced by components with much higher concentrations than the target substances are shown. Compared to conventional GC-FID, the signal-to-noise ratio has been increased by a factor of 10 with mpGC-FID. Correspondingly, the detection limits for BTEX in CO 2 have been lowered from 10 to 1 ppb each. This has been achieved despite the presence of detectable components (methane and methanol) with a concentration about 1000 times higher than the target substances. The robustness and reliability of mpGC has been proven in a two-month field test in a chemical production plant.

Nano- and Microdelivery Systems for Marine Bioactive Lipids

PubMed Central

Pereira, David M.; Valentão, Patrícia; Andrade, Paula B.

2014-01-01

There is an increasing body of evidence of the positive impact of several marine lipids on human health. These compounds, which include ω-3 polyunsaturated fatty acids, have been shown to improve blood lipid profiles and exert anti-inflammatory and cardioprotective effects. The high instability of these compounds to oxidative deterioration and their hydrophobicity have a drastic impact in their pharmacokinetics. Thus, the bioavailability of these compounds may be affected, resulting in their inability to reach the target sites at effective concentrations. In this regard; micro/nanoparticles can offer a wide range of solutions that can prevent the degradation of targeted molecules, increase their absorption, uptake and bioavailability. In this work we will present the options currently available concerning micro- and nanodelivery systems for marine lipids; with emphasis on micro/nanoparticles; such as micro/nanocapsules and emulsions. A wide range of bottom-up approaches using casein, chitosan, cyclodextrins, among others; will be discussed. PMID:25522314

Distinct molecular targets including SLO-1 and gap junctions are engaged across a continuum of ethanol concentrations in Caenorhabditis elegans

PubMed Central

Dillon, James; Andrianakis, Ioannis; Mould, Richard; Ient, Ben; Liu, Wei; James, Christopher; O'Connor, Vincent; Holden-Dye, Lindy

2013-01-01

Ethanol (alcohol) interacts with diverse molecular effectors across a range of concentrations in the brain, eliciting intoxication through to sedation. Invertebrate models including the nematode worm Caenorhabditis elegans have been deployed for molecular genetic studies to inform on key components of these alcohol signaling pathways. C. elegans studies have typically employed external dosing with high (>250 mM) ethanol concentrations: A careful analysis of responses to low concentrations is lacking. Using the C. elegans pharyngeal system as a paradigm, we report a previously uncharacterized continuum of cellular and behavioral responses to ethanol from low (10 mM) to high (300 mM) concentrations. The complexity of these responses indicates that the pleiotropic action of ethanol observed in mammalian brain is conserved in this invertebrate model. We investigated two candidate ethanol effectors, the calcium-activated K+ channel SLO-1 and gap junctions, and show that they contribute to, but are not sole determinants of, the low- and high-concentration effects, respectively. Notably, this study shows cellular and whole organismal behavioral responses to ethanol in C. elegans that directly equate to intoxicating through to supralethal blood alcohol concentrations in humans and provides an important benchmark for interpretation of paradigms that seek to inform on human alcohol use disorders.—Dillon, J., Andrianakis, I., Mould, R., Ient, B., Liu, W., James, C., O'Connor, V., Holden-Dye, L. Distinct molecular targets including SLO-1 and gap junctions are engaged across a continuum of ethanol concentrations in Caenorhabditis elegans. PMID:23882127

Conceptual design of an ascent-phase interceptor missile

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

Salguero, D E

1994-11-01

A conceptual design for an air-launched interceptor missile to defend against theater ballistic missiles is presented. The missile is designed to intercept the target while ascending, during Or just after the boost phase, before it reaches exo-atmospheric flight. The interceptor consists of a two-stage booster and a shrouded kinetic-kill vehicle. This report concentrates on the booster design required to achieve reasonable standoff ranges. The kinetic-kill vehicle and shroud (the payload) is assumed to weigh 80 lb{sub m} (36 kg) and assumed to contain guidance computers for both the kill vehicle and the booster. The interceptor missile is about 6 mmore » long, .48 m in diameter and weighs about 900 kg. Allowing 25 sec for target detection, trajectory estimation, and interceptor launch, it can intercept 90 sec after target launch from a 220 km stand-off range at an altitude of 60 km. Trade-off studies show that the interceptor performance is most sensitive to the stage mass fractions (with the first-stage mass fraction the most important), the first-stage burn time and the payload weight.« less

Large-volume constant-concentration sampling technique coupling with surface-enhanced Raman spectroscopy for rapid on-site gas analysis

NASA Astrophysics Data System (ADS)

Zhang, Zhuomin; Zhan, Yisen; Huang, Yichun; Li, Gongke

2017-08-01

In this work, a portable large-volume constant-concentration (LVCC) sampling technique coupling with surface-enhanced Raman spectroscopy (SERS) was developed for the rapid on-site gas analysis based on suitable derivatization methods. LVCC sampling technique mainly consisted of a specially designed sampling cell including the rigid sample container and flexible sampling bag, and an absorption-derivatization module with a portable pump and a gas flowmeter. LVCC sampling technique allowed large, alterable and well-controlled sampling volume, which kept the concentration of gas target in headspace phase constant during the entire sampling process and made the sampling result more representative. Moreover, absorption and derivatization of gas target during LVCC sampling process were efficiently merged in one step using bromine-thiourea and OPA-NH4+ strategy for ethylene and SO2 respectively, which made LVCC sampling technique conveniently adapted to consequent SERS analysis. Finally, a new LVCC sampling-SERS method was developed and successfully applied for rapid analysis of trace ethylene and SO2 from fruits. It was satisfied that trace ethylene and SO2 from real fruit samples could be actually and accurately quantified by this method. The minor concentration fluctuations of ethylene and SO2 during the entire LVCC sampling process were proved to be < 4.3% and 2.1% respectively. Good recoveries for ethylene and sulfur dioxide from fruit samples were achieved in range of 95.0-101% and 97.0-104% respectively. It is expected that portable LVCC sampling technique would pave the way for rapid on-site analysis of accurate concentrations of trace gas targets from real samples by SERS.

Large-volume constant-concentration sampling technique coupling with surface-enhanced Raman spectroscopy for rapid on-site gas analysis.

PubMed

Zhang, Zhuomin; Zhan, Yisen; Huang, Yichun; Li, Gongke

2017-08-05

In this work, a portable large-volume constant-concentration (LVCC) sampling technique coupling with surface-enhanced Raman spectroscopy (SERS) was developed for the rapid on-site gas analysis based on suitable derivatization methods. LVCC sampling technique mainly consisted of a specially designed sampling cell including the rigid sample container and flexible sampling bag, and an absorption-derivatization module with a portable pump and a gas flowmeter. LVCC sampling technique allowed large, alterable and well-controlled sampling volume, which kept the concentration of gas target in headspace phase constant during the entire sampling process and made the sampling result more representative. Moreover, absorption and derivatization of gas target during LVCC sampling process were efficiently merged in one step using bromine-thiourea and OPA-NH 4 + strategy for ethylene and SO 2 respectively, which made LVCC sampling technique conveniently adapted to consequent SERS analysis. Finally, a new LVCC sampling-SERS method was developed and successfully applied for rapid analysis of trace ethylene and SO 2 from fruits. It was satisfied that trace ethylene and SO 2 from real fruit samples could be actually and accurately quantified by this method. The minor concentration fluctuations of ethylene and SO 2 during the entire LVCC sampling process were proved to be <4.3% and 2.1% respectively. Good recoveries for ethylene and sulfur dioxide from fruit samples were achieved in range of 95.0-101% and 97.0-104% respectively. It is expected that portable LVCC sampling technique would pave the way for rapid on-site analysis of accurate concentrations of trace gas targets from real samples by SERS. Copyright © 2017 Elsevier B.V. All rights reserved.

Improved Phenoxyalkylbenzimidazoles with Activity against Mycobacterium tuberculosis Appear to Target QcrB

PubMed Central

2017-01-01

The phenoxy alkyl benzimidazoles (PABs) have good antitubercular activity. We expanded our structure–activity relationship studies to determine the core components of PABs required for activity. The most potent compounds had minimum inhibitory concentrations against Mycobacterium tuberculosis in the low nanomolar range with very little cytotoxicity against eukaryotic cells as well as activity against intracellular bacteria. We isolated resistant mutants against PAB compounds, which had mutations in either Rv1339, of unknown function, or qcrB, a component of the cytochrome bc1 oxidase of the electron transport chain. QcrB mutant strains were resistant to all PAB compounds, whereas Rv1339 mutant strains were only resistant to a subset, suggesting that QcrB is the target. The discovery of the target for PAB compounds will allow for the improved design of novel compounds to target intracellular M. tuberculosis. PMID:29035551

Comparison of active and passive sampling strategies for the monitoring of pesticide contamination in streams

NASA Astrophysics Data System (ADS)

Assoumani, Azziz; Margoum, Christelle; Guillemain, Céline; Coquery, Marina

2014-05-01

The monitoring of water bodies regarding organic contaminants, and the determination of reliable estimates of concentrations are challenging issues, in particular for the implementation of the Water Framework Directive. Several strategies can be applied to collect water samples for the determination of their contamination level. Grab sampling is fast, easy, and requires little logistical and analytical needs in case of low frequency sampling campaigns. However, this technique lacks of representativeness for streams with high variations of contaminant concentrations, such as pesticides in rivers located in small agricultural watersheds. Increasing the representativeness of this sampling strategy implies greater logistical needs and higher analytical costs. Average automated sampling is therefore a solution as it allows, in a single analysis, the determination of more accurate and more relevant estimates of concentrations. Two types of automatic samplings can be performed: time-related sampling allows the assessment of average concentrations, whereas flow-dependent sampling leads to average flux concentrations. However, the purchase and the maintenance of automatic samplers are quite expensive. Passive sampling has recently been developed as an alternative to grab or average automated sampling, to obtain at lower cost, more realistic estimates of the average concentrations of contaminants in streams. These devices allow the passive accumulation of contaminants from large volumes of water, resulting in ultratrace level detection and smoothed integrative sampling over periods ranging from days to weeks. They allow the determination of time-weighted average (TWA) concentrations of the dissolved fraction of target contaminants, but they need to be calibrated in controlled conditions prior to field applications. In other words, the kinetics of the uptake of the target contaminants into the sampler must be studied in order to determine the corresponding sampling rate constants (Rs). Each constant links the mass of the a target contaminant accumulated in the sampler to its concentration in water. At the end of the field application, the Rs are used to calculate the TWA concentration of each target contaminant with the final mass of the contaminants accumulated in the sampler. Stir Bar Sorptive Extraction (SBSE) is a solvent free sample preparation technique dedicated to the analysis of moderately hydrophobic to hydrophobic compounds in liquid and gas samples. It is composed of a magnet enclosed in a glass tube coated with a thick film of polydimethysiloxane (PDMS). We recently developed the in situ application of SBSE as a passive sampling technique (herein named "Passive SBSE") for the monitoring of agricultural pesticides. The aim of this study is to perform the calibration of the passive SBSE in the laboratory, and to apply and compare this technique to active sampling strategies for the monitoring of 16 relatively hydrophobic to hydrophobic pesticides in streams, during 2 1-month sampling campaigns. Time-weighted averaged concentrations of the target pesticides obtained from passive SBSE were compared to the target pesticide concentrations of grab samples, and time-related and flow-dependent samples of the streams. Results showed passive SBSE as an efficient alternative to conventional active sampling strategies.

Magnetic nanoparticles as contrast agents for molecular imaging in medicine

NASA Astrophysics Data System (ADS)

O'Donnell, Matthew

2018-05-01

For over twenty years, superparamagnetic nanoparticles have been developed for a number of medical applications ranging from bioseparations, magnetic drug targeting, hyperthermia and imaging. Recent studies have shown that they can be functionalized for in vivo biological targeting, potentially enabling nanoagents for molecular imaging and site-localized drug delivery. Here we review several imaging technologies developed using functionalized superparamagnetic iron oxide nanoparticles (SPIONs) as targeted molecular agents. Several imaging modalities have exploited the large induced magnetic moment of SPIONs to create local mechanical force. Magnetic force microscopy can probe nanoparticle uptake in single cells. For in vivo applications, magnetomotive modulation of primary images in ultrasound (US), photoacoustics (PA), and optical coherence tomography (OCT) can help identify very small concentrations of nanoagents while simultaneously suppressing intrinsic background signals from tissue.

Frequency Selection for Multi-frequency Acoustic Measurement of Suspended Sediment

NASA Astrophysics Data System (ADS)

Chen, X.; HO, H.; Fu, X.

2017-12-01

Multi-frequency acoustic measurement of suspended sediment has found successful applications in marine and fluvial environments. Difficult challenges remain in regard to improving its effectiveness and efficiency when applied to high concentrations and wide size distributions in rivers. We performed a multi-frequency acoustic scattering experiment in a cylindrical tank with a suspension of natural sands. The sands range from 50 to 600 μm in diameter with a lognormal size distribution. The bulk concentration of suspended sediment varied from 1.0 to 12.0 g/L. We found that the commonly used linear relationship between the intensity of acoustic backscatter and suspended sediment concentration holds only at sufficiently low concentrations, for instance below 3.0 g/L. It fails at a critical value of concentration that depends on measurement frequency and the distance between the transducer and the target point. Instead, an exponential relationship was found to work satisfactorily throughout the entire range of concentration. The coefficient and exponent of the exponential function changed, however, with the measuring frequency and distance. Considering the increased complexity of inverting the concentration values when an exponential relationship prevails, we further analyzed the relationship between measurement error and measuring frequency. It was also found that the inversion error may be effectively controlled within 5% if the frequency is properly set. Compared with concentration, grain size was found to heavily affect the selection of optimum frequency. A regression relationship for optimum frequency versus grain size was developed based on the experimental results.

Potency of a tau fibrillization inhibitor is influenced by its aggregation state

PubMed Central

Congdon, Erin E.; Necula, Mihaela; Blackstone, Robert D.; Kuret, Jeff

2007-01-01

Tau fibrillization is a potential therapeutic target for Alzheimer’s and other neurodegenerative diseases. Several small molecule inhibitors of tau aggregation have been developed for this purpose. One of them, 3,3′-bis(β-hydroxyethyl)-9-ethyl-5,5′-dimethoxythiacarbocyanine iodide (N744), is a cationic thiacarbocyanine dye that inhibits recombinant tau filament formation when present at submicromolar concentrations. To prepare dosing regimens for testing N744 activity in biological models, its full concentration-effect relationship in the range 0.01 – 60 μM was examined in vitro by electron microscopy and laser light scattering methods. Results revealed that N744 concentration dependence was biphasic, with fibrillization inhibitory activity appearing at submicromolar concentration, but with relief of inhibition and increases in fibrillization apparent above 10 μM. Therefore, fibrillization was inhibited ≥50% only over a narrow concentration range, which was further reduced by filament stabilizing modifications such as tau pseudophosphorylation. N744 inhibitory activity also was paralleled by changes in its aggregation state, with dimer predominating at inhibitory concentrations and large dye aggregates appearing at high concentrations. Ligand dimerization was promoted by the presence of tau protein, which lowered the equilibrium dissociation constant for dimerization more than an order of magnitude relative to controls. The results suggest that ligand aggregation may play an important role in both inhibitory and disinhibitory phases of the concentration-effect curve, and may lead to complex dose response relationships in model systems. PMID:17559794

Risk analysis of the thermal sterilization process. Analysis of factors affecting the thermal resistance of microorganisms.

PubMed

Akterian, S G; Fernandez, P S; Hendrickx, M E; Tobback, P P; Periago, P M; Martinez, A

1999-03-01

A risk analysis was applied to experimental heat resistance data. This analysis is an approach for processing experimental thermobacteriological data in order to study the variability of D and z values of target microorganisms depending on the deviations range of environmental factors, to determine the critical factors and to specify their critical tolerance. This analysis is based on sets of sensitivity functions applied to a specific case of experimental data related to the thermoresistance of Clostridium sporogenes and Bacillus stearothermophilus spores. The effect of the following factors was analyzed: the type of target microorganism; nature of the heating substrate; pH, temperature; type of acid employed and NaCl concentration. The type of target microorganism to be inactivated, the nature of the substrate (reference or real food) and the heating temperature were identified as critical factors, determining about 90% of the alteration of the microbiological risk. The effect of the type of acid used for the acidification of products and the concentration of NaCl can be assumed to be negligible factors for the purposes of engineering calculations. The critical non-uniformity in temperature during thermobacteriological studies was set as 0.5% and the critical tolerances of pH value and NaCl concentration were 5%. These results are related to a specific case study, for that reason their direct generalization is not correct.

Variability in blood and blood component utilization as assessed by an anesthesia information management system.

PubMed

Frank, Steven M; Savage, Will J; Rothschild, Jim A; Rivers, Richard J; Ness, Paul M; Paul, Sharon L; Ulatowski, John A

2012-07-01

Data can be collected for various purposes with anesthesia information management systems. The authors describe methods for using data acquired from an anesthesia information management system to assess intraoperative utilization of blood and blood components. Over an 18-month period, data were collected on 48,086 surgical patients at a tertiary care academic medical center. All data were acquired with an automated anesthesia recordkeeping system. Detailed reports were generated for blood and blood component utilization according to surgical service and surgical procedure, and for individual surgeons and anesthesiologists. Transfusion hemoglobin trigger and target concentrations were compared among surgical services and procedures, and between individual medical providers. For all patients given erythrocytes, the mean transfusion hemoglobin trigger was 8.4 ± 1.5, and the target was 10.2 ± 1.5 g/dl. Variation was significant among surgical services (trigger range: 7.5 ± 1.2-9.5 ± 1.1, P = 0.0001; target range: 9.1 ± 1.2-11.3 ± 1.4 g/dl, P = 0.002), surgeons (trigger range: 7.2 ± 0.7-9.8 ± 1.0, P = 0.001; target range: 8.8 ± 0.9-11.8 ± 1.3 g/dl, P = 0.001), and anesthesiologists (trigger range: 7.2 ± 0.8-9.6 ± 1.2, P = 0.001; target range: 9.0 ± 0.9-11.7 ± 1.3 g/dl, P = 0.0004). The use of erythrocyte salvage, fresh frozen plasma, and platelets varied threefold to fourfold among individual surgeons compared with their peers performing the same surgical procedure. The use of data acquired from an anesthesia information management system allowed a detailed analysis of blood component utilization, which revealed significant variation among surgical services and surgical procedures, and among individual anesthesiologists and surgeons compared with their peers. Incorporating these methods of data acquisition and analysis into a blood management program could reduce unnecessary transfusions, an outcome that may increase patient safety and reduce costs.

Analysis of the Effects of Cell Stress and Cytotoxicity on In ...

EPA Pesticide Factsheets

Chemical toxicity can arise from disruption of specific biomolecular functions or through more generalized cell stress and cytotoxicity-mediated processes. Here, concentration-dependent responses of 1063 chemicals including pharmaceuticals, natural products, pesticidals, consumer, and industrial chemicals across a diverse battery of 821 in vitro assay endpoints from 7 high-throughput assay technology platforms were analyzed in order to better distinguish between these types of activities. Both cell-based and cell-free assays showed a rapid increase in the frequency of responses at concentrations where cell stress / cytotoxicity responses were observed in cell-based assays. Chemicals that were positive on at least two viability/cytotoxicity assays within the concentration range tested (typically up to 100 M) activated a median of 12% of assay endpoints while those that were not cytotoxic in this concentration range activated 1.3% of the assays endpoints. The results suggest that activity can be broadly divided into: (1) specific biomolecular interactions against one or more targets (e.g., receptors or enzymes) at concentrations below which overt cytotoxicity-associated activity is observed; and (2) activity associated with cell stress or cytotoxicity, which may result from triggering of specific cell stress pathways, chemical reactivity, physico-chemical disruption of proteins or membranes, or broad low-affinity non-covalent interactions. Chemicals showing a g

Removal efficiency of polycyclic aromatic hydrocarbons and phthalate esters by surface flow wetland in Shunyi district, Beijing

NASA Astrophysics Data System (ADS)

Li, Binghua; Liu, Licai; Han, Li; Yang, Yong

2017-03-01

The surface flow wetland (SFW) system was located on Shunyi district, Beijing. It was built to treat industrial wastewater and domestic sewage, which were looked as its influent. Here sixteen polycyclic aromatic hydrocarbons (PAHs) and six phthalate esters (PAEs) were detected by gas chromatography-mass spectrometry (GC-MS).To determine treatment effect of SFW system, concentrations of targeted compounds in the influent were compared with those in the effluent. Results showed typical compounds of industrial wastewater were naphthalene (NAP), phenanthrene (PHE), dibutyl phthalate (DBP), di-(2-ethylhexyl) phthalate (DEHP), and their concentrations were ranged from 122.6 ng.L-1 to 760.6 ng.L-1. However typical compounds of domestic sewage were NAP, anthracene (ANT), PHE, DBP, diethyl phthalate (DEP), DEHP, and their concentrations were ranged from 280 ng.L-1 to 7998.1 ng.L-1. Typical compounds of effluent were NAP, PHE, DBP, DEHP, and their concentrations changed between 4.2 ng.L-1 and 1430.74 ng.L-1. The removal rate of those compounds were 10% ~ 99%, and nineteen compounds removal rate reached above 70%.Therefore, it can be concluded that SFW system had a strong effect on the removal of these compounds.

Homogenous assay for protein detection based on proximity DNA hybridization and isothermal circular strand displacement amplification reaction.

PubMed

Zhang, Manjun; Li, Ruimin; Ling, Liansheng

2017-06-01

This work proposed a homogenous fluorescence assay for proteins, based on the target-triggered proximity DNA hybridization in combination with strand displacement amplification (SDA). It benefited from target-triggered proximity DNA hybridization to specifically recognize the target and SDA making recycling signal amplification. The system included a molecular beacon (MB), an extended probe (EP), and an assistant probe (AP), which were not self-assembly in the absence of target proteins, due to the short length of the designed complementary sequence among MB, EP, and AP. Upon addition of the target proteins, EP and AP are bound to the target proteins, which induced the occurrence of proximity hybridization between MB, EP, and AP and followed by strand displacement amplification. Through the primer extension, a tripartite complex of probes and target was displaced and recycled to hybridize with another MB, and the more opened MB enabled the detection signal to amplify. Under optimum conditions, it was used for the detection of streptavidin and thrombin. Fluorescence intensity was proportional to the concentration of streptavidin and thrombin in the range of 0.2-30 and 0.2-35 nmol/L, respectively. Furthermore, this fluorescent method has a good selectivity, in which the fluorescence intensity of thrombin was ~37-fold or even larger than that of the other proteins at the same concentration. It is a new and simple method for SDA-involved target protein detection and possesses a great potential for other protein detection in the future. Graphical abstract A homogenous assay for protein detection is based on proximity DNA hybridization and strand displacement amplification reaction.

Abiotic stress growth conditions induce different responses in kernel iron concentration across genotypically distinct maize inbred varieties

PubMed Central

Kandianis, Catherine B.; Michenfelder, Abigail S.; Simmons, Susan J.; Grusak, Michael A.; Stapleton, Ann E.

2013-01-01

The improvement of grain nutrient profiles for essential minerals and vitamins through breeding strategies is a target important for agricultural regions where nutrient poor crops like maize contribute a large proportion of the daily caloric intake. Kernel iron concentration in maize exhibits a broad range. However, the magnitude of genotype by environment (GxE) effects on this trait reduces the efficacy and predictability of selection programs, particularly when challenged with abiotic stress such as water and nitrogen limitations. Selection has also been limited by an inverse correlation between kernel iron concentration and the yield component of kernel size in target environments. Using 25 maize inbred lines for which extensive genome sequence data is publicly available, we evaluated the response of kernel iron density and kernel mass to water and nitrogen limitation in a managed field stress experiment using a factorial design. To further understand GxE interactions we used partition analysis to characterize response of kernel iron and weight to abiotic stressors among all genotypes, and observed two patterns: one characterized by higher kernel iron concentrations in control over stress conditions, and another with higher kernel iron concentration under drought and combined stress conditions. Breeding efforts for this nutritional trait could exploit these complementary responses through combinations of favorable allelic variation from these already well-characterized genetic stocks. PMID:24363659

The relative abundance of dimethylsulfoniopropionate (DMSP) among other zwitterions in branching coral at Heron Island, southern Great Barrier Reef.

PubMed

Swan, Hilton B; Deschaseaux, Elisabeth S M; Jones, Graham B; Eyre, Bradley D

2017-07-01

Dimethylsulfoniopropionate (DMSP) and eleven other target zwitterions were quantified in the branch tips of six Acropora species and Stylophora pistillata hard coral growing on the reef flat surrounding Heron Island in the southern Great Barrier Reef (GBR), Australia. Hydrophilic interaction liquid chromatography mass spectrometry (HILIC-MS) was used for sample analysis with isotope dilution MS applied to quantify DMSP. The concentration of DMSP was ten times greater in A. aspera than A. valida, with this difference being maintained throughout the spring, summer and winter seasons. In contrast, glycine betaine was present in significantly higher concentrations in these species during the summer than the winter. Exposure of branch tips of A. aspera to air and hypo-saline seawater for up to 1 h did not alter the concentrations of DMSP present in the coral when compared with control samples. DMSP was the most abundant target zwitterion in the six Acropora species examined, ranging from 44-78% of all target zwitterions in A. millepora and A. aspera, respectively. In contrast, DMSP only accounted for 7% in S. pistillata, with glycine betaine and stachydrine collectively accounting for 88% of all target zwitterions in this species. The abundance of DMSP in the six Acropora species examined points to Acropora coral being an important source for the biogeochemical cycling of sulfur throughout the GBR, since this reef-building branching coral dominates the coral cover of the GBR. Graphical Abstract HILIC-MS extracted ion chromatogram showing zwitterionic metabolites from the branching coral Acropora isopora.

Sirolimus Pharmacokinetics in Early Postmyeloablative Pediatric Blood and Marrow Transplantation

PubMed Central

Goyal, Rakesh K.; Han, Kelong; Wall, Donna A.; Pulsipher, Michael A.; Bunin, Nancy; Grupp, Stephan A.; Mada, Sripal R.; Venkataramanan, Raman

2014-01-01

This study examined the pharmacokinetics of sirolimus in pediatric allogeneic blood and marrow transplantation (BMT) recipients in the presence and absence of concomitant fluconazole. Forty pediatric BMT recipients received a daily oral dose of sirolimus and a continuous i.v. infusion of tacrolimus for graft-versus-host disease prophylaxis. Fluconazole was administered i.v. to 19 patients and orally to 6 patients. Full pharmacokinetic profiles of sirolimus within a single dosing interval were collected. Whole-blood sirolimus concentrations were measured by HPLC/mass spectrometry. Noncompartmental analysis was performed using WinNonlin. Nonlinear mixed-effects pharmacokinetic models were developed using NONMEM following standard procedures. The mean ± SD sirolimus trough level before the dose (C0) was 8.0 ± 4.6 ng/mL (range, 1.8–21.6 ng/mL). The peak concentration was 19.9 ± 11.8 ng/mL (range, 3.9–46.1 ng/mL), and the trough level 24 hours later (C24) was 9.1 ± 5.3 ng/mL (range, 1.0–19.1 ng/mL). The terminal disposition half-life (T1/2) was 24.5 ± 11.2 hours (range, 5.8–53.2 hours), and the area under the concentration-versus-time curve (AUC0–24) was 401.1 ± 316.3 ng·h/mL (range, 20.7–1332.3 ng·h/mL). In patients at steady state, C0 and C24 were closely correlated (R2 = 0.77) with a slope of 0.99, indicating the achievement of steady state. C24 was 1.7-fold greater (P = .036) and AUC0–24 was 2-fold greater (P = .012) in Caucasian patients (n = 22) compared with Hispanic patients (n = 9). The average apparent oral clearance was 3-fold greater (P = .001) and the apparent oral volume of distribution was 2-fold greater (P = .018) in patients age ≤12 years compared with those age >12 years. C24 was significantly lower in patients (n = 10) who developed grade III–IV aGVHD (n = 10) than in those with grade 0-II aGVHD (n = 22) (6.1 ± 2.9 ng/mL versus 9.4 ± 5.5 ng/mL; P = .044). Dose-normalized sirolimus trough concentrations were significantly higher in patients receiving concomitant fluconazole therapy compared with those not receiving fluconazole (C0: 3.9 ± 2.5 versus 2.4 ± 1.5 ng/mL/mg, P = .030; C24: 4.8 ± 3.3 versus 2.5 ± 1.7 ng/mL/mg, P = .018). This pharmacokinetic study of sirolimus in pediatric patients documents a large interindividual variability in the exposure of sirolimus. Steady-state trough blood concentrations were correlated with drug exposure. Trough concentrations were higher with a concomitant use of fluconazole and were higher in Caucasian patients than in Hispanic patients. Oral clearance was greater in children age ≤12 years than in older children and adolescents. With therapeutic drug monitoring, the majority (79%) of sirolimus trough levels could be maintained within the target range (3–12 ng/mL). This study provides a rationale and support for dose adjustments of sirolimus based on steady-state blood concentrations aimed at achieving a target concentration to minimize toxicity and maximize therapeutic benefits in pediatric BMT recipients. PMID:23266742

Electrical Connection of Enzyme Redox Centers to Electrodes

DTIC Science & Technology

1992-03-20

concentration in the target organ or the affected physiological function ; and a microcontroller or microprocessor calculating the dose and timing the delivery...followed by introduction of medical feedback loops will allow the pharmaceutical industry to expand its range of drug delivery methods. Today’s primary ...inhalation (derived of the large lung surface area) and continuous, non -invasive administration, in the case of iontophoresis. The use of these

Overweight Kidney Transplant Recipients Are at Risk of Being Overdosed Following Standard Bodyweight-Based Tacrolimus Starting Dose.

PubMed

Andrews, Louise M; de Winter, Brenda C M; Tang, Jiang-Tao; Shuker, Nauras; Bouamar, Rachida; van Schaik, Ron H N; Koch, Birgit C P; van Gelder, Teun; Hesselink, Dennis A

2017-02-01

Bodyweight-based dosing of tacrolimus (Tac) is considered standard care, even though the available evidence is thin. An increasing proportion of transplant recipients is overweight, prompting the question if the starting dose should always be based on bodyweight. For this analysis, data were used from a randomized-controlled trial in which patients received either a standard Tac starting dose or a dose that was based on CYP3A5 genotype. The hypothesis was that overweight patients would have Tac overexposure following standard bodyweight-based dosing. Data were available for 203 kidney transplant recipients, with a median body mass index (BMI) of 25.6 (range, 17.2-42.2). More than 50% of the overweight or obese patients had a Tac predose concentration above the target range. The CYP3A5 nonexpressers tended to be above target when they weighed more than 67.5 kg or had a BMI of 24.5 or higher. Dosing guidelines were proposed with a decrease up to 40% in Tac starting doses for different BMI groups. The dosing guideline for patients with an unknown genotype was validated using the fixed-dose versus concentration controlled data set. This study demonstrates that dosing Tac solely on bodyweight results in overexposure in more than half of overweight or obese patients.

Quantum cascade laser-based sensor system for nitric oxide detection

NASA Astrophysics Data System (ADS)

Tittel, Frank K.; Allred, James J.; Cao, Yingchun; Sanchez, Nancy P.; Ren, Wei; Jiang, Wenzhe; Jiang, Dongfang; Griffin, Robert J.

2015-01-01

Sensitive detection of nitric oxide (NO) at ppbv concentration levels has an important impact in diverse fields of applications including environmental monitoring, industrial process control and medical diagnostics. For example, NO can be used as a biomarker of asthma and inflammatory lung diseases such as chronic obstructive pulmonary disease. Trace gas sensor systems capable of high sensitivity require the targeting of strong rotational-vibrational bands in the mid-IR spectral range. These bands are accessible using state-of-the-art high heat load (HHL) packaged, continuous wave (CW), distributed feedback (DFB) quantum cascade lasers (QCLs). Quartz-enhanced photoacoustic spectroscopy (QEPAS) permits the design of fast, sensitive, selective, and compact sensor systems. A QEPAS sensor was developed employing a room-temperature CW DFB-QCL emitting at 5.26 μm with an optical excitation power of 60 mW. High sensitivity is achieved by targeting a NO absorption line at 1900.08 cm-1 free of interference by H2O and CO2. The minimum detection limit of the sensor is 7.5 and 1 ppbv of NO with 1and 100 second averaging time respectively . The sensitivity of the sensor system is sufficient for detecting NO in exhaled human breath, with typical concentration levels ranging from 24.0 ppbv to 54.0 ppbv.

Transcranial current stimulation focality using disc and ring electrode configurations: FEM analysis

NASA Astrophysics Data System (ADS)

Datta, Abhishek; Elwassif, Maged; Battaglia, Fortunato; Bikson, Marom

2008-06-01

We calculated the electric fields induced in the brain during transcranial current stimulation (TCS) using a finite-element concentric spheres human head model. A range of disc electrode configurations were simulated: (1) distant-bipolar; (2) adjacent-bipolar; (3) tripolar; and three ring designs, (4) belt, (5) concentric ring, and (6) double concentric ring. We compared the focality of each configuration targeting cortical structures oriented normal to the surface ('surface-radial' and 'cross-section radial'), cortical structures oriented along the brain surface ('surface-tangential' and 'cross-section tangential') and non-oriented cortical surface structures ('surface-magnitude' and 'cross-section magnitude'). For surface-radial fields, we further considered the 'polarity' of modulation (e.g. superficial cortical neuron soma hyper/depolarizing). The distant-bipolar configuration, which is comparable with commonly used TCS protocols, resulted in diffuse (un-focal) modulation with bi-directional radial modulation under each electrode and tangential modulation between electrodes. Increasing the proximity of the two electrodes (adjacent-bipolar electrode configuration) increased focality, at the cost of more surface current. At similar electrode distances, the tripolar-electrodes configuration produced comparable peak focality, but reduced radial bi-directionality. The concentric-ring configuration resulted in the highest spatial focality and uni-directional radial modulation, at the expense of increased total surface current. Changing ring dimensions, or use of two concentric rings, allow titration of this balance. The concentric-ring design may thus provide an optimized configuration for targeted modulation of superficial cortical neurons.

Sources and transport of contaminants of emerging concern: A two-year study of occurrence and spatiotemporal variation in a mixed land use watershed.

PubMed

Fairbairn, David J; Karpuzcu, M Ekrem; Arnold, William A; Barber, Brian L; Kaufenberg, Elizabeth F; Koskinen, William C; Novak, Paige J; Rice, Pamela J; Swackhamer, Deborah L

2016-05-01

The occurrence and spatiotemporal variation of 26 contaminants of emerging concern (CECs) were evaluated in 68 water samples in 2011-2012 in the Zumbro River watershed, Minnesota, U.S.A. Samples were collected across a range of seasonal/hydrological conditions from four stream sites that varied in associated land use and presence of an upstream wastewater treatment plant (WWTP). Selected CECs included human/veterinary pharmaceuticals, personal care products, pesticides, phytoestrogens, and commercial/industrial compounds. Detection frequencies and concentrations varied, with atrazine, metolachlor, acetaminophen, caffeine, DEET, and trimethoprim detected in more than 70% of samples, acetochlor, mecoprop, carbamazepine, and daidzein detected in 30%-50% of samples, and 4-nonylphenol, cotinine, sulfamethoxazole, erythromycin, tylosin, and carbaryl detected in 10%-30% of samples. The remaining target CECs were not detected in water samples. Three land use-associated trends were observed for the detected CECs. Carbamazepine, 4-nonylphenol, erythromycin, sulfamethoxazole, tylosin, and carbaryl profiles were WWTP-dominated, as demonstrated by more consistent loading and significantly greater concentrations downstream of the WWTP and during low-flow seasons. In contrast, acetaminophen, trimethoprim, DEET, caffeine, cotinine, and mecoprop patterns demonstrated both seasonally-variable non-WWTP-associated and continual WWTP-associated influences. Surface water studies of CECs often target areas near WWTPs. This study suggests that several CECs often characterized as effluent-associated have additional important sources such as septic systems or land-applied biosolids. Finally, agricultural herbicide (atrazine, acetochlor, and metolachlor) profiles were strongly influenced by agricultural land use and seasonal application-runoff, evident by significantly greater concentrations and loadings at upstream sites and in early summer when application and precipitation rates are greatest. Our results indicate that CEC monitoring studies should consider a range of land uses, seasonality, and transport pathways in relation to concentrations and loadings. This knowledge can augment CEC monitoring programs to result in more accurate source, occurrence, and ecological risk characterizations, more precisely targeted mitigation initiatives, and ultimately, enhanced environmental decision-making. Copyright © 2016 Elsevier B.V. All rights reserved.

A targeted metabolomic protocol for short-chain fatty acids and branched-chain amino acids.

PubMed

Zheng, Xiaojiao; Qiu, Yunping; Zhong, Wei; Baxter, Sarah; Su, Mingming; Li, Qiong; Xie, Guoxiang; Ore, Brandon M; Qiao, Shanlei; Spencer, Melanie D; Zeisel, Steven H; Zhou, Zhanxiang; Zhao, Aihua; Jia, Wei

2013-08-01

Research in obesity and metabolic disorders that involve intestinal microbiota demands reliable methods for the precise measurement of the short-chain fatty acids (SCFAs) and branched-chain amino acids (BCAAs) concentration. Here, we report a rapid method of simultaneously determining SCFAs and BCAAs in biological samples using propyl chloroformate (PCF) derivatization followed by gas chromatography mass spectrometry (GC-MS) analysis. A one-step derivatization using 100 µL of PCF in a reaction system of water, propanol, and pyridine (v/v/v = 8:3:2) at pH 8 provided the optimal derivatization efficiency. The best extraction efficiency of the derivatized products was achieved by a two-step extraction with hexane. The method exhibited good derivatization efficiency and recovery for a wide range of concentrations with a low limit of detection for each compound. The relative standard deviations (RSDs) of all targeted compounds showed good intra- and inter-day (within 7 days) precision (< 10%), and good stability (< 20%) within 4 days at room temperature (23-25 °C), or 7 days when stored at -20 °C. We applied our method to measure SCFA and BCAA levels in fecal samples from rats administrated with different diet. Both univariate and multivariate statistics analysis of the concentrations of these target metabolites could differentiate three groups with ethanol intervention and different oils in diet. This method was also successfully employed to determine SCFA and BCAA in the feces, plasma and urine from normal humans, providing important baseline information of the concentrations of these metabolites. This novel metabolic profile study has great potential for translational research.

Efficacy of Testosterone Suppression with Sustained-Release Triptorelin in Advanced Prostate Cancer.

PubMed

Breul, Jürgen; Lundström, Eija; Purcea, Daniela; Venetz, Werner P; Cabri, Patrick; Dutailly, Pascale; Goldfischer, Evan R

2017-02-01

Androgen deprivation therapy (ADT) is a mainstay of treatment against advanced prostate cancer (PC). As a treatment goal, suppression of plasma testosterone levels to <50 ng/dl has been established over decades. Evidence is growing though that suppression to even lower levels may add further clinical benefit. Therefore, we undertook a pooled retrospective analysis on the efficacy of 1-, 3-, and 6-month sustained-release (SR) formulations of the gonadotropin-releasing hormone (GnRH) agonist triptorelin to suppress serum testosterone concentrations beyond current standards. Data of 920 male patients with PC enrolled in 9 prospective studies using testosterone serum concentrations as primary endpoint were pooled. Patients aged 42-96 years had to be eligible for ADT and to be either naïve to hormonal treatment or have undergone appropriate washout prior to enrolment. Patients were treated with triptorelin SR formulations for 2-12 months. Primary endpoints of this analysis were serum testosterone concentrations under treatment and success rates overall and per formulation, based on a testosterone target threshold of 20 ng/dl. After 1, 3, 6, 9, and 12 months of treatment, 79%, 92%, 93%, 90%, and 91% of patients reached testosterone levels <20 ng/dl, respectively. For the 1-, 3-, and 6-month formulations success rates ranged from 80-92%, from 83-93%, and from 65-97% with median (interquartile range) serum testosterone values of 2.9 (2.9-6.5), 5.0 (2.9-8.7), and 8.7 (5.8-14.1) ng/dl at study end, respectively. In the large majority of patients, triptorelin SR formulations suppressed serum testosterone concentrations to even <20 ng/dl. Testosterone should be routinely monitored in PC patients on ADT although further studies on the clinical benefit of very low testosterone levels and the target concentrations are still warranted.

Phosphorescent nanosensors for in vivo tracking of histamine levels.

PubMed

Cash, Kevin J; Clark, Heather A

2013-07-02

Continuously tracking bioanalytes in vivo will enable clinicians and researchers to profile normal physiology and monitor diseased states. Current in vivo monitoring system designs are limited by invasive implantation procedures and biofouling, limiting the utility of these tools for obtaining physiologic data. In this work, we demonstrate the first success in optically tracking histamine levels in vivo using a modular, injectable sensing platform based on diamine oxidase and a phosphorescent oxygen nanosensor. Our new approach increases the range of measurable analytes by combining an enzymatic recognition element with a reversible nanosensor capable of measuring the effects of enzymatic activity. We use these enzyme nanosensors (EnzNS) to monitor the in vivo histamine dynamics as the concentration rapidly increases and decreases due to administration and clearance. The EnzNS system measured kinetics that match those reported from ex vivo measurements. This work establishes a modular approach to in vivo nanosensor design for measuring a broad range of potential target analytes. Simply replacing the recognition enzyme, or both the enzyme and nanosensor, can produce a new sensor system capable of measuring a wide range of specific analytical targets in vivo.

Occurrence and estrogenic activity of steroid hormones in Chinese streams: A nationwide study based on a combination of chemical and biological tools.

PubMed

Yao, Bo; Li, Rui; Yan, Shuwen; Chan, Shen-An; Song, Weihua

2018-05-18

Steroid hormones (SHs) are continuously released into the aquatic environment through various pathways after being excreted by humans and animals, interfere with the normal function of the endocrine system and may affect the physiology and reproduction of exposed aquatic life. To conduct a nationwide investigation of the occurrence and biological effects of SHs in surface river/steam water in China, we quantitated 27 selected SHs in 217 surface water samples by solid-phase extraction (SPE) tandem LC-MS/MS and used a recombinant yeast estrogen assay to screen extracts of the water samples for estrogenic activities. SHs were commonly found in the surface water samples, and their levels were typically in the ng L -1 range. Estrone (E1) and estriol (E3) were normally present in several to dozens of times higher concentrations than estradiol (E2) and 17-a-Ethinylestradiol (EE2). The high concentrations (mean > 1 μg L -1 ) of Sum SHs were primarily obtained in areas under extreme water stress, specifically the eastern coastal areas. Source apportionment based on the profiles of the target compounds indicated that 54.5% of the SHs in target samples came from freshly discharged untreated sewage. The estrogen equivalent (EEQ (bio) ) values ranged from 0.01 to 40.27 ng L -1 , and the calculated EEQ (EEQ (cal) ) values were generally lower than the corresponding EEQ (bio) values for all samples. E2 was the main contributor to the estrogenicity among the three estrogens, with a contribution ratio of 82.8%. The risk quotient values of E2 were highest and ranged from 1.55 to 782.95, and 76.0% of the target surface samples displayed the greatest environmental risk. We concluded that the impacts of SHs on humans in Chinese surface waters should not be ignored and that certain actions should be taken to decrease the levels of SHs in source waters, especially measures targeting SHs in untreated wastewater from the vast rural areas. Copyright © 2018. Published by Elsevier Ltd.

Solid phase extraction with high polarity Carb/PSA as composite fillers prior to UPLC-MS/MS to determine six bisphenols and alkylphenols in trace level hotpot seasoning.

PubMed

Dong, Hao; Zeng, Xiaofang; Bai, Weidong

2018-08-30

The present study reports an ultra high-performance liquid chromatography tandem mass spectrometry method for the simultaneous determination of six bisphenols (bisphenol A, bisphenol B and bisphenol F) and alkylphenols (4-nonylphenol, 4-n-nonylphenol and octylphenol) in hotpot seasoning. Samples were dispersed in n-hexane after addition of internal standards bisphenol A-d 4 and 4-n-nonylphenol-d 4 . Sample solutions were then centrifuged, and the supernatants purified using solid phase extraction with high polarity Carb/PSA composite fillers. Six target analytes were separated on a Waters ACQUITY BEH C18 column by gradient elution with methanol and 0.05% ammonium hydroxide in water as the mobile phase, and determined under multiple reactions monitoring mode. The limits of detection and quantitation, matrix effect, recovery and precision of the method were investigated. Results were linear in the concentration range 0.1-250 µg/L for all compounds of interest, with R 2  > 0.9950. Limits of detection were in the range 0.1-0.4 μg/kg, and limits of quantitation were between 0.5 μg/kg and 1.0 μg/kg. The mean recoveries for negative samples at three spiked concentrations were in the range 87.9%-102.4%, and the intra-day precision and inter-day precision were in the ranges 2.1-8.2% and 4.8-11.2%, respectively. This method is accurate and sensitive, and had good clean-up characteristics, which might apply to screening and quantitation of target bisphenols and alkylphenols in hotpot seasoning. Copyright © 2018 Elsevier Ltd. All rights reserved.

Non-target evaluation of contaminants in honey bees and pollen samples by gas chromatography time-of-flight mass spectrometry.

PubMed

Hakme, E; Lozano, A; Gómez-Ramos, M M; Hernando, M D; Fernández-Alba, A R

2017-10-01

This work presents a non-targeted screening approach for the detection and quantitation of contaminants in bees and pollen, collected from the same hive, by GC-EI-ToF-MS. It consists of a spectral library datasets search using a compound database followed by a manual investigation and analytical standard confirmation together with semi-quantitation purposes. Over 20% of the compounds found automatically by the library search could not be confirmed manually. This number of false positive detections was mainly a consequence of an inadequate ion ratio criterion (±30%), not considered in the automatic searching procedure. Eight compounds were detected in bees and pollen. They include insecticides/acaricides (chlorpyrifos, coumaphos, fluvalinate-tau, chlorfenvinphos, pyridaben, and propyl cresol) at a concentration range of 1-1207 μg kg -1 , herbicides (oxyfluorfen) at a concentration range of 212-1773 μg kg -1 and a growth regulator hormone (methoprene). Some compounds were detected only in pollen; such as herbicides (clomazone), insecticides/acaricides and fungicides used to control Varroa mites as benzylbenzoate, bufencarb, allethrin, permethrin, eugenol and cyprodinil. Additional compounds were detected only in bees: flamprop-methyl, 2-methylphenol (2-49 μg kg -1 ) and naphthalene (1-23 μg kg -1 ). The proposed method presents important advantages as it can avoid the use of an unachievable number of analytical standards considered target compounds "a priori" but not present in the analyzed samples. Copyright © 2017 Elsevier Ltd. All rights reserved.

Melanin targeting for intracellular drug delivery: Quantification of bound and free drug in retinal pigment epithelial cells.

PubMed

Rimpelä, Anna-Kaisa; Hagström, Marja; Kidron, Heidi; Urtti, Arto

2018-05-31

Melanin binding affects drug distribution and retention in pigmented ocular tissues, thereby affecting drug response, duration of activity and toxicity. Therefore, it is a promising possibility for drug targeting and controlled release in the pigmented cells and tissues. Intracellular unbound drug concentrations determine pharmacological and toxicological actions, but analyses of unbound vs. total drug concentrations in pigmented cells are lacking. We studied intracellular binding and cellular drug uptake in pigmented retinal pigment epithelial cells and in non-pigmented ARPE-19 cells with five model drugs (chloroquine, propranolol, timolol, diclofenac, methotrexate). The unbound drug fractions in pigmented cells were 0.00016-0.73 and in non-pigmented cells 0.017-1.0. Cellular uptake (i.e. distribution ratio Kp), ranged from 1.3 to 6300 in pigmented cells and from 1.0 to 25 in non-pigmented cells. Values for intracellular bioavailability, F ic , were similar in both cells types (although larger variation in pigmented cells). In vitro melanin binding parameters were used to predict intracellular unbound drug fraction and cell uptake. Comparison of predictions with experimental data indicates that other factors (e.g. ion-trapping, lipophilicity-related binding to other cell components) also play a role. Melanin binding is a major factor that leads to cellular uptake and unbound drug fractions of a range of 3-4 orders of magnitude indicating that large reservoirs of melanin bound drug can be generated in the cells. Understanding melanin binding has important implications on retinal drug targeting, efficacy and toxicity. Copyright © 2017. Published by Elsevier B.V.

A pH-independent DNA nanodevice for quantifying chloride transport in organelles of living cells.

PubMed

Saha, Sonali; Prakash, Ved; Halder, Saheli; Chakraborty, Kasturi; Krishnan, Yamuna

2015-07-01

The concentration of chloride ions in the cytoplasm and subcellular organelles of living cells spans a wide range (5-130 mM), and is tightly regulated by intracellular chloride channels or transporters. Chloride-sensitive protein reporters have been used to study the role of these chloride regulators, but they are limited to a small range of chloride concentrations and are pH-sensitive. Here, we show that a DNA nanodevice can precisely measure the activity and location of subcellular chloride channels and transporters in living cells in a pH-independent manner. The DNA nanodevice, called Clensor, is composed of sensing, normalizing and targeting modules, and is designed to localize within organelles along the endolysosomal pathway. It allows fluorescent, ratiometric sensing of chloride ions across the entire physiological regime. We used Clensor to quantitate the resting chloride concentration in the lumen of acidic organelles in Drosophila melanogaster. We showed that lumenal lysosomal chloride, which is implicated in various lysosomal storage diseases, is regulated by the intracellular chloride transporter DmClC-b.

A pH-independent DNA nanodevice for quantifying chloride transport in organelles of living cells

NASA Astrophysics Data System (ADS)

Saha, Sonali; Prakash, Ved; Halder, Saheli; Chakraborty, Kasturi; Krishnan, Yamuna

2015-07-01

The concentration of chloride ions in the cytoplasm and subcellular organelles of living cells spans a wide range (5-130 mM), and is tightly regulated by intracellular chloride channels or transporters. Chloride-sensitive protein reporters have been used to study the role of these chloride regulators, but they are limited to a small range of chloride concentrations and are pH-sensitive. Here, we show that a DNA nanodevice can precisely measure the activity and location of subcellular chloride channels and transporters in living cells in a pH-independent manner. The DNA nanodevice, called Clensor, is composed of sensing, normalizing and targeting modules, and is designed to localize within organelles along the endolysosomal pathway. It allows fluorescent, ratiometric sensing of chloride ions across the entire physiological regime. We used Clensor to quantitate the resting chloride concentration in the lumen of acidic organelles in Drosophila melanogaster. We showed that lumenal lysosomal chloride, which is implicated in various lysosomal storage diseases, is regulated by the intracellular chloride transporter DmClC-b.

Setting cumulative emissions targets to reduce the risk of dangerous climate change

PubMed Central

Zickfeld, Kirsten; Eby, Michael; Matthews, H. Damon; Weaver, Andrew J.

2009-01-01

Avoiding “dangerous anthropogenic interference with the climate system” requires stabilization of atmospheric greenhouse gas concentrations and substantial reductions in anthropogenic emissions. Here, we present an inverse approach to coupled climate-carbon cycle modeling, which allows us to estimate the probability that any given level of carbon dioxide (CO2) emissions will exceed specified long-term global mean temperature targets for “dangerous anthropogenic interference,” taking into consideration uncertainties in climate sensitivity and the carbon cycle response to climate change. We show that to stabilize global mean temperature increase at 2 °C above preindustrial levels with a probability of at least 0.66, cumulative CO2 emissions from 2000 to 2500 must not exceed a median estimate of 590 petagrams of carbon (PgC) (range, 200 to 950 PgC). If the 2 °C temperature stabilization target is to be met with a probability of at least 0.9, median total allowable CO2 emissions are 170 PgC (range, −220 to 700 PgC). Furthermore, these estimates of cumulative CO2 emissions, compatible with a specified temperature stabilization target, are independent of the path taken to stabilization. Our analysis therefore supports an international policy framework aimed at avoiding dangerous anthropogenic interference formulated on the basis of total allowable greenhouse gas emissions. PMID:19706489

Setting cumulative emissions targets to reduce the risk of dangerous climate change.

PubMed

Zickfeld, Kirsten; Eby, Michael; Matthews, H Damon; Weaver, Andrew J

2009-09-22

Avoiding "dangerous anthropogenic interference with the climate system" requires stabilization of atmospheric greenhouse gas concentrations and substantial reductions in anthropogenic emissions. Here, we present an inverse approach to coupled climate-carbon cycle modeling, which allows us to estimate the probability that any given level of carbon dioxide (CO2) emissions will exceed specified long-term global mean temperature targets for "dangerous anthropogenic interference," taking into consideration uncertainties in climate sensitivity and the carbon cycle response to climate change. We show that to stabilize global mean temperature increase at 2 degrees C above preindustrial levels with a probability of at least 0.66, cumulative CO2 emissions from 2000 to 2500 must not exceed a median estimate of 590 petagrams of carbon (PgC) (range, 200 to 950 PgC). If the 2 degrees C temperature stabilization target is to be met with a probability of at least 0.9, median total allowable CO2 emissions are 170 PgC (range, -220 to 700 PgC). Furthermore, these estimates of cumulative CO2 emissions, compatible with a specified temperature stabilization target, are independent of the path taken to stabilization. Our analysis therefore supports an international policy framework aimed at avoiding dangerous anthropogenic interference formulated on the basis of total allowable greenhouse gas emissions.

Carbon nanotube-based labels for highly sensitive colorimetric and aggregation-based visual detection of nucleic acids

NASA Astrophysics Data System (ADS)

Lee, Ai Cheng; Ye, Jian-Shan; Ngin Tan, Swee; Poenar, Daniel P.; Sheu, Fwu-Shan; Kiat Heng, Chew; Meng Lim, Tit

2007-11-01

A novel carbon nanotube (CNT) derived label capable of dramatic signal amplification of nucleic acid detection and direct visual detection of target hybridization has been developed. Highly sensitive colorimetric detection of human acute lymphocytic leukemia (ALL) related oncogene sequences amplified by the novel CNT-based label was demonstrated. Atomic force microscope (AFM) images confirmed that a monolayer of horseradish peroxidase and detection probe molecules was immobilized along the carboxylated CNT carrier. The resulting CNT labels significantly enhanced the nucleic acid assay sensitivity by at least 1000 times compared to that of conventional labels used in enzyme-linked oligosorbent assay (ELOSA). An excellent detection limit of 1 × 10-12 M (60 × 10-18 mol in 60 µl) and a four-order wide dynamic range of target concentration were achieved. Hybridizations using these labels were coupled to a concentration-dependent formation of visible dark aggregates. Targets can thus be detected simply with visual inspection, eliminating the need for expensive and sophisticated detection systems. The approach holds promise for ultrasensitive and low cost visual inspection and colorimetric nucleic acid detection in point-of-care and early disease diagnostic application.

Ionization enhancement in atmospheric pressure chemical ionization and suppression in electrospray ionization between target drugs and stable-isotope-labeled internal standards in quantitative liquid chromatography/tandem mass spectrometry.

PubMed

Liang, H R; Foltz, R L; Meng, M; Bennett, P

2003-01-01

The phenomena of ionization suppression in electrospray ionization (ESI) and enhancement in atmospheric pressure chemical ionization (APCI) were investigated in selected-ion monitoring and selected-reaction monitoring modes for nine drugs and their corresponding stable-isotope-labeled internal standards (IS). The results showed that all investigated target drugs and their co-eluting isotope-labeled IS suppress each other's ionization responses in ESI. The factors affecting the extent of suppression in ESI were investigated, including structures and concentrations of drugs, matrix effects, and flow rate. In contrast to the ESI results, APCI caused seven of the nine investigated target drugs and their co-eluting isotope-labeled IS to enhance each other's ionization responses. The mutual ionization suppression or enhancement between drugs and their isotope-labeled IS could possibly influence assay sensitivity, reproducibility, accuracy and linearity in quantitative liquid chromatography/mass spectrometry (LC/MS) and liquid chromatography/tandem mass spectrometry (LC/MS/MS). However, calibration curves were linear if an appropriate IS concentration was selected for a desired calibration range to keep the response factors constant. Copyright 2003 John Wiley & Sons, Ltd.

Use of Protein G Microcolumns in Chromatographic Immunoassays: A Comparison of Competitive Binding Formats

PubMed Central

Pfaunmiller, Erika L.; Anguizola, Jeanethe A.; Milanuk, Mitchell L.; Carter, NaTasha; Hage, David S.

2016-01-01

Affinity microcolumns containing protein G were used as general platforms for creating chromatographic-based competitive binding immunoassays. Human serum albumin (HSA) was used as a model target for this work and HSA tagged with a near infrared fluorescent dye was utilized as the label. The protein G microcolumns were evaluated for use in several assay formats, including both solution-based and column-based competitive binding immunoassays and simultaneous or sequential injection formats. All of these methods were characterized by using the same amounts of labeled HSA and anti-HSA antibodies per sample, as chosen for the analysis of a protein target in the low-to-mid ng/mL range. The results were used to compare these formats in terms of their response, precision, limits of detection, and analysis time. All these methods gave detection limits in the range of 8–19 ng/mL and precisions ranging from ± 5% to ± 10% when using an injection flow rate of 0.10 mL/min. The column-based sequential injection immunoassay provided the best limit of detection and the greatest change in response at low target concentrations, while the solution-based simultaneous injection method had the broadest linear and dynamic ranges. These results provided valuable guidelines that can be employed to develop and extend the use of protein G microcolumns and these competitive binding formats to other protein biomarkers or biological agents of clinical or pharmaceutical interest. PMID:26777776

Analysis of Technology for Compact Coherent Lidar

NASA Technical Reports Server (NTRS)

Amzajerdian, Farzin

1997-01-01

In view of the recent advances in the area of solid state and semiconductor lasers has created new possibilities for the development of compact and reliable coherent lidars for a wide range of applications. These applications include: Automated Rendezvous and Capture, wind shear and clear air turbulence detection, aircraft wake vortex detection, and automobile collision avoidance. The work performed by the UAH personnel under this Delivery Order, concentrated on design and analyses of a compact coherent lidar system capable of measuring range and velocity of hard targets, and providing air mass velocity data. The following is the scope of this work. a. Investigate various laser sources and optical signal detection configurations in support of a compact and lightweight coherent laser radar to be developed for precision range and velocity measurements of hard and fuzzy targets. Through interaction with MSFC engineers, the most suitable laser source and signal detection technique that can provide a reliable compact and lightweight laser radar design will be selected. b. Analyze and specify the coherent laser radar system configuration and assist with its optical and electronic design efforts. Develop a system design including its optical layout design. Specify all optical components and provide the general requirements of the electronic subsystems including laser beam modulator and demodulator drivers, detector electronic interface, and the signal processor. c. Perform a thorough performance analysis to predict the system measurement range and accuracy. This analysis will utilize various coherent laser radar sensitivity formulations and different target models.

Drug Concentration Thresholds Predictive of Therapy Failure and Death in Children With Tuberculosis: Bread Crumb Trails in Random Forests.

PubMed

Swaminathan, Soumya; Pasipanodya, Jotam G; Ramachandran, Geetha; Hemanth Kumar, A K; Srivastava, Shashikant; Deshpande, Devyani; Nuermberger, Eric; Gumbo, Tawanda

2016-11-01

 The role of drug concentrations in clinical outcomes in children with tuberculosis is unclear. Target concentrations for dose optimization are unknown.  Plasma drug concentrations measured in Indian children with tuberculosis were modeled using compartmental pharmacokinetic analyses. The children were followed until end of therapy to ascertain therapy failure or death. An ensemble of artificial intelligence algorithms, including random forests, was used to identify predictors of clinical outcome from among 30 clinical, laboratory, and pharmacokinetic variables.  Among the 143 children with known outcomes, there was high between-child variability of isoniazid, rifampin, and pyrazinamide concentrations: 110 (77%) completed therapy, 24 (17%) failed therapy, and 9 (6%) died. The main predictors of therapy failure or death were a pyrazinamide peak concentration <38.10 mg/L and rifampin peak concentration <3.01 mg/L. The relative risk of these poor outcomes below these peak concentration thresholds was 3.64 (95% confidence interval [CI], 2.28-5.83). Isoniazid had concentration-dependent antagonism with rifampin and pyrazinamide, with an adjusted odds ratio for therapy failure of 3.00 (95% CI, 2.08-4.33) in antagonism concentration range. In regard to death alone as an outcome, the same drug concentrations, plus z scores (indicators of malnutrition), and age <3 years, were highly ranked predictors. In children <3 years old, isoniazid 0- to 24-hour area under the concentration-time curve <11.95 mg/L × hour and/or rifampin peak <3.10 mg/L were the best predictors of therapy failure, with relative risk of 3.43 (95% CI, .99-11.82).  We have identified new antibiotic target concentrations, which are potential biomarkers associated with treatment failure and death in children with tuberculosis. © The Author 2016. Published by Oxford University Press for the Infectious Diseases Society of America.

Terbinafine in combination with other antifungal agents for treatment of resistant or refractory mycoses: investigating optimal dosing regimens using a physiologically based pharmacokinetic model.

PubMed

Dolton, Michael J; Perera, Vidya; Pont, Lisa G; McLachlan, Andrew J

2014-01-01

Terbinafine is increasingly used in combination with other antifungal agents to treat resistant or refractory mycoses due to synergistic in vitro antifungal activity; high doses are commonly used, but limited data are available on systemic exposure, and no assessment of pharmacodynamic target attainment has been made. Using a physiologically based pharmacokinetic (PBPK) model for terbinafine, this study aimed to predict total and unbound terbinafine concentrations in plasma with a range of high-dose regimens and also calculate predicted pharmacodynamic parameters for terbinafine. Predicted terbinafine concentrations accumulated significantly during the first 28 days of treatment; the area under the concentration-time curve (AUC)/MIC ratios and AUC for the free, unbound fraction (fAUC)/MIC ratios increased by 54 to 62% on day 7 of treatment and by 80 to 92% on day 28 compared to day 1, depending on the dose regimen. Of the high-dose regimens investigated, 500 mg of terbinafine taken every 12 h provided the highest systemic exposure; on day 7 of treatment, the predicted AUC, maximum concentration (Cmax), and minimum concentration (Cmin) were approximately 4-fold, 1.9-fold, and 4.4-fold higher than with a standard-dose regimen of 250 mg once daily. Close agreement was seen between the concentrations predicted by the PBPK model and the observed concentrations, indicating good predictive performance. This study provides the first report of predicted terbinafine exposure in plasma with a range of high-dose regimens.

Determination of 48 fragrance allergens in toys using GC with ion trap MS/MS.

PubMed

Lv, Qing; Zhang, Qing; Li, Wentao; Li, Haiyu; Li, Pi; Ma, Qiang; Meng, Xianshuang; Qi, Meiling; Bai, Hua

2013-11-01

This paper presents a method for the simultaneous determination of 48 fragrance allergens in four types of toys (plastic toys, play clays, plush toys, and paper toys) based on GC with ion trap MS/MS. Compared with single-stage MS, MS/MS is superior in terms of the qualification and quantification of a large range of compounds in complicated matrices. Procedures for extraction and purification were optimized for each toy type. The method proved to be linear over a wide range of concentrations for all analytes with correlation coefficients between 0.9768 and 0.9999. Validation parameters, namely, LODs and LOQs, ranged from 0.005-5.0 and from 0.02-20 mg/kg, respectively. Average recoveries of target compounds (spiked at three concentration levels) were in the range of 79.5-109.1%. Intraday and interday repeatabilities of the proposed method varied from 0.7-10.5% and from 3.1-13.4%, respectively. The proposed method was used to monitor fragrance allergens in commercial toy products. Our findings indicate that this method is an accurate and effective technique for analyzing fragrance allergens in materials composed of complex components. © 2013 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

Simultaneous generation of aptamers to multiple gamma-carboxyglutamic acid proteins from a focused aptamer library using DeSELEX and convergent selection.

PubMed

Layzer, Juliana M; Sullenger, Bruce A

2007-01-01

By using the in vitro selection method SELEX against the complex mixture of GLA proteins and utilizing methods to deconvolute the resulting ligands, we were able to successfully generate 2'-ribo purine, 2'-fluoro pyrimidine aptamers to various individual targets in the GLA protein proteome that ranged in concentration from 10 nM to 1.4 microM in plasma. Perhaps not unexpectedly, the majority of the aptamers isolated following SELEX bind the most abundant protein in the mixture, prothrombin (FII), with high affinity. We show that by deselecting the dominant prothrombin aptamer the selection can be redirected. By using this DeSELEX approach, we were able to shift the selection toward other sequences and to less abundant protein targets and obtained an aptamer to Factor IX (FIX). We also demonstrate that by using an RNA library that is focused around a proteome, purified protein targets can then be used to rapidly generate aptamers to the protein targets that are rare in the initial mixture such as Factor VII (FVII) and Factor X (FX). Moreover, for all four proteins targeted (FII, FVII, FIX, and FX), aptamers were identified that could inhibit the individual protein's activitity in coagulation assays. Thus, by applying the concepts of DeSELEX and focused library selection, aptamers specific for any protein in a particular proteome can theoretically be generated, even when the proteins in the mixture are present at very different concentrations.

Occurrence of naproxen, ibuprofen, and diclofenac residues in wastewater and river water of KwaZulu-Natal Province in South Africa.

PubMed

Madikizela, Lawrence Mzukisi; Chimuka, Luke

2017-07-01

The present paper reports a detailed study that is based on the monitoring of naproxen, ibuprofen, and diclofenac in Mbokodweni River and wastewater treatment plants (WWTPs) located around the city of Durban in KwaZulu-Natal Province of South Africa. Target compounds were extracted from water samples using a multi-template molecularly imprinted solid-phase extraction prior to separation and quantification on a high-performance liquid chromatography equipped with photo diode array detector. The analytical method yielded the detection limits of 0.15, 1.00, and 0.63 μg/L for naproxen, ibuprofen, and diclofenac, respectively. Solid-phase extraction method was evaluated for its performance using deionized water samples that were spiked with 5 and 50 μg/L of target compounds. Recoveries were greater than 80% for all target compounds with RSD values in the range of 4.1 to 10%. Target compounds were detected in most wastewater and river water samples with ibuprofen being the most frequently detected pharmaceutical. Maximum concentrations detected in river water for naproxen, ibuprofen, and diclofenac were 6.84, 19.2, and 9.69 μg/L, respectively. The concentrations of target compounds found in effluent and river water samples compared well with some studies. The analytical method employed in this work is fast, selective, sensitive, and affordable; therefore, it can be used routinely to evaluate the occurrence of acidic pharmaceuticals in South African water resources.

Mitochondria-Targeted Vitamin E Protects Skin from UVB-Irradiation.

PubMed

Kim, Won-Serk; Kim, Ikyon; Kim, Wang-Kyun; Choi, Ju-Yeon; Kim, Doo Yeong; Moon, Sung-Guk; Min, Hyung-Keun; Song, Min-Kyu; Sung, Jong-Hyuk

2016-05-01

Mitochondria-targeted vitamin E (MVE) is designed to accumulate within mitochondria and is applied to decrease mitochondrial oxidative damage. However, the protective effects of MVE in skin cells have not been identified. We investigated the protective effect of MVE against UVB in dermal fibroblasts and immortalized human keratinocyte cell line (HaCaT). In addition, we studied the wound-healing effect of MVE in animal models. We found that MVE increased the proliferation and survival of fibroblasts at low concentration (i.e., nM ranges). In addition, MVE increased collagen production and downregulated matrix metalloproteinase1. MVE also increased the proliferation and survival of HaCaT cells. UVB increased reactive oxygen species (ROS) production in fibroblasts and HaCaT cells, while MVE decreased ROS production at low concentration. In an animal experiment, MVE accelerated wound healing from laser-induced skin damage. These results collectively suggest that low dose MVE protects skin from UVB irradiation. Therefore, MVE can be developed as a cosmetic raw material.

Target analysis of primary aromatic amines combined with a comprehensive screening of migrating substances in kitchen utensils by liquid chromatography-high resolution mass spectrometry.

PubMed

Sanchis, Yovana; Coscollà, Clara; Roca, Marta; Yusà, Vicent

2015-06-01

An analytical strategy including both the quantitative target analysis of 8 regulated primary aromatic amines (PAAs), as well as a comprehensive post-run target screening of 77 migrating substances, was developed for nylon utensils, using liquid chromatography-orbitrap-high resolution mass spectrometry (LC-HRMS) operating in full scan mode. The accurate mass data were acquired with a resolving power of 50,000 FWHM (scan speed, 2 Hz), and by alternating two acquisition events, ESI+ with and without fragmentation. The target method was validated after statistical optimization of the main ionization and fragmentation parameters. The quantitative method presented appropriate performance to be used in official monitoring with recoveries ranging from 78% to 112%, precision in terms of Relative Standard Deviation (RSD) was less than 15%, and the limits of quantification were between 2 and 2.5 µg kg(-1). For post-target screening, a customized theoretical database was built for food contact material migrants, including bisphenols, phthalates, and other amines. For identification purposes, accurate exact mass (<5 ppm) and some diagnostic ions including fragments were used. The strategy was applied to 10 real samples collected from different retailers in the Valencian Region (Spain) during 2014. Six out of eight target PAAs were detected in at least one sample in the target analysis. The most frequently detected compounds were 4,4'-methylenedianiline and aniline, with concentrations ranging from 2.4 to 19,715 µg kg(-1) and 2.5 to 283 µg kg(-1), respectively. Two phthalates were identified and confirmed in the post-run target screening analysis. Copyright © 2015 Elsevier B.V. All rights reserved.

Identifying atmospheric monitoring needs for Space Station Freedom

NASA Technical Reports Server (NTRS)

Casserly, Dennis M.

1989-01-01

The atmospheric monitoring needs for Space Station Freedom were identified by examining the following from an industrial hygiene perspective: the experiences of past missions; ground based tests of proposed life support systems; the unique experimental and manufacturing facilities; the contaminant load model; metabolic production; and a fire. A target list of compounds to be monitored is presented and information is provided relative to the frequency of analysis, concentration ranges, and locations for monitoring probes.

Nanoparticles for magnetic biosensing systems

NASA Astrophysics Data System (ADS)

Kurlyandskaya, G. V.; Novoselova, Iu. P.; Schupletsova, V. V.; Andrade, R.; Dunec, N. A.; Litvinova, L. S.; Safronov, A. P.; Yurova, K. A.; Kulesh, N. A.; Dzyuman, A. N.; Khlusov, I. A.

2017-06-01

The further development of magnetic biosensors requires a better understanding of the interaction between living systems and magnetic nanoparticles (MNPs). We describe our experience of fabrication of stable ferrofluids (FF) using electrostatic or steric stabilization of iron oxide MNPs obtained by laser target evaporation. Controlled amounts of FF were used for in vitro experiments with human mesenchymal stem cells. Their morphofunctional responses in the Fe concentration range 2-1000 maximum tolerated dose revealed no cytotoxicity.

Real-time assays with molecular beacons and other fluorescent nucleic acid hybridization probes.

PubMed

Marras, Salvatore A E; Tyagi, Sanjay; Kramer, Fred Russell

2006-01-01

A number of formats for nucleic acid hybridization have been developed to identify DNA and RNA sequences that are involved in cellular processes and that aid in the diagnosis of genetic and infectious diseases. The introduction of hybridization probes with interactive fluorophore pairs has enabled the development of homogeneous hybridization assays for the direct identification of nucleic acids. A change in the fluorescence of these probes indicates the presence of a target nucleic acid, and there is no need to separate unbound probes from hybridized probes. The advantages of homogeneous hybridization assays are their speed and simplicity. In addition, homogeneous assays can be combined with nucleic acid amplification, enabling the detection of rare target nucleic acids. These assays can be followed in real time, providing quantitative determination of target nucleic acids over a broad range of concentrations.

Trace determination of organophosphate esters in white wine, red wine, and beer samples using dispersive liquid-liquid microextraction combined with ultra-high-performance liquid chromatography-tandem mass spectrometry.

PubMed

Pang, Long; Yang, Huiqiang; Yang, Peijie; Zhang, Hongzhong; Zhao, Jihong

2017-08-15

In this study, dispersive liquid-liquid microextraction coupled with ultra-high-performance liquid chromatography-tandem mass spectrometry was developed for the analysis of five representative organophosphate esters (OPEs) in wine samples. Under optimized conditions, the proposed method resulted in good linearity (R 2 >0.9933) over the range of 0.1-100μgL -1 , with limits of detection (LODs, S/N =3) and quantification (LOQs, S/N =10) in the ranges of 0.48-18.8ngL -1 and 1.58-62.5ngL -1 , respectively. Inter- and intra-assay precisions of RSD% ranged from 3.21% to 6.13% and from 1.69% to 7.63%, respectively. The spiked recoveries of target OPEs from white wine, red wine, and beer samples were in the ranges of 80-122%, 76-120%, and 76-110%, respectively, at two different concentration levels. The total concentrations of five OPEs found in white wine, red wine, and beer samples were in the ranges of 0.29-0.85μgL -1 , 1.00-3.05μgL -1 , and 0.86-1.47μgL -1 , respectively. Copyright © 2017 Elsevier Ltd. All rights reserved.

DNA Damage Dependence on the Subcellular Distribution of Low-Energy Beta Emitters

NASA Astrophysics Data System (ADS)

Cutaia, Claudia; Alloni, Daniele; Mariotti, Luca; Friedland, Werner; Ottolenghi, Andrea

One of the main issues of low-energy internal emitters is related to the short ranges of beta particles, compared to the dimensions of the biological targets (e.g. the cell nucleus). Also depending on the chemical form, the radionuclide may be more concentrated in the cytoplasm of the target cell (in our calculations a human fibroblast in interphase) and consequently the conventional dosimetry may overestimate the dose to the nucleus; whereas if the radionuclide is more concentrated in the nuclei of the cells there is a risk of underestimating the nucleus dose. The computer code PARTRAC was modified to calculate the energy depositions in the nucleus and the DNA damage for different relative concentrations of the radionuclide in the nucleus and in the cytoplasm. The nuclides considered in the simulations were Tritium (the electrons emitted due to the β - decay have an average energy of 5.7 keV, corresponding to an average range of 0.42 µm) and Nickel-63 (the electrons emitted have an average energy of 17 keV corresponding to an average range of 5 µm). In the case of Tritium, the dose in the nucleus due the tracks generated outside this region is 15% of the average dose in the cell, whereas in the case of Nickel-63 the dose in the nucleus resulted to be 64% of the average dose in the cell. The distributions of DNA fragments as a function of the relative concentration of the nuclides in the nucleus and in the cytoplasm, were also calculated. In the same conditions, the number of complex lesions (which have a high probability of inducing lethal damage to the cells) per Gy (circa 0.5-1) and the total number of double strand breaks (DSBs) per Gy (circa 40) were also calculated. To complete the characterization of the effects of internal emitters inside the cell the distributions of DSBs per chromosome were studied for different radionuclide distributions in the cell. The results obtained from these simulations show the possible overestimation or underestimation of the risk, (particularly for Tritium intake), due to the distribution of the low energy emitters at subcellular levels.

Toxicity reference values for chlorophacinone and their application for assessing anticoagulant rodenticide risk to raptors.

PubMed

Rattner, Barnett A; Horak, Katherine E; Lazarus, Rebecca S; Schultz, Sandra L; Knowles, Susan; Abbo, Benjamin G; Volker, Steven F

2015-05-01

Despite widespread use and benefit, there are growing concerns regarding hazards of second-generation anticoagulant rodenticides to non-target wildlife which may result in expanded use of first-generation compounds, including chlorophacinone (CPN). The toxicity of CPN over a 7-day exposure period was investigated in American kestrels (Falco sparverius) fed either rat tissue mechanically-amended with CPN, tissue from rats fed Rozol(®) bait (biologically-incorporated CPN), or control diets (tissue from untreated rats or commercial bird of prey diet) ad libitum. Nominal CPN concentrations in the formulated diets were 0.15, 0.75 and 1.5 µg/g food wet weight, and measured concentrations averaged 94 % of target values. Kestrel food consumption was similar among groups and body weight varied by less than 6 %. Overt signs of intoxication, liver CPN residues, and changes in prothrombin time (PT), Russell's viper venom time (RVVT) and hematocrit, were generally dose-dependent. Histological evidence of hemorrhage was present at all CPN dose levels, and most frequently observed in pectoral muscle and heart. There were no apparent differences in toxicity between mechanically-amended and biologically-incorporated CPN diet formulations. Dietary-based toxicity reference values at which clotting times were prolonged in 50 % of the kestrels were 79.2 µg CPN consumed/kg body weight-day for PT and 39.1 µg/kg body weight-day for RVVT. Based upon daily food consumption of kestrels and previously reported CPN concentrations found in small mammals following field baiting trials, these toxicity reference values might be exceeded by free-ranging raptors consuming such exposed prey. Tissue-based toxicity reference values for coagulopathy in 50 % of exposed birds were 0.107 µg CPN/g liver wet weight for PT and 0.076 µg/g liver for RVVT, and are below the range of residue levels reported in raptor mortality incidents attributed to CPN exposure. Sublethal responses associated with exposure to environmentally realistic concentrations of CPN could compromise survival of free-ranging raptors, and should be considered in weighing the costs and benefits of anticoagulant rodenticide use in pest control and eradication programs.

Radiation-induced biologic bystander effect elicited in vitro by targeted radiopharmaceuticals labeled with alpha-, beta-, and auger electron-emitting radionuclides.

PubMed

Boyd, Marie; Ross, Susan C; Dorrens, Jennifer; Fullerton, Natasha E; Tan, Ker Wei; Zalutsky, Michael R; Mairs, Robert J

2006-06-01

Recent studies have shown that indirect effects of ionizing radiation may contribute significantly to the effectiveness of radiotherapy by sterilizing malignant cells that are not directly hit by the radiation. However, there have been few investigations of the importance of indirect effects in targeted radionuclide treatment. Our purpose was to compare the induction of bystander effects by external beam gamma-radiation with those resultant from exposure to 3 radiohaloanalogs of metaiodobenzylguanidine (MIBG): (131)I-MIBG (low-linear-energy-transfer [LET] beta-emitter), (123)I-MIBG (potentially high-LET Auger electron emitter), and meta-(211)At-astatobenzylguanidine ((211)At-MABG) (high-LET alpha-emitter). Two human tumor cell lines-UVW (glioma) and EJ138 (transitional cell carcinoma of bladder)-were transfected with the noradrenaline transporter (NAT) gene to enable active uptake of MIBG. Medium from cells that accumulated the radiopharmaceuticals or were treated with external beam radiation was transferred to cells that had not been exposed to radioactivity, and clonogenic survival was determined in donor and recipient cultures. Over the dose range 0-9 Gy of external beam radiation of donor cells, 2 Gy caused 30%-40% clonogenic cell kill in recipient cultures. This potency was maintained but not increased by higher dosage. In contrast, no corresponding saturation of bystander cell kill was observed after treatment with a range of activity concentrations of (131)I-MIBG, which resulted in up to 97% death of donor cells. Cellular uptake of (123)I-MIBG and (211)At-MABG induced increasing recipient cell kill up to levels that resulted in direct kill of 35%-70% of clonogens. Thereafter, the administration of higher activity concentrations of these high-LET emitters was inversely related to the kill of recipient cells. Over the range of activity concentrations examined, neither direct nor indirect kill was observed in cultures of cells not expressing the NAT and, thus, incapable of active uptake of MIBG. Potent toxins are generated specifically by cells that concentrate radiohalogenated MIBG. These may be LET dependent and distinct from those elicited by conventional radiotherapy.

Disruption of hepatic mitochondrial bioenergetics is not a primary mechanism for the toxicity of methoprene - relevance for toxicological assessment.

PubMed

Monteiro, J P; Oliveira, P J; Moreno, A J M; Jurado, A S

2008-07-01

Methoprene (isopropyl(2E,4E)-11-methoxy-3,7,11-trimethyl-2,4-dodecadienoate) is an insect growth regulator generally used to control insect populations by preventing insect maturation. So far, the effects of the insecticide on mitochondrial bioenergetics were not investigated. In the present work, liver mitochondria from Wistar rats were isolated and features of mitochondrial physiology were characterized in the presence of methoprene. High concentrations of methoprene, in the range of 40-100 nmol/mg of protein could decrease the transmembrane electric potential (Delta Psi) developed by mitochondria and, at the highest concentration, methoprene prevented complete Delta Psi repolarization after ADP addition. The effect was more evident using succinate than with ascorbate+TMPD as substrate. State 3 respiration was approximately 60% inhibited by 80 nmol of methoprene/mg of protein, while state 4 respiration, within the same range of methoprene concentrations, showed a slight increase, when both glutamate-malate and succinate were used as substrates. Additionally, FCCP-stimulated respiration was inhibited to an extent comparable to the effect on state 3, which suggests an interaction of methoprene with the respiratory chain, more evident with glutamate/malate as substrate. The activity of complex I (NADH-ubiquinone oxidorreductase) and that of the segment comprehending complexes II and III (succinate-cytochrome c reductase) were decreased in the presence of methoprene (approximately 60% and 85% of inhibition, respectively, with 300 nmol of methoprene/mg of protein), while the activities of cytochrome c oxidase and ATPase do not seem to be affected. Furthermore, the action of methoprene on the mitochondrial permeability transition was also studied, showing that the insecticide (in the range of 30-80 nmol mg(-1) of protein) decreases the susceptibility of liver mitochondria to the opening of the transition pore, even in non-energized mitochondria. These results lead to the conclusion that methoprene interference with hepatic mitochondrial function occurs only for high concentrations, which implies that the noxious effects of the insecticide reported for a number of non-target organisms are not fully attributable to mitochondrial effects. Therefore, it seems that mitochondrial activity does not represent the primary target for methoprene toxic action.

A ventilation intervention study in classrooms to improve indoor air quality: the FRESH study.

PubMed

Rosbach, Jeannette T M; Vonk, Machiel; Duijm, Frans; van Ginkel, Jan T; Gehring, Ulrike; Brunekreef, Bert

2013-12-17

Classroom ventilation rates often do not meet building standards, although it is considered to be important to improve indoor air quality. Poor indoor air quality is thought to influence both children's health and performance. Poor ventilation in The Netherlands most often occurs in the heating season. To improve classroom ventilation a tailor made mechanical ventilation device was developed to improve outdoor air supply. This paper studies the effect of this intervention. The FRESH study (Forced-ventilation Related Environmental School Health) was designed to investigate the effect of a CO2 controlled mechanical ventilation intervention on classroom CO2 levels using a longitudinal cross-over design. Target CO2 concentrations were 800 and 1200 parts per million (ppm), respectively. The study included 18 classrooms from 17 schools from the north-eastern part of The Netherlands, 12 experimental classrooms and 6 control classrooms. Data on indoor levels of CO2, temperature and relative humidity were collected during three consecutive weeks per school during the heating seasons of 2010-2012. Associations between the intervention and weekly average indoor CO2 levels, classroom temperature and relative humidity were assessed by means of mixed models with random school-effects. At baseline, mean CO2 concentration for all schools was 1335 ppm (range: 763-2000 ppm). The intervention was able to significantly decrease CO2 levels in the intervention classrooms (F (2,10) = 17.59, p < 0.001), with a mean decrease of 491 ppm. With the target set at 800 ppm, mean CO2 was 841 ppm (range: 743-925 ppm); with the target set at 1200 ppm, mean CO2 was 975 ppm (range: 887-1077 ppm). Although the device was not capable of precisely achieving the two predefined levels of CO2, our study showed that classroom CO2 levels can be reduced by intervening on classroom ventilation using a CO2 controlled mechanical ventilation system.

Quantitative Cross-Species Extrapolation between Humans and Fish: The Case of the Anti-Depressant Fluoxetine

PubMed Central

Margiotta-Casaluci, Luigi; Owen, Stewart F.; Cumming, Rob I.; de Polo, Anna; Winter, Matthew J.; Panter, Grace H.; Rand-Weaver, Mariann; Sumpter, John P.

2014-01-01

Fish are an important model for the pharmacological and toxicological characterization of human pharmaceuticals in drug discovery, drug safety assessment and environmental toxicology. However, do fish respond to pharmaceuticals as humans do? To address this question, we provide a novel quantitative cross-species extrapolation approach (qCSE) based on the hypothesis that similar plasma concentrations of pharmaceuticals cause comparable target-mediated effects in both humans and fish at similar level of biological organization (Read-Across Hypothesis). To validate this hypothesis, the behavioural effects of the anti-depressant drug fluoxetine on the fish model fathead minnow (Pimephales promelas) were used as test case. Fish were exposed for 28 days to a range of measured water concentrations of fluoxetine (0.1, 1.0, 8.0, 16, 32, 64 µg/L) to produce plasma concentrations below, equal and above the range of Human Therapeutic Plasma Concentrations (HTPCs). Fluoxetine and its metabolite, norfluoxetine, were quantified in the plasma of individual fish and linked to behavioural anxiety-related endpoints. The minimum drug plasma concentrations that elicited anxiolytic responses in fish were above the upper value of the HTPC range, whereas no effects were observed at plasma concentrations below the HTPCs. In vivo metabolism of fluoxetine in humans and fish was similar, and displayed bi-phasic concentration-dependent kinetics driven by the auto-inhibitory dynamics and saturation of the enzymes that convert fluoxetine into norfluoxetine. The sensitivity of fish to fluoxetine was not so dissimilar from that of patients affected by general anxiety disorders. These results represent the first direct evidence of measured internal dose response effect of a pharmaceutical in fish, hence validating the Read-Across hypothesis applied to fluoxetine. Overall, this study demonstrates that the qCSE approach, anchored to internal drug concentrations, is a powerful tool to guide the assessment of the sensitivity of fish to pharmaceuticals, and strengthens the translational power of the cross-species extrapolation. PMID:25338069

Are standard doses of piperacillin sufficient for critically ill patients with augmented creatinine clearance?

PubMed

Udy, Andrew A; Lipman, Jeffrey; Jarrett, Paul; Klein, Kerenaftali; Wallis, Steven C; Patel, Kashyap; Kirkpatrick, Carl M J; Kruger, Peter S; Paterson, David L; Roberts, Michael S; Roberts, Jason A

2015-01-30

The aim of this study was to explore the impact of augmented creatinine clearance and differing minimum inhibitory concentrations (MIC) on piperacillin pharmacokinetic/pharmacodynamic (PK/PD) target attainment (time above MIC (fT>MIC)) in critically ill patients with sepsis receiving intermittent dosing. To be eligible for enrolment, critically ill patients with sepsis had to be receiving piperacillin-tazobactam 4.5 g intravenously (IV) by intermittent infusion every 6 hours for presumed or confirmed nosocomial infection without significant renal impairment (defined by a plasma creatinine concentration greater than 171 μmol/L or the need for renal replacement therapy). Over a single dosing interval, blood samples were drawn to determine unbound plasma piperacillin concentrations. Renal function was assessed by measuring creatinine clearance (CLCR). A population PK model was constructed, and the probability of target attainment (PTA) for 50% and 100% fT>MIC was calculated for varying MIC and CLCR values. In total, 48 patients provided data. Increasing CLCR values were associated with lower trough plasma piperacillin concentrations (P < 0.01), such that with an MIC of 16 mg/L, 100% fT>MIC would be achieved in only one-third (n = 16) of patients. Mean piperacillin clearance was approximately 1.5-fold higher than in healthy volunteers and correlated with CLCR (r = 0.58, P < 0.01). A reduced PTA for all MIC values, when targeting either 50% or 100% fT>MIC, was noted with increasing CLCR measures. Standard intermittent piperacillin-tazobactam dosing is unlikely to achieve optimal piperacillin exposures in a significant proportion of critically ill patients with sepsis, owing to elevated drug clearance. These data suggest that CLCR can be employed as a useful tool to determine whether piperacillin PK/PD target attainment is likely with a range of MIC values.

Attribution of the discrepancy between ELISA and LC-MS/MS assay results of a PEGylated scaffold protein in post-dose monkey plasma samples due to the presence of anti-drug antibodies.

PubMed

Wang, Shujie J; Wu, Steven T; Gokemeijer, Jochem; Fura, Aberra; Krishna, Murli; Morin, Paul; Chen, Guodong; Price, Karen; Wang-Iverson, David; Olah, Timothy; Weiner, Russell; Tymiak, Adrienne; Jemal, Mohammed

2012-01-01

High-performance liquid chromatography-tandem mass spectrometry (LC-MS/MS) and enzyme-linked immunosorbent assay (ELISA) methods were developed for the quantification of a PEGylated scaffold protein drug in monkey plasma samples. The LC-MS/MS method was based on the extraction of the therapeutic protein with a water-miscible organic solvent and the subsequent trypsin digestion of the extract followed by the detection of a surrogate peptide. The assay was linear over a range of 10-3,000 ng/mL. The ELISA method utilized a therapeutic target-binding format in which the recombinant target antigen was used to capture the drug in the sample, followed by detection with an anti-PEG monoclonal antibody. The assay range was 30-2,000 ng/mL. A correlation study between the two methods was performed by measuring the drug concentrations in plasma samples from a single-dose pharmacokinetic (PK) study in cynomolgus monkeys following a 5-mg/kg subcutaneous administration (n = 4). In the early time points of the PK profile, the drug concentrations obtained by the LC-MS/MS method agreed very well with those obtained by the ELISA method. However, at later time points, the drug concentrations measured by the LC-MS/MS method were consistently higher than those measured by the ELISA method. The PK parameters calculated based on the concentration data showed that the two methods gave equivalent peak exposure (C(max)) at 24-48 h. However, the LC-MS/MS results exhibited about 1.53-fold higher total exposure (AUC(tot)) than the ELISA results. The discrepancy between the LC-MS/MS and ELISA results was investigated by conducting immunogenicity testing, anti-drug antibody (ADA) epitope mapping, and Western blot analysis of the drug concentrations coupled with Protein G separation. The results demonstrated the presence of ADA specific to the engineered antigen-binding region of the scaffold protein drug that interfered with the ability of the drug to bind to the target antigen used in the ELISA method. In the presence of the ADAs, the ELISA method measured only the active circulating drug (target-binding), while the LC-MS/MS method measured the total circulating drug. The work presented here indicates that the bioanalysis of protein drugs may be complicated owing to the presence of drug-binding endogenous components or ADAs in the post-dose (incurred) samples. The clear understanding of the behavior of different bioanalytical techniques vis-à-vis the potentially interfering components found in incurred samples is critical in selecting bioanalytical strategies for measuring protein drugs.

Concentrations and variability of organophosphate esters, halogenated flame retardants, and polybrominated diphenyl ethers in indoor and outdoor air in Stockholm, Sweden.

PubMed

Wong, Fiona; de Wit, Cynthia A; Newton, Seth R

2018-05-10

We investigated the concentrations and temporal variability of organophospate esters (OPEs), halogenated flame retardants (HFRs) and polybrominated diphenyl ethers (PBDEs) in indoor and outdoor urban air in Stockholm, Sweden over one year (2014-2015) period. The median concentrations of the three target chemical groups (OPEs, HFRs, PBDEs) were 1-2 orders of magnitude higher in indoor air than outdoor urban air. OPEs were the most abundant target FRs with median concentrations in indoor (Σ 10 OPE = 340 000 pg/m 3 ) and outdoor urban (Σ 10 OPEs = 3100 pg/m 3 ) air, being 3 orders of magnitude greater than for HFRs in indoor (Σ 15 HFRs = 120 pg/m 3 ) and outdoor urban (Σ 15 HFRs = 1.6 pg/m 3 ) air. In indoor air, PBDE concentrations (Σ 17 PBDEs = 33 pg/m 3 ) were lower than for the HFRs, but in outdoor urban air, concentrations (Σ 17 PBDEs = 1.1 pg/m 3 ) were similar to HFRs. The most abundant OPEs in both the indoor and outdoor urban air were tris(2-butoxyethyl)phosphate (TBOEP), tris(chloroisopropyl)phosphate (TCIPP), tris(2-chloroethyl)phosphate (TCEP), tri-n-butyl-phosphate (TnBP), triphenyl phosphate (TPhP) and tris(1,3-dichloroisopropyl)phosphate (TDCIPP). TCIPP in indoor air was found in the highest concentrations and showed the greatest temporal variability, which ranged from 85 000 to 1 900 000 pg/m 3 during the one-year sampling period. We speculate that activities in the building, e.g. floor cleaning, polishing, construction, introduction of new electronics and changes in ventilation rate could explain its variation. Some OPEs (TnBP, TCEP, TCIPP, TDCIPP and TPhP), HFRs/PBDEs (pentabromotoluene, 2, 3-dibromopropyl 2, 4, 6-tribromophenyl ether, hexabromobenzene, BDE-28, -47, and -99) in outdoor urban air showed seasonality, with increased concentrations during the warm period (p < 0.05, Pearson's r ranged from -0.45 to -0.91). The observed seasonality for OPEs was probably due to changes in primary emission, and those for the HFRs and PBDEs was likely due to re-volatilization from contaminated surfaces. Copyright © 2018. Published by Elsevier Ltd.

Ground-water contamination from lead shot at Prime Hook National Wildlife Refuge, Sussex County, Delaware

USGS Publications Warehouse

Soeder, Daniel J.; Miller, Cherie V.

2003-01-01

Prime Hook National Wildlife Refuge is located in southeastern Delaware in coastal lowlands along the margin of Delaware Bay. For 37 years, the Broadkiln Sportsman?s Club adjacent to the refuge operated a trap-shooting range, with the clay-target launchers oriented so that the expended lead shot from the range dropped into forested wetland areas on the refuge property. Investigators have estimated that up to 58,000 shotgun pellets per square foot are present in locations on the refuge where the lead shot fell to the ground. As part of the environmental risk assessment for the site, the U.S. Geological Survey (USGS) investigated the potential for lead contamination in ground water. Results from two sampling rounds in 19 shallow wells indicate that elevated levels of dissolved lead are present in ground water at the site. The lead and associated metals, such as antimony and arsenic (common shotgun pellet alloys), are being transported along shallow ground-water flowpaths toward an open-water slough in the forested wetland adjacent to the downrange target area. Water samples from wells located along the bank of the slough contained dissolved lead concentrations higher than 400 micrograms per liter, and as high as 1 milligram per liter. In contrast, a natural background concentration of lead from ground water in a well upgradient from the site is about 1 microgram per liter. Two water samples collected several months apart from the slough directly downgradient of the shooting range contained 24 and 212 micrograms per liter of lead, respectively. The data indicate that lead from a concentrated deposit of shotgun pellets on the refuge has been mobilized through a combination of acidic water conditions and a very sandy, shallow, unconfined aquifer, and is moving along ground-water flowpaths toward the surface-water drainage. Data from this study will be used to help delineate the lead plume, and determine the fate and transport of lead from the source area.

Toxicity of the bionematicide 1,4-naphthoquinone on non-target soil organisms.

PubMed

Chelinho, S; Maleita, C M N; Francisco, R; Braga, M E M; da Cunha, M J M; Abrantes, I; de Sousa, H C; Morais, P V; Sousa, J P

2017-08-01

The main goal of the present study was to evaluate the ecotoxicological effects of 1,4-naphthoquinone (1,4-NTQ), a natural-origin compound presenting nematicidal activity, that can be obtained from walnut husk, in plants and soil invertebrates, including non-target soil nematode communities. This research was part of an ongoing project that aims to develop environmentally-friendly nematicides obtained from agricultural residues. The battery of ISO tests included emergence and growth of corn (Zea mays) and rape (Brassica napus); avoidance with the earthworm Eisenia andrei and the collembolan Folsomia candida; and reproduction with the previous species plus the enchytraeid Enchytraeus crypticus. A novel soil nematode community assay was also performed. ISO tests and nematode assays were conducted using a natural uncontaminated soil that was spiked with a range of 1,4-NTQ concentrations. Toxicity of 1,4-NTQ was found for all test-species and the most sensitive were F. candida and E. andrei. After 7 days of exposure to 1,4-NTQ, nematode abundance decreased along the concentration gradient, and a partial recovery was observed after 14 days (1,4-NTQ <48 mg kg -1 soil). The number of nematode families consistently decreased in both periods. Overall, results indicate that a 1,4-NTQ concentration of <20 mg kg -1 could be environmentally safe but preliminary data suggest that it might be ineffective for the target-nematodes, root-knot nematodes, Meloidogyne spp., and root-lesion nematodes, Pratylenchus spp. In addition, if higher dosages of 1,4-NTQ bionematicide are necessary, the potential recovery of non-target organisms under real field scenarios also needs to be assessed. Copyright © 2017 Elsevier Ltd. All rights reserved.

Determination of Organophosphorus Pesticides in Soil by Dispersive Liquid–Liquid Microextraction and Gas Chromatography

PubMed Central

Yang, Zhonghua; Liu, Yu; Liu, Donghui; Zhou, Zhiqiang

2012-01-01

In this article, a rapid and sensitive sample pretreatment technique for the determination of organophosphorus pesticides (OPPs) in soil samples is developed by using dispersive liquid–liquid microextraction (DLLME) combined with gas chromatography–flame photometric detection. Experimental conditions, including the kind of extraction and disperser solvent and their volumes, the extraction time, and the salt addition, are investigated, and the following experiment factors are used: 20 µL chlorobenzene as the extraction solvent; 1.0 mL acetonitrile as the disperser solvent; no addition of salt; and an extraction time of 1 min. Under the optimum conditions, the linearities for the three target OPPs (ethoprophos, chlorpyriphos, and profenofos) are obtained by five points in the concentration range of 2.5–1500 µg/kg, and three replicates are used for each point. Correlation coefficients vary from 0.9987 to 0.9997. The repeatability is tested by spiking soil samples at a concentration level of 5.0 µg/kg. The relative standard deviation (n = 3) varied between 2.0% and 6.6%. The limits of detection, based on a signal-to-noise ratio (S/N) of 3, range from 200 to 500 pg/g. This method is applied to the analysis of the spiked samples S1, S2, and S3, which are collected from the China Agriculture University's orchard, lawn, and garden, respectively. The recoveries for each target analyte are in the range between 87.9% and 108.0%, 87.4% and 108.0%, and 86.7% and 107.2%, respectively. PMID:22291051

Targeting an antioxidant to mitochondria decreases cardiac ischemia-reperfusion injury.

PubMed

Adlam, Victoria J; Harrison, Joanne C; Porteous, Carolyn M; James, Andrew M; Smith, Robin A J; Murphy, Michael P; Sammut, Ivan A

2005-07-01

Mitochondrial oxidative damage contributes to a wide range of pathologies, including cardiovascular disorders and neurodegenerative diseases. Therefore, protecting mitochondria from oxidative damage should be an effective therapeutic strategy. However, conventional antioxidants have limited efficacy due to the difficulty of delivering them to mitochondria in situ. To overcome this problem, we developed mitochondria-targeted antioxidants, typified by MitoQ, which comprises a lipophilic triphenylphosphonium (TPP) cation covalently attached to a ubiquinol antioxidant. Driven by the large mitochondrial membrane potential, the TPP cation concentrates MitoQ several hundred-fold within mitochondria, selectively preventing mitochondrial oxidative damage. To test whether MitoQ was active in vivo, we chose a clinically relevant form of mitochondrial oxidative damage: cardiac ischemia-reperfusion injury. Feeding MitoQ to rats significantly decreased heart dysfunction, cell death, and mitochondrial damage after ischemia-reperfusion. This protection was due to the antioxidant activity of MitoQ within mitochondria, as an untargeted antioxidant was ineffective and accumulation of the TPP cation alone gave no protection. Therefore, targeting antioxidants to mitochondria in vivo is a promising new therapeutic strategy in the wide range of human diseases such as Parkinson's disease, diabetes, and Friedreich's ataxia where mitochondrial oxidative damage underlies the pathology.

A critical evaluation of liquid chromatography with hybrid linear ion trap-Orbitrap mass spectrometry for the determination of acidic contaminants in wastewater effluents.

PubMed

Cahill, Michael G; Dineen, Brian A; Stack, Mary A; James, Kevin J

2012-12-28

Acidic pesticide and pharmaceutical contaminants were pre-concentrated and extracted from wastewater samples (500 mL) using solid-phase extraction. Analyte recoveries were 79-96%, with % RSD values in the range, 1.7-7.4%. Analyte identification and quantification were carried out using liquid chromatography-mass spectrometry (LC-MS) with hybrid linear ion trap (LIT) Orbitrap instrumentation. Using a resolution setting of 30,000 FWHM, full-scan MS analysis was performed using heated electrospray ionization (HESI) in negative mode. The high mass resolution capabilities of the Orbitrap MS were exploited for the determination of trace contaminants allowing facile discrimination between analytes and matrix. The dependant scan functions of the Orbitrap MS using higher collisional dissociation (HCD) and LIT MS were evaluated for the confirmation of analytes at trace concentration levels. Mass accuracy for target contaminants using this method was less than 2 ppm. The limits of quantitation (LOQs) were in the range, 2.1-27 ng/L. The inter-day accuracy and precision were measured over a five-day period at two concentrations. The % relative errors were in the range, 0.30-7.7%, and the % RSD values were in the range, 1.5-5.5%. Using this method, 2,4-D, mecoprop, ibuprofen, naproxene and gemfibrozil were identified in several wastewater treatment plants in Ireland. Copyright © 2012 Elsevier B.V. All rights reserved.

Spatial distribution of perchlorate, iodide and thiocyanate in the aquatic environment of Tianjin, China: environmental source analysis.

PubMed

Qin, Xiaolei; Zhang, Tao; Gan, Zhiwei; Sun, Hongwen

2014-09-01

Although China is the largest producer of fireworks (perchlorate-containing products) in the world, the pathways through which perchlorate enters the environment have not been characterized completely in this country. In this study, perchlorate, iodide and thiocyanate were measured in 101 water samples, including waste water, surface water, sea water and paired samples of rain water and surface runoff collected in Tianjin, China. The concentrations of the target anions were generally on the order of rain>surface water≈waste water treatment plant (WWTP) influent>WWTP effluent. High concentrations of perchlorate, iodide and thiocyanate were detected in rain samples, ranging from 0.35 to 27.3 (median: 4.05), 0.51 to 8.33 (2.92), and 1.31 to 107 (5.62) ngmL(-)(1), respectively. Furthermore, the concentrations of the target anions in rain samples were significantly (r=0.596-0.750, p<0.01) positively correlated with the concentrations obtained in the paired surface runoff samples. The anions tested showed a clear spatial distribution, and higher concentrations were observed in the upper reaches of rivers, sea waters near the coast, and rain-surface runoff pairs sampled in urban areas. Our results revealed that precipitation may act as an important source of perchlorate, iodide and thiocyanate in surface water. Moreover, iodide concentrations in the Haihe River and Dagu Drainage Canal showed a good correlation with an ideal marker (acesulfame) of domestic waste water, indicating that input from domestic waste water was an important source of iodide in the surface waters of Tianjin. Copyright © 2014 Elsevier Ltd. All rights reserved.

[The establishment and application of the method with virus concentration and detection in drinking water].

PubMed

Ye, Xiao-yan; Xiao, Wen-qing; Huang, Xia-ning; Zhang, Yong-lu; Cao, Yu-guang; Gu, Kang-ding

2012-07-01

This study aimed to construct an effective method to concentrate and detect virus in drinking water, and human adenovirus pollution status in actual water samples was monitored by constructed method. The concentration efficient of NanoCeram filter for the first concentration with source water and drinking water and the concentration efficient of the different concentrations of PEG 8000 for the second concentration were assessed by spiking f₂ bacteriophage into water samples. The standard of human adenovirus for real-time PCR was constructed by T-A clone. The plasmid obtained was identified through sequence analyzing and consistency check comparing to target gene fragment was conducted by using blast algorithm. Then, real-time PCR was constructed to quantify the concentration of human adenovirus using the plasmid as standard. Water samples were concentrated by using NanoCeram filter on the spot and then concentrated for the second time by PEG/NaCl in 2011. The DNA of concentrated samples were extracted for the quantification of human adenovirus in real-time PCR subsequently to monitor the pollution of human adenovirus in water. For the first concentration by NanoCeram filter, the recovery rates were (51.63 ± 26.60)% in source water and (50.27 ± 14.35)% in treated water, respectively. For the second concentration, the highest recovery rate was reached to (90.09 ± 10.50)% at the concentration of 0.13 kg/L of PEG 8000. The sequence identity score of standard of adenovirus for real time PCR and adenovirus gene was 99%, implying that it can be successfully used to quantification with human adenovirus. The levels of human adenovirus in the water samples sampled in 2011 ranged from 4.13×10³ to 2.20×10⁶ copies/L in source water, while range from 5.57×10² to 7.52×10⁵ copies/L in treated water and the removal efficiency range was (75.49 ± 11.71)%. NanoCeram filers combined with PEG/NaCl was an effective method to concentrate virus in aquatic environment. There was a large number of human adenovirus in source water, and it is not sufficient to remove them thoroughly through conventional water treatment processes.

Effects of Resolution, Range, and Image Contrast on Target Acquisition Performance.

PubMed

Hollands, Justin G; Terhaar, Phil; Pavlovic, Nada J

2018-05-01

We sought to determine the joint influence of resolution, target range, and image contrast on the detection and identification of targets in simulated naturalistic scenes. Resolution requirements for target acquisition have been developed based on threshold values obtained using imaging systems, when target range was fixed, and image characteristics were determined by the system. Subsequent work has examined the influence of factors like target range and image contrast on target acquisition. We varied the resolution and contrast of static images in two experiments. Participants (soldiers) decided whether a human target was located in the scene (detection task) or whether a target was friendly or hostile (identification task). Target range was also varied (50-400 m). In Experiment 1, 30 participants saw color images with a single target exemplar. In Experiment 2, another 30 participants saw monochrome images containing different target exemplars. The effects of target range and image contrast were qualitatively different above and below 6 pixels per meter of target for both tasks in both experiments. Target detection and identification performance were a joint function of image resolution, range, and contrast for both color and monochrome images. The beneficial effects of increasing resolution for target acquisition performance are greater for closer (larger) targets.

A targeted metabolomic protocol for short-chain fatty acids and branched-chain amino acids

PubMed Central

Zheng, Xiaojiao; Qiu, Yunping; Zhong, Wei; Baxter, Sarah; Su, Mingming; Li, Qiong; Xie, Guoxiang; Ore, Brandon M.; Qiao, Shanlei; Spencer, Melanie D.; Zeisel, Steven H.; Zhou, Zhanxiang; Zhao, Aihua; Jia, Wei

2013-01-01

Research in obesity and metabolic disorders that involve intestinal microbiota demands reliable methods for the precise measurement of the short-chain fatty acids (SCFAs) and branched-chain amino acids (BCAAs) concentration. Here, we report a rapid method of simultaneously determining SCFAs and BCAAs in biological samples using propyl chloroformate (PCF) derivatization followed by gas chromatography mass spectrometry (GC-MS) analysis. A one-step derivatization using 100 µL of PCF in a reaction system of water, propanol, and pyridine (v/v/v = 8:3:2) at pH 8 provided the optimal derivatization efficiency. The best extraction efficiency of the derivatized products was achieved by a two-step extraction with hexane. The method exhibited good derivatization efficiency and recovery for a wide range of concentrations with a low limit of detection for each compound. The relative standard deviations (RSDs) of all targeted compounds showed good intra- and inter-day (within 7 days) precision (< 10%), and good stability (< 20%) within 4 days at room temperature (23–25 °C), or 7 days when stored at −20 °C. We applied our method to measure SCFA and BCAA levels in fecal samples from rats administrated with different diet. Both univariate and multivariate statistics analysis of the concentrations of these target metabolites could differentiate three groups with ethanol intervention and different oils in diet. This method was also successfully employed to determine SCFA and BCAA in the feces, plasma and urine from normal humans, providing important baseline information of the concentrations of these metabolites. This novel metabolic profile study has great potential for translational research. PMID:23997757

Comparison of pesticides and other compounds in carpet dust samples collected from used vacuum cleaner bags and from a high-volume surface sampler.

PubMed Central

Colt, J S

1998-01-01

Epidemiologic studies of the association between residential pesticide use and cancer risk require an assessment of past pesticide exposures. Pesticide levels in carpet dust are believed to reflect long-term pesticide use. Recent epidemiologic studies have found collection of dust samples using the high-volume surface sampler (HVS3) to be expensive and cumbersome. We compared the levels of pesticides and other compounds in dust obtained from subjects' personal used vacuum cleaner bags to that collected by the HVS3 to see if this simpler method could replace the HVS3 in epidemiologic research. We visited the homes of 15 subjects, took the used bags from their vacuums, and collected carpet dust samples with the HVS3. The samples were analyzed for 42 target compounds: 26 pesticides, 10 polycyclic aromatic hydrocarbons (PAHs), and six polychlorinated biphenyl (PCB) congeners using GC/MS in selected ion monitoring mode. The two methods agreed in detecting the presence of the target compounds between 80% and 100% of the time. Neither sampling method was consistently more sensitive. The median target compound concentrations were similar, and a paired t-test showed no significant differences. For many compounds, the concentrations of compounds in the HVS3 samples were higher than those in the used bag samples at the upper end of the concentration ranges. However, the Spearman rank correlation coefficients were 0.85 or higher for most compounds, indicating that homes would be ranked similarly using both methods. Overall, there appears to be no clear difference in the quality of the pesticide, PAH, or PCB concentration data for the two dust collection methods. Images Figure 1 PMID:9799187

Measuring the stopping power of α particles in compact bone for BNCT

NASA Astrophysics Data System (ADS)

Provenzano, L.; Rodríguez, L. M.; Fregenal, D.; Bernardi, G.; Olivares, C.; Altieri, S.; Bortolussi, S.; González, S. J.

2015-01-01

The stopping power of α particles in thin films of decalcified sheep femur, in the range of 1.5 to 5.0 MeV incident energy, was measured by transmission of a backscattered beam from a heavy target. Additionally, the film elemental composition was determined by Rutherford Backscattering Spectrometry (RBS). These data will be used to measure boron concentration in thin films of bone using a spectrometry technique developed by the University of Pavia, since the concentration ratio between healthy tissue and tumor is of fundamental importance in Boron Neutron Capture Therapy (BNCT). The present experimental data are compared with numerical simulation results and with tabulated stopping power data of non-decalcified human bone.

NMR diffusion and relaxation studies of 2-nitroimidazole and albumin interactions

NASA Astrophysics Data System (ADS)

Wijesekera, Dj; Willis, Scott A.; Gupta, Abhishek; Torres, Allan M.; Zheng, Gang; Price, William S.

2018-03-01

Nitroimidazole derivatives are of current interest in the development of hypoxia targeting agents and show potential in the establishment of quantitative measures of tumor hypoxia. In this study, the binding of 2-nitroimidazole to albumin was probed using NMR diffusion and relaxation measurements. Binding studies were conducted at three different protein concentrations (0.23, 0.30 and 0.38 mM) with drug concentrations ranging from 0.005-0.16 M at 298 K. Quantitative assessments of the binding model were made by evaluating the number of binding sites, n, and association constant, K. These were determined to be 21 ± 3 and 53 ± 4 M- 1, respectively.

Distribution of Cu, Co, As, and Fe in mine waste, sediment, soil, and water in and around mineral deposits and mines of the Idaho Cobalt Belt, USA

USGS Publications Warehouse

Gray, John E.; Eppinger, Robert G.

2012-01-01

The distribution of Cu, Co, As and Fe was studied downstream from mines and deposits in the Idaho Cobalt Belt (ICB), the largest Co resource in the USA. To evaluate potential contamination in ecosystems in the ICB, mine waste, stream sediment, soil, and water were collected and analyzed for Cu, Co, As and Fe in this area. Concentrations of Cu in mine waste and stream sediment collected proximal to mines in the ICB ranged from 390 to 19,000 μg/g, exceeding the USEPA target clean-up level and the probable effect concentration (PEC) for Cu of 149 μg/g in sediment; PEC is the concentration above which harmful effects are likely in sediment dwelling organisms. In addition concentrations of Cu in mine runoff and stream water collected proximal to mines were highly elevated in the ICB and exceeded the USEPA chronic criterion for aquatic organisms of 6.3 μg/L (at a water hardness of 50 mg/L) and an LC50 concentration for rainbow trout of 14 μg/L for Cu in water. Concentrations of Co in mine waste and stream sediment collected proximal to mines varied from 14 to 7400 μg/g and were highly elevated above regional background concentrations, and generally exceeded the USEPA target clean-up level of 80 μg/g for Co in sediment. Concentrations of Co in water were as high as in 75,000 μg/L in the ICB, exceeding an LC50 of 346 μg/L for rainbow trout for Co in water by as much as two orders of magnitude, likely indicating an adverse effect on trout. Mine waste and stream sediment collected in the ICB also contained highly elevated As concentrations that varied from 26 to 17,000 μg/g, most of which exceeded the PEC of 33 μg/g and the USEPA target clean-up level of 35 μg/g for As in sediment. Conversely, most water samples had As concentrations that were below the 150 μg/L chronic criterion for protection of aquatic organisms and the USEPA target clean-up level of 14 μg/L. There is abundant Fe oxide in streams in the ICB and several samples of mine runoff and stream water exceeded the chronic criterion for protection of aquatic organisms of 1000 μg/L for Fe. There has been extensive remediation of mined areas in the ICB, but because some mine waste remaining in the area contains highly elevated Cu, Co, As and Fe, inhalation or ingestion of mine waste particulates may lead to human exposure to these elements.

Quantitation without Calibration: Response Profile as an Indicator of Target Amount.

PubMed

Debnath, Mrittika; Farace, Jessica M; Johnson, Kristopher D; Nesterova, Irina V

2018-06-21

Quantitative assessment of biomarkers is essential in numerous contexts from decision-making in clinical situations to food quality monitoring to interpretation of life-science research findings. However, appropriate quantitation techniques are not as widely addressed as detection methods. One of the major challenges in biomarker's quantitation is the need to have a calibration for correlating a measured signal to a target amount. The step complicates the methodologies and makes them less sustainable. In this work we address the issue via a new strategy: relying on position of response profile rather than on an absolute signal value for assessment of a target's amount. In order to enable the capability we develop a target-probe binding mechanism based on a negative cooperativity effect. A proof-of-concept example demonstrates that the model is suitable for quantitative analysis of nucleic acids over a wide concentration range. The general principles of the platform will be applicable toward a variety of biomarkers such as nucleic acids, proteins, peptides, and others.

Portable and sensitive quantitative detection of DNA based on personal glucose meters and isothermal circular strand-displacement polymerization reaction.

PubMed

Xu, Xue-tao; Liang, Kai-yi; Zeng, Jia-ying

2015-02-15

A portable and sensitive quantitative DNA detection method based on personal glucose meters and isothermal circular strand-displacement polymerization reaction was developed. The target DNA triggered target recycling process, which opened capture DNA. The released target then found another capture DNA to trigger another polymerization cycle, which was repeated for many rounds, resulting in the multiplication of the DNA-invertase conjugation on the surface of Streptavidin-MNBs. The DNA-invertase was used to catalyze the hydrolysis of sucrose into glucose for PGM readout. There was a liner relationship between the signal of PGM and the concentration of target DNA in the range of 5.0 to 1000 fM, which is lower than some DNA detection method. In addition, the method exhibited excellent sequence selectivity and there was almost no effect of biological complex to the detection performance, which suggested our method can be successfully applied to DNA detection in real biological samples. Copyright © 2014 Elsevier B.V. All rights reserved.

Sorption and toxicity reduction of pharmaceutically active compounds and endocrine disrupting chemicals in the presence of colloidal humic acid.

PubMed

Kim, Injeong; Kim, Hyo-Dong; Jeong, Tae-Yong; Kim, Sang Don

This study investigated the toxicity changes and sorption of pharmaceuticals and endocrine disrupters in the presence of humic acid (HA). For the sorption experiment, a dead end filtration (DEF) system was used to separate bound and free-form target compounds. An algae growth inhibition test and E-screen assay were conducted to estimate the toxic effect of pharmaceutically active compounds (PhACs) and endocrine disrupting chemicals (EDCs), respectively. The permeate concentration was confirmed using liquid chromatography-mass spectrometry. In the sorption test, we observed significant sorption of PhACs and EDCs on colloidal HA, except for sulfamethoxazole (SMX). The values of log KCOC derived from DEF determinations ranged from 4.40 to 5.03. The removal efficiency varied with the HA concentration and the target chemical properties. Tetracycline and 4-octylphenol showed the highest sorption or removal efficiency (≈50%), even at 5 mg C/L HA. The algal growth inhibition of PhACs and the estrogenic effects of EDCs were significantly decreased in proportion to HA concentrations, except for SMX. In addition, the chemical analysis results showed a positive relationship with the bioassay results. Consequently, the sorption of PhACs and EDCs onto colloidal HA should be emphasized in natural environments because it significantly reduces bioavailable concentrations and toxicity to aquatic organisms.

Real-time label-free quantitative fluorescence microscopy-based detection of ATP using a tunable fluorescent nano-aptasensor platform

NASA Astrophysics Data System (ADS)

Shrivastava, Sajal; Sohn, Il-Yung; Son, Young-Min; Lee, Won-Il; Lee, Nae-Eung

2015-11-01

Although real-time label-free fluorescent aptasensors based on nanomaterials are increasingly recognized as a useful strategy for the detection of target biomolecules with high fidelity, the lack of an imaging-based quantitative measurement platform limits their implementation with biological samples. Here we introduce an ensemble strategy for a real-time label-free fluorescent graphene (Gr) aptasensor platform. This platform employs aptamer length-dependent tunability, thus enabling the reagentless quantitative detection of biomolecules through computational processing coupled with real-time fluorescence imaging data. We demonstrate that this strategy effectively delivers dose-dependent quantitative readouts of adenosine triphosphate (ATP) concentration on chemical vapor deposited (CVD) Gr and reduced graphene oxide (rGO) surfaces, thereby providing cytotoxicity assessment. Compared with conventional fluorescence spectrometry methods, our highly efficient, universally applicable, and rational approach will facilitate broader implementation of imaging-based biosensing platforms for the quantitative evaluation of a range of target molecules.Although real-time label-free fluorescent aptasensors based on nanomaterials are increasingly recognized as a useful strategy for the detection of target biomolecules with high fidelity, the lack of an imaging-based quantitative measurement platform limits their implementation with biological samples. Here we introduce an ensemble strategy for a real-time label-free fluorescent graphene (Gr) aptasensor platform. This platform employs aptamer length-dependent tunability, thus enabling the reagentless quantitative detection of biomolecules through computational processing coupled with real-time fluorescence imaging data. We demonstrate that this strategy effectively delivers dose-dependent quantitative readouts of adenosine triphosphate (ATP) concentration on chemical vapor deposited (CVD) Gr and reduced graphene oxide (rGO) surfaces, thereby providing cytotoxicity assessment. Compared with conventional fluorescence spectrometry methods, our highly efficient, universally applicable, and rational approach will facilitate broader implementation of imaging-based biosensing platforms for the quantitative evaluation of a range of target molecules. Electronic supplementary information (ESI) available. See DOI: 10.1039/c5nr05839b

Multicenter Evaluation of the ePlex Respiratory Pathogen Panel for the Detection of Viral and Bacterial Respiratory Tract Pathogens in Nasopharyngeal Swabs

PubMed Central

England, Matthew R.; Jurcic Smith, Kristen L.; He, Taojun; Wijetunge, Dona Saumya; Chamberland, Robin R.; Menegus, Marilyn; Swierkosz, Ella M.; Jerris, Robert C.; Greene, Wallace

2017-01-01

ABSTRACT The performance of the new ePlex Respiratory Pathogen (RP) panel (GenMark Diagnostics) for the simultaneous detection of 19 viruses (influenza A virus; influenza A H1 virus; influenza A 2009 H1 virus; influenza A H3 virus; influenza B virus; adenovirus; coronaviruses [HKU1, OC43, NL63, and 229E]; human rhinovirus/enterovirus; human metapneumovirus; parainfluenza viruses 1, 2, 3, and 4; and respiratory syncytial virus [RSV] [RSV subtype A and RSV subtype B]) and 2 bacteria (Mycoplasma pneumoniae and Chlamydia pneumoniae) was evaluated. Prospectively and retrospectively collected nasopharyngeal swab (NPS) specimens (n = 2,908) were evaluated by using the ePlex RP panel, with the bioMérieux/BioFire FilmArray Respiratory Panel (BioFire RP) as the comparator method. Discordance analysis was performed by using target-specific PCRs and bidirectional sequencing. The reproducibility of the assay was evaluated by using reproducibility panels comprised of 6 pathogens. The overall agreement between the ePlex RP and BioFire RP results was >95% for all targets. Positive percent agreement with the BioFire RP result for viruses ranged from 85.1% (95% confidence interval [CI], 80.2% to 88.9%) to 95.1% (95% CI, 89.0% to 97.9%), while negative percent agreement values ranged from 99.5% (95% CI, 99.1% to 99.7%) to 99.8% (95% CI, 99.5% to 99.9%). Additional testing of discordant targets (12%; 349/2,908) confirmed the results of ePlex RP for 38% (131/349) of samples tested. Reproducibility was 100% for all targets tested, with the exception of adenovirus, for which reproducibilities were 91.6% at low virus concentrations and 100% at moderate virus concentrations. The ePlex RP panel offers a new, rapid, and sensitive “sample-to-answer” multiplex panel for the detection of the most common viral and bacterial respiratory pathogens. PMID:29212701

Effects of wind direction on coarse and fine particulate matter concentrations in southeast Kansas.

PubMed

Guerra, Sergio A; Lane, Dennis D; Marotz, Glen A; Carter, Ray E; Hohl, Carrie M; Baldauf, Richard W

2006-11-01

Field data for coarse particulate matter ([PM] PM10) and fine particulate matter (PM2.5) were collected at selected sites in Southeast Kansas from March 1999 to October 2000, using portable MiniVol particulate samplers. The purpose was to assess the influence on air quality of four industrial facilities that burn hazardous waste in the area located in the communities of Chanute, Independence, Fredonia, and Coffeyville. Both spatial and temporal variation were observed in the data. Variation because of sampling site was found to be statistically significant for PM10 but not for PM2.5. PM10 concentrations were typically slightly higher at sites located within the four study communities than at background sites. Sampling sites were located north and south of the four targeted sources to provide upwind and downwind monitoring pairs. No statistically significant differences were found between upwind and downwind samples for either PM10 or PM2.5, indicating that the targeted sources did not contribute significantly to PM concentrations. Wind direction can frequently contribute to temporal variation in air pollutant concentrations and was investigated in this study. Sampling days were divided into four classifications: predominantly south winds, predominantly north winds, calm/variable winds, and winds from other directions. The effect of wind direction was found to be statistically significant for both PM10 and PM2.5. For both size ranges, PM concentrations were typically highest on days with predominantly south winds; days with calm/variable winds generally produced higher concentrations than did those with predominantly north winds or those with winds from "other" directions. The significant effect of wind direction suggests that regional sources may exert a large influence on PM concentrations in the area.

Carbon nanosphere-based fluorescence aptasensor for targeted detection of breast cancer cell MCF-7.

PubMed

Yang, Dandan; Liu, Mei; Xu, Jing; Yang, Chao; Wang, Xiaoxiao; Lou, Yongbing; He, Nongyue; Wang, Zhifei

2018-08-01

In this work, carbon nanosphere (CNS)-based fluorescence "turn off/on" aptasensor was developed for targeted detection of breast cancer cell MCF-7 by conjugation with FAM (a dye)-labeled mucin1 (MUC1) aptamer P0 (P0-FAM), which can recognize MUC1 protein overexpressed on the surface of MCF-7. Different from other carbon based fluorescence quenching materials, CNSs prepared by the carbonization of glucose not only have the high fluorescence quenching efficiency (98.8%), but also possess negligible cytotoxicity (in the concentration range of 0-1 mg/mL, which is 10 times higher than that of traditional carbon nanotubes or graphene oxide (0-100 µg/mL)). As for the detection of the mimic of the tumor antigen MUC1, the resulting fluorescence intensity increases nearly linearly in the range of 0-6 μM with the limit of detection (LOD) of 25 nM. Copyright © 2018 Elsevier B.V. All rights reserved.

Sulphur-Containing Heterocycles as Antimycobacterial Agents: Recent Advances in Thiophene and Thiadiazole Derivatives.

PubMed

Krátký, Martin; Vinsova, Jarmila

2016-01-01

The global tuberculosis epidemic and emergence of drug resistance call for intensive research on new antimycobacterial agents. Recent development is focused mainly on heterocyclic molecules. In many cases, introduction of sulphur has improved antimicrobial activity; many drugs feature a sulphur heterocycle. Thiophene derivatives and thiadiazoles including derived ortho-condensed heterocycles have been found to have a wide range of biological activities. This review highlights the recent progress in the field with a focus on whole-cell antimycobacterial activity of the agents as well as targeting of enzymes from Mycobacterium tuberculosis. Some of the compounds have exhibited high activity with submicromolar minimum inhibitory concentrations including activity against drug-resistant strains and/or IC50 values for a range of enzymes as their targets (InhA, dehydroquinase, Pks13, carbonic anhydrases, DprE1). Mechanisms of action, toxicity, and structure-activity relationships are also discussed. Several compounds have exhibited promising in vitro and in vivo activities and safety profiles, thus constituting novel, promising leads.

Overweight Kidney Transplant Recipients Are at Risk of Being Overdosed Following Standard Bodyweight-Based Tacrolimus Starting Dose

PubMed Central

Andrews, Louise M.; de Winter, Brenda C.M.; Tang, Jiang-Tao; Shuker, Nauras; Bouamar, Rachida; van Schaik, Ron H.N.; Koch, Birgit C.P.; van Gelder, Teun; Hesselink, Dennis A.

2017-01-01

Background Bodyweight-based dosing of tacrolimus (Tac) is considered standard care, even though the available evidence is thin. An increasing proportion of transplant recipients is overweight, prompting the question if the starting dose should always be based on bodyweight. Methods For this analysis, data were used from a randomized-controlled trial in which patients received either a standard Tac starting dose or a dose that was based on CYP3A5 genotype. The hypothesis was that overweight patients would have Tac overexposure following standard bodyweight-based dosing. Results Data were available for 203 kidney transplant recipients, with a median body mass index (BMI) of 25.6 (range, 17.2-42.2). More than 50% of the overweight or obese patients had a Tac predose concentration above the target range. The CYP3A5 nonexpressers tended to be above target when they weighed more than 67.5 kg or had a BMI of 24.5 or higher. Dosing guidelines were proposed with a decrease up to 40% in Tac starting doses for different BMI groups. The dosing guideline for patients with an unknown genotype was validated using the fixed-dose versus concentration controlled data set. Conclusions This study demonstrates that dosing Tac solely on bodyweight results in overexposure in more than half of overweight or obese patients. PMID:28361113

Identifying mechanism-of-action targets for drugs and probes

PubMed Central

Gregori-Puigjané, Elisabet; Setola, Vincent; Hert, Jérôme; Crews, Brenda A.; Irwin, John J.; Lounkine, Eugen; Marnett, Lawrence; Roth, Bryan L.; Shoichet, Brian K.

2012-01-01

Notwithstanding their key roles in therapy and as biological probes, 7% of approved drugs are purported to have no known primary target, and up to 18% lack a well-defined mechanism of action. Using a chemoinformatics approach, we sought to “de-orphanize” drugs that lack primary targets. Surprisingly, targets could be easily predicted for many: Whereas these targets were not known to us nor to the common databases, most could be confirmed by literature search, leaving only 13 Food and Drug Administration—approved drugs with unknown targets; the number of drugs without molecular targets likely is far fewer than reported. The number of worldwide drugs without reasonable molecular targets similarly dropped, from 352 (25%) to 44 (4%). Nevertheless, there remained at least seven drugs for which reasonable mechanism-of-action targets were unknown but could be predicted, including the antitussives clemastine, cloperastine, and nepinalone; the antiemetic benzquinamide; the muscle relaxant cyclobenzaprine; the analgesic nefopam; and the immunomodulator lobenzarit. For each, predicted targets were confirmed experimentally, with affinities within their physiological concentration ranges. Turning this question on its head, we next asked which drugs were specific enough to act as chemical probes. Over 100 drugs met the standard criteria for probes, and 40 did so by more stringent criteria. A chemical information approach to drug-target association can guide therapeutic development and reveal applications to probe biology, a focus of much current interest. PMID:22711801

Trifunctional molecular beacon-mediated quadratic amplification for highly sensitive and rapid detection of mercury(II) ion with tunable dynamic range.

PubMed

Zhao, Yue; Liu, Huaqing; Chen, Feng; Bai, Min; Zhao, Junwu; Zhao, Yongxi

2016-12-15

Analyses of target with low abundance or concentration varying over many orders of magnitude are severe challenges faced by numerous assay methods due to their modest sensitivity and limited dynamic range. Here, we introduce a homogeneous and rapid quadratic polynomial amplification strategy through rational design of a trifunctional molecular beacon, which serves as not only a reporter molecule but also a bridge to couple two stage amplification modules without adding any reaction components or process other than basic linear amplification. As a test bed for our studies, we took mercury(II) ion as an example and obtained a high sensitivity with detection limit down to 200 pM within 30min. In order to create a tunable dynamic range, homotropic allostery is employed to modulate the target specific binding. When the number of metal binding site varies from 1 to 3, signal response is programmed accordingly with useful dynamic range spanning 50, 25 and 10 folds, respectively. Furthermore, the applicability of the proposed method in river water and biological samples are successfully verified with good recovery and reproducibility, indicating considerable potential for its practicality in complex real samples. Copyright © 2016 Elsevier B.V. All rights reserved.

Pharmacodynamic analysis of ceftriaxone, gatifloxacin,and levofloxacin against Streptococcus pneumoniae with the use of Monte Carlo simulation.

PubMed

Frei, Christopher R; Burgess, David S

2005-09-01

To evaluate the pharmacodynamics of four intravenous antimicrobial regimens-ceftriaxone 1 g, gatifloxacin 400 mg, levofloxacin 500 mg, and levofloxacin 750 mg, each every 24 hours-against recent Streptococcus pneumoniae isolates. Pharmacodynamic analysis using Monte Carlo simulation. The Surveillance Network (TSN) 2002 database. Streptococcus pneumoniae isolates (7866 isolates) were stratified according to penicillin susceptibilities as follows: susceptible (4593), intermediate (1986), and resistant (1287). Risk analysis software was used to simulate 10,000 patients by integrating published pharmacokinetic parameters, their variability, and minimum inhibitory concentration (MIC) distributions from the TSN database. Probability of target attainment was determined for percentage of time above the MIC (%T > MIC) from 0-100% for ceftriaxone and area under the concentration-time curve (AUC):MIC ratio from 0-150 for the fluoroquinolones. For ceftriaxone, probability of target attainment remained 90% or greater against the three isolate groups until a %T > MIC of 70% or greater, and it remained 90% or greater against susceptible and intermediate isolates over the entire interval (%T > MIC 0-100%). For levofloxacin 500 mg, probability of target attainment was 90% at an AUC:MIC < or = 30, but the curve declined sharply with further increases in pharmacodynamic target. Levofloxacin 750 mg achieved a probability of target attainment of 99% at an AUC:MIC ratio < or = 30; the probability remained approximately 90% until a target of 70 or greater, when it declined steeply. Gatifloxacin demonstrated a high probability (99%) of target attainment at an AUC:MIC ratio < or = 30, and it remained above 90% until a target of 70. Ceftriaxone maintained high probability of target attainment over a broad range of pharmacodynamic targets regardless of penicillin susceptibility (%T > MIC 0-60%). Levofloxacin 500 mg maintained high probability of target attainment for AUC:MIC ratios 0-30; whereas, levofloxacin 750 mg and gatifloxacin maintained high probability of target attainment for AUC:MIC ratios 0-60. Rate of decline in the pharmacodynamic curve was most pronounced for the two levofloxacin regimens and more gradual for gatifloxacin and ceftriaxone.

Sedation-analgesia with propofol and remifentanil: concentrations required to avoid gag reflex in upper gastrointestinal endoscopy.

PubMed

Borrat, Xavier; Valencia, José Fernando; Magrans, Rudys; Gimenez-Mila, Marc; Mellado, Ricard; Sendino, Oriol; Perez, Maria; Nunez, Matilde; Jospin, Mathieu; Jensen, Erik Weber; Troconiz, Inaki; Gambus, Pedro L

2015-07-01

The purpose of this study was to identify optimal target propofol and remifentanil concentrations to avoid a gag reflex in response to insertion of an upper gastrointestinal endoscope. Patients presenting for endoscopy received target-controlled infusions (TCI) of both propofol and remifentanil for sedation-analgesia. Patients were randomized to 4 groups of fixed target effect-site concentrations: remifentanil 1 ng•mL (REMI 1) or 2 ng•mL (REMI 2) and propofol 2 μg•mL (PROP 2) or 3 μg•mL (PROP 3). For each group, the other drug (propofol for the REMI groups and vice versa) was increased or decreased using the "up-down" method based on the presence or absence of a gag response in the previous patient. A modified isotonic regression method was used to estimate the median effective Ce,50 from the up-down method in each group. A concentration-effect (sigmoid Emax) model was built to estimate the corresponding Ce,90 for each group. These data were used to estimate propofol bolus doses and remifentanil infusion rates that would achieve effect-site concentrations between Ce,50 and Ce,90 when a TCI system is not available for use. One hundred twenty-four patients were analyzed. To achieve between a 50% and 90% probability of no gag response, propofol TCIs were between 2.40 and 4.23 μg•mL (that could be achieved with a bolus of 1 mg•kg) when remifentanil TCI was fixed at 1 ng•mL, and target propofol TCIs were between 2.15 and 2.88 μg•mL (that could be achieved with a bolus of 0.75 mg•kg) when remifentanil TCI was fixed at 2 ng•mL. Remifentanil ranges were 1.00 to 4.79 ng•mL and 0.72 to 3.19 ng•mL when propofol was fixed at 2 and 3 μg•mL, respectively. We identified a set of propofol and remifentanil TCIs that blocked the gag response to endoscope insertion in patients undergoing endoscopy. Propofol bolus doses and remifentanil infusion rates designed to achieve similar effect-site concentrations can be used to prevent gag response when TCI is not available.

Effect of surfactant concentration on the evaporation of droplets on cotton (Gossypium hirsutum L.) leaves.

PubMed

Zhou, Zhaolu; Cao, Chong; Cao, Lidong; Zheng, Li; Xu, Jun; Li, Fengmin; Huang, Qiliang

2018-04-05

The evaporation kinetics of pesticide droplets deposited on a leaf surface can affect their application efficiency. Evaporation of droplets on the hydrophobic leaves has received considerable attention, but little is known about hydrophilic leaf surfaces. In this study, the effect of surfactant concentration on the evaporation of droplets deposited on cotton leaves was investigated. The evaporation time is roughly decreased for concentrations ranging from 0% to 0.01% and increased from 0.01% to 0.10%. Contrary to the widely held belief that pesticide retention on target crops can rapidly be formed only with surfactant concentrations exceeding the CMC (critical micelle concentration), this study demonstrates that, on hydrophilic cotton leaves, fast evaporation of the droplet at surfactant concentrations of 0.01% (CMC) can reduce the volume quickly, lower the loss point and enhance pesticide retention. In addition, the evolution of droplet volume, height and contact angle on the cotton leaf surface were measured to confirm this conclusion. The result presented herein can be used to guide the use of surfactants and pesticides in agriculture. Copyright © 2018 Elsevier B.V. All rights reserved.

Accumulation of steroid hormones in soil and its adjacent aquatic environment from a typical intensive vegetable cultivation of North China.

PubMed

Zhang, Feng-Song; Xie, Yun-Feng; Li, Xue-Wen; Wang, Dai-Yi; Yang, Lin-Sheng; Nie, Zhi-Qiang

2015-12-15

Steroid hormones released from manure agricultural application are a matter of global concern. The residual levels of steroid hormones were studied in a typical intensive vegetable cultivation area in northeast China, with a long history of heavy manure application. Seven steroids (estrone, 17α-estradiol, 17β-estradiol, estriol, testosterone, androstendione and progesterone) were analyzed from soil sampled from vegetable greenhouses, from sediments and water from the adjacent drainage ditch and from the groundwater. The results showed that target steroids were detected in the soil samples, with detection frequencies varying from 3.13 to 100%. The steroid concentrations varied substantially in soils, ranging from below the detection limit to 109.7μg·kg(-1). Three steroids-progesterone, androstendione and estrone-were found to have relatively high residue concentrations in soil, with maximum concentrations of 109.7, 9.83 and 13.30μg·kg(-1), respectively. In adjacent groundwater, all the steroids, with the exception of estrone, were detected in one or more of the 13 groundwater samples. The concentrations of steroids in groundwater ranged from below the method detection limit to 2.38ng·L(-1). Six of the seven (excluding androstendione) were detected in drainage ditch water samples, with concentrations ranging from below the detection limit to 14ng·L(-1). Progesterone, androstendione and estrone accumulated relatively easily in soils; their concentrations in groundwater were lower than those of other steroids. The concentrations of testosterone and estriol were relatively low in soil, while in groundwater were higher than those of other steroids. The residual levels of steroids in soil and groundwater showed a clear spatial variation in the study area. The residual levels of steroid hormones in soil varied substantially between differently planted greenhouses. Copyright © 2015. Published by Elsevier B.V.

Maximum a posteriori Bayesian estimation of mycophenolic Acid area under the concentration-time curve: is this clinically useful for dosage prediction yet?

PubMed

Staatz, Christine E; Tett, Susan E

2011-12-01

This review seeks to summarize the available data about Bayesian estimation of area under the plasma concentration-time curve (AUC) and dosage prediction for mycophenolic acid (MPA) and evaluate whether sufficient evidence is available for routine use of Bayesian dosage prediction in clinical practice. A literature search identified 14 studies that assessed the predictive performance of maximum a posteriori Bayesian estimation of MPA AUC and one report that retrospectively evaluated how closely dosage recommendations based on Bayesian forecasting achieved targeted MPA exposure. Studies to date have mostly been undertaken in renal transplant recipients, with limited investigation in patients treated with MPA for autoimmune disease or haematopoietic stem cell transplantation. All of these studies have involved use of the mycophenolate mofetil (MMF) formulation of MPA, rather than the enteric-coated mycophenolate sodium (EC-MPS) formulation. Bias associated with estimation of MPA AUC using Bayesian forecasting was generally less than 10%. However some difficulties with imprecision was evident, with values ranging from 4% to 34% (based on estimation involving two or more concentration measurements). Evaluation of whether MPA dosing decisions based on Bayesian forecasting (by the free website service https://pharmaco.chu-limoges.fr) achieved target drug exposure has only been undertaken once. When MMF dosage recommendations were applied by clinicians, a higher proportion (72-80%) of subsequent estimated MPA AUC values were within the 30-60 mg · h/L target range, compared with when dosage recommendations were not followed (only 39-57% within target range). Such findings provide evidence that Bayesian dosage prediction is clinically useful for achieving target MPA AUC. This study, however, was retrospective and focussed only on adult renal transplant recipients. Furthermore, in this study, Bayesian-generated AUC estimations and dosage predictions were not compared with a later full measured AUC but rather with a further AUC estimate based on a second Bayesian analysis. This study also provided some evidence that a useful monitoring schedule for MPA AUC following adult renal transplant would be every 2 weeks during the first month post-transplant, every 1-3 months between months 1 and 12, and each year thereafter. It will be interesting to see further validations in different patient groups using the free website service. In summary, the predictive performance of Bayesian estimation of MPA, comparing estimated with measured AUC values, has been reported in several studies. However, the next step of predicting dosages based on these Bayesian-estimated AUCs, and prospectively determining how closely these predicted dosages give drug exposure matching targeted AUCs, remains largely unaddressed. Further prospective studies are required, particularly in non-renal transplant patients and with the EC-MPS formulation. Other important questions remain to be answered, such as: do Bayesian forecasting methods devised to date use the best population pharmacokinetic models or most accurate algorithms; are the methods simple to use for routine clinical practice; do the algorithms actually improve dosage estimations beyond empirical recommendations in all groups that receive MPA therapy; and, importantly, do the dosage predictions, when followed, improve patient health outcomes?

Terbinafine in Combination with Other Antifungal Agents for Treatment of Resistant or Refractory Mycoses: Investigating Optimal Dosing Regimens Using a Physiologically Based Pharmacokinetic Model

PubMed Central

Dolton, Michael J.; Perera, Vidya; Pont, Lisa G.

2014-01-01

Terbinafine is increasingly used in combination with other antifungal agents to treat resistant or refractory mycoses due to synergistic in vitro antifungal activity; high doses are commonly used, but limited data are available on systemic exposure, and no assessment of pharmacodynamic target attainment has been made. Using a physiologically based pharmacokinetic (PBPK) model for terbinafine, this study aimed to predict total and unbound terbinafine concentrations in plasma with a range of high-dose regimens and also calculate predicted pharmacodynamic parameters for terbinafine. Predicted terbinafine concentrations accumulated significantly during the first 28 days of treatment; the area under the concentration-time curve (AUC)/MIC ratios and AUC for the free, unbound fraction (fAUC)/MIC ratios increased by 54 to 62% on day 7 of treatment and by 80 to 92% on day 28 compared to day 1, depending on the dose regimen. Of the high-dose regimens investigated, 500 mg of terbinafine taken every 12 h provided the highest systemic exposure; on day 7 of treatment, the predicted AUC, maximum concentration (Cmax), and minimum concentration (Cmin) were approximately 4-fold, 1.9-fold, and 4.4-fold higher than with a standard-dose regimen of 250 mg once daily. Close agreement was seen between the concentrations predicted by the PBPK model and the observed concentrations, indicating good predictive performance. This study provides the first report of predicted terbinafine exposure in plasma with a range of high-dose regimens. PMID:24126579

Design, Synthesis and Evaluation of Novel 2,5,6-Trisubstituted Benzimidazoles Targeting FtsZ as Antitubercular Agents

PubMed Central

Park, Bora; Awasthi, Divya; Chowdhury, Soumya R.; Melief, Eduard H.; Kumar, Kunal; Knudson, Susan E.; Slayden, Richard A.; Ojima, Iwao

2014-01-01

Filamenting temperature-sensitive protein Z (FtsZ), an essential cell division protein, is a promising target for the drug discovery of new-generation antibacterial agents against various bacterial pathogens. As a part of SAR studies on benzimidazoles, we have synthesized a library of 376 novel 2,5,6-trisubstituted benzimidazoles, bearing ether or thioether linkage at the 6-position. In a preliminary HTP screening against Mtb H37Rv, 108 compounds were identified as hits at a cut off concentration of 5 μg/mL. Among those hits, 10 compounds exhibited MIC values in the range of 0.63–12.5 μg/mL. Light scattering assay and TEM analysis with the most potent compound 5a clearly indicate that its molecular target is Mtb-FtsZ. Also, the Kd of 5a with Mtb-FtsZ was determined to be 1.32 μM. PMID:24726304

Targeting the Cytochrome bc1 Complex of Leishmania Parasites for Discovery of Novel Drugs.

PubMed

Ortiz, Diana; Forquer, Isaac; Boitz, Jan; Soysa, Radika; Elya, Carolyn; Fulwiler, Audrey; Nilsen, Aaron; Polley, Tamsen; Riscoe, Michael K; Ullman, Buddy; Landfear, Scott M

2016-08-01

Endochin-like quinolones (ELQs) are potent and specific inhibitors of cytochrome bc1 from Plasmodium falciparum and Toxoplasma gondii and show promise for novel antiparasitic drug development. To determine whether the mitochondrial electron transport chain of Leishmania parasites could be targeted similarly for drug development, we investigated the activity of 134 structurally diverse ELQs. A cohort of ELQs was selectively toxic to amastigotes of Leishmania mexicana and L. donovani, with 50% inhibitory concentrations (IC50s) in the low micromolar range, but the structurally similar hydroxynaphthoquinone buparvaquone was by far the most potent inhibitor of electron transport, ATP production, and intracellular amastigote growth. Cytochrome bc1 is thus a promising target for novel antileishmanial drugs, and further improvements on the buparvaquone scaffold are warranted for development of enhanced therapeutics. Copyright © 2016, American Society for Microbiology. All Rights Reserved.

Pharmacist-led implementation of a vancomycin guideline across medical and surgical units: impact on clinical behavior and therapeutic drug monitoring outcomes

PubMed Central

Phillips, Cameron J; Gordon, David L

2015-01-01

Background Vancomycin is the antibiotic of choice for the treatment of serious infections such as methicillin-resistant Staphylococcus aureus (MRSA). Inappropriate prescribing of vancomycin can lead to therapeutic failure, antibiotic resistance, and drug toxicity. Objective To examine the effectiveness of pharmacist-led implementation of a clinical practice guideline for vancomycin dosing and monitoring in a teaching hospital. Methods An observational pre–post study design was undertaken to evaluate the implementation of the vancomycin guideline. The implementation strategy principally involved education, clinical vignettes, and provision of pocket guidelines to accompany release of the guideline to the hospital Intranet. The target cohort for clinical behavioral change was junior medical officers, as they perform the majority of prescribing and monitoring of vancomycin in hospitals. Assessment measures were recorded for vancomycin prescribing, therapeutic drug monitoring, and patient outcomes. Results Ninety-nine patients, 53 pre- and 46 post-implementation, were included in the study. Prescribing of a loading dose increased from 9% to 28% (P=0.02), and guideline adherence to starting maintenance dosing increased from 53% to 63% (P=0.32). Dose adjustment by doctors when blood concentrations were outside target increased from 53% to 71% (P=0.12), and correct timing of initial concentration measurement increased from 43% to 57% (P=0.23). Appropriately timed trough concentrations improved from 73% to 81% (P=0.08). Pre-dose (trough) concentrations in target range rose from 33% to 44% (P=0.10), while potentially toxic concentrations decreased from 32% to 21% (P=0.05) post-implementation. Infection cure rates for patients increased from 85% to 96% (P=0.11) after the guideline was implemented. Conclusion The implementation strategy employed in this study demonstrated potential effectiveness, and should prompt additional larger studies to optimize strategies that will translate into improved clinical practice using vancomycin. PMID:29354529

A Feasibility Study of Nonlinear Spectroscopic Measurement of Magnetic Nanoparticles Targeted to Cancer Cells.

PubMed

Ficko, Bradley W; NDong, Christian; Giacometti, Paolo; Griswold, Karl E; Diamond, Solomon G

2017-05-01

Magnetic nanoparticles (MNPs) are an emerging platform for targeted diagnostics in cancer. An important component needed for translation of MNPs is the detection and quantification of targeted MNPs bound to tumor cells. This study explores the feasibility of a multifrequency nonlinear magnetic spectroscopic method that uses excitation and pickup coils and is capable of discriminating between quantities of bound and unbound MNPs in 0.5 ml samples of KB and Igrov human cancer cell lines. The method is tested over a range of five concentrations of MNPs from 0 to 80 μg/ml and five concentrations of cells from 50 to 400 000 count per ml. A linear model applied to the magnetic spectroscopy data was able to simultaneously measure bound and unbound MNPs with agreement between the model-fit and lab assay measurements (p < 0.001). The detectable iron of the presented method to bound and unbound MNPs was < 2 μg in a 0.5 ml sample. The linear model parameters used to determine the quantities of bound and unbound nanoparticles in KB cells were also used to measure the bound and unbound MNP in the Igrov cell line and vice versa. Nonlinear spectroscopic measurement of MNPs may be a useful method for studying targeted MNPs in oncology. Determining the quantity of bound and unbound MNP in an unknown sample using a linear model represents an exciting opportunity to translate multifrequency nonlinear spectroscopy methods to in vivo applications where MNPs could be targeted to cancer cells.

[Monitoring plan of environmental contaminants in sheep milk from areas next to an Italian contaminated site named «Aree industriali di Porto Torres e discarica di Calancoi» (Industrial areas of Porto Torres and landfill of Calancoi) in Sardinia Region (Southern Italy)].

PubMed

Sgarangella, Francesco; Bitti, Giuseppe; Suelzu, Maria Caterina; Desini, Pietro; Piras, Patrizia; Fiori, Gianuario; Cossu, Maurizio; Chessa, Giannina

2016-01-01

to assess concentration levels of dioxins, PCBs, and chemical elements in sheep milk produced in areas close to the Italian contaminated site (CS) located in the North-West of Sardinia (Southern Italy), named «Aree industriali di Porto Torres e discarica di Calancoi» (i.e., industrial areas of Porto Torres and landfill of Calancoi). monitoring plan of environmental contaminants on zootechnical productions based on analysis of dioxins, PCBs, heavy metals (Cd, Hg, Pb), and other elements (As, Be, Cr, Ni, Tl , Zn) in sheep bulk milk. 60 samples of sheep bulk milk were collected in rural farms where animals were fed mainly with forage and feed produced in the CS: 30 samples from farms located near the industrial area of Porto Torres and 30 taken from farms spread out the landfill area of Calancoi, a former waste dump in the East of Sassari city. the concentration levels of target substances were determined and compared to legal thresholds fixed on EU regulations. concentrations of target substances in all samples were below the maximum limits set by EU regulations. Dioxins and DL-PCBs (expressed as the sum) were in the range 0.20-1.30 pg WHO-TEQ/g fat, NDL-PCB (sum of the six marker congeners) were in the range 0.50-7.50 ng/g, while concentrations of all heavy metals were not detectable or were near the limit of quantitation of the method. Undetectable concentrations were also observed for the toxic elements beryllium and thallium. concentration levels of micro-pollutants in milk samples were significantly lower than the legal thresholds. Concentrations and congener profiles showed no relevant differences compared to milk samples from areas with low environmental impact, therefore consumption of milk from the studied area do not produce a higher intake of contaminants respect to the regional milk. The results of this study do not make the resident population safe from health risks caused by critical issue of the CS, but provide information limited to the safety of the milk from these areas, without showing peculiar contamination and hazard for food from local sheep farms.

Assessment of free fetal DNA concentration in maternal plasma during the first trimester of pregnancy: comparative study between EDTA and PPT tubes - pilot study.

PubMed

Chadud, Carolina Schneider; Araujo Júnior, Edward; Martinhago, Ciro Dresh; Andari, Viviane Cristina Mello; Tedesco, Giselle Darahem; Bussamra, Luiz Claudio Silva; Aoki, Tsutomu

2015-01-01

To compare ethylenediamine tetraacetic acid (EDTA) tubes and plasma preparation tubes (PPT) for evaluating maternal plasma during the first trimester of pregnancy. A cross-sectional study was conducted on 24 male fetuses in women between 6 and 14 weeks of pregnancy. Blood samples (10 mL) were collected and stored in EDTA and PPT tubes. Subsequently, the samples were centrifuged and sent for free fetal DNA extraction by means of the polymerase chain reaction (PCR) technique. The reactions were performed in a real time PCR machine for detecting the amplification products. The genome region chosen for performing the PCR reactions was a target specific for the Y chromosome, in which the DYS-14 marker was amplified only when the DNA was of male sex. The free fetal DNA concentration was given by the threshold cycle (TC). To compare the tubes, the paired Student t-test was used. The mean gestational age was 11.08 ± 2.30 weeks (range: 6-14). The mean TC for PPT was 30.08 ± 1.05 (range: 27.08-32.61) and for EDTA, 30.23 ± 0.96 (range: 28.01-32.09), but without statistical significance (p=0.357). We did not observe any statistically significant difference in free fetal DNA concentration between the EDTA and PPT tubes.

Relationship between atmospheric pollution in the residential area and concentrations of polycyclic aromatic hydrocarbons (PAHs) in human breast milk.

PubMed

Pulkrabova, Jana; Stupak, Michal; Svarcova, Andrea; Rossner, Pavel; Rossnerova, Andrea; Ambroz, Antonin; Sram, Radim; Hajslova, Jana

2016-08-15

Human milk is an important source of beneficial nutrients and antibodies for newborns and infants and, under certain circumstances, its analysis may provide information on mothers' and infants' exposure to various contaminants. In the presented study, we have introduced the new analytical approach for analysis of 24 highly occurring polycyclic aromatic hydrocarbons (PAHs) in this indicator matrix. The sample preparation procedure is based on an ethyl acetate extraction of milk; the transfer of analytes into an organic layer is enhanced by addition of inorganic salts, i.e. sodium chloride and magnesium sulphate. Following the clean-up of a crude extract on silica SPE columns, gas chromatography coupled to triple quadrupole mass spectrometry is used for PAH identification and quantitation. The average recoveries of targeted PAHs from spiked samples were in the range of 68-110% with repeatabilities below 30% and method quantitation limits ranging from 0.03 to 0.3ng/g lipid weight. This newly validated method was successfully applied for analyses of 324 human milk samples collected from nonsmoking women during two sampling periods (summer and winter) in two residential areas in the Czech Republic differing in atmospheric pollution by PAHs. From 24 targeted analytes 17 were detected at least in one sample. Phenantherene, fluoranthrene, pyrene and fluorene were the most abundant compounds found at average concentration of 13.81, 1.80, 0.86, and 2.01ng/g lipid weight respectively. Comparing the data from two sampling periods, in both areas higher concentrations were measured in samples collected during winter. Also in the highly industrialized locality with heavily contaminated air PAH amounts in milk were higher than in the control locality. These first data on PAH concentrations in human milk collected in the Czech Republic are comparable with measurements for nonsmoking women reported earlier in the United States but significantly lower than results from China, Turkey or Italy. Copyright © 2016 Elsevier B.V. All rights reserved.

Development of analysis of volatile polyfluorinated alkyl substances in indoor air using thermal desorption-gas chromatography-mass spectrometry.

PubMed

Wu, Yaoxing; Chang, Victor W-C

2012-05-18

The study attempts to utilize thermal desorption (TD) coupled with gas chromatography-mass spectrometry (GC-MS) for determination of indoor airborne volatile polyfluorinated alkyl substances (PFASs), including four fluorinated alcohols (FTOHs), two fluorooctane sulfonamides (FOSAs), and two fluorooctane sulfonamidoethanols (FOSEs). Standard stainless steel tubes of Tenax/Carbograph 1 TD were employed for low-volume sampling and exhibited minimal breakthrough of target analytes in sample collection. The method recoveries were in the range of 88-119% for FTOHs, 86-138% for FOSAs, exhibiting significant improvement compared with other existing air sampling methods. However, the widely reported high method recoveries of FOSEs were also observed (139-210%), which was probably due to the structural differences between FOSEs and internal standards. Method detection limit, repeatability, linearity, and accuracy were reported as well. The approach has been successfully applied to routine quantification of targeted PFASs in indoor environment of Singapore. The significantly shorter sampling time enabled the observation of variations of concentrations of targeted PFASs within different periods of a day, with higher concentration levels at night while ventilation systems were shut off. This indicated the existence of indoor sources and the importance of building ventilation and air conditioning system. Copyright © 2012 Elsevier B.V. All rights reserved.

Occurrence and preliminarily environmental risk assessment of selected pharmaceuticals in the urban rivers, China

PubMed Central

Zhou, Haidong; Ying, Tianqi; Wang, Xuelian; Liu, Jianbo

2016-01-01

Twelve selected pharmaceuticals including antibiotics, analgesics, antiepileptics and lipid regulators were analysed and detected in water samples collected from 18 sampling sections along the three main urban rivers in Yangpu District of Shanghai, China during four sampling campaigns. Besides, algal growth inhibition test was conducted to preliminarily assess the eco-toxicology induced by the target pharmaceuticals in the rivers. Mean levels for most of target compounds were generally below 100 ng/L at sampling sections, with the exception of caffeine and paracetamol presenting considerably high concentration. The detected pharmaceuticals in the urban rivers ranged from

Antibiotic regimen based on population analysis of residing persister cells eradicates Staphylococcus epidermidis biofilms

PubMed Central

Yang, Shoufeng; Hay, Iain D.; Cameron, David R.; Speir, Mary; Cui, Bintao; Su, Feifei; Peleg, Anton Y.; Lithgow, Trevor; Deighton, Margaret A.; Qu, Yue

2015-01-01

Biofilm formation is a major pathogenicity strategy of Staphylococcus epidermidis causing various medical-device infections. Persister cells have been implicated in treatment failure of such infections. We sought to profile bacterial subpopulations residing in S. epidermidis biofilms, and to establish persister-targeting treatment strategies to eradicate biofilms. Population analysis was performed by challenging single biofilm cells with antibiotics at increasing concentrations ranging from planktonic minimum bactericidal concentrations (MBCs) to biofilm MBCs (MBCbiofilm). Two populations of “persister cells” were observed: bacteria that survived antibiotics at MBCbiofilm for 24/48 hours were referred to as dormant cells; those selected with antibiotics at 8 X MICs for 3 hours (excluding dormant cells) were defined as tolerant-but-killable (TBK) cells. Antibiotic regimens targeting dormant cells were tested in vitro for their efficacies in eradicating persister cells and intact biofilms. This study confirmed that there are at least three subpopulations within a S. epidermidis biofilm: normal cells, dormant cells, and TBK cells. Biofilms comprise more TBK cells and dormant cells than their log-planktonic counterparts. Using antibiotic regimens targeting dormant cells, i.e. effective antibiotics at MBCbiofilm for an extended period, might eradicate S. epidermidis biofilms. Potential uses for this strategy are in antibiotic lock techniques and inhaled aerosolized antibiotics. PMID:26687035

Occurrence and preliminarily environmental risk assessment of selected pharmaceuticals in the urban rivers, China

NASA Astrophysics Data System (ADS)

Zhou, Haidong; Ying, Tianqi; Wang, Xuelian; Liu, Jianbo

2016-10-01

Twelve selected pharmaceuticals including antibiotics, analgesics, antiepileptics and lipid regulators were analysed and detected in water samples collected from 18 sampling sections along the three main urban rivers in Yangpu District of Shanghai, China during four sampling campaigns. Besides, algal growth inhibition test was conducted to preliminarily assess the eco-toxicology induced by the target pharmaceuticals in the rivers. Mean levels for most of target compounds were generally below 100 ng/L at sampling sections, with the exception of caffeine and paracetamol presenting considerably high concentration. The detected pharmaceuticals in the urban rivers ranged from

On-chip transduction of nucleic acid hybridization using spatial profiles of immobilized quantum dots and fluorescence resonance energy transfer.

PubMed

Tavares, Anthony J; Noor, M Omair; Vannoy, Charles H; Algar, W Russ; Krull, Ulrich J

2012-01-03

The glass surface of a glass-polydimethylsiloxane (PDMS) microfluidic channel was modified to develop a solid-phase assay for quantitative determination of nucleic acids. Electroosmotic flow (EOF) within channels was used to deliver and immobilize semiconductor quantum dots (QDs), and electrophoresis was used to decorate the QDs with oligonucleotide probe sequences. These processes took only minutes to complete. The QDs served as energy donors in fluorescence resonance energy transfer (FRET) for transduction of nucleic acid hybridization. Electrokinetic injection of fluorescent dye (Cy3) labeled oligonucleotide target into a microfluidic channel and subsequent hybridization (within minutes) provided the proximity for FRET, with emission from Cy3 being the analytical signal. The quantification of target concentration was achieved by measurement of the spatial length of coverage by target along a channel. Detection of femtomole quantities of target was possible with a dynamic range spanning an order of magnitude. The assay provided excellent resistance to nonspecific interactions of DNA. Further selectivity of the assay was achieved using 20% formamide, which allowed discrimination between a fully complementary target and a 3 base pair mismatch target at a contrast ratio of 4:1. © 2011 American Chemical Society

Adapting an Evidence-Based Intervention Targeting HIV-Infected Prisoners in Malaysia

PubMed Central

Copenhaver, Michael M.; Tunku, Noor; Ezeabogu, Ifeoma; Potrepka, Jessica; Zahari, Muhammad Muhsin A.; Kamarulzaman, Adeeba; Altice, Frederick L.

2011-01-01

HIV-infected prisoners in Malaysia represent a critical target population for secondary HIV risk reduction interventions and care. We report on the process and outcome of our formative research aimed at systematically selecting and adapting an EBI designed to reduce secondary HIV risk and improve adherence to antiretroviral therapy among soon-to-be-released HIV-infected prisoners. Our formative work involved a critical examination of established EBIs and associated published reports complemented by data elicited through structured interviews and focus groups with key stakeholders, members of the target population, and their family members. Based on all information, we adapted the Holistic Health Recovery Program targeting people living with HIV (HHRP+), an EBI, to consist of eight 2-hour sessions that cover a range of specified topics so that participants may individually apply intervention content as needed to accommodate their particular substance abuse, HIV risk, and antiretroviral adherence issues. This study provides a complete example of the process of selecting and adapting an EBI—taking into account both empirical evidence and input from target organization stakeholders and target population members and their families—for use in real world prison settings where high-risk populations are concentrated. PMID:21860786

Impacts of traffic and rainfall characteristics on heavy metals build-up and wash-off from urban roads.

PubMed

Mahbub, Parvez; Ayoko, Godwin A; Goonetilleke, Ashantha; Egodawatta, Prasanna; Kokot, Serge

2010-12-01

An investigation into the effects of changes in urban traffic characteristics due to rapid urbanisation and the predicted changes in rainfall characteristics due to climate change on the build-up and wash-off of heavy metals was carried out in Gold Coast, Australia. The study sites encompassed three different urban land uses. Nine heavy metals commonly associated with traffic emissions were selected. The results were interpreted using multivariate data analysis and decision making tools, such as principal component analysis (PCA), fuzzy clustering (FC), PROMETHEE, and GAIA. Initial analyses established high, low, and moderate traffic scenarios as well as low, low to moderate, moderate, high, and extreme rainfall scenarios for build-up and wash-off investigations. GAIA analyses established that moderate to high traffic scenarios could affect the build-up, while moderate to high rainfall scenarios could affect the wash-off of heavy metals under changed conditions. However, in wash-off, metal concentrations in 1-75 μm fraction were found to be independent of the changes to rainfall characteristics. In build-up, high traffic activities in commercial and industrial areas influenced the accumulation of heavy metal concentrations in particulate size range from 75 - >300 μm, whereas metal concentrations in finer size range of <1-75 μm were not affected. As practical implications, solids <1 μm and organic matter from 1 - >300 μm can be targeted for removal of Ni, Cu, Pb, Cd, Cr, and Zn from build-up, while organic matter from <1 - >300 μm can be targeted for removal of Cd, Cr, Pb, and Ni from wash-off. Cu and Zn need to be removed as free ions from most fractions in wash-off.

Atmospheric Concentrations of Persistent Organic Pollutants in the Southern Ocean

NASA Astrophysics Data System (ADS)

Vlahos, P.; Edson, J.; Cifuentes, A.; McGillis, W. R.; Zappa, C.

2008-12-01

Long-range transport of persistent organic pollutant (POPs) is a global concern. Remote regions such as the Southern Ocean are greatly under-sampled though critical components in understanding POPs cycling. Over 20 high-volume air samples were collected in the Southern Ocean aboard the RV Brown during the GASEX III experiment between Mar 05 to April 9 2008. The relatively stationary platform (51S,38W) enabled the collection of a unique atmospheric time series at this open ocean station. Air sampling was also conducted across transects from Punto Arenas, Chile and to Montevideo, Uruguay. Samples were collected using glass sleeves packed with poly-urethane foam plugs and C-18 resin in order to collect target organic pollutants (per-fluorinated compounds, currently and historically used pesticides) in this under-sampled region. Here we present POPs concentrations and trends over the sampled period and compare variations with air parcel back trajectories to establish potential origins of their long-range transport.

Assessment of TBT and organic booster biocide contamination in seawater from coastal areas of South Korea.

PubMed

Kim, Nam Sook; Shim, Won Joon; Yim, Un Hyuk; Hong, Sang Hee; Ha, Sung Yong; Han, Gi Myung; Shin, Kyung-Hoon

2014-01-15

Seawater samples from major enclosed bays, fishing ports, and harbors of Korea were analyzed to determine levels of tributyltin (TBT) and booster biocides, which are antifouling agents used as alternatives to TBT. TBT levels were in the range of not detected (nd) to 23.9 ng Sn/L. Diuron and Irgarol 1051, at concentration ranges of 35-1360 ng/L and nd to 14 ng/L, respectively, were the most common alternative biocides present in seawater, with the highest concentrations detected in fishing ports. Hot spots were identified where TBT levels exceeded environmental quality targets even 6 years after a total ban on its use in Korea. Diuron exceeded the UK environmental quality standard (EQS) value in 73% of the fishing port samples, 64% of the major bays, and 42% of the harbors. Irgarol 1051 levels were marginally below the Dutch and UK EQS values at all sites. Copyright © 2013 Elsevier Ltd. All rights reserved.

Melanoma-targeted delivery system (part 1): design, synthesis and evaluation of releasable disulfide drug by glutathione.

PubMed

El Aissi, Radhia; Chezal, Jean-Michel; Tarrit, Sébastien; Chavignon, Olivier; Moreau, Emmanuel

2015-08-28

Here we describe the design and synthesis of a prodrug developed for pigmented melanoma therapy, consisting of a Melanin-Targeting Probe (MTP) conjugated to 5-iodo-2'-deoxyuridine (IUdR) with a reduction-sensitive pre-determined breaking point. Compared with the non-cleavable conjugate (17b), prodrug (17a) bearing a self-immolative disulfide linker achieved complete release of IUdR within 20 min in the presence of reducing agents such as DTT or glutathione. Analytical results also showed that prodrug (17a) was more sensitive than parent non-cleavable conjugate (17b) for a concentration range of glutathione similar to that found in the intracellular compartment of tumours. Copyright © 2015 Elsevier Masson SAS. All rights reserved.

Extrapolation procedures in Mott electron polarimetry

NASA Technical Reports Server (NTRS)

Gay, T. J.; Khakoo, M. A.; Brand, J. A.; Furst, J. E.; Wijayaratna, W. M. K. P.; Meyer, W. V.; Dunning, F. B.

1992-01-01

In standard Mott electron polarimetry using thin gold film targets, extrapolation procedures must be used to reduce the experimentally measured asymmetries A to the values they would have for scattering from single atoms. These extrapolations involve the dependent of A on either the gold film thickness or the maximum detected electron energy loss in the target. A concentric cylindrical-electrode Mott polarimeter, has been used to study and compare these two types of extrapolations over the electron energy range 20-100 keV. The potential systematic errors which can result from such procedures are analyzed in detail, particularly with regard to the use of various fitting functions in thickness extrapolations, and the failure of perfect energy-loss discrimination to yield accurate polarizations when thick foils are used.

Concentrations of polybrominated diphenyl ethers (PBDEs) in central air-conditioner filter dust and relevance of non-dietary exposure in occupational indoor environments in Greece.

PubMed

Besis, Athanasios; Katsoyiannis, Athanasios; Botsaropoulou, Elisavet; Samara, Constantini

2014-05-01

Polybrominated Diphenyl Ethers (PBDEs) are ubiquitous in the indoor environment owing to their use in consumer products and various studies around the world have found higher concentrations indoors than outdoors. Central air conditioner (A/C) systems have been widely used in many workplaces, therefore, studying of PBDEs in central A/C filter dust is useful to better understand the occurrences and health implications of PBDEs in indoor environments. The present study examined the occurrence of PBDEs in central A/C filter dust collected from various workplaces (n = 20) in Thessaloniki, Greece. The sum concentrations of 21 target congeners (∑21PBDE) in A/C dust ranged between 84 and 4062 ng g(-1) with a median value of 1092 ng g(-1), while BDE-209 was found to be the most abundant BDE congener. The daily intake via dust ingestion of PBDEs estimated for the employees of the occupational settings ranged from 3 to 45 ng day(-1) (median 12 ng day(-1)). Copyright © 2014 Elsevier Ltd. All rights reserved.

Final Report - Enhanced LAW Glass Formulation Testing, VSL-07R1130-1, Rev. 0, dated 10/05/07

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

Kruger, Albert A.; Pegg, I. L.; Matlack, K. S.

2013-11-13

The principal objective of this work was to extend the glass formulation methodology developed in the earlier work [2, 5, 6] for Envelope A, B and C waste compositions for development of compliant glass compositions targeting five high sodium-sulfur waste loading regions. This was accomplished through a combination of crucible-scale tests, and tests on the DM10 melter system. The DM10 was used for several previous tests on LAW compositions to determine the maximum feed sulfur concentrations that can be processed without forming secondary sulfate phases on the surface of the melt pool. This melter is the most efficient melter platformmore » for screening glass compositions over a wide range of sulfate concentrations and therefore was selected for the present tests. The tests were conducted to provide information on melter processing characteristics and off-gas data, including sulfur incorporation and partitioning. As described above, the main objective was to identify the limits of waste loading in compliant glass formulations spanning the range of expected Na{sub 2}O and SO{sub 3} concentrations in the LAW glasses.« less

PAHs, NITRO-PAHs, HOPANES, AND STERANES IN LAKE TROUT FROM LAKE MICHIGAN

PubMed Central

Huang, Lei; Chernyak, Sergei M.; Batterman, Stuart A.

2015-01-01

The present study examines concentrations and risks of polycyclic aromatic hydrocarbons (PAHs), nitro-PAHs (NPAHs), steranes, and hopanes in lake trout collected in Lake Michigan. A total of 74 fish were collected in 2 seasons at 3 offshore sites. The total PAH concentration (Σ9PAH) in whole fish ranged from 223 pg/g to 1704 pg/g wet weight, and PAH concentrations and profiles were similar across season, site, and sex. The total NPAH (Σ9NPAH) concentrations ranged from 0.2 pg/g to 31 pg/g wet weight, and carcinogenic compounds, including 1-nitropyrene and 6-nitrochrysene, were detected. In the fall, NPAH concentrations were low at the Illinois site (0.2–0.5 pg/g wet wt), and site profiles differed considerably; in the spring, concentrations and profiles were similar across sites, possibly reflecting changes in fish behavior. In the fall, the total sterane (Σ5Sterane) and total hopane (Σ2Hopane) levels reached 808 pg/g and 141 pg/g wet weight, respectively, but concentrations in the spring were 10 times lower. Concentrations in eggs (fall only) were on the same order of magnitude as those in whole fish. These results demonstrate the presence of target semivolatile organic compounds in a top predator fish, and are consistent with PAH biodilution observed previously. Using the available toxicity information for PAHs and NPAHs, the expected cancer risk from consumption of lake trout sampled are low. However, NPAHs contributed a significant portion of the toxic equivalencies in some samples. The present study provides the first measurements of NPAHs in freshwater fish, and results suggest that additional assessment is warranted. PMID:24764175

Relationship between peroxisome proliferator-activated receptor alpha activity and cellular concentration of 14 perfluoroalkyl substances in HepG2 cells.

PubMed

Rosenmai, Anna Kjerstine; Ahrens, Lutz; le Godec, Théo; Lundqvist, Johan; Oskarsson, Agneta

2018-02-01

Peroxisome proliferator-activated receptor alpha (PPARα) is a molecular target for perfluoroalkyl substances (PFASs). Little is known about the cellular uptake of PFASs and how it affects the PPARα activity. We investigated the relationship between PPARα activity and cellular concentration in HepG2 cells of 14 PFASs, including perfluoroalkyl carboxylates (PFCAs), perfluoroalkyl sulfonates and perfluorooctane sulfonamide (FOSA). Cellular concentrations were determined by high-performance liquid chromatography-tandem mass spectrometry and PPARα activity was determined in transiently transfected cells by reporter gene assay. Cellular uptake of the PFASs was low (0.04-4.1%) with absolute cellular concentrations in the range 4-2500 ng mg -1 protein. Cellular concentration of PFCAs increased with perfluorocarbon chain length up to perfluorododecanoate. PPARα activity of PFCAs increased with chain length up to perfluorooctanoate. The maximum induction of PPARα activity was similar for short-chain (perfluorobutanoate and perfluoropentanoate) and long-chain PFCAs (perfluorododecanoate and perfluorotetradecanoate) (approximately twofold). However, PPARα activities were induced at lower cellular concentrations for the short-chain homologs compared to the long-chain homologs. Perfluorohexanoate, perfluoroheptanoate, perfluorooctanoate, perfluorononanoate (PFNA) and perfluorodecanoate induced PPARα activities >2.5-fold compared to controls. The concentration-response relationships were positive for all the tested compounds, except perfluorooctane sulfonate PFOS and FOSA, and were compound-specific, as demonstrated by differences in the estimated slopes. The relationships were steeper for PFCAs with chain lengths up to and including PFNA than for the other studied PFASs. To our knowledge, this is the first report establishing relationships between PPARα activity and cellular concentration of a broad range of PFASs. Copyright © 2017 John Wiley & Sons, Ltd.

Silver metal nanoparticles study for biomedical and green house applications

NASA Astrophysics Data System (ADS)

Rauwel, E.; Simón-Gracia, L.; Guha, M.; Rauwel, P.; Kuunal, S.; Wragg, D.

2017-02-01

Metallic nanoparticles (MNP) with diameters ranging from 2 to 100nm have received extensive attention during the past decades due to their many potential applications. This paper presents a structural and cytotoxicity study of silver metal nanoparticles targeted towards biomedical applications. Spherical Ag MNPs of diameter from 20 to 50 nm have been synthesized. The encapsulation of Ag MNPs inside pH-sensitive polymersomes has been also studied for the development of biomedical applications. A cytotoxicity study of the Ag MNPs against primary prostatic cancer cell line (PPC-1) has demonstrated a high mortality rate for concentrations ranging from 100 to 200mg/L. The paper will discuss the potential for therapeutic treatments of these Ag MNPs.

Qualification of a Multi-Channel Infrared Laser Absorption Spectrometer for Monitoring CO, HCl, HCN, HF, and CO2 Aboard Manned Spacecraft

NASA Technical Reports Server (NTRS)

Briggs, Ryan M.; Frez, Clifford; Forouhar, Siamak; May, Randy D.; Meyer, Marit E.; Kulis, Michael J.; Berger, Gordon M.

2015-01-01

Monitoring of specific combustion products can provide early-warning detection of accidental fires aboard manned spacecraft and also identify the source and severity of combustion events. Furthermore, quantitative in situ measurements are important for gauging levels of exposure to hazardous gases, particularly on long-duration missions where analysis of returned samples becomes impractical. Absorption spectroscopy using tunable laser sources in the 2 to 5 micrometer wavelength range enables accurate, unambiguous detection of CO, HCl, HCN, HF, and CO2, which are produced in varying amounts through the heating of electrical components and packaging materials commonly used aboard spacecraft. Here, we report on calibration and testing of a five-channel laser absorption spectrometer designed to accurately monitor ambient gas-phase concentrations of these five compounds, with low-level detection limits based on the Spacecraft Maximum Allowable Concentrations. The instrument employs a two-pass absorption cell with a total optical pathlength of 50 cm and a dedicated infrared semiconductor laser source for each target gas. We present results from testing the five-channel sensor in the presence of trace concentrations of the target compounds that were introduced using both gas sources and oxidative pyrolysis (non-flaming combustion) of solid material mixtures.

Instrumentation to Support the Research Program of Pulsed Laser Deposition of Polymer Nanocomposite Films

DTIC Science & Technology

2015-05-19

ablated the targets in the same spots during the PLD process. The beams quickly created craters in these spots. That led to cracks and rapid (in...nanoparticles in the near-IR range taken with the newly acquired (with the support from the DoD Grant) UV -VIS-NIR Spectrophotometer Cary from Varian. As...reagent film has the capability of recovering from the exposure to very high ammonia concentrations without experiencing any irreversible damage . Based on

Charge transfer during individual collisions in ice growing by riming

NASA Technical Reports Server (NTRS)

Avila, Eldo E.; Caranti, Giorgio M.

1991-01-01

The charging of a target by riming in the wind was studied in the temperature range of (-10, -18 C). For each temperature, charge transfers of both signs are observed and, according to the environmental conditions, one of them prevails. The charge is more positive as the liquid water concentration is increased at any particular temperature. It is found that even at the low impact velocities used (5 m/s) there is abundant evidence of fragmentation following the collision.

Targeted RNA-Sequencing with Competitive Multiplex-PCR Amplicon Libraries

PubMed Central

Blomquist, Thomas M.; Crawford, Erin L.; Lovett, Jennie L.; Yeo, Jiyoun; Stanoszek, Lauren M.; Levin, Albert; Li, Jia; Lu, Mei; Shi, Leming; Muldrew, Kenneth; Willey, James C.

2013-01-01

Whole transcriptome RNA-sequencing is a powerful tool, but is costly and yields complex data sets that limit its utility in molecular diagnostic testing. A targeted quantitative RNA-sequencing method that is reproducible and reduces the number of sequencing reads required to measure transcripts over the full range of expression would be better suited to diagnostic testing. Toward this goal, we developed a competitive multiplex PCR-based amplicon sequencing library preparation method that a) targets only the sequences of interest and b) controls for inter-target variation in PCR amplification during library preparation by measuring each transcript native template relative to a known number of synthetic competitive template internal standard copies. To determine the utility of this method, we intentionally selected PCR conditions that would cause transcript amplification products (amplicons) to converge toward equimolar concentrations (normalization) during library preparation. We then tested whether this approach would enable accurate and reproducible quantification of each transcript across multiple library preparations, and at the same time reduce (through normalization) total sequencing reads required for quantification of transcript targets across a large range of expression. We demonstrate excellent reproducibility (R2 = 0.997) with 97% accuracy to detect 2-fold change using External RNA Controls Consortium (ERCC) reference materials; high inter-day, inter-site and inter-library concordance (R2 = 0.97–0.99) using FDA Sequencing Quality Control (SEQC) reference materials; and cross-platform concordance with both TaqMan qPCR (R2 = 0.96) and whole transcriptome RNA-sequencing following “traditional” library preparation using Illumina NGS kits (R2 = 0.94). Using this method, sequencing reads required to accurately quantify more than 100 targeted transcripts expressed over a 107-fold range was reduced more than 10,000-fold, from 2.3×109 to 1.4×105 sequencing reads. These studies demonstrate that the competitive multiplex-PCR amplicon library preparation method presented here provides the quality control, reproducibility, and reduced sequencing reads necessary for development and implementation of targeted quantitative RNA-sequencing biomarkers in molecular diagnostic testing. PMID:24236095

A tissue dose-based comparative exposure assessment of manganese using physiologically based pharmacokinetic modeling—The importance of homeostatic control for an essential metal

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

Gentry, P. Robinan, E-mail: rgentry@ramboll.com

A physiologically-based pharmacokinetic (PBPK) model (Schroeter et al., 2011) was applied to simulate target tissue manganese (Mn) concentrations following occupational and environmental exposures. These estimates of target tissue Mn concentrations were compared to determine margins of safety (MOS) and to evaluate the biological relevance of applying safety factors to derive acceptable Mn air concentrations. Mn blood concentrations measured in occupational studies permitted verification of the human PBPK models, increasing confidence in the resulting estimates. Mn exposure was determined based on measured ambient air Mn concentrations and dietary data in Canada and the United States (US). Incorporating dietary and inhalation exposuresmore » into the models indicated that increases in target tissue concentrations above endogenous levels only begin to occur when humans are exposed to levels of Mn in ambient air (i.e. > 10 μg/m{sup 3}) that are far higher than those currently measured in Canada or the US. A MOS greater than three orders of magnitude was observed, indicating that current Mn air concentrations are far below concentrations that would be required to produce the target tissue Mn concentrations associated with subclinical neurological effects. This application of PBPK modeling for an essential element clearly demonstrates that the conventional application of default factors to “convert” an occupational exposure to an equivalent continuous environmental exposure, followed by the application of safety factors, is not appropriate in the case of Mn. PBPK modeling demonstrates that the relationship between ambient Mn exposures and dose-to-target tissue is not linear due to normal tissue background levels and homeostatic controls. - Highlights: • Manganese is an essential nutrient, adding complexity to its risk assessment. • Nonlinearities in biological processes are important for manganese risk assessment. • A PBPK model was used to estimate target tissue concentrations of manganese. • An MOS approach also considered target tissue concentrations for ambient exposures. • Relationships between ambient Mn exposures and dose-to-target tissue are not linear.« less

Biotherapeutic formulation factors affecting metal leachables from stainless steel studied by design of experiments.

PubMed

Zhou, Shuxia; Evans, Brad; Schöneich, Christian; Singh, Satish K

2012-03-01

Trace amounts of metals are inevitably present in biotherapeutic products. They can arise from various sources. The impact of common formulation factors such as protein concentration, antioxidant, metal chelator concentration and type, surfactant, pH, and contact time with stainless steel on metal leachables was investigated by a design of experiments approach. Three major metal leachables, iron, chromium, and nickel were monitored by inductively coupled plasma-mass spectrometry. It was observed that among all the tested factors, contact time, metal chelator concentration, and protein concentration were statistically significant factors with higher temperature resulting in higher levels of leached metals. Within a pH range of 5.5-6.5, solution pH played a minor role for chromium leaching at 25°C. No statistically significant difference was observed due to type of chelator, presence of antioxidant, or surfactant. In order to optimize a biotherapeutic formulation to achieve a target drug product shelf life with acceptable quality, each formulation component must be evaluated for its impact.

Growth Recovery of Lemna gibba and Lemna minor Following a 7-Day Exposure to the Herbicide Diuron.

PubMed

Burns, Mitchell; Hanson, Mark L; Prosser, Ryan S; Crossan, Angus N; Kennedy, Ivan R

2015-08-01

In agricultural catchments, aquatic ecosystems can experience a pulse exposure to pesticides. Following such exposure, non-target organisms that are not extirpated may recover. This paper investigates the potential of two duckweed species (Lemna minor and Lemna gibba) to recover from a 7-day exposure to different concentrations (0.4-208 µg L(-1)) of the herbicide diuron. There was significant inhibition in the growth and biomass after the initial 7-day exposure (e.g. frond number EC50=59.2 and 52.2 µg L(-1) for L. minor and L. gibba, respectively). Following transfer to clean media, recovery (the highest concentration yielding no significant difference in the effect endpoint from the control) was observed for all effects endpoints at concentrations ranging 60-111 µg L(-1) for L. minor and 60-208 µg L(-1) for L. gibba. These results suggest that recovery is possible for primary producers at environmentally relevant concentrations considered significant in ecological risk assessment.

Characterization of occurrence, sources and sinks of perfluoroalkyl and polyfluoroalkyl substances (PFASs) in a tropical urban catchment.

PubMed

Chen, Huiting; Reinhard, Martin; Nguyen, Tung Viet; You, Luhua; He, Yiliang; Gin, Karina Yew-Hoong

2017-08-01

Understanding the sources, occurrence and sinks of perfluoroalkyl and polyfluoroalkyl substances (PFASs) in the urban water cycle is important to protect and utilize local water resources. Concentrations of 22 target PFASs and general water quality parameters were determined monthly for a year in filtered water samples from five tributaries and three sampling stations of an urban water body. Of the 22 target PFASs, 17 PFASs were detected with a frequency >93% including PFCAs: C4-C12 perfluoroalkyl carboxylates, C4, C6, C8, and C10 perfluoroalkane sulfonates, perfluorooctane sulfonamides and perfluorooctane sulfonamide substances (FOSAMs), C10 perfluoroalkyl phosphonic acid (C10 PFPA), 6:2 fluorotelomer sulfonic acid (6:2 FTSA) and C8/C8 perfluoroalkyl phosphinic acid (C8/C8-PFPIA). The most abundant PFASs in water were PFBS (1.4-55 ng/L), PFBA (1.0-23 ng/L), PFOS (1.5-24 ng/L) and PFOA (2.0-21 ng/L). In the tributaries, PFNA concentrations ranged from 1.2 to 87.1 ng/L except in the May 2013 samples of two tributaries, which reached 520 and 260 ng/L. Total PFAS concentrations in the sediment samples ranged from 1.6 to 15 ng/g d.w. with EtFOSAA, PFDoA, PFOS and PFDA being the dominant species. Based on water and sediment data, two types of sources were inferred: one-time or intermittent point sources and continuous non-point sources. FOSAMs and PFOS released continually from non-point sources, C8/C8 PFPIA, PFDoA and PFUnA was released from point sources. The highly water soluble short-chain PFASs including PFBA, PFPeA and PFBS remained predominantly in the water column. The factors governing solution phase concentrations appear to be compound hydrophobicity and sorption to suspended particles. Correlation of the dissolved phase concentrations with precipitation data suggested stormwater was a significant source of PFBA, PFBS, PFUnA and PFDoA. Negative correlations with precipitation indicated sources feeding FOSAA and FOSA directly into the tributaries. Copyright © 2017 Elsevier Ltd. All rights reserved.

A cooperative-binding split aptamer assay for rapid, specific and ultra-sensitive fluorescence detection of cocaine in saliva† †Electronic supplementary information (ESI) available: Optimization of Mg2+ and ATMND concentrations for our CBSA-based ATMND-binding assay; ATMND-reported calibration curve for CBSA-5325 at various cocaine concentrations; ATMND binding affinity for the cocaine-assembled CBSA-5325; K D of 38-GC and different 38-GC mutants for cocaine as characterized by ITC; stem length effects on cocaine-induced CBSA assembly; spectra of CBSA-5335-based fluorescence detection of cocaine in 1× binding buffer; characterization of cocaine binding affinity of CBSA-5335 and PSA using ITC; fluorescence detection of cocaine in saliva with our fluorophore/quencher modified CBSA-5335; calibration curve of our CBSA-5335-based fluorophore/quencher assay in 1× binding buffer and 10% saliva at cocaine concentrations ranging from 0 to 10 μM; bias and precision of the CBSA-5335-based fluorophore/quencher assay; comparison of amplification-free split-aptamer assays for cocaine detection; sequence ID and DNA sequences used in this work. See DOI: 10.1039/c6sc01833e Click here for additional data file.

PubMed Central

Yu, Haixiang; Canoura, Juan; Guntupalli, Bhargav; Lou, Xinhui

2017-01-01

Sensors employing split aptamers that reassemble in the presence of a target can achieve excellent specificity, but the accompanying reduction of target affinity mitigates any overall gains in sensitivity. We for the first time have developed a split aptamer that achieves enhanced target-binding affinity through cooperative binding. We have generated a split cocaine-binding aptamer that incorporates two binding domains, such that target binding at one domain greatly increases the affinity of the second domain. We experimentally demonstrate that the resulting cooperative-binding split aptamer (CBSA) exhibits higher target binding affinity and is far more responsive in terms of target-induced aptamer assembly compared to the single-domain parent split aptamer (PSA) from which it was derived. We further confirm that the target-binding affinity of our CBSA can be affected by the cooperativity of its binding domains and the intrinsic affinity of its PSA. To the best of our knowledge, CBSA-5335 has the highest cocaine affinity of any split aptamer described to date. The CBSA-based assay also demonstrates excellent performance in target detection in complex samples. Using this CBSA, we achieved specific, ultra-sensitive, one-step fluorescence detection of cocaine within fifteen minutes at concentrations as low as 50 nM in 10% saliva without signal amplification. This limit of detection meets the standards recommended by the European Union's Driving under the Influence of Drugs, Alcohol and Medicines program. Our assay also demonstrates excellent reproducibility of results, confirming that this CBSA-platform represents a robust and sensitive means for cocaine detection in actual clinical samples. PMID:28451157

Quick generation of Raman spectroscopy based in-process glucose control to influence biopharmaceutical protein product quality during mammalian cell culture.

PubMed

Berry, Brandon N; Dobrowsky, Terrence M; Timson, Rebecca C; Kshirsagar, Rashmi; Ryll, Thomas; Wiltberger, Kelly

2016-01-01

Mitigating risks to biotherapeutic protein production processes and products has driven the development of targeted process analytical technology (PAT); however implementing PAT during development without significantly increasing program timelines can be difficult. The development of a monoclonal antibody expressed in a Chinese hamster ovary (CHO) cell line via fed-batch processing presented an opportunity to demonstrate capabilities of altering percent glycated protein product. Glycation is caused by pseudo-first order, non-enzymatic reaction of a reducing sugar with an amino group. Glucose is the highest concentration reducing sugar in the chemically defined media (CDM), thus a strategy controlling glucose in the production bioreactor was developed utilizing Raman spectroscopy for feedback control. Raman regions for glucose were determined by spiking studies in water and CDM. Calibration spectra were collected during 8 bench scale batches designed to capture a wide glucose concentration space. Finally, a PLS model capable of translating Raman spectra to glucose concentration was built using the calibration spectra and spiking study regions. Bolus feeding in mammalian cell culture results in wide glucose concentration ranges. Here we describe the development of process automation enabling glucose setpoint control. Glucose-free nutrient feed was fed daily, however glucose stock solution was fed as needed according to online Raman measurements. Two feedback control conditions were executed where glucose was controlled at constant low concentration or decreased stepwise throughout. Glycation was reduced from ∼9% to 4% using a low target concentration but was not reduced in the stepwise condition as compared to the historical bolus glucose feeding regimen. © 2015 American Institute of Chemical Engineers.

Speciation of arsenic in exfoliated urinary bladder epithelial cells from individuals exposed to arsenic in drinking water.

PubMed

Hernández-Zavala, Araceli; Valenzuela, Olga L; Matousek, Tomás; Drobná, Zuzana; Dĕdina, Jirí; García-Vargas, Gonzalo G; Thomas, David J; Del Razo, Luz M; Stýblo, Miroslav

2008-12-01

The concentration of arsenic in urine has been used as a marker of exposure to inorganic As (iAs). Relative proportions of urinary metabolites of iAs have been identified as potential biomarkers of susceptibility to iAs toxicity. However, the adverse effects of iAs exposure are ultimately determined by the concentrations of iAs metabolites in target tissues. In this study we examined the feasibility of analyzing As species in cells that originate in the urinary bladder, a target organ for As-induced cancer in humans. Exfoliated bladder epithelial cells (BECs) were collected from urine of 21 residents of Zimapan, Mexico, who were exposed to iAs in drinking water. We determined concentrations of iAs, methyl-As (MAs), and dimethyl-As (DMAs) in urine using conventional hydride generation-cryotrapping-atomic absorption spectrometry (HG-CT-AAS). We used an optimized HG-CT-AAS technique with detection limits of 12-17 pg As for analysis of As species in BECs. All urine samples and 20 of 21 BEC samples contained detectable concentrations of iAs, MAs, and DMAs. Sums of concentrations of these As species in BECs ranged from 0.18 to 11.4 ng As/mg protein and in urine from 4.8 to 1,947 ng As/mL. We found no correlations between the concentrations or ratios of As species in BECs and in urine. These results suggest that urinary levels of iAs metabolites do not necessarily reflect levels of these metabolites in the bladder epithelium. Thus, analysis of As species in BECs may provide a more effective tool for risk assessment of bladder cancer and other urothelial diseases associated with exposures to iAs.

Armored RNA as Virus Surrogate in a Real-Time Reverse Transcriptase PCR Assay Proficiency Panel

PubMed Central

Hietala, S. K.; Crossley, B. M.

2006-01-01

In recent years testing responsibilities for high-consequence pathogens have been expanded from national reference laboratories into networks of local and regional laboratories in order to support enhanced disease surveillance and to test for surge capacity. This movement of testing of select agents and high-consequence pathogens beyond reference laboratories introduces a critical need for standardized, noninfectious surrogates of disease agents for use as training and proficiency test samples. In this study, reverse transcription-PCR assay RNA targets were developed and packaged as armored RNA for use as a noninfectious, quantifiable synthetic substitute for four high-consequence animal pathogens: classical swine fever virus; foot-and-mouth disease virus; vesicular stomatitis virus, New Jersey serogroup; and vesicular stomatitis virus, Indiana serogroup. Armored RNA spiked into oral swab fluid specimens mimicked virus-positive clinical material through all stages of the reverse transcription-PCR testing process, including RNA recovery by four different commercial extraction procedures, reverse transcription, PCR amplification, and real-time detection at target concentrations consistent with the dynamic ranges of the existing real-time PCR assays. The armored RNA concentrations spiked into the oral swab fluid specimens were stable under storage conditions selected to approximate the extremes of time and temperature expected for shipping and handling of proficiency panel samples, including 24 h at 37°C and 2 weeks at temperatures ranging from ambient room temperature to −70°C. The analytic test performance, including the reproducibility over the dynamic range of the assays, indicates that armored RNA can provide a noninfectious, quantifiable, and stable virus surrogate for specific assay training and proficiency test purposes. PMID:16390950

Understanding the dynamics of superparamagnetic particles under the influence of high field gradient arrays

NASA Astrophysics Data System (ADS)

Barnsley, Lester C.; Carugo, Dario; Aron, Miles; Stride, Eleanor

2017-03-01

The aim of this study was to characterize the behaviour of superparamagnetic particles in magnetic drug targeting (MDT) schemes. A 3-dimensional mathematical model was developed, based on the analytical derivation of the trajectory of a magnetized particle suspended inside a fluid channel carrying laminar flow and in the vicinity of an external source of magnetic force. Semi-analytical expressions to quantify the proportion of captured particles, and their relative accumulation (concentration) as a function of distance along the wall of the channel were also derived. These were expressed in terms of a non-dimensional ratio of the relevant physical and physiological parameters corresponding to a given MDT protocol. The ability of the analytical model to assess magnetic targeting schemes was tested against numerical simulations of particle trajectories. The semi-analytical expressions were found to provide good first-order approximations for the performance of MDT systems in which the magnetic force is relatively constant over a large spatial range. The numerical model was then used to test the suitability of a range of different designs of permanent magnet assemblies for MDT. The results indicated that magnetic arrays that emit a strong magnetic force that varies rapidly over a confined spatial range are the most suitable for concentrating magnetic particles in a localized region. By comparison, commonly used magnet geometries such as button magnets and linear Halbach arrays result in distributions of accumulated particles that are less efficient for delivery. The trajectories predicted by the numerical model were verified experimentally by acoustically focusing magnetic microbeads flowing in a glass capillary channel, and optically tracking their path past a high field gradient Halbach array.

Quantification of the Adenylate Cyclase Toxin of Bordetella pertussis In Vitro and during Respiratory Infection

PubMed Central

Eby, Joshua C.; Gray, Mary C.; Warfel, Jason M.; Paddock, Christopher D.; Jones, Tara F.; Day, Shandra R.; Bowden, James; Poulter, Melinda D.; Donato, Gina M.; Merkel, Tod J.

2013-01-01

Whooping cough results from infection of the respiratory tract with Bordetella pertussis, and the secreted adenylate cyclase toxin (ACT) is essential for the bacterium to establish infection. Despite extensive study of the mechanism of ACT cytotoxicity and its effects over a range of concentrations in vitro, ACT has not been observed or quantified in vivo, and thus the concentration of ACT at the site of infection is unknown. The recently developed baboon model of infection mimics the prolonged cough and transmissibility of pertussis, and we hypothesized that measurement of ACT in nasopharyngeal washes (NPW) from baboons, combined with human and in vitro data, would provide an estimate of the ACT concentration in the airway during infection. NPW contained up to ∼108 CFU/ml B. pertussis and 1 to 5 ng/ml ACT at the peak of infection. Nasal aspirate specimens from two human infants with pertussis contained bacterial concentrations similar to those in the baboons, with 12 to 20 ng/ml ACT. When ∼108 CFU/ml of a laboratory strain of B. pertussis was cultured in vitro, ACT production was detected in 60 min and reached a plateau of ∼60 ng/ml in 6 h. Furthermore, when bacteria were brought into close proximity to target cells by centrifugation, intoxication was increased 4-fold. Collectively, these data suggest that at the bacterium-target cell interface during infection of the respiratory tract, the concentration of ACT can exceed 100 ng/ml, providing a reference point for future studies of ACT and pertussis pathogenesis. PMID:23429530

Nanoengineered capsules for selective SERS analysis of biological samples

NASA Astrophysics Data System (ADS)

You, Yil-Hwan; Schechinger, Monika; Locke, Andrea; Coté, Gerard; McShane, Mike

2018-02-01

Metal nanoparticles conjugated with DNA oligomers have been intensively studied for a variety of applications, including optical diagnostics. Assays based on aggregation of DNA-coated particles in proportion to the concentration of target analyte have not been widely adopted for clinical analysis, however, largely due to the nonspecific responses observed in complex biofluids. While sample pre-preparation such as dialysis is helpful to enable selective sensing, here we sought to prove that assay encapsulation in hollow microcapsules could remove this requirement and thereby facilitate more rapid analysis on complex samples. Gold nanoparticle-based assays were incorporated into capsules comprising polyelectrolyte multilayer (PEMs), and the response to small molecule targets and larger proteins were compared. Gold nanoparticles were able to selectively sense small Raman dyes (Rhodamine 6G) in the presence of large protein molecules (BSA) when encapsulated. A ratiometric based microRNA-17 sensing assay exhibited drastic reduction in response after encapsulation, with statistically-significant relative Raman intensity changes only at a microRNA-17 concentration of 10 nM compared to a range of 0-500 nM for the corresponding solution-phase response.

An Assessment of the Effect of Rotenone on Selected Non-Target Aquatic Fauna

PubMed Central

Dalu, Tatenda; Wasserman, Ryan J.; Jordaan, Martine; Froneman, William P.; Weyl, Olaf L. F.

2015-01-01

Rotenone, a naturally occurring ketone, is widely employed for the management of invasive fish species. The use of rotenone poses serious challenges to conservation practitioners due to its impacts on non-target organisms including amphibians and macroinvertebrates. Using laboratory studies, we investigated the effects of different rotenone concentrations (0, 12.5, 25, 37.5, 50, 100 μg L-1) on selected invertebrate groups; Aeshnidae, Belostomatids, Decapods, Ephemeroptera, Pulmonata and zooplankton over a period of 18 hours. Based on field observations and body size, we hypothesized that Ephemeropterans and zooplankton would be more susceptible to rotenone than Decapods, Belostomatids and snails. Experimental results supported this hypothesis and mortality and behaviour effects varied considerably between taxa, ranging from no effect (crab Potamonuates sidneyi) to 100% mortality (Daphnia pulex and Paradiaptomus lamellatus). Planktonic invertebrates were particularly sensitive to rotenone even at very low concentrations. Future research should investigate the recovery time of invertebrate communities after the application of rotenone and conduct field assessments assessing the longer term effects of rotenone exposure on the population dynamics of those less sensitive organisms. PMID:26540301

Determination of dissolved-phase pesticides in surface water from the Yakima River basin, Washington, using the Goulden large-sample extractor and gas chromatography/mass spectrometer

USGS Publications Warehouse

Foster, Gregory D.; Gates, Paul M.; Foreman, William T.; McKenzie, Stuart W.; Rinella, Frank A.

1993-01-01

Concentrations of pesticides in the dissolved phase of surface water samples from the Yakima River basin, WA, were determined using preconcentration in the Goulden large-sample extractor (GLSE) and gas chromatography/mass spectrometry (GC/MS) analysis. Sample volumes ranging from 10 to 120 L were processed with the GLSE, and the results from the large-sample analyses were compared to those derived from 1-L continuous liquid-liquid extractions Few of the 40 target pesticides were detected in 1-L samples, whereas large-sample preconcentration in the GLSE provided detectable levels for many of the target pesticides. The number of pesticides detected in GLSE processed samples was usually directly proportional to sample volume, although the measured concentrations of the pesticides were generally lower at the larger sample volumes for the same water source. The GLSE can be used to provide lower detection levels relative to conventional liquid-liquid extraction in GC/MS analysis of pesticides in samples of surface water.

Screening of extraction methods for glycoproteins from jellyfish ( Rhopilema esculentum) oral-arms by high performance liquid chromatography

NASA Astrophysics Data System (ADS)

Ren, Guoyan; Li, Bafang; Zhao, Xue; Zhuang, Yongliang; Yan, Mingyan; Hou, Hu; Zhang, Xiukun; Chen, Li

2009-03-01

In order to select an optimum extraction method for the target glycoprotein (TGP) from jellyfish ( Rhopilema esculentum) oral-arms, a high performance liquid chromatography (HPLC)-assay for the determination of the TGP was developed. Purified target glycoprotein was taken as a standard glycoprotein. The results showed that the calibration curves for peak area plotted against concentration for TGP were linear ( r = 0.9984, y = 4.5895 x+47.601) over concentrations ranging from 50 to 400 mgL-1. The mean extraction recovery was 97.84% (CV2.60%). The fractions containing TGP were isolated from jellyfish ( R. esculentum) oral-arms by four extraction methods: 1) water extraction (WE), 2) phosphate buffer solution (PBS) extraction (PE), 3) ultrasound-assisted water extraction (UA-WE), 4) ultrasound-assisted PBS extraction (UA-PE). The lyophilized extract was dissolved in Milli-Q water and analyzed directly on a short TSK-GEL G4000PWXL (7.8 mm×300 mm) column. Our results indicated that the UA-PE method was the optimum extraction method selected by HPLC.

Distribution, mass load and environmental impact of multiple-class pharmaceuticals in conventional and upgraded municipal wastewater treatment plants in East China.

PubMed

Yuan, Xiangjuan; Qiang, Zhimin; Ben, Weiwei; Zhu, Bing; Qu, Jiuhui

2015-03-01

The occurrence, fate and environmental impact of 30 pharmaceuticals including sulfonamides, fluoroquinolones, tetracyclines, macrolides, dihydrofolate reductase inhibitors, β-blockers, antiepileptics, lipid regulators, and stimulants were studied in two municipal wastewater treatment plants (WWTPs) located in Wuxi City, East China. A total of 23 pharmaceuticals were detected in wastewater samples, with a maximum concentration of 16.1 μg L(-1) (caffeine) in the influent and 615.5 ng L(-1) (azithromycin) in the effluent; 19 pharmaceuticals were detected in sludge samples at concentrations up to 12.13 mg kg(-1), with ofloxacin, azithromycin and norfloxacin being the predominant species. Mass balance analysis showed that biodegradation primarily accounted for the removal of sulfonamides, most of the macrolides, and other miscellaneous pharmaceuticals, while adsorption onto the sludge was the primary removal pathway for fluoroquinolones, tetracylines, and azithromycin during biological treatment. The total mass loads of target pharmaceuticals per capita in the two WWTPs were in the ranges of 2681.8-4333.3, 248.0-416.6 and 214.6-374.5 μg per day per inhabitant in the influent, effluent and dewatered sludge, respectively. The upgraded Plant A adopting the combined anaerobic/anoxic/oxic and moving bed biofilm process exhibited a much higher removal of target pharmaceuticals than the conventional Plant B adopting the C-Orbal oxidation ditch process. The concentration levels of sulfamethoxazole, ofloxacin, ciprofloxacin and clarithromycin in the effluent, ofloxacin in the sludge, and the mixture of all target pharmaceuticals in both effluent and sludge posed a high risk to algae in aquatic environments.

Ecotoxicological risk assessment and seasonal variation of some pharmaceuticals and personal care products in the sewage treatment plant and surface water bodies (lakes).

PubMed

Archana, G; Dhodapkar, Rita; Kumar, Anupama

2017-08-10

This paper reports the seasonal variation and environmental quality control data for five fingerprint pharmaceuticals and personal care products (PPCPs) (acetaminophen ciprofloxacin, caffeine, irgasan and benzophenone) in the influent and the effluent of the sewage treatment plant (STP) and surface water bodies (six major lakes) in and around Nagpur, one of the "A class city" in the central India over a period of 1 year. The target compounds were analysed using developed offline solid-phase extraction (SPE) coupled with reversed phase high-performance liquid chromatography (RP-HPLC-PDA) method. All the five PPCPs were found in the influent, whereas four were found in the effluent of the STP. However, in the surface water bodies, three PPCPs were detected in all the seasons. Above PPCPs were present in the concentration range of 1-174 μg L -1 in the surface water bodies, 12-373 μg L -1 in the influent and 11-233 μg L -1 in the effluent of the STP. Amongst the five PPCPs, caffeine was found to be in higher concentration as compared to others. The seasonal trends indicate higher concentrations of PPCPs in summer season and lowest in the rainy season. Additionally, physico-chemical characterisations (inorganic and organic parameters) of the collected samples were performed to access the anthropogenic pollution. Ecotoxicological risk assessment was done to appraise the degree of toxicity of the targeted compounds. Hazard quotient (HQ) values were found to be < 1 indicating no adverse effect on the targeted organism.

Capstone Depleted Uranium Aerosol Biokinetics, Concentrations, and Doses

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

Guilmette, Raymond A.; Miller, Guthrie; Parkhurst, MaryAnn

2009-02-26

One of the principal goals of the Capstone Depleted Uranium (DU) Aerosol Study was to quantify and characterize DU aerosols generated inside armored vehicles by perforation with a DU penetrator. This study consequently produced a database in which the DU aerosol source terms were specified both physically and chemically for a variety of penetrator-impact geometries and conditions. These source terms were used to calculate radiation doses and uranium concentrations for various scenarios as part of the Capstone DU Human Health Risk Assessment (HHRA). This paper describes the scenario-related biokinetics of uranium, and summarizes intakes, chemical concentrations to the organs, andmore » E(50) and HT(50) for organs and tissues based on exposure scenarios for personnel in vehicles at the time of perforation as well as for first responders. For a given exposure scenario (duration time and breathing rates), the range of DU intakes among the target vehicles and shots was not large, about a factor of 10, with the lowest being from a ventilated operational Abrams tank and the highest being for an unventilated Abrams with DU penetrator perforating DU armor. The ranges of committed effective doses were more scenario-dependent than were intakes. For example, the largest range, a factor of 20, was shown for scenario A, a 1-min exposure, whereas, the range was only a factor of two for the first-responder scenario (E). In general, the committed effective doses were found to be in the tens of mSv. The risks ascribed to these doses are discussed separately.« less

Single Nanochannel-Aptamer-Based Biosensor for Ultrasensitive and Selective Cocaine Detection.

PubMed

Wang, Jian; Hou, Jue; Zhang, Huacheng; Tian, Ye; Jiang, Lei

2018-01-17

Ultrasensitive and selective detection of molecules at nano or sub-nanomolar level is very important for many areas such as early diagnosis and drug testing. Herein, we report a high-sensitive cocaine sensor based on a single nanochannel coupled with DNA aptamers. The single nanochannel-aptamer-based biosensor can recognize cocaine molecules with an excellent sensitivity and good selectivity. A linear relationship between target cocaine concentration and output ionic current is obtained in a wide concentration range of cocaine from 1 nM to 10 μM. The cocaine sensor also shows a detection limit down to 1 nM. This study provides a new avenue to develop new nanochannel-aptamer-based biosensors for rapid and ultratrace detection of a variety of illicit drugs.

Concentrations and sources of VOCs in urban domestic and public microenvironments.

PubMed

Kim, Y M; Harrad, S; Harrison, R M

2001-03-15

Concentrations of 15 VOCs including 1,3-butadiene, benzene, and styrene were measured in a wide range of urban microenvironments, viz: homes, offices, restaurants, pubs, department stores, coach and train stations, cinemas, libraries, laboratories, perfume shops, heavily trafficked roadside locations, buses, trains, and automobiles. For most target VOCs-including 1,3-butadiene and benzene-mean concentrations at heavily trafficked roadside locations were exceeded by those in automobiles and were comparable to those in pubs and train stations. With regard to indoor-outdoor relationships in homes, this study revealed higher mean indoor concentrations, no correlation between simultaneously measured indoor and outdoor concentrations, and significantly different patterns of diurnal variation. Thus-in poorly ventilated buildings-indoor emission source strength is considered a more significant influence on VOC concentrations than infiltration of outdoor air. In the six smoking homes studied, environmental tobacco smoke (ETS) was found to make a substantial contribution to concentrations of 1,3-butadiene. This finding was based on the significantly higher concentrations detected in smoking compared to nonsmoking homes, the significant correlation between 1,3-butadiene concentrations and those of 3-ethenylpyridine (an ETS marker), factor analysis, and the results of a source apportionment exercise based on ratios of 1,3-butadiene to 3-ethenylpyridine.

Impact of certain plants and synthetic molluscicides on some fresh water snails and fish.

PubMed

Mosta-Fa, B B; el-Deeb, Fatma A; Ismail, Nahid M; el-Said, K M

2005-12-01

The LC50 (78, 85 ppm) and LC90 (88, 135 ppm) of Anagalis arvensis and Calendula micrantha respectively against Biomphalaria alexandrina were higher than those of the non-target snails, Physa acuta, Planorbis planorbis, Helisoma duryi and Melanoides tuberculata. In contrast, the LC50 of Niclosamide (0.11 ppm) and Copper sulphate (CuSO4) (0.42 ppm) against B. alexandrina were lower than those of the non-target snails. The mortalities percentage among non-target snails ranged between 0.0 & 20% when sublethal concentrations of CuSO4 against B. alexandrina mixed with those of C. micrantha and between 0.0 & 40% when mixed with A. arvensis. Mortalities ranged between 0.0 & 50% when Niclosamide was mixed with each of A. arvensis and C. micrantha. A. arvensis induced 100% mortality on Oreochromis niloticus after 48 hrs exposure and after 24 hrs for Gambusia affinis. C. micrantha was non-toxic to the fish. The survival rate of O. niloticus and G. affinis after 48 hrs exposure to 0.11 ppm of Niclosamide were 83.3% & 100% respectively. These rates were 91.7% & 93.3% respectively when each of the two fish species was exposed to 0.42 ppm of CuSO4. Mixture of sub-lethal concentrations of A. arvensis against B. alexandrina and those of Niclosamide or CuSO4 at ratios 10:40 & 25:25 induced 66.6% mortalities on O. niloticus and 83.3% at 40:10. These mixtures caused 100% mortalities on G. affinis at all ratios. A. arvensis CuSO4 mixtures at 10:40 induced 83.3% & 40% mortalities on O. niloticus and G. affinis respectively and 100% mortalities on both fish species at ratios 25:25 & 40:10. A mixture of sub-lethal concentrations of C. micrantha against B. alexandrina and of Niclosamide or CuSO4 caused mortalities of O. niloticus between 0.0 & 33.3% and between 5% & 35% of G. affinis. The residue of Cu in O. niloticus were 4.69, 19.06 & 25.37 mg/1kgm fish after 24, 48 & 72 hrs exposure to LC0 of CuSO4 against B. alexandrina respectively.

Oxygen delivery using neonatal self-inflating bags without reservoirs.

PubMed

Sugiura, Takahiro; Urushibata, Rei; Komatsu, Kenji; Shioda, Tsutomu; Ota, Tatsuki; Sato, Megumi; Okubo, Yumiko; Fukuoka, Tetsuya; Hosono, Shigeharu; Tamura, Masanori

2017-02-01

Guidelines recommend avoiding excessive oxygen during neonatal resuscitation. Recent studies have suggested that oxygen titration can be achieved using a self-inflating bag, but data on the effectiveness of resuscitators used in neonatal ventilation are scarce, The aim of this study was therefore to determine the amount of oxygen delivered using several brands of neonatal self-inflating resuscitation bags without reservoirs under different conditions with regard to oxygen flow rate, ventilation rate (VR), peak inspiratory pressure (PIP) range, and test lung compliance. Oxygen concentration was measured under a variety of conditions. Combinations of oxygen flow rate (10, 5.0, 3.0 and 1.0 L/min), VR (40, 60 inflations/min), PIP range (20-25 cmH 2 O, 35-40 cmH 2 O), and test lung compliance (0.6, 1.0, 3.0, and 5.0 mL/cmH 2 O) were examined using six kinds of self-inflating bag. Delivered oxygen concentration varied widely (30.1-96.7%) and had a significant positive correlation with gas flow rate in all of the bags. Delivered oxygen concentration was also negatively correlated with PIP in all of the bags and with VR in some of them. Test lung compliance did not affect delivered oxygen concentration. The use of neonatal resuscitation self-inflating bags without reservoirs resulted in different delivered oxygen concentrations depending on gas flow rate, VR, PIP, and manufacturer, but not on lung compliance. This suggests that targeted oxygen concentrations could be delivered, even in lungs with decreased compliance, during resuscitation. © 2016 Japan Pediatric Society.

Influence of target reflection on three-dimensional range gated reconstruction.

PubMed

Chua, Sing Yee; Wang, Xin; Guo, Ningqun; Tan, Ching Seong

2016-08-20

The range gated technique is a promising laser ranging method that is widely used in different fields such as surveillance, industry, and military. In a range gated system, a reflected laser pulse returned from the target scene contains key information for range reconstruction, which directly affects the system performance. Therefore, it is necessary to study the characteristics and effects of the target reflection factor. In this paper, theoretical and experimental analyses are performed to investigate the influence of target reflection on three-dimensional (3D) range gated reconstruction. Based on laser detection and ranging (LADAR) and bidirectional reflection distribution function (BRDF) theory, a 3D range gated reconstruction model is derived and the effect on range accuracy is analyzed from the perspectives of target surface reflectivity and angle of laser incidence. Our theoretical and experimental study shows that the range accuracy is proportional to the target surface reflectivity, but it decreases when the angle of incidence increases to adhere to the BRDF model. The presented findings establish a comprehensive understanding of target reflection in 3D range gated reconstruction, which is of interest to various applications such as target recognition and object modeling. This paper provides a reference for future improvement to perform accurate range compensation or correction.

The effect of fresh gas flow rate and type of anesthesia machine on time to reach target sevoflurane concentration.

PubMed

Shin, Hye Won; Yu, Hae Na; Bae, Go Eun; Huh, Hyub; Park, Ji Yong; Kim, Ji Young

2017-01-19

Anesthesia machines have been developed by the application of new technology for rapid and easier control of anesthetic concentration. In this study, we used a test lung to investigate whether the time taken to reach the target sevoflurane concentration varies with the rate of fresh gas flow (FGF) and type of anesthesia machine (AM). We measured the times taken to reach the target sevoflurane concentration (2 minimum alveolar concentration = 4%) at variable rates of FGF (0.5, 1, or 3 L/min) and different types of AM (Primus ® , Perseus ® , and Zeus ® [Zeus ® -F; Zeus ® fresh gas mode, Zeus ® -A; Zeus ® auto-mode]). Concomitant ventilation was supplied using 100% O 2. The AMs were connected to a test lung. A sevoflurane vaporizer setting of 6% was used in Primus ® , Perseus ® , and Zeus ® -F; a target end-tidal setting of 4% was used in Zeus ® -A (from a vaporizer setting of 0%). The time taken to reach the target concentration was measured in every group. When the same AM was used (Primus ® , Perseus ® , or Zeus ® -F), the times to target concentration shortened as the FGF rate increased (P < 0.05). Conversely, when the same FGF rate was used, but with different AMs, the time to target concentration was shortest in Perseus ® , followed by Primus ® , and finally by Zeus ® -F (P < 0.05). With regards to both modes of Zeus ® , at FGF rates of 0.5 and 1 L/min, the time to target concentration was shorter in Zeus ® -A than in Zeus ® -F; however, the time was longer in Zeus ® -A than in Zeus ® -F at FGF rate of 3 L/min (P < 0.05). Shorter times taken to reach the target concentration were associated with high FGF rates, smaller internal volume of the AM, proximity of the fresh gas inlets to patients, absence of a decoupling system, and use of blower-driven ventilators in AM.

Granular activated carbon adsorption of MIB in the presence of dissolved organic matter.

PubMed

Summers, R Scott; Kim, Soo Myung; Shimabuku, Kyle; Chae, Seon-Ha; Corwin, Christopher J

2013-06-15

Based on the results of over twenty laboratory granular activated carbon (GAC) column runs, models were developed and utilized for the prediction of 2-methylisoborneol (MIB) breakthrough behavior at parts per trillion levels and verified with pilot-scale data. The influent MIB concentration was found not to impact the concentration normalized breakthrough. Increasing influent background dissolved organic matter (DOM) concentration was found to systematically decrease the GAC adsorption capacity for MIB. A series of empirical models were developed that related the throughput in bed volumes for a range of MIB breakthrough targets to the influent DOM concentration. The proportional diffusivity (PD) designed rapid small-scale column test (RSSCT) could be directly used to scale-up MIB breakthrough performance below 15% breakthrough. The empirical model to predict the throughput to 50% breakthrough based on the influent DOM concentration served as input to the pore diffusion model (PDM) and well-predicted the MIB breakthrough performance below a 50% breakthrough. The PDM predictions of throughput to 10% breakthrough well simulated the PD-RSSCT and pilot-scale 10% MIB breakthrough. Copyright © 2013 Elsevier Ltd. All rights reserved.

CMOS Amperometric ADC With High Sensitivity, Dynamic Range and Power Efficiency for Air Quality Monitoring.

PubMed

Li, Haitao; Boling, C Sam; Mason, Andrew J

2016-08-01

Airborne pollutants are a leading cause of illness and mortality globally. Electrochemical gas sensors show great promise for personal air quality monitoring to address this worldwide health crisis. However, implementing miniaturized arrays of such sensors demands high performance instrumentation circuits that simultaneously meet challenging power, area, sensitivity, noise and dynamic range goals. This paper presents a new multi-channel CMOS amperometric ADC featuring pixel-level architecture for gas sensor arrays. The circuit combines digital modulation of input currents and an incremental Σ∆ ADC to achieve wide dynamic range and high sensitivity with very high power efficiency and compact size. Fabricated in 0.5 [Formula: see text] CMOS, the circuit was measured to have 164 dB cross-scale dynamic range, 100 fA sensitivity while consuming only 241 [Formula: see text] and 0.157 [Formula: see text] active area per channel. Electrochemical experiments with liquid and gas targets demonstrate the circuit's real-time response to a wide range of analyte concentrations.

Estimation of Microbial Concentration in Food Products from Qualitative, Microbiological Test Data with the MPN Technique.

PubMed

Fujikawa, Hiroshi

2017-01-01

Microbial concentration in samples of a food product lot has been generally assumed to follow the log-normal distribution in food sampling, but this distribution cannot accommodate the concentration of zero. In the present study, first, a probabilistic study with the most probable number (MPN) technique was done for a target microbe present at a low (or zero) concentration in food products. Namely, based on the number of target pathogen-positive samples in the total samples of a product found by a qualitative, microbiological examination, the concentration of the pathogen in the product was estimated by means of the MPN technique. The effects of the sample size and the total sample number of a product were then examined. Second, operating characteristic (OC) curves for the concentration of a target microbe in a product lot were generated on the assumption that the concentration of a target microbe could be expressed with the Poisson distribution. OC curves for Salmonella and Cronobacter sakazakii in powdered formulae for infants and young children were successfully generated. The present study suggested that the MPN technique and the Poisson distribution would be useful for qualitative microbiological test data analysis for a target microbe whose concentration in a lot is expected to be low.

Hybrid nanoporous silicon optical biosensor architectures for biological sample analysis

NASA Astrophysics Data System (ADS)

Bonanno, Lisa M.; Zheng, Hong; DeLouise, Lisa A.

2010-02-01

This work focuses on demonstrating proof-of-concept for a novel nanoparticle optical signal amplification scheme employing hybrid porous silicon (PSi) sensors. We are investigating the development of target responsive hydrogels integrated with PSi optical transducers. These hybrid-PSi sensors can be designed to provide a tunable material response to target concentration ranging from swelling to complete chain dissolution. The corresponding refractive index changes are significant and readily detected by the PSi transducer. However, to increase signal to noise, lower the limit of detection, and provide a visual read out capability, we are investigating the incorporation of high refractive index nanoparticles (NP) into the hydrogel for optical signal amplification. These NPs can be nonspecifically encapsulated, or functionalized with bioactive ligands to bind polymer chains or participate in cross linking. In this work, we demonstrate encapsulation of high refractive index QD nanoparticles into a 5wt% polyacrylamide hydrogel crosslinked with N,N'-methylenebisacrylamide (BIS) and N,N Bis-acryloyl cystamine (BAC). A QD loading (~0.29 wt%) produced a 2X larger optical shift compared to the control. Dissolution of disulphide crosslinks, using Tris[2-carboxyethyl] phosphine (TCEP) reducing agent, induced gel swelling and efficient QD release. We believe this hybrid sensor concept constitutes a versatile technology platform capable of detecting a wide range of bio/chemical targets provided target analogs can be linked to the polymer backbone and crosslinks can be achieved with target responsive multivalent receptors, such a antibodies. The optical signal amplification scheme will enable a lower limit of detection sensitivity not yet demonstrated with PSi technology and colorimetric readout visible to the naked eye.

Choline and polyunsaturated fatty acids in preterm infants' maternal milk.

PubMed

Maas, Christoph; Franz, Axel R; Shunova, Anna; Mathes, Michaela; Bleeker, Christine; Poets, Christian F; Schleicher, Erwin; Bernhard, Wolfgang

2017-06-01

Choline, docosahexaenoic acid (DHA), and arachidonic acid (ARA) are essential to fetal development, particularly of the brain. These components are actively enriched in the fetus. Deprivation from placental supply may therefore result in impaired accretion in preterm infants. To determine choline, choline metabolites, DHA, and ARA in human breast milk (BM) of preterm infants compared to BM of term born infants. We collected expressed BM samples from 34 mothers (N = 353; postnatal day 6-85), who had delivered 35 preterm infants undergoing neonatal intensive care (postmenstrual age 30 weeks, range 25.4-32.0), and from mothers after term delivery (N = 9; postnatal day 6-118). Target metabolites were analyzed using tandem mass spectrometry and gas chromatography and reported as medians and 25th/75th percentiles. In BM, choline was mainly present in the form of phosphocholine and glycerophosphocholine, followed by free choline, phosphatidylcholine, sphingomyelin, and lyso-phosphatidylcholine. In preterm infants' BM total choline ranged from 61 to 360 mg/L (median: 158 mg/L) and was decreased compared to term infants' BM (range 142-343 mg/L; median: 258 mg/L; p < 0.01). ARA and DHA comprised 0.81 (range: 0.46-1.60) and 0.43 (0.15-2.42) % of total preterm BM lipids, whereas term BM values were 0.68 (0.52-0.88) and 0.35 (0.18-0.75) %, respectively. Concentrations of all target parameters decreased after birth, and frequently 150 ml/kg/d BM did not meet the estimated fetal accretion rates. Following preterm delivery, BM choline concentrations are lower, whereas ARA and DHA levels are comparable versus term delivery. Based on these findings we suggest a combined supplementation of preterm infants' BM with choline, ARA and DHA combined to improve the nutritional status of preterm infants. This study was registered at www.clinicaltrials.gov. Identifier: NCT01773902.

The New MIRUS System for Short-Term Sedation in Postsurgical ICU Patients.

PubMed

Romagnoli, Stefano; Chelazzi, Cosimo; Villa, Gianluca; Zagli, Giovanni; Benvenuti, Francesco; Mancinelli, Paola; Arcangeli, Giulio; Dugheri, Stefano; Bonari, Alessandro; Tofani, Lorenzo; Belardinelli, Andrea; De Gaudio, A Raffaele

2017-09-01

To evaluate the feasibility and safety of the MIRUS system (Pall International, Sarl, Fribourg, Switzerland) for sedation with sevoflurane for postsurgical ICU patients and to evaluate atmospheric pollution during sedation. Prospective interventional study. Surgical ICU. February 2016 to December 2016. Postsurgical patients requiring ICU admission, mechanical ventilation, and sedation. Sevoflurane was administered with the MIRUS system targeted to a Richmond Agitation Sedation Scale from -3 to -5 by adaptation of minimum alveolar concentration. Data collected included Richmond Agitation Sedation Scale, minimum alveolar concentration, inspired and expired sevoflurane fraction, wake-up times, duration of sedation, sevoflurane consumption, respiratory and hemodynamic data, Simplified Acute Physiology Score II, Sepsis-related Organ Failure Assessment, and laboratory data and biomarkers of organ injury. Atmospheric pollution was monitored at different sites: before sevoflurane delivery (baseline) and during sedation with the probe 15 cm up to the MIRUS system (S1) and 15 cm from the filter-Reflector group (S2). Sixty-two patients were enrolled in the study. No technical failure occurred. Median Richmond Agitation Sedation Scale was -4.5 (interquartile range, -5 to -3.6) with sevoflurane delivered at a median minimum alveolar concentration of 0.45% (interquartile range, 0.4-0.53) yielding a mean inspiratory and expiratory concentrations of 0.79% (SD, 0.24) and 0.76% (SD, 0.18), respectively. Median awakening time was 4 minutes (2.2-5 min). Median duration of sevoflurane administration was 3.33 hours (2.33-5.75 hr), range 1-19 hours with a mean consumption of 7.89 mL/hr (SD, 2.99). Hemodynamics remained stable over the study period, and no laboratory data indicated liver or kidney injury or dysfunction. Median sevoflurane room air concentration was 0.10 parts per million (interquartile range, 0.07-0.15), 0.17 parts per million (interquartile range, 0.14-0.27), and 0.15 parts per million (interquartile range, 0.07-0.19) at baseline, S1, and S2, respectively. The MIRUS system is a promising and safe alternative for short-term sedation with sevoflurane of ICU patients. Atmospheric pollution is largely below the recommended thresholds (< 5 parts per million). Studies extended to more heterogeneous population of patients undergoing longer duration of sedation are needed to confirm these observations.

Combination of cascade chemical reactions with graphene-DNA interaction to develop new strategy for biosensor fabrication.

PubMed

Zhu, Xiaoli; Sun, Liya; Chen, Yangyang; Ye, Zonghuang; Shen, Zhongming; Li, Genxi

2013-09-15

Graphene, a single atom thick and two dimensional carbon nano-material, has been proven to possess many unique properties, one of which is the recent discovery that it can interact with single-stranded DNA through noncovalent π-π stacking. In this work, we demonstrate that a new strategy to fabricate many kinds of biosensors can be developed by combining this property with cascade chemical reactions. Taking the fabrication of glucose sensor as an example, while the detection target, glucose, may regulate the graphene-DNA interaction through three cascade chemical reactions, electrochemical techniques are employed to detect the target-regulated graphene-DNA interaction. Experimental results show that in a range from 5μM to 20mM, the glucose concentration is in a natural logarithm with the logarithm of the amperometric response, suggesting a best detection limit and detection range. The proposed biosensor also shows favorable selectivity, and it has the advantage of no need for labeling. What is more, by controlling the cascade chemical reactions, detection of a variety of other targets may be achieved, thus the strategy proposed in this work may have a wide application potential in the future. Copyright © 2013 Elsevier B.V. All rights reserved.

Effect of triclosan on reproduction, DNA damage and heat shock protein gene expression of the earthworm Eisenia fetida.

PubMed

Lin, Dasong; Li, Ye; Zhou, Qixing; Xu, Yingming; Wang, Di

2014-12-01

Triclosan (TCS) is released into the terrestrial environment via the application of sewage sludge and reclaimed water to agricultural land. More attention has been paid to its effect on non-target soil organisms. In the present study, chronic toxic effects of TCS on earthworms at a wide range of concentrations were investigated. The reproduction, DNA damage, and expression levels of heat shock protein (Hsp70) gene of earthworms were studied as toxicity endpoints. The results showed that the reproduction of earthworms were significantly reduced (p < 0.05) after exposure to the concentrations ranges from 50 to 300 mg kg(-1), with a half-maximal effective concentration (EC50) of 142.11 mg kg(-1). DNA damage, detected by the comet assay, was observed and there was a clear significant (R(2) = 0.941) relationship between TCS concentrations and DNA damage, with the EC50 value of 8.85 mg kg(-1). The expression levels of Hsp70 gene of earthworms were found to be up-regulated under the experimental conditions. The expression level of hsp70 gene increased, up to about 2.28 folds that in the control at 50 mg kg(-1). The EC50 value based on the Hsp70 biomarker was 1.79 mg kg(-1). Thus, among the three toxicity endpoints, the Hsp70 gene was more sensitive to TCS in soil.

Tuning the metal-insulator transition of VO2 by introducing W dopants via a combinatorial approach

NASA Astrophysics Data System (ADS)

Liang, Yangang; Lee, Seunghun; Zhang, Xiaohang; Takeuchi, Ichiro

We have systematically studied the structural phase transition and the electronic properties of composition spread V1-xWxO2 (0 <= x <= 0.037) thin films fabricated on silicon (001) and c-cut sapphire substrates through combinatorial pulsed laser deposition of a V2O5 target and a WO3 target. Our in-situ temperature-dependent x-ray diffraction measurements reveal a gradual change in the film structure from a monoclinic phase to a tetragonal phase via an intermediate mixture of the two as the concentration of tungsten increases from 0% to 3.7% at 300 K. At 358 K, the film is found to be in a tetragonal phase for the entire composition range we studied. The results also suggest that the volume of the unit cell increases as the concentration of tungsten increases. Electrical transport results further show that both the phase transition temperature and the width of the hysteresis loop decrease with the increasing of the concentration of tungsten. Especially, epitaxial V1-xWxO2 films fabricated on c-cut sapphire substrates show narrower hysteresis loop compared to textured V1-xWxO2 films fabricated on Si (100) substrates. In addition, the Hall effect measurements on the epitaxial V1-xWxO2 thin films at various temperature points provide important information for the change in the electronic structure upon increasing the concentration of tungsten. This work was supported by CNAM.

Quantification of Methane Gas Flux and Bubble Fate on the Eastern Siberian Arctic Shelf Utilizing Calibrated Split-beam Echosounder Data.

NASA Astrophysics Data System (ADS)

Weidner, E. F.; Mayer, L. A.; Weber, T. C.; Jerram, K.; Jakobsson, M.; Chernykh, D.; Ananiev, R.; Mohammad, R.; Semiletov, I. P.

2016-12-01

On the Eastern Siberian Arctic Shelf (ESAS) subsea permafrost, shallow gas hydrates, and trapped free gas hold an estimated 1400 Gt of methane. Recent observations of methane bubble plumes and high concentrations of dissolved methane in the water column indicate methane release via ebullition. Methane gas released from the shallow ESAS (<50 m average depth) has high potential to be transported to the atmosphere. To directly and quantitatively address the magnitude of methane flux and the fate of rising bubbles in the ESAS, methane seeps were mapped with a broadband split-beam echosounder as part of the Swedish-Russian-US Arctic Ocean Investigation of Climate-Cryosphere-Carbon Interactions program (SWERUS-C3). Acoustic measurements were made over a broad range of frequencies (16 to 29 kHz). The broad bandwidth provided excellent discrimination of individual targets in the water column, allowing for the identification of single bubbles. Absolute bubble target strength values were determined by compensating apparent target strength measurements for beam pattern effects via standard calibration techniques. The bubble size distribution of seeps with individual bubble signatures was determined by exploiting bubble target strength models over the broad range of frequencies. For denser seeps, with potential higher methane flux, bubble size distribution was determined via extrapolation from seeps in similar geomorphological settings. By coupling bubble size distributions with rise velocity measurements, which are made possible by split-beam target tracking, methane gas flux can be estimated. Of the 56 identified seeps in the SWERUS data set, individual bubbles scatterers were identified in more than half (31) of the seeps. Preliminary bubble size distribution results indicate bubble radii range from 0.75 to 3.0 mm, with relatively constant bubble size distribution throughout the water column. Initial rise velocity observations indicate bubble rise velocity increases with decreasing depth, seemingly independent of bubble radius.

Exposure-Response Modeling to Characterize the Relationship Between Ixekizumab Serum Drug Concentrations and Efficacy Responses at Week 12 in Patients With Moderate to Severe Plaque Psoriasis.

PubMed

Chigutsa, Emmanuel; de Mendizabal, Nieves Velez; Chua, Laiyi; Heathman, Michael; Friedrich, Stuart; Jackson, Kimberley; Reich, Kristian

2018-06-07

Ixekizumab, a high-affinity monoclonal antibody, selectively targets interleukin-17A and has been shown to be efficacious in the treatment of moderate to severe psoriasis. The objective was to describe the relationship between ixekizumab concentrations and efficacy response (static Physician Global Assessment [sPGA] and the Psoriasis Activity and Severity Index [PASI) scores] after 12 weeks of ixekizumab treatment in psoriasis patients from 3 phase 3 studies. Data from 2888 psoriasis patients randomized to receive placebo or 80 mg ixekizumab every 2 weeks or every 4 weeks were analyzed. Separate logistic regression models describing the relationship between ixekizumab concentrations and sPGA or PASI scores at week 12 were used to determine the probability of patients achieving a response and to investigate the impact of various patient factors other than drug concentrations on response rates. Both dosing regimens were efficacious, with higher rates of response achieved with the higher range of observed ixekizumab concentrations after every-2-week dosing. Although higher bodyweight, palmoplantar involvement, lower baseline disease state, or high baseline C-reactive protein were associated with slightly lower response rates, the magnitude of effect of these factors on sPGA(0,1) response was small, with all subgroups able to achieve high levels of response. Other factors tested had no effect including age, sex, and antidrug antibody status. Logistic regression modeling of ixekizumab concentration and efficacy data accurately identified the proportion of responders using sPGA or PASI end points. The higher concentration ranges achieved with 80 mg every 2 weeks versus every 4 weeks were associated with higher response levels. © 2018, The American College of Clinical Pharmacology.

Long-term monitoring of persistent organic pollutants (POPs) at the Norwegian Troll station in Dronning Maud Land, Antarctica

NASA Astrophysics Data System (ADS)

Kallenborn, R.; Breivik, K.; Eckhardt, S.; Lunder, C. R.; Manø, S.; Schlabach, M.; Stohl, A.

2013-03-01

A first long-term monitoring of selected persistent organic pollutants (POPs) in Antarctic air has been conducted at the Norwegian Research station Troll (Dronning Maud Land). As target contaminants 32 PCB congeners, a- and g-hexachlorocyclohexane (HCH), trans- and cis-chlordane, trans- and cis-nonachlor, p,p'- and o,p-DDT, DDD, DDE as well as hexachlorobenzene (HCB) were selected. The monitoring program with weekly samples taken during the period 2007-2010 was coordinated with the parallel program at the Norwegian Arctic monitoring site (Zeppelin mountain, Ny-Ålesund, Svalbard) in terms of priority compounds, sampling schedule as well as analytical methods. The POP concentration levels found in Antarctica were considerably lower than Arctic atmospheric background concentrations. Similar as observed for Arctic samples, HCB is the predominant POP compound with levels of around 22 pg m-3 throughout the entire monitoring period. In general, the following concentration distribution was found for the Troll samples analyzed: HCB > Sum HCH > Sum PCB > Sum DDT > Sum chlordanes. Atmospheric long-range transport was identified as a major contamination source for POPs in Antarctic environments. Several long-range transport events with elevated levels of pesticides and/or compounds with industrial sources were identified based on retroplume calculations with a Lagrangian particle dispersion model (FLEXPART). The POP levels determined in Troll air were compared with 1 concentrations found in earlier measurement campaigns at other Antarctic research stations from the past 18 yr. Except for HCB for which similar concentration distributions were observed in all sampling campaigns, concentrations in the recent Troll samples were lower than in samples collected during the early 1990s. These concentration reductions are obviously a direct consequence of international regulations restricting the usage of POP-like chemicals on a worldwide scale.

Field-based evaluation of semipermeable membrane devices (SPMDs) as passive air samplers of polyaromatic hydrocarbons (PAHs)

USGS Publications Warehouse

Bartkow, M.E.; Huckins, J.N.; Muller, J.F.

2004-01-01

Semipermeable membrane devices (SPMDs) have been used as passive air samplers of semivolatile organic compounds in a range of studies. However, due to a lack of calibration data for polyaromatic hydrocarbons (PAHs), SPMD data have not been used to estimate air concentrations of target PAHs. In this study, SPMDs were deployed for 32 days at two sites in a major metropolitan area in Australia. High-volume active sampling systems (HiVol) were co-deployed at both sites. Using the HiVol air concentration data from one site, SPMD sampling rates were measured for 12 US EPA Priority Pollutant PAHs and then these values were used to determine air concentrations at the second site from SPMD concentrations. Air concentrations were also measured at the second site with co-deployed HiVols to validate the SPMD results. PAHs mostly associated with the vapour phase (Fluorene to Pyrene) dominated both the HiVol and passive air samples. Reproducibility between replicate passive samplers was satisfactory (CV<20%) for the majority of compounds. Sampling rates ranged between 0.6 and 6.1 m3 d-1. SPMD-based air concentrations were calculated at the second site for each compound using these sampling rates and the differences between SPMD-derived air concentrations and those measured using a HiVol were, on average, within a factor of 1.5. The dominant processes for the uptake of PAHs by SPMDs were also assessed. Using the SPMD method described herein, estimates of particulate sorbed airborne PAHs with five rings or greater were within 1.8-fold of HiVol measured values. ?? 2004 Elsevier Ltd. All rights reserved.

Quick and simple sample treatment for multiresidue analysis of bisphenols, bisphenol diglycidyl ethers and their derivatives in canned food prior to liquid chromatography and fluorescence detection.

PubMed

Alabi, A; Caballero-Casero, N; Rubio, S

2014-04-04

We report herein a multiresidue method for canned food determination of 12 bisphenols [bisphenol A (BPA), bisphenol B (BPB), bisphenol F (BPF), bisphenol E (BPE)], bisphenol diglycidyl ethers [bisphenol F diglycidyl ether (BFDGE), bisphenol A diglycidyl ether (BADGE)] and their derivatives [BADGE·2H2O, BADGE·H2O, BADGE·HCl·H2O, BADGE·HCl, BADGE·2HCl and BFDGE·2HCl]. The method was based on the microextraction of the target contaminants in 200mg food sample with 600 μL of a supramolecular solvent made up of inverse aggregates of tetradecanol, followed by analysis of the extract by liquid chromatography/fluorescence detection using external calibration. Chromatographic separation of all target compounds, including the ortho-ortho, ortho-para and para-para isomers of BFDGE and BFDGE·2HCl, was achieved with baseline separation (Resolution ≥ 1.52). No concentration of the extracts was required, the microextraction took about 30 min and several samples could be simultaneous treated. Method validation was carried out according to the recommendations of the European Commission Decision 2002/657/EC. Quantitation limits for the different analytes ranged between 0.9 and 3.5 μg kg(-1). Repeatability and reproducibility, expressed as relative standard deviation, were in the ranges 1.8-6.8% and 4.4-8.1%. The method was applied to the analysis of the target compounds in different food categories including vegetables, legumes, fruits, fish and seafood, meat product and grain. Recoveries in samples were within the range 80-110%. Only BPF and BPE were undetected in the canned food analyzed. The concentration found for the rest of bisphenols, diglycidyl ethers and derivatives was in the range 7.1-959 μg kg(-1). The study of the isomeric distribution of BFDGE and BFDGE·2HCl in food showed that they are preferentially present as one of the isomeric forms, that highlighting for further studies. The analytical and operational characteristics of this multiresidue method make it suitable for monitoring programs intended for the assessment of human exposure to bisphenols, diglycidyl ethers and derivatives from diet. Copyright © 2014 Elsevier B.V. All rights reserved.

Laser range profiling for small target recognition

NASA Astrophysics Data System (ADS)

Steinvall, Ove; Tulldahl, Michael

2016-05-01

The detection and classification of small surface and airborne targets at long ranges is a growing need for naval security. Long range ID or ID at closer range of small targets has its limitations in imaging due to the demand on very high transverse sensor resolution. It is therefore motivated to look for 1D laser techniques for target ID. These include vibrometry, and laser range profiling. Vibrometry can give good results but is also sensitive to certain vibrating parts on the target being in the field of view. Laser range profiling is attractive because the maximum range can be substantial, especially for a small laser beam width. A range profiler can also be used in a scanning mode to detect targets within a certain sector. The same laser can also be used for active imaging when the target comes closer and is angular resolved. The present paper will show both experimental and simulated results for laser range profiling of small boats out to 6-7 km range and a UAV mockup at close range (1.3 km). We obtained good results with the profiling system both for target detection and recognition. Comparison of experimental and simulated range waveforms based on CAD models of the target support the idea of having a profiling system as a first recognition sensor and thus narrowing the search space for the automatic target recognition based on imaging at close ranges. The naval experiments took place in the Baltic Sea with many other active and passive EO sensors beside the profiling system. Discussion of data fusion between laser profiling and imaging systems will be given. The UAV experiments were made from the rooftop laboratory at FOI.

AFIR: A Dimensionless Potency Metric for Characterizing the Activity of Monoclonal Antibodies

PubMed Central

Ramakrishna, R

2017-01-01

For monoclonal antibody (mAb) drugs, soluble targets may accumulate several thousand fold after binding to the drug. Time course data of mAb and total target is often collected and, although free target is more closely related to clinical effect, it is difficult to measure. Therefore, mathematical models of this data are used to predict target engagement. In this article, a “potency factor” is introduced as an approximation for the model‐predicted target inhibition. This potency factor is defined to be the time‐Averaged Free target concentration to Initial target concentration Ratio (AFIR), and it depends on three key quantities: the average drug concentration at steady state; the binding affinity; and the degree of target accumulation. AFIR provides the intuition for how changes in dosing regimen and binding affinity affect target capture and AFIR can be used to predict the druggability of new targets and the expected benefits of more potent, second‐generation mAbs. PMID:28375563

Moving target parameter estimation of SAR after two looks cancellation

NASA Astrophysics Data System (ADS)

Gan, Rongbing; Wang, Jianguo; Gao, Xiang

2005-11-01

Moving target detection of synthetic aperture radar (SAR) by two looks cancellation is studied. First, two looks are got by the first and second half of the synthetic aperture. After two looks cancellation, the moving targets are reserved and stationary targets are removed. After that, a Constant False Alarm Rate (CFAR) detector detects moving targets. The ground range velocity and cross-range velocity of moving target can be got by the position shift between the two looks. We developed a method to estimate the cross-range shift due to slant range moving. we estimate cross-range shift by Doppler frequency center. Wigner-Ville Distribution (WVD) is used to estimate the Doppler frequency center (DFC). Because the range position and cross range before correction is known, estimation of DFC is much easier and efficient. Finally experiments results show that our algorithms have good performance. With the algorithms we can estimate the moving target parameter accurately.

Water-quality assessment of part of the upper Mississippi River basin, Minnesota and Wisconsin - Volatile organic compounds in surface and ground water, 1978-94

USGS Publications Warehouse

Andrews, W.J.; Fallon, J.D.; Kroening, S.E.

1995-01-01

Examination of water-quality data from widely distributed sampling networks of river sites and wells in the study area led to the following conclusions: 1) trace amounts of chlorinated VOC's were detected sporadically in waters of the Mississippi, Minnesota, St. Croix, and Vermillion Rivers; 2) benzene, ethylbenzene, toluene, and meta+paraxylene were detected sporadically in waters sampled from the chain of lakes used as the municipal supply for St. Paul, Minnesota; 3) the target VOC's were detected in less than five percent of ground-water samples at relatively low concentrations, generally near detection limits which ranged from 1 to 5 micrograms per liter; 4) VOC's were generally detected at similar frequencies, but at higher concentrations, in water samples from wells completed in sand and gravel aquifers than in water samples from wells completed in bedrock aquifers; 5) VOC's were most commonly detected in ground water in the vicinity of identifiable emission sites of VOC's, such as landfills, dumps, or major industries; 6) trichloroethene, a commonly used degreasing agent in dry cleaning, metal cleaning and cleaning septic lines, was the most frequently detected target VOC in ground water sampled from wells completed in both sand and gravel and bedrock aquifers; 7) wells producing water with detectable concentrations of the target VOC's tended to be shallower than wells producing water with no detectable concentrations of those compounds, but the differences in well depths were not statistically significant at a 95 percent confidence level; and 8) chlorination of water substantially increased the frequency of detection of trihalomethane compounds. The low frequencies of detection of the target VOC's and THM's in surface and ground water sampled from widely distributed sampling networks in the study area indicate that, although there are thousands of sites which can potentially emit these compounds to water, soil, and the atmosphere, these compounds have not had a widespread measurable effect on the quality of surface and ground water in the study area.

Magnetic bead-based enzyme-chromogenic substrate system for ultrasensitive colorimetric immunoassay accompanying cascade reaction for enzymatic formation of squaric acid-iron(III) chelate.

PubMed

Lai, Wenqiang; Tang, Dianping; Zhuang, Junyang; Chen, Guonan; Yang, Huanghao

2014-05-20

This work reports on a simple and feasible colorimetric immunoassay with signal amplification for sensitive determination of prostate-specific antigen (PSA, used as a model) at an ultralow concentration by using a new enzyme-chromogenic substrate system. We discovered that glucose oxidase (GOx), the enzyme broadly used in enzyme-linked immunosorbent assay (ELISA), has the ability to stimulate in situ formation of squaric acid (SQA)-iron(III) chelate. GOx-catalyzed oxidization of glucose leads to the formation of gluconic acid and hydrogen peroxide (H2O2). The latter can catalytically oxidize iron(II) to iron(III), which can rapidly (<1 min) coordinate with the SQA. Formation of the iron-squarate complex causes the color of the solution to change from bluish purple to bluish red accompanying the increasing absorbance with the increment of iron(III) concentration. On the basis of the SQA-iron(III) system, a new immunoassay protocol with GOx-labeled anti-PSA detection antibody can be designed for the detection of target PSA on capture antibody-functionalized magnetic immunosensing probe, monitored by recording the color or absorbance (λ = 468 nm) of the generated SQA-iron(III) chelate. The absorbance intensity shows to be dependent on the concentration of target PSA. A linear dependence between the absorbance and target PSA concentration is obtained under optimal conditions in the range from 1.0 pg mL(-1) to 30 ng mL(-1) with a detection limit (LOD) of 0.5 pg mL(-1) (0.5 ppt) estimated at the 3Sblank level. The sensitivity displays to be 3-5 orders of magnitude better than those of most commercialized human PSA ELISA kits. In addition, the developed colorimetric immunoassay was validated by assaying 12 human serum samples, receiving in good accordance with those obtained by the commercialized PSA ELISA kit. Importantly, the SQA-based immunosensing system can be further extended for the detection of other low-abundance proteins or biomarkers by controlling the target antibody.

Proximity fuze

DOEpatents

Harrison, Thomas R.

1989-08-22

A proximity fuze system includes an optical ranging apparatus, a detonation circuit controlled by the optical ranging apparatus, and an explosive charge detonated by the detonation cirtcuit. The optical ranging apparatus includes a pulsed laser light source for generating target ranging light pulses and optical reference light pulses. A single lens directs ranging pulses to a target and collects reflected light from the target. An optical fiber bundle is used for delaying the optical reference pulses to correspond to a predetermined distance from the target. The optical ranging apparatus includes circuitry for providing a first signal depending upon the light pulses reflected from the target, a second signal depending upon the light pulses from the optical delay fiber bundle, and an output signal when the first and second signals coincide with each other. The output signal occurs when the distance from the target is equal to the predetermined distance form the target. Additional circuitry distinguishes pulses reflected from the target from background solar radiation.

32 CFR 644.526 - Reporting target ranges.

Code of Federal Regulations, 2010 CFR

2010-07-01

... 32 National Defense 4 2010-07-01 2010-07-01 true Reporting target ranges. 644.526 Section 644.526... and Improvements § 644.526 Reporting target ranges. All Reports of Excess to GSA covering lands which have been used as target ranges of any kind will contain an affirmative or negative statement in regard...

32 CFR 644.526 - Reporting target ranges.

Code of Federal Regulations, 2011 CFR

2011-07-01

... 32 National Defense 4 2011-07-01 2011-07-01 false Reporting target ranges. 644.526 Section 644.526... and Improvements § 644.526 Reporting target ranges. All Reports of Excess to GSA covering lands which have been used as target ranges of any kind will contain an affirmative or negative statement in regard...

[Determination of triclosan and triclocarban in human breast milk by solid-phase extraction and ultra performance liquid chromatography-tandem mass spectrometry].

PubMed

Zhang, Pin; Zhang, Jing; Shi, Ying; Shao, Bing

2015-03-01

An analytical method was developed to simultaneously detect triclosan (TCS) and triclocarban (TCC) in human breast milk using solid-phase extraction (SPE) with ultra performance liquid chromatography-tandem mass spectrometry (UPLC-MS/MS). Samples were extracted by acetonitrile and purified with C -18 SPE cartridge after enzymolysis with β-glucuronidase/arylsulfatase. The chromatographic separation was performed on a Waters ACQUITY UPLC™ HSS T3 column (100 mm x 2. 1 mm, 1. 8 µm) with gradient elution using methanol and water at a flow rate of 0. 3 ml/min. The target analytes were assayed by triple quadrupole mass spectrometer operating in the negative ion mode. Quantification was performed by isotopic internal standard calibration. Satisfactory linearity (r2 > 0. 999) was obtained over the range of 0. 2 - 20. 0 µg/L and 0. 02 - 2. 0 µg/L for triclosan and triclocarban, respectively, with the limits of quantifications (LOQs) of 0. 41 and 0. 03 µg/kg. Average recoveries of two target compounds (spiked at three concentration levels) ranged from 100. 2% to 119. 3%, with the relative standard deviations (RSDs) between 5. 91% and 11. 31% (n =6). Twenty-five real samples (n = 25) were detected containing TCS and TCC at concentrations of < LOQ - 0. 77 µg/kg and < LOQ - 4. 28 µg/kg, respectively. Due to its high sensitivity and good reproductivity, this method can be applied to analyze TCS and TCC in human breast milk.

Ionic liquid as a mobile phase additive in high-performance liquid chromatography for the simultaneous determination of eleven fluorescent whitening agents in paper materials.

PubMed

Wang, Qing; Chen, Xianbo; Qiu, Bin; Zhou, Liang; Zhang, Hui; Xie, Juan; Luo, Yan; Wang, Bin

2016-04-01

In the present study, 11 4,4'-diaminostilbene-2,2'-disulfonic acid based fluorescent whitening agents with different numbers of sulfonic acid groups were separated by using an ionic liquid as a mobile phase additive in high-performance liquid chromatography with fluorescence detection. The effects of ionic liquid concentration, pH of mobile phase B, and composition of mobile phase A on the separation of fluorescent whitening agents were systematically investigated. The ionic liquid tetrabutylammonium tetrafluoroborate is superior to tetrabutylammomnium bromide for the separation of the fluorescent whitening agents. The optimal separation conditions were an ionic liquid concentration at 8 mM and the pH of mobile phase B at 8.5 with methanol as mobile phase A. The established method exhibited low limits of detection (0.04-0.07 ng/mL) and wide linearity ranges (0.30-20 ng/mL) with high linear correlation coefficients from 0.9994 to 0.9998. The optimized procedure was applied to analyze target analytes in paper samples with satisfactory results. Eleven target analytes were quantified, and the recoveries of spiked paper samples were in the range of 85-105% with the relative standard deviations from 2.1 to 5.1%. The obtained results indicated that the method was efficient for detection of 11 fluorescent whitening agents. © 2016 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

Relative range error evaluation of terrestrial laser scanners using a plate, a sphere, and a novel dual-sphere-plate target.

PubMed

Muralikrishnan, Bala; Rachakonda, Prem; Lee, Vincent; Shilling, Meghan; Sawyer, Daniel; Cheok, Geraldine; Cournoyer, Luc

2017-12-01

Terrestrial laser scanners (TLS) are a class of 3D imaging systems that produce a 3D point cloud by measuring the range and two angles to a point. The fundamental measurement of a TLS is range. Relative range error is one component of the overall range error of TLS and its estimation is therefore an important aspect in establishing metrological traceability of measurements performed using these systems. Target geometry is an important aspect to consider when realizing the relative range tests. The recently published ASTM E2938-15 mandates the use of a plate target for the relative range tests. While a plate target may reasonably be expected to produce distortion free data even at far distances, the target itself needs careful alignment at each of the relative range test positions. In this paper, we discuss relative range experiments performed using a plate target and then address the advantages and limitations of using a sphere target. We then present a novel dual-sphere-plate target that draws from the advantages of the sphere and the plate without the associated limitations. The spheres in the dual-sphere-plate target are used simply as fiducials to identify a point on the surface of the plate that is common to both the scanner and the reference instrument, thus overcoming the need to carefully align the target.

LPI studies with grazing incidence irradiation at the Nike laser

NASA Astrophysics Data System (ADS)

Weaver, J.; Kehne, D.; Schmitt, A.; Obenschain, S.; Serlin, V.; Oh, J.; Lehmberg, R.; Seely, J.

2013-10-01

Studies of laser plasma instabilities (LPI) at the Nike laser facility at NRL have previously concentrated on planar targets irradiated with their surface normal aligned to the central axis of the laser. Shots with planar targets rotated up 60° to the laser have shown changes in thresholds for the two-plasmon decay instability and stimulated Raman scattering near the quarter critical region. In the case of rotated low-Z targets, spectra were observed to shift to lower wavelength and were substantially stronger in the visible and ultraviolet spectral ranges. The low-Z target data show growth at an incident intensity slightly below (~30%) the threshold values observed at normal incidence. A rapid rise in signal level over the same laser intensities was also observed in the hard x-ray data which serve as an overall indicator of LPI activity. Shots with rotated planar high-Z targets showed that the visible and ultraviolet emissions dropped significantly when compared to low-Z targets in the same geometry. This presentation will include results from upcoming experiments to determine the LPI signal for low-Z, high-Z, and high-Z coated targets at lower laser intensities for several angles of target rotation. Shots with widely separated laser beams are also planned to explore cross beam energy transport at Nike. Work supported by DoE/NNSA.

A systematic review of dosing frequency with bone-targeted agents for patients with bone metastases from breast cancer

PubMed Central

Hutton, Brian; Addison, Christina L.; Campbell, Kaitryn; Fergusson, Dean; Mazarello, Sasha; Clemons, Mark

2013-01-01

Background Bone-targeted agents are usually administered to breast cancer patients with bone metastases every 3–4 weeks. Less frequent (‘de-escalated’) treatment may provide similar benefits with improved safety and reduced cost. Methods To systematically review randomised trials comparing de-escalated treatment with bone-targeted agents (i.e. every 12–16 weeks) to standard treatment (i.e. every 3–4 weeks), a formal systematic review of the literature was performed. Two individuals independently screened citations and full text articles. Random effects meta-analyses of clinically important outcomes were planned provided homogeneous studies were identified. Results Five relevant studies (n=1287 patients) were identified. Sample size ranged from 38 to 425. Information on outcomes including occurrence of SREs, bone pain, urinary N-telopeptide concentrations, serum C-telopeptide concentrations, pain medication use and safety outcomes was not consistently available. Two trials were non-inferiority studies, two dose-response evaluations and one was a pilot study. Bone-targeted agents use varied between studies, as did duration of prior therapy. Patient populations were considered heterogeneous in several ways, and thus no meta-analyses were performed. Observations from the included studies suggest there is potential that 3 month de-escalated treatment may provide similar benefits compared to 3–4 weekly treatment and that lower doses of zoledronic acid and denosumab might be equally effective. Conclusions Studies comparing standard and de-escalated treatment with bone-targeted agents in breast cancer are rare. The benefits of standard treatment compared to de-escalated therapy on important clinical outcomes remain unclear. Future pragmatic studies must be conducted to determine the merits of this approach. PMID:26909282

An albumin-based gold nanocomposites as potential dual mode CT/MRI contrast agent

NASA Astrophysics Data System (ADS)

Zhao, Wenjing; Chen, Lina; Wang, Zhiming; Huang, Yuankui; Jia, Nengqin

2018-02-01

In pursuit of the biological detection applications, recent years have witnessed the prosperity of novel multi-modal nanoprobes. In this study, biocompatible bovine serum albumin (BSA)-coated gold nanoparticles (Au NPs) containing Gd (III) as the contrast agent for both X-ray CT and T1-weighted MR imaging is reported. Firstly, the Au NPs with BSA coating (Au@BSA) was prepared through a moderate one-pot reduction route in the presence of hydrazine hydrate as reducer. Sequentially, the BSA coating enables modification of diethylenetriaminepentaacetic acid (DTPA) as well as targeting reagent hyaluronic acid (HA), and further chelation of Gd (III) ions led to the formation of biomimetic nanoagent HA-targeted Gd-Au NPs (HA-targeted Au@BSA-Gd-DTPA). Several techniques were used to thoroughly characterize the formed HA-targeted Gd-Au NPs. As expected, the as-prepared nanoagent with mean diameter of 13.82 nm exhibits not only good colloid stablility and water dispersibility, but also satisfying low cytotoxicity and hemocompatibility in the tested concentration range. Additionally, for the CT phantoms, the obtained nanocomplex shows an improved contrast in CT scanning than that of Au@BSA as well as small molecule iodine-based CT contrast agents such as iopromide. Meanwhile, for the T1-weighted MRI images, there is a linear increase of contrast with concentration of Gd for the two cases of HA-targeted Gd-Au NPs and Magnevist. Strikingly, the nanoagent we explored displays a relatively higher r1 relaxivity than that of commercial MR contrast agents. Therefore, this newly constructed nanoagent could be used as contrast agents for synergistically enhanced X-ray CT and MR phantoms, holding promising potential for future biomedical applications.

Redox polymer and probe DNA tethered to gold electrodes for enzyme-amplified amperometric detection of DNA hybridization.

PubMed

Kavanagh, Paul; Leech, Dónal

2006-04-15

The detection of nucleic acids based upon recognition surfaces formed by co-immobilization of a redox polymer mediator and DNA probe sequences on gold electrodes is described. The recognition surface consists of a redox polymer, [Os(2,2'-bipyridine)2(polyvinylimidazole)(10)Cl](+/2+), and a model single DNA strand cross-linked and tethered to a gold electrode via an anchoring self-assembled monolayer (SAM) of cysteamine. Hybridization between the immobilized probe DNA of the recognition surface and a biotin-conjugated target DNA sequence (designed from the ssrA gene of Listeria monocytogenes), followed by addition of an enzyme (glucose oxidase)-avidin conjugate, results in electrical contact between the enzyme and the mediating redox polymer. In the presence of glucose, the current generated due to the catalytic oxidation of glucose to gluconolactone is measured, and a response is obtained that is binding-dependent. The tethering of the probe DNA and redox polymer to the SAM improves the stability of the surface to assay conditions of rigorous washing and high salt concentration (1 M). These conditions eliminate nonspecific interaction of both the target DNA and the enzyme-avidin conjugate with the recognition surfaces. The sensor response increases linearly with increasing concentration of target DNA in the range of 1 x 10(-9) to 2 x 10(-6) M. The detection limit is approximately 1.4 fmol, (corresponding to 0.2 nM of target DNA). Regeneration of the recognition surface is possible by treatment with 0.25 M NaOH solution. After rehybridization of the regenerated surface with the target DNA sequence, >95% of the current is recovered, indicating that the redox polymer and probe DNA are strongly bound to the surface. These results demonstrate the utility of the proposed approach.

A ventilation intervention study in classrooms to improve indoor air quality: the FRESH study

PubMed Central

2013-01-01

Background Classroom ventilation rates often do not meet building standards, although it is considered to be important to improve indoor air quality. Poor indoor air quality is thought to influence both children’s health and performance. Poor ventilation in The Netherlands most often occurs in the heating season. To improve classroom ventilation a tailor made mechanical ventilation device was developed to improve outdoor air supply. This paper studies the effect of this intervention. Methods The FRESH study (Forced-ventilation Related Environmental School Health) was designed to investigate the effect of a CO2 controlled mechanical ventilation intervention on classroom CO2 levels using a longitudinal cross-over design. Target CO2 concentrations were 800 and 1200 parts per million (ppm), respectively. The study included 18 classrooms from 17 schools from the north-eastern part of The Netherlands, 12 experimental classrooms and 6 control classrooms. Data on indoor levels of CO2, temperature and relative humidity were collected during three consecutive weeks per school during the heating seasons of 2010–2012. Associations between the intervention and weekly average indoor CO2 levels, classroom temperature and relative humidity were assessed by means of mixed models with random school-effects. Results At baseline, mean CO2 concentration for all schools was 1335 ppm (range: 763–2000 ppm). The intervention was able to significantly decrease CO2 levels in the intervention classrooms (F (2,10) = 17.59, p < 0.001), with a mean decrease of 491 ppm. With the target set at 800 ppm, mean CO2 was 841 ppm (range: 743–925 ppm); with the target set at 1200 ppm, mean CO2 was 975 ppm (range: 887–1077 ppm). Conclusions Although the device was not capable of precisely achieving the two predefined levels of CO2, our study showed that classroom CO2 levels can be reduced by intervening on classroom ventilation using a CO2 controlled mechanical ventilation system. PMID:24345039

Worldwide drinking water occurrence and levels of newly-identified perfluoroalkyl and polyfluoroalkyl substances.

PubMed

Kaboré, Hermann A; Vo Duy, Sung; Munoz, Gabriel; Méité, Ladji; Desrosiers, Mélanie; Liu, Jinxia; Sory, Traoré Karim; Sauvé, Sébastien

2018-03-01

In the last decade or so, concerns have arisen with respect to the widespread occurrence of perfluoroalkyl acids (PFAAs) in the environment, food, drinking water, and humans. In this study, the occurrence and levels of a large range of perfluoroalkyl and polyfluoroalkyl substances (PFASs) were investigated in drinking water (bottled and tap water samples) from various locations around the world. Automated off-line solid phase extraction followed by ultra-high-performance liquid chromatography coupled to high-resolution mass spectrometry was used to analyze PFASs of various chain lengths and functional groups. In total, 29 target and 104 suspect-target PFASs were screened in drinking water samples (n=97) from Canada and other countries (Burkina Faso, Chile, Ivory Coast, France, Japan, Mexico, Norway, and the USA) in 2015-2016. Out of the 29 PFASs quantitatively analyzed, perfluorocarboxylates (PFCAs: C 4/14 ), perfluoroalkane sulfonates (PFSAs: C 4 , C 6 , C 8 ), and perfluoroalkyl acid precursors (e.g., 5:3 fluorotelomer carboxylate (5:3 FTCA)) were recurrently detected in drinking water samples (concentration range:

Sequential derivatization of polar organic compounds in cloud water using O-(2,3,4,5,6-pentafluorobenzyl)hydroxylamine hydrochloride, N,O-bis(trimethylsilyl)trifluoroacetamide, and gas-chromatography/mass spectrometry analysis.

PubMed

Sagona, Jessica A; Dukett, James E; Hawley, Harmonie A; Mazurek, Monica A

2014-10-03

Cloud water samples from Whiteface Mountain, NY were used to develop a combined sampling and gas chromatography-mass spectrometric (GCMS) protocol for evaluating the complex mixture of highly polar organic compounds (HPOC) present in this atmospheric medium. Specific HPOC of interest were mono- and di keto-acids which are thought to originate from photochemical reactions of volatile unsaturated hydrocarbons from biogenic and manmade emissions and be a major fraction of atmospheric carbon. To measure HPOC mixtures and the individual keto-acids in cloud water, samples first must be derivatized for clean elution and measurement, and second, have low overall background of the target species as validated by GCMS analysis of field and laboratory blanks. Here, we discuss a dual derivatization method with PFBHA and BSTFA which targets only organic compounds that contain functional groups reacting with both reagents. The method also reduced potential contamination by minimizing the amount of sample processing from the field through the GCMS analysis steps. Once derivatized only gas chromatographic separation and selected ion monitoring (SIM) are needed to identify and quantify the polar organic compounds of interest. Concentrations of the detected total keto-acids in individual cloud water samples ranged from 27.8 to 329.3ngmL(-1) (ppb). Method detection limits for the individual HPOC ranged from 0.17 to 4.99ngmL(-1) and the quantification limits for the compounds ranged from 0.57 to 16.64ngmL(-1). The keto-acids were compared to the total organic carbon (TOC) results for the cloud water samples with concentrations of 0.607-3.350mgL(-1) (ppm). GCMS analysis of all samples and blanks indicated good control of the entire collection and analysis steps. Selected ion monitoring by GCMS of target keto-acids was essential for screening the complex organic carbon mixtures present at low ppb levels in cloud water. It was critical for ensuring high levels of quality assurance and quality control and for the correct identification and quantification of key marker compounds. Copyright © 2014 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.

Target-responsive aptamer release from manganese dioxide nanosheets for electrochemical sensing of cocaine with target recycling amplification.

PubMed

Chen, Zongbao; Lu, Minghua

2016-11-01

A novel electrochemical sensing platform based on manganese dioxide (MnO2) nanosheets was developed for sensitive screening of target cocaine with the signal amplification. Ferrocene-labeled cocaine aptamers were initially immobilized onto MnO2 nanosheets-modified screen-printed carbon electrode because of π-stacking interaction between nucleobases and nanosheets. The immobilized ferrocene-aptamer activated the electrical contact with the electrode, thereby resulting in the sensor circuit to switch on. Upon target cocaine introduction, the analyte reacted with the aptamer and caused the dissociation of ferrocene-aptamer from the electrode, thus giving rise to the detection circuit to switch off. The released aptamer was cleaved by DNase I with target recycling. Under optimal conditions, the decreasing percentage of the electronic signal relative to background current increased with the increasing cocaine concentration in the dynamic range of 0.1-20nM, and the detection limit was 32pM. The reproducibility, selectivity and method accuracy were acceptable. Importantly, this concept offers promise for rapid, simple, and cost-effective analysis of cocaine biological samples without the needs of sample separation and multiple washing steps. Copyright © 2016 Elsevier B.V. All rights reserved.

Prediction of Drug-Target Interactions and Drug Repositioning via Network-Based Inference

PubMed Central

Jiang, Jing; Lu, Weiqiang; Li, Weihua; Liu, Guixia; Zhou, Weixing; Huang, Jin; Tang, Yun

2012-01-01

Drug-target interaction (DTI) is the basis of drug discovery and design. It is time consuming and costly to determine DTI experimentally. Hence, it is necessary to develop computational methods for the prediction of potential DTI. Based on complex network theory, three supervised inference methods were developed here to predict DTI and used for drug repositioning, namely drug-based similarity inference (DBSI), target-based similarity inference (TBSI) and network-based inference (NBI). Among them, NBI performed best on four benchmark data sets. Then a drug-target network was created with NBI based on 12,483 FDA-approved and experimental drug-target binary links, and some new DTIs were further predicted. In vitro assays confirmed that five old drugs, namely montelukast, diclofenac, simvastatin, ketoconazole, and itraconazole, showed polypharmacological features on estrogen receptors or dipeptidyl peptidase-IV with half maximal inhibitory or effective concentration ranged from 0.2 to 10 µM. Moreover, simvastatin and ketoconazole showed potent antiproliferative activities on human MDA-MB-231 breast cancer cell line in MTT assays. The results indicated that these methods could be powerful tools in prediction of DTIs and drug repositioning. PMID:22589709

Simple high-performance liquid chromatographic method to monitor vigabatrin, and preliminary review of concentrations determined in epileptic patients.

PubMed

George, S; Gill, L; Braithwaite, R A

2000-05-01

A simple and rapid high-performance liquid chromatographic method has been developed for the determination of vigabatrin concentrations in plasma or serum. The assay uses only 100 microL of specimen and has been found to be linear over a concentration range of 1 to 50 mg/L. The limit of detection has been determined as 1 mg/L, and the between-batch coefficient of variation for the two internal quality controls routinely analysed (n = 33) has been found to be less than 5%. There was no evidence of interferences in the assay from other commonly prescribed anti-epileptic drugs. This method has been applied to routine clinical specimens to determine the concentration of vigabatrin in 47 patient specimens over a 12-month period. It was found that only 63% of the male group and 53% of the female group were within the proposed target concentration of 5 to 35 mg/L. In addition, it was found that 26% of the male group and 36% of the female group were found to have concentrations below 5 mg/L, which may indicate lack of compliance and/or lack of therapeutic efficacy of treatment.

Concentrations of heavy metals in marine wild fishes captured from the southern sea of Korea and associated health risk assessments

NASA Astrophysics Data System (ADS)

Hwang, Dong-Woon; Kim, Seong-Soo; Kim, Seong-Gil; Kim, Dong-Sun; Kim, Tae-Hoon

2017-12-01

Concentrations of heavy metals (As, Cd, Cr, Cu, Hg, Pb, and Zn) were determined in edible parts (muscle) of 34 marine wild fish caught from the southern sea of Korea in 2007 and 2008 in order to understand the accumulation pattern of heavy metals in wild fish and to assess the potential health risk posed by fish consumption. The highest concentrations in the muscle of 17 pelagic and 17 demersal fishes were Zn and As, respectively, while the lowest concentration in both fishes was Cd. The mean concentrations of all metals except As in wild fish were much lower than the regulatory limits for fish and fishery products applied in a number of countries. Unlike other metals, As concentration in wild fish of this study region was relatively higher than that found in other country. Estimated daily intake (EDI) of the metals was in the range of 0.05% to 22.5% of the provisional maximum tolerable daily intakes (PMTDI). Similarly, the target hazard quotient (THQ) was below 1.0 for each metal. These results imply that the consumption of the investigated wild fish do not cause significant adverse health effects.

Monitoring of 45 pesticides in Lebanese surface water using Polar Organic Chemical Integrative Sampler (POCIS)

NASA Astrophysics Data System (ADS)

Aisha, Al Ashi; Hneine, Wael; Mokh, Samia; Devier, Marie-Hélène; Budzinski, Hélèn; Jaber, Farouk

2017-09-01

The aim of this study is to assess the dissolved concentration of 45 pesticides in the surface waters of the Lebanese Republic using Polar Organic Chemical Integrative Sampler "POCIS". All of the sampling sites are located in the major agricultural land areas in Lebanon. POCIS (n = 3) were deployed at Ibrahim River, Qaraoun Lake and Hasbani River for a duration of 14 days. The total concentration of pesticides ranged from not detected (nd) to 137.66 ng.L-1. Chlorpyrifos, DDE-pp, diazinon and Fenpropathrin were the most abundant compounds. Qaraoun Lake and Hasbani River were found to be more polluted than Ibrahim River, since they receive large amounts of waste water derived from nearby agricultural lands and they had the lowest dilution factor. The aqueous average concentration of the target compounds were estimated using sampling rates obtained from the literature. Comparison between Time Weighed Average concentrations "TWA" using POCIS and spot sampling is presented. Results showed that POCIS TWA concentrations are in agreement with spot sampling concentrations for Ibrahim and Hasbani Rivers. The toxicity of the major detected pesticides on three representative aquatic species ( Daphnia magna, Scenedesmus quadricauda and Oncorhynchus mykiss) is also reported.

Endocrine disruptors in freshwater streams of Hesse, Germany: changes in concentration levels in the time span from 2003 to 2005.

PubMed

Quednow, Kristin; Püttmann, Wilhelm

2008-03-01

Four small freshwater streams in the region known as Hessisches Ried in Germany were investigated with respect to the temporal and spatial concentration variations of the endocrine disruptors bisphenol A (BPA), 4-tert-octylphenol (4-tert-OP), and the technical isomer mixture of 4-nonylphenol (tech.-4-NP). Measured concentrations of the target compounds in the river water samples ranged from <20 ng/l to 1927 ng/l, <10 ng/l to 770 ng/l, and <10 ng/l to 420 ng/l for BPA, 4-tert-OP and tech.-4-NP, respectively. BPA levels were, with the exception of two samples, below the predicted no-effect concentration (PNEC) for water organisms. Tech.-4-NP concentrations showed a significant tendency of decreasing concentrations during the sampling period. This is mainly attributed to the implementation of the European Directive 2003/53/EG, which restricts both the marketing and use of nonylphenols. Results from the analysis of additionally collected water samples from sewage treatment plant (STP) effluents indicate that the STPs cannot be the only sources for tech.-4-NP found in the river water.

Enzyme-enhanced fluorescence detection of DNA on etched optical fibers.

PubMed

Niu, Shu-yan; Li, Quan-yi; Ren, Rui; Zhang, Shu-sheng

2009-05-15

A novel DNA biosensor based on enzyme-enhanced fluorescence detection on etched optical fibers was developed. The hybridization complex of DNA probe and biotinylated target was formed on the etched optical fiber, and was then bound with streptavidin labeled horseradish peroxidase (streptavidin-HRP). The target DNA was quantified through the fluorescent detection of bi-p,p'-4-hydroxyphenylacetic acid (DBDA) generated from the substrate 4-hydroxyphenylacetic acid (p-HPA) under the catalysis of HRP, with a detection limit of 1 pM and a linear range from 1.69 pM to 169 pM. It is facile to regenerate this sensor through surface treatment with concentrated urea solution. It was discovered that the sensor can retain 70% of its original activity after three detection-regeneration cycles.

Quantitative assessment of airborne exposures generated during common cleaning tasks: a pilot study

PubMed Central

2010-01-01

Background A growing body of epidemiologic evidence suggests an association between exposure to cleaning products with asthma and other respiratory disorders. Thus far, these studies have conducted only limited quantitative exposure assessments. Exposures from cleaning products are difficult to measure because they are complex mixtures of chemicals with a range of physicochemical properties, thus requiring multiple measurement techniques. We conducted a pilot exposure assessment study to identify methods for assessing short term, task-based airborne exposures and to quantitatively evaluate airborne exposures associated with cleaning tasks simulated under controlled work environment conditions. Methods Sink, mirror, and toilet bowl cleaning tasks were simulated in a large ventilated bathroom and a small unventilated bathroom using a general purpose, a glass, and a bathroom cleaner. All tasks were performed for 10 minutes. Airborne total volatile organic compounds (TVOC) generated during the tasks were measured using a direct reading instrument (DRI) with a photo ionization detector. Volatile organic ingredients of the cleaning mixtures were assessed utilizing an integrated sampling and analytic method, EPA TO-17. Ammonia air concentrations were also measured with an electrochemical sensor embedded in the DRI. Results Average TVOC concentrations calculated for 10 minute tasks ranged 0.02 - 6.49 ppm and the highest peak concentrations observed ranged 0.14-11 ppm. TVOC time concentration profiles indicated that exposures above background level remained present for about 20 minutes after cessation of the tasks. Among several targeted VOC compounds from cleaning mixtures, only 2-BE was detectable with the EPA method. The ten minute average 2- BE concentrations ranged 0.30 -21 ppm between tasks. The DRI underestimated 2-BE exposures compared to the results from the integrated method. The highest concentration of ammonia of 2.8 ppm occurred during mirror cleaning. Conclusions Our results indicate that airborne exposures from short-term cleaning tasks can remain in the air even after tasks' cessation, suggesting potential exposures to anyone entering the room shortly after cleaning. Additionally, 2-BE concentrations from cleaning could approach occupational exposure limits and warrant further investigation. Measurement methods applied in this study can be useful for workplace assessment of airborne exposures during cleaning, if the limitations identified here are addressed. PMID:21118559

REMOTE SENSING OF CH4 BY COMBINING LIDAR AND OPTICAL CORRELATION SPECTROSCOPY : FIRST EXPERIMENTAL RESULTS B. Thomas1, A. Miffre1, G. David1, J.P. Cariou2, P. Rairoux1 1Laboratoire de Spectrométrie Ionique et Moléculaire, CNRS, UMR 5579 Université Lyon 1, 10 rue Ada Byron, 69622 Villeurbanne, France, patrick.rairoux@univ-lyon1.fr 2Leosphere France, 14-16 rue Jean Rostand, 91400 Orsay, France, jpcariou@leosphere.fr

NASA Astrophysics Data System (ADS)

Thomas, B.; Miffre, A.; David, G.; Cariou, J.; Rairoux, P.

2012-12-01

In this contribution, we present a new methodology, called OCS-lidar, to remotely evaluate trace gas concentrations in the atmosphere (B. Thomas et al, 2012), as well as the first methane concentration measurements using this methodology. It is based on combining the Optical Correlation Spectroscopy (OCS) method with laser remote sensing technique (lidar). As displayed on figure 1, an Acoustic Optical Programmable Dispersive Filter is coupled with spectrally broadened femtosecond laser pulses to achieve the optical correlation between the emitted laser pulse and the methane absorption cross-section. In a first time, statistical and systematical errors of the OCS-lidar methodology have been evaluated thanks to a numerical model. The detection noise, interfering trace gases, temperature and pressure variations as well as laser pulse-to-pulse fluctuations have been considered. OCS-lidar simulations for methane concentration measurements have been achieved for background concentration (1.5 to 3 ppm), low (tens of ppm) and high sources (hundreds of ppm). Results show that background measurements are possible in the hour range while sources assessment and localization can be achieved in 10 minutes range up to 3 km range. Then, first methane concentration experimental measurements by using the OCS-lidar methodology will be presented. The laser source is an Oscillator Parametric Amplifier with emitting wavelength from 1.1 to 2 μm with 0.2 mJ at 1 kHz repetition rate. An AOPDF is used to generate correlated and non-correlated (or reference) signal. Experimental results on background methane concentration and on remote point source measurements will be presented, showing the achieved sensitivity and accuracy in both geophysical conditions.igure 1. Scheme of the OCS-Lidar principle. A broadened laser source centered on λ0-wavelength, with power spectral density P0, is used to create spectrally shaped power density P0M1 and P0M2, which are respectively correlated and anti-correlated to the target gas absorption cross-section σ(λ), (M1 and M2 are the wavelength dependent AOPDF-transmissions). In the atmosphere, these two emitted laser pulses, which undergo different absorptions due to the target gas presence, methane in our case, give rise to the output OCS-Lidar signals P1 and P2, after collection by a Lidar receiver and detection on an optical detector D.

Clinical and pharmacokinetic results with a new ultrashort-acting calcium antagonist, clevidipine, following gradually increasing intravenous doses to healthy volunteers

PubMed Central

Ericsson, H; Fakt, C; Jolin-Mellgård, Å; Nordlander, M; Sohtell, L; Sunzel, M; Regårdh, C G

1999-01-01

Aims To investigate the tolerability and safety of clevidipine in healthy male volunteers during intravenous infusion at gradually increasing dose rates and to obtain preliminary information on the pharmacokinetics and pharmacodynamic effects of the drug. Methods Twenty-five subjects were enrolled in the study and twenty-one of them were included twice, resulting in a total of forty-six study entries encompassing 20 min infusions of clevidipine at target dose rates ranging from 0.12 to 48 nmol min−1 kg−1. Haemodynamic variables and adverse events were recorded throughout the study. Concentrations of clevidipine and its primary metabolite, H 152/81, were followed in whole blood, and the pharmacokinetics were evaluated by non-compartmental and compartmental analysis. An Emax model was fitted to the effect on mean arterial pressure (MAP) over heart rate (HR) and the corresponding blood concentrations of clevidipine. Results Clevidipine was administered up to a target dose rate of 48 nmol min−1 kg−1, where a pre-determined escape criterion was reached (HR>120 beats min−1) and the study was stopped. The most common adverse events were flush and headache, which can be directly related to the mechanism of action of clevidipine. There was a linear relationship between blood concentration and dose rate in the range studied. The median clearance value determined by non-compartmental analysis was 0.125 l min−1 kg−1. Applying the population approach to the sparse data on clevidipine concentrations, an open two compartment pharmacokinetic model was found to be the best model in describing the disposition of the drug. The population mean clearance value determined by this method was 0.121 l min−1 kg−1, and the volume of distribution at steady state was 0.56 l kg−1. The initial half-life, contributing by more than 80% to the total area under the blood concentration-time curve following i.v. bolus administration, was 1.8 min, and the terminal half-life was 9.5 min. At the highest dose rates, MAP was reduced by approximately 10%, and the HR reached the pre-determined escape criterion for this study (>120 beats min−1). Conclusions Clevidipine is well tolerated and safe in healthy volunteers at dose rates up to at least 48 nmol min−1 kg−1. The pharmacokinetics are linear over a wide dose range. Clevidipine is a high clearance drug with extremely short half-lives. The effect of clevidipine on the blood pressure was marginal, probably due to a compensatory baroreflex activation in this population of healthy volunteers. A simple Emax model adequately describes the relationship between the pharmacodynamic response (MAP/HR) and the blood concentrations of clevidipine. PMID:10336577

Targeted Analyte Detection by Standard Addition Improves Detection Limits in MALDI Mass Spectrometry

PubMed Central

Eshghi, Shadi Toghi; Li, Xingde; Zhang, Hui

2014-01-01

Matrix-assisted laser desorption/ionization has proven an effective tool for fast and accurate determination of many molecules. However, the detector sensitivity and chemical noise compromise the detection of many invaluable low-abundance molecules from biological and clinical samples. To challenge this limitation, we developed a targeted analyte detection (TAD) technique. In TAD, the target analyte is selectively elevated by spiking a known amount of that analyte into the sample, thereby raising its concentration above the noise level, where we take advantage of the improved sensitivity to detect the presence of the endogenous analyte in the sample. We assessed TAD on three peptides in simple and complex background solutions with various exogenous analyte concentrations in two MALDI matrices. TAD successfully improved the limit of detection (LOD) of target analytes when the target peptides were added to the sample in a concentration close to optimum concentration. The optimum exogenous concentration was estimated through a quantitative method to be approximately equal to the original LOD for each target. Also, we showed that TAD could achieve LOD improvements on an average of 3-fold in a simple and 2-fold in a complex sample. TAD provides a straightforward assay to improve the LOD of generic target analytes without the need for costly hardware modifications. PMID:22877355

Targeted analyte detection by standard addition improves detection limits in matrix-assisted laser desorption/ionization mass spectrometry.

PubMed

Toghi Eshghi, Shadi; Li, Xingde; Zhang, Hui

2012-09-18

Matrix-assisted laser desorption/ionization (MALDI) has proven an effective tool for fast and accurate determination of many molecules. However, the detector sensitivity and chemical noise compromise the detection of many invaluable low-abundance molecules from biological and clinical samples. To challenge this limitation, we developed a targeted analyte detection (TAD) technique. In TAD, the target analyte is selectively elevated by spiking a known amount of that analyte into the sample, thereby raising its concentration above the noise level, where we take advantage of the improved sensitivity to detect the presence of the endogenous analyte in the sample. We assessed TAD on three peptides in simple and complex background solutions with various exogenous analyte concentrations in two MALDI matrices. TAD successfully improved the limit of detection (LOD) of target analytes when the target peptides were added to the sample in a concentration close to optimum concentration. The optimum exogenous concentration was estimated through a quantitative method to be approximately equal to the original LOD for each target. Also, we showed that TAD could achieve LOD improvements on an average of 3-fold in a simple and 2-fold in a complex sample. TAD provides a straightforward assay to improve the LOD of generic target analytes without the need for costly hardware modifications.

Optimal Target Range of Closed-Loop Inspired Oxygen Support in Preterm Infants: A Randomized Cross-Over Study.

PubMed

van den Heuvel, Maria Elisabeth Nicoletta; van Zanten, Henriette A; Bachman, Tom E; Te Pas, Arjan B; van Kaam, Anton H; Onland, Wes

2018-06-01

To investigate the effect of different pulse oximetry (SpO 2 ) target range settings during automated fraction of inspired oxygen control (A-FiO 2 ) on time spent within a clinically set SpO 2 alarm range in oxygen-dependent infants on noninvasive respiratory support. Forty-one preterm infants (gestational age [median] 26 weeks, age [median] 21 days) on FiO 2  >0.21 receiving noninvasive respiratory support were subjected to A-FiO 2 using 3 SpO 2 target ranges (86%-94%, 88%-92%, or 89%-91%) in random order for 24 hours each. Before switching to the next target range, SpO 2 was manually controlled for 24 hours (washout period). The primary outcome was the time spent within the clinically set alarm limits of 86%-94%. The percent time within the 86%-94% SpO 2 alarm range was similar for all 3 A-FiO 2 target ranges (74%). Time spent in hyperoxemia was not significantly different between target ranges. However, the time spent in severe hypoxemia (SpO 2  <80%) was significantly reduced during the narrowed target ranges of A-FiO 2 (88%-92%; 1.9%, 89%-91%; 1.7%) compared with the wide target range (86%-94%; 3.4%, P < .001). There were no differences between the 88%-92% and 89-91% target range. Narrowing the target range of A-FiO 2 to the desired median ±2% is effective in reducing the time spent in hypoxemia, without increasing the risk of hyperoxemia. www.trialregister.nl: NTR4368. Copyright © 2018 Elsevier Inc. All rights reserved.

Distribution of pesticides, PAHs, PCBs, and bioavailable metals in depositional sediments of the lower Missouri River, USA

USGS Publications Warehouse

Echols, K.R.; Brumbaugh, W.G.; Orazio, C.E.; May, T.W.; Poulton, B.C.; Peterman, P.H.

2008-01-01

The lower Missouri River was studied to determine the distribution of selected persistent organic pollutants and bioavailable metals in depositional sediments. Nineteen sites between Omaha, Nebraska and Jefferson City, Missouri were sampled. This stretch of the river receives point-source and non-point-source inputs from industrial, urban, and agricultural activities. As part of an ecological assessment of the river, concentrations of 29 legacy organochlorine pesticides (OC pesticides), including chlordanes, DDTs, and hexachlorocyclohexanes; a select list of current-use pesticides, including trifluralin, diazinon, chlorpyrifos, and permethrin, polycyclic aromatic hydrocarbons (PAHs), polychlorinated biphenyls (PCBs), divalent metals (copper, nickel, zinc, cadmium, and lead), and polybrominated diphenyl ethers (PBDEs) were determined. Concentrations (dry weight basis) of OC pesticides in the sediments were less than 1 ng/g, with the exception of the backwater sediment collected from the mouth of the Blue River in the Kansas City metropolitan area, which contained up to 20 ng/g total chlordane, 8.1 ng/g p,p???-DDE, 1.5 ng/g lindane, 4.8 ng/g dieldrin, and 3 ng/g endrin. Concentrations of chlorpyrifos and permethrin ranged from less than 1 ng/g to 5.5 ng/g and 44 ng/g, respectively. Concentrations of PCBs ranged from less than 11 ng/g to 250 ng/g, with the Blue River and Sibley sediments containing 100 and 250 ng/g total PCBs, respectively. Concentrations of total PAHs at 17 of the 19 sites ranged from 250 to 700 ng/g, whereas the Riverfront and Blue River sites in Kansas City contained 1100 ng/g and nearly 4000 ng/g, respectively. Concentrations of the metals did not vary significantly among most sites; however, the Blue River site contained elevated concentrations of zinc (104 ??g/g), cadmium (0.7 ??g/g), and lead (34 ??g/g) compared to the other sites. The moderately high concentrations of acid-volatile sulfide in the sediments suggest a low potential for metal toxicity to benthic organisms along this reach of the Missouri River. The depositional area sediments contained concentrations of the targeted persistent organic chemicals and metals that were below published probable effect level concentrations. ?? 2008 Springer Science+Business Media, LLC.

Evaluation of on-line concentration coupled to liquid chromatography tandem mass spectrometry for the quantification of neonicotinoids and fipronil in surface water and tap water.

PubMed

Montiel-León, Juan Manuel; Duy, Sung Vo; Munoz, Gabriel; Amyot, Marc; Sauvé, Sébastien

2018-04-01

A study was initiated to investigate a fast and reliable method for the determination of selected systemic insecticides in water matrixes and to evaluate potential sources of bias in their analysis. Acetamiprid, clothianidin, desnitro-imidacloprid, dinotefuran, fipronil, imidacloprid, nitenpyram, thiacloprid, and thiamethoxam were amenable to analysis via on-line sample enrichment hyphenated to ultra-high-performance liquid chromatography tandem mass spectrometry. The selection of on-line solid-phase extraction parameters was dictated by a multicriterion desirability approach. A 2-mL on-line injection volume with a 1500 μL min -1 loading flow rate met the objectives sought in terms of chromatographic requirements, extraction efficiency, sensitivity, and precision. A total analysis time of 8 min per sample was obtained with method limits of detection in the range of 0.1-5 ng L -1 for the scope of targeted analytes. Automation at the sample concentration step yielded intraday and interday precisions in the range of 1-23 and 2-26%, respectively. Factors that could affect the whole method accuracy were further evaluated in matrix-specific experiments. The impact of the initial filtration step on analyte recovery was evaluated in ultra-pure water, tap water, and surface water. Out of the nine membranes tested, glass fiber filters and polyester filters appeared as the most appropriate materials. Sample storage stability was also investigated across the three matrix types; the targeted analytes displayed suitable stability during 28 days at either 4 °C or - 20 °C, with little deviations (± 10%) with respect to the initial T 0 concentration. Method applicability was demonstrated in a range of tap water and surface water samples from the province of Québec, Canada. Results from the present survey indicated a predominance of thiamethoxam (< 0.5-10 and 3-61 ng L -1 in tap water and river water, respectively), clothianidin (< 0.5-6 and 2-88 ng L -1 in tap water and river water, respectively), and imidacloprid (< 0.1-1 and 0.8-38 ng L -1 in tap water and river water, respectively) among the targeted analytes. Graphical abstract ᅟ Development of solid-phase extraction coupled on-line to UHPLC-MS/MS for the rapid screening of systemic insecticides in water.

Fragment properties at the catastrophic disruption threshold: The effect of the parent body’s internal structure

NASA Astrophysics Data System (ADS)

Jutzi, Martin; Michel, Patrick; Benz, Willy; Richardson, Derek C.

2010-05-01

Numerical simulations of asteroid breakups, including both the fragmentation of the parent body and the gravitational interactions between the fragments, have allowed us to reproduce successfully the main properties of asteroid families formed in different regimes of impact energy, starting from a non-porous parent body. In this paper, using the same approach, we concentrate on a single regime of impact energy, the so-called catastrophic threshold usually designated by QD*, which results in the escape of half of the target's mass. Thanks to our recent implementation of a model of fragmentation of porous materials, we can characterize QD* for both porous and non-porous targets with a wide range of diameters. We can then analyze the potential influence of porosity on the value of QD*, and by computing the gravitational phase of the collision in the gravity regime, we can characterize the collisional outcome in terms of the fragment size and ejection speed distributions, which are the main outcome properties used by collisional models to study the evolutions of the different populations of small bodies. We also check the dependency of QD* on the impact speed of the projectile. In the strength regime, which corresponds to target sizes below a few hundreds of meters, we find that porous targets are more difficult to disrupt than non-porous ones. In the gravity regime, the outcome is controlled purely by gravity and porosity in the case of porous targets. In the case of non-porous targets, the outcome also depends on strength. Indeed, decreasing the strength of non-porous targets make them easier to disrupt in this regime, while increasing the strength of porous targets has much less influence on the value of QD*. Therefore, one cannot say that non-porous targets are systematically easier or more difficult to disrupt than porous ones, as the outcome highly depends on the assumed strength values. In the gravity regime, we also confirm that the process of gravitational reaccumulation is at the origin of the largest remnant's mass in both cases. We then propose some power-law relationships between QD* and both target's size and impact speed that can be used in collisional evolution models. The resulting fragment size distributions can also be reasonably fitted by a power-law whose exponent ranges between -2.2 and -2.7 for all target diameters in both cases and independently on the impact velocity (at least in the small range investigated between 3 and 5 km/s). Then, although ejection velocities in the gravity regime tend to be higher from porous targets, they remain on the same order as the ones from non-porous targets.

Microgels for multiplex and direct fluorescence detection

NASA Astrophysics Data System (ADS)

Causa, Filippo; Aliberti, Anna; Cusano, Angela M.; Battista, Edmondo; Netti, Paolo A.

2015-05-01

Blood borne oligonucleotides fragments contain useful clinical information whose detection and monitoring represent the new frontier in liquid biopsy as they can transform the current diagnosis procedure. For instance, recent studies have identified a new class of circulating biomarkers such as s miRNAs, and demonstrated that changes in their concentration are closely associated with the development of cancer and other pathologies. However, direct detection of miRNAs in body fluids is particularly challenging and demands high sensitivity -concentration range between atto to femtomolarspecificity, and multiplexing Here we report on engineered multifunctional microgels and innovative probe design for a direct and multiplex detection of relevant clinical miRNAs in fluorescence by single particle assay. Polyethyleneglycol-based microgels have a coreshell architecture with two spectrally encoded fluorescent dyes for multiplex analyses and are endowed with fluorescent probes for miRNA detection. Encoding and detection fluorescence signals are distinguishable by not overlapping emission spectra. Tuneable fluorescence probe conjugation and corresponding emission confinement on single microgel allows for enhanced target detection. Such suspension array has indeed high selectivity and sensitivity with a detection limit of 10-15 M and a dynamic range from 10-9 to 10-15 M. We believe that sensitivity in the fM concentration range, signal background minimization, multiplexed capability and direct measurement of such microgels will translate into diagnostic benefits opening up new roots toward liquid biopsy in the context of point-of-care testing through an easy and fast detection of sensitive diagnostic biomarkers directly in serum.

Thermodynamics of Micelle Formation and Membrane Fusion Modulate Antimicrobial Lipopeptide Activity

PubMed Central

Lin, Dejun; Grossfield, Alan

2015-01-01

Antimicrobial lipopeptides (AMLPs) are antimicrobial drug candidates that preferentially target microbial membranes. One class of AMLPs, composed of cationic tetrapeptides attached to an acyl chain, have minimal inhibitory concentrations in the micromolar range against a range of bacteria and fungi. Previously, we used coarse-grained molecular dynamics simulations and free energy methods to study the thermodynamics of their interaction with membranes in their monomeric state. Here, we extended the study to the biologically relevant micellar state, using, to our knowledge, a novel reaction coordinate based on hydrophobic contacts. Using umbrella sampling along this reaction coordinate, we identified the critical transition states when micelles insert into membranes. The results indicate that the binding of these AMLP micelles to membranes is thermodynamically favorable, but in contrast to the monomeric case, there are significant free energy barriers. The height of these free energy barriers depends on the membrane composition, suggesting that the AMLPs’ ability to selectively target bacterial membranes may be as much kinetic as thermodynamic. This mechanism highlights the importance of considering oligomeric state in solution as criterion when optimizing peptides or lipopeptides as antibiotic leads. PMID:26287627

Photoinitiator Nucleotide for Quantifying Nucleic Acid Hybridization

PubMed Central

Johnson, Leah M.; Hansen, Ryan R.; Urban, Milan; Kuchta, Robert D.; Bowman, Christopher N.

2010-01-01

This first report of a photoinitiator-nucleotide conjugate demonstrates a novel approach for sensitive, rapid and visual detection of DNA hybridization events. This approach holds potential for various DNA labeling schemes and for applications benefiting from selective DNA-based polymerization initiators. Here, we demonstrate covalent, enzymatic incorporation of an eosin-photoinitiator 2′-deoxyuridine-5′-triphosphate (EITC-dUTP) conjugate into surface-immobilized DNA hybrids. Subsequent radical chain photoinitiation from these sites using an acrylamide/bis-acrylamide formulation yields a dynamic detection range between 500pM and 50nM of DNA target. Increasing EITC-nucleotide surface densities leads to an increase in surface-based polymer film heights until achieving a film height plateau of 280nm ±20nm at 610 ±70 EITC-nucleotides/μm2. Film heights of 10–20 nm were obtained from eosin surface densities of approximately 20 EITC-nucleotides/μm2 while below the detection limit of ~10 EITC-nucleotides/μm2, no detectable films were formed. This unique threshold behavior is utilized for instrument-free, visual quantification of target DNA concentration ranges. PMID:20337438

Stepwise kinetic equilibrium models of quantitative polymerase chain reaction.

PubMed

Cobbs, Gary

2012-08-16

Numerous models for use in interpreting quantitative PCR (qPCR) data are present in recent literature. The most commonly used models assume the amplification in qPCR is exponential and fit an exponential model with a constant rate of increase to a select part of the curve. Kinetic theory may be used to model the annealing phase and does not assume constant efficiency of amplification. Mechanistic models describing the annealing phase with kinetic theory offer the most potential for accurate interpretation of qPCR data. Even so, they have not been thoroughly investigated and are rarely used for interpretation of qPCR data. New results for kinetic modeling of qPCR are presented. Two models are presented in which the efficiency of amplification is based on equilibrium solutions for the annealing phase of the qPCR process. Model 1 assumes annealing of complementary targets strands and annealing of target and primers are both reversible reactions and reach a dynamic equilibrium. Model 2 assumes all annealing reactions are nonreversible and equilibrium is static. Both models include the effect of primer concentration during the annealing phase. Analytic formulae are given for the equilibrium values of all single and double stranded molecules at the end of the annealing step. The equilibrium values are then used in a stepwise method to describe the whole qPCR process. Rate constants of kinetic models are the same for solutions that are identical except for possibly having different initial target concentrations. Analysis of qPCR curves from such solutions are thus analyzed by simultaneous non-linear curve fitting with the same rate constant values applying to all curves and each curve having a unique value for initial target concentration. The models were fit to two data sets for which the true initial target concentrations are known. Both models give better fit to observed qPCR data than other kinetic models present in the literature. They also give better estimates of initial target concentration. Model 1 was found to be slightly more robust than model 2 giving better estimates of initial target concentration when estimation of parameters was done for qPCR curves with very different initial target concentration. Both models may be used to estimate the initial absolute concentration of target sequence when a standard curve is not available. It is argued that the kinetic approach to modeling and interpreting quantitative PCR data has the potential to give more precise estimates of the true initial target concentrations than other methods currently used for analysis of qPCR data. The two models presented here give a unified model of the qPCR process in that they explain the shape of the qPCR curve for a wide variety of initial target concentrations.

Chlorotoxin-Conjugated Multifunctional Dendrimers Labeled with Radionuclide 131I for Single Photon Emission Computed Tomography Imaging and Radiotherapy of Gliomas.

PubMed

Zhao, Lingzhou; Zhu, Jingyi; Cheng, Yongjun; Xiong, Zhijuan; Tang, Yueqin; Guo, Lilei; Shi, Xiangyang; Zhao, Jinhua

2015-09-09

Chlorotoxin-conjugated multifunctional dendrimers labeled with radionuclide 131I were synthesized and utilized for targeted single photon emission computed tomography (SPECT) imaging and radiotherapy of cancer. In this study, generation five amine-terminated poly(amidoamine) dendrimers were used as a platform to be sequentially conjugated with polyethylene glycol (PEG), targeting agent chlorotoxin (CTX), and 3-(4'-hydroxyphenyl)propionic acid-OSu (HPAO). This was followed by acetylation of the remaining dendrimer terminal amines and radiolabeling with 131I to form the targeted theranostic dendrimeric nanoplatform. We show that the dendrimer platform possessing approximately 7.7 CTX and 21.1 HPAO moieties on each dendrimer displays excellent cytocompatibility in a given concentration range (0-20 μM) and can specifically target cancer cells overexpressing matrix metallopeptidase 2 (MMP2) due to the attached CTX. With the attached HPAO moiety having the phenol group, the dendrimer platform can be effectively labeled with radioactive 131I with good stability and high radiochemical purity. Importantly, the 131I labeling renders the dendrimer platform with an ability to be used for targeted SPECT imaging and radiotherapy of an MMP2-overexpressing glioma model in vivo. The developed radiolabeled multifunctional dendrimeric nanoplatform may hold great promise to be used for targeted theranostics of human gliomas.

An Optical Biosensing Strategy Based on Selective Light Absorption and Wavelength Filtering from Chromogenic Reaction

PubMed Central

Chun, Hyeong Jin; Han, Yong Duk; Park, Yoo Min; Kim, Ka Ram; Lee, Seok Jae

2018-01-01

To overcome the time and space constraints in disease diagnosis via the biosensing approach, we developed a new signal-transducing strategy that can be applied to colorimetric optical biosensors. Our study is focused on implementation of a signal transduction technology that can directly translate the color intensity signals—that require complicated optical equipment for the analysis—into signals that can be easily counted with the naked eye. Based on the selective light absorption and wavelength-filtering principles, our new optical signaling transducer was built from a common computer monitor and a smartphone. In this signal transducer, the liquid crystal display (LCD) panel of the computer monitor served as a light source and a signal guide generator. In addition, the smartphone was used as an optical receiver and signal display. As a biorecognition layer, a transparent and soft material-based biosensing channel was employed generating blue output via a target-specific bienzymatic chromogenic reaction. Using graphics editor software, we displayed the optical signal guide patterns containing multiple polygons (a triangle, circle, pentagon, heptagon, and 3/4 circle, each associated with a specified color ratio) on the LCD monitor panel. During observation of signal guide patterns displayed on the LCD monitor panel using a smartphone camera via the target analyte-loaded biosensing channel as a color-filtering layer, the number of observed polygons changed according to the concentration of the target analyte via the spectral correlation between absorbance changes in a solution of the biosensing channel and color emission properties of each type of polygon. By simple counting of the changes in the number of polygons registered by the smartphone camera, we could efficiently measure the concentration of a target analyte in a sample without complicated and expensive optical instruments. In a demonstration test on glucose as a model analyte, we could easily measure the concentration of glucose in the range from 0 to 10 mM. PMID:29509682

An Optical Biosensing Strategy Based on Selective Light Absorption and Wavelength Filtering from Chromogenic Reaction.

PubMed

Chun, Hyeong Jin; Han, Yong Duk; Park, Yoo Min; Kim, Ka Ram; Lee, Seok Jae; Yoon, Hyun C

2018-03-06

To overcome the time and space constraints in disease diagnosis via the biosensing approach, we developed a new signal-transducing strategy that can be applied to colorimetric optical biosensors. Our study is focused on implementation of a signal transduction technology that can directly translate the color intensity signals-that require complicated optical equipment for the analysis-into signals that can be easily counted with the naked eye. Based on the selective light absorption and wavelength-filtering principles, our new optical signaling transducer was built from a common computer monitor and a smartphone. In this signal transducer, the liquid crystal display (LCD) panel of the computer monitor served as a light source and a signal guide generator. In addition, the smartphone was used as an optical receiver and signal display. As a biorecognition layer, a transparent and soft material-based biosensing channel was employed generating blue output via a target-specific bienzymatic chromogenic reaction. Using graphics editor software, we displayed the optical signal guide patterns containing multiple polygons (a triangle, circle, pentagon, heptagon, and 3/4 circle, each associated with a specified color ratio) on the LCD monitor panel. During observation of signal guide patterns displayed on the LCD monitor panel using a smartphone camera via the target analyte-loaded biosensing channel as a color-filtering layer, the number of observed polygons changed according to the concentration of the target analyte via the spectral correlation between absorbance changes in a solution of the biosensing channel and color emission properties of each type of polygon. By simple counting of the changes in the number of polygons registered by the smartphone camera, we could efficiently measure the concentration of a target analyte in a sample without complicated and expensive optical instruments. In a demonstration test on glucose as a model analyte, we could easily measure the concentration of glucose in the range from 0 to 10 mM.

Monitoring the clean-up operation of agricultural fields flooded with red mud in Hungary.

PubMed

Uzinger, Nikolett; Rékási, Márk; Anton, Áron D; Koós, Sándor; László, Péter; Anton, Attila

2016-12-01

In the course of the clean-up operation after the red mud inundation in 2010, red mud was removed from the soil surface in places where the layer was more than 5 cm deep. Before its removal, the red mud seeped into the soil. In 2012, soil samples were taken from depths of 0 to 20 and 20 to 40 cm on some of the affected areas. The parameters investigated were pH, organic matter, salt%, and the total and mobile fractions of various elements. The values recorded in 2012 were compared with those measured immediately after the removal of the red mud in 2010 and with the background and clean-up target concentrations. The pH values remained below the designated limit, while the salt content only exhibited values in the weakly salty range on areas at the greatest distance from the dam. In the central part of the inundated area, total Na contents above the 900 mg/kg target value were observed, but the Na content in the 0-20-cm layer generally exhibited a decrease due to leaching. The pH and As concentration also showed a decline on several areas compared with the values recorded in 2010. Total As and Co contents in excess of the target values were recorded on the lowest-lying part of the flooded area, probably because the finest red mud particles were deposited the furthest from the dam, where they seeped into the soil. Nevertheless, the mobility and plant availability of both elements remained moderate. The total contents of both Co and Mo, however, exhibited a significant rise compared with both the background value and the 2010 data. The monitoring of the cleaned-up areas showed that after a 2-year period element concentrations that exceeded the target values and could be attributed to the red mud pollution were only detectable on the lowest-lying areas.

The impact of intermittent versus continuous exposure to EGFR tyrosine kinase inhibitor on selection of EGFR T790M-mutant drug-resistant clones in a lung cancer cell line carrying activating EGFR mutation

PubMed Central

Lee, Youngjoo; Choi, Yu-Ra; Kim, Kyoung-Yeon; Shin, Dong Hoon

2016-01-01

Drug-resistant cell lines are essential tools for investigating the mechanisms of resistance to molecular-targeted anti-cancer drugs. However, little is known about how to establish clinically relevant drug-resistant cell lines. Our study examined the impact of a drug-free period on the establishment of a cell line with clinically relevant resistance to molecular-targeted drugs. We used PC9 cells, a lung cancer cell line carrying EGFR mutation, because this is a validated target for EGFR tyrosine kinase inhibitors (TKI). PC9 cells were intermittently or continuously exposed to increasing concentrations of gefitinib (0.01 μM to 1.0 μM) and the emergence of the most common acquired resistance mutation in EGFR, T790M, was determined. T790M was detected at a 25-fold lower drug concentration in cells continuously exposed to gefitinib (PC9/GRc) than in cells intermittently exposed to gefitinib (PC9/GRi) (0.04 μM vs 1.0 μM, respectively). The mutation frequencies at those drug concentrations were 19.8% and 8.0% in PC9/GRc and PC9/GRi cells, respectively. After drug-free culture for 8 weeks, resistance to gefitinib decreased in the PC9/GRi cells but not in the PC9/GRc cells. In the PC9/GRc cells, the frequency of the T790M mutation was consistently about 20% from 0.04 μM to 1.0 μM of gefitinib. In the PC9/GRc cells, the T790M mutation was detected in all single-cell clones, at frequencies ranging from 7.0% to 37.0%, with a median of 19.5% (95% confidence interval, 17.3%–20.9%). In conclusion, compared with intermittent drug exposure, continuous exposure might select better minor drug-resistant clones when creating cell lines resistant to molecular-targeted drugs. PMID:27270313

The impact of intermittent versus continuous exposure to EGFR tyrosine kinase inhibitor on selection of EGFR T790M-mutant drug-resistant clones in a lung cancer cell line carrying activating EGFR mutation.

PubMed

Lee, Youngjoo; Choi, Yu-Ra; Kim, Kyoung-Yeon; Shin, Dong Hoon

2016-07-12

Drug-resistant cell lines are essential tools for investigating the mechanisms of resistance to molecular-targeted anti-cancer drugs. However, little is known about how to establish clinically relevant drug-resistant cell lines. Our study examined the impact of a drug-free period on the establishment of a cell line with clinically relevant resistance to molecular-targeted drugs. We used PC9 cells, a lung cancer cell line carrying EGFR mutation, because this is a validated target for EGFR tyrosine kinase inhibitors (TKI). PC9 cells were intermittently or continuously exposed to increasing concentrations of gefitinib (0.01 μM to 1.0 μM) and the emergence of the most common acquired resistance mutation in EGFR, T790M, was determined. T790M was detected at a 25-fold lower drug concentration in cells continuously exposed to gefitinib (PC9/GRc) than in cells intermittently exposed to gefitinib (PC9/GRi) (0.04 μM vs 1.0 μM, respectively). The mutation frequencies at those drug concentrations were 19.8% and 8.0% in PC9/GRc and PC9/GRi cells, respectively. After drug-free culture for 8 weeks, resistance to gefitinib decreased in the PC9/GRi cells but not in the PC9/GRc cells. In the PC9/GRc cells, the frequency of the T790M mutation was consistently about 20% from 0.04 μM to 1.0 μM of gefitinib. In the PC9/GRc cells, the T790M mutation was detected in all single-cell clones, at frequencies ranging from 7.0% to 37.0%, with a median of 19.5% (95% confidence interval, 17.3%-20.9%). In conclusion, compared with intermittent drug exposure, continuous exposure might select better minor drug-resistant clones when creating cell lines resistant to molecular-targeted drugs.

Prospective Evaluation of a Model-Based Dosing Regimen for Amikacin in Preterm and Term Neonates in Clinical Practice

PubMed Central

De Cock, R. F. W.; Allegaert, K.; Vanhaesebrouck, S.; Danhof, M.; Knibbe, C. A. J.

2015-01-01

Based on a previously derived population pharmacokinetic model, a novel neonatal amikacin dosing regimen was developed. The aim of the current study was to prospectively evaluate this dosing regimen. First, early (before and after second dose) therapeutic drug monitoring (TDM) observations were evaluated for achieving target trough (<3 mg/liter) and peak (>24 mg/liter) levels. Second, all observed TDM concentrations were compared with model-predicted concentrations, whereby the results of a normalized prediction distribution error (NPDE) were considered. Subsequently, Monte Carlo simulations were performed. Finally, remaining causes limiting amikacin predictability (i.e., prescription errors and disease characteristics of outliers) were explored. In 579 neonates (median birth body weight, 2,285 [range, 420 to 4,850] g; postnatal age 2 days [range, 1 to 30 days]; gestational age, 34 weeks [range, 24 to 41 weeks]), 90.5% of the observed early peak levels reached 24 mg/liter, and 60.2% of the trough levels were <3 mg/liter (93.4% ≤5 mg/liter). Observations were accurately predicted by the model without bias, which was confirmed by the NPDE. Monte Carlo simulations showed that peak concentrations of >24 mg/liter were reached at steady state in almost all patients. Trough values of <3 mg/liter at steady state were documented in 78% to 100% and 45% to 96% of simulated cases with and without ibuprofen coadministration, respectively; suboptimal trough levels were found in patients with postnatal age <14 days and current weight of >2,000 g. Prospective evaluation of a model-based neonatal amikacin dosing regimen resulted in optimized peak and trough concentrations in almost all patients. Slightly adapted dosing for patient subgroups with suboptimal trough levels was proposed. This model-based approach improves neonatal dosing individualization. PMID:26248375

Determination of acidic pharmaceuticals and potential endocrine disrupting compounds in wastewaters and spring waters by selective elution and analysis by gas chromatography-mass spectrometry.

PubMed

Gibson, Richard; Becerril-Bravo, Elías; Silva-Castro, Vanessa; Jiménez, Blanca

2007-10-26

Although the trend in development of analytical methods for emerging contaminants is towards reduced sample preparation and increased detector selectivity, there are still benefits from removal of matrix material during sample preparation. This paper describes a simple method for acidic pharmaceuticals and a range of potential endocrine disrupting compounds in untreated wastewaters and spring waters. It is based on separation of the two classes during elution from the extraction cartridge with final analysis by gas chromatography-mass spectrometry. 3,4-D was used as the recovery standard for the acids while 4-n-nonylphenol and [2H4]estrone were used for the endocrine disrupters; mean recoveries varied between 89% and 111%. The method was also extensively validated by fortification with the target compounds. Recoveries of acids were from 68% to 97% with relative standard deviations generally less than 10% and recoveries of endocrine disrupters were 68-109% with relative standard deviations less than 20%. Detection limits varied from 0.005 to 1 ng/L in spring water, and from 0.5 to 100 ng/L in untreated wastewater. Concentrations of the analytes in the wastewater ranged from 0.018 to 22.4 microg/L. Values were comparable to reported data, although concentrations were generally relatively high, probably because of a lack of treatment. Triclosan, phthalates, estrone, 17beta-estradiol, ibuprofen, and naproxen were present in the spring water from aquifers recharged indirectly with this wastewater after its use for irrigation; concentrations ranged from 0.01 to 25.0 ng/L. The much lower concentrations compared to wastewater indicate effective removal processes on passage through the soil and subsoil.

Warming caused by cumulative carbon emissions towards the trillionth tonne.

PubMed

Allen, Myles R; Frame, David J; Huntingford, Chris; Jones, Chris D; Lowe, Jason A; Meinshausen, Malte; Meinshausen, Nicolai

2009-04-30

Global efforts to mitigate climate change are guided by projections of future temperatures. But the eventual equilibrium global mean temperature associated with a given stabilization level of atmospheric greenhouse gas concentrations remains uncertain, complicating the setting of stabilization targets to avoid potentially dangerous levels of global warming. Similar problems apply to the carbon cycle: observations currently provide only a weak constraint on the response to future emissions. Here we use ensemble simulations of simple climate-carbon-cycle models constrained by observations and projections from more comprehensive models to simulate the temperature response to a broad range of carbon dioxide emission pathways. We find that the peak warming caused by a given cumulative carbon dioxide emission is better constrained than the warming response to a stabilization scenario. Furthermore, the relationship between cumulative emissions and peak warming is remarkably insensitive to the emission pathway (timing of emissions or peak emission rate). Hence policy targets based on limiting cumulative emissions of carbon dioxide are likely to be more robust to scientific uncertainty than emission-rate or concentration targets. Total anthropogenic emissions of one trillion tonnes of carbon (3.67 trillion tonnes of CO(2)), about half of which has already been emitted since industrialization began, results in a most likely peak carbon-dioxide-induced warming of 2 degrees C above pre-industrial temperatures, with a 5-95% confidence interval of 1.3-3.9 degrees C.

Ultrasensitive, real-time analysis of biomarkers in breath using tunable external cavity laser and off-axis cavity-enhanced absorption spectroscopy

NASA Astrophysics Data System (ADS)

Bayrakli, Ismail; Akman, Hatice

2015-03-01

A robust biomedical sensor for ultrasensitive detection of biomarkers in breath based on a tunable external cavity laser (ECL) and an off-axis cavity-enhanced absorption spectroscopy (OA-CEAS) using an amplitude stabilizer is developed. A single-mode, narrow-linewidth, tunable ECL is demonstrated. A broadly coarse wavelength tuning range of 720 cm-1 for the spectral range between 6890 and 6170 cm-1 is achieved by rotating the diffraction grating forming a Littrow-type external-cavity configuration. A mode-hop-free tuning range of 1.85 cm-1 is obtained. The linewidths below 140 kHz are recorded. The ECL is combined with an OA-CEAS to perform laser chemical sensing. Our system is able to detect any molecule in breath at concentrations to the ppbv range that have absorption lines in the spectral range between 1450 and 1620 nm. Ammonia is selected as target molecule to evaluate the performance of the sensor. Using the absorption line of ammonia at 6528.76 cm-1, a minimum detectable absorption coefficient of approximately 1×10-8 cm-1 is demonstrated for 256 averages. This is achieved for a 1.4-km absorption path length and a 2-s data-acquisition time. These results yield a detection sensitivity of approximately 8.6×10-10 cm-1 Hz-1/2. Ammonia in exhaled breath is analyzed and found in a concentration of 870 ppb for our example.

Ultrasensitive, real-time analysis of biomarkers in breath using tunable external cavity laser and off-axis cavity-enhanced absorption spectroscopy.

PubMed

Bayrakli, Ismail; Akman, Hatice

2015-03-01

A robust biomedical sensor for ultrasensitive detection of biomarkers in breath based on a tunable external cavity laser (ECL) and an off-axis cavity-enhanced absorption spectroscopy (OA-CEAS) using an amplitude stabilizer is developed. A single-mode, narrow-linewidth, tunable ECL is demonstrated. A broadly coarse wavelength tuning range of 720 cm⁻¹ for the spectral range between 6890 and 6170 cm⁻¹ is achieved by rotating the diffraction grating forming a Littrow-type external-cavity configuration. A mode-hop-free tuning range of 1.85 cm⁻¹ is obtained. The linewidths below 140 kHz are recorded. The ECL is combined with an OA-CEAS to perform laser chemical sensing. Our system is able to detect any molecule in breath at concentrations to the ppbv range that have absorption lines in the spectral range between 1450 and 1620 nm. Ammonia is selected as target molecule to evaluate the performance of the sensor. Using the absorption line of ammonia at 6528.76 cm⁻¹, a minimum detectable absorption coefficient of approximately 1×10⁻⁸ cm⁻¹ is demonstrated for 256 averages. This is achieved for a 1.4-km absorption path length and a 2-s data-acquisition time. These results yield a detection sensitivity of approximately 8.6×10⁻¹⁰ cm⁻¹ Hz(-1/2). Ammonia in exhaled breath is analyzed and found in a concentration of 870 ppb for our example.

Trace analysis of pesticides in paddy field water by direct injection using liquid chromatography-quadrupole-linear ion trap-mass spectrometry.

PubMed

Pareja, Lucía; Martínez-Bueno, M J; Cesio, Verónica; Heinzen, Horacio; Fernández-Alba, A R

2011-07-29

A multiresidue method was developed for the quantification and confirmation of 70 pesticides in paddy field water. After its filtration, water was injected directly in a liquid chromatograph coupled to a hybrid triple quadrupole-linear ion trap-mass spectrometer (QqLIT). The list of target analytes included organophosphates, phenylureas, sulfonylureas, carbamates, conazoles, imidazolinones and others compounds widely used in different countries where rice is cropped. Detection and quantification limits achieved were in the range from 0.4 to 80 ng L(-1) and from 2 to 150 ng L(-1), respectively. Correlation coefficients for the calibration curves in the range 0.1-50 μg L(-1) were higher than 0.99 except for diazinon (0.1-25 μg L(-1)). Only 9 pesticides presented more than 20% of signal suppression/enhancement, no matrix effect was observed in the studied conditions for the rest of the target pesticides. The method developed was used to investigate the occurrence of pesticides in 59 water samples collected in paddy fields located in Spain and Uruguay. The study shows the presence of bensulfuron methyl, tricyclazole, carbendazim, imidacloprid, tebuconazole and quinclorac in a concentration range from 0.08 to 7.20 μg L(-1). Copyright © 2011 Elsevier B.V. All rights reserved.

Variable Linezolid Exposure in Intensive Care Unit Patients-Possible Role of Drug-Drug Interactions.

PubMed

Töpper, Christoph; Steinbach, Cathérine L; Dorn, Christoph; Kratzer, Alexander; Wicha, Sebastian G; Schleibinger, Michael; Liebchen, Uwe; Kees, Frieder; Salzberger, Bernd; Kees, Martin G

2016-10-01

Standard doses of linezolid may not be suitable for all patient groups. Intensive care unit (ICU) patients in particular may be at risk of inadequate concentrations. This study investigated variability of drug exposure and its potential sources in this population. Plasma concentrations of linezolid were determined by high-performance liquid chromatography in a convenience sample of 20 ICU patients treated with intravenous linezolid 600 mg twice daily. Ultrafiltration applying physiological conditions (pH 7.4/37°C) was used to determine the unbound fraction. Individual pharmacokinetic (PK) parameters were estimated by population PK modeling. As measures of exposure to linezolid, area under the concentration-time curve (AUC) and trough concentrations (Cmin) were calculated and compared with published therapeutic ranges (AUC 200-400 mg*h/L, Cmin 2-10 mg/L). Coadministered inhibitors or inducers of cytochrome P450 and/or P-glycoprotein were noted. Data from 18 patients were included into the PK evaluation. Drug exposure was highly variable (median, range: AUC 185, 48-618 mg*h/L, calculated Cmin 2.92, 0.0062-18.9 mg/L), and only a minority of patients had values within the target ranges (6 and 7, respectively). AUC and Cmin were linearly correlated (R = 0.98), and classification of patients (underexposed/within therapeutic range/overexposed) according to AUC or Cmin was concordant in 15 cases. Coadministration of inhibitors was associated with a trend to higher drug exposure, whereas 3 patients treated with levothyroxine showed exceedingly low drug exposure (AUC ∼60 mg*h/L, Cmin <0.4 mg/L). The median unbound fraction in all 20 patients was 90.9%. Drug exposure after standard doses of linezolid is highly variable and difficult to predict in ICU patients, and therapeutic drug monitoring seems advisable. PK drug-drug interactions might partly be responsible and should be further investigated; protein binding appears to be stable and irrelevant.

SU-F-T-361: Dose Enhancement Due to Nanoparticle Addition in Skin Radiotherapy: A Monte Carlo Study Using Kilovoltage Photon Beams

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

Zheng, X; Chow, J

Purpose: This study investigated the dose enhancement due to addition of nanoparticles with different types and concentrations in skin radiotherapy using kilovoltage photon beams. Methods: An inhomogeneous water phantom (15×15×10 cm{sup 3}) having the skin target layer (0.5–5 mm), added with different concentrations (3–40 mg/ml) of nanoparticles (Au, Pt, I, Ag and Fe{sub 2}O{sub 3}), was irradiated by the 105 and 220 kVp photon beams produced by a Gulmay D3225 Orthovoltage unit. The circular cone of 5-cm diameter and source-to-surface distance of 20 cm were used. Doses in the skin target layer with and without adding the nanoparticles were calculatedmore » using Monte Carlo simulation (the EGSnrc code) through the macroscopic approach. Dose enhancement ratio (DER), defined as the ratio of dose at the target with nanoparticle addition to the dose without addition, was calculated for each type and concentration of nanoparticle in different target thickness. Results: For Au nanoparticle, DER dependence on target thickness for the 220 kVp photon beams was not significant. However, DER for Au nanoparticle was found decreasing with an increase of target thickness when the nanoparticle concentration was increased from 18 to 40 mg/ml using the 105 kVp photon beams. For nanoparticle concentration of 40 mg/ml, DER variation with target thickness was not significant for the 220 kVp photon beams, but DEF was found decreasing with the target thickness when lower energy of photon beam (105 kVp) was used. DEF was found increasing with an increase of nanoparticle concentration. The higher the DEF increasing rate, the higher the atomic number of the nanoparticle except I and Ag for the same target thickness. Conclusion: It is concluded that nanoparticle addition can result in dose enhancement in kilovoltage skin radiotherapy. Moreover, the DER is related to the photon beam energy, target thickness, atomic number and concentration of nanoparticles.« less

Determining the release of radionuclides from tank waste residual solids. FY2015 report

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

King, William D.; Hobbs, David T.

Methodology development for pore water leaching studies has been continued to support Savannah River Site High Level Waste tank closure efforts. For FY2015, the primary goal of this testing was the achievement of target pH and Eh values for pore water solutions representative of local groundwater in the presence of grout or grout-representative (CaCO 3 or FeS) solids as well as waste surrogate solids representative of residual solids expected to be present in a closed tank. For oxidizing conditions representative of a closed tank after aging, a focus was placed on using solid phases believed to be controlling pH andmore » E h at equilibrium conditions. For three pore water conditions (shown below), the target pH values were achieved to within 0.5 pH units. Tank 18 residual surrogate solids leaching studies were conducted over an E h range of approximately 630 mV. Significantly higher Eh values were achieved for the oxidizing conditions (ORII and ORIII) than were previously observed. For the ORII condition, the target Eh value was nearly achieved (within 50 mV). However, E h values observed for the ORIII condition were approximately 160 mV less positive than the target. E h values observed for the RRII condition were approximately 370 mV less negative than the target. Achievement of more positive and more negative E h values is believed to require the addition of non-representative oxidants and reductants, respectively. Plutonium and uranium concentrations measured during Tank 18 residual surrogate solids leaching studies under these conditions (shown below) followed the general trends predicted for plutonium and uranium oxide phases, assuming equilibrium with dissolved oxygen. The highest plutonium and uranium concentrations were observed for the ORIII condition and the lowest concentrations were observed for the RRII condition. Based on these results, it is recommended that these test methodologies be used to conduct leaching studies with actual Tank 18 residual solids material. Actual waste testing will include leaching evaluations of technetium and neptunium, as well as plutonium and uranium.« less

Proximity fuze

DOEpatents

Harrison, T.R.

1987-07-10

A proximity fuze system includes an optical ranging apparatus, a detonation circuit controlled by the optical ranging apparatus, and an explosive charge detonated by the detonation circuit. The optical ranging apparatus includes a pulsed laser light source for generating target ranging light pulses and optical reference light pulses. A single lens directs ranging pulses to a target and collects reflected light from the target. An optical fiber bundle is used for delaying the optical reference pulses to correspond to a predetermined distance from the target. The optical ranging apparatus includes circuitry for providing a first signal depending upon the light pulses reflected from the target, a second signal depending upon the light pulses from the optical delay fiber bundle, and an output signal when the first and second signals coincide with each other. The output signal occurs when the distance from the target is equal to the predetermined distance from the target. Additional circuitry distinguishes pulses reflected from the target from background solar radiation. 3 figs.

Resolution verification targets for airborne and spaceborne imaging systems at the Stennis Space Center

NASA Astrophysics Data System (ADS)

McKellip, Rodney; Yuan, Ding; Graham, William; Holland, Donald E.; Stone, David; Walser, William E.; Mao, Chengye

1997-06-01

The number of available spaceborne and airborne systems will dramatically increase over the next few years. A common systematic approach toward verification of these systems will become important for comparing the systems' operational performance. The Commercial Remote Sensing Program at the John C. Stennis Space Center (SSC) in Mississippi has developed design requirements for a remote sensing verification target range to provide a means to evaluate spatial, spectral, and radiometric performance of optical digital remote sensing systems. The verification target range consists of spatial, spectral, and radiometric targets painted on a 150- by 150-meter concrete pad located at SSC. The design criteria for this target range are based upon work over a smaller, prototypical target range at SSC during 1996. This paper outlines the purpose and design of the verification target range based upon an understanding of the systems to be evaluated as well as data analysis results from the prototypical target range.

Proximity fuze

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

Harrison, T.R.

1987-07-10

A proximity fuze system includes an optical ranging apparatus, a detonation circuit controlled by the optical ranging apparatus, and an explosive charge detonated by the detonation circuit. The optical ranging apparatus includes a pulsed laser light source for generating target ranging light pulses and optical reference light pulses. A single lens directs ranging pulses to a target and collects reflected light from the target. An optical fiber bundle is used for delaying the optical reference pulses to correspond to a predetermined distance from the target. The optical ranging apparatus includes circuitry for providing a first signal depending upon the lightmore » pulses reflected from the target, a second signal depending upon the light pulses from the optical delay fiber bundle, and an output signal when the first and second signals coincide with each other. The output signal occurs when the distance from the target is equal to the predetermined distance from the target. Additional circuitry distinguishes pulses reflected from the target from background solar radiation. 3 figs.« less

Proximity fuze

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

Harrison, T.R.

1989-08-22

A proximity fuze system is described. It includes an optical ranging apparatus, a detonation circuit controlled by the optical ranging apparatus, and an explosive charge detonated by the detonation circuit. The optical ranging apparatus includes a pulsed laser light source for generating target ranging light pulses and optical reference light pulses. A single lens directs ranging pulses to a target and collects reflected light from the target. An optical fiber bundle is used for delaying the optical reference pulses to correspond to a predetermined distance from the target. The optical ranging apparatus includes circuitry for providing a first signal dependingmore » upon the light pulses reflected from the target, a second signal depending upon the light pulses from the optical delay fiber bundle, and an output signal when the first and second signals coincide with each other. The output signal occurs when the distance from the target is equal to the predetermined distance from the target. Additional circuitry distinguishes pulses reflected from the target from background solar radiation.« less

Environmental contamination of ready meals by polychlorinated biphenyls (PCBs).

PubMed

Adenugba, Adeola A; McMartin, Dena W; Beck, Angus

2012-01-01

The level of polychlorinated biphenyls (PCBs) contamination in ready meals was investigated to determine exposure compared to other foodstuffs. Chilled ready meals from nine categories (ambient, Chinese, Indian, Traditional UK, Italian, American Tex-Mex, Vegetarian and Organic), and three samples within each category were Soxhlet extracted in triplicate with hexane for 24 h, followed by a clean-up on deactivated silica gel. The cleaned extracts were concentrated to 1 ml under N(2) gas and analyzed on gas chromatography mass spectrometry (GC-MS) for 7 target PCBs (congeners 28, 52, 101, 118, 153, 138, and 180). Individual congener concentrations ranged from non-detectable to 0.40 ng g(-1) (wet weight). The cumulative concentration of all congeners (ΣPCBs) ranged between 0.20 and 1.00 ng g(-1) (wet weight). These values translate into exposure levels of less than 1 μg kg(-1)day(-1) for reference men and women of 70 and 57 kg, respectively. This preliminary study demonstrates that ready meals, like many other foods, are contaminated by PCBs and may represent an important route of human exposure given contemporary changes in consumer food choice. Even though low levels of contamination were observed, long-term exposure for population groups consuming a high volume of ready meals may have cause for concern regarding chronic health risks.

An assessment of the concentrations of pharmaceutical compounds in wastewater treatment plants on the island of Gran Canaria (Spain).

PubMed

Guedes-Alonso, Rayco; Afonso-Olivares, Cristina; Montesdeoca-Esponda, Sarah; Sosa-Ferrera, Zoraida; Santana-Rodríguez, José Juan

2013-12-01

An assessment of the concentrations of thirteen different therapeutic pharmaceutical compounds was conducted on water samples obtained from different wastewater treatment plants (WWTPs) using solid phase extraction and high- and ultra-high-performance liquid chromatography with mass spectrometry detection (HPLC-MS/MS and UHPLC-MS/MS), was carried out. The target compounds included ketoprofen and naproxen (anti-inflammatories), bezafibrate (lipid-regulating), carbamazepine (anticonvulsant), metamizole (analgesic), atenolol (β-blocker), paraxanthine (stimulant), fluoxetine (antidepressant), and levofloxacin, norfloxacin, ciprofloxacin, enrofloxacin and sarafloxacin (fluoroquinolone antibiotics). The relative standard deviations obtained in method were below 11%, while the detection and quantification limits were in the range of 0.3 - 97.4 ng·L(-1) and 1.1 - 324.7 ng·L(-1), respectively. The water samples were collected from two different WWTPs located on the island of Gran Canaria in Spain over a period of one year. The first WWTP (denoted as WWTP1) used conventional activated sludge for the treatment of wastewater, while the other plant (WWTP2) employed a membrane bioreactor system for wastewater treatment. Most of the pharmaceutical compounds detected in this study during the sampling periods were found to have concentrations ranging between 0.02 and 34.81 μg·L(-1).

Long-term monitoring of persistent organic pollutants (POPs) at the Norwegian Troll station in Dronning Maud Land, Antarctica

NASA Astrophysics Data System (ADS)

Kallenborn, R.; Breivik, K.; Eckhardt, S.; Lunder, C. R.; Manø, S.; Schlabach, M.; Stohl, A.

2013-07-01

A first long-term monitoring of selected persistent organic pollutants (POPs) in Antarctic air has been conducted at the Norwegian research station Troll (Dronning Maud Land). As target contaminants 32 PCB congeners, α- and γ-hexachlorocyclohexane (HCH), trans- and cis-chlordane, trans- and cis-nonachlor, p,p'- and o,p-DDT, DDD, DDE as well as hexachlorobenzene (HCB) were selected. The monitoring program with weekly samples taken during the period 2007-2010 was coordinated with the parallel program at the Norwegian Arctic monitoring site (Zeppelin mountain, Ny-Ålesund, Svalbard) in terms of priority compounds, sampling schedule as well as analytical methods. The POP concentration levels found in Antarctica were considerably lower than Arctic atmospheric background concentrations. Similar to observations for Arctic samples, HCB is the predominant POP compound, with levels of around 22 pg m-3 throughout the entire monitoring period. In general, the following concentration distribution was found for the Troll samples analyzed: HCB > Sum HCH > Sum PCB > Sum DDT > Sum chlordanes. Atmospheric long-range transport was identified as a major contamination source for POPs in Antarctic environments. Several long-range transport events with elevated levels of pesticides and/or compounds with industrial sources were identified based on retroplume calculations with a Lagrangian particle dispersion model (FLEXPART).

Confirmation of a meteoritic component in impact-melt rocks of the Chesapeake Bay impact structure, Virginia, USA - Evidence from osmium isotopic and PGE systematics

USGS Publications Warehouse

Lee, S.R.; Horton, J. Wright; Walker, R.J.

2006-01-01

The osmium isotope ratios and platinum-group element (PGE) concentrations of impact-melt rocks in the Chesapeake Bay impact structure were determined. The impact-melt rocks come from the cored part of a lower-crater section of suevitic crystalline-clast breccia in an 823 m scientific test hole over the central uplift at Cape Charles, Virginia. The 187Os/188Os ratios of impact-melt rocks range from 0.151 to 0.518. The rhenium and platinum-group element (PGE) concentrations of these rocks are 30-270?? higher than concentrations in basement gneiss, and together with the osmium isotopes indicate a substantial meteoritic component in some impact-melt rocks. Because the PGE abundances in the impact-melt rocks are dominated by the target materials, interelemental ratios of the impact-melt rocks are highly variable and nonchondritic. The chemical nature of the projectile for the Chesapeake Bay impact structure cannot be constrained at this time. Model mixing calculations between chondritic and crustal components suggest that most impact-melt rocks include a bulk meteoritic component of 0.01-0.1% by mass. Several impact-melt rocks with lowest initial 187Os/188Os ratios and the highest osmium concentrations could have been produced by additions of 0.1%-0.2% of a meteoritic component. In these samples, as much as 70% of the total Os may be of meteoritic origin. At the calculated proportions of a meteoritic component (0.01-0.1% by mass), no mixtures of the investigated target rocks and sediments can reproduce the observed PGE abundances of the impact-melt rocks, suggesting that other PGE enrichment processes operated along with the meteoritic contamination. Possible explanations are 1) participation of unsampled target materials with high PGE abundances in the impact-melt rocks, and 2) variable fractionations of PGE during syn- to post-impact events. ?? The Meteoritical Society, 2006.

Bi-spectral index, entropy and predicted plasma propofol concentrations with target controlled infusions in Indian patients.

PubMed

Puri, Goverdhan D; Mathew, Preethy J; Sethu Madhavan, J; Hegde, Harihar V; Fiehn, Andreas

2011-10-01

Many processed electroencephalographic signals are used now to help the anaesthesiologist titrate the depth of sedation. We investigated the relationship between target plasma propofol concentration and objective end-points of sedation- Bispectral Index (BIS), State Entropy (SE) and Response Entropy (RE)-at clinical end-points as assessed by Modified Observer Assessment of Alertness/sedation Scale (MOAAS) in Indian patients. Eighteen ASA 1 and 2 Indian adult patients scheduled to undergo elective surgery were included. The target control infusion (TCI) of propofol was administered using 'Diprifusor'. The level of sedation was assessed using MOAAS by the anaesthesiologist. BIS, SE, RE were recorded throughout. TCI was started at 0.5 μg/ml and increased by 0.5 μg/ml every 6 min till MOAAS scores reached 0 or there was sustained BIS value less than 30. The EC(50) and EC(95) of predicted plasma propofol concentration for loss of consciousness (assessed by loss of response to verbal command), were 2.3 and 2.8 μg/ml respectively and for loss of response to painful stimuli (trapezius squeeze) were 4.0 and 5.0 μg/ml respectively. The BIS and entropy values (EC(50) and EC(95)) for loss of consciousness and response to painful stimuli in Indian patients were estimated. The preliminary relation of target plasma propofol concentration with BIS was found to be BIS = 100.5-16.4 × (Target concentration). The target plasma propofol concentrations required to produce unconsciousness and loss of response to painful stimuli in Indian patients have been estimated. Also, the relations between target plasma concentration and objective measures of different levels of anaesthesia have been established.

Design, synthesis and evaluation of novel 2,5,6-trisubstituted benzimidazoles targeting FtsZ as antitubercular agents.

PubMed

Park, Bora; Awasthi, Divya; Chowdhury, Soumya R; Melief, Eduard H; Kumar, Kunal; Knudson, Susan E; Slayden, Richard A; Ojima, Iwao

2014-05-01

Filamenting temperature-sensitive protein Z (FtsZ), an essential cell division protein, is a promising target for the drug discovery of new-generation antibacterial agents against various bacterial pathogens. As a part of SAR studies on benzimidazoles, we have synthesized a library of 376 novel 2,5,6-trisubstituted benzimidazoles, bearing ether or thioether linkage at the 6-position. In a preliminary HTP screening against Mtb H37Rv, 108 compounds were identified as hits at a cut off concentration of 5 μg/mL. Among those hits, 10 compounds exhibited MIC values in the range of 0.63-12.5 μg/mL. Light scattering assay and TEM analysis with the most potent compound 5a clearly indicate that its molecular target is Mtb-FtsZ. Also, the Kd of 5a with Mtb-FtsZ was determined to be 1.32 μM. Copyright © 2014 Elsevier Ltd. All rights reserved.

Towards Discovery and Targeted Peptide Biomarker Detection Using nanoESI-TIMS-TOF MS

NASA Astrophysics Data System (ADS)

Garabedian, Alyssa; Benigni, Paolo; Ramirez, Cesar E.; Baker, Erin S.; Liu, Tao; Smith, Richard D.; Fernandez-Lima, Francisco

2018-05-01

In the present work, the potential of trapped ion mobility spectrometry coupled to TOF mass spectrometry (TIMS-TOF MS) for discovery and targeted monitoring of peptide biomarkers from human-in-mouse xenograft tumor tissue was evaluated. In particular, a TIMS-MS workflow was developed for the detection and quantification of peptide biomarkers using internal heavy analogs, taking advantage of the high mobility resolution (R = 150-250) prior to mass analysis. Five peptide biomarkers were separated, identified, and quantified using offline nanoESI-TIMS-CID-TOF MS; the results were in good agreement with measurements using a traditional LC-ESI-MS/MS proteomics workflow. The TIMS-TOF MS analysis permitted peptide biomarker detection based on accurate mobility, mass measurements, and high sequence coverage for concentrations in the 10-200 nM range, while simultaneously achieving discovery measurements of not initially targeted peptides as markers from the same proteins and, eventually, other proteins. [Figure not available: see fulltext.

High sensitivity gas sensor based on high-Q suspended polymer photonic crystal nanocavity

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

Clevenson, Hannah, E-mail: hannahac@mit.edu; Desjardins, Pierre; Gan, Xuetao

2014-06-16

We present high-sensitivity, multi-use optical gas sensors based on a one-dimensional photonic crystal cavity. These devices are implemented in versatile, flexible polymer materials which swell when in contact with a target gas, causing a measurable cavity length change. This change causes a shift in the cavity resonance, allowing precision measurements of gas concentration. We demonstrate suspended polymer nanocavity sensors and the recovery of sensors after the removal of stimulant gas from the system. With a measured quality factor exceeding 10{sup 4}, we show measurements of gas concentration as low as 600 parts per million (ppm) and an experimental sensitivity ofmore » 10 ppm; furthermore, we predict detection levels in the parts-per-billion range for a variety of gases.« less

Magnetoresistive DNA chips based on ac field focusing of magnetic labels

NASA Astrophysics Data System (ADS)

Ferreira, H. A.; Cardoso, F. A.; Ferreira, R.; Cardoso, S.; Freitas, P. P.

2006-04-01

A study was made on the sensitivity of a magnetoresistive DNA-chip platform being developed for cystic fibrosis diagnostics. The chip, comprised of an array of 2.5×80 μm2 U-shaped spin-valve sensors integrated within current line structures for magnetic label manipulation, enabled the detection at 30 Hz of 250 nm magnetic nanoparticles from 100 pM down to the pM range (or a target DNA concentration of 500 pM). It was observed that the sensor response increased linearly with label concentration. Noise spectra obtained for these sensors showed a thermal noise of 10-17 V2/Hz with a 1/f knee at 50 kHz at a 1 mA sense current, showing that lower detection limits are possible.

Past, present and future concentrations of ground-level ozone and potential impacts on ecosystems and human health in northern Europe.

PubMed

Karlsson, Per Erik; Klingberg, Jenny; Engardt, Magnuz; Andersson, Camilla; Langner, Joakim; Karlsson, Gunilla Pihl; Pleijel, Håkan

2017-01-15

This review summarizes new information on the current status of ground-level ozone in Europe north of the Alps. There has been a re-distribution in the hourly ozone concentrations in northern Europe during 1990-2015. The highest concentrations during summer daytime hours have decreased while the summer night-time and winter day- and night-time concentrations have increased. The yearly maximum 8-h mean concentrations ([O 3 ] 8h,max ), a metric used to assess ozone impacts on human health, have decreased significantly during 1990-2015 at four out of eight studied sites in Fennoscandia and northern UK. Also the annual number of days when the yearly [O 3 ] 8h,max exceeded the EU Environmental Quality Standard (EQS) target value of 60ppb has decreased. In contrast, the number of days per year when the yearly [O 3 ] 8h,max exceeded 35ppb has increased significantly at two sites, while it decreased at one far northern site. [O 3 ] 8h,max is predicted not to exceed 60ppb in northern UK and Fennoscandia after 2020. However, the WHO EQS target value of 50ppb will still be exceeded. The AOT40 May-July and AOT40 April-September metrics, used for the protection of vegetation, have decreased significantly at three and four sites, respectively. The EQS for the protection of forests, AOT40 April-September 5000ppbh, is projected to no longer be exceeded for most of northern Europe sometime before the time period 2040-2059. However, if the EQS is based on Phytotoxic Ozone Dose (POD), POD 1 , it may still be exceeded by 2050. The increasing trend for low and medium range ozone concentrations in combination with a decrease in high concentrations indicate that a new control strategy, with a larger geographical scale than Europe and including methane, is needed for ozone abatement in northern Europe. Copyright © 2016 Elsevier B.V. All rights reserved.

Detection and identification of plasma progesterone metabolites in the female Florida manatee (Trichechus manatus latirostris) using GC/MS/MS.

PubMed

Tripp, K M; Dubois, M; Delahaut, P; Verstegen, J P

2009-08-01

Florida manatees (Trichechus manatus latirostris) have relatively low peripheral concentrations of progesterone (P4). The objective of this study was to determine if these relatively low P4 concentrations are associated with a high ratio of progestin metabolites and to document metabolite concentrations from individual blood samples obtained from manatees during diestrus or pregnancy. Metabolites known to exist in elephants-terrestrial manatee relatives-were targeted. These included 5alpha-reduced progestins (5alpha-pregnane-3,20-dione [5alpha-DHP] and 3alpha-hydroxy-5alpha-pregnan-20-one [5alpha-P3-OH]) and 17alpha-hydroxyprogesterone (17alpha-OHP), which occurs in Asian elephants. An additional, inactive metabolite, 20alpha-hydroxyprogesterone (20alpha-OHP), indicative of P4 overproduction, was also targeted. Progesterone itself was the predominant progestin detected in pregnant and nonpregnant manatee plasma (n = 10) using gas chromatography-mass spectrometry with tandem quadrupole detectors (GC/MS/MS). Progesterone concentrations in pregnant females varied from early (moderate to high) through mid and late (low) pregnancy. Progesterone concentrations ranged from low to high in nonpregnant, nonlactating females. The most commonly detected metabolite was 5alpha-P3-OH (n = 7), which occurred in pregnant (lower limit of detection [LLOD] to high) and nonpregnant (trace to high) females. The 5alpha-DHP metabolite was also detected in pregnant (LLOD to moderate) and nonpregnant (low) females. The 17alpha-OHP metabolite was not detected in any tested female. The 20alpha-OHP metabolite was detected in one nonpregnant, nonlactating, captive female (LLOD). Metabolites were most prevalent during early pregnancy, concurrent with maximum P4 concentrations. Based on their concentrations in peripheral circulation, we inferred that these metabolites may have, opposite to elephants, a limited physiologic role during luteal, pregnant, and nonpregnant phases in the manatee.

Ground-water-quality assessment of the Central Oklahoma aquifer, Oklahoma; hydrologic, water-quality, and quality-assurance data 1987-90

USGS Publications Warehouse

Ferree, D.M.; Christenson, S.C.; Rea, A.H.; Mesander, B.A.

1992-01-01

This report presents data collected from 202 wells between June 1987 and September 1990 as part of the Central Oklahoma aquifer pilot study of the National Water-Quality Assessment Program. The report describes the sampling networks, the sampling procedures, and the results of the ground-water quality and quality-assurance sample analyses. The data tables consist of information about the wells sampled and the results of the chemical analyses of ground water and quality-assurance sampling. Chemical analyses of ground-water samples in four sampling networks are presented: A geochemical network, a low-density survey bedrock network, a low-density survey alluvium and terrace deposits network, and a targeted urban network. The analyses generally included physical properties, major ions, nutrients, trace substances, radionuclides, and organic constituents. The chemical analyses of the ground-water samples are presented in five tables: (1) Physical properties and concentrations of major ions, nutrients, and trace substances; (2) concentrations of radionuclides and radioactivities; (3) carbon isotope ratios and delta values (d-values) of selected isotopes; (4) concentrations of organic constituents; and (5) organic constituents not reported in ground-water samples. The quality of the ground water sampled varied substantially. The sum of constituents (dissolved solids) concentrations ranged from 71 to 5,610 milligrams per liter, with 38 percent of the wells sampled exceeding the Secondary Maximum Contaminant Level of 500 milligrams per liter established under the Safe Drinking Water Act. Values of pH ranged from 5.7 to 9.2 units with 20 percent of the wells outside the Secondary Maximum Contaminant Level of 6.5 to 8.5 units. Nitrite plus nitrate concentrations ranged from less than 0.1 to 85 milligrams per liter with 8 percent of the wells exceeding the proposed Maximum Contaminant Level of 10 milligrams per liter. Concentrations of trace substances were highly variable, ranging from below the reporting level to concentrations over the Maximum Contaminant Levels for several constituents (arsenic, barium, cadmium, chromium, lead, and selenium). Radionuclide activities also were highly variable. Gross alpha radioactivity ranged from 0.1 to 210 picocuries per liter as 230thorium. Of the wells sampled, 20 percent exceeded the proposed Maximum Contaminant Level of 15 picocuries per liter for gross alpha radioactivity. Organic constituents were detected in 39 percent of the 170 wells sampled for organic constituents; in most cases concentrations were at or near the laboratory minimum reporting levels. Ten of the wells sampled for organic constituents had one or more constituents (chlordane, dieldrin, heptachlor epoxide, trichloroethylene, 1,1-dichloroethylene, 1,1,1-trichloroethane) at concentrations equal to or greater than the Maximum Contaminant Level or acceptable concentrations as suggested in the Environmental Protection Agency's Health Advisory Summaries. Quality-assurance sampling included duplicate samples, repeated samples, blanks, spikes, and blind samples. These samples proved to be essential in evaluating the accuracy of the data, particularly in the case of volatile organic constituents.

The Influence of the Severity of Chronic Virus-Related Liver Disease on Propofol Requirements during Propofol-Remifentanil Anesthesia

PubMed Central

Wu, Jian; Huang, Su-Qin; Chen, Qing-Lian

2013-01-01

Purpose The purpose of this study was to investigate the influence of chronic virus-related liver disease severity on propofol requirements. Materials and Methods In this study, 48 male patients with chronic hepatitis B infection were divided into three groups according to Child-Turcotte-Pugh classification of liver function (groups A, B, and C with mild, moderate and severe liver disease, respectively). After intubation, propofol concentration was adjusted by ±0.3 µg/mL increments to maintain bispectral index in the range of 40-60. Target propofol concentrations at anesthesia initiation, pre-intubation and pre-incision were recorded. Results The initial concentration used in group C was significantly lower than that used in group A or B (p<0.05), whereas no difference was observed between groups A and B. At pre-intubation, the actual required concentration of propofol increased significantly (3.2 µg/mL) in group A (p<0.05), which lead to significant differences between the groups (p<0.05). At pre-incision, the requirements for propofol decreased significantly in both groups A and B (3.0 µg/mL and 2.7 µg/mL, respectively) compared with those at pre-intubation (p<0.05), and were significantly different for all three groups (p<0.05), with group C demonstrating the lowest requirement (2.2 µg/mL). The required concentrations of propofol at pre-incision were similar to those at induction. Conclusion In this study, propofol requirements administered by target-controlled infusion to maintain similar depths of hypnosis were shown to depend on the severity of chronic virus-related liver dysfunction. In other words, patients with the most severe liver dysfunction required the least amount of propofol. PMID:23225825

Investigation of Classical Organic and Ionic Liquid Cosolvents for Early-Stage Screening in Fragment-Based Inhibitor Design with Unrelated Bacterial and Human Dihydrofolate Reductases.

PubMed

Toulouse, Jacynthe L; Abraham, Sarah M J; Kadnikova, Natalia; Bastien, Dominic; Gauchot, Vincent; Schmitzer, Andreea R; Pelletier, Joelle N

Drug design by methods such as fragment screening requires effective solubilization of millimolar concentrations of small organic compounds while maintaining the properties of the biological target. We investigate four organic solvents and three 1-butyl-3-methylimidazolium (BMIm)-based ionic liquids (ILs) as cosolvents to establish conditions for screening two structurally unrelated dihydrofolate reductases (DHFRs) that are prime drug targets. Moderate concentrations (10%-15%) of cosolvents had little effect on inhibition of the microbial type II R67 DHFR and of human DHFR (hDHFR), while higher concentrations of organic cosolvents generally decreased activity of both DHFRs. In contrast, a specific IL conserved the activity of one DHFR, while severely reducing the activity of the other, and vice versa, illustrating the differing effect of ILs on distinct protein folds. Most of the cosolvents investigated preserved the fold of R67 DHFR and had little effect on binding of the cofactor NADPH, but reduced the productive affinity for its substrate. In contrast, cosolvents resulted in modest structural destabilization of hDHFR with little effect on productive affinity. We conclude that the organic cosolvents, methanol, dimethylformamide, and dimethylsulfoxide, offer the most balanced conditions for early-stage compound screening as they maintain sufficient biological activity of both DHFRs while allowing for compound dissolution in the millimolar range. However, IL cosolvents showed poor capacity to solubilize organic compounds at millimolar concentrations, mitigating their utility in early-stage screening. Nonetheless, ILs could provide an alternative to classical organic cosolvents when low concentrations of inhibitors are used, as when characterizing higher affinity inhibitors.

A survey of metal profiles in some traditional alcoholic beverages in Nigeria.

PubMed

Iwegbue, Chukwujindu M A; Ojelum, Anwuli L; Bassey, Francisca I

2014-11-01

The concentrations of Cd, Pb, Ni, Cr, Cu, Co, Fe, Mn, Zn, Mg, Ca, K, and Na were determined in some traditional alcoholic beverages (oil palm wine, raphia palm wine, burukutu, pito, ogogoro) consumed in southern Nigeria, with a view to providing information on the dietary intakes of essential metals and exposure of humans to toxic metals. The concentrations of these 13 elements were determined by atomic spectrometry after nitric acid/hydrogen peroxide digestion. The mean concentrations of the metals (mg/L) in the samples ranged from 0.02 to 0.05 for Cd; 0.01 to 0.19 for Pb; nd to 0.11 for Ni, nd to 0.15 for Cr; 0.09 to 0.60 for Cu; 0.01-0.08 for Co; 0.30 to 10.3 for Fe; 0.02 to 3.97 for Mn; 0.12 to 3.84 for Zn; 2.08 to 301.3 for Mg; 2.21 to 49.2 for Ca; 35.05 to 926.1 for K; 6.30-58.1 for Na. The mean concentrations of metals in these alcoholic beverages were below statutory limits for the metals in alcoholic beverages and were similar to concentrations found in other alcoholic beverages in the literature. The estimated daily intakes of metals from the consumption of these alcoholic beverages were less than 2% of the recommended dietary allowance values except for Cd and Pb. The individual and combined metals target hazard quotient values were less than 1 except for raphia palm wine and burukutu. From the estimated target hazard, no long life health concerns of metals are associated with the consumption of these alcoholic beverages.

Different removal behaviours of multiple trace antibiotics in municipal wastewater chlorination.

PubMed

Li, Bing; Zhang, Tong

2013-06-01

The chlorination behaviours of 12 antibiotics belonging to six classes at environmentally relevant concentrations were systematically examined under typical conditions relevant to municipal wastewater chlorination. Cefotaxime, cefalexin, ampicillin and tetracycline were completely removed under all three initial free chlorine dosages (5 mg/L, 10 mg/L, and 15 mg/L). The removal efficiencies of sulphamethoxazole, sulphadiazine, roxithromycin, anhydro-erythromycin, ofloxacin, and trimethoprim were closely correlated to the residual free chlorine concentration, and no further significant mass removal was observed after the residual free chlorine concentration decreased to less than ≈ 0.75 mg/L. Ammonia plays a critical role during chlorination because of its competition with antibiotics for free chlorine to form combined chlorine, which reacts slowly with these antibiotics. Except for norfloxacin and ciprofloxacin, the removal behaviours of the 10 other target antibiotics under ammonia nitrogen concentrations ranging from 2 to 15 mg/L were characterised by a rapid initial removal rate upon contact with free chlorine during the first 5 s-1 min (depending on the specific antibiotic and ammonia nitrogen concentration) and then a much slower removal rate. Free chlorine was responsible for the reaction with antibiotics during the rapid stage (first 5 s-1 min), whereas combined chlorine reacted with antibiotics in the subsequent slow stage. Combined chlorine can remove norfloxacin and ciprofloxacin at a relatively faster rate. The presence of suspended solids at 30 mg/L slightly decreased the antibiotic removal rate. The kinetic rate constants decreased by 2.1-13.9%, while the half-lives increased by 2.0-15.0% compared to those of a 0 mg/L suspended solid for the target antibiotics. Copyright © 2013 Elsevier Ltd. All rights reserved.

Visible and near-infrared spectral signatures for adulteration assessment of extra virgin olive oil

NASA Astrophysics Data System (ADS)

Mignani, A. G.; Ciaccheri, L.; Ottevaere, H.; Thienpont, H.; Conte, L.; Marega, M.; Cichelli, A.; Attilio, C.; Cimato, A.

2010-04-01

Because of its high price, the extra virgin olive oil is frequently target for adulteration with lower quality oils. This paper presents an innovative optical technique capable of quantifying the adulteration of extra virgin olive oil caused by lowergrade olive oils. It relies on spectral fingerprinting the test liquid by means of diffuse-light absorption spectroscopy carried out by optical fiber technology in the wide 400-1700 nm spectral range. Then, a smart multivariate processing of spectroscopic data is applied for immediate prediction of adulterant concentration.

Laser range profiling for small target recognition

NASA Astrophysics Data System (ADS)

Steinvall, Ove; Tulldahl, Michael

2017-03-01

Long range identification (ID) or ID at closer range of small targets has its limitations in imaging due to the demand for very high-transverse sensor resolution. This is, therefore, a motivation to look for one-dimensional laser techniques for target ID. These include laser vibrometry and laser range profiling. Laser vibrometry can give good results, but is not always robust as it is sensitive to certain vibrating parts on the target being in the field of view. Laser range profiling is attractive because the maximum range can be substantial, especially for a small laser beam width. A range profiler can also be used in a scanning mode to detect targets within a certain sector. The same laser can also be used for active imaging when the target comes closer and is angularly resolved. Our laser range profiler is based on a laser with a pulse width of 6 ns (full width half maximum). This paper will show both experimental and simulated results for laser range profiling of small boats out to a 6 to 7-km range and a unmanned arrial vehicle (UAV) mockup at close range (1.3 km). The naval experiments took place in the Baltic Sea using many other active and passive electro-optical sensors in addition to the profiling system. The UAV experiments showed the need for a high-range resolution, thus we used a photon counting system in addition to the more conventional profiler used in the naval experiments. This paper shows the influence of target pose and range resolution on the capability of classification. The typical resolution (in our case 0.7 m) obtainable with a conventional range finder type of sensor can be used for large target classification with a depth structure over 5 to 10 m or more, but for smaller targets such as a UAV a high resolution (in our case 7.5 mm) is needed to reveal depth structures and surface shapes. This paper also shows the need for 3-D target information to build libraries for comparison of measured and simulated range profiles. At closer ranges, full 3-D images should be preferable.

Multi-facet concentrator of solar setup for irradiating the objects placed in a target plane with solar light

DOEpatents

Lewandowski, Allan A.; Yampolskiy, Vladislav; Alekseev, Valerie; Son, Valentin

2001-01-01

According to the proposed invention, this technical result is achieved so that many-facet concentrator of a solar setup for exposure of objects, placed in a target plane, to the action of solar radiation containing a supporting frame and facets differing by that the facets of the concentrator are chosen with spherical focusing reflective surfaces of equal focal lengths and with selective coatings reflecting a desired spectral fraction of solar radiation, and are arranged on the supporting frame symmetrically with respect to the common axis of the concentrator, their optical axes being directed to the single point on the optical axis of the concentrator located before the nominal focus point of the concentrator and determining the position of arranging the target plane.

Removal of naproxen and bezafibrate by activated sludge under aerobic conditions: kinetics and effect of substrates.

PubMed

Tang, Ying; Li, Xiao-Ming; Xu, Zhen-Cheng; Guo, Qing-Wei; Hong, Cheng-Yang; Bing, Yong-Xin

2014-01-01

Naproxen and bezafibrate fall into the category of pharmaceuticals that have been widely detected in the aquatic environment, and one of the major sources is the effluent discharge from wastewater treatment plants. This study investigated the sorption and degradation kinetics of naproxen and bezafibrate in the presence of activated sludge under aerobic conditions. Experimental results indicated that the adsorption of pharmaceuticals by activated sludge was rapid, and the relative adsorbabilities of the two-target compounds were based on their log Kow and pKa values. The adsorption data could be well interpreted by the pseudo-second-order kinetic model. The degradation process could be described by the pseudo-first-order kinetic model, whereas the pseudo-second-order kinetics were also well suited to describe the degradation process of the selected compounds at low concentrations. Bezafibrate was more easily degraded by activated sludge compared with naproxen. The spiked concentration of the two-target compounds was negatively correlated with k1 and k2s , indicating that the substrate inhibition effect occurred at the range of studied concentrations. Chemical oxygen demand (COD) did not associate with naproxen degradation; thus, COD is not an alternative method that could be applied to investigate natural organic matter's impact on degradation of pharmaceuticals by activated sludge. © 2013 International Union of Biochemistry and Molecular Biology, Inc.

Eggshell membrane-based biotemplating of mixed hemimicelle/admicelle as a solid-phase extraction adsorbent for carcinogenic polycyclic aromatic hydrocarbons.

PubMed

Wang, Weidong; Chen, Bo; Huang, Yuming

2014-08-13

A new solid-phase extraction (SPE) format was demonstrated, based on eggshell membrane (ESM) templating of the mixed hemimicelle/admicelle of linear alkylbenzenesulfonates (LAS) as an adsorbent for the enrichment of carcinogenic polycyclic aromatic hydrocarbons (PAHs) in environmental aqueous samples. The LAS mixed hemimicelle/admicelle formation and SPE of the target PAHs were conducted simultaneously by adding the organic target and LAS through a column filled with 500 mg of ESM. The effect of various factors, including LAS concentration, solution pH, ionic strength, and humic acid concentration on the recoveries of PAHs were investigated and optimized. The results showed that LAS concentration and solution pH had obvious effect on extraction of PAHs, and the recoveries of PAHs compounds decreased in the presence of salt and humic acid. Under the optimized analytical conditions, the present method could respond down to 0.1-8.6 ng/L PAHs with a linear calibration ranging from 0.02 to 10 μg/L, showing a good PAHs enrichment ability with high sensitivity. The developed method was used satisfactorily for the detection of PAHs in environmental water samples. The mixed hemimicelle/admicelle adsorbent exhibited high extraction efficiency to PAHs and good selectivity with respect to natural organic matter and was advantageous over commercial C₁₈ adsorbent, for example, high extraction yield, high breakthrough volume, and easy regeneration.

Final Report for Intravenous Fluid Generation (IVGEN) Spaceflight Experiment

NASA Technical Reports Server (NTRS)

McQuillen, John B.; McKay, Terri L.; Griffin, DeVon W.; Brown, Dan F.; Zoldak, John T.

2011-01-01

NASA designed and operated the Intravenous Fluid Generation (IVGEN) experiment onboard the International Space Station (ISS), Increment 23/24, during May 2010. This hardware was a demonstration experiment to generate intravenous (IV) fluid from ISS Water Processing Assembly (WPA) potable water using a water purification technique and pharmaceutical mixing system. The IVGEN experiment utilizes a deionizing resin bed to remove contaminants from feedstock water to a purity level that meets the standards of the United States Pharmacopeia (USP), the governing body for pharmaceuticals in the United States. The water was then introduced into an IV bag where the fluid was mixed with USP-grade crystalline salt to produce USP normal saline (NS). Inline conductivity sensors quantified the feedstock water quality, output water purity, and NS mixing uniformity. Six 1.5-L bags of purified water were produced. Two of these bags were mixed with sodium chloride to make 0.9 percent NS solution. These two bags were returned to Earth to test for compliance with USP requirements. On-orbit results indicated that all of the experimental success criteria were met with the exception of the salt concentration. Problems with a large air bubble in the first bag of purified water resulted in a slightly concentrated saline solution of 117 percent of the target value of 0.9 g/L. The second bag had an inadequate amount of salt premeasured into the mixing bag resulting in a slightly deficient salt concentration of 93.8 percent of the target value. The USP permits a range from 95 to 105 percent of the target value. The testing plans for improvements for an operational system are also presented.

Achieving Consistent Multiple Daily Low-Dose Bacillus anthracis Spore Inhalation Exposures in the Rabbit Model

PubMed Central

Barnewall, Roy E.; Comer, Jason E.; Miller, Brian D.; Gutting, Bradford W.; Wolfe, Daniel N.; Director-Myska, Alison E.; Nichols, Tonya L.; Taft, Sarah C.

2012-01-01

Repeated low-level exposures to biological agents could occur before or after the remediation of an environmental release. This is especially true for persistent agents such as B. anthracis spores, the causative agent of anthrax. Studies were conducted to examine aerosol methods needed for consistent daily low aerosol concentrations to deliver a low-dose (less than 106 colony forming units (CFU) of B. anthracis spores) and included a pilot feasibility characterization study, acute exposure study, and a multiple 15 day exposure study. This manuscript focuses on the state-of-the-science aerosol methodologies used to generate and aerosolize consistent daily low aerosol concentrations and resultant low inhalation doses to rabbits. The pilot feasibility characterization study determined that the aerosol system was consistent and capable of producing very low aerosol concentrations. In the acute, single day exposure experiment, targeted inhaled doses of 1 × 102, 1 × 103, 1 × 104, and 1 × 105 CFU were used. In the multiple daily exposure experiment, rabbits were exposed multiple days to targeted inhaled doses of 1 × 102, 1 × 103, and 1 × 104 CFU. In all studies, targeted inhaled doses remained consistent from rabbit-to-rabbit and day-to-day. The aerosol system produced aerosolized spores within the optimal mass median aerodynamic diameter particle size range to reach deep lung alveoli. Consistency of the inhaled dose was aided by monitoring and recording respiratory parameters during the exposure with real-time plethysmography. Overall, the presented results show that the animal aerosol system was stable and highly reproducible between different studies and over multiple exposure days. PMID:22919662

An invertebrate model of the developmental neurotoxicity of insecticides: effects of chlorpyrifos and dieldrin in sea urchin embryos and larvae.

PubMed Central

Buznikov, G A; Nikitina, L A; Bezuglov, V V; Lauder, J M; Padilla, S; Slotkin, T A

2001-01-01

Chlorpyrifos targets mammalian brain development through a combination of effects directed at cholinergic receptors and intracellular signaling cascades that are involved in cell differentiation. We used sea urchin embryos as an invertebrate model system to explore the cellular mechanisms underlying the actions of chlorpyrifos and to delineate the critical period of developmental vulnerability. Sea urchin embryos and larvae were exposed to chlorpyrifos at different stages of development ranging from early cell cleavages through the prism stage. Although early cleavages were unaffected even at high chlorpyrifos concentrations, micromolar concentrations added at the mid-blastula stage evoked a prominent change in cell phenotype and overall larval structure, with appearance of pigmented cells followed by their accumulation in an extralarval cap that was extruded from the animal pole. At higher concentrations (20-40 microM), these abnormal cells constituted over 90% of the total cell number. Studies with cholinergic receptor blocking agents and protein kinase C inhibitors indicated two distinct types of effects, one mediated through stimulation of nicotinic cholinergic receptors and the other targeting intracellular signaling. The effects of chlorpyrifos were not mimicked by chlorpyrifos oxon, the active metabolite that inhibits cholinesterase, nor by nonorganophosphate cholinesterase inhibitors. Dieldrin, an organochlorine that targets GABA(A )receptors, was similarly ineffective. The effects of chlorpyrifos and its underlying cholinergic and signaling-related mechanisms parallel prior findings in mammalian embryonic central nervous system. Invertebrate test systems may thus provide both a screening procedure for potential neuroteratogenesis by organophosphate-related compounds, as well as a system with which to uncover novel mechanisms underlying developmental vulnerability. PMID:11485862

Pesticides in streams of the United States : initial results from the National Water-Quality Assessment Program

USGS Publications Warehouse

Larson, Steven J.; Gilliom, Robert J.; Capel, Paul D.

1999-01-01

Water samples from 58 rivers and streams across the United States were analyzed for pesticides as part of the National Water-Quality Assessment Program of the U.S. Geological Survey. The sampling sites represent 37 diverse agricultural basins, 11 urban basins, and 10 basins with mixed land use. Forty-six pesticides and pesticide degradation products were analyzed in approximately 2,200 samples collected from 1992 to 1995. The target compounds account for approximately 70 percent of national agricultural use in terms of the mass of pesticides applied annually. All the target compounds were detected in one or more samples. Herbicides generally were detected more frequently and at higher concentrations than insecticides. Nationally, 11 herbicides, 1 herbicide degradation product, and 3 insecticides were detected in more than 10 percent of samples. The number of target compounds detected at each site ranged from 7 to 37. The herbicides atrazine, metolachlor, prometon, and simazine were detected most frequently; among the insecticides, carbaryl, chlorpyrifos, and diazinon were detected the most frequently. Distinct differences in pesticide occurrence were observed in streams draining the various agricultural settings. Relatively high levels of several herbicides occurred as seasonal pulses in corn-growing areas. Several insecticides were frequently detected in areas where the dominant crops consist of orchards and vegetables. The number of pesticides detected and their concentrations were lower in wheat-growing areas than in most other agricultural areas. In most urban areas, the herbicides prometon and simazine and the insecticides carbaryl, chlorpyrifos, diazinon, and malathion were commonly detected. Concentrations of pesticides rarely exceeded standards and criteria established for drinking water, but some pesticides commonly exceeded criteria established for the protection of aquatic life.

Determination of glycated albumin using boronic acid-derived agarose beads on paper-based devices.

PubMed

Ko, Euna; Tran, Van-Khue; Geng, Yanfang; Kim, Min Ki; Jin, Ga Hyun; Son, Seong Eun; Hur, Won; Seong, Gi Hun

2018-01-01

Self-monitoring of glycated albumin (GA), a useful glycemic marker, is an established method for preventing diabetes complications. Here, the paper-based lateral flow assay devices were developed for the sensitive detection of GA and the total human serum albumin (tHSA) in self-monitoring diabetes patients. Boronic acid-derived agarose beads were packed into a hole on a lateral flow channel. These well-coordinated agarose beads were used to capture GA through specific cis-diol interactions and to enhance the colorimetric signals by concentrating the target molecules. The devices exhibited large dynamic ranges (from 10  μ g/ml to 10 mg/ml for GA and from 10 mg/ml to 50 mg/ml for tHSA) and low detection limits (7.1  μ g/ml for GA and 4.7 mg/ml for tHSA), which cover the range of GA concentration in healthy plasma, which is 0.21-1.65 mg/ml (0.6%-3%). In determining the unknown GA concentrations in two commercial human plasma samples, the relative percentage difference between the values found by a standard ELISA kit and those found by our developed devices was 2.62% and 8.80%, which are within an acceptable range. The measurements of GA and tHSA were completed within 20 min for the total sample-to-answer diagnosis, fulfilling the demand for rapid analysis. Furthermore, the recovery values ranged from 99.4% to 110% in device accuracy tests. These results indicate that the developed paper-based device with boronic acid-derived agarose beads is a promising platform for GA and tHSA detection as applied to self-monitoring systems.

Determination of 89 drugs and other micropollutants in unfiltered wastewater and freshwater by LC-MS/MS: an alternative sample preparation approach.

PubMed

Asimakopoulos, Alexandros G; Kannan, Pranav; Higgins, Sean; Kannan, Kurunthachalam

2017-10-01

A liquid chromatography-triple quadrupole-tandem mass spectrometry (LC-qQq-MS/MS) method was developed for simultaneous determination of 89 legal neuropsychiatric pharmaceuticals and illicit drugs (both parent compounds and metabolites) and other micropollutants in unfiltered wastewater and freshwater. The target chemicals fall under the classes of amphetamine-type stimulants, cocaine compounds, opiates and opioids, benzodiazepines, lysergic compounds, antipsychotics, anesthetics, antiepileptics, antidepressants, sympathomimetics, cannabinoids, blood thinners, antihistamines, β-blockers, caffeine derivatives, nicotine derivatives, z-drugs, new designer drugs, and Alzheimer medications. The sample preparation procedure was designed for unfiltered wastewater and freshwater without the need to separate the particulate matter (if any) from the aqueous phase prior to extraction. Samples were pre-concentrated by rotary evaporation in the presence of a solvent. Method precision (absolute values; N = 6 replicate analyses at the fortification level of 50 ng, k = 6 days) for 87 out of 89 target analytes ranged from 2.8 to 34% (RSD %). The limits of detection ranged from 0.11 to 202 ng L -1 , and the matrix effects ranged from +16 to -84%. A total of 10 samples, 8 wastewater, 1 drinking water, and 1 lake water, were collected from New York State, USA, and were analyzed for the target compounds to demonstrate the applicability of the developed method. This is the first study to report the analysis of multiple classes of pharmaceuticals, illicit drugs, and other micropollutants in unfiltered wastewater. Graphical abstract Analysis of 89 micropollutants in unfiltered wastewater by LC-MS/MS.

Design of multiplex calibrant plasmids, their use in GMO detection and the limit of their applicability for quantitative purposes owing to competition effects.

PubMed

Debode, Frédéric; Marien, Aline; Janssen, Eric; Berben, Gilbert

2010-03-01

Five double-target multiplex plasmids to be used as calibrants for GMO quantification were constructed. They were composed of two modified targets associated in tandem in the same plasmid: (1) a part of the soybean lectin gene and (2) a part of the transgenic construction of the GTS40-3-2 event. Modifications were performed in such a way that each target could be amplified with the same primers as those for the original target from which they were derived but such that each was specifically detected with an appropriate probe. Sequence modifications were done to keep the parameters of the new target as similar as possible to those of its original sequence. The plasmids were designed to be used either in separate reactions or in multiplex reactions. Evidence is given that with each of the five different plasmids used in separate wells as a calibrant for a different copy number, a calibration curve can be built. When the targets were amplified together (in multiplex) and at different concentrations inside the same well, the calibration curves showed that there was a competition effect between the targets and this limits the range of copy numbers for calibration over a maximum of 2 orders of magnitude. Another possible application of multiplex plasmids is discussed.

Survey of polyfluorinated chemicals (PFCs) in the atmosphere over the northeast Atlantic Ocean

NASA Astrophysics Data System (ADS)

Shoeib, Mahiba; Vlahos, Penny; Harner, Tom; Peters, Andrew; Graustein, Margaret; Narayan, Julie

2010-08-01

High volume air sampling in Bermuda, Sable Island (Nova Scotia) and along a cruise track from the Gulf of Mexico to northeast coast of the USA, was carried out to assess air concentrations, particle-gas partitioning and transport of polyfluorinated chemicals (PFCs) in this region. Samples were collected in the summer of 2007. Targeted compounds included the neutral PFCs: fluorotelomer alcohols (FTOHs), perfluoroalkyl sulfonamides (FOSAs) and perfluoroalkyl sulfonamido ethanols (FOSEs). Among the FTOHs, 8:2 FTOH was dominant in all samples. Sum of the concentration of FTOHs (gas+particle phase) were higher in Bermuda (mean, 34 pg m -3) compared to Sable Island (mean, 16 pg m -3). In cruise samples, sum of FTOHs were highly variable (mean, 81 pg m -3) reflecting contributions from land-based sources in the northeast USA with concentrations reaching as high as 156 pg m -3. Among the FOSAs and FOSEs, MeFOSE was dominant in all samples. In Bermuda, levels of MeFOSE were exceptionally high (mean, 62 pg m -3), exceeding the FTOHs. Sable Island samples also exhibited the dominance of MeFOSE but at a lower concentration (mean, 15 pg m -3). MeFOSE air concentrations (pg m -3) in cruise samples ranged from 1.6 to 73 and were not linked to land-based sources. In fact high concentrations of MeFOSE observed in Bermuda were associated with air masses that originated over the Atlantic Ocean. The partitioning to particles for 8:2 FTOH, 10:2 FTOH, MeFOSE and EtFOSE ranged from as high as 15 to 42% for cruise samples to 0.9 to 14% in Bermuda. This study provides key information for validating and developing partitioning and transport models for the PFCs.

Occurrence and fate of benzotriazoles UV filters in a typical residential wastewater treatment plant in Harbin, China.

PubMed

Zhao, Xue; Zhang, Zi-Feng; Xu, Lei; Liu, Li-Yan; Song, Wei-Wei; Zhu, Fu-Jie; Li, Yi-Fan; Ma, Wan-Li

2017-08-01

Benzotriazoles (BTs) UV filters are widely used as ultraviolet absorbents for our daily products, which received increasing attention in the past decades. Residential wastewater treatment plant (WWTP) is both an important sink for wastewater and a key pollution source for receiving water for these chemicals. In this study, pretreatment and gas chromatography-tandem mass spectrometry analysis method were developed to determine the occurrence and fate of 9 BTs UV filters in wastewater and sludge from the WWTP with anaerobic-oxic treatment process (A/O) and biological aerated filter treatment process (BAF). Totally, 81 wastewater samples and 11 sludge samples were collected in four seasons. In wastewater, UV-326 and UV-329 were frequently detected, while the highest mean concentrations were detected for UV-234 and UV-329. The concentrations were in the range of 85% in A/O process and 60-77% in BAF process except for UV-350, which was more difficult to remove with lower removal efficiencies of 33.3% for both A/O and BAF. All the target chemicals except for UV-320 were detected in sludge samples with the mean concentration ranging from 0.90 ng/g to 303.39 ng/g. There was no significant difference with concentrations and removal efficiency among different seasons. Higher detection frequency and concentration of BTs UV filters in downstream of the receiving water system indicated the contribution of effluent of the WWTP. Compared with other rivers, the lower concentrations in surface water in the Songhua River indicated light pollution status with of BTs UV filters. Copyright © 2017 Elsevier Ltd. All rights reserved.

False-negative rate, limit of detection and recovery efficiency performance of a validated macrofoam-swab sampling method for low surface concentrations of Bacillus anthracis Sterne and Bacillus atrophaeus spores

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

Piepel, G. F.; Deatherage Kaiser, B. L.; Amidan, B. G.

The performance of a macrofoam-swab sampling method was evaluated using Bacillus anthracis Sterne (BAS) and Bacillus atrophaeus Nakamura (BG) spores applied at nine low target amounts (2-500 spores) to positive-control plates and test coupons (2 in × 2 in) of four surface materials (glass, stainless steel, vinyl tile, and plastic). Test results from cultured samples were used to evaluate the effects of surrogate, surface concentration, and surface material on recovery efficiency (RE), false negative rate (FNR), and limit of detection. For RE, surrogate and surface material had statistically significant effects, but concentration did not. Mean REs were the lowest formore » vinyl tile (50.8% with BAS and 40.2% with BG) and the highest for glass (92.8% with BAS and 71.4% with BG). FNR values ranged from 0 to 0.833 for BAS and 0 to 0.806 for BG; values increased as concentration decreased in the range tested (0.078 to 19.375 CFU/cm2). Surface material also had a statistically significant effect. A FNR-concentration curve was fit for each combination of surrogate and surface material. For both surrogates, the FNR curves tended to be the lowest for glass and highest for vinyl title. The FNR curves for BG tended to be higher than for BAS at lower concentrations, especially for glass. Results using a modified Rapid Viability-Polymerase Chain Reaction (mRV-PCR) analysis method were also obtained. The mRV-PCR results and comparisons to the culture results will be discussed in a subsequent article.« less

Recovery Efficiency, False Negative Rate, and Limit of Detection Performance of a Validated Macrofoam-Swab Sampling Method with Low Surface Concentrations of Two Bacillus anthracis Surrogates

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

Piepel, Gregory F.; Hutchison, Janine R.; Kaiser, Brooke L. D.

The performance of a macrofoam-swab sampling method was evaluated using Bacillus anthracis Sterne (BAS) and Bacillus atrophaeus Nakamura (BG) spores applied at nine low target amounts (2-500 spores) to positive-control plates and test coupons (2 in × 2 in) of four surface materials (glass, stainless steel, vinyl tile, and plastic). Test results from cultured samples were used to evaluate the effects of surrogate, surface concentration, and surface material on recovery efficiency (RE), false negative rate (FNR), and limit of detection. For RE, surrogate and surface material had statistically significant effects, but concentration did not. Mean REs were the lowest formore » vinyl tile (50.8% with BAS, 40.2% with BG) and the highest for glass (92.8% with BAS, 71.4% with BG). FNR values ranged from 0 to 0.833 for BAS and 0 to 0.806 for BG, with values increasing as concentration decreased in the range tested (0.078 to 19.375 CFU/cm2, where CFU denotes ‘colony forming units’). Surface material also had a statistically significant effect. A FNR-concentration curve was fit for each combination of surrogate and surface material. For both surrogates, the FNR curves tended to be the lowest for glass and highest for vinyl title. The FNR curves for BG tended to be higher than for BAS at lower concentrations, especially for glass. Results using a modified Rapid Viability-Polymerase Chain Reaction (mRV-PCR) analysis method were also obtained. The mRV-PCR results and comparisons to the culture results are discussed in a separate report.« less

Recovery Efficiency, False Negative Rate, and Limit of Detection Performance of a Validated Macrofoam-Swab Sampling Method with Low Surface Concentrations of Two Bacillus anthracis Surrogates

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

Piepel, Gregory F.; Hutchison, Janine R.; Deatherage Kaiser, Brooke L

The performance of a macrofoam-swab sampling method was evaluated using Bacillus anthracis Sterne (BAS) and Bacillus atrophaeus Nakamura (BG) spores applied at nine low target amounts (2-500 spores) to positive-control plates and test coupons (2 in. × 2 in.) of four surface materials (glass, stainless steel, vinyl tile, and plastic). Test results from cultured samples were used to evaluate the effects of surrogate, surface concentration, and surface material on recovery efficiency (RE), false negative rate (FNR), and limit of detection. For RE, surrogate and surface material had statistically significant effects, but concentration did not. Mean REs were the lowest formore » vinyl tile (50.8% with BAS, 40.2% with BG) and the highest for glass (92.8% with BAS, 71.4% with BG). FNR values ranged from 0 to 0.833 for BAS and 0 to 0.806 for BG, with values increasing as concentration decreased in the range tested (0.078 to 19.375 CFU/cm 2, where CFU denotes ‘colony forming units’). Surface material also had a statistically significant effect. A FNR-concentration curve was fit for each combination of surrogate and surface material. For both surrogates, the FNR curves tended to be the lowest for glass and highest for vinyl title. The FNR curves for BG tended to be higher than for BAS at lower concentrations, especially for glass. Results using a modified Rapid Viability-Polymerase Chain Reaction (mRV-PCR) analysis method were also obtained. The mRV-PCR results and comparisons to the culture results will be discussed in a subsequent report.« less

Biophysical damage in metallo-enzyme and mammalian cells by Cu-K X-rays and radioisotopes

NASA Astrophysics Data System (ADS)

Younis, Abdul-Redha Sahib

In the fields of radiobiology and nuclear medicine there is considerable interest in the important role played by Auger electron cascades caused by inner-shell ionisation in realistic risk. It is necessary to quantify this risk when radionuclides are used on a routine basis as investigative, diagnostic and radiotherapeutic tools, whether the applications involve incorporated electron capture radionuclides or K-shell ionisation of selected stable nuclides by X-rays, as in "photon activation therapy". Relevant published survival data on biological damage caused by the internal emitters 125I, 77Br, 3H, 33P, 131I and 32P which are incorporated into the DNA of mammalian cells, bacteria (E. Coli) and bacteriophages have been collected and the results re-analysed in terms of the parameters of a new damage model to determine an inactivation cross-section for each internal emitter. These quality parameters are the absolute specification of radiation quality and are compared with cross-sections similarly determined for the effects of external radiations from heavy charged particles and photons (chapter 2). The inactivation probabilities obtained for the nuclides 125I, 77Br and 3H extend over a wide range of values depending on the type of nuclide and its distribution, the type of sensitive target and its shape and distribution, and the environmental temperature during both irradiation and post-irradiation incubation. The higher values approach those determined for heavy charged particles with the same mean free path for primary ionisation, and are an order of magnitude larger than would be expected for external irradiation with photon generated electrons. The results for 33P, 131I and 32P nuclides are appreciably smaller than that expected for external irradiation since the long range electrons dissipate most of their energy out of the sensitive target. A theoretical equation for X-ray production by accelerated electrons incident on a thick target has been revised by including factors to compensate for backscattering, direct and indirect ionisation, attenuation in the target and the incident angle of electrons (chapter 3). An electron accelerator X-ray machine capable of delivering monoenergetic photons up to 4.8 gray/sec exposure dose rate from four different targets has been designed, constructed and tested (chapter 4) The biophysical mechanisms of direct and indirect radiation action has also been studied using the metallo-enzyme dihydroorotic dehydrogenase. The enzyme was irradiated both in dry state and in solution at different concentrations and at different dose rates using monoenergetic Cu-K photons from our X-ray machine. A technique was developed whereby it was possible to isolate and quantify each type of radiation action (chapter 5). The inactivation of the enzyme in both solution and in dry state was found to be a single-hit/single-target process. It was also found that in solution the inactivation of the enzyme was dose-rate-and concentration-dependent with efficiency of radical inactivation has an exponential dependence on dose-rate and the inverse of the enzyme concentration. A new model for the inactivation of the enzyme has been suggested and its parameters, namely direct and indirect cross-sections, geometrical cross-section, saturated concentration constant, root mean square diffusion constant, mean free path of radicals absorption, life time and G value of radical production, have been determined. It is expected that this model can be generalised to suit other enzymes (chapter 6).

Study on relationship between expression level and molecular conformations of gene drugs targeting to hepatoma cells in vitro

PubMed Central

Yang, Dong-Ye; Lu, Fang-Gen; Tang, Xi-Xiang; Zhao, Shui-Ping; Ouyang, Chun-Hui; Wu, Xiao-Ping; Liu, Xiao-Wei; Wu, Xiao-Ying

2003-01-01

AIM: To increase exogenous gene expression level by modulating molecular conformations of targeting gene drugs. METHODS: The full length cDNAs of both P40 and P35 subunits of human interleukin 12 were amplified through polymerase chain reaction (PCR) and cloned into eukaryotic expressing vectors pcDNA3.1 (±) to construct plasmids of P (+)/IL-12, P (+)/P40 and P (-)/P35. These plasmids were combined with ASOR-PLL to form two targeting gene drugs [ASOR-PLL-P (+)/IL-12 and ASOR-PLL-P (+)/P40 + ASOR-PLL-P (-)/P35] in optimal ratios. The conformations of these two drugs at various concentrations adjuvant were examined under electron microscope (EM) and the drugs were transfected into HepG2 (ASGr+) cells. Semi-quantitative reverse transcription polymerase chain reaction (RT-PCR) was performed with total RNA extracted from the transfected cells to determine the hIL12 mRNA transcript level. The hIL12 protein in the cultured supernatant was measured with enzyme-linked immunosorbent assay (ELISA) 48 hours after transfection. RESULTS: Targeting gene drugs, whose structures were granular and circle-like and diameters ranged from 25 nm to 150 nm, had the highest hIL-12 expression level. The hIL-12 expression level in the group co-transfected with ASOR-PLL-P (+)/P40 and ASOR-PLL-P (-)/P35 was higher than that of ASOR-PLL-P (+)/IL-12 transfected group. CONCLUSION: The molecular conformations of targeting gene drugs play an important role in exogenous gene expression level, the best structures are granular and circle-like and their diameters range from 25 nm to 150 nm. The sizes and linking styles of exogenous genes also have some effects on their expression level. PMID:12970883

A sensitive electrochemical aptasensor for multiplex antibiotics detection based on high-capacity magnetic hollow porous nanotracers coupling exonuclease-assisted cascade target recycling.

PubMed

Yan, Zhongdan; Gan, Ning; Li, Tianhua; Cao, Yuting; Chen, Yinji

2016-04-15

A multiplex electrochemical aptasensor was developed for simultaneous detection of two antibiotics such as chloramphenicol (CAP) and oxytetracycline (OTC), and high-capacity magnetic hollow porous nanotracers coupling exonuclease-assisted target recycling was used to improve sensitivity. The cascade amplification process consists of the exonuclease-assisted target recycling amplification and metal ions encoded magnetic hollow porous nanoparticles (MHPs) to produce voltammetry signals. Upon the specific recognition of aptamers to targets (CAP and OTC), exonuclease I (Exo I) selectively digested the aptamers which were bound with CAP and OTC, then the released CAP and OTC participated new cycling to produce more single DNA, which can act as trigger strands to hybrid with nanotracers to generate further signal amplification. MHPs were used as carriers to load more amounts of metal ions and coupling with Exo I assisted cascade target recycling can amplify the signal for about 12 folds compared with silica based nanotracers. Owing to the dual signal amplification, the linear range between signals and the concentrations of CAP and OTC were obtained in the range of 0.0005-50 ng mL(-1). The detection limits of CAP and OTC were 0.15 and 0.10 ng mL(-1) (S/N=3) which is more than 2 orders lower than commercial enzyme-linked immunosorbent immunoassay (ELISA) method, respectively. The proposed method was successfully applied to simultaneously detection of CAP and OTC in milk samples. Besides, this aptasensor can be applied to other antibiotics detection by changing the corresponding aptamer. The whole scheme is facile, selective and sensitive enough for antibiotics screening in food safety. Copyright © 2015 Elsevier B.V. All rights reserved.

Chemical-exchange-saturation-transfer magnetic resonance imaging to map gamma-aminobutyric acid, glutamate, myoinositol, glycine, and asparagine: Phantom experiments

NASA Astrophysics Data System (ADS)

Oh, Jang-Hoon; Kim, Hyug-Gi; Woo, Dong-Cheol; Jeong, Ha-Kyu; Lee, Soo Yeol; Jahng, Geon-Ho

2017-03-01

The physical and technical development of chemical-exchange-saturation-transfer (CEST) magnetic resonance imaging (MRI) using clinical 3 T MRI was explored with the goal of mapping asparagine (Asn), gamma-aminobutyric acid (GABA), glutamate (Glu), glycine (Gly), and myoinositol (MI), which exist in the brain. Phantoms with nine different conditions at concentrations of 10, 30, and 50 mM and pH values of 5.6, 6.2, and 7.4 were prepared for the five target molecules to evaluate the dependence of the CEST effect in the concentration, the pH, and the amplitude of the applied radiofrequency field B1. CEST images in the offset frequency range of ±6 parts per million (ppm) were acquired using a pulsed radio-frequency saturation scheme with a clinical 3 T MRI system. A voxel-based main magnetic field B0 inhomogeneity correction, where B0 is the center frequency offset at zero ppm, was performed by using the spline interpolation method to fit the full Z-spectrum to estimate the center frequency. A voxel-based CEST asymmetry map was calculated to evaluate amide (-NH), amine (-NH2), and hydroxyl (-OH) groups for the five target molecules. The CEST effect for Glu, GABA, and Gly clearly increased with increasing concentrations. The CEST effect for MI was minimal, with no noticeable differences at different concentrations. The CEST effect for Glu and Gly increased with increasing acidity. The highest CEST asymmetry for GABA was observed at pH 6.2. The CEST effect for Glu, GABA, and Gly increased with increasing B1 amplitude. For all target molecules, the CEST effect for the human 3 T MRI system increased with increasing concentration and B1 amplitude, but varied with pH, depending on the characteristics of the molecules. The CEST effect for MI may be not suitable with clinical MRI systems. These results show that CEST imaging in the brain with the amine protons by using 3 T MRI is possible for several neuronal diseases.

Doxorubicin-conjugated bacteriophages carrying anti-MHC class I chain-related A for targeted cancer therapy in vitro.

PubMed

Phumyen, Achara; Jantasorn, Siriporn; Jumnainsong, Amonrat; Leelayuwat, Chanvit

2014-01-01

Cancer therapy by systemic administration of anticancer drugs, besides the effectiveness shown on cancer cells, demonstrated the side effects and cytotoxicity on normal cells. The targeted drug-carrying nanoparticles may decrease the required drug concentration at the site and the distribution of drugs to normal tissues. Overexpression of major histocompatibility complex class I chain-related A (MICA) in cancer is useful as a targeted molecule for the delivery of doxorubicin to MICA-expressing cell lines. The application of 1-ethyl-3-[3-dimethylaminopropyl] carbodiimide (EDC) chemistry was employed to conjugate the major coat protein of bacteriophages carrying anti-MICA and doxorubicin in a mildly acid condition. Doxorubicin (Dox) on phages was determined by double fluorescence of phage particles stained by M13-fluorescein isothiocyanate (FITC) and drug autofluorescence by flow cytometry. The ability of anti-MICA on phages to bind MICA after doxorubicin conjugation was evaluated by indirect enzyme-linked immunosorbent assay. One cervical cancer and four cholangiocarcinoma cell lines expressing MICA were used as models to evaluate targeting activity by cell cytotoxicity test. Flow cytometry and indirect enzyme-linked immunosorbent assay demonstrated that most of the phages (82%) could be conjugated with doxorubicin, and the Dox-carrying phage-displaying anti-MICA (Dox-phage) remained the binding activity against MICA. Dox-phage was more efficient than free drugs in killing all the cell lines tested. The half maximal inhibitory concentration (IC50) values of Dox-phage were lower than those of free drugs at approximately 1.6-6 times depending on MICA expressions and the cell lines tested. Evidently, the application of 1-ethyl-3-[3-dimethylaminopropyl] carbodiimide chemistry is effective to conjugate doxorubicin and major coat protein of bacteriophages without destroying binding activity of MICA antibodies. Dox-carrying bacteriophages targeting MICA have been successfully developed and may enable a broad range of applications in cancer-targeting chemotherapy.

Molecular-receptor-specific, non-toxic, near-infrared-emitting Au cluster-protein nanoconjugates for targeted cancer imaging

NASA Astrophysics Data System (ADS)

Retnakumari, Archana; Setua, Sonali; Menon, Deepthy; Ravindran, Prasanth; Muhammed, Habeeb; Pradeep, Thalappil; Nair, Shantikumar; Koyakutty, Manzoor

2010-02-01

Molecular-receptor-targeted imaging of folate receptor positive oral carcinoma cells using folic-acid-conjugated fluorescent Au25 nanoclusters (Au NCs) is reported. Highly fluorescent Au25 clusters were synthesized by controlled reduction of Au+ ions, stabilized in bovine serum albumin (BSA), using a green-chemical reducing agent, ascorbic acid (vitamin-C). For targeted-imaging-based detection of cancer cells, the clusters were conjugated with folic acid (FA) through amide linkage with the BSA shell. The bioconjugated clusters show excellent stability over a wide range of pH from 4 to 14 and fluorescence efficiency of ~5.7% at pH 7.4 in phosphate buffer saline (PBS), indicating effective protection of nanoclusters by serum albumin during the bioconjugation reaction and cell-cluster interaction. The nanoclusters were characterized for their physico-chemical properties, toxicity and cancer targeting efficacy in vitro. X-ray photoelectron spectroscopy (XPS) suggests binding energies correlating to metal Au 4f7/2~83.97 eV and Au 4f5/2~87.768 eV. Transmission electron microscopy and atomic force microscopy revealed the formation of individual nanoclusters of size ~1 nm and protein cluster aggregates of size ~8 nm. Photoluminescence studies show bright fluorescence with peak maximum at ~674 nm with the spectral profile covering the near-infrared (NIR) region, making it possible to image clusters at the 700-800 nm emission window where the tissue absorption of light is minimum. The cell viability and reactive oxygen toxicity studies indicate the non-toxic nature of the Au clusters up to relatively higher concentrations of 500 µg ml-1. Receptor-targeted cancer detection using Au clusters is demonstrated on FR+ve oral squamous cell carcinoma (KB) and breast adenocarcinoma cell MCF-7, where the FA-conjugated Au25 clusters were found internalized in significantly higher concentrations compared to the negative control cell lines. This study demonstrates the potential of using non-toxic fluorescent Au nanoclusters for the targeted imaging of cancer.

Onboard calibration igneous targets for the Mars Science Laboratory Curiosity rover and the Chemistry Camera laser induced breakdown spectroscopy instrument

NASA Astrophysics Data System (ADS)

Fabre, C.; Maurice, S.; Cousin, A.; Wiens, R. C.; Forni, O.; Sautter, V.; Guillaume, D.

2011-03-01

Accurate characterization of the Chemistry Camera (ChemCam) laser-induced breakdown spectroscopy (LIBS) on-board composition targets is of prime importance for the ChemCam instrument. The Mars Science Laboratory (MSL) science and operations teams expect ChemCam to provide the first compositional results at remote distances (1.5-7 m) during the in situ analyses of the Martian surface starting in 2012. Thus, establishing LIBS reference spectra from appropriate calibration standards must be undertaken diligently. Considering the global mineralogy of the Martian surface, and the possible landing sites, three specific compositions of igneous targets have been determined. Picritic, noritic, and shergottic glasses have been produced, along with a Macusanite natural glass. A sample of each target will fly on the MSL Curiosity rover deck, 1.56 m from the ChemCam instrument, and duplicates are available on the ground. Duplicates are considered to be identical, as the relative standard deviation (RSD) of the composition dispersion is around 8%. Electronic microprobe and laser ablation inductively coupled plasma mass spectrometry (LA ICP-MS) analyses give evidence that the chemical composition of the four silicate targets is very homogeneous at microscopic scales larger than the instrument spot size, with RSD < 5% for concentration variations > 0.1 wt.% using electronic microprobe, and < 10% for concentration variations > 0.01 wt.% using LA ICP-MS. The LIBS campaign on the igneous targets performed under flight-like Mars conditions establishes reference spectra for the entire mission. The LIBS spectra between 240 and 900 nm are extremely rich, hundreds of lines with high signal-to-noise, and a dynamical range sufficient to identify unambiguously major, minor and trace elements. For instance, a first LIBS calibration curve has been established for strontium from [Sr] = 284 ppm to [Sr] = 1480 ppm, showing the potential for the future calibrations for other major or minor elements.

Label-free DNA hybridization detection and single base-mismatch discrimination using CE-ICP-MS assay.

PubMed

Li, Yan; Sun, Shao-kai; Yang, Jia-lin; Jiang, Yan

2011-12-07

Detecting a specific DNA sequence and discriminating single base-mismatch is critical to clinical diagnosis, paternity testing, forensic sciences, food and drug industry, pathology, genetics, environmental monitoring, and anti-bioterrorism. To this end, capillary electrophoresis (CE) coupled with the inductively coupled plasma mass spectrometry (ICP-MS) method is developed using the displacing interaction between the target ssDNA and the competitor Hg(2+) for the first time. The thymine-rich capture ssDNA 1 is interacted with the competitor Hg(2+), forming an assembled complex in a hairpin-structure between the thymine bases arrangement at both sides of the capture ssDNA 1. In the presence of a target ssDNA with stronger affinity than that of the competitor Hg(2+), the energetically favorable hybridization between capture ssDNA 1 and the target ssDNA destroys the hairpin-structure and releases the competitor as free Hg(2+), which was then read out and accurately quantified by CE-ICP-MS assay. Under the optimal CE separation conditions, free Hg(2+) ions and its capture ssDNA 1 adduct were baseline separated and detected on-line by ICP-MS; the increased peak intensity of free Hg(2+) against the concentration of perfectly complementary target ssDNA was linear over the concentration range of 30-600 nmol L(-1) with a limit of detection of 8 nmol L(-1) (3s, n = 11) in the pre-incubated mixture containing 1 μmol L(-1) Hg(2+) and 0.2 μmol L(-1) capture ssDNA 1. This new assay method is simple in design since any target ssDNA binding can in principle result in free Hg(2+) release by 6-fold Hg(2+) signal amplification, avoiding oligonucleotide labeling or assistance by excess signal transducer and signal reporter to read out the target. Due to element-specific detection of ICP-MS in our assay procedure, the interference from the autofluorescence of substrata was eliminated.

Unified anomaly suppression and boundary extraction in laser radar range imagery based on a joint curve-evolution and expectation-maximization algorithm.

PubMed

Feng, Haihua; Karl, William Clem; Castañon, David A

2008-05-01

In this paper, we develop a new unified approach for laser radar range anomaly suppression, range profiling, and segmentation. This approach combines an object-based hybrid scene model for representing the range distribution of the field and a statistical mixture model for the range data measurement noise. The image segmentation problem is formulated as a minimization problem which jointly estimates the target boundary together with the target region range variation and background range variation directly from the noisy and anomaly-filled range data. This formulation allows direct incorporation of prior information concerning the target boundary, target ranges, and background ranges into an optimal reconstruction process. Curve evolution techniques and a generalized expectation-maximization algorithm are jointly employed as an efficient solver for minimizing the objective energy, resulting in a coupled pair of object and intensity optimization tasks. The method directly and optimally extracts the target boundary, avoiding a suboptimal two-step process involving image smoothing followed by boundary extraction. Experiments are presented demonstrating that the proposed approach is robust to anomalous pixels (missing data) and capable of producing accurate estimation of the target boundary and range values from noisy data.

Nanostructure sensor of presence and concentration of a target molecule

NASA Technical Reports Server (NTRS)

Schipper, John F. (Inventor)

2009-01-01

Method and system (i) to determine when a selected target molecule is present or absent in a fluid, (2) to estimate concentration of the target molecule in the fluid and (3) estimate possible presence of a second (different) target molecule in the fluid, by analyzing differences in resonant frequencies of vibration of a thin beam suspended in the fluid, after the fluid has moved across the beam.

Targeted Therapies for Myeloma and Metastatic Bone Cancers

DTIC Science & Technology

2007-02-01

increased efficacy in the targeted microenvironment, and the ultimate opportunity to reverse catastrophic disease processes . Furthermore, targeted...concentrate the resulting nanoparticles using centrifuge concentrator tubes and we have integrated this processing step into our nanoparticle...is unaffected by this slightly altered approach. Furthermore, this modified method avoids a lengthy column separation process that diminishes the

What is the acceptable hemolysis index for the measurements of plasma potassium, LDH and AST?

PubMed

Rousseau, Nathalie; Pige, Raphaëlle; Cohen, Richard; Pecquet, Matthieu

2016-06-01

Hemolysis is a cause of variability in test results for plasma potassium, LDH and AST and is a non-negligible part of measurement uncertainty. However, allowable levels of hemolysis provided by reagent suppliers take neither analytical variability (trueness and precision) nor the measurand into account. Using a calibration range of hemolysis, we measured the plasma concentrations of potassium, LDH and AST, and hemolysis indices with a Cobas C501 analyzer (Roche Diagnostics(®), Meylan, France). Based on the allowable total error (according to Ricós et al.) and the expanded measurement uncertainty equation we calculated the maximum allowable bias for two concentrations of each measurand. Finally, we determined the allowable hemolysis indices for all three measurands. We observed a linear relationship between the observed increases of concentration and hemolysis indices. The LDH measurement was the most sensitive to hemolysis, followed by AST and potassium measurements. The determination of the allowable hemolysis index depends on the targeted measurand, its concentration and the chosen level of requirement of allowable total error.

Occurrence and removal of pharmaceutically active compounds in sewage treatment plants with different technologies

USGS Publications Warehouse

Ying, Guang-Guo; Kookana, Rai S.; Kolpin, Dana W.

2009-01-01

Occurrence of eight selected pharmaceutically active compounds (PhACs; caffeine, carbamazepine, triclosan, gemfibrozil, diclofenac, ibuprofen, ketoprofen and naproxen) were investigated in effluents from fifteen sewage treatment plants (STPs) across South Australia. In addition, a detailed investigation into the removal of these compounds was also carried out in four STPs with different technologies (Plant A: conventional activated sludge; plant B: two oxidation ditches; plant C: three bioreactors; and plant D: ten lagoons in series). The concentrations of these compounds in the effluents from the fifteen STPs showed substantial variations among the STPs, with their median concentrations ranging from 26 ng/L for caffeine to 710 ng/L for carbamazepine. Risk assessment based on the "worst case scenario" of the monitoring data from the present study suggested potential toxic risks to aquatic organisms posed by carbamazepine, triclosan and diclofenac associated with such effluent discharge. With the exception of carbamazepine and gemfibrozil, significant concentration decreases between influent and effluent were observed in the four STPs studied in more detail. Biodegradation was found to be the main mechanism for removing concentrations from the liquid waste stream for the PhACs within the four STPs, while adsorption onto sludge appeared to be a minor process for all target PhACs except for triclosan. Some compounds (e.g. gemfibrozil) exhibited variable removal efficiencies within the four STPs. Plant D (10 lagoons in series) was least efficient in the removal of the target PhACs; significant biodegradation of these compounds only occurred from the sixth or seventh lagoon.

Occurrence and removal of pharmaceutically active compounds in sewage treatment plants with different technologies.

PubMed

Ying, Guang-Guo; Kookana, Rai S; Kolpin, Dana W

2009-08-01

Occurrence of eight selected pharmaceutically active compounds (PhACs; caffeine, carbamazepine, triclosan, gemfibrozil, diclofenac, ibuprofen, ketoprofen and naproxen) were investigated in effluents from fifteen sewage treatment plants (STPs) across South Australia. In addition, a detailed investigation into the removal of these compounds was also carried out in four STPs with different technologies (Plant A: conventional activated sludge; plant B: two oxidation ditches; plant C: three bioreactors; and plant D: ten lagoons in series). The concentrations of these compounds in the effluents from the fifteen STPs showed substantial variations among the STPs, with their median concentrations ranging from 26 ng/L for caffeine to 710 ng/L for carbamazepine. Risk assessment based on the "worst case scenario" of the monitoring data from the present study suggested potential toxic risks to aquatic organisms posed by carbamazepine, triclosan and diclofenac associated with such effluent discharge. With the exception of carbamazepine and gemfibrozil, significant concentration decreases between influent and effluent were observed in the four STPs studied in more detail. Biodegradation was found to be the main mechanism for removing concentrations from the liquid waste stream for the PhACs within the four STPs, while adsorption onto sludge appeared to be a minor process for all target PhACs except for triclosan. Some compounds (e.g. gemfibrozil) exhibited variable removal efficiencies within the four STPs. Plant D (10 lagoons in series) was least efficient in the removal of the target PhACs; significant biodegradation of these compounds only occurred from the sixth or seventh lagoon.

Multi-residue analysis of legacy POPs and emerging organic contaminants in Singapore's coastal waters using gas chromatography-triple quadrupole tandem mass spectrometry.

PubMed

Zhang, Hui; Bayen, Stéphane; Kelly, Barry C

2015-08-01

A gas chromatography-triple quadrupole mass spectrometry (GC-MS/MS) based method was developed for determination of 86 hydrophobic organic compounds in seawater. Solid-phase extraction (SPE) was employed for sequestration of target analytes in the dissolved phase. Ultrasound assisted extraction (UAE) and florisil chromatography were utilized for determination of concentrations in suspended sediments (particulate phase). The target compounds included multi-class hydrophobic contaminants with a wide range of physical-chemical properties. This list includes several polycyclic and nitro-aromatic musks, brominated and chlorinated flame retardants, methyl triclosan, chlorobenzenes, organochlorine pesticides (OCPs) and polychlorinated biphenyls (PCBs). Spiked MilliQ water and seawater samples were used to evaluate the method performance. Analyte recoveries were generally good, with the exception of some of the more volatile target analytes (chlorobenzenes and bromobenzenes). The method is very sensitive, with method detection limits typically in the low parts per quadrillion (ppq) range. Analysis of 51 field-collected seawater samples (dissolved and particulate-bound phases) from four distinct coastal sites around Singapore showed trace detection of several polychlorinated biphenyl congeners and other legacy POPs, as well as several current-use emerging organic contaminants (EOCs). Polycyclic and nitro-aromatic musks, bromobenzenes, dechlorane plus isomers (syn-DP, anti-DP) and methyl triclosan were frequently detected at appreciable levels (2-20,000pgL(-1)). The observed concentrations of the monitored contaminants in Singapore's marine environment were generally comparable to previously reported levels in other coastal marine systems. To our knowledge, these are the first measurements of these emerging contaminants of concern in Singapore or Southeast Asia. The developed method may prove beneficial for future environmental monitoring of hydrophobic organic contaminants in marine environments. Further, the study provides novel information regarding several potentially hazardous contaminants of concern in Singapore's marine environment, which will aid future risk assessment initiatives. Copyright © 2015 Elsevier B.V. All rights reserved.

Cascades, ``Blobby'' Turbulence, and Target Pattern Formation in Elastic Systems: A New Take on Classic Themes in Plasma Turbulence

NASA Astrophysics Data System (ADS)

Fan, Xiang

2017-10-01

Concerns central to understanding turbulence and transport include: 1) Dynamics of dual cascades in EM turbulence; 2) Understanding `negative viscosity phenomena' in drift-ZF systems; 3) The physics of blobby turbulence (re: SOL). Here, we present a study of a simple model - that of Cahn-Hilliard Navier-Stokes (CHNS) Turbulence - which sheds important new light on these issues. The CHNS equations describe the motion of binary fluid undergoing a second order phase transition and separation called spinodal decomposition. The CHNS system and 2D MHD are analogous, as they both contain a vorticity equation and a ``diffusion'' equation. The CHNS system differs from 2D MHD by the appearance of negative diffusivity, and a nonlinear dissipative flux. An analogue of the Alfven wave exists in the 2D CHNS system. DNS shows that mean square concentration spectrum Hkψ scales as k - 7 / 3 in the elastic range. This suggests an inverse cascade of Hψ . However, the kinetic energy spectrum EkK scales as k-3 , as in the direct enstrophy cascade range for a 2D fluid (not MHD!). The resolution is that the feedback of capillarity acts only at blob interfaces. Thus, as blob merger progresses, the packing fraction of interfaces decreases, thus explaining the weakened surface tension feedback and the outcome for EkK. We also examine the evolution of scalar concentration in a single eddy in the Cahn-Hilliard system. This extends the classic problem of flux expulsion in 2D MHD. The simulation results show that a target pattern is formed. Target pattern is a meta stable state, since the band merger process continues on a time scale exponentially long relative to the eddy turnover time. Band merger resembles step merger in drift-ZF staircases. This material is based upon work supported by the U.S. Department of Energy, Office of Science, Office of Fusion Energy Sciences, under Award Number DE-FG02-04ER54738.

Towards microbial fermentation metabolites as markers for health benefits of prebiotics.

PubMed

Verbeke, Kristin A; Boobis, Alan R; Chiodini, Alessandro; Edwards, Christine A; Franck, Anne; Kleerebezem, Michiel; Nauta, Arjen; Raes, Jeroen; van Tol, Eric A F; Tuohy, Kieran M

2015-06-01

Available evidence on the bioactive, nutritional and putative detrimental properties of gut microbial metabolites has been evaluated to support a more integrated view of how prebiotics might affect host health throughout life. The present literature inventory targeted evidence for the physiological and nutritional effects of metabolites, for example, SCFA, the potential toxicity of other metabolites and attempted to determine normal concentration ranges. Furthermore, the biological relevance of more holistic approaches like faecal water toxicity assays and metabolomics and the limitations of faecal measurements were addressed. Existing literature indicates that protein fermentation metabolites (phenol, p-cresol, indole, ammonia), typically considered as potentially harmful, occur at concentration ranges in the colon such that no toxic effects are expected either locally or following systemic absorption. The endproducts of saccharolytic fermentation, SCFA, may have effects on colonic health, host physiology, immunity, lipid and protein metabolism and appetite control. However, measuring SCFA concentrations in faeces is insufficient to assess the dynamic processes of their nutrikinetics. Existing literature on the usefulness of faecal water toxicity measures as indicators of cancer risk seems limited. In conclusion, at present there is insufficient evidence to use changes in faecal bacterial metabolite concentrations as markers of prebiotic effectiveness. Integration of results from metabolomics and metagenomics holds promise for understanding the health implications of prebiotic microbiome modulation but adequate tools for data integration and interpretation are currently lacking. Similarly, studies measuring metabolite fluxes in different body compartments to provide a more accurate picture of their nutrikinetics are needed.

A novel active-passive sampling approach for measuring time-averaged concentrations of pollutants in water.

PubMed

Amato, Elvio D; Covaci, Adrian; Town, Raewyn M; Hereijgers, Jonas; Bellekens, Ben; Giacometti, Valentina; Breugelmans, Tom; Weyn, Maarten; Dardenne, Freddy; Bervoets, Lieven; Blust, Ronny

2018-06-14

Passive sampling with in situ devices offers several advantages over traditional sampling methods (i.e., discrete spot sampling), however, data interpretation from conventional passive samplers is hampered by difficulties in estimating the thickness of the diffusion layer at the sampler/medium interface (δ), often leading to inaccurate determinations of target analyte concentrations. In this study, the performance of a novel device combining active and passive sampling was investigated in the laboratory. The active-passive sampling (APS) device is comprised of a diffusion cell fitted with a pump and a flowmeter. Three receiving phases traditionally used in passive sampling devices (i.e., chelex resin, Oasis HLB, and silicone rubber), were incorporated in the diffusion cell and allowed the simultaneous accumulation of cationic metals, polar, and non-polar organic compounds, respectively. The flow within the diffusion cell was accurately controlled and monitored, and, combined with diffusion coefficients measurements, enabled the average δ to be estimated. Strong agreement between APS and time-averaged total concentrations measured in discrete water samples was found for most of the substances investigated. Accuracies for metals ranged between 87 and 116%, except Cu and Pb (∼50%), whilst accuracies between 64 and 101%, and 92 and 151% were achieved for polar and non-polar organic compounds, respectively. These results indicate that, via a well-defined in situ preconcentration step, the proposed APS approach shows promise for monitoring the concentration of a range of pollutants in water. Copyright © 2018 Elsevier Ltd. All rights reserved.

Measurements of major VOCs released into the closed cabin environment of different automobiles under various engine and ventilation scenarios.

PubMed

Kim, Ki-Hyun; Szulejko, Jan E; Jo, Hyo-Jae; Lee, Min-Hee; Kim, Yong-Hyun; Kwon, Eilhann; Ma, Chang-Jin; Kumar, Pawan

2016-08-01

Volatile organic compounds (VOCs) in automobile cabins were measured quantitatively to describe their emission characteristics in relation to various idling scenarios using three used automobiles (compact, intermediate sedan, and large sedan) under three different idling conditions ([1] cold engine off and ventilation off, [2] exterior air ventilation with idling warm engine, and [3] internal air recirculation with idling warm engine). The ambient air outside the vehicle was also analyzed as a reference. A total of 24 VOCs (with six functional groups) were selected as target compounds. Accordingly, the concentration of 24 VOC quantified as key target compounds averaged 4.58 ± 3.62 ppb (range: 0.05 (isobutyl alcohol) ∼ 38.2 ppb (formaldehyde)). Moreover, if their concentrations are compared between different automobile operational modes: the 'idling engine' levels (5.24 ± 4.07) was 1.3-5 times higher than the 'engine off' levels (4.09 ± 3.23) across all 3 automobile classes. In summary, automobile in-cabin VOC emissions are highly contingent on changes in engine and ventilation modes. Copyright © 2016 Elsevier Ltd. All rights reserved.

Health risk assessment of trace elements via dietary intake of 'non-piscine protein source' foodstuffs (meat, milk and egg) in Bangladesh.

PubMed

Shaheen, Nazma; Ahmed, Md Kawser; Islam, Md Saiful; Habibullah-Al-Mamun, Md; Tukun, Avonti Basak; Islam, Saiful; M A Rahim, Abu Torab

2016-04-01

Concentrations of six trace elements [chromium (Cr), nickel (Ni), copper (Cu), cadmium (Cd), lead (Pb) and arsenic (As)] were assessed in 'non-piscine protein source' foodstuffs (meat, milk and eggs) to evaluate contamination level and human health risks in Bangladesh. The range of Cr, Ni, Cu, Cd, Pb and As in the investigated foodstuffs was 1.24-2.17, 1.29-2.56, 0.92-2.31, 0.12-0.44, 0.15-0.48 and 0.14-0.57 mg kg fresh weight(-1), respectively. The estimated mean levels of most of the elements were higher than the maximum allowable concentration (MAC) for dietary foods. The estimated daily intakes (EDIs) of Cr and Cd were higher than the maximum tolerable daily intake (MTDI) for children, indicating that they are more susceptible to toxic elements through food consumption. The target hazard quotients (THQs) and target carcinogenic risk (TCR) of As (THQ > 1 and TCR > 10(-4)) for both the adults and children suggest that the consumers of non-piscine foodstuffs (especially cow milk and chicken meat) are exposed chronically to metal pollution with carcinogenic and non-carcinogenic health consequences.

Development and validation of a solid-phase extraction gas chromatography–mass spectrometry method for the simultaneous quantification of methadone, heroin, cocaine and metabolites in sweat

PubMed Central

Brunet, Bertrand R.; Barnes, Allan J.; Scheidweiler, Karl B.; Mura, Patrick

2009-01-01

A sensitive and specific method is presented to simultaneously quantify methadone, heroin, cocaine and metabolites in sweat. Drugs were eluted from sweat patches with sodium acetate buffer, followed by SPE and quantification by GC/MS with electron impact ionization and selected ion monitoring. Daily calibration for anhydroecgonine methyl ester, ecgonine methyl ester, cocaine, benzoylecgonine (BE), codeine, morphine, 6-acetylcodeine, 6-acetylmorphine (6AM), heroin (5–1000 ng/patch) and methadone (10–1000 ng/patch) achieved determination coefficients of >0.995, and calibrators quantified to within ±20% of the target concentrations. Extended calibration curves (1000–10,000 ng/patch) were constructed for methadone, cocaine, BE and 6AM by modifying injection techniques. Within (N=5) and between-run (N=20) imprecisions were calculated at six control levels across the dynamic ranges with coefficients of variation of <6.5%. Accuracies at these concentrations were ±11.9% of target. Heroin hydrolysis during specimen processing was <11%. This novel assay offers effective monitoring of drug exposure during drug treatment, workplace and criminal justice monitoring programs. PMID:18607576

Label-Free Nanopore Biosensor for Rapid and Highly Sensitive Cocaine Detection in Complex Biological Fluids.

PubMed

Rauf, Sana; Zhang, Ling; Ali, Asghar; Liu, Yang; Li, Jinghong

2017-02-24

Detection of very low amounts of illicit drugs such as cocaine in clinical fluids like serum continues to be important for many areas in the fight against drug trafficking. Herein, we constructed a label-free nanopore biosensor for rapid and highly sensitive detection of cocaine in human serum and saliva samples based on target-induced strand release strategy. In this bioassay, an aptamer for cocaine was prehybridized with a short complementary DNA. Owing to cocaine specific binding with aptamer, the short DNA strand was displaced from aptamer and translocation of this output DNA through α-hemolysin nanopore generated distinct spike-like current blockages. When plotted in double-logarithmic scale, a linear relationship between target cocaine concentration and output DNA event frequency was obtained in a wide concentration range from 50 nM to 100 μM of cocaine, with the limit of detection down to 50 nM. In addition, this aptamer-based sensor method was successfully applied for cocaine detection in complex biological fluids like human saliva and serum samples with great selectivity. Simple preparation, low cost, rapid, label-free, and real sample detection are the motivating factors for practical application of the proposed biosensor.

Designing multilayered nanoplatforms for SERS-based detection of genetically modified organisms

NASA Astrophysics Data System (ADS)

Uluok, Saadet; Guven, Burcu; Eksi, Haslet; Ustundag, Zafer; Tamer, Ugur; Boyaci, Ismail Hakki

2015-01-01

In this study, the multilayered surface-enhanced Raman spectroscopy (SERS) platforms were developed for the analysis of genetically modified organisms (GMOs). For this purpose, two molecules [11-mercaptoundecanoic acid (11-MUA) and 2-mercaptoethylamine (2-MEA)] were attached with Aurod and Auspherical nanoparticles to form multilayered constructions on the gold (Au)slide surface. The best multilayered platform structure was chosen depending on SERS enhancement, and this surface was characterised with atomic force microscopy (AFM) and attenuated total reflectance Fourier transform infrared spectroscopy. After the optimum multilayered SERS platform and nanoparticle interaction was identified, the oligonucleotides on the Aurod nanoparticles and Auslide were combined to determine target concentrations from the 5,5'-dithiobis (2-nitrobenzoic acid) (DTNB) signals using SERS. The correlation between the SERS intensities for DTNB and target concentrations was found to be linear within a range of 10 pM to 1 µM, and with a detection limit of 34 fM. The selectivity and specificity of the developed sandwich assay were tested using negative and positive controls, and nonsense and real sample studies. The obtained results showed that the multilayered SERS sandwich method allows for sensitive, selective, and specific detection of oligonucleotide sequences.

A Quasi-Experiment To Study the Impact of Vancomycin Area under the Concentration-Time Curve-Guided Dosing on Vancomycin-Associated Nephrotoxicity

PubMed Central

Finch, Natalie A.; Zasowski, Evan J.; Murray, Kyle P.; Mynatt, Ryan P.; Zhao, Jing J.; Yost, Raymond; Pogue, Jason M.

2017-01-01

ABSTRACT Evidence suggests that maintenance of vancomycin trough concentrations at between 15 and 20 mg/liter, as currently recommended, is frequently unnecessary to achieve the daily area under the concentration-time curve (AUC24) target of ≥400 mg · h/liter. Many patients with trough concentrations in this range have AUC24 values in excess of the therapeutic threshold and within the exposure range associated with nephrotoxicity. On the basis of this, the Detroit Medical Center switched from trough concentration-guided dosing to AUC-guided dosing to minimize potentially unnecessary vancomycin exposure. The primary objective of this analysis was to assess the impact of this intervention on vancomycin-associated nephrotoxicity in a single-center, retrospective quasi-experiment of hospitalized adult patients receiving intravenous vancomycin from 2014 to 2015. The primary analysis compared the incidence of nephrotoxicity between patients monitored by assessment of the AUC24 and those monitored by assessment of the trough concentration. Multivariable logistic and Cox proportional hazards regression examined the independent association between the monitoring strategy and nephrotoxicity. Secondary analysis compared vancomycin exposures (total daily dose, AUC, and trough concentrations) between monitoring strategies. Overall, 1,280 patients were included in the analysis. After adjusting for severity of illness, comorbidity, duration of vancomycin therapy, and concomitant receipt of nephrotoxins, AUC-guided dosing was independently associated with lower nephrotoxicity by both logistic regression (odds ratio, 0.52; 95% confidence interval [CI], 0.34 to 0.80; P = 0.003) and Cox proportional hazards regression (hazard ratio, 0.53; 95% CI, 0.35 to 0.78; P = 0.002). AUC-guided dosing was associated with lower total daily vancomycin doses, AUC values, and trough concentrations. Vancomycin AUC-guided dosing was associated with reduced nephrotoxicity, which appeared to be a result of reduced vancomycin exposure. PMID:28923869

A Quasi-Experiment To Study the Impact of Vancomycin Area under the Concentration-Time Curve-Guided Dosing on Vancomycin-Associated Nephrotoxicity.

PubMed

Finch, Natalie A; Zasowski, Evan J; Murray, Kyle P; Mynatt, Ryan P; Zhao, Jing J; Yost, Raymond; Pogue, Jason M; Rybak, Michael J

2017-12-01

Evidence suggests that maintenance of vancomycin trough concentrations at between 15 and 20 mg/liter, as currently recommended, is frequently unnecessary to achieve the daily area under the concentration-time curve (AUC 24 ) target of ≥400 mg · h/liter. Many patients with trough concentrations in this range have AUC 24 values in excess of the therapeutic threshold and within the exposure range associated with nephrotoxicity. On the basis of this, the Detroit Medical Center switched from trough concentration-guided dosing to AUC-guided dosing to minimize potentially unnecessary vancomycin exposure. The primary objective of this analysis was to assess the impact of this intervention on vancomycin-associated nephrotoxicity in a single-center, retrospective quasi-experiment of hospitalized adult patients receiving intravenous vancomycin from 2014 to 2015. The primary analysis compared the incidence of nephrotoxicity between patients monitored by assessment of the AUC 24 and those monitored by assessment of the trough concentration. Multivariable logistic and Cox proportional hazards regression examined the independent association between the monitoring strategy and nephrotoxicity. Secondary analysis compared vancomycin exposures (total daily dose, AUC, and trough concentrations) between monitoring strategies. Overall, 1,280 patients were included in the analysis. After adjusting for severity of illness, comorbidity, duration of vancomycin therapy, and concomitant receipt of nephrotoxins, AUC-guided dosing was independently associated with lower nephrotoxicity by both logistic regression (odds ratio, 0.52; 95% confidence interval [CI], 0.34 to 0.80; P = 0.003) and Cox proportional hazards regression (hazard ratio, 0.53; 95% CI, 0.35 to 0.78; P = 0.002). AUC-guided dosing was associated with lower total daily vancomycin doses, AUC values, and trough concentrations. Vancomycin AUC-guided dosing was associated with reduced nephrotoxicity, which appeared to be a result of reduced vancomycin exposure. Copyright © 2017 American Society for Microbiology.

Antibacterial, antifungal and cytotoxic evaluation of some new quinazolinone derivatives

PubMed Central

Hassanzadeh, F.; Jafari, E.; Hakimelahi, G.H.; Khajouei, M. Rahmani; Jalali, M.; Khodarahmi, G.A.

2012-01-01

Quinazolinone ring system is renown because of its wide spectrum of pharmacological activities due to various substitutions on this ring system. In this study, the minimum inhibitory concentration of the synthesized compounds in our laboratory was determined by micro dilution Alamar Blue® Assay against six strains of bacteria (three Gram-positive and three Gram-negative) and three strains of fungi. Following a broth micro dilution minimum inhibitory concentration (MIC) test, Minimum Bactericidal Concentration (MBC) and Minimum Fungicidal Concentration (MFC) tests were performed. Cytotoxic effects of the compounds were measured using the MTT colorimetric assay on HeLa cell line. Results of antimicrobial screening showed that compounds had better bacteriostatic activity against Gram-negative bacteria. Results from MBC revealed that these compounds had more significant bacteriostatic than bactericidal activities. Nearly all screened compounds showed good activity against C. albicans and A. niger. Results from MFC indicated that these compounds had better fungistatic rather than fungicidal activities. The synthesized target molecules were found to exhibit different cytotoxicity in the range of 10 to 100 μM on HeLa cell line. Compounds 6 and 7 exhibited acceptable cytotoxicity approximately 50% at 10 μM concentration. PMID:23181085

Proof of the quantitative potential of immunofluorescence by mass spectrometry.

PubMed

Toki, Maria I; Cecchi, Fabiola; Hembrough, Todd; Syrigos, Konstantinos N; Rimm, David L

2017-03-01

Protein expression in formalin-fixed, paraffin-embedded patient tissue is routinely measured by Immunohistochemistry (IHC). However, IHC has been shown to be subject to variability in sensitivity, specificity and reproducibility, and is generally, at best, considered semi-quantitative. Mass spectrometry (MS) is considered by many to be the criterion standard for protein measurement, offering high sensitivity, specificity, and objective molecular quantification. Here, we seek to show that quantitative immunofluorescence (QIF) with standardization can achieve quantitative results comparable to MS. Epidermal growth factor receptor (EGFR) was measured by quantitative immunofluorescence in 15 cell lines with a wide range of EGFR expression, using different primary antibody concentrations, including the optimal signal-to-noise concentration after quantitative titration. QIF target measurement was then compared to the absolute EGFR concentration measured by Liquid Tissue-selected reaction monitoring mass spectrometry. The best agreement between the two assays was found when the EGFR primary antibody was used at the optimal signal-to-noise concentration, revealing a strong linear regression (R 2 =0.88). This demonstrates that quantitative optimization of titration by calculation of signal-to-noise ratio allows QIF to be standardized to MS and can therefore be used to assess absolute protein concentration in a linear and reproducible manner.

Detection of stain formation on teeth by oral antiseptic solution using fiber optic displacement sensor

NASA Astrophysics Data System (ADS)

Rahman, H. A.; Rahim, H. R. A.; Harun, S. W.; Yasin, M.; Apsari, R.; Ahmad, H.; Wan Abas, W. A. B.

2013-02-01

The application of a simple intensity modulated fiber optic displacement sensor for the detection of stain formation on human teeth is demonstrated. The proposed sensor uses a concentric type bundled plastic optical fiber (POF) as a probe in conjunction with the surfaces of five human teeth as the reflecting targets. Prior to the experiment, the stains were produced extrinsically by soaking the teeth in different concentrations of oral antiseptic solution containing hexetidine. The concentration of the oral antiseptic solution is measured in volume%. For a concentration change from 0% to 80%, the peak voltage decreases exponentially from 1.15 mV to 0.41 mV with a measured resolution of 0.48% and 1.75% for concentration ranges of 0-40% and 40-80%, respectively. The correlation between the detector output and variation in the color of human tooth surface has successfully been examined. Simple in design and low in cost, this sensor can detect color changes due to hexetidine-induced stain on a tooth surface in a fast and convenient way. Thus, this sensor will be very promising in esthetic dentistry, dental color matching techniques, chemical and biomedical applications.

Cysteine-Zn2+ complexes: unique molecular switches for inducible nitric oxide synthase-derived NO.

PubMed

Kröncke, K D

2001-11-01

Nitric oxide (NO) in the low nanomolar range acts as a transcellular messenger molecule to initiate regulatory and physiological responses in nearby target cells via binding to the soluble guanylate cyclase heme moiety. Higher NO concentrations, as synthesized by the inducible NO synthase (iNOS) during inflammatory processes, show additional effects: NO may react with O2, yielding nitrogen oxides like N2O3 that are able to nitrosate thiols. A variety of proteins involved in very different functions of the cell contain cysteine-Zn2+ complexes. Effects of NO on different proteins containing cysteine-Zn2+ domains and playing essential roles during transcription, protein folding, and proteolysis are discussed. It is suggested that iNOS-derived NO acts as a signal molecule targeting cysteine-Zn2+ linkages, thus enabling cells to react toward nitrosative stress.

The characteristics simulation of FMCW laser backscattering signals

NASA Astrophysics Data System (ADS)

Liu, Bohu; Song, Chengtian; Duan, Yabo

2018-04-01

A Monte Carlo simulation model of FMCW laser transmission in a smoke interference environment was established in this paper. The aerosol extinction coefficient and scattering coefficient changed dynamically in the simulation according to the smoke concentration variation, aerosol particle distributions and photon spatial positions. The simulation results showed that the smoke backscattering interference produced a number of amplitude peaks in the beat signal spectrum; the SNR of target echo signal to smoke interference was related to the transmitted laser wavelength and the aerosol particle size distribution; a better SNR could be obtained when the laser wavelength was in the range of 560-1660 nm. The characteristics of FMCW laser backscattering signals generated by simulation are consistent with the theoretical analysis. Therefore, this study was greatly helpful for improving the ability of identifying target and anti-interference in the further research.

RGD-functionalized ultrasmall iron oxide nanoparticles for targeted T1-weighted MR imaging of gliomas

NASA Astrophysics Data System (ADS)

Luo, Yu; Yang, Jia; Yan, Yu; Li, Jingchao; Shen, Mingwu; Zhang, Guixiang; Mignani, Serge; Shi, Xiangyang

2015-08-01

We report a convenient approach to prepare ultrasmall Fe3O4 nanoparticles (NPs) functionalized with an arginylglycylaspartic acid (RGD) peptide for in vitro and in vivo magnetic resonance (MR) imaging of gliomas. In our work, stable sodium citrate-stabilized Fe3O4 NPs were prepared by a solvothermal route. Then, the carboxylated Fe3O4 NPs stabilized with sodium citrate were conjugated with polyethylene glycol (PEG)-linked RGD. The formed ultrasmall RGD-functionalized nanoprobe (Fe3O4-PEG-RGD) was fully characterized using different techniques. We show that these Fe3O4-PEG-RGD particles with a size of 2.7 nm are water-dispersible, stable, cytocompatible and hemocompatible in a given concentration range, and display targeting specificity to glioma cells overexpressing αvβ3 integrin in vitro. With the relatively high r1 relaxivity (r1 = 1.4 mM-1 s-1), the Fe3O4-PEG-RGD particles can be used as an efficient nanoprobe for targeted T1-weighted positive MR imaging of glioma cells in vitro and the xenografted tumor model in vivo via an active RGD-mediated targeting pathway. The developed RGD-functionalized Fe3O4 NPs may hold great promise to be used as a nanoprobe for targeted T1-weighted MR imaging of different αvβ3 integrin-overexpressing cancer cells or biological systems.We report a convenient approach to prepare ultrasmall Fe3O4 nanoparticles (NPs) functionalized with an arginylglycylaspartic acid (RGD) peptide for in vitro and in vivo magnetic resonance (MR) imaging of gliomas. In our work, stable sodium citrate-stabilized Fe3O4 NPs were prepared by a solvothermal route. Then, the carboxylated Fe3O4 NPs stabilized with sodium citrate were conjugated with polyethylene glycol (PEG)-linked RGD. The formed ultrasmall RGD-functionalized nanoprobe (Fe3O4-PEG-RGD) was fully characterized using different techniques. We show that these Fe3O4-PEG-RGD particles with a size of 2.7 nm are water-dispersible, stable, cytocompatible and hemocompatible in a given concentration range, and display targeting specificity to glioma cells overexpressing αvβ3 integrin in vitro. With the relatively high r1 relaxivity (r1 = 1.4 mM-1 s-1), the Fe3O4-PEG-RGD particles can be used as an efficient nanoprobe for targeted T1-weighted positive MR imaging of glioma cells in vitro and the xenografted tumor model in vivo via an active RGD-mediated targeting pathway. The developed RGD-functionalized Fe3O4 NPs may hold great promise to be used as a nanoprobe for targeted T1-weighted MR imaging of different αvβ3 integrin-overexpressing cancer cells or biological systems. Electronic supplementary information (ESI) available: Additional experimental results. See DOI: 10.1039/c5nr04003e

Bioprospecting for secondary metabolites in the entomopathogenic bacterium Photorhabdus luminescens subsp. sonorensis.

PubMed

Orozco, Rousel A; Molnár, István; Bode, Helge; Stock, S Patricia

2016-11-01

Crude extracts of in vitro and in vivo cultures of two strains of Photorhabdus l. sonorensis (Enterobacteriaceae) were analyzed by TLC, HPLC-UV and LC-MS. Nine unique compounds with mass/charge ratios (m/z) ranging from 331.3 to 713.5 were found in MS analyses. Bioactivity of extracts was assessed on a selection of plant pathogens/pests and non-target species. Caborca strain extracts showed the highest activity against Helicoverpa zea (Lepidoptera: Noctuidae) neonates at all concentrations tested. Mortality ranged from 11% (at 10μg/ml) to 37% (at 40μg/ml). Strain CH35 extracts showed the highest nematicidal activity on Meloidogyne incognita (Tylenchida: Meloidogynidae) at 40μg/ml. Low to no nematicidal activity was observed against the non-target species Steinernema carpocapsae (Rhabditida: Steinernematidae) and Caenorhabditis elegans (Rhabditida: Rhabditidae). Caborca extracts exhibited a strong antibiotic effect on Pseudomonas syringae (Pseudomonadales: Pseudomonadacedae) at 40μg/ml, while both Caborca and CH35 extracts inhibited the growth of Bacillus subitillis (Bacillales: Bacillaceae) at 40μg/ml. All extracts strongly inhibited the growth of the fungus Fusarium oxysporum (Hypocreales: Nectriceae) but not that of Alternaria alternata (Pleosporales: Pleosporaceae). Contrastingly, a moderate to high inhibitory effect was denoted on the non-target biocontrol fungus Beauveria bassiana (Hypocreales: Clavivipitaceae). Crown Copyright © 2016. Published by Elsevier Inc. All rights reserved.

Newborn screening by matrix-assisted laser desorption/ionization mass spectrometry based on parylene-matrix chip.

PubMed

Kim, Jo-Il; Noh, Joo-Yoon; Kim, Mira; Park, Jong-Min; Song, Hyun-Woo; Kang, Min-Jung; Pyun, Jae-Chul

2017-08-01

Newborn screening for diagnosis of phenylketonuria, homocystinuria, and maple syrup urine disease have been conducted by analyzing the concentration of target amino acids using matrix-assisted laser desorption/ionization time-of-flight mass spectrometry (MALDI-ToF MS) based on parylene-matrix chip. Parylene-matrix chip was applied to MALDI-ToF MS analysis reducing the matrix peaks significantly at low mass-to-charge ratio range (m/z < 500). Reproducibility of inter-spot and intra-spot analyses of amino acids was less than 10%. Methanol extraction was adopted for simple and rapid sample preparation of serum before mass spectrometric analysis showing 13.3 to 45% of extraction efficiency. Calibration curves for diagnosis of neonatal metabolic disorders were obtained by analyzing methanol-extracted serum spiked with target amino acids using MALDI-ToF MS. They showed good linearity (R 2  > 0.98) and the LODs were ranging from 9.0 to 22.9 μg/mL. Effect of proteins in serum was estimated by comparing MALDI-ToF mass spectra of amino acids-spiked serum before and after the methanol extraction. Interference of other amino acids on analysis of target analyte was determined to be insignificant. From these results, MALDI-ToF MS based on parylene-matrix chip could be applicable to medical diagnosis of neonatal metabolic disorders. Copyright © 2017 Elsevier Inc. All rights reserved.

Concentration of perrhenate and pertechnetate solutions

DOEpatents

Knapp, F.F.; Beets, A.L.; Mirzadeh, S.; Guhlke, S.

1998-03-17

A method is described for preparing a concentrated solution of a carrier-free radioisotope which includes the steps of: (a) providing a generator column loaded with a composition containing a parent radioisotope; (b) eluting the generator column with an eluent solution which includes a salt of a weak acid to elute a target daughter radioisotope from the generator column in a first eluate; (c) eluting a cation-exchange column with the first eluate to exchange cations of the salt for hydrogen ions and to elute the target daughter radioisotope and a weak acid in a second eluate; (d) eluting an anion-exchange column with the second eluate to trap and concentrate the target daughter radioisotope and to elute the weak acid solution therefrom; and (e) eluting the concentrated target daughter radioisotope from the anion-exchange column with a saline solution. 1 fig.

Concentration of perrhenate and pertechnetate solutions

DOEpatents

Knapp, Furn F.; Beets, Arnold L.; Mirzadeh, Saed; Guhlke, Stefan

1998-01-01

A method of preparing a concentrated solution of a carrier-free radioisotope which includes the steps of: a. providing a generator column loaded with a composition containing a parent radioisotope; b. eluting the generator column with an eluent solution which includes a salt of a weak acid to elute a target daughter radioisotope from the generator column in a first eluate. c. eluting a cation-exchange column with the first eluate to exchange cations of the salt for hydrogen ions and to elute the target daughter radioisotope and a weak acid in a second eluate; d. eluting an anion-exchange column with the second eluate to trap and concentrate the target daughter radioisotope and to elute the weak acid solution therefrom; and e. eluting the concentrated target daughter radioisotope from the anion-exchange column with a saline solution.

Geochemical characterization of water, sediment, and biota affected by mercury contamination and acidic drainage from historical gold mining, Greenhorn Creek, Nevada County, California, 1999-2001

USGS Publications Warehouse

Alpers, Charles N.; Hunerlach, Michael P.; May, Jason T.; Hothem, Roger L.; Taylor, Howard E.; Antweiler, Ronald C.; De Wild, John F.; Lawler, David A.

2005-01-01

In 1999, the U.S. Geological Survey (USGS) initiated studies of mercury and methylmercury occurrence, transformation, and transport in the Bear River and Yuba River watersheds of the northwestern Sierra Nevada. Because these watersheds were affected by large-scale, historical gold extraction using mercury amalgamation beginning in the 1850s, they were selected for a pilot study of mercury transport by the USGS and other cooperating agencies. This report presents data on methylmercury (MeHg) and total mercury (THg) concentrations in water, bed sediment, invertebrates, and frogs collected at 40 stations during 1999-2001 in the Greenhorn Creek drainage, a major tributary to Bear River. Results document several mercury contamination ?hot spots? that represent potential targets for ongoing and future remediation efforts at abandoned mine sites in the study area. Water-quality samples were collected one or more times at each of 29 stations. The concentrations of total mercury in 45 unfiltered water samples ranged from 0.80 to 153,000 nanograms per liter (ng/L); the median was 9.6 ng/L. Total mercury concentrations in filtered water (41 samples) ranged from less than 0.3 to 8,000 ng/L; the median was 2.7 ng/L. Concentrations of methylmercury in the unfiltered water (40 samples) ranged from less than 0.04 to 9.1 ng/L; the median was 0.07 ng/L. Methylmercury in filtered water (13 samples) ranged from less than 0.04 to 0.27 ng/L; the median was 0.04 ng/L. Acidic drainage with pH values as low as 3.4 was encountered in some of the mined areas. Elevated concentrations of aluminum, cadmium, copper, iron, manganese, nickel, and zinc were found at several stations, especially in the more acidic water samples. Total mercury concentrations in sediment were determined by laboratory and field methods. Total mercury concentrations (determined by laboratory methods) in ten samples from eight stations ranged from about 0.0044 to 12 ?g/g (microgram per gram, equivalent to parts per million). Methylmercury concentrations in these samples ranged from less than 0.00011 to 0.0095 ?g/g. A field panning method was used to determine the concentration of liquid elemental mercury in 22 samples from 14 stations. Measured quantities of elemental mercury recovered by panning ranged from a trace amount estimated at 100 milligrams per kilogram (equivalent to parts per million) to 45,000 milligrams per kilogram (equivalent to 4.5 per cent, by weight). In total, 194 invertebrate samples were collected at 31 stations; 78 of the samples were analyzed for concentrations of THg and MeHg and used to calculate MeHg to THg ratios. A total of 69 frog samples were collected at 19 stations, and all were analyzed only for THg. Ranges of MeHg concentrations (?g/g, wet weight) in invertebrate samples and number of samples (n) were 0.0012-0.048 for banana slugs (Arionidae, n = 27), 0.027-0.39 for dobsonflies (Corydalidae, n = 14), 0.029-0.50 for predaceous diving beetles (Dytiscidae, n = 31), 0.026-0.52 for predaceous stoneflies (Perlidae, n = 18), 0.011-1.6 for dragonflies (Odonata, n = 46), and 0.061-0.55 for water striders (Gerridae, n = 56). The ratio of MeHg to THg in invertebrates was greater than 50 percent for 74 of 78 samples. The data from this reconnaissance sampling effort have been used by land-management agencies in selecting abandoned mine sites for remediation. The Forest Service has remediated the Sailor Flat site, and the Bureau of Land Management has initiated plans to remediate the Boston Mine drainage tunnel.

Evaluation of toxicity and estrogenicity of the landfill-concentrated leachate during advanced oxidation treatment: chemical analyses and bioanalytical tools.

PubMed

Wang, Guifang; Lu, Gang; Zhao, Jiandi; Yin, Pinghe; Zhao, Ling

2016-08-01

Landfill-concentrated leachate from membrane separation processes is a potential pollution source for the surroundings. In this study, the toxicity and estrogenicity potentials of concentrated leachate prior to and during UV-Fenton and Fenton treatments were assessed by a combination of chemical (di (2-ethylhexyl) phthalate and dibutyl phthalate were chosen as targets) and biological (Daphnia magna, Chlorella vulgaris, and E-screen assay) analyses. Removal efficiencies of measured di (2-ethylhexyl) phthalate and dibutyl phthalate were more than 97 % after treatment with the two methods. Biological tests showed acute toxicity effects on D. magna tests in untreated concentrated leachate samples, whereas acute toxicity on C. vulgaris tests was not observed. Both treatment methods were found to be efficient in reducing acute toxicity effects on D. magna tests. The E-screen test showed concentrated leachate had significant estrogenicity, UV-Fenton and Fenton treatment, especially the former, were effective methods for reducing estrogenicity of concentrated leachate. The EEQchem (estradiol equivalent concentration) of all samples could only explain 0.218-5.31 % range of the EEQbio. These results showed that UV-Fenton reagent could be considered as a suitable method for treatment of concentrated leachate, and the importance of the application of an integrated (biological + chemical) analytical approach for a comprehensive evaluation of treatment suitability.

Predicting Drug Concentration‐Time Profiles in Multiple CNS Compartments Using a Comprehensive Physiologically‐Based Pharmacokinetic Model

PubMed Central

Yamamoto, Yumi; Välitalo, Pyry A.; Huntjens, Dymphy R.; Proost, Johannes H.; Vermeulen, An; Krauwinkel, Walter; Beukers, Margot W.; van den Berg, Dirk‐Jan; Hartman, Robin; Wong, Yin Cheong; Danhof, Meindert; van Hasselt, John G. C.

2017-01-01

Drug development targeting the central nervous system (CNS) is challenging due to poor predictability of drug concentrations in various CNS compartments. We developed a generic physiologically based pharmacokinetic (PBPK) model for prediction of drug concentrations in physiologically relevant CNS compartments. System‐specific and drug‐specific model parameters were derived from literature and in silico predictions. The model was validated using detailed concentration‐time profiles from 10 drugs in rat plasma, brain extracellular fluid, 2 cerebrospinal fluid sites, and total brain tissue. These drugs, all small molecules, were selected to cover a wide range of physicochemical properties. The concentration‐time profiles for these drugs were adequately predicted across the CNS compartments (symmetric mean absolute percentage error for the model prediction was <91%). In conclusion, the developed PBPK model can be used to predict temporal concentration profiles of drugs in multiple relevant CNS compartments, which we consider valuable information for efficient CNS drug development. PMID:28891201

A Rapid and Quantitative Flow Cytometry Method for the Analysis of Membrane Disruptive Antimicrobial Activity.

PubMed

O'Brien-Simpson, Neil M; Pantarat, Namfon; Attard, Troy J; Walsh, Katrina A; Reynolds, Eric C

2016-01-01

We describe a microbial flow cytometry method that quantifies within 3 hours antimicrobial peptide (AMP) activity, termed Minimum Membrane Disruptive Concentration (MDC). Increasing peptide concentration positively correlates with the extent of bacterial membrane disruption and the calculated MDC is equivalent to its MBC. The activity of AMPs representing three different membranolytic modes of action could be determined for a range of Gram positive and negative bacteria, including the ESKAPE pathogens, E. coli and MRSA. By using the MDC50 concentration of the parent AMP, the method provides high-throughput, quantitative screening of AMP analogues. A unique feature of the MDC assay is that it directly measures peptide/bacteria interactions and lysed cell numbers rather than bacteria survival as with MIC and MBC assays. With the threat of multi-drug resistant bacteria, this high-throughput MDC assay has the potential to aid in the development of novel antimicrobials that target bacteria with improved efficacy.

Reducing PEC uncertainty in coastal zones: a case study on carbamazepine, oxcarbazepine and their metabolites.

PubMed

Fenet, Hélène; Arpin-Pont, Lauren; Vanhoutte-Brunier, Alice; Munaron, Dominique; Fiandrino, Annie; Martínez Bueno, Maria-Jesus; Boillot, Clotilde; Casellas, Claude; Mathieu, Olivier; Gomez, Elena

2014-07-01

Concentrations of the antiepileptic drugs carbamazepine (Cbz), oxcarbazepine (OxCz) and their main metabolites were predicted in a wastewater treatment plant (WTP) and in the vicinity of its submarine outfall located in a Mediterranean coastal zone. Refined predicted environmental concentrations (PECs) were calculated in effluents based on consumption data and human excretion rates. PECs were estimated in the sea using the hydrodynamic MARS 3D model integrating meteorological data, oceanic conditions (wind, tide, atmospheric pressure), freshwater and sewage inputs. Measured environmental concentrations (MECs) were compared to PECs to assess the estimation relevance. In the coastal zone, PEC and MEC were in the same magnitude range. Modeling of Cbz diffusion and advection just above the submarine outfall showed the influence of the thermocline during summer, with low diffusion of Cbz from the bottom to the surface. This work allowed understanding the dispersion of target compounds and deserved further development for a better acknowledgement of vulnerability at local scales. Copyright © 2014 Elsevier Ltd. All rights reserved.

Failure of the public health testing program for ballast water treatment systems.

PubMed

Cohen, Andrew N; Dobbs, Fred C

2015-02-15

Since 2004, an international testing program has certified 53 shipboard treatment systems as meeting ballast water discharge standards, including limits on certain microbes to prevent the spread of human pathogens. We determined how frequently certification tests failed a minimum requirement for a meaningful evaluation, that the concentration of microbes in the untreated (control) discharge must exceed the regulatory limit for treated discharges. In 95% of cases where the result was accepted as evidence that the treatment system reduced microbes to below the regulatory limit, the discharge met the limit even without treatment. This shows that the certification program for ballast water treatment systems is dysfunctional in protecting human health. In nearly all cases, the treatment systems would have equally well "passed" these tests even if they had never been turned on. Protocols must require minimum concentrations of targeted microbes in test waters, reflecting the upper range of concentrations in waters where ships operate. Copyright © 2014 Elsevier Ltd. All rights reserved.

Streamwater nitrate concentrations in six agricultural catchments in Scotland.

PubMed

Hooda, P S; Moynagh, M; Svoboda, I F; Thurlow, M; Stewart, M; Thomson, M; Anderson, H A

1997-08-01

The concentrations of nitrate-N (NO3-N) in catchment inputs and outputs have been compared and contrasted between 6 farm catchments in Scotland, 3 in the West and 3 in the North-East. Forms of intensive animal farming ranging between beef and dairy cattle, sheep and poultry give different sources for potential NO3-N leakage from the systems. While stream reaches bordered by intensive cereal production give rise to the largest inputs to surface waters, climatic influences result in the more-efficient use of fertilizer- and farm waste-N in the West, and an enhanced potential for N-loss to waters in the cooler North-East, regardless of the N-inputs being considerably lower in the latter region. Although the EC Nitrate Directive limit of 11.3 mg NO3-N 1(-1) was not exceeded, peak values occurring during summer baseflows and autumn soil rewetting were commonly larger than the 'target' maximum concentration of 5.65 mg NO3-N 1-1.

Measurement of the para-hydrogen concentration in the ISIS moderators using neutron transmission and thermal conductivity

NASA Astrophysics Data System (ADS)

Romanelli, Giovanni; Rudić, Svemir; Zanetti, Matteo; Andreani, Carla; Fernandez-Alonso, Felix; Gorini, Giuseppe; Krzystyniak, Maciej; Škoro, Goran

2018-04-01

We present an experimental study to determine the para-hydrogen concentration in the hydrogen moderators at the ISIS pulsed neutron and muon source. The experimental characterisation is based on neutron transmission experiments performed on the VESUVIO spectrometer, and thermal conductivity measurements using the TOSCA para-hydrogen rig. A reliable estimation of the level of para-hydrogen concentration in the hydrogen moderators is of crucial importance in the framework of a current project to completely refurbish the first target station at ISIS. Moreover, we report a new measurement of the total neutron cross section for normal hydrogen at 15 K on the broad energy range 3 meV -10 eV suggesting a revision of the most recent nuclear libraries for incident neutron energies lower than 10 meV. Finally, we characterise systematic errors affecting the para-hydrogen level estimation due to conversion from para to ortho hydrogen, as a function of the time a batch of gas spends in every component of our gas panel and apparatus.

Accumulation patterns of lipophilic organic contaminants in surface sediments and in economic important mussel and fish species from Jakarta Bay, Indonesia.

PubMed

Dwiyitno; Dsikowitzky, Larissa; Nordhaus, Inga; Andarwulan, Nuri; Irianto, Hari Eko; Lioe, Hanifah Nuryani; Ariyani, Farida; Kleinertz, Sonja; Schwarzbauer, Jan

2016-09-30

Non-target screening analyses were conducted in order to identify a wide range of organic contaminants in sediment and animal tissue samples from Jakarta Bay. High concentrations of di-iso-propylnaphthalenes (DIPNs), linear alkylbenzenes (LABs) and polycyclic aromatic hydrocarbons (PAHs) were detected in all samples, whereas phenylmethoxynaphthalene (PMN), DDT and DDT metabolites (DDX) were detected at lower concentrations. In order to evaluate the uptake and accumulation by economic important mussel (Perna viridis) and fish species, contaminant patterns of DIPNs, LABs and PAHs in different compartments were compared. Different patterns of these contaminant groups were found in sediment and animal tissue samples, suggesting compound-specific accumulation and metabolism processes. Significantly higher concentrations of these three contaminant groups in mussel tissue as compared to fish tissue from Jakarta Bay were found. Because P. viridis is an important aquaculture species in Asia, this result is relevant for food safety. Copyright © 2016 Elsevier Ltd. All rights reserved.

Multi-residue analysis of 26 organochlorine pesticides in Alpinia oxyphylla by GC-ECD after solid phase extraction and acid cleanup.

PubMed

Zhao, Xiangsheng; Zhou, Yakui; Kong, Weijun; Gong, Bao; Chen, Deli; Wei, Jianhe; Yang, Meihua

2016-04-01

A simple and effective multi-residue method was developed and validated for the analysis of 26 organochlorine pesticide residues in Alpinia oxyphylla by a gas chromatography with an electron capture detector (GC-ECD). The target pesticides were extracted by sonication and cleaned up with florisil solid phase extraction and sulphuric acid. Some crucial parameters, including extraction solvent and time, sorbent type, elute solvent and concentration of sulphuric acid were optimized to improve the performance of sample preparation procedure. The optimized method gave high sensitivity with detection limit ranging from 0.1 to 2.0μg/kg. Matrix-matched calibration was employed for the quantification, and a wide linear range (from 1.0 to 1000μg/kg) with r(2) values ranging from 0.9971 to 0.9998 was obtained. For the majority of the tested pesticides, the average recoveries were in acceptable range (between 70% and 110%) with relative standard deviation values below 15.0%. Matrix effect was evaluated for target compounds through the study of ratio of peak area obtained in the solvent and blank matrix. The proposed method was applied to simultaneously analyze 26 pesticides in 55 batches of Alpinia oxyphylla samples. 3 samples were found to be positive with four pesticides (α-BHC, quintozene, trans-chlordane and op'-DDD), which were confirmed by gas chromatography-mass spectrometry (GC-MS) in selective ion monitoring (SIM) mode. Copyright © 2016 Elsevier B.V. All rights reserved.

Impurities in Tc-99m radiopharmaceutical solution obtained from Mo-100 in cyclotron.

PubMed

Tymiński, Zbigniew; Saganowski, Paweł; Kołakowska, Ewa; Listkowska, Anna; Ziemek, Tomasz; Cacko, Daniel; Dziel, Tomasz

2018-04-01

The gamma emitting impurities in 99m Tc solution obtained from enriched molybdenum 100 Mo metallic target after its irradiation in a cyclotron were measured using a high-purity germanium (HPGe) detector. The radioactivity range of tested samples of 99m Tc was rather low, in the range from 0.34 to 2.39 MBq, thus creating a challenge to investigate the standard measurement HPGe system for impurity detection and quantification. In the process of 99m Tc separation from irradiated target the AnaLig® Tc-02 resin, Dionex H + and Alumina A columns were used. Fractions of eluates from various steps of separation process were taken and measured for radionuclidic purity. The overall measurement sensitivity of gamma emitters in terms of minimum detectable activity (MDA) was found at the level of 14-70Bq with emission lines in range of 36 - 1836keV resulting in impurity content range of 6.7 × 10 -4 to 3.4 × 10 -3 % for 93 Tc, 93m Tc, 94 Tc, 94m Tc, 95 Tc, 95m Tc, 96 Tc 96 Nb, 97 Nb, 99 Mo contaminants and 9.4 × 10 -3 % for 97m Tc. The usefulness of the chosen measurement conditions and the method applied to testing the potential contaminators was proved by reaching satisfactory results of MDAs less than the criteria of impurity concentration of all nuclides specified in the European Pharmacopoeia. Copyright © 2017 Elsevier Ltd. All rights reserved.

Development of Targeted Nonionic Surfactant Vesicles for Treatment of Vascular Injury

DTIC Science & Technology

2008-12-01

antibody and containing drug atorvastatin (test substance-low drug concentration) Test (high) 2. Surfactant vesicle coated with antibody and...containing atorvastatin (test substance-high drug concentration) Control (targeted no drug) 3. Surfactant vesicle coated with antibody and containing...buffered saline solution Control (non targeted with drug) 4. Surfactant vesicle without antibody containing atorvastatin Control (free drug

Occurrence and fate of most prescribed antibiotics in different water environments of Tehran, Iran.

PubMed

Mirzaei, Roya; Yunesian, Masud; Nasseri, Simin; Gholami, Mitra; Jalilzadeh, Esfandiyar; Shoeibi, Shahram; Mesdaghinia, Alireza

2018-04-01

The presence of most prescribed antibiotic compounds from four therapeutic classes (β-lactam, cephalosporins, macrolides, fluoroquinolones) were studied at two full-scale WWTPs, two rivers, thirteen groundwater resources, and five water treatment plants in Tehran. Analytical methodology was based on high performance liquid chromatography/tandem mass spectrometry after solid-phase extraction. Samples were collected at 33 sample locations on three sampling periods over four months from June to August 2016. None of the target antibiotics were detected in groundwater resources and water treatment plants, while seven out of nine target antibiotics were analyzed in two studied river waters as well as the influent and effluent of wastewater treatment plants at concentrations ranging from

Graphene-coated polystyrene-divinylbenzene dispersive solid-phase extraction coupled with supercritical fluid chromatography for the rapid determination of 10 allergenic disperse dyes in industrial wastewater samples.

PubMed

Lou, Chaoyan; Wu, Can; Zhang, Kai; Guo, Dandan; Jiang, Lei; Lu, Yang; Zhu, Yan

2018-05-18

Allergenic disperse dyes are a group of environmental contaminants, which are toxic and mutagenic to human beings. In this work, a method of dispersive solid-phase extraction (d-SPE) using graphene-coated polystyrene-divinylbenzene (G@PS-DVB) microspheres coupled with supercritical fluid chromatography (SFC) was proposed for the rapid determination of 10 allergenic disperse dyes in industrial wastewater samples. G@PS-DVB microspheres were synthesized by coating graphene (G) sheets onto polystyrene-divinylbenzene (PS-DVB) polymers. Such novel sorbents were employed in d-SPE for the purification and concentration of allergenic disperse dyes in wastewater samples prior to the determination by SFC with UV detection. To achieve the maximum extraction efficiency for the target dyes, several parameters influencing d-SPE process such as sorbent dosage, extraction time, desorption conditions were investigated. SFC conditions including stationary phase, modifier composition and percentage, column temperature, backpressure and flow rate were optimized to well separate the allergenic disperse dyes. Under the optimum conditions, satisfactory linear relationship (R ≥ 0.9989) was observed with the concentration of dyes ranging from 0.02 to 10.0 μg/mL. The limits of detection (LOD, S/N = 3) for the ten dyes were in the range of 1.1-15.6 ng/mL. Recoveries for the spiked samples were between 89.1% and 99.7% with relative standard deviations (RSD) lower than 10.5% in all cases. The proposed method is time-saving, green, precise and repeatable for the analysis of the target dyes. Furthermore, the application of G@PS-DVB based d-SPE process can be potentially expanded to isolate and concentrate other aromatic compounds in various matrices and supercritical fluid chromatography methodology featuring rapidity, accuracy and green will be an ideal candidate for the analysis of these compounds. Copyright © 2018 Elsevier B.V. All rights reserved.

Serum Testosterone (T) Level Variability in T Gel-Treated Older Hypogonadal Men: Treatment Monitoring Implications

PubMed Central

Pak, Youngju; Wang, Christina; Liu, Peter Y.; Bhasin, Shalender; Gill, Thomas M.; Matsumoto, Alvin M.; Pahor, Marco; Surampudi, Prasanth; Snyder, Peter J.

2015-01-01

Context: The optimal frequency for on-treatment serum T measurement used for dose adjustment after transdermal T gel application is unknown, especially in older men with thinner skin and slower metabolic clearance. Objectives: The objectives of the study was to determine the variability of postgel application serum T concentrations and assess whether single levels are reflective of average serum T concentrations over 24 hours (Cavg0–24). Design: This was a double-blinded, placebo-controlled randomized trial. Setting: The study was conducted at five academic centers. Participants: Forty-seven symptomatic men 65 years old or older with an average of two morning T concentration less than 275 ng/dL participated in the study. Intervention(s): Transdermal T or placebo gel was applied for 120 ± 14 days. Monthly dose adjustments were made if necessary to target serum T between 400 and 500 to 800 ng/dL. Main Outcome Measures: Variability of serum T 2 hours after the gel application on two outpatient visits and at multiple time points over 24 hours during the inpatient day was measured. Results: On-treatment T levels varied substantially on the 2 ambulatory days and over 24 hours during the inpatient day. Ambulatory 2-hour postapplication T levels did not correlate significantly with either 2-hour postapplication serum T or Cavg0–24 measured during the inpatient day. Only 22.2% of men receiving T had a Cavg0–24 within the target range of 500–800 ng/dL; 81.5% had a Cavg0–24 within the broader 300–1000 ng/dL range. Conclusion: Large within-individual variations in serum T after T gel application render ambulatory 2-hour postapplication T level a poor indicator of average serum T on another day. Our data point out the limitations of dose adjustments based on a single postapplication serum T measurement. PMID:26120790

Methane mitigation shows significant benefits towards achieving the 1.5 degree target.

NASA Astrophysics Data System (ADS)

Collins, W.; Webber, C.; Cox, P. M.; Huntingford, C.; Lowe, J. A.; Sitch, S.

2017-12-01

Most analyses of allowable carbon emissions to achieve the 1.5 degree target implicitly assume that the ratio of CO2 to non-CO2 greenhouse gases remains near constant, and that all radiative forcing factors have similar impacts on land and ocean carbon storage. Here we determine how plausible reductions in methane emissions will make the carbon targets more feasible. We account for the latest estimates of the methane radiative effect as well as the indirect effects of methane on ozone. We particularly address the differing effects of methane and CO2 mitigation on the land carbon storage including via reduced concentrations of surface ozone. The methodology uses an intermediate complexity climate model (IMOGEN) coupled to a land surface model (JULES) which represents the details of the terrestrial carbon cycle. The carbon emissions inputs to IMOGEN are varied to find allowable pathways consistent with the Paris 1.5 K or 2.0 K targets. The IMOGEN physical parameters are altered to represent the climate characteristics of 38 CMIP5 models (such as climate sensitivity) to provide bounds on the range of allowable CO2 emissions. We examine the effects of three different methane mitigation options that are broadly consistent with the ranges in the SSP scenarios: little mitigation, cost-optimal mitigation, and maximal mitigation. The land and ocean carbon storage increases with methane mitigation, allowing more flexibility in CO2 emission reduction. This is mostly since CO2 fertilisation is reduced less with high methane mitigation, with a small contribution from reduced plant damage with lower surface ozone levels.

Scale-up of a physiologically-based pharmacokinetic model to predict the disposition of monoclonal antibodies in monkeys.

PubMed

Glassman, Patrick M; Chen, Yang; Balthasar, Joseph P

2015-10-01

Preclinical assessment of monoclonal antibody (mAb) disposition during drug development often includes investigations in non-human primate models. In many cases, mAb exhibit non-linear disposition that relates to mAb-target binding [i.e., target-mediated disposition (TMD)]. The goal of this work was to develop a physiologically-based pharmacokinetic (PBPK) model to predict non-linear mAb disposition in plasma and in tissues in monkeys. Physiological parameters for monkeys were collected from several sources, and plasma data for several mAbs associated with linear pharmacokinetics were digitized from prior literature reports. The digitized data displayed great variability; therefore, parameters describing inter-antibody variability in the rates of pinocytosis and convection were estimated. For prediction of the disposition of individual antibodies, we incorporated tissue concentrations of target proteins, where concentrations were estimated based on categorical immunohistochemistry scores, and with assumed localization of target within the interstitial space of each organ. Kinetics of target-mAb binding and target turnover, in the presence or absence of mAb, were implemented. The model was then employed to predict concentration versus time data, via Monte Carlo simulation, for two mAb that have been shown to exhibit TMD (2F8 and tocilizumab). Model predictions, performed a priori with no parameter fitting, were found to provide good prediction of dose-dependencies in plasma clearance, the areas under plasma concentration versu time curves, and the time-course of plasma concentration data. This PBPK model may find utility in predicting plasma and tissue concentration versus time data and, potentially, the time-course of receptor occupancy (i.e., mAb-target binding) to support the design and interpretation of preclinical pharmacokinetic-pharmacodynamic investigations in non-human primates.

A long-lived tritiated titanium target for fast neutron production

NASA Astrophysics Data System (ADS)

Hughey, B. J.

1995-03-01

Diagnostic techniques using neutron beams have a broad spectrum of applications in advanced manufacturing, explosives and contraband detection, medicine, and industry. The most suitable nuclear reaction for producing large fluxes of fast neutrons at low bombarding energy is the H(d,n)-3 He-4, i.e. d-T, reaction. The lifetime of currently used d-T neutron generators is limited by the gradual evolution of tritium gas from the target during bombardment. This paper is a report of work in progress to develop a method for inhibiting the replacement of tritium with beam deuterons and thus preventing the evolution of tritium gas leading to reduced neutron yield. It is anticipated that tritiated target lifetime can be increased by at least an order of magnitude by using a range-thin tritiated titanium target mounted on a substrate with a high hydrogen diffusivity, such as niobium. Lifetime can be further enhanced by increasing the deuteron beam bombarding energy from the typical value of 200 keV to 600 keV. The results of experiments demonstrating the effect of hydrogen diffusion coefficient on concentration of implanted beam deuterons in candidate substrate materials (Cu, Pd, and Nb) are presented, and issues relevant to the fabrication of a tritiated titanium target on a niobium substrate are discussed.

D/H and Water Concentrations of Submarine MORB Glass Around the World: Analytical Aspects, Standardization, and (re)defining Mantle D/H Ranges

NASA Astrophysics Data System (ADS)

Bindeman, I. N.; Dixon, J. E.; Langmuir, C. H.; Palandri, J. L.

2015-12-01

The advent and calibration of the Thermal Combustion Element Analyzer (TCEA) continuous flow system coupled with the large-radius mass spectrometer MAT253 permits precise (±0.02 wt.% H2O, ±1-3‰ D/H) measurements in 1-10 mg of volcanic glass (0.1 wt.% H2O requires ~10 mg glass), which permits the targeting of small amounts of the freshest concentrate. This is a >100 factor reduction in sample size over conventional methods, four times over more common Delta series instruments. We investigated in triplicate 115 samples of submarine MORB glasses ranging from water-poor (0.1-0.2wt%) to water-rich (1.2-1.5wt%). These samples were previously investigated for major and trace elements, radiogenic isotopes; a large subset of these samples coming from the FAZAR expedition were studied previously by FTIR for water concentration. We also ran samples previously studied by the conventional off-line technique: MORB glass including those from the Easter Platform and the Alvin 526-1 standard (0.2wt% H2O). We observe excellent 1:1 correspondence (1.02x+0.02, R2=0.94) of wt% water by FTIR and TCEA suggesting complete extraction of water and no dependence on water concentration. We measure 51‰ total range in D/H that correlates with all other chemical and isotopic indicators of mantle enrichment, with the heaviest values occurring in the most enriched samples. When used uncorrected values of H2 gas run against H2 gas of known composition, this range agrees nicely with previous D/H range for MORB (-30 to -90‰), measured for samples run conventionally. Uncorrected analyses of Alvin glass 526-1 gives -66‰. When run against SMOW, SLAP and -41‰ water sealed in silver cups, the range is shifted by -15‰; when standardization is done by with three commonly used mica standards as is done most commonly in different labs, the range is shifted downward by -30-32‰. There are no isotopic offsets related to total water or D/H range requiring different slope or non-linear correction. The NBS30 mica standard has been recently shown to be heavier and more heterogeneous than previously thought, and older conventional methods that relied on Pt reduction unreliable. Based on these new TCEA results, the D/H values of MORB and mantle samples may need to be revised to lighter values by 15‰.

Testing of SNS-032 in a Panel of Human Neuroblastoma Cell Lines with Acquired Resistance to a Broad Range of Drugs.

PubMed

Löschmann, Nadine; Michaelis, Martin; Rothweiler, Florian; Zehner, Richard; Cinatl, Jaroslav; Voges, Yvonne; Sharifi, Mohsen; Riecken, Kristoffer; Meyer, Jochen; von Deimling, Andreas; Fichtner, Iduna; Ghafourian, Taravat; Westermann, Frank; Cinatl, Jindrich

2013-12-01

Novel treatment options are needed for the successful therapy of patients with high-risk neuroblastoma. Here, we investigated the cyclin-dependent kinase (CDK) inhibitor SNS-032 in a panel of 109 neuroblastoma cell lines consisting of 19 parental cell lines and 90 sublines with acquired resistance to 14 different anticancer drugs. Seventy-three percent of the investigated neuroblastoma cell lines and all four investigated primary tumor samples displayed concentrations that reduce cell viability by 50% in the range of the therapeutic plasma levels reported for SNS-032 (<754 nM). Sixty-two percent of the cell lines and two of the primary samples displayed concentrations that reduce cell viability by 90% in this concentration range. SNS-032 also impaired the growth of the multidrug-resistant cisplatin-adapted UKF-NB-3 subline UKF-NB-3(r)CDDP(1000) in mice. ABCB1 expression (but not ABCG2 expression) conferred resistance to SNS-032. The antineuroblastoma effects of SNS-032 did not depend on functional p53. The antineuroblastoma mechanism of SNS-032 included CDK7 and CDK9 inhibition-mediated suppression of RNA synthesis and subsequent depletion of antiapoptotic proteins with a fast turnover rate including X-linked inhibitor of apoptosis (XIAP), myeloid cell leukemia sequence 1 (Mcl-1), baculoviral IAP repeat containing 2 (BIRC2; cIAP-1), and survivin. In conclusion, CDK7 and CDK9 represent promising drug targets and SNS-032 represents a potential treatment option for neuroblastoma including therapy-refractory cases.

Testing of SNS-032 in a Panel of Human Neuroblastoma Cell Lines with Acquired Resistance to a Broad Range of Drugs12

PubMed Central

Löschmann, Nadine; Michaelis, Martin; Rothweiler, Florian; Zehner, Richard; Cinatl, Jaroslav; Voges, Yvonne; Sharifi, Mohsen; Riecken, Kristoffer; Meyer, Jochen; von Deimling, Andreas; Fichtner, Iduna; Ghafourian, Taravat; Westermann, Frank; Cinatl, Jindrich

2013-01-01

Novel treatment options are needed for the successful therapy of patients with high-risk neuroblastoma. Here, we investigated the cyclin-dependent kinase (CDK) inhibitor SNS-032 in a panel of 109 neuroblastoma cell lines consisting of 19 parental cell lines and 90 sublines with acquired resistance to 14 different anticancer drugs. Seventy-three percent of the investigated neuroblastoma cell lines and all four investigated primary tumor samples displayed concentrations that reduce cell viability by 50% in the range of the therapeutic plasma levels reported for SNS-032 (<754 nM). Sixty-two percent of the cell lines and two of the primary samples displayed concentrations that reduce cell viability by 90% in this concentration range. SNS-032 also impaired the growth of the multidrug-resistant cisplatin-adapted UKF-NB-3 subline UKF-NB-3rCDDP1000 in mice. ABCB1 expression (but not ABCG2 expression) conferred resistance to SNS-032. The antineuroblastoma effects of SNS-032 did not depend on functional p53. The antineuroblastoma mechanism of SNS-032 included CDK7 and CDK9 inhibition-mediated suppression of RNA synthesis and subsequent depletion of antiapoptotic proteins with a fast turnover rate including X-linked inhibitor of apoptosis (XIAP), myeloid cell leukemia sequence 1 (Mcl-1), baculoviral IAP repeat containing 2 (BIRC2; cIAP-1), and survivin. In conclusion, CDK7 and CDK9 represent promising drug targets and SNS-032 represents a potential treatment option for neuroblastoma including therapy-refractory cases. PMID:24466371

Gold nanoparticle enhancement of stereotactic radiosurgery for neovascular age-related macular degeneration

NASA Astrophysics Data System (ADS)

Ngwa, Wilfred; Makrigiorgos, G. Mike; Berbeco, Ross I.

2012-10-01

Age-related macular degeneration (AMD) is the leading cause of blindness in developed countries for people over the age of 50. In this work, the dosimetric feasibility of using gold nanoparticles (AuNP) as radiosensitizers to enhance kilovoltage stereotactic radiosurgery for neovascular AMD is investigated. Microdosimetry calculations at the sub-cellular level were carried out to estimate the radiation dose enhancement to individual nuclei in neovascular AMD endothelial cells (nDEF) due to photon-induced photo-/Auger electrons from x-ray-irradiated AuNP. The nDEF represents the ratio of radiation doses to the endothelial cell nuclei with and without AuNP. The calculations were carried out for a range of feasible AuNP local concentrations using the clinically applicable 100 kVp x-ray beam parameters employed by a commercially available x-ray therapy system. The results revealed nDEF values of 1.30-3.26 for the investigated concentration range of 1-7 mg g-1, respectively. In comparison, for the same concentration range, nDEF values of 1.32-3.40, 1.31-3.33, 1.29-3.19, 1.28-3.12 were calculated for 80, 90, 110 and 120 kVp x-rays, respectively. Meanwhile, calculations as a function of distance from the AuNP showed that the dose enhancement, for 100 kVp, is markedly confined to the targeted neovascular AMD endothelial cells where AuNP are localized. These findings provide impetus for considering the application of AuNP to enhance therapeutic efficacy during stereotactic radiosurgery for neovascular AMD.

Lower early postnatal oxygen saturation target and risk of ductus arteriosus closure failure.

PubMed

Inomata, Kei; Taniguchi, Shinji; Yonemoto, Hiroki; Inoue, Takeshi; Kawase, Akihiko; Kondo, Yuichi

2016-11-01

Early postnatal hyperoxia is a major risk factor for retinopathy of prematurity (ROP) in extremely premature infants. To reduce the occurrence of ROP, we adopted a lower early postnatal oxygen saturation (SpO 2 ) target range (85-92%) from April 2011. Lower SpO 2 target range, however, may lead to hypoxemia and an increase in the risk of ductus arteriosus (DA) closure failure. The aim of this study was therefore to determine whether a lower SpO 2 target range, during the early postnatal stage, increases the risk of DA closure failure. Infants born at <28 weeks' gestation were enrolled in this study. Oxygen saturation target range during the first postnatal 72 h was 84-100% in study period 1 and 85-92% in period 2. Eighty-two infants were included in period 1, and 61 were included in period 2. The lower oxygen saturation target range increased the occurrence of hypoxemia during the first postnatal 72 h. Prevalence of DA closure failure in period 2 (21%) was significantly higher than that in period 1 (1%). On multivariate logistic regression analysis, the lower oxygen saturation target range was an independent risk factor for DA closure failure. Lower early postnatal oxygen saturation target range increases the risk of DA closure failure. © 2016 Japan Pediatric Society.

Pharmacist-managed dose adjustment feedback using therapeutic drug monitoring of vancomycin was useful for patients with methicillin-resistant Staphylococcus aureus infections: a single institution experience

PubMed Central

Hirano, Ryuichi; Sakamoto, Yuichi; Kitazawa, Junichi; Yamamoto, Shoji; Tachibana, Naoki

2016-01-01

Background Vancomycin (VCM) requires dose adjustment based on therapeutic drug monitoring. At Aomori Prefectural Central Hospital, physicians carried out VCM therapeutic drug monitoring based on their experience, because pharmacists did not participate in the dose adjustment. We evaluated the impact of an Antimicrobial Stewardship Program (ASP) on attaining target VCM trough concentrations and pharmacokinetics (PK)/pharmacodynamics (PD) parameters in patients with methicillin-resistant Staphylococcus aureus (MRSA) infections. Materials and methods The ASP was introduced in April 2012. We implemented a prospective audit of prescribed VCM dosages and provided feedback based on measured VCM trough concentrations. In a retrospective pre- and postcomparison study from April 2007 to December 2011 (preimplementation) and from April 2012 to December 2014 (postimplementation), 79 patients were treated for MRSA infection with VCM, and trough concentrations were monitored (pre, n=28; post, n=51). In 65 patients (pre, n=15; post, n=50), 24-hour area under the concentration–time curve (AUC 0–24 h)/minimum inhibitory concentration (MIC) ratios were calculated. Results Pharmacist feedback, which included recommendations for changing dose or using alternative anti-MRSA antibiotics, was highly accepted during postimplementation (88%, 29/33). The number of patients with serum VCM concentrations within the therapeutic range (10–20 μg/mL) was significantly higher during postimplementation (84%, 43/51) than during preimplementation (39%, 11/28) (P<0.01). The percentage of patients who attained target PK/PD parameters (AUC 0–24 h/MIC >400) was significantly higher during postimplementation (84%, 42/50) than during preimplementation (53%, 8/15; P=0.013). There were no significant differences in nephrotoxicity or mortality rate. Conclusion Our ASP increased the percentage of patients that attained optimal VCM trough concentrations and PK/PD parameters, which contributed to the appropriate use of VCM in patients with MRSA infections. PMID:27789965

The effect of ammonia on canine polymorphonuclear cells.

PubMed

Breheny, Craig R; Mellanby, Richard J; Hamilton, Julie A; Gow, Adam G

2018-06-24

Hyperammonaemia is a common complication of liver disease in dogs. High concentrations of ammonia can be detrimental to dogs with liver disease for several reasons, notably by causing hepatic encephalopathy (HE) which describes the wide range of neurological abnormalities ranging from altered behaviour to seizures that are well recognised complications in dogs with hepatic disorders. In human patients with liver disease, hyperammonaemia has also been linked to the development of other systemic complications such as dysregulation of the innate immune system. In contrast, the effects of hyperammonaemia on the canine innate immune system is currently unknown. The aim of this study was to investigate the effects of ammonia on the oxidative burst activity of canine polymorphonuclear cells in vitro. Blood obtained from healthy dogs (n = 8) was incubated with escalating concentrations of ammonia ranging from 0 to 250 μM, and the percentage of cells experiencing an oxidative burst was evaluated using a commercial kit (Phagoburst™) and flow cytometry. The spontaneous oxidative burst was evaluated without stimulation and also following stimulation with E coli. The pH of the blood was also measured at the differing ammonia concentrations. There was an increase in the percentage of cells experiencing a spontaneous oxidative burst from ammonia concentrations of 125 μM (p = <0.05) and above (p = <0.01), with a 4.9 fold increase at 200 μM (p = < 0.001). In those cells stimulated with E coli, incubation with increasing ammonia concentrations did not result in a significant difference in oxidative burst from baseline (p = 0.953). There was no statistically significant difference between the pH of the blood at the various ammonia concentrations (p = 0.2) suggesting that the difference in spontaneous oxidative burst was due to the ammonia rather than simply a change in pH conditions. In summary, the spontaneous oxidative burst of neutrophils was significantly increased from baseline. This supports a potential role of ammonia in contributing to innate immune system dysfunction in dogs with liver disease, and may present a future therapeutic target.

Monostatic lidar in weak-to-strong turbulence

NASA Astrophysics Data System (ADS)

Andrews, L. C.; Phillips, R. L.

2001-07-01

A heuristic scintillation model previously developed for weak-to-strong irradiance fluctuations of a spherical wave is extended in this paper to the case of a monostatic lidar configuration. As in the previous model, we account for the loss of spatial coherence as the optical wave propagates through atmospheric turbulence by eliminating the effects of certain turbulent scale sizes that exist between the scale size of the spatial coherence radius of the beam and that of the scattering disc. These mid-range scale-size effects are eliminated through the formal introduction of spatial scale frequency filters that continually adjust spatial cut-off frequencies as the optical wave propagates. In addition, we also account for correlations that exist in the incident wave to the target and the echo wave from the target arising from double-pass propagation through the same random inhomogeneities of the atmosphere. We separately consider the case of a point target and a diffuse target, concentrating on both the enhanced backscatter effect in the mean irradiance and the increase in scintillation in a monostatic channel. Under weak and strong irradiance fluctuations our asymptotic expressions are in agreement with previously published asymptotic results.

Lactosaminated- N-succinyl chitosan nanoparticles for hepatocyte-targeted delivery of acyclovir

NASA Astrophysics Data System (ADS)

Jain, Nivrati; Rajoriya, Vaibhav; Jain, Prateek Kumar; Jain, Ashish Kumar

2014-01-01

The present study discusses lactose-acyclovir- N-succinyl chitosan nanoparticles (Lac- N-Suc-CSNP) using lactose as an asialoglycoprotein receptor (ASGPR) ligand for hepatic parenchymatic cells targeting. For this purpose, N-succinyl chitosan nanoparticles ( N-Suc-CSNP) were prepared previously by ionotropic gelation method and lactose was conjugated to the free amino terminal group of chitosan. Lactose conjugation with N-Suc-CSNP was confirmed by FT-IR and zeta potential measurements. The Lac- N-Suc-CSNP obtained were characterized for their morphology, particle size, polydispersity index, and zeta potential. The Lac- N-Suc-CSNP showed spherical in shape with 220.3 ± 5.0 nm size range, +4.1 ± 0.2 mV zeta potential, 62.5 ± 1.2 % acyclovir entrapment efficiency and showed 27.3 ± 0.9 % cumulative acyclovir release up to 72 h. The acyclovir concentration from Lac- N-Suc-CSNP was found to be 19.9 ± 1.62 μg/g after 24 h administration revealed remarkably targeting potential to the hepatocytes and keep at a high level during the experiment. These results suggest that Lac- N-Suc-CSNP are potentially vector for hepatocytes targeting.

Estimation of Freely-Dissolved Concentrations of Polychlorinated Biphenyls, 2,3,7,8-Substituted Congeners and Homologs of Polychlorinated dibenzo-p-dioxins and Dibenzofurans in Water for Development of Total Maximum Daily Loadings for the Bluestone River Watershed, Virginia and West Virginia

USGS Publications Warehouse

Gale, Robert W.

2007-01-01

The Commonwealth of Virginia Department of Environmental Quality, working closely with the State of West Virginia Department of Environmental Protection and the U.S. Environmental Protection Agency is undertaking a polychlorinated biphenyl source assessment study for the Bluestone River watershed. The study area extends from the Bluefield area of Virginia and West Virginia, targets the Bluestone River and tributaries suspected of contributing to polychlorinated biphenyl, polychlorinated dibenzo-p-dioxin and dibenzofuran contamination, and includes sites near confluences of Big Branch, Brush Fork, and Beaver Pond Creek. The objectives of this study were to gather information about the concentrations, patterns, and distribution of these contaminants at specific study sites to expand current knowledge about polychlorinated biphenyl impacts and to identify potential new sources of contamination. Semipermeable membrane devices were used to integratively accumulate the dissolved fraction of the contaminants at each site. Performance reference compounds were added prior to deployment and used to determine site-specific sampling rates, enabling estimations of time-weighted average water concentrations during the deployed period. Minimum estimated concentrations of polychlorinated biphenyl congeners in water were about 1 picogram per liter per congener, and total concentrations at study sites ranged from 130 to 18,000 picograms per liter. The lowest concentration was 130 picograms per liter, about threefold greater than total hypothetical concentrations from background levels in field blanks. Polychlorinated biphenyl concentrations in water fell into three groups of sites: low (130-350 picogram per liter); medium (640-3,500 picogram per liter; and high (11,000-18,000 picogram per liter). Concentrations at the high sites, Beacon Cave and Beaverpond Branch at the Resurgence, were about four- to sixfold higher than concentrations estimated for the medium group of sites. Minimum estimated concentrations of polychlorinated dibenzo-p-dioxin and dibenzofuran congeners in water were about 0.2 to 1 femtograms per liter. Estimated total concentrations of 2,3,7,8-substituted congeners in water at study sites ranged from less than 1 to 22,000 femtograms per liter and less than 1 to 2,300 femtograms per liter for polychlorinated dibenzo-p-dioxin and dibenzofuran congeners, respectively. Total concentrations of 2,3,7,8-substituted congeners in water were comprised largely of octachlorodibenzo-p-dioxin and dibenzofuran, with less than 10 percent of the total contributed by concentrations of other congeners, mainly 2,3,7,8-heptachlorodibenzo-p-dioxin and dibenzofuran. Of special interest for this study was 2,3,7,8-tetrachlorodibenzo-p-dioxin with a regulatory surface water-quality criterion of 1,200 femtograms per liter. Estimated concentrations in water ranged from 0.5 to 41 femtograms per liter. Concentrations in water were less than 5 femtograms per liter at all study sites, except the Bluefield Westside Sewage Treatment Plan, with an estimated concentration of 41 femtograms per liter. Estimated total concentrations of homologs of polychlorinated dibenzo-p-dioxins and dibenzofurans in water at the study sites ranged from 3,200 to 36,000 femtograms per liter and 210-4,800 femtograms per liter, respectively. Again, homologs of polychlorinated dibenzo-p-dioxins and dibenzofurans in water were comprised largely of octachlorodibenzo-p-dioxin and dibenzofuran.

Comparison of concentrations and profiles of polycyclic aromatic hydrocarbon metabolites in bile of fishes from offshore oil platforms and natural reefs along the California coast

USGS Publications Warehouse

Gale, Robert W.; Tanner, Michael J.; Love, Milton S.; Nishimoto, Mary M.; Schroeder, Donna M.

2012-01-01

To determine the environmental consequences of decommissioning offshore oil platforms on local and regional fish populations, contaminant loads in reproducing adults were investigated at seven platform sites and adjacent, natural sites. Specimens of three species (Pacific sanddab, Citharichthys sordidus; kelp rockfish, Sebastes atrovirens; and kelp bass, Paralabrax clathratus) residing at platforms and representing the regional background within the Santa Barbara Channel and within the San Pedro Basin were collected. Some of the most important contaminant classes related to oil operations are polycyclic aromatic hydrocarbons (PAHs) because of their potential toxicity and carcinogenicity. However, acute exposure cannot be related directly to PAH tissue concentrations because of rapid metabolism of the parent chemicals in fish; therefore, PAH metabolites in bile were measured, targeting free hydroxylated PAHs (OH-PAHs) liberated by enzymatic hydrolysis of the bound PAH glucuronides and sulfates. An ion-pairing method was developed for confirmatory analysis that targeted PAH glucuronides and sulfates. Concentrations of hydroxylated PAHs in all samples (76 fish from platforms and 64 fish from natural sites) were low, ranging from less than the limits of detection (5 to 120 nanograms per milliliter bile; 0.03 to 42 nanograms per milligram protein) to a maximum of 320 nanograms per milliliter bile (32 nanograms per milligram protein). A previously proposed dosimeter of PAH exposure in fish, 1-hydroxypyrene, was not detected at any platform site. Low concentrations of 1-hydroxypyrene were detected in 3 of 12 kelp rockfish collected from a natural reef site off Santa Barbara. The most prevalent OH-PAH, 2-hydroxyfluorene, was detected at low concentrations in seven fish of various species; of these, four were from two of the seven platform sites. The greatest concentrations of 2-hydroxyfluorene were found in three fish of various species from Platform Holly and were only about threefold above low, yet quantifiable, concentrations found in three fish from Horseshoe Reef, East Anacapa Island, and Coche Point natural sites; the mean concentrations among all sampling sites were not measurably different.

Passive range estimation using dual baseline triangulation

NASA Astrophysics Data System (ADS)

Pieper, Ronald J.; Cooper, Alfred W.; Pelegris, G.

1996-03-01

Modern combat systems based on active radar sensing suffer disadvantages against low-flying targets in cluttered backgrounds. Use of passive infrared sensors with these systems, either in cooperation or as an alternative, shows potential for improving target detection and declaration range for targets crossing the horizon. Realization of this potential requires fusion of target position data from dissimilar sensors, or passive sensor measurement of target range. The availability of passive sensors that can supply both range and bearing data on such targets would significantly extend the robustness of an integrated ship self-defense system. This paper considers a new method of range determination with passive sensors based on the principle of triangulation, extending the principle to two orthogonal baselines. The performance of single or double baseline triangulation depends on sensor bearing precision and direction to target. An expression for maximum triangulation range at a required accuracy is derived as a function of polar angle relative to the center of the dual-baseline system. Limitations in the dual- baseline model due to the geometrically assessed horizon are also considered.

Development of a multianalyte method based on micro-matrix-solid-phase dispersion for the analysis of fragrance allergens and preservatives in personal care products.

PubMed

Celeiro, Maria; Guerra, Eugenia; Lamas, J Pablo; Lores, Marta; Garcia-Jares, Carmen; Llompart, Maria

2014-05-30

An effective, simple and low cost sample preparation method based on matrix solid-phase dispersion (MSPD) followed by gas chromatography-mass spectrometry (GC-MS) or gas chromatography-triple quadrupole-mass spectrometry (GC-MS/MS) has been developed for the rapid simultaneous determination of 38 cosmetic ingredients, 25 fragrance allergens and 13 preservatives. All target substances are frequently used in cosmetics and personal care products and they are subjected to use restrictions or labeling requirements according to the EU Cosmetic Directive. The extraction procedure was optimized on real non-spiked rinse-off and leave-on cosmetic products by means of experimental designs. The final miniaturized process required the use of only 0.1g of sample and 1 mL of organic solvent, obtaining a final extract ready for analysis. The micro-MSPD method was validated showing satisfactory performance by GC-MS and GC-MS/MS analysis. The use of GC coupled to triple quadrupole mass detection allowed to reach very low detection limits (low ng g(-1)) improving, at the same time, method selectivity. In an attempt to improve the chromatographic analysis of preservatives, the inclusion of a derivatization step was also assessed. The proposed method was applied to a broad range of cosmetics and personal care products (shampoos, body milk, moisturizing milk, toothpaste, hand creams, gloss lipstick, sunblock, deodorants and liquid soaps among others), demonstrating the extended use of these substances. The concentration levels were ranging from the sub parts per million to the parts per mill. The number of target fragrance allergens per samples was quite high (up to 16). Several fragrances (linalool, farnesol, hexylcinnamal, and benzyl benzoate) have been detected at levels >0.1% (1,000 μg g(-1)). As regards preservatives, phenoxyethanol was the most frequently found additive reaching quite high concentration (>1,500 μg g(-1)) in five cosmetic products. BHT was detected in eight samples, in two of them (a baby care product and a lipstick) at high concentrations (>1,000 μg g(-1)). Methyl paraben was also found at high levels (>1,700 μg g(-1)) in three leave-on samples. Finally, triclosan was found at the maximum concentration limit (0.3%) laid down by the European regulation in two deodorant samples, and the total paraben concentration was close to the maximum concentration permitted (0.8%) in one leave-on sample (body milk). Copyright © 2014 Elsevier B.V. All rights reserved.

Systematic review: the applications of nanotechnology in gastroenterology.

PubMed

Brakmane, G; Winslet, M; Seifalian, A M

2012-08-01

Over the past 30 years, nanotechnology has evolved dramatically. It has captured the interest of variety of fields from computing and electronics to biology and medicine. Recent discoveries have made invaluable changes to future prospects in nanomedicine; and introduced the concept of theranostics. This term offers a patient specific 'two in one' modality that comprises of diagnostic and therapeutic tools. Not only nanotechnology has shown great impact on improvements in drug delivery and imaging techniques, but also there have been several ground-breaking discoveries in regenerative medicine. Gastroenterology invites multidisciplinary approach owing to high complexity of gastrointestinal (GI) system; it includes physicians, surgeons, radiologists, pharmacologists and many more. In this article, we concentrate on current developments in nano-gastroenterology. Literature search was performed using Web of Science and Pubmed search engines with terms--nanotechnology, nanomedicine and gastroenterology. Article search was concentrated on developments since 2005. We have described original and innovative approaches in gastrointestinal drug delivery, inflammatory disease and cancer-target treatments. Here, we have reviewed advances in GI imaging using nanoparticles as fluorescent contrast, and their potential for site-specific targeting. This review has also depicted various approaches and novel discoveries in GI regenerative medicine using nanomaterials for scaffold designs and induced pluripotent stem cells as cell source. Developments in nanotechnology have opened new range of possibilities to help our patients. This includes novel drug delivery vehicles, diagnostic tools for early and targeted disease detection and nanocomposite materials for tissue constructs to overcome cosmetic or physical disabilities. © 2012 Blackwell Publishing Ltd.

Repellence of plant essential oils to Dermanyssus gallinae and toxicity to the non-target invertebrate Tenebrio molitor.

PubMed

George, D R; Sparagano, O A E; Port, G; Okello, E; Shiel, R S; Guy, J H

2009-05-26

With changes in legislation and consumer demand, alternatives to synthetic acaricides to manage the poultry red mite Dermanyssus gallinae (De Geer) in laying hen flocks are increasingly needed. These mites may cause losses in egg production, anaemia and even death of hens. It may be possible to use plant-derived products as D. gallinae repellents, especially if such products have a minimal impact on non-target organisms. An experiment was conducted with D. gallinae to assess the repellence of a range of plant essential oils, previously found to be of varying toxicity (relatively highly toxic to non-toxic) to this pest. Experiments were also undertaken to assess the toxicity of these products to mealworm beetles (Tenebrio molitor L.), a non-target invertebrate typical of poultry production systems. Results showed that all seven essential oils tested (manuka, thyme, palmarosa, caraway, spearmint, black pepper and juniper leaf) were repellent to D. gallinae at 0.14mg oil/cm(3) (initial concentration) during the first 2 days of study. Thyme essential oil appeared to be the most effective, where repellence lasted until the end of the study period (13 days). At the same concentration toxicity to T. molitor differed, with essential oils of palmarosa and manuka being no more toxic to adult beetles than the control. There was neither a significant association between the rank toxicity and repellence of oils to D. gallinae, nor the toxicity of oils to D. gallinae (as previously determined) and T. molitor.

Spectrophotometric, colorimetric and visually detection of Pseudomonas aeruginosa ETA gene based gold nanoparticles DNA probe and endonuclease enzyme

NASA Astrophysics Data System (ADS)

Amini, Bahram; Kamali, Mehdi; Salouti, Mojtaba; Yaghmaei, Parichehreh

2018-06-01

Colorimetric DNA detection is preferred over other methods for clinical molecular diagnosis because it does not require expensive equipment. In the present study, the colorimetric method based on gold nanoparticles (GNPs) and endonuclease enzyme was used for the detection of P. aeruginosa ETA gene. Firstly, the primers and probe for P. aeruginosa exotoxin A (ETA) gene were designed and checked for specificity by the PCR method. Then, GNPs were synthesized using the citrate reduction method and conjugated with the prepared probe to develop the new nano-biosensor. Next, the extracted target DNA of the bacteria was added to GNP-probe complex to check its efficacy for P. aeruginosa ETA gene diagnosis. A decrease in absorbance was seen when GNP-probe-target DNA cleaved into the small fragments of BamHI endonuclease due to the weakened electrostatic interaction between GNPs and the shortened DNA. The right shift of the absorbance peak from 530 to 562 nm occurred after adding the endonuclease. It was measured using a UV-VIS absorption spectroscopy that indicates the existence of the P. aeruginosa ETA gene. Sensitivity was determined in the presence of different concentrations of target DNA of P. aeruginosa. The results obtained from the optimized conditions showed that the absorbance value has linear correlation with concentration of target DNA (R: 0.9850) in the range of 10-50 ng mL-1 with the limit detection of 9.899 ng mL-1. Thus, the specificity of the new method for detection of P. aeruginosa was established in comparison with other bacteria. Additionally, the designed assay was quantitatively applied to detect the P. aeruginosa ETA gene from 103 to 108 CFU mL-1 in real samples with a detection limit of 320 CFU mL-1.

Continuous low-level aquatic monitoring (CLAM) samplers for pesticide contaminant screening in urban runoff: Analytical approach and a field test case.

PubMed

Ensminger, Michael P; Vasquez, Martice; Tsai, Hsing-Ju; Mohammed, Sarah; Van Scoy, A; Goodell, Korena; Cho, Gail; Goh, Kean S

2017-10-01

Monitoring of surface waters for organic contaminants is costly. Grab water sampling often results in non-detects for organic contaminants due to missing a pulse event or analytical instrumentation limitations with a small sample size. Continuous Low-Level Aquatic Monitoring (CLAM) samplers (C.I.Agent ® Solutions) continually extract and concentrate organic contaminants in surface water onto a solid phase extraction disk. Utilizing CLAM samplers, we developed a broad spectrum analytical screen for monitoring organic contaminants in urban runoff. An intermediate polarity solid phase, hydrophobic/lipophilic balance (HLB), was chosen as the sorbent for the CLAM to target a broad range of compounds. Eighteen urban-use pesticides and pesticide degradates were targeted for analysis by LC/MS/MS, with recoveries between 59 and 135% in laboratory studies. In field studies, CLAM samplers were deployed at discrete time points from February 2015 to March 2016. Half of the targeted chemicals were detected with reporting limits up to 90 times lower than routine 1-L grab samples with good precision between field replicates. In a final deployment, CLAM samplers were compared to 1-L water samples. In this side-by-side comparison, imidacloprid, fipronil, and three fipronil degradates were detected by the CLAM sampler but only imidacloprid and fipronil sulfone were detected in the water samples. However, concentrations of fipronil sulfone and imidacloprid were significantly lower with the CLAM and a transient spike of diuron was not detected. Although the CLAM sampler has limitations, it can be a powerful tool for development of more focused and informed monitoring efforts based on pre-identified targets in the field. Copyright © 2017 Elsevier Ltd. All rights reserved.

Quantitative spatially resolved measurement of tissue chromophore concentrations using photoacoustic spectroscopy: application to the measurement of blood oxygenation and haemoglobin concentration.

PubMed

Laufer, Jan; Delpy, Dave; Elwell, Clare; Beard, Paul

2007-01-07

A new approach based on pulsed photoacoustic spectroscopy for non-invasively quantifying tissue chromophore concentrations with high spatial resolution has been developed. The technique is applicable to the quantification of tissue chromophores such as oxyhaemoglobin (HbO(2)) and deoxyhaemoglobin (HHb) for the measurement of physiological parameters such as blood oxygen saturation (SO(2)) and total haemoglobin concentration. It can also be used to quantify the local accumulation of targeted contrast agents used in photoacoustic molecular imaging. The technique employs a model-based inversion scheme to recover the chromophore concentrations from photoacoustic measurements. This comprises a numerical forward model of the detected time-dependent photoacoustic signal that incorporates a multiwavelength diffusion-based finite element light propagation model to describe the light transport and a time-domain acoustic model to describe the generation, propagation and detection of the photoacoustic wave. The forward model is then inverted by iteratively fitting it to measurements of photoacoustic signals acquired at different wavelengths to recover the chromophore concentrations. To validate this approach, photoacoustic signals were generated in a tissue phantom using nanosecond laser pulses between 740 nm and 1040 nm. The tissue phantom comprised a suspension of intralipid, blood and a near-infrared dye in which three tubes were immersed. Blood at physiological haemoglobin concentrations and oxygen saturation levels ranging from 2% to 100% was circulated through the tubes. The signal amplitude from different temporal sections of the detected photoacoustic waveforms was plotted as a function of wavelength and the forward model fitted to these data to recover the concentrations of HbO(2) and HHb, total haemoglobin concentration and SO(2). The performance was found to compare favourably to that of a laboratory CO-oximeter with measurement resolutions of +/-3.8 g l(-1) (+/-58 microM) and +/-4.4 g l(-1) (+/-68 microM) for the HbO(2) and HHb concentrations respectively and +/-4% for SO(2) with an accuracy in the latter in the range -6%-+7%.

Quantitative spatially resolved measurement of tissue chromophore concentrations using photoacoustic spectroscopy: application to the measurement of blood oxygenation and haemoglobin concentration

NASA Astrophysics Data System (ADS)

Laufer, Jan; Delpy, Dave; Elwell, Clare; Beard, Paul

2007-01-01

A new approach based on pulsed photoacoustic spectroscopy for non-invasively quantifying tissue chromophore concentrations with high spatial resolution has been developed. The technique is applicable to the quantification of tissue chromophores such as oxyhaemoglobin (HbO2) and deoxyhaemoglobin (HHb) for the measurement of physiological parameters such as blood oxygen saturation (SO2) and total haemoglobin concentration. It can also be used to quantify the local accumulation of targeted contrast agents used in photoacoustic molecular imaging. The technique employs a model-based inversion scheme to recover the chromophore concentrations from photoacoustic measurements. This comprises a numerical forward model of the detected time-dependent photoacoustic signal that incorporates a multiwavelength diffusion-based finite element light propagation model to describe the light transport and a time-domain acoustic model to describe the generation, propagation and detection of the photoacoustic wave. The forward model is then inverted by iteratively fitting it to measurements of photoacoustic signals acquired at different wavelengths to recover the chromophore concentrations. To validate this approach, photoacoustic signals were generated in a tissue phantom using nanosecond laser pulses between 740 nm and 1040 nm. The tissue phantom comprised a suspension of intralipid, blood and a near-infrared dye in which three tubes were immersed. Blood at physiological haemoglobin concentrations and oxygen saturation levels ranging from 2% to 100% was circulated through the tubes. The signal amplitude from different temporal sections of the detected photoacoustic waveforms was plotted as a function of wavelength and the forward model fitted to these data to recover the concentrations of HbO2 and HHb, total haemoglobin concentration and SO2. The performance was found to compare favourably to that of a laboratory CO-oximeter with measurement resolutions of ±3.8 g l-1 (±58 µM) and ±4.4 g l-1 (±68 µM) for the HbO2 and HHb concentrations respectively and ±4% for SO2 with an accuracy in the latter in the range -6%-+7%.

A novel portable filtration system for sampling and concentration of microorganisms: Demonstration on marine microalgae with subsequent quantification using IC-NASBA.

PubMed

Loukas, Christos-Moritz; Mowlem, Matthew C; Tsaloglou, Maria-Nefeli; Green, Nicolas G

2018-05-01

This paper presents a novel portable sample filtration/concentration system, designed for use on samples of microorganisms with very low cell concentrations and large volumes, such as water-borne parasites, pathogens associated with faecal matter, or toxic phytoplankton. The example application used for demonstration was the in-field collection and concentration of microalgae from seawater samples. This type of organism is responsible for Harmful Algal Blooms (HABs), an example of which is commonly referred to as "red tides", which are typically the result of rapid proliferation and high biomass accumulation of harmful microalgal species in the water column or at the sea surface. For instance, Karenia brevis red tides are the cause of aquatic organism mortality and persistent blooms may cause widespread die-offs of populations of other organisms including vertebrates. In order to respond to, and adequately manage HABs, monitoring of toxic microalgae is required and large-volume sample concentrators would be a useful tool for in situ monitoring of HABs. The filtering system presented in this work enables consistent sample collection and concentration from 1 L to 1 mL in five minutes, allowing for subsequent benchtop sample extraction and analysis using molecular methods such as NASBA and IC-NASBA. The microalga Tetraselmis suecica was successfully detected at concentrations ranging from 2 × 10 5  cells/L to 20 cells/L. Karenia brevis was also detected and quantified at concentrations between 10 cells/L and 10 6  cells/L. Further analysis showed that the filter system, which concentrates cells from very large volumes with consequently more reliable sampling, produced samples that were more consistent than the independent non-filtered samples (benchtop controls), with a logarithmic dependency on increasing cell numbers. This filtering system provides simple, rapid, and consistent sample collection and concentration for further analysis, and could be applied to a wide range of different samples and target organisms in situations lacking laboratories. Copyright © 2018. Published by Elsevier B.V.

Pharmacokinetic Steady-States Highlight Interesting Target-Mediated Disposition Properties.

PubMed

Gabrielsson, Johan; Peletier, Lambertus A

2017-05-01

In this paper, we derive explicit expressions for the concentrations of ligand L, target R and ligand-target complex RL at steady state for the classical model describing target-mediated drug disposition, in the presence of a constant-rate infusion of ligand. We demonstrate that graphing the steady-state values of ligand, target and ligand-target complex, we obtain striking and often singular patterns, which yield a great deal of insight and understanding about the underlying processes. Deriving explicit expressions for the dependence of L, R and RL on the infusion rate, and displaying graphs of the relations between L, R and RL, we give qualitative and quantitive information for the experimentalist about the processes involved. Understanding target turnover is pivotal for optimising these processes when target-mediated drug disposition (TMDD) prevails. By a combination of mathematical analysis and simulations, we also show that the evolution of the three concentration profiles towards their respective steady-states can be quite complex, especially for lower infusion rates. We also show how parameter estimates obtained from iv bolus studies can be used to derive steady-state concentrations of ligand, target and complex. The latter may serve as a template for future experimental designs.

Clinical pharmacology of AMG 181, a gut-specific human anti-α4β7 monoclonal antibody, for treating inflammatory bowel diseases

PubMed Central

Pan, Wei-Jian; Köck, Kathleen; Rees, William A; Sullivan, Barbara A; Evangelista, Christine M; Yen, Mark; Andrews, Jane M; Radford-Smith, Graham L; Prince, Peter J; Reynhardt, Kaz O; Doherty, David R; Patel, Sonal K; Krill, Christine D; Zhou, Kefei; Shen, Jing; Smith, Lynn E; Gow, Jason M; Lee, Jonathan; Treacy, Anthony M; Yu, Zhigang; Platt, Virginia M; Borie, Dominic C

2014-01-01

Aims AMG 181 pharmacokinetics/pharmacodynamics (PK/PD), safety, tolerability and effects after single subcutaneous (s.c.) or intravenous (i.v.) administration were evaluated in a randomized, double-blind, placebo-controlled study. Methods Healthy male subjects (n= 68) received a single dose of AMG 181 or placebo at 0.7, 2.1, 7, 21, 70 mg s.c. (or i.v.), 210 mg s.c. (or i.v.), 420 mg i.v. or placebo. Four ulcerative colitis (UC) subjects (n= 4, male : female 2:2) received 210 mg AMG 181 or placebo s.c. (3:1). AMG 181 concentration, anti-AMG 181-antibody (ADA), α4β7 receptor occupancy (RO), target cell counts, serum C-reactive protein, fecal biomarkers and Mayo score were measured. Subjects were followed 3–9 months after dose. Results Following s.c. dosing, AMG 181 was absorbed with a median tmax ranging between 2–10 days and a bioavailability between 82% and 99%. Cmax and AUC increased dose-proportionally and approximately dose-proportionally, respectively, within the 70–210 mg s.c. and 70–420 mg i.v. ranges. The linear β-phase t1/2 was 31 (range 20–48) days. Target-mediated disposition occurred at serum AMG 181 concentrations of less than 1 μg ml−1. The PD effect on α4β7 RO showed an EC50 of 0.01 μg ml−1. Lymphocytes, eosinophils, CD4+ T cells and subset counts were unchanged. AMG 181-treated UC subjects were in remission with mucosal healing at weeks 6, 12 and/or 28. The placebo-treated UC subject experienced colitis flare at week 6. No ADA or AMG 181 treatment-related serious adverse events were observed. Conclusions AMG 181 has PK/PD, safety, and effect profiles suitable for further testing in subjects with inflammatory bowel diseases. PMID:24803302

The contribution of rice agriculture to methylmercury in surface waters: A review of data from the Sacramento Valley, California

USGS Publications Warehouse

Tanner, K. Christy; Windham-Myers, Lisamarie; Fleck, Jacob; Tate, Kenneth W.; McCord, Stephen A.; Linquist, Bruce A.

2017-01-01

Methylmercury (MeHg) is a bioaccumulative pollutant produced in and exported from flooded soils, including those used for rice (Oriza sativa L.) production. Using unfiltered aqueous MeHg data from MeHg monitoring programs in the Sacramento River watershed from 1996 to 2007, we assessed the MeHg contribution from rice systems to the Sacramento River. Using a mixed-effects regression analysis, we compared MeHg concentrations in agricultural drainage water from rice-dominated regions (AgDrain) to MeHg concentrations in the Sacramento and Feather Rivers, both upstream and downstream of AgDrain inputs. We also calculated MeHg loads from AgDrains and the Sacramento and Feather Rivers. Seasonally, MeHg concentrations were higher during November through May than during June through October, but the differences varied by location. Relative to upstream, November through May AgDrain least-squares mean MeHg concentration (0.18 ng L−1, range 0.15–0.23 ng L−1) was 2.3-fold higher, while June through October AgDrain mean concentration (0.097 ng L−1, range 0.6–1.6 ng L−1) was not significantly different from upstream. June through October AgDrain MeHg loads contributed 10.7 to 14.8% of the total Sacramento River MeHg load. Missing flow data prevented calculation of the percent contribution of AgDrains in November through May. At sites where calculation was possible, November through May loads made up 70 to 90% of the total annual load. Elevated flow and MeHg concentration in November through May both contribute to the majority of the AgDrain MeHg load occurring during this period. Methylmercury reduction efforts should target elevated November through May MeHg concentrations in AgDrains. However, our findings suggest that the contribution and environmental impact of rice is an order of magnitude lower than previous studies in the California Yolo Bypass.

Management of early renal anaemia: diagnostic work-up, iron therapy, epoetin therapy.

PubMed

Van Wyck, D B

2000-01-01

Effective management of early anaemia in the course of chronic renal insufficiency requires the following: (i) implementing an efficient diagnostic strategy to exclude common contributing factors; (ii) initiating epoetin therapy for the majority of patients; for and (iii) ensuring adequate iron supply erythropoiesis. Diagnostic inquiry is warranted whenever the haemoglobin concentration is below the normal range adjusted for age and gender. The most efficient diagnostic approach is to assume erythropoietin deficiency, exclude iron deficiency, and pursue further diagnostic tests only when red-cell indices are abnormal or when leukopenia or thrombocytopenia are also present. Macrocytosis should prompt an inquiry into alcoholism, B12 deficiency, or folate deficiency. Microcytosis suggests iron deficiency or thalassaemia. Associated cytopenias raise the possibility of alcohol toxicity, pernicious anaemia, malignancy, or myelodysplastic syndrome. Epoetin therapy is warranted whenever the haemoglobin concentration has fallen below 10.0 g/dl. To initiate therapy prior to dialysis, epoetin should be administered at an average dose of 100 IU/kg/week (80-120 IU/kg/week, 50-150 IU/kg/ week) by subcutaneous injection. Haemoglobin concentration should be monitored every 2 weeks and the epoetin dose adjusted by increments or decrements of 25% to maintain a rate of rise of haemoglobin concentration of 0.2-0.6 g/dl (0.3 0.6 g/dl/week, 0.2-0.5 g/dl/week). When the target range is achieved, the dose of epoetin should be continually adjusted to maintain a stable haemoglobin concentration. Transferrin saturation and ferritin concentration should be monitored monthly, and sufficient iron provided to maintain transferrin saturation above 20%. The lower the haemoglobin concentration, the greater the likelihood that future intravenous iron will be required. Oral iron supplements should be avoided, since they are costly, ineffective, and troublesome to patients. Finally, a blunted therapeutic response to epoetin therapy provides important diagnostic information and gnostic inquiry.

Method of passive ranging from infrared image sequence based on equivalent area

NASA Astrophysics Data System (ADS)

Yang, Weiping; Shen, Zhenkang

2007-11-01

The information of range between missile and targets is important not only to missile controlling component, but also to automatic target recognition, so studying the technique of passive ranging from infrared images has important theoretic and practical meanings. Here we tried to get the range between guided missile and target and help to identify targets or dodge a hit. The issue of distance between missile and target is currently a hot and difficult research content. As all know, infrared imaging detector can not range so that it restricts the functions of the guided information processing system based on infrared images. In order to break through the technical puzzle, we investigated the principle of the infrared imaging, after analysing the imaging geometric relationship between the guided missile and the target, we brought forward the method of passive ranging based on equivalent area and provided mathematical analytic formulas. Validating Experiments demonstrate that the presented method has good effect, the lowest relative error can reach 10% in some circumstances.

Occurrence and fate of select psychoactive pharmaceuticals and antihypertensives in two wastewater treatment plants in New York State, USA.

PubMed

Subedi, Bikram; Kannan, Kurunthachalam

2015-05-01

The fates of psychoactive pharmaceuticals, including two antischizophrenics, six sedative-hypnotic-anxiolytics, four antidepressants, four antihypertensives, and their select metabolites, were determined in two wastewater treatment plants (WWTPs) in the Albany area of New York. All target psychoactive pharmaceuticals and their metabolites were found at a mean concentration that ranged from 0.98 (quetiapine) to 1220 ng/L (atenolol) in wastewater and from 0.26 (lorazepam) to 1490 ng/g dry weight (sertraline) in sludge. In this study, the fraction of psychoactive pharmaceuticals that was sorbed to suspended particulate matter (SPM) was calculated for the first time. Over 50% of the total mass of aripiprazole, norquetiapine, norsertraline, citalopram, desmethyl citalopram, propranolol, verapamil, and norverapamil was found sorbed to SPM in the influent. The mass loadings, i.e., influx, of target psychoactive pharmaceuticals in WWTPs ranged from 0.91 (diazepam) to 347 mg/d/1000 inhabitants (atenolol), whereas the environmental emissions ranged from 0.01 (dehydro-aripiprazole) to 316 mg/d/1000 inhabitants (atenolol). The highest calculated removal efficiencies were found for antischizophrenics (quetiapine=88%; aripiprazole=71%). However, the removal of some psychoactive pharmaceuticals through adsorption onto sludge was minimal (<1% of the initial mass load), which suggests that bio-degradation and/or chemical-transformation are the dominant mechanisms of removal of these pharmaceuticals in WWTPs. Copyright © 2015 Elsevier B.V. All rights reserved.

Development of sensitive determination method for fungicides from environmental water samples with Titanate nanotube array micro-solid phase extraction prior to high performance liquid chromatography.

PubMed

Huang, Yunrui; Zhou, Qingxiang; Xie, Guohong

2013-01-01

Fungicides have been widely used throughout the world, and the resulted pollution has absorbed great attention in recent years. Present study described an effective measurement technique for fungicides including thiram, metalaxyl, diethofencarb, myclobutanil and tebuconazole in environmental water samples. A micro-solid phase extraction (μSPE) was developed utilizing ordered TiO(2) nanotube array for determination of target fungicides prior to a high performance liquid chromatography (HPLC). The experimental results indicated that TiO(2) nanotube arrays demonstrated excellent merits on the preconcentration of fungicides, and excellent linear relationship between peak area and the concentration of fungicides was obtained in the range of 0.1-50 μg L(-1). The detection limits for the targeted fungicides were in the range of 0.016-0.086 μg L(-1) (S/N=3). Four real environmental water samples were used to validate the applicability of the proposed method, and good spiked recoveries in the range of 73.9-114% were achieved. A comparison of present method with conventional solid phase extraction was made and the results exhibited that proposed method resulted in better recoveries. The results demonstrated that this μ-SPE technique was a viable alternative for the analysis of fungicides in complex samples. Copyright © 2012 Elsevier Ltd. All rights reserved.

Optically Stimulated Luminescence Analysis Method for High Dose Rate Using an Optical Fiber Type Dosimeter

NASA Astrophysics Data System (ADS)

Ueno, Katsunori; Tominaga, Kazuo; Tadokoro, Takahiro; Ishizawa, Koji; Takahashi, Yoshinori; Kuwabara, Hitoshi

2016-08-01

The investigation of air dose rates at locations in the Fukushima Dai-ichi Nuclear Power Station is necessary for safe removal of the molten nuclear fuel. The target performance for the investigation is to analyze a dose rate in the range of 10-3 Gy/h to 102 Gy/h with a measurement precision of ±4.0% full scale (F.S.) at a measurement interval of 60 s. In order to achieve this target, the authors proposed an optically stimulated luminescence (OSL) analysis method using prompt OSL for a wide dynamic range of dose rates; the OSL is generated using BaFBr:Eu with a fast decay time constant. The luminescence intensity by prompt OSL was formulated by the electron concentration of the trapping state during gamma ray and stimulation light irradiations. The prototype OSL monitor using BaFBr:Eu was manufactured for investigation of prompt OSL and evaluation of the measurement precision. The time dependence of the luminescence intensity by prompt OSL was analyzed by irradiating the OSL sensor in a 60Co irradiation facility. The measured dose rates were obtained in a prompt mode and an accumulating mode with a precision of ±3.3% F.S. for the dose rate range of 9.5 ×10-4 Gy/h to 1.2 ×102 Gy/h.

Formulation and optimization of coated PLGA – Zidovudine nanoparticles using factorial design and in vitro in vivo evaluations to determine brain targeting efficiency

PubMed Central

Peter Christoper, G.V.; Vijaya Raghavan, C.; Siddharth, K.; Siva Selva Kumar, M.; Hari Prasad, R.

2013-01-01

In the current study zidovudine loaded PLGA nanoparticles were prepared, coated and further investigated for its effectiveness in brain targeting. IR and DSC studies were performed to determine the interaction between excipients used and to find out the nature of drug in the formulation. Formulations were prepared by adopting 23 factorial designs to evaluate the effects of process and formulation variables. The prepared formulations were subjected for in vitro and in vivo evaluations. In vitro evaluations showed particle size below 100 nm, entrapment efficiency of formulations ranges of 28–57%, process yield of 60–76% was achieved and drug release for the formulations were in the range of 50–85%. The drug release from the formulations was found to follow Higuchi release pattern, n–value obtained after Korsemeyer plot was in the range of 0.56–0.78. In vivo evaluations were performed in mice after intraperitoneal administration of zidovudine drug solution, uncoated and coated formulation. Formulation when coated with Tween 80 achieved a higher concentration in the brain than that of the drug in solution and of the uncoated formulation. Stability studies indicated that there was no degradation of the drug in the formulation after 90 days of preparation when stored in refrigerated condition. PMID:24648825

Neuromuscular performance of maximal voluntary explosive concentric contractions is influenced by angular acceleration.

PubMed

Hahn, D; Bakenecker, P; Zinke, F

2017-12-01

Torque production during maximal voluntary explosive contractions is considered to be a functionally more relevant neuromuscular measure than steady-state torque, but little is known about accelerated concentric contractions. This study investigated torque, muscle activity, and fascicle behavior during isometric and fast concentric contractions of quadriceps femoris. Ten participants performed maximal voluntary explosive isometric, isovelocity, and additional concentric knee extensions at angular accelerations ranging from 700 to 4000° s -2 that resulted in an angular velocity of 300° s -1 at 40° knee flexion. Concentric torque at 40° knee flexion was corrected for inertia, and the corresponding isometric torque was matched to the time when the target knee angle of 40° was reached during concentric contractions. Electromyography of quadriceps femoris and hamstrings and ultrasound of vastus lateralis were measured to determine muscle activity, fascicle length, and fascicle velocity (FV). The faster the acceleration, the more torque was produced during concentric contractions at 40° knee flexion, which was accompanied by a reduction in FV. In comparison with isometric conditions, concentric quadriceps muscle activity was increased and torque during accelerations ≥3000° s -2 equaled the time-matched isometric torque. Our results provide novel evidence that acceleration influences torque production during maximal voluntary explosive concentric contractions. This is suggested to be due to series elasticity and reduced force depression. © 2016 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

Trends and advances in food analysis by real-time polymerase chain reaction.

PubMed

Salihah, Nur Thaqifah; Hossain, Mohammad Mosharraf; Lubis, Hamadah; Ahmed, Minhaz Uddin

2016-05-01

Analyses to ensure food safety and quality are more relevant now because of rapid changes in the quantity, diversity and mobility of food. Food-contamination must be determined to maintain health and up-hold laws, as well as for ethical and cultural concerns. Real-time polymerase chain reaction (RT-PCR), a rapid and inexpensive quantitative method to detect the presence of targeted DNA-segments in samples, helps in determining both accidental and intentional adulterations of foods by biological contaminants. This review presents recent developments in theory, techniques, and applications of RT-PCR in food analyses, RT-PCR addresses the limitations of traditional food analyses in terms of sensitivity, range of analytes, multiplexing ability, cost, time, and point-of-care applications. A range of targets, including species of plants or animals which are used as food ingredients, food-borne bacteria or viruses, genetically modified organisms, and allergens, even in highly processed foods can be identified by RT-PCR, even at very low concentrations. Microfluidic RT-PCR eliminates the separate sample-processing step to create opportunities for point-of-care analyses. We also cover the challenges related to using RT-PCR for food analyses, such as the need to further improve sample handling.

Measurements of the differential cross sections for recoil tritons in 4He- 3T scattering at energies between 0.5 and 2.5 MeV

NASA Astrophysics Data System (ADS)

Sawicki, J. A.

1988-03-01

Differential cross-sections for recoil detection of tritons from elastic scattering of α-particles on tritium were measured at forward recoil angles from 10° and 40° and over incident 4He energies ranging from 0.5 to 2.5 MeV. Thin solid state targets consisted of about 10 16T {at.}/{cm 2} either absorbed in a thin film of titanium or implanted at low energy in the matrix of amorphous silicon. The recoil yields were normalized against the yields of the T(d, α)n reaction measured on the same targets. It is found that the cross sections obtained are considerably enhanced as compared to the Rutherford recoil cross section, what can be attributed to the combined effect of Coulomb and nuclear potentials and formation of compound 7Li nuclei. The applications of the elastic recoil detection as a means for depth profiling of tritium in materials are briefly considered. The measured dependence of the triton recoil cross section on the incident energy of 4He + ions allows profiling the concentration of tritium across a range ˜ l μm below the surface of solids.

Pulsed—Laser Deposition Of Oxide Thin Films And Laser—Induced Breakdown Spectroscopy Of Multi—Element Materials

NASA Astrophysics Data System (ADS)

Pedarnig, Johannes D.

2010-10-01

New results of the Linz group on pulsed—laser deposition (PLD) of oxide thin films and on laser—induced breakdown spectroscopy (LIBS) of multi-element materials are reported. High-Tc superconducting (HTS) films with enhanced critical current density Jc are produced by laser ablation of novel nano-composite ceramic targets. The targets contain insulating nano-particles that are embedded into the YBa2Cu3O7 matrix. Epitaxial double-layers of lithium-doped and aluminum-doped ZnO are deposited on r-cut sapphire substrates. Acoustic over-modes in the GHz range are excited by piezoelectric actuation of layers. Smooth films of rare-earth doped glass are produced by F2—laser ablation. The transport properties of HTS thin films are modified by light—ion irradiation. Thin film nano—patterning is achieved by masked ion beam irradiation. LIBS is employed to analyze trace elements in industrial iron oxide powder and reference polymer materials. Various trace elements of ppm concentration are measured in the UV/VIS and vacuum-UV spectral range. Quantitative LIBS analysis of major components in oxide materials is performed by calibration-free methods.

The cubicon method for concentrating membrane proteins in the cubic mesophase.

PubMed

Ma, Pikyee; Weichert, Dietmar; Aleksandrov, Luba A; Jensen, Timothy J; Riordan, John R; Liu, Xiangyu; Kobilka, Brian K; Caffrey, Martin

2017-09-01

The lipid cubic phase (in meso) method is an important approach for generating crystals and high-resolution X-ray structures of integral membrane proteins. However, as a consequence of instability, it can be impossible-using traditional methods-to concentrate certain membrane proteins and complexes to values suitable for in meso crystallization and structure determination. The cubicon method described here exploits the amphiphilic nature of membrane proteins and their natural tendency to partition preferentially into lipid bilayers from aqueous solution. Using several rounds of reconstitution, the protein concentration in the bilayer of the cubic mesophase can be ramped up stepwise from less than a milligram per milliliter to tens of milligrams per milliliter for crystallogenesis. The general applicability of the method is demonstrated with five integral membrane proteins: the β 2 -adrenergic G protein-coupled receptor (β 2 AR), the peptide transporter (PepT St ), diacylglycerol kinase (DgkA), the alginate transporter (AlgE) and the cystic fibrosis transmembrane conductance regulator (CFTR). In the cases of β 2 AR, PepT St , DgkA and AlgE, an effective 20- to 45-fold concentration was realized, resulting in a protein-laden mesophase that allowed the formation of crystals using the in meso method and structure determination to resolutions ranging from 2.4 Å to 3.2 Å. In addition to opening up in meso crystallization to a broader range of integral membrane protein targets, the cubicon method should find application in situations that require membrane protein reconstitution in a lipid bilayer at high concentrations. These applications include functional and biophysical characterization studies for ligand screening, drug delivery, antibody production and protein complex formation. A typical cubicon experiment can be completed in 3-5 h.