A laboratory-scale pretreatment and hydrolysis assay for determination of reactivity in cellulosic biomass feedstocks.

PubMed

Wolfrum, Edward J; Ness, Ryan M; Nagle, Nicholas J; Peterson, Darren J; Scarlata, Christopher J

2013-11-14

The rapid determination of the release of structural sugars from biomass feedstocks is an important enabling technology for the development of cellulosic biofuels. An assay that is used to determine sugar release for large numbers of samples must be robust, rapid, and easy to perform, and must use modest amounts of the samples to be tested.In this work we present a laboratory-scale combined pretreatment and saccharification assay that can be used as a biomass feedstock screening tool. The assay uses a commercially available automated solvent extraction system for pretreatment followed by a small-scale enzymatic hydrolysis step. The assay allows multiple samples to be screened simultaneously, and uses only ~3 g of biomass per sample. If the composition of the biomass sample is known, the results of the assay can be expressed as reactivity (fraction of structural carbohydrate present in the biomass sample released as monomeric sugars). We first present pretreatment and enzymatic hydrolysis experiments on a set of representative biomass feedstock samples (corn stover, poplar, sorghum, switchgrass) in order to put the assay in context, and then show the results of the assay applied to approximately 150 different feedstock samples covering 5 different materials. From the compositional analysis data we identify a positive correlation between lignin and structural carbohydrates, and from the reactivity data we identify a negative correlation between both carbohydrate and lignin content and total reactivity. The negative correlation between lignin content and total reactivity suggests that lignin may interfere with sugar release, or that more mature samples (with higher structural sugars) may have more recalcitrant lignin. The assay presented in this work provides a robust and straightforward method to measure the sugar release after pretreatment and saccharification that can be used as a biomass feedstock screening tool. We demonstrated the utility of the assay by identifying correlations between feedstock composition and reactivity in a population of 150 samples.

Construction of a D-amino acid oxidase reactor based on magnetic nanoparticles modified by a reactive polymer and its application in screening enzyme inhibitors.

PubMed

Mu, Xiaoyu; Qiao, Juan; Qi, Li; Liu, Ying; Ma, Huimin

2014-08-13

Developing facile and high-throughput methods for exploring pharmacological inhibitors of D-amino acid oxidase (DAAO) has triggered increasing interest. In this work, DAAO was immobilized on the magnetic nanoparticles, which were modified by a biocompatible reactive polymer, poly(glycidyl methacrylate) (PGMA) via an atom transfer radical polymerization technique. Interestingly, the enzyme immobilization process was greatly promoted with the assistance of a lithium perchlorate catalyst. Meanwhile, a new amino acid ionic liquid (AAIL) was successfully synthesized and employed as the efficient chiral ligand in a chiral ligand exchange capillary electrophoresis (CLE-CE) system for chiral separation of amino acids (AAs) and quantitation of methionine, which was selected as the substrate of DAAO. Then, the apparent Michaelis-Menten constants in the enzyme system were determined with the proposed CLE-CE method. The prepared DAAO-PGMA-Fe3O4 nanoparticles exhibited excellent reusability and good stability. Moreover, the enzyme reactor was successfully applied in screening DAAO inhibitors. These results demonstrated that the enzyme could be efficiently immobilized on the polymer-grafted magnetic nanoparticles and that the obtained enzyme reactor has great potential in screening enzyme inhibitors, further offering new insight into monitoring the relevant diseases.

Combinatorial electrochemical synthesis and screening of Pt-WO3 catalysts for electro-oxidation of methanol

NASA Astrophysics Data System (ADS)

Jayaraman, Shrisudersan; Baeck, Sung-Hyeon; Jaramillo, Thomas F.; Kleiman-Shwarsctein, Alan; McFarland, Eric W.

2005-06-01

An automated system for high-throughput electrochemical synthesis and screening of fuel cell electro-oxidation catalysts is described. This system consists of an electrode probe that contains counter and reference electrodes that can be positioned inside an array of electrochemical cells created within a polypropylene block. The electrode probe is attached to an automated of X-Y-Z motion system. An externally controlled potentiostat is used to apply the electrochemical potential to the catalyst substrate. The motion and electrochemical control are integrated using a user-friendly software interface. During automated synthesis the deposition potential and/or current may be controlled by a pulse program triggered by the software using a data acquisition board. The screening includes automated experiments to obtain cyclic voltammograms. As an example, a platinum-tungsten oxide (Pt-WO3) library was synthesized and characterized for reactivity towards methanol electro-oxidation.

76 FR 79692 - Agency Information Collection Activities; Submission for Office of Management and Budget Review...

Federal Register 2010, 2011, 2012, 2013, 2014

2011-12-22

... the FDA regulations designed to ensure the continued safety, purity, and potency of the product. In... components found to be reactive by a screening test for evidence of certain communicable disease agent(s) or collected from a donor with a record of a reactive screening test. Furthermore, Sec. Sec. 610.40(h)(2)(ii)(C...

Pyridoxylamine reactivity kinetics as an amine based nucleophile for screening electrophilic dermal sensitizers

PubMed Central

Chipinda, Itai; Mbiya, Wilbes; Adigun, Risikat Ajibola; Morakinyo, Moshood K.; Law, Brandon F.; Simoyi, Reuben H.; Siegel, Paul D.

2015-01-01

Chemical allergens bind directly, or after metabolic or abiotic activation, to endogenous proteins to become allergenic. Assessment of this initial binding has been suggested as a target for development of assays to screen chemicals for their allergenic potential. Recently we reported a nitrobenzenethiol (NBT) based method for screening thiol reactive skin sensitizers, however, amine selective sensitizers are not detected by this assay. In the present study we describe an amine (pyridoxylamine (PDA)) based kinetic assay to complement the NBT assay for identification of amine-selective and non-selective skin sensitizers. UV-Vis spectrophotometry and fluorescence were used to measure PDA reactivity for 57 chemicals including anhydrides, aldehydes, and quinones where reaction rates ranged from 116 to 6.2 × 10−6 M−1 s−1 for extreme to weak sensitizers, respectively. No reactivity towards PDA was observed with the thiol-selective sensitizers, non-sensitizers and prohaptens. The PDA rate constants correlated significantly with their respective murine local lymph node assay (LLNA) threshold EC3 values (R2 = 0.76). The use of PDA serves as a simple, inexpensive amine based method that shows promise as a preliminary screening tool for electrophilic, amine-selective skin sensitizers. PMID:24333919

The persistence of hepatitis C virus transmission risk in China despite serologic screening of blood donations.

PubMed

Wang, Jingxing; Liu, Jing; Huang, Yi; Wright, David J; Li, Julin; Zhou, Zhongmin; He, Weilan; Yang, Tonghan; Yao, Fuzhu; Zhu, Xiangming; Wen, Guoxin; Bi, Xinhong; Tiemuer, Mei-hei-li; Wen, Xiuqiong; Huang, Mei; Cao, Ru'an; Yun, Zhongqiao; Lü, Yunlai; Ma, Hongli; Guo, Nan; Yu, Qilu; Ness, Paul; Shan, Hua

2013-10-01

A total of 2%-2.9% of the population in China is infected with hepatitis C virus (HCV). This study estimated the prevalence and incidence of HCV among Chinese blood donors. We examined whole blood and apheresis platelet donations at five Chinese blood centers in 2008 to 2010. All donations were screened using two rounds of testing for alanine aminotransferase, antibody to human immunodeficiency virus Types 1 and 2, hepatitis B surface antigen, anti-HCV, and syphilis. Screening reactivity is defined by a reactive result in one or both rounds of screening tests. Confirmatory tests (Ortho third-generation HCV enzyme immunoassay, Johnson & Johnson) were performed on anti-HCV screening-reactive samples. Confirmatory positive rates among first-time donors (prevalence) and repeat donors (incidence) were calculated by blood center and demographic categories. Donor characteristics associated with HCV confirmatory status among first-time donors were examined using trend test and multivariable logistic regression analysis. Among 821,314 donations, 40% came from repeat donors. The overall anti-HCV screening-reactive rate was 0.48%. Estimated HCV prevalence was 235 per 100,000 first-time donors; incidence was 10 per 100,000 person-years in repeat donors. In multivariable logistic regression analysis, first-time donors older than 25 years displayed higher HCV prevalence than the younger donors. Less education is associated with higher HCV prevalence. Donors 26 to 35 years old and those above 45 years displayed the highest incidence rate. High prevalence and incidence in donors indicate high residual risks for transfusion-transmitted HCV in Chinese patients. Implementation of minipool nucleic acid testing in routine donation screening may prevent a substantial number of transfusion-transmitted HCV infections. © 2013 American Association of Blood Banks.

Evaluation of the CDC proposed laboratory HIV testing algorithm among men who have sex with men (MSM) from five US metropolitan statistical areas using specimens collected in 2011.

PubMed

Masciotra, Silvina; Smith, Amanda J; Youngpairoj, Ae S; Sprinkle, Patrick; Miles, Isa; Sionean, Catlainn; Paz-Bailey, Gabriela; Johnson, Jeffrey A; Owen, S Michele

2013-12-01

Until recently most testing algorithms in the United States (US) utilized Western blot (WB) as the supplemental test. CDC has proposed an algorithm for HIV diagnosis which includes an initial screen with a Combo Antigen/Antibody 4th generation-immunoassay (IA), followed by an HIV-1/2 discriminatory IA of initially reactive-IA specimens. Discordant results in the proposed algorithm are resolved by nucleic acid-amplification testing (NAAT). Evaluate the results obtained with the CDC proposed laboratory-based algorithm using specimens from men who have sex with men (MSM) obtained in five metropolitan statistical areas (MSAs). Specimens from 992 MSM from five MSAs participating in the CDC's National HIV Behavioral Surveillance System in 2011 were tested at local facilities and CDC. The five MSAs utilized algorithms of various screening assays and specimen types, and WB as the supplemental test. At the CDC, serum/plasma specimens were screened with 4th generation-IA and the Multispot HIV-1/HIV-2 discriminatory assay was used as the supplemental test. NAAT was used to resolve discordant results and to further identify acute HIV infections from all screened-non-reactive missed by the proposed algorithm. Performance of the proposed algorithm was compared to site-specific WB-based algorithms. The proposed algorithm detected 254 infections. The WB-based algorithms detected 19 fewer infections; 4 by oral fluid (OF) rapid testing and 15 by WB supplemental testing (12 OF and 3 blood). One acute infection was identified by NAAT from all screened-non-reactive specimens. The proposed algorithm identified more infections than the WB-based algorithms in a high-risk MSM population. OF testing was associated with most of the discordant results between algorithms. HIV testing with the proposed algorithm can increase diagnosis of infected individuals, including early infections. Published by Elsevier B.V.

Lack of cross-reactivity of Ambien (zolpidem) with drugs in standard urine drug screens.

PubMed

Piergies, A A; Sainati, S; Roth-Schechter, B

1997-04-01

To determine in healthy volunteers (men and women; 18 to 40 years old) the potential cross-reactivity of Ambien (zolpidem) and/or its metabolites with drugs that are screened by the Syva EMIT II and the Abbott ADx urine drug screens assays. Open-label, fixed-treatment sequence of 1 night each of treatment with zolpidem (10 mg) and temazepam (15 mg). Clinical Pharmacology Unit within a teaching hospital. Over a 24-hour period, presence or absence of positive results on the Syva EMIT II or the Abbott ADx urine drug assay system, each performed at two different laboratory assay sites. Following ingestion of zolpidem, no subject had any positive response in either laboratory to the Syva EMIT II or the Abbott ADx urine drug screen assays at 0, 4, 8, 12, and 24 hours postdose. During the same time period, all subjects had measurable zolpidem plasma concentrations at 1.5 and 8 hours postdose, with mean concentrations of 115.2 ng/mL and 30.1 ng/mL, respectively (in agreement with its half-life of 2.5 hours). The positive response rate at 10 hours after ingestion of Restoril (temazepam) among the four laboratory/assay combinations ranged from 36.8% to 73.7%, a range that is within the reported response rates for these tests. These data indicate that zolpidem will not cross-react in standard urine drug screens with benzodiazepines, opiates, barbiturates, cocaine, cannabinoids, or amphetamines.

Towards a rational approach for heavy-atom derivative screening in protein crystallography

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

Agniswamy, Johnson; Joyce, M. Gordon; Hammer, Carl H.

2008-04-01

Heavy-atom derivatization is routinely used in protein structure determination and is thus of critical importance in structural biology. In order to replace the current trial-and-error heavy-atom derivative screening with a knowledge-based rational derivative-selection method, the reactivity of more than 40 heavy-atom compounds over a wide range of buffer and pH values was systematically examined using peptides which contained a single reactive amino-acid residue. Heavy-atom derivatization is routinely used in protein structure determination and is thus of critical importance in structural biology. In order to replace the current trial-and-error heavy-atom derivative screening with a knowledge-based rational derivative-selection method, the reactivity ofmore » more than 40 heavy-atom compounds over a wide range of buffer and pH values was systematically examined using peptides which contained a single reactive amino-acid residue. Met-, Cys- and His-containing peptides were derivatized against Hg, Au and Pt compounds, while Tyr-, Glu-, Asp-, Asn- and Gln-containing peptides were assessed against Pb compounds. A total of 1668 reactive conditions were examined using mass spectrometry and were compiled into heavy-atom reactivity tables. The results showed that heavy-atom derivatization reactions are highly linked to buffer and pH, with the most accommodating buffer being MES at pH 6. A group of 21 compounds were identified as most successful irrespective of ligand or buffer/pH conditions. To assess the applicability of the peptide heavy-atom reactivity to proteins, lysozyme crystals were derivatized with a list of peptide-reactive compounds that included both known and new compounds for lysozyme derivatization. The results showed highly consistent heavy-atom reactivities between the peptides and lysozyme.« less

Detection and identification of occult HBV in blood donors in Taiwan using a commercial, multiplex, multi-dye nucleic acid amplification technology screening test.

PubMed

Lin, K T; Chang, C L; Tsai, M H; Lin, K S; Saldanha, J; Hung, C M

2014-02-01

The ability of a new generation commercial, multiplex, multi-dye test from Roche, the cobas TaqScreen MPX test, version 2.0, to detect and identify occult HBV infections was evaluated using routine donor samples from Kaohsiung Blood Bank, Taiwan. A total of 5973 samples were tested by nucleic acid amplification technology (NAT); 5898 in pools of six, 66 in pools of less than six and nine samples individually. NAT-reactive samples were retested with alternative NAT tests, and follow-up samples from the donors were tested individually by NAT and for all the HBV serological markers. Eight NAT-only-reactive donors were identified, and follow-up samples were obtained from six of the donors. The results indicated that all eight donors had an occult HBV infection with viral loads <12 IU/ml. The cobas(®) TaqScreen MPX test, version 2.0, has an advantage over the current Roche blood screening test, the cobas TaqScreen MPX test, for screening donations in countries with a high prevalence of occult HBV infections since the uncertainty associated with identifying samples with very low viremia is removed by the ability of the test to identify the viral target in samples that are reactive with the cobas TaqScreen MPX test, version 2.0. © 2013 International Society of Blood Transfusion.

Reactivity of coal in direct hydrogenation processes: Technical progress report, March-May 1987

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

Baldwin, R.M.; Miller, R.L.

Research during the past quarter centered on continuation of two facets related to the study of coal reactivity in direct hydrogenation liquefaction processes. Five coals from the Argonne Premium coal collection were liquefied at three temperature levels in order to gather data for kinetic analysis purposes. Conversion of these coals to THF-, toluene-, and hexane-solubles was determined at temperatures of 425, 400, and 375 C, and nominal reaction times of 3, 5, 10, 15, and 40 minutes in the microautoclave batch reaction system. Preliminary mathematical modeling of the data using simple irreversible rate expressions and more complex formulations based onmore » a statistical distribution of activation energies was initiated in order to investigate the feasibility of utilizing activation energy as an additional reactivity screening factor. Use of complex models such as the Anthony-Howard formulation for purposes of activation energy determination from liquefaction data at one temperature level was further examined. Five of the 21 coals from the Penn State Premium coal sample bank were liquefied at the standard reactivity screening conditions, and the rate and extent of conversion to THF-, and toluene-, and hexane-solubles quantified. These data were added to the existing data base containing similar information for the prior coal suites from the Exxon and Argonne collections, and preliminary correlational efforts for reactivity vs. coal properties were initiated. Prior conclusions regarding the effect of rank on the rate and extent of conversion were qualitatively verified from the data collected. 1 ref., 13 figs., 2 tabs.« less

High-performance liquid chromatography coupled with post-column dual-bioactivity assay for simultaneous screening of xanthine oxidase inhibitors and free radical scavengers from complex mixture.

PubMed

Li, D Q; Zhao, J; Li, S P

2014-06-06

Xanthine oxidase (XO) can catalyze hypoxanthine and xanthine to generate uric acid and reactive oxygen species (ROS), including superoxide anion radical (O₂(•-)) and hydrogen peroxide. XO inhibitors and free radical scavengers are beneficial to the treatment of gout and many related diseases. In the present study, an on-line high-performance liquid chromatography (HPLC) coupled with post-column dual-bioactivity assay was established and successfully applied to simultaneously screening of XO inhibitors and free radical scavengers from a complex mixture, Oroxylum indicum extract. The integrated system of HPLC separation, bioactivity screening and mass spectrometry identification was proved to be simple and effective for rapid and sensitive screening of individual bioactive compounds in complex mixtures. Copyright © 2014 Elsevier B.V. All rights reserved.

Contemporary screening approaches to reaction discovery and development.

PubMed

Collins, Karl D; Gensch, Tobias; Glorius, Frank

2014-10-01

New organic reactivity has often been discovered by happenstance. Several recent research efforts have attempted to leverage this to discover new reactions. In this Review, we attempt to unify reported approaches to reaction discovery on the basis of the practical and strategic principles applied. We concentrate on approaches to reaction discovery as opposed to reaction development, though conceptually groundbreaking approaches to identifying efficient catalyst systems are also considered. Finally, we provide a critical overview of the utility and application of the reported methods from the perspective of a synthetic chemist, and consider the future of high-throughput screening in reaction discovery.

Adhesive Development for Military Bridging

DTIC Science & Technology

1988-11-08

resins investigated were hydrocarbon epoxy novolacs (HEN XP71756.00 and .01), epoxy phenol novolacs (DEN 438), diglycidyl ether of bisphenol A (Epon 828... Resin Systems for Water Resistant Adhesives IV Results and Discussion A. Resin Blending and Processibility B. First-Level Screening C. Second-Level...and insensitivity to minor processing errors. To accomplish this, base resins with hydrophobic character and curatives with low-temperature reactivity

Laboratory and epidemiologic evaluation of an enzyme immunoassay for antibodies to HTLV-III

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

Ward, J.W.; Grindon, A.J.; Feorino, P.M.

1986-07-18

The enzyme immunoassays (EIAs) for antibody to human T-cell lymphotropic virus type III (HTLV-III) were rapidly adopted for screening donated blood and plasma. To evaluate the significance of a positive EIA reaction, test performance was examined in a blood bank screening program. Specimens were tested by EIA, Western blot assay, and HTLV-III/lymphadenopathy-associated virus (LAV) culture. The EIA was positive in 0.25% of 67 190 blood donations. Specimens were categorized and 57.3% had low (weak) reactivity, 12.7% had moderate reactivity, and 30.0% had high reactivity. Highly reactive specimens were strongly associated with a positive Western blot or culture (86.7%) in contrastmore » to moderately and weekly reactive specimens (1.9%). Twenty-five of 29 donors interviewed with a highly reactive EIA had risk factors for HTLV-III/LAV infection. Risk factors were not identified for 74 of 75 interviewed donors with specimens of lower reactivity. The minimum calculated specificity was 99.82%. The use of the HTLV-III EIA has virtually eliminated the use of blood and plasma for HTLV-III/LAV infected donors.« less

Reactive case detection for malaria elimination: real-life experience from an ongoing program in Swaziland.

PubMed

Sturrock, Hugh J W; Novotny, Joe M; Kunene, Simon; Dlamini, Sabelo; Zulu, Zulisile; Cohen, Justin M; Hsiang, Michelle S; Greenhouse, Bryan; Gosling, Roly D

2013-01-01

As countries move towards malaria elimination, methods to identify infections among populations who do not seek treatment are required. Reactive case detection, whereby individuals living in close proximity to passively detected cases are screened and treated, is one approach being used by a number of countries including Swaziland. An outstanding issue is establishing the epidemiologically and operationally optimal screening radius around each passively detected index case. Using data collected between December 2009 and June 2012 from reactive case detection (RACD) activities in Swaziland, we evaluated the effect of screening radius and other risk factors on the probability of detecting cases by reactive case detection. Using satellite imagery, we also evaluated the household coverage achieved during reactive case detection. Over the study period, 250 cases triggered RACD, which identified a further 74 cases, showing the value of RACD over passive surveillance alone. Results suggest that the odds of detecting a case within the household of the index case were significantly higher than in neighbouring households (odds ratio (OR) 13, 95% CI 3.1-54.4). Furthermore, cases were more likely to be detected when RACD was conducted within a week of the index presenting at a health facility (OR 8.7, 95% CI 1.1-66.4) and if the index household had not been sprayed with insecticide (OR sprayed vs not sprayed 0.11, 95% CI 0.03-0.46). The large number of households missed during RACD indicates that a 1 km screening radius may be impractical in such resource limited settings such as Swaziland. Future RACD in Swaziland could be made more effective by achieving high coverage amongst individuals located near to index cases and in areas where spraying has not been conducted. As well as allowing the programme to implement RACD more rapidly, this would help to more precisely define the optimal screening radius.

A randomized trial to evaluate the use of text messaging, letter and telephone call reminders to improve return of blood donors with reactive serologic tests

PubMed Central

Porto-Ferreira, Francisco Augusto; de Almeida-Neto, Cesar; Murphy, Edward L.; de Camargo Montebello, Sandra; Nogueira, Fátima Aparecida Hangai; Koga da Silva, Edina Mariko; MacFarland, William; Custer, Brian

2016-01-01

Introduction Low return rates for notification and counseling among donors with reactive serologic screening tests have been reported worldwide. A randomized trial to test the effectiveness of text message, letter or telephone call reminders to improve return among non-responding first-time blood donors with reactive serologic tests was conducted. Methods Donors with serologically reactive screening test results who had a cell phone and resided in the metropolitan telephone area code of São Paulo in the period from August 2013 through July 2014 were eligible. A consecutive sample of first-time donors with reactive screening tests who had not responded to a standard letter requesting the donor return to the blood center were randomly assigned to receive a text, a new letter or a telephone call requesting return for notification and counseling. Return rates were measured over the subsequent 30 days. Results Return following a phone call reminder was better than a text message (39.8% vs. 28.4%; OR=1.66; 95%CI 1.05–2.64) but not better than a letter (39.8% vs. 34.4%; OR=1.32; 95%CI 0.83–2.12). Older age was a predictor of higher rate of return with each year increase in age associated with a 2% increase in the odds of return (OR=1.02; 95%CI 1.01–1.04). Conclusion In non-responding serologic reactive donors, telephone call led to a higher return rate than text message. The results of this study suggest that use of text messages, while attractive for its simplicity, will not lead to increased donor notification success following serologically reactive marker results from blood donation in Brazil. PMID:27774609

Routine screening of blood donations at Qingdao central blood bank, China, for hepatitis B virus (HBV) DNA with a real-time, multiplex nucleic acid test for HBV, hepatitis C virus, and human immunodeficiency virus Types 1 and 2.

PubMed

Yang, Zhongsi; Xu, Lei; Liu, Li; Feng, Qiuxia; Zhang, Longmu; Ma, Weijuan; Saldanha, John; Wang, Mingmin; Zhao, Lin

2013-10-01

The Roche cobas TaqScreen MPX test was used to evaluate the rate of hepatitis B surface antigen (HBsAg)-negative donations that were hepatitis B virus (HBV) DNA reactive from June 2010 to January 2011 in Qingdao, China. HBsAg-negative samples from 65,800 voluntary blood donors were tested with the cobas TaqScreen MPX test in pools of 6 on the Roche cobas s 201 blood screening platform. Samples positive for HBV DNA and negative for HBsAg were quantitated with the Roche COBAS AmpliPrep/COBAS TaqMan HBV test. In addition, serologic tests for HBsAg, hepatitis B surface antibody, anti-hepatitis B core antigen (anti-HBc), anti-hepatitis B e antigen (anti-HBe), and hepatitis B e antigen (HBe) were done using the Roche electrochemiluminescence immunoassay. A total of 80 nucleic acid amplification technology (NAT) test-reactive pools were identified and 59 pools (74%) resolved to a reactive sample. All samples were HBV DNA reactive and the viral load in each sample was quantitated. The viral loads of the samples ranged from less than 20 to 34,600 IU/mL; 13 samples (22%) had viral loads of more than 20 IU/mL, 27 samples (45.8%) had viral loads of less than 20 IU/mL, and 19 samples (32.2%) had undetectable viral loads. Of the 59 NAT-reactive samples, 40 (67.8%) were anti-HBc positive. Fifteen of the 59 samples could not be confirmed as NAT reactive either by an alternative NAT test or by serology. The HBV NAT yield in blood donors in Qingdao is 0.06% (38/65,800). This study confirmed the value of NAT for interdicting HBV-positive donations and preventing transfusion-transmitted HBV infections. © 2013 American Association of Blood Banks.

Biomimetic trapping cocktail to screen reactive metabolites: use of an amino acid and DNA motif mixture as light/heavy isotope pairs differing in mass shift.

PubMed

Hosaka, Shuto; Honda, Takuto; Lee, Seon Hwa; Oe, Tomoyuki

2018-06-01

Candidate drugs that can be metabolically transformed into reactive electrophilic products, such as epoxides, quinones, and nitroso compounds, are of special concern because subsequent covalent binding to bio-macromolecules can cause adverse drug reactions, such as allergic reactions, hepatotoxicity, and genotoxicity. Several strategies have been reported for screening reactive metabolites, such as a covalent binding assay with radioisotope-labeled drugs and a trapping method followed by LC-MS/MS analyses. Of these, a trapping method using glutathione is the most common, especially at the early stage of drug development. However, the cysteine of glutathione is not the only nucleophilic site in vivo; lysine, histidine, arginine, and DNA bases are also nucleophilic. Indeed, the glutathione trapping method tends to overlook several types of reactive metabolites, such as aldehydes, acylglucuronides, and nitroso compounds. Here, we introduce an alternate way for screening reactive metabolites as follows: A mixture of the light and heavy isotopes of simplified amino acid motifs and a DNA motif is used as a biomimetic trapping cocktail. This mixture consists of [ 2 H 0 ]/[ 2 H 3 ]-1-methylguanidine (arginine motif, Δ 3 Da), [ 2 H 0 ]/[ 2 H 4 ]-2-mercaptoethanol (cysteine motif, Δ 4 Da), [ 2 H 0 ]/[ 2 H 5 ]-4-methylimidazole (histidine motif, Δ 5 Da), [ 2 H 0 ]/[ 2 H 9 ]-n-butylamine (lysine motif, Δ 9 Da), and [ 13 C 0 , 15 N 0 ]/[ 13 C 1 , 15 N 2 ]-2'-deoxyguanosine (DNA motif, Δ 3 Da). Mass tag triggered data-dependent acquisition is used to find the characteristic doublet peaks, followed by specific identification of the light isotope peak using MS/MS. Forty-two model drugs were examined using an in vitro microsome experiment to validate the strategy. Graphical abstract Biomimetic trapping cocktail to screen reactive metabolites.

Comparison of Traditional and Reverse Syphilis Screening Algorithms in Medical Health Checkups.

PubMed

Nah, Eun Hee; Cho, Seon; Kim, Suyoung; Cho, Han Ik; Chai, Jong Yil

2017-11-01

The syphilis diagnostic algorithms applied in different countries vary significantly depending on the local syphilis epidemiology and other considerations, including the expected workload, the need for automation in the laboratory and budget factors. This study was performed to investigate the efficacy of traditional and reverse syphilis diagnostic algorithms during general health checkups. In total, 1,000 blood specimens were obtained from 908 men and 92 women during their regular health checkups. Traditional screening and reverse screening were applied to the same specimens using automatic rapid plasma regain (RPR) and Treponema pallidum latex agglutination (TPLA) tests, respectively. Specimens that were reverse algorithm (TPLA) reactive, were subjected to a second treponemal test performed by using the chemiluminescent microparticle immunoassay (CMIA). Of the 1,000 specimens tested, 68 (6.8%) were reactive by reverse screening (TPLA) compared with 11 (1.1%) by traditional screening (RPR). The traditional algorithm failed to detect 48 specimens [TPLA(+)/RPR(-)/CMIA(+)]. The median TPLA cutoff index (COI) was higher in CMIA-reactive cases than in CMIA-nonreactive cases (90.5 vs 12.5 U). The reverse screening algorithm could detect the subjects with possible latent syphilis who were not detected by the traditional algorithm. Those individuals could be provided with opportunities for evaluating syphilis during their health checkups. The COI values of the initial TPLA test may be helpful in excluding false-positive TPLA test results in the reverse algorithm. © The Korean Society for Laboratory Medicine

Identification and verification of the anabolic steroid boldenone in equine blood and urine by HPLC/ELISA.

PubMed

Hagedorn, H W; Schulz, R; Jaeschke, G

1994-01-01

An enzyme linked immunosorbent assay (ELISA) was developed to detect the anabolic steroid boldenone in equine blood and urine. The polyclonal antiserum was raised in rabbits, employing boldenone-17-hemisuccinate-bovine serum albumin as antigen. Boldenone-17-hemisuccinate-horseradish peroxidase served as enzyme conjugate. Sensitivity of the assay was 26.0 +/- 3.0 pg/well. Among the endogenous steroids tested only progesterone and testosterone exhibited moderate cross-reactivities, 3.4 and 2.5%, respectively. These cross-reactivities are of no importance for the boldenone assay. For the reduction of background levels, screening for boldenone of equine serum was performed after extraction. Urine samples were determined directly after dilution, omitting hydrolysis of boldenone conjugates. Positive screening results were confirmed by means of two independent HPLC systems combined with off-line detection, employing the boldenone ELISA. Methandienone served as internal standard to ascertain retention factors. In horses treated with boldenone-17-undecylenate the presence of boldenone in serum was confirmed up to 28 days and in unhydrolyzed urine up to 56 days post applicationem.

Level of C - reactive protein as an indicator for prognosis of premature uterine contractions.

PubMed

Najat Nakishbandy, Bayar M; Barawi, Sabat A M

2014-01-01

high concentrations of maternal C-reactive protein have been associated with adverse pregnancy outcome, and premature uterine contraction may be predicted by elevated levels of C-reactive protein. This may ultimately be simple and cost-effective enough to introduce as a low-risk screening program. an observational case control study was performed from May 1st, 2010 to December 1st, 2010 at Maternity Teaching Hospital-Erbil/ Kurdistan Region/ Iraq. The sample size was (200) cases. Hundred of them were presented with premature uterine contractions at 24(+0)-36(+6) weeks. The other hundred were control group at same gestational ages. The level of C-reactive protein was determined in both groups and both groups were followed till delivery. (93) out of (100) women with premature uterine contractions had elevated level of C-Reactive protein and 91% delivered prematurely while in the control group only (9) out of (100) women had elevated level of C-reactive protein and only 8% of them delivered preterm. Differences were statistically highly significant. C-reactive protein can be used as a biomarker in prediction of premature delivery when it is associated with premature uterine contractions. As well it can be used as a screening test to detect cases that are at risk of premature delivery.

Old yellow enzymes protect against acrolein toxicity in the yeast Saccharomyces cerevisiae.

PubMed

Trotter, Eleanor W; Collinson, Emma J; Dawes, Ian W; Grant, Chris M

2006-07-01

Acrolein is a ubiquitous reactive aldehyde which is formed as a product of lipid peroxidation in biological systems. In this present study, we screened the complete set of viable deletion strains in Saccharomyces cerevisiae for sensitivity to acrolein to identify cell functions involved in resistance to reactive aldehydes. We identified 128 mutants whose gene products are localized throughout the cell. Acrolein-sensitive mutants were distributed among most major biological processes but particularly affected gene expression, metabolism, and cellular signaling. Surprisingly, the screen did not identify any antioxidants or similar stress-protective molecules, indicating that acrolein toxicity may not be mediated via reactive oxygen species. Most strikingly, a mutant lacking an old yellow enzyme (OYE2) was identified as being acrolein sensitive. Old yellow enzymes are known to reduce alpha,beta-unsaturated carbonyl compounds in vitro, but their physiological roles have remained uncertain. We show that mutants lacking OYE2, but not OYE3, are sensitive to acrolein, and overexpression of both isoenzymes increases acrolein tolerance. Our data indicate that OYE2 is required for basal levels of tolerance, whereas OYE3 expression is particularly induced following acrolein stress. Despite the range of alpha,beta-unsaturated carbonyl compounds that have been identified as substrates of old yellow enzymes in vitro, we show that old yellow enzymes specifically mediate resistance to small alpha,beta-unsaturated carbonyl compounds, such as acrolein, in vivo.

Procalcitonin and C-reactive protein as markers of bacterial infection in critically ill children at onset of systemic inflammatory response syndrome.

PubMed

Simon, Liliana; Saint-Louis, Patrick; Amre, Devendra K; Lacroix, Jacques; Gauvin, France

2008-07-01

To compare the accuracy of procalcitonin and C-reactive protein as diagnostic markers of bacterial infection in critically ill children at the onset of systemic inflammatory response syndrome (SIRS). Prospective cohort study. Tertiary care, university-affiliated pediatric intensive care unit (PICU). Consecutive patients with SIRS. From June to December 2002, all PICU patients were screened daily to include cases of SIRS. At inclusion (onset of SIRS), procalcitonin and C-reactive protein levels as well as an array of cultures were obtained. Diagnosis of bacterial infection was made a posteriori by an adjudicating process (consensus of experts unaware of the results of procalcitonin and C-reactive protein). Baseline and daily data on severity of illness, organ dysfunction, and outcome were collected. Sixty-four patients were included in the study and were a posteriori divided into the following groups: bacterial SIRS (n = 25) and nonbacterial SIRS (n = 39). Procalcitonin levels were significantly higher in patients with bacterial infection compared with patients without bacterial infection (p = .01). The area under the receiver operating characteristic curve for procalcitonin was greater than that for C-reactive protein (0.71 vs. 0.65, respectively). A positive procalcitonin level (>or=2.5 ng/mL), when added to bedside clinical judgment, increased the likelihood of bacterial infection from 39% to 92%, while a negative C-reactive protein level (<40 mg/L) decreased the probability of bacterial infection from 39% to 2%. Procalcitonin is better than C-reactive protein for differentiating bacterial from nonbacterial SIRS in critically ill children, although the accuracy of both tests is moderate. Diagnostic accuracy could be enhanced by combining these tests with bedside clinical judgment.

Reaction of photochemical resists used in screen printing under the influence of digitally modulated ultra violet light

NASA Astrophysics Data System (ADS)

Gmuender, T.

2017-02-01

Different chemical photo-reactive emulsions are used in screen printing for stencil production. Depending on the bandwidth, optical power and depth of field from the optical system, the reaction / exposure speed has a diverse value. In this paper, the emulsions get categorized and validated in a first step. After that a mathematical model gets developed and adapted due to heuristic experience to estimate the exposure speed under the influence of digitally modulated ultra violet (UV) light. The main intention is to use the technical specifications (intended wavelength, exposure time, distance to the stencil, electrical power, stencil configuration) in the emulsion data sheet primary written down with an uncertainty factor for the end user operating with large projector arc lamps and photo films. These five parameters are the inputs for a mathematical formula which gives as an output the exposure speed for the Computer to Screen (CTS) machine calculated for each emulsion / stencil setup. The importance of this work relies in the possibility to rate with just a few boundaries the performance and capacity of an exposure system used in screen printing instead of processing a long test series for each emulsion / stencil configuration.

Behavioral Reactivity and Approach-Withdrawal Bias in Infancy

PubMed Central

Hane, Amie Ashley; Fox, Nathan A.; Henderson, Heather A.; Marshall, Peter J.

2008-01-01

Seven hundred and seventy nine infants were screened at 4 months of age for motor and emotional reactivity. At age 9 months, infants who showed extreme patterns of motor and negative (n = 75) or motor and positive (n = 73) reactivity and an unselected control group (n = 86) were administered the Laboratory Temperament Assessment Battery (Lab-TAB), and baseline electroencephalogram (EEG) data were collected. Negatively reactive infants showed significantly more avoidance than positively reactive infants and displayed a pattern of right frontal EEG asymmetry. Positively reactive infants exhibited significantly more approach behavior than controls and exhibited a pattern of left frontal asymmetry. Results support the notion that approach-withdrawal bias underlies reactivity in infancy. PMID:18793079

A strategical re-thinking on National Blood Donor Pool: Anti-HBc positivity related re-entry mechanisms.

PubMed

Yilmaz, Soner; Unlu, Aytekin; Cetinkaya, Riza Aytac; Yapar, Mehmet; Avci, Ismail Yasar; Yilmaz, Sebahattin; Eyigun, Can Polat

2016-04-01

Screening of blood donations for antibodies against hepatitis B core antigen (anti-HBc) is used to prevent transfusion transmitted hepatitis B virus (HBV) infection. In this study, we studied the magnitude of blood donor gain by using a re-entry mechanism in our Blood Bank of Gulhane Military Academy of Medicine. Between January and May 2013, 5148 voluntary blood donors were screened by ELISA method for HBsAg, anti-HBc total and other screening markers, prospectively. Samples with repeated reactivity for the presence of anti-HBc were further tested with four supplemental assays. We detected 515 (10%) anti-HBc positive and 4612 (90%) anti-HBc negative cases in 5127 HBsAg negative serum samples. A total of 461 (89.5%) blood units were reactive for at least one additional serologic parameter and 54 were (10.5%) negative. Isolated anti-HBc positivity rate was 1.3% (69/5127). In the isolated anti-HBc positive samples, 54 were also anti-HBe and HBeAg negative. HBV DNA was not detected in any of the samples. Applying the EDQM criteria would decrease our blood donor loss from 10% to 5.4%. As alternative re-entry mechanisms have already been presented in the literature, institution of a new policy is needed to enhance the limited blood donor pool in our system. Copyright © 2016. Published by Elsevier Ltd.

A rational approach to heavy-atom derivative screening

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

Joyce, M. Gordon; Radaev, Sergei; Sun, Peter D., E-mail: psun@nih.gov

2010-04-01

In order to overcome the difficulties associated with the ‘classical’ heavy-atom derivatization procedure, an attempt has been made to develop a rational crystal-free heavy-atom-derivative screening method and a quick-soak derivatization procedure which allows heavy-atom compound identification. Despite the development in recent times of a range of techniques for phasing macromolecules, the conventional heavy-atom derivatization method still plays a significant role in protein structure determination. However, this method has become less popular in modern high-throughput oriented crystallography, mostly owing to its trial-and-error nature, which often results in lengthy empirical searches requiring large numbers of well diffracting crystals. In addition, the phasingmore » power of heavy-atom derivatives is often compromised by lack of isomorphism or even loss of diffraction. In order to overcome the difficulties associated with the ‘classical’ heavy-atom derivatization procedure, an attempt has been made to develop a rational crystal-free heavy-atom derivative-screening method and a quick-soak derivatization procedure which allows heavy-atom compound identification. The method includes three basic steps: (i) the selection of likely reactive compounds for a given protein and specific crystallization conditions based on pre-defined heavy-atom compound reactivity profiles, (ii) screening of the chosen heavy-atom compounds for their ability to form protein adducts using mass spectrometry and (iii) derivatization of crystals with selected heavy-metal compounds using the quick-soak method to maximize diffraction quality and minimize non-isomorphism. Overall, this system streamlines the process of heavy-atom compound identification and minimizes the problem of non-isomorphism in phasing.« less

A model for routine hospital-wide HIV screening: lessons learned and public health implications.

PubMed

Maxwell, Celia J; Sitapati, Amy M; Abdus-Salaam, Sayyida S; Scott, Victor; Martin, Marsha; Holt-Brockenbrough, Maya E; Retland, Nicole L

2010-12-01

Approximately 232700 (21%) of Americans are unaware of their HIV-seropositive status; this represents a potential for virus transmission. Revised recommendations from the Centers for Disease Control for HIV screening promote routine screening in the health care setting. We describe the implementation of a hospital-wide routine HIV screening program in the District of Columbia. Rapid HIV testing was conducted at Howard University Hospital on consenting patients at least 18 years of age using the OraSure OraQuick Advance Rapid HIV-1/2 Antibody Test. The study population includes Howard University Hospital patients who were offered HIV screening over a 12-month period at no cost. Screened patients received immediate test results and, for those patients found to be preliminarily reactive, confirmatory testing and linkage to care were offered. Of the 12836 patients who were offered testing, 7528 (58.6%) consented. Preliminary reactive test results were identified in 176 patients (2.3%). Overall, 45.5% were confirmed, of which 82.5% were confirmed positive. Screening protocol changes have led to 100% confirmation since implementation. Hospital-wide routine HIV screening is feasible and can be implemented effectively and efficiently. The HIV screening campaign instituted at Howard University Hospital identified a substantial number of HIV-positive individuals and provided critical connection to follow-up testing, counseling, and disease management services.

Frictional behavior and adhesion of Ag and Au films applied to aluminum oxide by oxygen-ion assisted Screen Cage Ion Plating (SCIP)

NASA Technical Reports Server (NTRS)

Spalvins, Talivaldis; Sliney, Harold E.

1994-01-01

A modified dc-diode ion plating system, by utilizing a metallic screen cage as a cathode, is introduced for coating nonconductors such as ceramics. Screen cage ion plating (SCIP) is used to apply Ag and Au lubricating films on aluminum oxide surfaces. This process has excellent ability to coat around corners to produce three-dimensional coverage of the substrate. A dramatic increase in adhesion is achieved when plating is performed in a reactive 50 percent O2 - 50 percent Ar glow discharge compared to the adhesion when plating is performed in 100 percent Ar. The presence of oxygen ion assistance contributes to the excellent adhesion as measured in a pull-type adhesion tester. The Ag and Au film adhesion is significantly increased (less than 70MPa) and generally exceeds the cohesion of the substrate such that portions of the alumina are pulled out.

Screening of post-mortem tissue donors for Coxiella burnetii infection after large outbreaks of Q fever in The Netherlands

PubMed Central

2014-01-01

Background After the largest outbreaks of Q fever ever recorded in history occurred in the Netherlands, concern arose that Coxiella may be transmitted via donated tissues of latent or chronically infected donors. The Dutch Health Council recently advised to screen tissue donors, donating high risk tissues, for Coxiella infection. Methods After validation of an enzyme immunoassay (EIA) test for IgG antibodies against phase 2 of C. burnetii for use on post-mortem samples, serum samples of 1033 consecutive Dutch post-mortem tissue donors were tested for IgG antibodies against phase 2 of C. burnetii. Confirmation of reactive results was done by immunofluorescence assay (IFA). All available tissues (corneas, heart valves, skin and bone marrow) from donors with IgG reactivity were tested for presence of Coxiella DNA by PCR. Risk factors for IgG reactivity were investigated. Results After validation of the tests for use on post-mortem samples, 50/1033 donors (4.8%) screened positive for phase 2 anti-Coxiella IgG by EIA, and 31 were confirmed by IFA (3.0%). One donor showed a serological profile compatible with chronic infection. All tested tissues (25 corneas, 6 heart valves, 4 skin and 3 bone marrow) from donors with IgG reactivity tested negative for the presence of Coxiella DNA. Except for living in a postal code area with a high number of Q fever notifications, no risk factors for IgG reactivity were found. Conclusions The strong correlation between notifications and seroprevalence confirms that the used assays are sufficiently specific for use on post-mortem samples, although one has to be aware of differences between batches. Thus, this study provides a validated method for screening tissue donors for infection with Coxiella burnetii that can be used in future outbreaks. PMID:24393298

Cloning and characterization of profilin (Pru du 4), a cross-reactive almond (Prunus dulcis) allergen.

PubMed

Tawde, Pallavi; Venkatesh, Yeldur P; Wang, Fang; Teuber, Suzanne S; Sathe, Shridhar K; Roux, Kenneth H

2006-10-01

The identity of allergenic almond proteins is incomplete. Our objective was to characterize patient IgE reactivity to a recombinant and corresponding native almond allergen. An almond cDNA library was screened with sera from patients with allergy for IgE binding proteins. Two reactive clones were sequenced, and 1 was expressed. The expressed recombinant allergen and its native counterpart (purified from unprocessed almond flour) were assayed by 1-dimensional and 2-dimensional gel electrophoresis, dot blot, and ELISA, and screened for cross-reactivity with grass profilin. The 2 selected clones encoded profilin (designated Pru du 4) sequences that differed by 2 silent mutations. By dot-blot analyses, 6 of 18 patient sera (33%) reacted with the recombinant Pru du 4 protein, and 8 of 18 (44%) reacted with the native form. ELISA results were similar. Almond and ryegrass profilins were mutually inhibitable. Two-dimensional immunoblotting revealed the presence of more than 1 native almond profilin isoform. The strength of reactivity of some patients' serum IgE differed markedly between assays and between native and recombinant profilins. Almond nut profilin is an IgE-binding food protein that is cross-reactive with grass pollen profilin and is susceptible to denaturation, resulting in variable reactivity between assay types and between patients. Serum IgE of nearly half of the tested patients with almond allergy reacts with almond nut profilin. Because most patients also had pollinosis, the well-known cross-reactivity between pollen and food profilins could account for this pattern of reactivity.

In vitro screening of Fe2+-chelating effect by a Fenton's reaction-luminol chemiluminescence system.

PubMed

Wada, Mitsuhiro; Komatsu, Hiroaki; Ikeda, Rie; Aburjai, Talal A; Alkhalil, Suleiman M; Kuroda, Naotaka; Nakashima, Kenichiro

2014-11-01

In vitro screening of a Fe(2+) -chelating effect using a Fenton's reaction-luminol chemiluminescence (CL) system is described. The luminescence between the reactive oxygen species generated by the Fenton's reaction and luminol was decreased on capturing Fe(2+) using a chelator. The proposed method can prevent the consumption of expensive seed compounds (drug discovery candidates) owing to the high sensitivity of CL detection. Therefore, the assay could be performed using small volumes of sample solution (150 μL) at micromolar concentrations. After optimization of the screening conditions, the efficacies of conventional chelators such as ethylenediaminetetraacetic acid (EDTA), diethylentriaminepentaacetic acid (DETAPAC), deferoxamine, deferiprone and 1,10-phenanthroline were examined. EC50 values for these compounds (except 1,10-phenanthroline) were in the range 3.20 ± 0.87 to 9.57 ± 0.64 μM (n = 3). Rapid measurement of the Fe(2+)-chelating effect with an assay run time of a few minutes could be achieved using the proposed method. In addition, the specificity of the method was discussed. Copyright © 2014 John Wiley & Sons, Ltd.

Reducing Schoolchildren With Reactive Aggression Through Child, Parent, and Conjoint Parent-Child Group Interventions: A Longitudinal Outcome Effectiveness Study.

PubMed

Fung, Annis Lai Chu

2017-10-10

This study was the first to evaluate the effectiveness of three different group interventions to reduce children's reactive aggression based on the social information processing (SIP) model. In the first stage of screening, 3,734 children of Grades 4-6 completed the Reactive-Proactive Aggression Questionnaire (RPQ) to assess their reactive and proactive aggression. Respondents with a total score of z ≥ 1 on the RPQ were shortlisted for the second stage of screening by qualitative interview. Interviews with 475 children were conducted to select those who showed reactive aggression featuring a hostile attributional bias. Finally, 126 children (97 males and 29 females) aged 8 to 14 (M = 9.71, SD = 1.23) were selected and randomly assigned to one of the three groups: a child group, a parent group, and a parent-child group. A significant Time × Intervention effect was found for general and reactive aggression. The parent-child group and child group showed a significant drop in general aggression and reactive aggression from posttest to 6-month follow-up, after controlling for baseline scores, sex, and age. However, the parent group showed no treatment effect: reactive aggression scores were significantly higher than those in the child group at 6-month follow-up. This study has provided strong evidence that children with reactive aggression need direct and specific treatment to reconstruct the steps of the SIP involving the selection and interpretation of cues. The intervention could help to prevent severe violent crimes at the later stage of a reactive aggressor. © 2017 Family Process Institute.

In vitro screening of 50 highly prescribed drugs for thiol adduct formation--comparison of potential for drug-induced toxicity and extent of adduct formation.

PubMed

Gan, Jinping; Ruan, Qian; He, Bing; Zhu, Mingshe; Shyu, Wen C; Humphreys, W Griffith

2009-04-01

Reactive metabolite formation has been associated with drug-induced liver, skin, and hematopoietic toxicity of many drugs that has resulted in serious clinical toxicity, leading to clinical development failure, black box warnings, or, in some cases, withdrawal from the market. In vitro and in vivo screening for reactive metabolite formation has been proposed and widely adopted in the pharmaceutical industry with the aim of minimizing the property and thus the risk of drug-induced toxicity (DIT). One of the most common screening methods is in vitro thiol trapping of reactive metabolites. Although it is well-documented that many hepatotoxins form thiol adducts, there is no literature describing the adduct formation potential of safer drugs that are widely used. The objective of this study was to quantitatively assess the thiol adduct formation potential of 50 drugs (10 associated with DIT and 40 not associated) and document apparent differences in adduct formation between toxic and safer drugs. Dansyl glutathione was used as a trapping agent to aid the quantitation of adducts following in vitro incubation of drugs with human liver microsomes in the presence and absence of NADPH. Metabolic turnover of these drugs was also monitored by LC/UV. Overall, 15 out of the 50 drugs screened formed detectable levels of thiol adducts. There were general trends toward more positive findings in the DIT group vs the non-DIT group. These trends became more marked when the relative amount of thiol adducts was taken into account and improved further when dose and total daily reactive metabolite burdens were considered. In conclusion, there appears to be a general trend between the extent of thiol adduct formation and the potential for DIT, which would support the preclinical measurement and minimization of the property through screening of thiol adduct formation as part of an overall discovery optimization paradigm.

Prevalence of Zoonotic and Vector-Borne Infections Among Afghan National Army Recruits in Afghanistan.

PubMed

Todd, Catherine S; Mansoor, Ghulam Farooq; Buhler, Cyril; Rahimi, Habiburrahman; Zekria, Rohullah; Fernandez, Stefan; Mikhail, Amy F W; Scott, Paul T; Yingst, Samuel L

2016-08-01

To measure prevalence of prior/current Plasmodium vivax and Plasmodium falciparum (PV and PF), Brucella spp. (BR), dengue virus (DENV), Leishmania donovani (visceral leishmaniasis; VL), and Crimean-Congo hemorrhagic fever (CCHF) virus exposure among Afghan National Army (ANA) recruits. Randomly chosen, nationally representative serum samples from consenting men aged 18-40 years and who were screened between February 2010 and January 2011 were tested, with ∼25 samples/province. Samples were screened for PV and PF antigens and VL antibody with rapid diagnostic tests. Reactive malaria screening results were confirmed with polymerase chain reaction assay. Enzyme-linked immunosorbent assays were used to screen for CCHF and DENV antibodies; reactive DENV samples were confirmed with the plaque-reduction neutralization test. BR screening and confirmatory testing was performed with slide and tube agglutination, respectively. Correlates of BR titres >1:80 were analyzed using logistic regression. Of 809 participants contributing specimens, 62% had previously lived outside Afghanistan, predominantly in Pakistan and Iran. CCHF (4.1%, n = 33), DENV (2.1%, n = 17), and VL (1.0%, n = 8) antibody prevalence was low. For PV and PF, only 7 out of 56 reactive samples had detectable nucleic acid. For BR, 8.0% (n = 65) of samples had screening titers >1:40, of which 83.1% had confirmatory titers >1:80. Participants from Kabul and surrounding provinces had lower odds (OR = 0.19, 95% CI: 0.04-1.00) of BR antibody compared with other regions. BR exposure was relatively common with a nearly national distribution, whereas geographic distribution for other pathogens aligned roughly with the expected vector distribution. Public health protection measures should include vector control, food safety, and enhanced diagnostics for acute febrile illness.

Dual-hormone stress reactivity predicts downstream war-zone stress-evoked PTSD.

PubMed

Josephs, Robert A; Cobb, Adam R; Lancaster, Cynthia L; Lee, Han-Joo; Telch, Michael J

2017-04-01

The crucial role of the hypothalamic-pituitary-adrenal axis (HPA) in stress-related homeostasis suggests dysregulated HPA involvement in the pathogenesis of post-traumatic stress disorder (PTSD), yet most studies examining linkages between HPA axis measures and PTSD have yielded null findings. One untested explanation for this inconsistency is a failure to account for simultaneous adrenal and gonadal influence. Here we tested the singular and interactive effects of cortisol (C R ) and testosterone (T R ) reactivity as moderators of war-zone stress evoked PTSD emergence in the war-zone. U.S. soldiers (N=120) scheduled for deployment to Iraq completed pre-deployment measures of C R and T R stress reactivity to a CO 2 inhalation challenge. Once deployed, monthly assessments of exposure to traumatic war-zone stressors and PTSD symptoms were collected via a web-based assessment system. Cortisol hypo-reactivity potentiated the pathogenic impact of war-zone stressors only in soldiers for whom the CO 2 challenge did not elevate testosterone, suggesting that the dual hormone stress reactivity profile of blunted cortisol and testosterone may confer increased risk for PTSD emergence by potentiating the pathogenic effects of war-zone stressors. Findings underscore the utility of assessing both HPA and HPG stress reactivity when assessing PTSD vulnerability and may help inform efforts for enhanced soldier screening and inoculation to war-zone stressors. Copyright © 2017 Elsevier Ltd. All rights reserved.

Biomonitoring of Organophosphorus Agent Exposure by Reactivation of Cholinesterase Enzyme Based on Carbon Nanotube-Enhanced Flow-Injection Amperometric Detection

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

Du, Dan; Wang, Jun; Smith, Jordan N.

2009-11-15

A portable, rapid, and sensitive assessment of sub-clinical organophosphorus (OPs) agent exposure based on reactivation of cholinesterase (ChE) from OP-inhibited ChE using rat saliva (in vitro) was developed using an electrochemical sensor coupled with a microflow-injection system. The sensor was based on a carbon nanotube (CNT)-modified screen printed carbon electrode (SPE), which was integrated into a flow cell. Due to the extent of inter-individual ChE activity variability, ChE biomonitoring often requires an initial base-line determination (non-inhibited) of enzyme activity which is then directly compared with activity after OP exposure. This manuscript described an alternative strategy where reactivation of the phosphorylatedmore » enzyme was exploited to enable measurement of both inhibited and baseline ChE activity (i.e. after reactivation) in the same sample. The use of CNT makes the electrochemical detection of the products from enzymatic reactions more feasible with extremely high sensitivity and at low potentials. Paraoxon was selected as a model OP compound for in vitro inhibition studies. Some experiment parameters, (e.g. inhibition and reactivation times), have been optimized such that, 92 - 95% ChE reactivation can be achieved over a broad range of ChE inhibition (5 - 94 %) with paraoxon. The extent of enzyme inhibition using this electrochemical sensor correlates well with conventional enzyme activity measurements.« less

High-throughput screening of T7 phage display and protein microarrays as a methodological approach for the identification of IgE-reactive components.

PubMed

San Segundo-Acosta, Pablo; Garranzo-Asensio, María; Oeo-Santos, Carmen; Montero-Calle, Ana; Quiralte, Joaquín; Cuesta-Herranz, Javier; Villalba, Mayte; Barderas, Rodrigo

2018-05-01

Olive pollen and yellow mustard seeds are major allergenic sources with high clinical relevance. To aid with the identification of IgE-reactive components, the development of sensitive methodological approaches is required. Here, we have combined T7 phage display and protein microarrays for the identification of allergenic peptides and mimotopes from olive pollen and mustard seeds. The identification of these allergenic sequences involved the construction and biopanning of T7 phage display libraries of mustard seeds and olive pollen using sera from allergic patients to both biological sources together with the construction of phage microarrays printed with 1536 monoclonal phages from the third/four rounds of biopanning. The screening of the phage microarrays with individual sera from allergic patients enabled the identification of 10 and 9 IgE-reactive unique amino acid sequences from olive pollen and mustard seeds, respectively. Five immunoreactive amino acid sequences displayed on phages were selected for their expression as His6-GST tag fusion proteins and validation. After immunological characterization, we assessed the IgE-reactivity of the constructs. Our results show that protein microarrays printed with T7 phages displaying peptides from allergenic sources might be used to identify allergenic components -peptides, proteins or mimotopes- through their screening with specific IgE antibodies from allergic patients. Copyright © 2018 Elsevier B.V. All rights reserved.

Hepatitis B reactivation and rituximab: a new boxed warning and considerations for solid organ transplantation.

PubMed

Martin, S T; Cardwell, S M; Nailor, M D; Gabardi, S

2014-04-01

Use of rituximab, a chimeric monoclonal antibody directed at the CD20 antigen, continues to increase in solid organ transplantation (SOT) for several off-label uses. In September 2013, the United States Food and Drug Administration (FDA) issued a Drug Safety Communication to oncology, rheumatology and pharmacy communities outlining a new Boxed Warning for rituximab. Citing 109 cases of fatal hepatitis B virus (HBV) reactivation in persons receiving rituximab therapy with previous or chronic HBV infection documented in their Adverse Event Reporting System (AERS), the FDA recommends screening for HBV serologies in all patients planned to receive rituximab and antiviral prophylaxis in any patient with a positive history of HBV infection. There is a lack of data pertaining to this topic in the SOT population despite an increase in off-label indications. Previous reports suggest patients receiving rituximab, on average, were administered six doses prior to HBV reactivation. Recommendations on prophylaxis, treatment and re-challenging patients with therapy after resolution of reactivation remain unclear. Based on data from the FDA AERS and multiple analyses in oncology, SOT providers utilizing rituximab should adhere to the FDA warnings and recommendations regarding HBV reactivation until further data are available in the SOT population. © Copyright 2014 The American Society of Transplantation and the American Society of Transplant Surgeons.

In vitro screening techniques for reactive metabolites for minimizing bioactivation potential in drug discovery.

PubMed

Prakash, Chandra; Sharma, Raman; Gleave, Michelle; Nedderman, Angus

2008-11-01

Drug induced toxicity remains one of the major reasons for failures of new pharmaceuticals, and for the withdrawal of approved drugs from the market. Efforts are being made to reduce attrition of drug candidates, and to minimize their bioactivation potential in the early stages of drug discovery in order to bring safer compounds to the market. Therefore, in addition to potency and selectivity; drug candidates are now selected on the basis of acceptable metabolism/toxicology profiles in preclinical species. To support this, new approaches have been developed, which include extensive in vitro methods using human and animal hepatic cellular and subcellular systems, recombinant human drug metabolizing enzymes, increased automation for higher-throughput screens, sensitive analytical technologies and in silico computational models to assess the metabolism aspects of the new chemical entities. By using these approaches many compounds that might have serious adverse reactions associated with them are effectively eliminated before reaching clinical trials, however some toxicities such as those caused by idiosyncratic responses, are not detected until a drug is in late stages of clinical trials or has become available to the market. One of the proposed mechanisms for the development of idiosyncratic drug toxicity is the bioactivation of drugs to form reactive metabolites by drug metabolizing enzymes. This review discusses the different approaches to, and benefits of using existing in vitro techniques, for the detection of reactive intermediates in order to minimize bioactivation potential in drug discovery.

The Improvement of Ion Plated Ag and Au Film Adherence to Si3N4 and SiC Surfaces for Increased Tribological Performance

NASA Technical Reports Server (NTRS)

Spalvins, Talivaldis

1998-01-01

A modified dc-diode plating system, utilizing a metallic screen cage as a cathode and referred as SCREEN CAGE ION PLATING (SCIP), is used to deposit Ag and Au lubricating films on Si3N4 and SiC surfaces. When deposition is performed in Ar or N2, glow discharge, the surface displays poor adhesive strength (less than 5 MPa). A dramatic increase in adhesive strength (less than 80 MPa) is achieved when plating is performed in a reactive 50% 02 + 50% Ar glow discharge. The excited/ionized oxygen species (O2(+)/O(+) in the glow discharge contribute to the oxidation of the Si3N4 or SiC surfaces as determined by X-ray Photoelectron Spectroscopy (XTS) depth profiling. The reactively sputter-oxidized S3N4 or SiC surfaces and the activated-oxidized-metastable Ag or Au species formed in the plasma cooperatively contribute to the increased adherence. As a result, the linear thermal expansion coefficient mismatch at the interface is reduced. These lubricating Ag and Au films under sliding conditions reduce the friction coefficient by a factor of 2-1/2 to 4.

Modeling Reactivity to Biological Macromolecules with a Deep Multitask Network

PubMed Central

2016-01-01

Most small-molecule drug candidates fail before entering the market, frequently because of unexpected toxicity. Often, toxicity is detected only late in drug development, because many types of toxicities, especially idiosyncratic adverse drug reactions (IADRs), are particularly hard to predict and detect. Moreover, drug-induced liver injury (DILI) is the most frequent reason drugs are withdrawn from the market and causes 50% of acute liver failure cases in the United States. A common mechanism often underlies many types of drug toxicities, including both DILI and IADRs. Drugs are bioactivated by drug-metabolizing enzymes into reactive metabolites, which then conjugate to sites in proteins or DNA to form adducts. DNA adducts are often mutagenic and may alter the reading and copying of genes and their regulatory elements, causing gene dysregulation and even triggering cancer. Similarly, protein adducts can disrupt their normal biological functions and induce harmful immune responses. Unfortunately, reactive metabolites are not reliably detected by experiments, and it is also expensive to test drug candidates for potential to form DNA or protein adducts during the early stages of drug development. In contrast, computational methods have the potential to quickly screen for covalent binding potential, thereby flagging problematic molecules and reducing the total number of necessary experiments. Here, we train a deep convolution neural network—the XenoSite reactivity model—using literature data to accurately predict both sites and probability of reactivity for molecules with glutathione, cyanide, protein, and DNA. On the site level, cross-validated predictions had area under the curve (AUC) performances of 89.8% for DNA and 94.4% for protein. Furthermore, the model separated molecules electrophilically reactive with DNA and protein from nonreactive molecules with cross-validated AUC performances of 78.7% and 79.8%, respectively. On both the site- and molecule-level, the model’s performances significantly outperformed reactivity indices derived from quantum simulations that are reported in the literature. Moreover, we developed and applied a selectivity score to assess preferential reactions with the macromolecules as opposed to the common screening traps. For the entire data set of 2803 molecules, this approach yielded totals of 257 (9.2%) and 227 (8.1%) molecules predicted to be reactive only with DNA and protein, respectively, and hence those that would be missed by standard reactivity screening experiments. Site of reactivity data is an underutilized resource that can be used to not only predict if molecules are reactive, but also show where they might be modified to reduce toxicity while retaining efficacy. The XenoSite reactivity model is available at http://swami.wustl.edu/xenosite/p/reactivity. PMID:27610414

First Zika-positive donations in the continental United States.

PubMed

Galel, Susan A; Williamson, Phillip C; Busch, Michael P; Stanek, Danielle; Bakkour, Sonia; Stone, Mars; Lu, Kai; Jones, Scott; Rossmann, Susan N; Pate, Lisa Lee

2017-03-01

Zika virus (ZIKV) has spread in the Americas, including parts of the southern United States, and infection can be associated with serious complications, including congenital brain abnormalities. Probable transfusion transmission of ZIKV has been documented in Brazil. Preemptive testing of blood donations for ZIKV RNA was implemented in southern US states at risk of local transmission using a test approved under a Food and Drug Administration (FDA) investigational new drug application, cobas Zika. Screening was expanded after issuance of an updated FDA guidance. Donations reactive on initial screening were further tested by nucleic acid and antibody tests to determine the donor status. Of 358,786 donations from US states screened by individual donation testing, 23 were initially reactive on cobas Zika. Fourteen of these represented probable ZIKV infection based on reactivity on additional nucleic acid testing or anti-Zika immunoglobulin M. Ten of the 14 donors reported travel to an identified ZIKV-active area within 90 days before donation (median time from end of travel to donation, 25 days; range, 6-71 days). Three donors with travel history also had a potential sexual exposure. Only seven of the 14 donations with probable ZIKV infection were detectable upon 1:6 dilution to simulate minipool testing. The estimated specificity of the cobas Zika test was 99.997%. Screening of donations for ZIKV RNA can interdict ZIKV-infected donors. Donor risk factors include travel more than 4 weeks before donation and sexual exposure. Minipool screening would have detected only 50% of the RNA-positive donations. © 2017 The Authors Transfusion published by Wiley Periodicals, Inc. on behalf of AABB.

Let the right one in: a microeconomic approach to partner choice in mutualisms.

PubMed

Archetti, Marco; Ubeda, Francisco; Fudenberg, Drew; Green, Jerry; Pierce, Naomi E; Yu, Douglas W

2011-01-01

One of the main problems impeding the evolution of cooperation is partner choice. When information is asymmetric (the quality of a potential partner is known only to himself), it may seem that partner choice is not possible without signaling. Many mutualisms, however, exist without signaling, and the mechanisms by which hosts might select the right partners are unclear. Here we propose a general mechanism of partner choice, "screening," that is similar to the economic theory of mechanism design. Imposing the appropriate costs and rewards may induce the informed individuals to screen themselves according to their types and therefore allow a noninformed individual to establish associations with the correct partners in the absence of signaling. Several types of biological symbioses are good candidates for screening, including bobtail squid, ant-plants, gut microbiomes, and many animal and plant species that produce reactive oxygen species. We describe a series of diagnostic tests for screening. Screening games can apply to the cases where by-products, partner fidelity feedback, or host sanctions do not apply, therefore explaining the evolution of mutualism in systems where it is impossible for potential symbionts to signal their cooperativeness beforehand and where the host does not punish symbiont misbehavior.

Combinatorially Screened Peptide as Targeted Covalent Binder: Alteration of Bait-Conjugated Peptide to Reactive Modifier.

PubMed

Uematsu, Shuta; Tabuchi, Yudai; Ito, Yuji; Taki, Masumi

2018-06-01

A peptide-type covalent binder for a target protein was obtained by combinatorial screening of fluoroprobe-conjugated peptide libraries on bacteriophage T7. The solvatochromic fluoroprobe works as a bait during the affinity selection process of phage display. To obtain the targeted covalent binder, the bait in the selected consensus peptide was altered into a reactive warhead possessing a sulfonyl fluoride. The reaction efficiency and site/position specificity of the covalent conjugation between the binder and the target protein were evaluated by liquid chromatography-tandem mass spectrometry (LC-MS/MS), and rationalized by a protein-ligand docking simulation.

QUALITATIVE MEASUREMENTS OF IGE AND IGG IN HUMAN ASTHMATIC SERUM FOR MOLD REACTIVITY

EPA Science Inventory

Rational: Molds have the ability to induce allergic asthma-like responses in mouse models; however, their role in human disease is unclear. This study was to develop a screening tool for reactivity of human sera to mold extracts by using a minimal amount of sera for a qual...

High-throughput identification of promiscuous inhibitors from screening libraries with the use of a thiol-containing fluorescent probe.

PubMed

McCallum, Megan M; Nandhikonda, Premchendar; Temmer, Jonathan J; Eyermann, Charles; Simeonov, Anton; Jadhav, Ajit; Yasgar, Adam; Maloney, David; Arnold, Alexander Leggy

2013-07-01

Testing small molecules for their ability to modify cysteine residues of proteins in the early stages of drug discovery is expected to accelerate our ability to develop more selective drugs with lesser side effects. In addition, this approach also enables the rapid evaluation of the mode of binding of new drug candidates with respect to thiol reactivity and metabolism by glutathione. Herein, we describe the development of a fluorescence-based high-throughput assay that allows the identification of thiol-reactive compounds. A thiol-containing fluorescent probe, MSTI, was synthesized and used to evaluate small molecules from the Library of Pharmacologically Active Compounds (LOPAC) collection of bioactive molecules. LOPAC compounds that are known to react with sulfur nucleophiles were identified with this assay, for example, irreversible protease inhibitors, nitric oxide-releasing compounds, and proton-pump inhibitors. The results confirm that both electrophilic and redox reactive compounds can be quickly identified in a high-throughput manner, enabling the assessment of screening libraries with respect to thiol-reactive compounds.

Influence of Parameters of a Reactive Interatomic Potential on the Properties of Saturated Hydrocarbons

DTIC Science & Technology

2017-01-01

Methodology 3 2.1 Modified Embedded-Atom Method Theory 3 2.1.1 Embedding Energy Function 3 2.1.2 Screening Factor 8 2.1.3 Modified Embedded-Atom...Simulation Methodology 2.1 Modified Embedded-Atom Method Theory In the EAM and MEAM formalisms1,2,5 the total energy of a system of atoms (Etot) is...An interatomic potential for saturated hydrocarbons using the modified embedded-atom method (MEAM), a semiempirical many-body potential based on

Quaternary and tertiary aldoxime antidotes for organophosphate exposure in a zebrafish model system

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

Schmidt, Hayden R.; Radić, Zoran; Taylor, Palmer

The zebrafish is rapidly becoming an important model system for screening of new therapeutics. Here we evaluated the zebrafish as a potential pharmacological model for screening novel oxime antidotes to organophosphate (OP)-inhibited acetylcholinesterase (AChE). The k{sub i} values determined for chlorpyrifos oxon (CPO) and dichlorvos (DDVP) showed that CPO was a more potent inhibitor of both human and zebrafish AChE, but overall zebrafish AChE was less sensitive to OP inhibition. In contrast, aldoxime antidotes, the quaternary ammonium 2-PAM and tertiary amine RS-194B, showed generally similar overall reactivation kinetics, k{sub r}, in both zebrafish and human AChE. However, differences between themore » K{sub ox} and k{sub 2} constants suggest that zebrafish AChE associates more tightly with oximes, but has a slower maximal reactivation rate than human AChE. Homology modeling suggests that these kinetic differences result from divergences in the amino acids lining the entrance to the active site gorge. Although 2-PAM had the more favorable in vitro reactivation kinetics, RS-194B was more effective antidote in vivo. In intact zebrafish embryos, antidotal treatment with RS-194B rescued embryos from OP toxicity, whereas 2-PAM had no effect. Dechorionation of the embryos prior to antidotal treatment allowed both 2-PAM and RS-194B to rescue zebrafish embryos from OP toxicity. Interestingly, RS-194B and 2-PAM alone increased cholinergic motor activity in dechorionated embryos possibly due to the reversible inhibition kinetics, K{sub i} and αK{sub i}, of the oximes. Together these results demonstrate that the zebrafish at various developmental stages provides an excellent model for investigating membrane penetrant antidotes to OP exposure. - Highlights: • Zebrafish AChE shares significant structural similarities with human AChE. • OP-inhibited zebrafish and human AChE exhibit similar reactivation kinetics. • The zebrafish chorion is permeable to BBB penetrant and not charged aldoximes. • Zebrafish are a good aquatic model for studying centrally acting antidotes.« less

Community-Based Study Recruitment of American Indian Cigarette Smokers and Electronic Cigarette Users.

PubMed

Carroll, Dana Mowls; Brame, Lacy S; Stephens, Lancer D; Wagener, Theodore L; Campbell, Janis E; Beebe, Laura A

2018-02-01

Data on the effectiveness of strategies for the recruitment of American Indians (AIs) into research is needed. This study describes and compares methods for identifying and recruiting AI tobacco users into a pilot study. Community-based strategies were used to recruit smokers (n = 35), e-cigarette users (n = 28), and dual users (n = 32) of AI descent. Recruitment was considered proactive if study staff contacted the individual at a pow wow, health fair, or vape shop and participation on-site or reactive if the individual contacted the study staff and participation occurred later. Screened, eligible, participated and costs and time spent were compared with Chi square tests. To understand AI descent, the relationship between number of AI grandparents and AI blood quantum was examined. Number of participants screened via the proactive strategy was similar to the reactive strategy (n = 84 vs. n = 82; p-value = 0.8766). A significantly greater proportion of individuals screened via the proactive than the reactive strategy were eligible (77 vs. 50%; p-value = 0.0002) and participated (75 vs. 39%; p-value = < 0.0001). Per participant cost and time estimated for the proactive strategy was $89 and 87 min compared to $79 and 56 min for the reactive strategy. Proportion at least half AI blood quantum was 32, 33, and 70% among those with 2, 3, and 4 AI grandparents, respectively (p = 0.0017). Proactive strategies resulted in two-thirds of the sample, but required more resources than reactive strategies. Overall, we found both strategies were feasible and resulted in the ability to reach sample goals. Lastly, number of AI biological grandparents may be a good, non-invasive indicator of AI blood quantum.

Recommendations for screening, monitoring, prevention, prophylaxis and therapy of hepatitis B virus reactivation in patients with haematologic malignancies and patients who underwent haematologic stem cell transplantation-a position paper.

PubMed

Sarmati, L; Andreoni, M; Antonelli, G; Arcese, W; Bruno, R; Coppola, N; Gaeta, G B; Galli, M; Girmenia, C; Mikulska, M; Pane, F; Perno, C F; Picardi, M; Puoti, M; Rambaldi, A; Svicher, V; Taliani, G; Gentile, G

2017-12-01

Hepatitis B virus (HBV) infection reactivation is associated with high morbidity and mortality in patients with haematologic malignancy and/or haematopoietic stem cell transplantation (HSCT). However, information on this issue is limited. The scope of this position paper is to provide recommendations on HBV screening, monitoring, prophylaxis, treatment and vaccination in the patients described above. These recommendations were developed from one meeting of experts attended by different Italian scientific societies as well as from a systematic literature review (of articles published through December 31, 2016) on HBV infection in haematologic patients and in patients who underwent haematopoietic stem cell transplantation published in the same issue of the journal. The Grading of Recommendations Assessment, Development and Evaluation (GRADE) methodology was used to assess each recommendation's quality. These recommendations provide the answers to the following questions: (a) HBV screening and monitoring: Who should be screened before chemotherapy? Which screening tests should be used? Should HBV-DNA detection be used to monitor HBV reactivation before starting antivirals? What is the best timeline to monitor HBV reactivation? (b) Prophylaxis in HBsAg-positive patients: Which antiviral drugs should be used to treat HBsAg-positive patients? How long should antiviral prophylaxis be provided to HBsAg-positive patients? (c) Prophylaxis in patients with resolved HBV infection: Which patients with resolved HBV infection should receive antiviral prophylaxis? Which antiviral drug should be used? How long should antiviral prophylaxis be provided? (d) HBV infection management strategy in autologous (auto-HSCT) and allogeneic HSCT (allo-HSCT): Which HSCT recipients should receive antiviral prophylaxis? Which antiviral drug should be used? How long should antiviral prophylaxis be provided? (e) Choice of antiviral drugs in the treatment of HBV reactivation: Should third-generation anti-HBV drugs be preferred to first- or second-generation antiviral drugs in the treatment of HBV reactivation with or without hepatitis flare in haematologic patients? (f) Immunization against HBV in patients with haematologic malignancies and/or patients who underwent HSCT: Should these patients be vaccinated? Which HBV vaccination schedule should be adopted? Haematologic patients should be screened for hepatitis B surface antigen (HBsAg) plus anti-hepatitis B core protein (HBc), and HBV DNA before chemotherapy. HBV DNA levels should be monitored monthly in all HBV-positive patients who do not receive prophylaxis. HBsAg-positive haematologic patients and those undergoing HSCT should receive third-generation antiviral therapy as prophylaxis. Anti-HBc-positive lymphoma patients and those receiving HSCT should receive antiviral prophylaxis. All HBV-negative haematologic patients should be vaccinated for HBV. The acquisition of data from well-designed studies is desirable in the near future. Copyright © 2017 European Society of Clinical Microbiology and Infectious Diseases. Published by Elsevier Ltd. All rights reserved.

Tuberculin reactivity in bacille Calmette-Guérin vaccinated populations: a compilation of international data.

PubMed

Joos, T J; Miller, W C; Murdoch, D M

2006-08-01

The effect of previously administered bacille Calmette-Guérin (BCG) vaccine on subsequent tuberculin skin tests (TSTs) complicates screening for latent tuberculosis infection (LTBI) in foreign-born persons. To determine the usefulness of the TST as a screening test for LTBI in foreign-born persons. A literature search was performed of published studies that compared tuberculin reactivity amongst BCG-vaccinated and non-vaccinated groups. The percentages of positive reactors in the two groups were then used to calculate a prevalence ratio. The prevalence ratio varied with the age of the groups tested and the incidence of TB in their countries of origin. The TST performed poorly in vaccinated persons of all ages from countries of low TB incidence, but was a useful screen for LTBI in vaccinated adults from countries of high and intermediate incidence. The test performed poorly as a screening method for vaccinated children under 2 years of age. Its usefulness in vaccinated children aged 2-14 years varied considerably. The usefulness of the TST as a screening method for LTBI depends on the age of the patient and the incidence of TB in their country of origin.

Desomorphine Screening Using Commercial Enzyme-Linked Immunosorbent Assays.

PubMed

Winborn, Jessica; Kerrigan, Sarah

2017-06-01

Desomorphine ("Krokodil") is a semi-synthetic opioid that has drawn attention as a recreational drug, particularly in Russia, neighboring former Soviet Republics, Eastern and Central Europe. It has no accepted medicinal uses and is currently a schedule I drug in the United States. In clandestine environments, desomorphine is synthesized from codeine using red phosphorous, hydroiodic acid and gasoline. Residual starting materials in illicit preparations have been associated with severe dermatological effects and extensive tissue necrosis. Desomorphine is not well studied, and there are limited reports concerning its pharmacology or detection in biological matrices. Immunoassays are widely relied upon for both antemortem and postmortem toxicology screening. Although desomorphine is an opioid of the phenanthrene-type, its ability to bind to conventional opioid antibodies has not been described. In this report we describe the cross-reactivity of desomorphine using six commercially available enzyme-linked immunosorbent assays (Immunalysis Opiates Direct ELISA, Immunalysis Oxycodone/Oxymorphone Direct ELISA, Randox Opiate ELISA, OraSure Technologies OTI Opiate Micro-plate EIA, Neogen Opiate Group ELISA and Neogen Oxycodone/Oxymorphone ELISA). Cross-reactivites were highly variable between assays, ranging from 77 to <2.5%. In general, assays directed towards morphine produced greater cross-reactivity with desomorphine than those directed towards oxycodone. The Immunalysis Opiates Direct ELISA produced the greatest cross-reactivity, although several of the assays evaluated produced cross-reactivity of a sufficient magnitude to be effective for desomorphine screening. © The Author 2017. Published by Oxford University Press. All rights reserved. For Permissions, please email: journals.permissions@oup.com.

Enhancing HIV Testing and Treatment among Men Who Have Sex with Men in China: A Pilot Model with Two-Rapid Tests, Single Blood Draw Session, and Intensified Case Management in Six Cities in 2013.

PubMed

Zhang, Dapeng; Lu, Hongyan; Zhuang, Minghua; Wu, Guohui; Yan, Hongjing; Xu, Jun; Wei, Xiaoli; Li, Chengmei; Meng, Sining; Fu, Xiaojing; Qi, Jinlei; Wang, Peng; Luo, Mei; Dai, Min; Yip, Ray; Sun, Jiangping; Wu, Zunyou

2016-01-01

To explore models to improve HIV testing, linkage to care and treatment among men who have sex with men (MSM) in cooperation with community-based organizations (CBOs) in China. We introduced a new model for HIV testing services targeting MSM in six cities in 2013.These models introduced provision of rapid HIV testing by CBO staff and streamlined processes for HIV screening, confirmation of initial reactive screening results, and linkage to care among diagnosed people. We monitored attrition along each step of the continuum of care from screening to treatment and compared program performance between 2012 and 2013. According to the providers of two rapid tests (HIV screening), four different services delivery models were examined in 2013: Model A = first screen at CDC, second at CDC (Model A = CDC+CDC), Model B = first and second screens at CBOs (Model B = CBO+CBO), Model C = first screen at CBO, second at Hospital (Model C = CBO+Hosp), and Model D = first screen at CBO, second at CDC (Model D = CBO+CDC). Logistic regressions were performed to assess advantages of different screening models of case finding and case management. Compared to 2012, the number of HIV screening tests performed for MSM increased 35.8% in 2013 (72,577 in 2013 vs. 53,455 in 2012). We observed a 5.6% increase in proportion of cases screened reactive receiving HIV confirmatory tests (93.9% in 2013 vs. 89.2% in 2012, χ2 = 48.52, p<0.001) and 65% reduction in loss to CD4 cell count tests (15% in 2013 vs. 43% in 2012, χ2 = 628.85, p<0.001). Regarding linkage to care and treatment, the 2013 pilot showed that the Model D had the highest rate of loss between screening reactive and confirmatory test among the four models, with 18.1% fewer receiving a second screening test and a further 5.9% loss among those receiving HIV confirmatory tests. The Model B and the Model C showed lower losses (0.8% and 1.3%) for newly diagnosed HIV positives receiving CD4 cell count tests, and higher rates of HIV positives referred to designated ART hospitals (88.0% and 93.3%) than the Model A and Model D (4.6% and 5.7% for CD4 cell count test, and 68.9% and 64.4% for referring to designated ART hospitals). The proportion of cases where the screening test was reactive that were commenced on ART was highest in Model C; 52.8% of cases commenced on ART compared to 38.9%, 34.2% and 21.1% in Models A, B and D respectively. Using Model A as a reference group, the multivariate logistic regression results also showed the advantages of Models B, C and D, which increased CD4 cell count test, referral to designated ART hospitals and initiation of ART, when controlling for program city and other factors. This study has demonstrated that involvement of CBOs in HIV rapid testing provision, streamlining testing and care procedures and early hospital case management can improve testing, linkage to, and retention in care and treatment among MSM in China.

A Patient with Grave's Disease and Tuberculous Lymphadenitis.

PubMed

Rahaman, M F; Chowdhury, M H; Khan, A H; Rahman, M; Barman, T K; Chowdhury, M J

2016-04-01

Immune reactivity between Mycobacteria and human antigens can play an important role in the pathogenesis of autoimmune disease. We report a case of Graves's disease and tuberculous lymphadenitis to explain the mechanism of correlation between immune-mediated diseases and tuberculosis and to raise awareness of the importance of screening for TB in this context, especially in endemic country. Screening for latent TB at immune mediated disease diagnosis and regular timely screening thereafter may be beneficial.

Synthesis and in-vitro reactivation screening of imidazolium aldoximes as reactivators of sarin and VX-inhibited human acetylcholinesterase (hAChE).

PubMed

Sharma, Rahul; Gupta, Bhanushree; Sahu, Arvind Kumar; Acharya, Jyotiranjan; Satnami, Manmohan L; Ghosh, Kallol K

2016-11-25

Post-treatment of organophosphate (OP) poisoning involves the application of oxime reactivator as an antidote. Structurally different oximes are widely studied to examine their kinetic and mechanistic behavior against OP-inhibited cholinesterase enzyme. A series of structurally related 1,3-disubstituted-2-[(hydroxyiminomethyl)alkyl]imidazolium halides (5a-5e, 9a-9c) were synthesized and further evaluated for their in-vitro reactivation ability to reactivate sarin- and VX-inhibited human acetylcholinesterase (hAChE). The observed results were compared with the reactivation efficacy of standard reactivators; 2-PAM, obidoxime and HI-6. Amongst the synthesized oximes, 5a, 9a and 9b were found to be most potent reactivators against sarin-inhibited hAChE while in case of VX only 9a exhibited comparable reactivity with 2-PAM. Incorporation of pyridinium ring to the imidazole ring resulted in substantial increase in the reactivation strength of prepared reactivator. Physicochemical properties of synthesized reactivators have also been evaluated. Copyright © 2016. Published by Elsevier Ireland Ltd.

Affective reactivity to cry sounds predicts young women's reactivity and behavior in a simulated caregiving task.

PubMed

Gustafson, Gwen E; Bisson, Jennifer B; MacDonald, Jillian M; Green, James A

2017-09-13

Different populations of adults (experienced vs. inexperienced caregivers, men vs. women, abusive vs. nonabusive parents, etc.) have been reported to differ in their affective reactions to the sounds of infant crying. These differences are thought to impact caregiving behavior and, in some instances, to affect long-term outcomes for infants. There can be great intra-group variation, however, even when group differences are significant; modeling developmental process will require a finer grained approach. We have undertaken a pair of studies intended to validate the Negative Affect Scale (NA) from the PANAS as a measure of individuals' affective reactivity to cry sounds. In Study 1, 306 young women who were not yet mothers listened either to infant crying or to birdsong. The results supported the NA as a measure of reactivity to crying. In Study 2, a new sample of 301 young women listened to crying in a screening task; a group of "high reactors" (n=21) and a group of "low reactors" (n=22) then participated in a simulated caregiving situation. Individuals' affective reactivity to the caregiving simulation mirrored their affective reactivity in the screening task, and rates and overall organization of caregiving behavior differed between the groups. Changes in negative affect, then, appear to be both a result of infant crying and a determinant of some aspects of caregiving behavior. Further studies will extend these laboratory results to real infants and their caregivers, and further validate the NA as a measure of individual differences in reactivity to cry sounds. Copyright © 2017 Elsevier Inc. All rights reserved.

The early implementation of Trypanosoma cruzi antibody screening of donors and donations within England: preempting a problem.

PubMed

Kitchen, Alan D; Hewitt, Patricia E; Chiodini, Peter L

2012-09-01

Trypanosoma cruzi is a parasitic infection endemic in Central and Southern America, but is spreading into nonendemic countries with migration of infected individuals from endemic countries. The parasite is transmitted by transfusion or transplantation and donation screening is performed routinely in endemic countries to prevent transmission. In situations where migrants from endemic countries have settled in nonendemic countries and present as donors (blood or other cellular products), intervention is required to prevent transfusion or transplantation transmission. A screening program for T. cruzi was developed and has been used successfully for over 10 years that includes donor selection and donation screening. Donor selection criteria to identify specific risk of T. cruzi infection were developed together with laboratory screening of donations for T. cruzi antibodies and the subsequent confirmation of screen reactivity. Since the introduction of T. cruzi screening in England in 1998, a total of 38,585 donors and donations have been screened for T. cruzi antibodies, of which 223 were repeat reactive on screening and referred for confirmation: 206 confirmed negative, 14 inconclusive, and three positive. Since the move in 2005 from donor qualification to donation release testing, 15,536 donations were collected and screened, of which 15,499 (99.8%) were T. cruzi antibody negative and released to inventory. An effective program to minimize risk of the transmission of T. cruzi infection via donations has been developed and implemented. Not only does the program minimize risk of transmission, it also minimizes the cumulative, and needless, loss of donors and donations that would ensue if permanent donor deferral alone was adopted. © 2012 American Association of Blood Banks.

Performance of the Alere Determine™ HIV-1/2 Ag/Ab Combo Rapid Test with algorithm-defined acute HIV-1 infection specimens.

PubMed

Parker, Monica M; Bennett, S Berry; Sullivan, Timothy J; Fordan, Sally; Wesolowski, Laura G; Wroblewski, Kelly; Gaynor, Anne M

2018-05-14

The capacity of HIV Antigen/Antibody (Ag/Ab) immunoassays (IA) to detect HIV-1 p24 antigen has resulted in improved detection of HIV-1 infections in comparison to Ab-only screening assays. Since its introduction in the US, studies have shown that the Determine HIV-1/2 Ag/Ab Combo assay (Determine Ag/Ab) detects HIV infection earlier than laboratory-based IgM/IgG-sensitive IAs, but its sensitivity for HIV-1 p24 Ag detection is reduced compared to laboratory-based Ag/Ab assays. However, further evaluation is needed to assess its capacity to detect acute HIV-1 infection. To assess the performance of Determine Ag/Ab in serum from acute HIV-1 infections. Select serum specimens that screened reactive on a laboratory-based Ag/Ab IA or IgM/IgG Ab-only IA, with a negative or indeterminate supplemental antibody test and detectable HIV-1 RNA were retrospectively tested with Determine Ag/Ab. Results were compared with those of the primary screening immunoassay to evaluate concordance within this set of algorithm-defined acute infections. Of 159 algorithm-defined acute HIV-1 specimens, Determine Ag/Ab was reactive for 105 resulting in 66.0% concordance. Of 125 that were initially detected by a laboratory-based Ag/Ab IA, 81 (64.8%) were reactive by Determine Ag/Ab. A total of 34 acute specimens were initially detected by a laboratory-based IgM/IgG Ab-only IA and 24 (70.6%) of those were reactive by Determine Ag/Ab. Due to their enhanced sensitivity, laboratory-based Ag/Ab IAs continue to be preferred over the Determine Ag/Ab as the screening method used by laboratories conducting HIV diagnostic testing on serum and plasma specimens. Copyright © 2018 The Authors. Published by Elsevier B.V. All rights reserved.

Hepatitis B virus DNA-positive, hepatitis B surface antigen-negative blood donations intercepted by anti-hepatitis B core antigen testing: the Canadian Blood Services experience.

PubMed

O'Brien, Sheila F; Fearon, Margaret A; Yi, Qi-Long; Fan, Wenli; Scalia, Vito; Muntz, Irene R; Vamvakas, Eleftherios C

2007-10-01

The benefit of introducing anti-hepatitis B core antigen (HBc) screening for intercepting potentially infectious donations missed by hepatitis B surface antigen (HBsAg) screening in Canada was studied. Anti-HBc testing of all donations was implemented in April 2005, along with antibody to hepatitis B surface antigen (anti-HBs) and hepatitis B virus (HBV) DNA supplemental testing of anti-HBc repeat-reactive, HBsAg-negative donations. The proportion of potentially infectious donations intercepted by anti-HBc over the initial 18 months of testing was calculated based on three assumptions relating infectivity of HBV DNA-positive units to anti-HBs levels. Lookback was conducted for all DNA-positive donations. Of 493,344 donors, 5,585 (1.13%) were repeat-reactive for the presence of anti-HBc, with 29 (0.52%) being HBV DNA-positive and HBsAg-negative. The proportion of potentially infectious donations intercepted by anti-HBc screening was 1 in 17,800 if all HBV DNA-positive donations were infectious, 1 in 26,900 if infectivity was limited to donations with an anti-HBs level of not more than 100 mIU per mL, and 1 in 69,300 if only donations with undetectable anti-HBs were infectious. For 279 components in the lookback study, no traced recipients were HBsAg-positive and 7 recipients were anti-HBc-reactive in association with 4 donors, 3 of whom had an anti-HBs level of more than 100 mIU per mL and 1 of whom had a level of 61 mIU per mL. Implementation of anti-HBc screening reduced the risk of transfusing potentially infectious units by at least as much as had been expected based on the literature. The lookback did not provide proof of transfusion transmission of HBV from HBV DNA-positive, anti-HBc-reactive, HBsAg-negative donors but it did not establish lack of transmission either.

Hepatitis B Virus Reactivation in the Setting of Cancer Chemotherapy and Other Immunosuppressive Drug Therapy

PubMed Central

Gonzalez, Stevan A.; Perrillo, Robert P.

2016-01-01

Hepatitis B virus reactivation (HBVr) is an important complication of immunosuppressive drug therapy (ISDT). It can occur with active or resolved hepatitis B virus (HBV) infection with a clinical spectrum that ranges from mild elevations in liver tests to fulminant hepatic failure. The risk of it occurring is determined by the interplay between HBV serological status, level of viremia, and the immunosuppressive potency of the drug(s) used. Reactivation is most common during treatment of hematologic malignancies but also occurs with chemotherapy for breast cancer and numerous other solid organ malignancies, organ transplant, and immune suppression for nonmalignant conditions. The expansion of new biologic treatments for malignant and nonmalignant disorders has enlarged the population at risk. Increased awareness of HBVr among healthcare providers who prescribe ISDT, adoption of routine HBV screening, and linking the results of screening to antiviral prophylaxis are needed to reduce the incidence of this potentially fatal but preventable disorder. PMID:27190320

The Use of Response to Intervention Practices for Behavior: An Examination of the Validity of a Screening Instrument

ERIC Educational Resources Information Center

Muyskens, Paul; Marston, Doug; Reschly, Amy L.

2007-01-01

Behavioral difficulties of school-aged students are typically dealt with in a reactive, rather than preventative manner. This article examines a proactive approach, consistent with the Response-to-Intervention model, using a screening measure designed to identify students at risk for behavior difficulties and targeting these students for early…

C-reactive protein as a screening test for HIV-associated pulmonary tuberculosis prior to antiretroviral therapy in South Africa.

PubMed

Shapiro, Adrienne E; Hong, Ting; Govere, Sabina; Thulare, Hilary; Moosa, Mahomed-Yunus; Dorasamy, Afton; Wallis, Carole L; Celum, Connie L; Grosset, Jacques; Drain, Paul K

2018-05-28

There is an urgent need for more accurate screening tests for tuberculosis(TB). We assessed the diagnostic accuracy of C-reactive protein (CRP) as a screening test for active TB in HIV-infected ambulatory adults. CRP levels were measured in blood collected at the time of HIV testing.Diagnostic accuracy of CRP for pulmonary TB was calculated (reference standard: TB culture), compared to the WHO 4-symptom screen, consisting of cough, fever, night sweats, and weight loss. Diagnostic accuracy was also calculated for CRP in a larger cohort of HIV-infected adults with a positive symptom screen (reference standard: clinical or microbiological TB). Among 425 HIV-infected outpatients systematically tested for pulmonary TB, TB culture was positive in 42 (10%), 279 (66%) had at least one TB-related symptom and 197 (46%) had a CRP >5 mg/L. The sensitivity of CRP and the TB symptom screen to detect TB was the same (90.5%; 95%CI 77.4-97.3) but specificity of CRP was higher than for the TB symptom screen (58.5% vs. 37.1%, p<0.001). Of persons with no symptoms and normal CRP, 99 (98%) had no TB. In another cohort of 749 patients presenting with at least one TB-related symptom and clinically evaluated, CRP had a sensitivity of 98.7% and specificity of 48.3%. In HIV-infected outpatients, CRP was as sensitive but substantially more specific than TB symptom screening. Use of CRP as a screening tool to exclude active TB could identify the same number of HIV-associated TB cases, but reduce the use of diagnostic sputum testing in TB-endemic regions.

Interference of daratumumab with pretransfusion testing, mimicking a high-titer, low avidity like antibody.

PubMed

Lin, Mei-Hwa; Liu, Fei-Yun; Wang, Hsiu-Mien; Cho, Hsin-Ching; Lo, Shyh-Chyi

2017-01-01

Daratumumab is a monoclonal immunoglobulin against CD38 and has been approved for treating patients with refractory multiple myeloma. The presence of daratumumab in the sera can interfere with pretransfusion testing due to the weakly expression of CD38 on red cells. The reactivity could be mistaken as autoantibody (if autocontrol is positive) or alloantibody (if autocontrol is negative). We present a case that demonstrates daratumumab could mimic a high titer low avidity (HTLA) alloantibody. A 34-year-old male patient of refractory myeloma was recruited in phase three clinical trial involving daratumumab. Samples were sent to the blood bank for pretransfusion testing. Without knowledge of patient having used daratumumab, we mistook the reactivity in the patient's sera as an HTLA antibody due to the results of negative autocontrol and high titers of antibody activity. Antibody screen showed a panreactive pattern and the reactivity against screening cells was up to a titer of 1: 1240. The reactivity was weaker against cord cells than adult cells, became weaker against ZZAP-treated cells and became negative against DDT-treated cells. A discussion with attending physician finally revealed the reactivity was due to the interference caused by daratumumab. The case demonstrates good communication is essential in performing pretransfusion testing for patients receiving daratumumab and other new biological regimens that can interfere with compatibility test.

Interference of daratumumab with pretransfusion testing, mimicking a high-titer, low avidity like antibody

PubMed Central

Lin, Mei-Hwa; Liu, Fei-Yun; Wang, Hsiu-Mien; Cho, Hsin-Ching; Lo, Shyh-Chyi

2017-01-01

Daratumumab is a monoclonal immunoglobulin against CD38 and has been approved for treating patients with refractory multiple myeloma. The presence of daratumumab in the sera can interfere with pretransfusion testing due to the weakly expression of CD38 on red cells. The reactivity could be mistaken as autoantibody (if autocontrol is positive) or alloantibody (if autocontrol is negative). We present a case that demonstrates daratumumab could mimic a high titer low avidity (HTLA) alloantibody. A 34-year-old male patient of refractory myeloma was recruited in phase three clinical trial involving daratumumab. Samples were sent to the blood bank for pretransfusion testing. Without knowledge of patient having used daratumumab, we mistook the reactivity in the patient's sera as an HTLA antibody due to the results of negative autocontrol and high titers of antibody activity. Antibody screen showed a panreactive pattern and the reactivity against screening cells was up to a titer of 1: 1240. The reactivity was weaker against cord cells than adult cells, became weaker against ZZAP-treated cells and became negative against DDT-treated cells. A discussion with attending physician finally revealed the reactivity was due to the interference caused by daratumumab. The case demonstrates good communication is essential in performing pretransfusion testing for patients receiving daratumumab and other new biological regimens that can interfere with compatibility test. PMID:28970695

Procalcitonin as a diagnostic test for sepsis in critically ill adults and after surgery or trauma: a systematic review and meta-analysis.

PubMed

Uzzan, Bernard; Cohen, Régis; Nicolas, Patrick; Cucherat, Michel; Perret, Gérard-Yves

2006-07-01

To quantify the accuracy of serum procalcitonin as a diagnostic test for sepsis, severe sepsis, or septic shock in adults in intensive care units or after surgery or trauma, alone and compared with C-reactive protein. To draw and compare the summary receiver operating characteristics curves for procalcitonin and C-reactive protein from the literature. MEDLINE (keywords: procalcitonin, intensive care, sepsis, postoperative sepsis, trauma); screening of the literature. Meta-analysis of all 49 published studies in medical, surgical, or polyvalent intensive care units or postoperative wards. Children, medical patients, and immunocompromised patients were excluded. Thirty-three studies fulfilled inclusion criteria (3,943 patients, 1,828 males, 922 females; mean age: 56.1 yrs; 1,825 patients with sepsis, severe sepsis, or septic shock; 1,545 with only systemic inflammatory response syndrome); eight studies could not be analyzed statistically. Global mortality rate was 29.3%. Global odds ratios for diagnosis of infection complicated by systemic inflammation were 15.7 for the 25 studies (2,966 patients) using procalcitonin (95% confidence interval, 9.1-27.1) and 5.4 for the 15 studies (1,322 patients) using C-reactive protein (95% confidence interval, 3.2-9.2). The summary receiver operating characteristics curve for procalcitonin was better than for C-reactive protein. In the 15 studies using both markers, the Q* value (intersection of summary receiver operating characteristics curve with the diagonal line where sensitivity equals specificity) was significantly higher for procalcitonin than for C-reactive protein (0.78 vs. 0.71, p = .02), the former test showing better accuracy. Procalcitonin represents a good biological diagnostic marker for sepsis, severe sepsis, or septic shock, difficult diagnoses in critically ill patients. Procalcitonin is superior to C-reactive protein. Procalcitonin should be included in diagnostic guidelines for sepsis and in clinical practice in intensive care units.

Screening of medicinal plant phytochemicals as natural antagonists of p53-MDM2 interaction to reactivate p53 functioning.

PubMed

Riaz, Muhammad; Ashfaq, Usman A; Qasim, Muhammad; Yasmeen, Erum; Ul Qamar, Muhammad T; Anwar, Farooq

2017-10-01

In most types of cancer, overexpression of murine double minute 2 (MDM2) often leads to inactivation of p53. The crystal structure of MDM2, with a 109-residue amino-terminal domain, reveals that MDM2 has a core hydrophobic region to which p53 binds as an amphipathic α helix. The interface depends on the steric complementarity between MDM2 and the hydrophobic region of p53. Especially, on p53's triad, amino acids Phe19, Trp23 and Leu26 bind to the MDM2 core. Results from studies suggest that the structural motif of both p53 and MDM2 can be attributed to similarities in the amphipathic α helix. Thus, in the current investigation it is hypothesized that the similarity in the structural motif might be the cause of p53 inactivation by MDM2. Hence, molecular docking and phytochemical screening approaches are appraised to inhibit the hydrophobic cleft of MDM2 and to stop p53-MDM2 interaction, resulting in reactivation of p53 activity. For this purpose, a library of 2295 phytochemicals were screened against p53-MDM2 to find potential candidates. Of these, four phytochemicals including epigallocatechin gallate, alvaradoin M, alvaradoin E and nordihydroguaiaretic acid were found to be potential inhibitors of p53-MDM2 interaction. The screened phytochemicals, derived from natural extracts, may have negligible side effects and can be explored as potent antagonists of p53-MDM2 interactions, resulting in reactivation of the normal transcription of p53.

Significance of isolated reactive treponemal chemiluminescence immunoassay results.

PubMed

Hunter, Michael G; Robertson, Peter W; Post, Jeffrey J

2013-05-01

Isolated reactive serum treponemal chemiluminescence immunoassay (CIA) specimens cause clinical uncertainty. Sera were screened by CIA, and reactive samples underwent reflex testing with rapid plasma reagin (RPR), Treponema pallidum particle agglutination (TPPA), and fluorescent treponemal antibody absorption (FTA Abs) assays. Samples reactive only on the CIA were deemed "isolated" reactive CIA samples. We undertook detailed review of a subset of subjects with isolated reactive CIA specimens. Of 28 261 specimens, 1171 (4.1%) were reactive on CIA, of which 133 (11.3%) had isolated CIA reactivity. Most subjects (66 of 82 [80.5%]) with isolated reactive CIA specimens were from high-prevalence populations. We found evidence of CIA, TPPA, and FTA Abs seroreversion. The median chemiluminescent signal-to-cutoff ratio was similar for isolated reactive CIA sera and sera that were reactive on either FTA Abs or TPPA assays (2.19 vs 2.32; P = .15) but lower than for sera reactive on both FTA Abs and TPPA assays (12.37; P < .001) or for sera reactive on RPR assays (25.53; P < .001). A total of 11 of 20 patients (55%) with an isolated reactive CIA specimen who underwent medical record review had previous or subsequent evidence of syphilis infection. Isolated reactive CIA specimens may represent true T. pallidum infection and may be found after seroreversion of traditional treponemal assays.

Subjective and physiological reactivity to chocolate images in high and low chocolate cravers.

PubMed

Rodríguez, Sonia; Fernández, María Carmen; Cepeda-Benito, Antonio; Vila, Jaime

2005-09-01

Cue-reactivity to chocolate images was assessed using self-report and physiological measures. From a pre-screening sample of 454, young women were selected and assigned to high and low chocolate craving groups (N = 36/group). The experimental procedure consisted in the elicitation and measurement of the cardiac defense and startle reflexes while viewing chocolate and standard affective images selected from the International Affective Picture System. In response to chocolate images, high cravers reported more pleasure and arousal but less control than low cravers. In high cravers, viewing chocolate images inhibited the cardiac defense but potentiated the startle reflex, as compared to low cravers. The results confirmed at the physiological level that the motivational state that underlies the experience of chocolate craving include both appetitive (inhibition of the defense reflex) and aversive (potentiation of the startle response) components. The findings supported a motivational conflict theory of chocolate craving.

Occult HBV reactivation induced by ibrutinib treatment: a case report.

PubMed

de Jésus Ngoma, Patrick; Kabamba, Benoît; Dahlqvist, Geraldine; Sempoux, Christine; Lanthier, Nicolas; Shindano, Tony; Van Den Neste, Eric; Horsmans, Yves

2015-12-01

Ibrutinib is a small molecule that has been recently developped for the treatment of B cell malignancies. Common side effects are diarrhoea, nausea, fatigue, infections, neutropenia and thrombocytopenia. Here we report the first case of Hepatitis B virus reactivation in a 80 years old chronic lymphocytic leukaemia patient receiving ibrutinib, suggesting that such treatment must be associated with HBV screening. © Acta Gastro-Enterologica Belgica.

[Design and evaluation of DAVIH VIH-2].

PubMed

Martín Alfonso, Dayamí; Silva Cabrera, Eladio; Pérez Guevara, María T; Díaz Herrera, Dervel F; Romero Martínez, Kenia; Díaz Torres, Héctor M; Lubián Caballero, Ana L; Ruiz Gutiérrez, Nancy; Ortiz Losada, Eva

2007-01-01

The results of the design and evaluation of DAVIH VIH-2 diagnosing system, an indirect Elisa for screening of HIV-2 antibodies, which uses a HIV-2 glycoprotein gp36 synthetic peptide in its solid phase, were exposed. In the system evaluation using WHO reference panels, 100% sensitivity, 99,81% specificity, 99,81% efficacy and very good concordance level (kappa = 0.978) were attained. Serum samples of 959 individuals with undetermined or negative results to the HIV-1 antibodies confirmation (DAVIH blot) were evaluated by the DAVIH VIH-2 system. Twenty four samples were reactive, six of which had confirmed HIV-2 antibodies. These results allowed recommending the introduction of this diagnostic kit in the HIV infection diagnosing algorithm in Cuba.

A First Application of Enzyme-Linked Immunosorbent Assay for Screening Cyclodiene Insecticides in Ground Water

USGS Publications Warehouse

Dombrowski, T.R.; Thurman, E.M.; Mohrman, G.B.

1996-01-01

A commercially available enzyme-linked immunosorbent assay (ELISA) plate kit for screening of cyclodiene insecticides (aldrin, chlordane, dieldrin, endosulfan, endrin, and heptachlor) was evaluated for sensitivity, cross reactivity, and overall performance using groundwater samples from a contaminated site. Ground-water contaminants included several pesticide compounds and their manufacturing byproducts, as well as many other organic and inorganic compounds. Cross-reactivity studies were carried out for the cyclodiene compounds, and results were compared to those listed by the manufacturer. Data obtained were used to evaluate the sensitivity of the ELISA kit to the cyclodiene compounds in ground water samples with a contaminated matrix. The method quantitation limit for the ELISA kit was 15 ??g/L (as chlordane). Of the 56 ground-water samples analyzed using the ELISA plate kits, more than 85% showed cyclodiene insecticide contamination. The ELISA kit showed excellent potential as a screening tool for sites with suspected groundwater contamination by insecticides.

Pre-Transplant Screening for Latent Adenovirus in Donors and Recipients

PubMed Central

Piatti, Gabriella

2016-01-01

Human adenoviruses are frequent cause of slight self-limiting infections in immune competent subjects, while causing life-threatening and disseminated diseases in immunocompromised patients, particularly in the subjects affected by acquired immunodeficiency syndrome and in bone marrow and organ transplant recipients. Here, infections interest lungs, liver, encephalon, heart, kidney and gastro enteric tract. To date, human adenoviruses comprise 51 serotypes grouped into seven species, among which species C especially possesses the capability to persist in infected tissues. From numerous works, it emerges that in the recipient, because of loss of immune-competence, both primary infection, via the graft or from the environment, and reactivated endogenous viruses can be responsible for transplantation related adenovirus disease. The transplants management should include the evaluation of anti-adenovirus pre-transplant screening similar to that concerning cytomegalovirus. The serological screening on cytomegalovirus immunity is currently performed to prevent viral reactivation from grafts and recipient, the viral spread and dissemination to different organs and apparatus, and potentially lethal outcome. PMID:27006724

Voice and gesture-based 3D multimedia presentation tool

NASA Astrophysics Data System (ADS)

Fukutake, Hiromichi; Akazawa, Yoshiaki; Okada, Yoshihiro

2007-09-01

This paper proposes a 3D multimedia presentation tool that allows the user to manipulate intuitively only through the voice input and the gesture input without using a standard keyboard or a mouse device. The authors developed this system as a presentation tool to be used in a presentation room equipped a large screen like an exhibition room in a museum because, in such a presentation environment, it is better to use voice commands and the gesture pointing input rather than using a keyboard or a mouse device. This system was developed using IntelligentBox, which is a component-based 3D graphics software development system. IntelligentBox has already provided various types of 3D visible, reactive functional components called boxes, e.g., a voice input component and various multimedia handling components. IntelligentBox also provides a dynamic data linkage mechanism called slot-connection that allows the user to develop 3D graphics applications by combining already existing boxes through direct manipulations on a computer screen. Using IntelligentBox, the 3D multimedia presentation tool proposed in this paper was also developed as combined components only through direct manipulations on a computer screen. The authors have already proposed a 3D multimedia presentation tool using a stage metaphor and its voice input interface. This time, we extended the system to make it accept the user gesture input besides voice commands. This paper explains details of the proposed 3D multimedia presentation tool and especially describes its component-based voice and gesture input interfaces.

Using pretest data to screen low-reactivity individuals in the autonomic-based concealed information test.

PubMed

Matsuda, Izumi; Ogawa, Tokihiro; Tsuneoka, Michiko; Verschuere, Bruno

2015-03-01

The concealed information test (CIT) can be used to assess whether an individual possesses crime-related information. However, its discrimination performance has room for improvement. We examined whether screening out participants who do not respond distinctively on a pretest improves the diagnosticity of a mock-crime CIT. Before conducting the CIT, we gave a pretest to 152 participants, 80 of whom were assigned as guilty. Pretest screening significantly improved the diagnostic value of the mock-crime CIT; however, it also led to a substantial number of undiagnosed participants (33.6%). Pretest screening holds promise, but its application would benefit from dedicated measures for screening out participants. © 2014 Society for Psychophysiological Research.

Global Profiling of Reactive Oxygen and Nitrogen Species in Biological Systems

PubMed Central

Zielonka, Jacek; Zielonka, Monika; Sikora, Adam; Adamus, Jan; Joseph, Joy; Hardy, Micael; Ouari, Olivier; Dranka, Brian P.; Kalyanaraman, Balaraman

2012-01-01

Herein we describe a high-throughput fluorescence and HPLC-based methodology for global profiling of reactive oxygen and nitrogen species (ROS/RNS) in biological systems. The combined use of HPLC and fluorescence detection is key to successful implementation and validation of this methodology. Included here are methods to specifically detect and quantitate the products formed from interaction between the ROS/RNS species and the fluorogenic probes, as follows: superoxide using hydroethidine, peroxynitrite using boronate-based probes, nitric oxide-derived nitrosating species with 4,5-diaminofluorescein, and hydrogen peroxide and other oxidants using 10-acetyl-3,7-dihydroxyphenoxazine (Amplex® Red) with and without horseradish peroxidase, respectively. In this study, we demonstrate real-time monitoring of ROS/RNS in activated macrophages using high-throughput fluorescence and HPLC methods. This global profiling approach, simultaneous detection of multiple ROS/RNS products of fluorescent probes, developed in this study will be useful in unraveling the complex role of ROS/RNS in redox regulation, cell signaling, and cellular oxidative processes and in high-throughput screening of anti-inflammatory antioxidants. PMID:22139901

Modeling Biodegradation and Reactive Transport: Analytical and Numerical Models

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

Sun, Y; Glascoe, L

The computational modeling of the biodegradation of contaminated groundwater systems accounting for biochemical reactions coupled to contaminant transport is a valuable tool for both the field engineer/planner with limited computational resources and the expert computational researcher less constrained by time and computer power. There exists several analytical and numerical computer models that have been and are being developed to cover the practical needs put forth by users to fulfill this spectrum of computational demands. Generally, analytical models provide rapid and convenient screening tools running on very limited computational power, while numerical models can provide more detailed information with consequent requirementsmore » of greater computational time and effort. While these analytical and numerical computer models can provide accurate and adequate information to produce defensible remediation strategies, decisions based on inadequate modeling output or on over-analysis can have costly and risky consequences. In this chapter we consider both analytical and numerical modeling approaches to biodegradation and reactive transport. Both approaches are discussed and analyzed in terms of achieving bioremediation goals, recognizing that there is always a tradeoff between computational cost and the resolution of simulated systems.« less

Management of psoriasis patients with hepatitis B or hepatitis C virus infection.

PubMed

Bonifati, Claudio; Lora, Viviana; Graceffa, Dario; Nosotti, Lorenzo

2016-07-28

The systemic therapies available for the management of Psoriasis (PsO) patients who cannot be treated with more conservative options, such as topical agents and/or phototherapy, with the exception of acitretin, can worsen or reactivate a chronic infection. Therefore, before administering immunosuppressive therapies with either conventional disease-modifying drugs (cDMARDs) or biological ones (bDMARDs) it is mandatory to screen patients for some infections, including hepatitis B virus (HBV) and hepatitis C virus (HCV). In particular, the patients eligible to receive an immunosuppressive drug must be screened for the following markers: antibody to hepatitis B core, antibody to hepatitis B surface antigen (anti-HBsAg), HBsAg, and antibody to HCV (anti-HCV). In case HBV or HCV infection is diagnosed, a close collaboration with a consultant hepatologist is needed before and during an immunosuppressive therapy. Concerning therapy with immunosuppressive drugs in PsO patients with HBV or HCV infection, data exist mainly for cyclosporine a (CyA) or bDMARDs (etanercept, adalimumab, infliximab, ustekinumab). The natural history of HBV and HCV infection differs significantly as well as the effect of immunosuppression on the aforementioned infectious diseases. As a rule, in the case of active HBV infection, systemic immunosuppressive antipsoriatic therapies must be deferred until the infection is controlled with an adequate antiviral treatment. Inactive carriers need to receive antiviral prophylaxis 2-4 wk before starting immunosuppressive therapy, to be continued after 6-12 mo from its suspension. Due to the risk of HBV reactivation, these patients should be monitored monthly for the first 3 mo and then every 3 mo for HBV DNA load together with transaminases levels. Concerning the patients who are occult HBV carriers, the risk of HBV reactivation is very low. Therefore, these patients generally do not need antiviral prophylaxis and the sera HBsAg and transaminases dosing can be monitored every 3 mo. Concerning PsO patients with chronic HCV infection their management with immunosuppressive drugs is less problematic as compared to those infected by HBV. In fact, HCV reactivation is an extremely rare event after administration of drugs such as CyA or tumor necrosis factor-α inhibitors. As a rule, these patients can be monitored measuring HCV RNA load, and ALT, aspartate transaminase, gamma-glutamyl-transferase, bilirubin, alkaline phosphatase, albumin and platelet every 3-6 mo. The present article provides an updated overview based on more recently reported data on monitoring and managing PsO patients who need systemic antipsoriatic treatment and have HBV or HCV infection as comorbidity.

The Howard University Hospital Experience with Routineized HIV Screening: A Progress Report*

PubMed Central

Scott, Victor F.; Sitapati, Amy; Martin, Sayyida; Summers, Pamela; Washington, Michael; Daniels, Fernando; Mouton, Charles; Bonney, George; Apprey, Victor; Webster, Virginia; Smith, Avemaria; Mountvarner, Geoffrey; Daftary, Monica; Maxwell, Celia J.

2009-01-01

Background: Howard University Hospital (HUH) is the first hospital in the nation to have instituted a hospital-wide routine rapid HIV screening campaign as recommended by the CDC for healthcare settings. Methods: HUH developed a protocol and implemented a hospital-wide routine HIV screening in October 2006. Rapid oral fluid-based HIV testing was conducted throughout the hospital using the OraSure OraQuick Advance Rapid HIV-1/2 Antibody Test. Patients with a preliminarily reactive test result were either referred for confirmatory testing or offered a Western Blot confirmatory test on-site and referred for follow-up care. This is a report on the progress of this program for the first eight months. Results: Of the 9,817 patients offered HIV testing, 5,642 consented. The mean age of the screened population was 40.7 years. Ninety percent of the patients screened were black and 55% were female. A preliminarily reactive test result was identified in 139 patients for a seroprevalence rate of 2.46%. Of these patients, 136, or 98% were black; 63% were male and 37% were female. HIV prevalence in the overall sample, among blacks, and among both black males and females peaked in the 40–54 year old age group. Challenges were experienced initially in securing confirmatory tests. Conclusions: Hospital-wide routine HIV screening is both possible and productive. The routine HIV screening campaign instituted at Howard University Hospital has identified a significant number of previously unidentified HIV positive persons. Success in assuring confirmatory testing and transition to care improved as time progressed. PMID:19768195

The Howard University Hospital experience with routineized HIV screening: a progress report.

PubMed

Scott, Victor F; Sitapati, Amy; Martin, Sayyida; Summers, Pamela; Washington, Michael; Daniels, Fernando; Mouton, Charles; Bonney, George; Apprey, Victor; Webster, Virginia; Smith, Avemaria; Mountvarner, Geoffrey; Daftary, Monica; Maxwell, Celia J

2009-01-01

Howard University Hospital (HUH) is the first hospital in the nation to have instituted a hospital-wide routine rapid HIV screening campaign as recommended by the CDC for healthcare settings. HUH developed a protocol and implemented a hospital-wide routine HIV screening in October 2006. Rapid oral fluid-based HIV testing was conducted throughout the hospital using the OraSure OraQuick Advance Rapid HIV-1/2 Antibody Test. Patients with a preliminarily reactive test result were either referred for confirmatory testing or offered a Western Blot confirmatory test on-site and referred for follow-up care. This is a report on the progress of this program for the first eight months. Of the 9,817 patients offered HIV testing, 5,642 consented. The mean age of the screened population was 40.7 years. Ninety percent of the patients screened were black and 55% were female. A preliminarily reactive test result was identified in 139 patients for a seroprevalence rate of 2.46%. Of these patients, 136, or 98% were black; 63% were male and 37% were female. HIV prevalence in the overall sample, among blacks, and among both black males and females peaked in the 40-54 year old age group. Challenges were experienced initially in securing confirmatory tests. Hospital-wide routine HIV screening is both possible and productive. The routine HIV screening campaign instituted at Howard University Hospital has identified a significant number of previously unidentified HIV positive persons. Success in assuring confirmatory testing and transition to care improved as time progressed.

Fetal acoustic stimulation test for early intrapartum fetal monitoring.

PubMed

Goonewardene, M; Hanwellage, K

2011-03-01

The fetal acoustic stimulation test (FAST) is a simple cost effective screening test for antenatal fetal monitoring. The aim of the study was to evaluate the FAST as a screening test for early intrapartum fetal well being. An initial non stress test (NST) followed by a FAST using corometric model 146 was carried out in 486 participants in early labour with uncomplicated singleton pregnancies and > 32 weeks gestation. A repeat NST was recorded in the participants who had an initial non reactive NST. The results of the NST and FAST were compared with fetal outcome. Maternal perception of fetal movements after FAST, results of NST before and after FAST, and the babies' 5 minute APGAR scores were measured. Of the 486 participants 413 (85%) noticed fetal movements after FAST. Initial NST was non reactive in 203 (42%) but 149 (31%) became reactive after FAST. Compared to the NST, FAST had a better sensitivity (97% vs 62%, p < 0.001), specificity (100% vs 87%, p = 0.017), positive predictive value (100% vs 98%, p = 0.024), negative predictive value (79% vs 17%, p < 0.001) and accuracy (99%vs 64%, p < 0.001) in predicting 5 minute APGAR < 7 in the baby. FAST is a reliable screening test for assessing fetal well being in early labour. It complements the NST and is better than the NST alone.

Computer-aided drug design of falcipain inhibitors: virtual screening, structure-activity relationships, hydration site thermodynamics, and reactivity analysis.

PubMed

Shah, Falgun; Gut, Jiri; Legac, Jennifer; Shivakumar, Devleena; Sherman, Woody; Rosenthal, Philip J; Avery, Mitchell A

2012-03-26

Falcipains (FPs) are hemoglobinases of Plasmodium falciparum that are validated targets for the development of antimalarial chemotherapy. A combined ligand- and structure-based virtual screening of commercial databases was performed to identify structural analogs of virtual screening hits previously discovered in our laboratory. A total of 28 low micromolar inhibitors of FP-2 and FP-3 were identified and the structure-activity relationship (SAR) in each series was elaborated. The SAR of the compounds was unusually steep in some cases and could not be explained by a traditional analysis of the ligand-protein interactions (van der Waals, electrostatics, and hydrogen bonds). To gain further insights, a statistical thermodynamic analysis of explicit solvent in the ligand binding domains of FP-2 and FP-3 was carried out to understand the roles played by water molecules in binding of these inhibitors. Indeed, the energetics associated with the displacement of water molecules upon ligand binding explained some of the complex trends in the SAR. Furthermore, low potency of a subset of FP-2 inhibitors that could not be understood by the water energetics was explained in the context of poor chemical reactivity of the reactive centers of these compounds. The present study highlights the importance of considering energetic contributors to binding beyond traditional ligand-protein interactions. © 2012 American Chemical Society

Molecular Quantum Similarity, Chemical Reactivity and Database Screening of 3D Pharmacophores of the Protein Kinases A, B and G from Mycobacterium tuberculosis.

PubMed

Morales-Bayuelo, Alejandro

2017-06-21

Mycobacterium tuberculosis remains one of the world's most devastating pathogens. For this reason, we developed a study involving 3D pharmacophore searching, selectivity analysis and database screening for a series of anti-tuberculosis compounds, associated with the protein kinases A, B, and G. This theoretical study is expected to shed some light onto some molecular aspects that could contribute to the knowledge of the molecular mechanics behind interactions of these compounds, with anti-tuberculosis activity. Using the Molecular Quantum Similarity field and reactivity descriptors supported in the Density Functional Theory, it was possible to measure the quantification of the steric and electrostatic effects through the Overlap and Coulomb quantitative convergence (alpha and beta) scales. In addition, an analysis of reactivity indices using global and local descriptors was developed, identifying the binding sites and selectivity on these anti-tuberculosis compounds in the active sites. Finally, the reported pharmacophores to PKn A, B and G, were used to carry out database screening, using a database with anti-tuberculosis drugs from the Kelly Chibale research group (http://www.kellychibaleresearch.uct.ac.za/), to find the compounds with affinity for the specific protein targets associated with PKn A, B and G. In this regard, this hybrid methodology (Molecular Mechanic/Quantum Chemistry) shows new insights into drug design that may be useful in the tuberculosis treatment today.

The Association of Posttraumatic Stress Disorder With Clinic and Ambulatory Blood Pressure in Healthy Adults.

PubMed

Edmondson, Donald; Sumner, Jennifer A; Kronish, Ian M; Burg, Matthew M; Oyesiku, Linda; Schwartz, Joseph E

2018-01-01

Posttraumatic stress disorder (PTSD) is associated with incident cardiovascular risk. We tested the association of PTSD with clinic and ambulatory blood pressure (ABP) in a sample of healthy participants and tested ABP reactivity to anxiety as a mechanism by which PTSD may influence blood pressure (BP). Participants were originally enrolled during workplace BP screenings at three sites; approximately 6 years (standard deviation = 1.0) later, they completed nine clinic BP assessments within three visits, 1 week apart. Before the third visit, participants were screened for PTSD (≥33 on the PTSD Checklist-Civilian) and depression (Beck Depression Inventory) and then completed 24-hour ABP monitoring with electronic diary assessment of anxiety (0-100) at each awake reading. Of 440 participants, 92 (21%) screened positive for PTSD. In regression models adjusted for depression and demographic and clinical variables, PTSD was associated with greater mean systolic BP (3.8 mm Hg clinic [95% confidence interval {CI}] = 1.1-6.5, p = .006), 3.0 mm Hg awake ABP [95% CI = 0.1-5.9, p = .04], and a nonsignificant 2.1 mm Hg ABP during sleep [95% CI = -1.0 to 5.1, p = .18]). PTSD was associated with greater 24-hour median anxiety (p < .001), and changes in anxiety were positively associated with concurrent systolic ABP (p < .001). ABP reactivity to anxiety was greater in participants with PTSD, which partially explained the association of PTSD with ABP. PTSD is associated with greater systolic BP, partly because of greater anxiety, and systolic BP reactivity to anxiety throughout the day. Daily anxiety and related BP reactivity may be targets for interventions to reduce the cardiovascular risk associated with PTSD.

Phage display of the serpin alpha-1 proteinase inhibitor randomized at consecutive residues in the reactive centre loop and biopanned with or without thrombin.

PubMed

Scott, Benjamin M; Matochko, Wadim L; Gierczak, Richard F; Bhakta, Varsha; Derda, Ratmir; Sheffield, William P

2014-01-01

In spite of the power of phage display technology to identify variant proteins with novel properties in large libraries, it has only been previously applied to one member of the serpin superfamily. Here we describe phage display of human alpha-1 proteinase inhibitor (API) in a T7 bacteriophage system. API M358R fused to the C-terminus of T7 capsid protein 10B was directly shown to form denaturation-resistant complexes with thrombin by electrophoresis and immunoblotting following exposure of intact phages to thrombin. We therefore developed a biopanning protocol in which thrombin-reactive phages were selected using biotinylated anti-thrombin antibodies and streptavidin-coated magnetic beads. A library consisting of displayed API randomized at residues 357 and 358 (P2-P1) yielded predominantly Pro-Arg at these positions after five rounds of thrombin selection; in contrast the same degree of mock selection yielded only non-functional variants. A more diverse library of API M358R randomized at residues 352-356 (P7-P3) was also probed, yielding numerous variants fitting a loose consensus of DLTVS as judged by sequencing of the inserts of plaque-purified phages. The thrombin-selected sequences were transferred en masse into bacterial expression plasmids, and lysates from individual colonies were screening for API-thrombin complexing. The most active candidates from this sixth round of screening contained DITMA and AAFVS at P7-P3 and inhibited thrombin 2.1-fold more rapidly than API M358R with no change in reaction stoichiometry. Deep sequencing using the Ion Torrent platform confirmed that over 800 sequences were significantly enriched in the thrombin-panned versus naïve phage display library, including some detected using the combined phage display/bacterial lysate screening approach. Our results show that API joins Plasminogen Activator Inhibitor-1 (PAI-1) as a serpin amenable to phage display and suggest the utility of this approach for the selection of "designer serpins" with novel reactivity and/or specificity.

Phage Display of the Serpin Alpha-1 Proteinase Inhibitor Randomized at Consecutive Residues in the Reactive Centre Loop and Biopanned with or without Thrombin

PubMed Central

Scott, Benjamin M.; Matochko, Wadim L.; Gierczak, Richard F.; Bhakta, Varsha; Derda, Ratmir; Sheffield, William P.

2014-01-01

In spite of the power of phage display technology to identify variant proteins with novel properties in large libraries, it has only been previously applied to one member of the serpin superfamily. Here we describe phage display of human alpha-1 proteinase inhibitor (API) in a T7 bacteriophage system. API M358R fused to the C-terminus of T7 capsid protein 10B was directly shown to form denaturation-resistant complexes with thrombin by electrophoresis and immunoblotting following exposure of intact phages to thrombin. We therefore developed a biopanning protocol in which thrombin-reactive phages were selected using biotinylated anti-thrombin antibodies and streptavidin-coated magnetic beads. A library consisting of displayed API randomized at residues 357 and 358 (P2–P1) yielded predominantly Pro-Arg at these positions after five rounds of thrombin selection; in contrast the same degree of mock selection yielded only non-functional variants. A more diverse library of API M358R randomized at residues 352–356 (P7–P3) was also probed, yielding numerous variants fitting a loose consensus of DLTVS as judged by sequencing of the inserts of plaque-purified phages. The thrombin-selected sequences were transferred en masse into bacterial expression plasmids, and lysates from individual colonies were screening for API-thrombin complexing. The most active candidates from this sixth round of screening contained DITMA and AAFVS at P7–P3 and inhibited thrombin 2.1-fold more rapidly than API M358R with no change in reaction stoichiometry. Deep sequencing using the Ion Torrent platform confirmed that over 800 sequences were significantly enriched in the thrombin-panned versus naïve phage display library, including some detected using the combined phage display/bacterial lysate screening approach. Our results show that API joins Plasminogen Activator Inhibitor-1 (PAI-1) as a serpin amenable to phage display and suggest the utility of this approach for the selection of “designer serpins” with novel reactivity and/or specificity. PMID:24427287

Serodiagnosis of Human Cysticercosis by Using Antigens from Vesicular Fluid of Taenia crassiceps Cysticerci

PubMed Central

Bueno, Ednéia C.; Snege, Miriam; Vaz, Adelaide J.; Leser, Paulo G.

2001-01-01

Neurocysticercosis (NC), caused by the presence of Taenia solium metacestodes in tissues, is a severe parasitic infection of the central nervous system with universal distribution. To determine the efficiency of enzyme-linked immunosorbent assay (ELISA) and immunoblot with antigens of T. crassiceps vesicular fluid (Tcra) compared to standard techniques (indirect immunofluorescence test [IFT] and complement fixation test [CFT]) using T. solium cysticerci (Tso) for the serodiagnosis of NC, we studied serum samples from 24 patients with NC, 30 supposedly healthy individuals, 76 blood bank donors, 45 individuals with other non-NC parasitoses, and 97 samples from individuals screened for cysticercosis serology (SC). The sensitivity observed was 100% for ELISA-Tso and ELISA-Tcra, 91.7% for the IFT, and 87.5% for the CFT. The specificity was 90% for ELISA-Tso, 96.7% for ELISA-Tcra, 50% for IFT, and 63.3% for CFT. The efficiency was highest for ELISA-Tcra, followed by ELISA-Tso, IFT, and CFT. Of the 23 samples from SC group, which were reactive to ELISA-Tso and/or ELISA-Tcra, only 3 were positive to immunblot-Tcra (specific peptides of 14- and 18-kDa) and to glycoprotein peptides purified from Tcra antigen (gp-Tcra), showing the low predictive value of ELISA for screening. None of the samples from the remaining groups showed specific reactivity in immunoblot-Tcra. These results demonstrate that ELISA-Tcra can be used as a screening method for the serodiagnosis of NC and support the need for specific tests for confirmation of the results. The immunoblot can be used as a confirmatory test both with Tcra and gp-Tcra, with the latter having an advantage in terms of visualization of the results. PMID:11687454

Identification of early HIV infections using the fourth generation Abbott ARCHITECT HIV Ag/Ab Combo chemiluminescent microparticle immunoassay (CIA) in San Diego County.

PubMed

Manlutac, Anna Liza M; Giesick, Jill S; McVay, Patricia A

2013-12-01

HIV screening assays have gone through several generations of development in an effort to narrow the "window period" of detection. Utilizing a fourth generation HIV screening assay has the potential to detect earlier HIV infection, thus reducing HIV-1 transmission. To identify acute infections to decrease HIV transmission in San Diego County. Serum specimens were collected from clients seen by multiple submitters in San Diego County. All acceptable specimens were screened using the 4th Gen Combo Assay. Initially reactive specimens were repeated in duplicate and if repeatedly reactive, were confirmed by HIV-1 Immunofluorescent Antibody Assay (IFA). IFA negative/inconclusive specimens were sent for HIV-1 NAT and HIV-2 antibody testing to referral laboratories. BioRad Multispot HIV-1/HIV-2 Rapid Test was also performed on a subset of specimens. Of 14,559 specimens received in 20 months, 14,517 specimens were tested. Of the 14,517 specimens that were tested, a total of 279 (1.9%) specimens were CIA repeatedly reactive and 240 of the 279 confirmed by HIV-1 IFA. Thirty-nine gave IFA negative/inconclusive result and 30 were further tested for HIV-1 NAT and 36 for HIV-2 antibody. Thirteen specimens were considered false positives by CIA and 17 specimens were classified as acute infections. Eleven of 39 IFA negative/inconclusive specimens were further tested by Multispot. Five of the 11 were positive by Multispot. The fourth generation Abbott ARCHITECT HIV Ag/Ab Combo Assay identified 17 patients who may have been missed by the prior HIV-1 screening assay used at San Diego County Public Health Laboratory. Copyright © 2013 Elsevier B.V. All rights reserved.

Inhibition of Epstein-Barr virus reactivation by the flavonoid apigenin.

PubMed

Wu, Chung-Chun; Fang, Chih-Yeu; Cheng, Yu-Jhen; Hsu, Hui-Yu; Chou, Sheng-Ping; Huang, Sheng-Yen; Tsai, Ching-Hwa; Chen, Jen-Yang

2017-01-05

Lytic reactivation of EBV has been reported to play an important role in human diseases, including NPC carcinogenesis. Inhibition of EBV reactivation is considered to be of great benefit in the treatment of virus-associated diseases. For this purpose, we screened for inhibitory compounds and found that apigenin, a flavonoid, seemed to have the ability to inhibit EBV reactivation. We performed western blotting, immunofluorescence and luciferase analyses to determine whether apigenin has anti-EBV activity. Apigenin inhibited expression of the EBV lytic proteins, Zta, Rta, EAD and DNase in epithelial and B cells. It also reduced the number of EBV-reactivating cells detectable by immunofluorescence analysis. In addition, apigenin has been found to reduce dramatically the production of EBV virions. Luciferase reporter analysis was performed to determine the mechanism by which apigenin inhibits EBV reactivation: apigenin suppressed the activity of the immediate-early (IE) gene Zta and Rta promoters, suggesting it can block initiation of the EBV lytic cycle. Taken together, apigenin inhibits EBV reactivation by suppressing the promoter activities of two viral IE genes, suggesting apigenin is a potential dietary compound for prevention of EBV reactivation.

Alkylation sensitivity screens reveal a conserved cross-species functionome

PubMed Central

Svilar, David; Dyavaiah, Madhu; Brown, Ashley R.; Tang, Jiang-bo; Li, Jianfeng; McDonald, Peter R.; Shun, Tong Ying; Braganza, Andrea; Wang, Xiao-hong; Maniar, Salony; St Croix, Claudette M.; Lazo, John S.; Pollack, Ian F.; Begley, Thomas J.; Sobol, Robert W.

2013-01-01

To identify genes that contribute to chemotherapy resistance in glioblastoma, we conducted a synthetic lethal screen in a chemotherapy-resistant glioblastoma derived cell line with the clinical alkylator temozolomide (TMZ) and an siRNA library tailored towards “druggable” targets. Select DNA repair genes in the screen were validated independently, confirming the DNA glycosylases UNG and MYH as well as MPG to be involved in the response to high dose TMZ. The involvement of UNG and MYH is likely the result of a TMZ-induced burst of reactive oxygen species. We then compared the human TMZ sensitizing genes identified in our screen with those previously identified from alkylator screens conducted in E. coli and S. cerevisiae. The conserved biological processes across all three species composes an Alkylation Functionome that includes many novel proteins not previously thought to impact alkylator resistance. This high-throughput screen, validation and cross-species analysis was then followed by a mechanistic analysis of two essential nodes: base excision repair (BER) DNA glycosylases (UNG, human and mag1, S. cerevisiae) and protein modification systems, including UBE3B and ICMT in human cells or pby1, lip22, stp22 and aim22 in S. cerevisiae. The conserved processes of BER and protein modification were dual targeted and yielded additive sensitization to alkylators in S. cerevisiae. In contrast, dual targeting of BER and protein modification genes in human cells did not increase sensitivity, suggesting an epistatic relationship. Importantly, these studies provide potential new targets to overcome alkylating agent resistance. PMID:23038810

Hepatitis B Virus Reactivation in the Setting of Cancer Chemotherapy and Other Immunosuppressive Drug Therapy.

PubMed

Gonzalez, Stevan A; Perrillo, Robert P

2016-06-01

Hepatitis B virus reactivation (HBVr) is an important complication of immunosuppressive drug therapy (ISDT). It can occur with active or resolved hepatitis B virus (HBV) infection with a clinical spectrum that ranges from mild elevations in liver tests to fulminant hepatic failure. The risk of it occurring is determined by the interplay between HBV serological status, level of viremia, and the immunosuppressive potency of the drug(s) used. Reactivation is most common during treatment of hematologic malignancies but also occurs with chemotherapy for breast cancer and numerous other solid organ malignancies, organ transplant, and immune suppression for nonmalignant conditions. The expansion of new biologic treatments for malignant and nonmalignant disorders has enlarged the population at risk. Increased awareness of HBVr among healthcare providers who prescribe ISDT, adoption of routine HBV screening, and linking the results of screening to antiviral prophylaxis are needed to reduce the incidence of this potentially fatal but preventable disorder. © The Author 2016. Published by Oxford University Press for the Infectious Diseases Society of America. All rights reserved. For permissions, e-mail journals.permissions@oup.com.

Contact allergy to reactive diluents and related aliphatic epoxy resins.

PubMed

Aalto-Korte, Kristiina; Kuuliala, Outi; Henriks-Eckerman, Maj-Len; Suuronen, Katri

2015-06-01

Diglycidyl ether of bisphenol A resin (DGEBA-R) is the most common sensitizer in epoxy systems, but a minority of patients also develop contact allergy to reactive diluents. To analyse the frequency and clinical relevance of allergic reactions to different epoxy reactive diluents and related aliphatic epoxy resins. Test files (January 1991 to June 2014) were screened, and the clinical records of patients with allergic reactions were analysed for occupation, concomitant allergic reactions, and exposure. A total of 67 patients reacted to at least one of the compounds. The largest numbers of allergic reactions were to phenyl glycidyl ether (PGE; n = 41), 1,4-butanediol diglycidyl ether (BDDGE; n = 34), and p-tert-butylphenyl glycidyl ether (PTBPGE; n = 19). Ten of the patients did not have contact allergy to DGEBA-R. The reactions of 5 of these were related to the use of BDDGE-containing products. We found no significant exposure to PGE or PTBPGE in patients sensitized to them, but some of the patients had used cresyl glycidyl ether-containing products. Allergic reactions to reactive diluents and related aliphatic epoxy resins usually occurred together with reactions to DGEBA-R. BDDGE was the clinically most significant compound, and was the sole cause of occupational allergic contact dermatitis in 3 patients. © 2015 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

Routine bacterial screening of apheresis platelets on Day 4 using a rapid test: a 4-year single-center experience.

PubMed

Dunbar, Nancy M; Kreuter, Justin D; Marx-Wood, Cynthia R; Dumont, Larry J; Szczepiorkowski, Zbigniew M

2013-10-01

The platelet (PLT) Pan Genera Detection test (PGD) is a rapid bacterial detection system used to screen PLTs for bacterial contamination. We report a single center 46-month experience with secondary screening of apheresis PLTs by PGD testing. Existing testing records of apheresis PLTs screened by PGD from July 2008 to April 2012 were reviewed. All PLT units were initially screened by routine postcollection culture methods. Secondary screening using PGD was performed for indated PLTs on PLT storage Day 4 and for outdated PLTs on Day 8. A total of 8535 apheresis PLTs were available in inventory during the study period. Of these, 5030 (58.9%) were dispensed and transfused before PGD testing and 3505 (41.1%) underwent PGD testing on Day 4. Twenty-five units tested on Day 4 were PGD initial reactive (0.71%). All were confirmed to be false positive by repeat PGD testing in triplicate (n=20) or by confirmatory culture (n=5). An additional 364 units that were PGD nonreactive on Day 4 were approved for transfusion on Day 6 or Day 7 due to urgent clinical need. A total of 371 outdated units underwent repeat PGD testing before discard on Day 8; all were nonreactive. Secondary PGD testing of culture-screened apheresis PLTs results in low yield in a medium-sized transfusion service. Use of PGD testing on Day 4 may allow for extension of the apheresis PLT shelf life to Day 7 for hospitals that face supply constraints. © 2013 American Association of Blood Banks.

Biologic therapy and screening for tuberculosis in a new service.

PubMed

Peters, Julie

Plaque psoriasis is a common skin condition that can greatly affect quality of life. Biologic therapy is an effective treatment, but it poses risks to patients, particularly concerning latent infections such as tuberculosis (TB), which may be reactivated. Medical practitioners therefore need to screen patients before commencing a biologic therapy. There are a number of screening tools for TB infection, which vary in efficacy depending on the patient being screened, and some tests can give a false-negative result for TB infection. It is important to screen for TB and to take a good clinical and lifestyle history before commencing biologic treatment. This article discusses the above in the context of setting up a dedicated clinic to monitor patients on biologic therapy for plaque psoriasis.

Evaluation of commercial enzyme-linked immunosorbent assays to identify psychedelic phenethylamines.

PubMed

Kerrigan, Sarah; Mellon, Monica Brady; Banuelos, Stephanie; Arndt, Crystal

2011-09-01

The 2C, 2C-T, and DO series of designer drugs pose a number of challenges to forensic toxicology laboratories. Although these drugs are seized by law enforcement agencies throughout the United States, they are not readily detected in forensic toxicology laboratories. A systematic evaluation of the cross-reactivity of 9 commercial enzyme-linked immunosorbent assays (ELISAs) was conducted using 11 designer drugs. Cross-reactivity was measured towards 2,5-dimethoxy-4-bromophenethylamine (2C-B), 2,5-dimethoxyphenethylamine (2C-H), 2,5-dimethoxy4-iodophenethylamine (2C-I), 2,5-dimethoxy-4ethylthiophenethylamine (2C-T-2), 2,5-dimethoxy-4isopropylthiophenethylamine (2C-T-4), 2,5-dimethoxy-4propylthiophenethylamine (2C-T-7), 2,5-dimethoxy-4bromoamphetamine (DOB), 2,5-dimethoxy-4-ethylamphetamine (DOET), 2,5-dimethoxy-4-iodoamphetamine (DOI), 2,5-dimethoxy-4-methylamphetamine (DOM), and 4methylthioamphetamine (4-MTA). Cross-reactivity towards the 2C, 2C-T, and DO series of psychedelic amphetamines was < 0.4%. Concentrations as high as 50,000 ng/mL in urine, which greatly exceed those expected in forensic case samples, were not sufficient to produce a positive result. The only substance to produce any measurable cross-reactivity was 4-MTA. Cross-reactivities of 5 and 7% were obtained using four methamphetamine/MDMA directed assays, 25 and 200% using two amphetamine-directed assays. The absence of any measurable cross-reactivity towards the 10 2C, 2C-T, and DO psychedelic phenethylamines makes it harder to detect these drugs using routine screening. As a consequence, laboratories that rely upon immunoassay rather than more broad spectrum chromatographic screening techniques, may fail to detect these powerful psychedelic substances.

A new discussion of the cutaneous vascular reactivity in sensitive skin: A sub-group of SS?

PubMed

Chen, S Y; Yin, J; Wang, X M; Liu, Y Q; Gao, Y R; Liu, X P

2018-02-02

Sensitive skin (SS) seems not to be a one-dimensional condition and many scholars concentrate on skin barrier disruption or sensorineural change, but few focus on its increased vascular reactivity. This study explored the possibility of using the different selection methods and measurement methods to verify a high vascular reactivity in SS without an impaired cutaneous barrier function. Sixty "self-perceived sensitive skin" volunteers were enlisted and each one completed three kinds of screening tests: assess cutaneous sensory using questionnaire survey and Lactic Acid Sting Test (LAST); assess barrier function using Sodium lauryl sulphate (SLS) skin irritation test and assess cutaneous vascular reactivity using 98% DMSO test and non-invasive measurement. Volunteers were divided into different groups based on response to SLS. The DMSO clinical score and the biophysical parameters obtained by non-invasive measurement were subsequently analysed. (1) The positive correlations could be seen between sum LAST score and sum DMSO score regardless of the observation time; (2) The biological parameters (CBF、a*values and L* values) are all keeping with DMSO score; (3) If the participants were divided into SLS reactors and non-reactors, a composition ratio of DMSO score was significant difference in these two groups and in SLS non-reactors, there were still seven participants showed high reaction to DMSO. There is a sub-group of SS for characteristics of a high vascular reactivity without an impaired cutaneous barrier function. The DMSO test and novel non-invasive measurements which are conducive to assess cutaneous vascular reactivity, combined with SLS skin irritation test could help us to screen this kind of SS. © 2018 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

Evaluation of commercial multi-drug oral fluid devices to identify 39 new amphetamine-designer drugs.

PubMed

Nieddu, Maria; Burrai, Lucia; Trignano, Claudia; Boatto, Gianpiero

2014-03-01

Recently, the diffusion on the black market of new psychoactive substances not controlled and often sold as 'legal highs', is exponentially increasing in Europe. Generally, the first analysis for these drugs involves an immunoassay screening in urine or plasma. Actually, there is growing interest in the use of oral fluid (OF) as alternative specimen over conventional biological fluids for drug testing, because of the significant advantages, as a non-invasive collection under direct observation without undue embarrassment or invasion of privacy, and a good correlation with plasma analytical data. Few assays have been developed for detection of new psychoactive compounds in biological samples, so it is important to investigate how they may or may not react in pre-existing commercial immunoassays. In this paper, two different multi-drugs oral fluid screen devices (OFDs) (Screen® Multi-Drug OFD and GIMA One Step Multi-Line Screen Test OFD) were evaluated to determine the cross-reactivity of thirty-nine new amphetamine designer drugs, including twelve substances officially recognized as illicit by italian legislation. Cross-reactivity towards most drugs analyzed was <1 in assays targeting amphetamine (AMP) or methamphetamine (MET). Only two (p-methoxyamphetamine and p-methoxymethamphetamine) of all tested amphetamines gave a positive result. Copyright © 2013 Elsevier Ireland Ltd. All rights reserved.

Role of Chemical Reactivity and Transition State Modeling for Virtual Screening.

PubMed

Karthikeyan, Muthukumarasamy; Vyas, Renu; Tambe, Sanjeev S; Radhamohan, Deepthi; Kulkarni, Bhaskar D

2015-01-01

Every drug discovery research program involves synthesis of a novel and potential drug molecule utilizing atom efficient, economical and environment friendly synthetic strategies. The current work focuses on the role of the reactivity based fingerprints of compounds as filters for virtual screening using a tool ChemScore. A reactant-like (RLS) and a product- like (PLS) score can be predicted for a given compound using the binary fingerprints derived from the numerous known organic reactions which capture the molecule-molecule interactions in the form of addition, substitution, rearrangement, elimination and isomerization reactions. The reaction fingerprints were applied to large databases in biology and chemistry, namely ChEMBL, KEGG, HMDB, DSSTox, and the Drug Bank database. A large network of 1113 synthetic reactions was constructed to visualize and ascertain the reactant product mappings in the chemical reaction space. The cumulative reaction fingerprints were computed for 4000 molecules belonging to 29 therapeutic classes of compounds, and these were found capable of discriminating between the cognition disorder related and anti-allergy compounds with reasonable accuracy of 75% and AUC 0.8. In this study, the transition state based fingerprints were also developed and used effectively for virtual screening in drug related databases. The methodology presented here provides an efficient handle for the rapid scoring of molecular libraries for virtual screening.

High throughput assay for evaluation of reactive carbonyl scavenging capacity.

PubMed

Vidal, N; Cavaille, J P; Graziani, F; Robin, M; Ouari, O; Pietri, S; Stocker, P

2014-01-01

Many carbonyl species from either lipid peroxidation or glycoxidation are extremely reactive and can disrupt the function of proteins and enzymes. 4-hydroxynonenal and methylglyoxal are the most abundant and toxic lipid-derived reactive carbonyl species. The presence of these toxics leads to carbonyl stress and cause a significant amount of macromolecular damages in several diseases. Much evidence indicates trapping of reactive carbonyl intermediates may be a useful strategy for inhibiting or decreasing carbonyl stress-associated pathologies. There is no rapid and convenient analytical method available for the assessment of direct carbonyl scavenging capacity, and a very limited number of carbonyl scavengers have been identified to date, their therapeutic potential being highlighted only recently. In this context, we have developed a new and rapid sensitive fluorimetric method for the assessment of reactive carbonyl scavengers without involvement glycoxidation systems. Efficacy of various thiol- and non-thiol-carbonyl scavenger pharmacophores was tested both using this screening assay adapted to 96-well microplates and in cultured cells. The scavenging effects on the formation of Advanced Glycation End-product of Bovine Serum Albumin formed with methylglyoxal, 4-hydroxynonenal and glucose-glycated as molecular models were also examined. Low molecular mass thiols with an α-amino-β-mercaptoethane structure showed the highest degree of inhibitory activity toward both α,β-unsaturated aldehydes and dicarbonyls. Cysteine and cysteamine have the best scavenging ability toward methylglyoxal. WR-1065 which is currently approved for clinical use as a protective agent against radiation and renal toxicity was identified as the best inhibitor of 4-hydroxynonenal.

Reactive modification of polyesters and their blends

NASA Astrophysics Data System (ADS)

Wan, Chen

2004-12-01

As part of a broader research effort to investigate the chemical modification of polyesters by reactive processing a low molecular weight (MW) unsaturated polyester (UP) and a higher MW saturated polyester, polyethylene terephthalate (PET), alone or blended with polypropylene (PP) were melt processed in a batch mixer and continuous twin screw extruders. Modification was monitored by on-line rheology and the products were characterized primarily by off-line rheology, morphology and thermal analysis. Efforts were made to establish processing/property relationships and provide an insight of the accompanying structural changes. The overall response of the reactively modified systems was found to be strongly dependent on the component characteristics, blend composition, type and concentrations of reactive additives and processing conditions. The work concluded that UP can be effectively modified through reactive melt processing. Its melt viscosity and MW can be increased through chemical reactions between organic peroxides (POX) and chain unsaturation or between MgO and carboxyl/hydroxyl end groups. Reactive blending of PP/UP blends through peroxide modification gave finer and more uniform morphology than unreacted blends and at a given PP/UP weight ratio more thermoplastic elastomers-like rheological behavior. This is due to the continuously decreasing viscosity ratio of PP/UP towards unity by the competing reactions between POX and the blend components and formation of PP-UP copolymers which serve as in-situ compatibilizers to promote better interfacial adhesion. Kinetics of the competing reactions were analyzed through a developed model. In addition to POX concentration and mixing efficiency, rheology and morphology of UP/PP bends were significantly affected by the addition of inorganic and organic coagents. Addition of coagents such as a difunctional maleimide, MgO and/or an anhydride functionalized PP during reactive blending offers effective means for tailoring the desired rheological and structural characteristics of the final products for potential applications such as low density extrusion foaming or compatibilization of immiscible polymer blends. Important modification conditions through coagents are identified and reaction mechanisms are proposed. A high MW saturated polyester, PET, can also be rheologically modified in extruders through low MW multifunctional anhydride and epoxy compounds by chain extension/branching. Several such modifiers were successfully screened in terms of their reactivity towards PET under controlled reactive extrusion conditions. A dianhydride with medium reactivity was then successfully used in a one-step reactive modification/extrusion foaming process to produce low density foams. A similar process was successfully used to produce small cell size foams from a four component system containing PET, PP and lesser amounts of a low molecular weight multifunctional epoxy compound and an acid functionalized polyolefin, the latter acting as compatibilizers.

Screening for novel central nervous system biomarkers in veterans with Gulf War Illness.

PubMed

Abou-Donia, Mohamed B; Conboy, Lisa A; Kokkotou, Efi; Jacobson, Eric; Elmasry, Eman M; Elkafrawy, Passent; Neely, Megan; Bass, Cameron R 'Dale'; Sullivan, Kimberly

2017-05-01

Gulf War illness (GWI) is primarily diagnosed by symptom report; objective biomarkers are needed that distinguish those with GWI. Prior chemical exposures during deployment have been associated in epidemiologic studies with altered central nervous system functioning in veterans with GWI. Previous studies from our group have demonstrated the presence of autoantibodies to essential neuronal and glial proteins in patients with brain injury and autoantibodies have been identified as candidate objective markers that may distinguish GWI. Here, we screened the serum of 20 veterans with GWI and 10 non-veteran symptomatic (low back pain) controls for the presence of such autoantibodies using Western blot analysis against the following proteins: neurofilament triplet proteins (NFP), tubulin, microtubule associated tau proteins (Tau), microtubule associated protein-2 (MAP-2), myelin basic protein (MBP), myelin associated glycoprotein (MAG), glial fibrillary acidic protein (GFAP), calcium-calmodulin kinase II (CaMKII) and glial S-100B protein. Serum reactivity was measured as arbitrary chemiluminescence units. As a group, veterans with GWI had statistically significantly higher levels of autoantibody reactivity in all proteins examined except S-100B. Fold increase of the cases relative to controls in descending order were: CaMKII 9.27, GFAP 6.60, Tau 4.83, Tubulin 4.41, MAG 3.60, MBP 2.50, NFP 2.45, MAP-2 2.30, S-100B 1.03. These results confirm the continuing presence of neuronal injury/gliosis in these veterans and are in agreement with the recent reports indicating that 25years after the war, the health of veterans with GWI is not improving and may be getting worse. Such serum autoantibodies may prove useful as biomarkers of GWI, upon validation of the findings using larger cohorts. Copyright © 2017 Elsevier Inc. All rights reserved.

Serological confirmatory testing of alveolar and cystic echinococcosis in clinical practice: results of a comparative study with commercialized and in-house assays.

PubMed

Reiter-Owona, Ingrid; Grüner, Beate; Frosch, Matthias; Hoerauf, Achim; Kern, Peter; Tappe, Dennis

2009-01-01

Sera of 50 patients with either cystic (CE) or alveolar echinococcosis (AE) in different clinical stages were examined for the presence of anti-Echinococcus-antibodies. Antibody-screening was performed with ELISA, IHA and IFAT, and confirmatory testing was done by the commercialized E. multilocularis-specific Em2plus-ELISA versus an in-house E. multilocularis-specific Em10-ELISA. Sera with discrepant confirmatory results were subjected to a commercial Echinococcus IgG Western blot (WB). In sera from patients with CE, the Em2plus-ELISA showed cross-reactions in 23.5%, whereas the Em10-ELISA did not exhibit any cross-reactivity. Cross-reactivity paralleled active infection with high antibody titers in the screening assays. In sera from patients with AE, confirmation by both ELISAs was achieved in 57.6%, mostly in patients with an advanced stage of the disease and high antibody titers in the screening assays. False-negative reactions of both ELISAs occurred in 30.3%, mostly in patients who had low antibody levels in the screening tests. The Em2plus-ELISA exhibited fewer false-negative reactions than the Em10-ELISA. The WB confirmed the positive results of either assay and was the assay with the highest reliability at different stages of CE and AE, followed by the Em2plus-ELISA for AE. High antibody titers in the screening assays will favour the detection of species-specific antibodies in either form.

Assessing salivary C-reactive protein: Longitudinal associations with systemic inflammation and cardiovascular disease risk in women exposed to intimate partner violence

PubMed Central

Out, Dorothée; Hall, Rosalie J.; Granger, Douglas A.; Page, Gayle G.; Woods, Stephanie J.

2012-01-01

This study evaluated individual differences in levels of C-reactive protein (CRP) measured in saliva, cross-sectionally and prospectively, in relation to systemic inflammation and risk for cardiovascular disease (CVD). Plasma and saliva samples, later assayed for CRP, were collected multiple times from an ethnically diverse group of women seeking help from domestic violence crisis shelters-agencies (N = 107; mean age at study start = 34 years). Plasma and saliva CRP levels were moderately associated cross-sectionally and across two years. There were indications that saliva CRP levels were, on average, higher in the morning than evening. Higher levels of saliva and plasma CRP were associated with a higher body mass index, but did not differ between women who did and did not smoke. Salivary CRP reliably discriminated between high and low levels of plasma CRP, using a clinically relevant cutoff point of 3 mg/L, recommended by the American Heart Association. Results build upon an emerging literature suggesting that under specific conditions levels of CRP in saliva may reflect low-grade inflammation and have the potential to serve as a screen for CVD risk status. PMID:22326517

Television screen time, but not computer use and reading time, is associated with cardio-metabolic biomarkers in a multiethnic Asian population: a cross-sectional study.

PubMed

Nang, Ei Ei Khaing; Salim, Agus; Wu, Yi; Tai, E Shyong; Lee, Jeannette; Van Dam, Rob M

2013-05-30

Recent evidence shows that sedentary behaviour may be an independent risk factor for cardiovascular diseases, diabetes, cancers and all-cause mortality. However, results are not consistent and different types of sedentary behaviour might have different effects on health. Thus the aim of this study was to evaluate the association between television screen time, computer/reading time and cardio-metabolic biomarkers in a multiethnic urban Asian population. We also sought to understand the potential mediators of this association. The Singapore Prospective Study Program (2004-2007), was a cross-sectional population-based study in a multiethnic population in Singapore. We studied 3305 Singaporean adults of Chinese, Malay and Indian ethnicity who did not have pre-existing diseases and conditions that could affect their physical activity. Multiple linear regression analysis was used to assess the association of television screen time and computer/reading time with cardio-metabolic biomarkers [blood pressure, lipids, glucose, adiponectin, C reactive protein and homeostasis model assessment of insulin resistance (HOMA-IR)]. Path analysis was used to examine the role of mediators of the observed association. Longer television screen time was significantly associated with higher systolic blood pressure, total cholesterol, triglycerides, C reactive protein, HOMA-IR, and lower adiponectin after adjustment for potential socio-demographic and lifestyle confounders. Dietary factors and body mass index, but not physical activity, were potential mediators that explained most of these associations between television screen time and cardio-metabolic biomarkers. The associations of television screen time with triglycerides and HOMA-IR were only partly explained by dietary factors and body mass index. No association was observed between computer/ reading time and worse levels of cardio-metabolic biomarkers. In this urban Asian population, television screen time was associated with worse levels of various cardio-metabolic risk factors. This may reflect detrimental effects of television screen time on dietary habits rather than replacement of physical activity.

The rapid formation of functional monolayers on silicon under mild conditions.

PubMed

Ciampi, Simone; Luais, Erwann; James, Michael; Choudhury, Moinul H; Darwish, Nadim A; Gooding, J Justin

2014-05-07

We report on an exceedingly mild chemical functionalization of hydrogen-terminated Si(100) with unactivated and unprotected bifunctional α,ω-dialkynes. Monolayer formation occurs rapidly in the dark, and at room temperature, from dilute solutions of an aromatic-conjugated acetylene. The method addresses the poor reactivity of p-type substrates under mild conditions. We suggest the importance of several factors, including an optimal orientation for electron transfer between the adsorbate and the Si surface, conjugation of the acetylenic function with a π-system, as well as the choice of a solvent system that favors electron transfer and screens Coulombic interactions between surface holes and electrons. The passivated Si(100) electrode is amenable to further functionalization and shown to be a viable model system for redox studies at non-oxide semiconductor electrodes in aqueous solutions.

Common Amino Acid Subsequences in a Universal Proteome—Relevance for Food Science

PubMed Central

Minkiewicz, Piotr; Darewicz, Małgorzata; Iwaniak, Anna; Sokołowska, Jolanta; Starowicz, Piotr; Bucholska, Justyna; Hrynkiewicz, Monika

2015-01-01

A common subsequence is a fragment of the amino acid chain that occurs in more than one protein. Common subsequences may be an object of interest for food scientists as biologically active peptides, epitopes, and/or protein markers that are used in comparative proteomics. An individual bioactive fragment, in particular the shortest fragment containing two or three amino acid residues, may occur in many protein sequences. An individual linear epitope may also be present in multiple sequences of precursor proteins. Although recent recommendations for prediction of allergenicity and cross-reactivity include not only sequence identity, but also similarities in secondary and tertiary structures surrounding the common fragment, local sequence identity may be used to screen protein sequence databases for potential allergens in silico. The main weakness of the screening process is that it overlooks allergens and cross-reactivity cases without identical fragments corresponding to linear epitopes. A single peptide may also serve as a marker of a group of allergens that belong to the same family and, possibly, reveal cross-reactivity. This review article discusses the benefits for food scientists that follow from the common subsequences concept. PMID:26340620

Field Demonstration of Sequential Iron Reduction and Aerobic Biodegradation of Nitrobenzene and 2,4-Dinitrotoluene

NASA Astrophysics Data System (ADS)

Robinson, T. L.; Gillham, R. W.; Gui, L.

2005-12-01

To demonstrate the in situ sequential degradation of nitrobenzene (NB) and 2,4-dinitrotoluene (2,4-DNT) using a granular iron permeable reactive barrier (PRB) and aerobic biodegradation zone, a field study is currently being conducted in a 24m long x 2m wide x 3m deep isolated section of the Borden aquifer (the ``gate''). This gate is closed on three sides by sealable-joint sheet piling keyed into the aquitard, and open to groundwater flow on the other, which, under natural conditions, is approximately parallel to the longest sides of the gate. The PRB was installed approximately 10 meters into the gate, and the oxygen injection system was installed approximately 18 meters into the gate. A hydraulic gradient was induced across the gate by pumping at the closed end via a fully-screened well, resulting in a groundwater velocity of 40-50 cm/day. Based on the results of laboratory tests, the first stage of the treatment system, involving the PRB, was expected to reduce nitrobenzene and 2,4-DNT to aniline and 2,4-diaminotoluene (2,4-DAT), respectively. Initial results show that portions of the nitrobenzene and 2,4-dinitrotoluene were transforming into their daughter products, aniline and 2,4-diaminotoluene, prior to the groundwater entering the permeable reactive barrier. Lab tests are ongoing to determine whether an indigenous bacterial population is capable of biotically transforming the nitro groups on the nitrobenzene and 2,4-DNT. In the second stage of the treatment system, oxygen was introduced via 4 10-inch diameter fully-screened wells spanning the width of the gate, each containing a Waterloo EmitterTM. The oxygen is expected to stimulate indigenous aerobic microbes in the aquifer to mineralize the aniline and 2,4-diaminotoluene, and the results from this are expected in the next few months.

Discordant human T-lymphotropic virus screening with Western blot confirmation: evaluation of the dual-test algorithm for US blood donations.

PubMed

Stramer, Susan L; Townsend, Rebecca L; Foster, Gregory A; Johnson, Ramona; Weixlmann, Barbara; Dodd, Roger Y

2018-03-01

Human T-lymphotropic virus (HTLV) blood donation screening has used a dual-testing algorithm beginning with either a chemiluminescent immunoassay or enzyme-linked immunosorbent screening assay (ELISA). Before the availability of a licensed HTLV supplemental assay, repeat-reactive (RR) samples on a first assay (Assay 1) were retested with a second screening assay (Assay 2). Donors with RR results by Assay 2 were deferred from blood donation and further tested using an unlicensed supplemental test to confirm reactivity while nonreactive (NR) donors remained eligible for donation until RR on a subsequent donation. This "dual-test" algorithm was replaced in May 2016 with the requirement that all RRs by Assay 1 be further tested by a licensed HTLV supplemental test (Western blot [WB]). In this study, we have requalified the dual-test algorithm using the available licensed HTLV WB. We tested 100 randomly selected HTLV RRs on screening Assay 1 (Abbott PRISM chemiluminescent immunoassay) but NR on screening Assay 2 (Avioq ELISA) by a Food and Drug Administration-licensed WB (MP Biomedicals) to ensure that no confirmed positives were among those that were RR by Assay 1 but NR by Assay 2. Of the 100 samples evaluated, 79 of 100 were WB seronegative, 21 of 100 indeterminate, and 0 of 100 seropositive. Of the 79 of 100 seronegative specimens, 73 of 79 did not express any bands on WB. We demonstrated that none of the 100 samples RR on Assay 1 but NR on Assay 2 were confirmed positive. This algorithm prevents such donors from requiring further testing and from being deferred. © 2018 AABB.

New meanings of thin-skinned: The contrasting attentional profiles of typical 12-month-olds who show high, and low, stress reactivity.

PubMed

Wass, Sam V; de Barbaro, Kaya; Clackson, Kaili; Leong, Victoria

2018-05-01

Previous research is inconsistent as to whether a more labile (faster-changing) autonomic system confers performance advantages, or disadvantages, in infants and children. To examine this, we presented a stimulus battery consisting of mixed static and dynamic viewing materials to a cohort of 63 typical 12-month-old infants. While viewing the battery, infants' spontaneous visual attention (looks to and away from the screen) was measured. Concurrently, arousal was recorded via heart rate (HR), electrodermal activity, head velocity, and peripheral movement levels. In addition, stress reactivity was assessed using a mild behavioral stressor (watching a video of another infant crying). We found that infants who were generally more attentive showed smaller HR increases to the stressor. However, they also showed greater phasic autonomic changes to attractive, attention-getting stimulus events, a faster rate of change of both look duration and of arousal, and more general oscillatory activity in arousal. Finally, 4 sessions of attention training were applied to a subset of the infants (24 trained, 24 active controls), which had the effect of increasing visual sustained attention. No changes in HR responses to stressor were observed as a result of training, but concomitant increases in arousal lability were observed. Our results point to 2 contrasting autonomic profiles: infants with high autonomic reactivity to stressors show short attention durations, whereas infants with lower autonomic reactivity show longer attention durations and greater arousal lability. (PsycINFO Database Record (c) 2018 APA, all rights reserved).

2'-Deoxyguanosine as a surrogate trapping agent for DNA reactive drug metabolites.

PubMed

Häkkinen, Merja R; Laine, Jaana E; Juvonen, Risto O; Auriola, Seppo; Häyrinen, Jukka; Pasanen, Markku

2011-11-10

Drug metabolism can result in the production of highly reactive metabolites that may form adducts with cellular macromolecules, and thus initiate adverse drug reactions, cause toxicity, and even require the withdrawal of drug from the market. In this study, a 2'-deoxyguanosine (dG)-based chemical trapping test system was developed for use as a fast screening tool for DNA adducting metabolites of new drug candidates. Reactive metabolites were generated from parent compounds in in vitro incubations with phenobarbital-induced mouse liver microsomes, human liver microsomes and different recombinant human CYP enzymes in the presence of dG. The formed dG-adducts were separated, characterized and their stability was studied by liquid chromatography-tandem mass spectrometry (LC-MS/MS). The method was evaluated with six test compounds, aflatoxin B1, estrone, clozapine, tolcapone, ticlopidine and imipramine. Estrone and aflatoxin B1 formed dG adducts with phenobarbital-induced mouse liver microsomes, human liver microsomes and human recombinant CYP enzymes. Adduct formation was also observed with tolcapone when phenobarbital-induced mouse liver microsomes were used as the enzyme source. The stability of each formed adduct was independent of the different enzyme sources. No dG-adducts were identified with ticlopidine, clozapine and imipramine. Compared to other classical DNA reactivity tests, e.g. Ames test, the present surrogate endpoint, the dG adduct, is faster, enables the characterization of the formed compounds, and also permits the investigation of more unstable adducts. Copyright © 2011 Elsevier Ireland Ltd. All rights reserved.

Application of a Persistent Dissolved-phase Reactive Treatment Zone for Mitigation of Mass Discharge from Sources Located in Lower-Permeability Sediments

PubMed Central

Marble, J.C.; Brusseau, M.L.; Carroll, K.C.; Plaschke, M.; Fuhrig, L.; Brinker, F.

2015-01-01

The purpose of this study is to examine the development and effectiveness of a persistent dissolved-phase treatment zone, created by injecting potassium permanganate solution, for mitigating discharge of contaminant from a source zone located in a relatively deep, low-permeability formation. A localized 1,1-dichloroethene (DCE) source zone comprising dissolved- and sorbed-phase mass is present in lower permeability strata adjacent to a sand/gravel unit in a section of the Tucson International Airport Area (TIAA) Superfund Site. The results of bench-scale studies conducted using core material collected from boreholes drilled at the site indicated that natural oxidant demand was low, which would promote permanganate persistence. The reactive zone was created by injecting a permanganate solution into multiple wells screened across the interface between the lower-permeability and higher-permeability units. The site has been monitored for nine years to characterize the spatial distribution of DCE and permanganate. Permanganate continues to persist at the site, and a substantial and sustained decrease in DCE concentrations in groundwater has occurred after the permanganate injection.. These results demonstrate successful creation of a long-term, dissolved-phase reactive-treatment zone that reduced mass discharge from the source. This project illustrates the application of in-situ chemical oxidation as a persistent dissolved-phase reactive-treatment system for lower-permeability source zones, which appears to effectively mitigate persistent mass discharge into groundwater. PMID:26300570

The Gap-Startle Paradigm for Tinnitus Screening in Animal Models: Limitations and Optimization

PubMed Central

Lobarinas, Edward; Hayes, Sarah H.; Allman, Brian L.

2012-01-01

In 2006, Turner and colleagues (Behav Neurosci, 120:188–195) introduced the gap-startle paradigm as a high-throughput method for tinnitus screening in rats. Under this paradigm, gap detection ability was assessed by determining the level of inhibition of the acoustic startle reflex produced by a short silent gap inserted in an otherwise continuous background sound prior to a loud startling stimulus. Animals with tinnitus were expected to show impaired gap detection ability (i.e., lack of inhibition of the acoustic startle reflex) if the background sound containing the gap was qualitatively similar to the tinnitus pitch. Thus, for the gap-startle paradigm to be a valid tool to screen for tinnitus, a robust startle response from which to inhibit must be present. Because recent studies have demonstrated that the acoustic startle reflex could be dramatically reduced following noise exposure, we endeavored to 1) modify the gap-startle paradigm to be more resilient in the presence of hearing loss, and 2) evaluate whether a reduction in startle reactivity could confound the interpretation of gap prepulse inhibition and lead to errors in screening for tinnitus. In the first experiment, the traditional broadband noise (BBN) startle stimulus was replaced by a bandpass noise in which the sound energy was concentrated in the lower frequencies (5–10 kHz) in order to maintain audibility of the startle stimulus after unilateral high frequency noise exposure (16 kHz). However, rats still showed a 57% reduction in startle amplitude to the bandpass noise post-noise exposure. A follow-up experiment on a separate group of rats with transiently-induced conductive hearing loss revealed that startle reactivity was better preserved when the BBN startle stimulus was replaced by a rapid airpuff to the back of the rats neck. Furthermore, it was found that transient unilateral conductive hearing loss, which was not likely to induce tinnitus, caused an impairment in gap prepulse inhibition as assessed with the traditional BBN gap-startle paradigm, resulting in a false-positive screening for tinnitus. Thus, the present study identifies significant caveats of the traditional gap-startle paradigm, and describes experimental parameters using an airpuff startle stimulus which may help to limit the negative consequences of reduced startle reactivity following noise exposure, thereby allowing researchers to better screen for tinnitus in animals with hearing loss. PMID:22728305

Reactivity of commercially available monoclonal antibodies to human CD antigens with peripheral blood leucocytes of dromedary camels (Camelus dromedarius)

PubMed Central

Hussen, Jamal; Shawaf, Turke; Al-herz, Abdulkareem Imran; Alturaifi, Hussain R.; Alluwaimi, Ahmed M.

2017-01-01

Monoclonal antibodies (mAbs) to cell surface molecules have been proven as a key tool for phenotypic and functional characterization of the cellular immune response. One of the major difficulties in studying camel cellular immunity consists in the lack of mAbs that dtect their leukocyte differentiation antigens. In the present study two-parameter flow cytometry was used to screen existing commercially available mAbs to human leukocyte antigens and major histocompatibility molecules (MHC) for their reactivity with camel leukocytes. The comparison of patterns of reactivity obtained after labelling human and camel leukocytes have shown that mAbs specific to human cluster of differentiation (CD) 18, CD11a, CD11b and CD14 are predicted to be cross-reactive with homologous camel antigens. PMID:28652982

Congenital syphilis.

PubMed

Cooper, Joshua M; Sánchez, Pablo J

2018-04-01

Congenital syphilis remains a major public health problem worldwide, and its incidence is increasing in the United States. This review highlights the ongoing problem of this preventable infection, and discusses vertical transmission and clinical manifestations while providing a practical algorithm for the evaluation and management of infants born to mothers with reactive serologic tests for syphilis. Every case of congenital syphilis must be seen as a failure of our public health system to provide optimal prenatal care to pregnant women, as congenital syphilis can be prevented by early and repeated prenatal serologic screening of mothers and penicillin treatment of infected women, their sexual partners, and their newborn infants. Copyright © 2018. Published by Elsevier Inc.

Reactive Power Compensation Method Considering Minimum Effective Reactive Power Reserve

NASA Astrophysics Data System (ADS)

Gong, Yiyu; Zhang, Kai; Pu, Zhang; Li, Xuenan; Zuo, Xianghong; Zhen, Jiao; Sudan, Teng

2017-05-01

According to the calculation model of minimum generator reactive power reserve of power system voltage stability under the premise of the guarantee, the reactive power management system with reactive power compensation combined generator, the formation of a multi-objective optimization problem, propose a reactive power reserve is considered the minimum generator reactive power compensation optimization method. This method through the improvement of the objective function and constraint conditions, when the system load growth, relying solely on reactive power generation system can not meet the requirement of safe operation, increase the reactive power reserve to solve the problem of minimum generator reactive power compensation in the case of load node.

Screening and Selection of New Antagonists of the RING-Mediated Hdm2/Hdmx Interaction

DTIC Science & Technology

2012-03-01

NUMBER (include area code) Standard Form 298 (Rev. 8-98) Prescribed by ANSI Std. Z39.18 W81XWH-10-1-0151 Screening and Selection of New ...in which individual bacteria express a different cyclotide. This comprises a new single cell-single compound approach to identify protein-protein... functionally inhibited at multiple steps to reactivate p53 function . Numbered circles indicate potential therapeutical targets for the development of Hdm2

Increased alloimmunisation and transfusion reaction reporting in patients with solid-phase panreactivity.

PubMed

Olofson, Andrea M; Chandler, Rachael M; Marx-Wood, Cynthia R; Babcock, Craig A; Dunbar, Nancy M

2017-11-01

Automated solid-phase antibody screening uses red blood cell (RBC) membranes immobilised on polystyrene test wells to detect RBC specific antibodies. Despite its time-saving and labour-saving benefits, this method produces a higher rate of nonspecific reactivity compared with manual screening. Solid-phase panreactivity (SPP) is characterised by panreactivity (ie, all test cells reacting) in solid-phase testing accompanied by a negative autocontrol and a lack of reactivity when the same screening cells are tested in tube. The mechanisms underlying SPP and its clinical significance remain unclear. The goals of this study were to describe the prevalence of SPP at our institution and determine the alloimmunisation and transfusion reaction rates within this population. Data were collected on all patients undergoing type and screen testing over a 6-year period. Study patients undergoing subsequent transfusion were evaluated for reported transfusion reactions and development of new alloantibodies. Of the 76 051 patients studied, 0.7% demonstrated SPP of which 11% developed new alloantibodies. The transfusion reaction reporting rate among patients with SPP was 2%. Our data suggest that patients with SPP have higher rates of reported transfusion reactions and alloantibody development compared with those without SPP. Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to http://www.bmj.com/company/products-services/rights-and-licensing/.

Chemical Probes for Molecular Imaging and Detection of Hydrogen Sulfide and Reactive Sulfur Species in Biological Systems

PubMed Central

2014-01-01

Hydrogen sulfide (H2S), a gaseous species produced by both bacteria and higher eukaryotic organisms, including mammalian vertebrates, has attracted attention in recent years for its contributions to human health and disease. H2S has been proposed as a cytoprotectant and gasotransmitter in many tissue types, including mediating vascular tone in blood vessels as well as neuromodulation in the brain. The molecular mechanisms dictating how H2S affects cellular signaling and other physiological events remain insufficiently understood. Furthermore, the involvement of H2S in metal-binding interactions and formation of related RSS such as sulfane sulfur may contribute to other distinct signaling pathways. Owing to its widespread biological roles and unique chemical properties, H2S is an appealing target for chemical biology approaches to elucidate its production, trafficking, and downstream function. In this context, reaction-based fluorescent probes offer a versatile set of screening tools to visualize H2S pools in living systems. Three main strategies used in molecular probe development for H2S detection include azide and nitro group reduction, nucleophilic attack, and CuS precipitation. Each of these approaches exploit the strong nucleophilicity and reducing potency of H2S to achieve selectivity over other biothiols. In addition, a variety of methods have been developed for the detection of other reactive sulfur species (RSS), including sulfite and bisulfite, as well as sulfane sulfur species and related modifications such as S-nitrosothiols. Access to this growing chemical toolbox of new molecular probes for H2S and related RSS sets the stage for applying these developing technologies to probe reactive sulfur biology in living systems. PMID:25474627

Evaluation of Immigrant Tuberculosis Screening in Industrialized Countries

PubMed Central

Pareek, Manish; Baussano, Iacopo; Abubakar, Ibrahim; Dye, Christopher

2012-01-01

In industrialized countries, tuberculosis (TB) cases are concentrated among immigrants and driven by reactivation of imported latent TB infection (LTBI). We examined mechanisms used to screen immigrants for TB and LTBI by sending an anonymous, 18-point questionnaire to 31 member countries of the Organisation for Economic Co-operation and Development. Twenty-nine (93.5%) of 31 responded; 25 (86.2%) screened immigrants for active TB. Fewer countries (16/29, 55.2%) screened for LTBI. Marked variations were observed in targeted populations for age (range <5 years of age to all age groups) and TB incidence in countries of origin of immigrants (>20 cases/100,000 population to >500 cases/100,000). LTBI screening was conducted in 11/16 countries by using the tuberculin skin test. Six countries used interferon-γ release assays, primarily to confirm positive tuberculin skin test results. Industrialized countries performed LTBI screening infrequently and policies varied widely. There is an urgent need to define the cost-effectiveness of LTBI screening strategies for immigrants. PMID:22931959

Use of an In Vivo FTA Assay to Assess the Magnitude, Functional Avidity and Epitope Variant Cross-Reactivity of T Cell Responses Following HIV-1 Recombinant Poxvirus Vaccination

PubMed Central

Wijesundara, Danushka K.; Ranasinghe, Charani; Jackson, Ronald J.; Lidbury, Brett A.; Parish, Christopher R.; Quah, Benjamin J. C.

2014-01-01

Qualitative characteristics of cytotoxic CD8+ T cells (CTLs) are important in measuring the effectiveness of CTLs in controlling HIV-1 infections. Indeed, in recent studies patients who are naturally resistant to HIV-1 infections have been shown to possess CTLs that are of high functional avidity and have a high capacity to recognize HIV epitope variants, when compared to HIV-1 infection progressors. When developing efficacious vaccines, assays that can effectively measure CTL quality specifically in vivo are becoming increasingly important. Here we report the use of a recently developed high-throughput multi-parameter technique, known as the fluorescent target array (FTA) assay, to simultaneously measure CTL killing magnitude, functional avidity and epitope variant cross-reactivity in real time in vivo. In the current study we have applied the FTA assay as a screening tool to assess a large cohort of over 20 different HIV-1 poxvirus vaccination strategies in mice. This screen revealed that heterologous poxvirus prime-boost vaccination regimes (i.e., recombinant fowlpox (FPV)-HIV prime followed by a recombinant vaccinia virus (VV)-HIV booster) were the most effective in generating high quality CTL responses in vivo. In conclusion, we have demonstrated how the FTA assay can be utilized as a cost effective screening tool (by reducing the required number of animals by >100 fold), to evaluate a large range of HIV-1 vaccination strategies in terms of CTL avidity and variant cross-reactivity in an in vivo setting. PMID:25170620

Use of an in vivo FTA assay to assess the magnitude, functional avidity and epitope variant cross-reactivity of T cell responses following HIV-1 recombinant poxvirus vaccination.

PubMed

Wijesundara, Danushka K; Ranasinghe, Charani; Jackson, Ronald J; Lidbury, Brett A; Parish, Christopher R; Quah, Benjamin J C

2014-01-01

Qualitative characteristics of cytotoxic CD8+ T cells (CTLs) are important in measuring the effectiveness of CTLs in controlling HIV-1 infections. Indeed, in recent studies patients who are naturally resistant to HIV-1 infections have been shown to possess CTLs that are of high functional avidity and have a high capacity to recognize HIV epitope variants, when compared to HIV-1 infection progressors. When developing efficacious vaccines, assays that can effectively measure CTL quality specifically in vivo are becoming increasingly important. Here we report the use of a recently developed high-throughput multi-parameter technique, known as the fluorescent target array (FTA) assay, to simultaneously measure CTL killing magnitude, functional avidity and epitope variant cross-reactivity in real time in vivo. In the current study we have applied the FTA assay as a screening tool to assess a large cohort of over 20 different HIV-1 poxvirus vaccination strategies in mice. This screen revealed that heterologous poxvirus prime-boost vaccination regimes (i.e., recombinant fowlpox (FPV)-HIV prime followed by a recombinant vaccinia virus (VV)-HIV booster) were the most effective in generating high quality CTL responses in vivo. In conclusion, we have demonstrated how the FTA assay can be utilized as a cost effective screening tool (by reducing the required number of animals by >100 fold), to evaluate a large range of HIV-1 vaccination strategies in terms of CTL avidity and variant cross-reactivity in an in vivo setting.

Clinical and immunological investigations of respiratory disease in workers using reactive dyes.

PubMed Central

Docker, A; Wattie, J M; Topping, M D; Luczynska, C M; Newman Taylor, A J; Pickering, C A; Thomas, P; Gompertz, D

1987-01-01

A questionnaire survey of over 400 workers handling reactive dyes showed that over 15% had work related respiratory or nasal symptoms. Forty nine employees with symptoms were referred to chest clinics for detailed assessment. It was considered that in 19 the symptoms could be attributed to an irritant response to a variety of chemicals, including hydrochloric acid vapour, sulphur dioxide, and reactive dyes. Symptoms in 24 were attributed to an allergic reaction to a specific agent; in most (21) to one or more reactive dyes. Two patterns of allergic lower respiratory symptoms were identified; an immediate response of short duration and a longer lasting response, usually of several hours, sometimes accompanied by nocturnal asthma. A radioallergosorbent test (RAST) screen containing the most commonly used reactive dyes was used to detect specific IgE. Allergic symptoms to reactive dyes were strongly associated with specific IgE (17/21 employees) and atopy (18/21). Irritant symptoms were also associated with atopy (13/19) but only weakly associated with specific IgE (7/19). PMID:3651352

Development of a Persistent Reactive Treatment Zone for Containment of Sources Located in Lower-Permeability Strata

NASA Astrophysics Data System (ADS)

Marble, J.; Carroll, K. C.; Brusseau, M. L.; Plaschke, M.; Brinker, F.

2013-12-01

Source zones located in relatively deep, low-permeability formations provide special challenges for remediation. Application of permeable reactive barriers, in-situ thermal, or electrokinetic methods would be expensive and generally impractical. In addition, the use of enhanced mass-removal approaches based on reagent injection (e.g., ISCO, enhanced-solubility reagents) is likely to be ineffective. One possible approach for such conditions is to create a persistent treatment zone for purposes of containment. This study examines the efficacy of this approach for containment and treatment of contaminants in a lower permeability zone using potassium permanganate (KMnO4) as the reactant. A localized 1,1-dichloroethene (DCE) source zone is present in a section of the Tucson International Airport Area (TIAA) Superfund Site. Characterization studies identified the source of DCE to be located in lower-permeability strata adjacent to the water table. Bench-scale studies were conducted using core material collected from boreholes drilled at the site to measure DCE concentrations and determine natural oxidant demand. The reactive zone was created by injecting ~1.7% KMnO4 solution into multiple wells screened within the lower-permeability unit. The site has been monitored for ~8 years to characterize the spatial distribution of DCE and permanganate. KMnO4 continues to persist at the site, demonstrating successful creation of a long-term reactive zone. Additionally, the footprint of the DCE contaminant plume in groundwater has decreased continuously with time. This project illustrates the application of ISCO as a reactive-treatment system for lower-permeability source zones, which appears to effectively mitigate persistent mass flux into groundwater.

Efficiency of a Malaria Reactive Test-and-Treat Program in Southern Zambia: A Prospective, Observational Study.

PubMed

Deutsch-Feldman, Molly; Hamapumbu, Harry; Lubinda, Jailos; Musonda, Michael; Katowa, Ben; Searle, Kelly M; Kobayashi, Tamaki; Shields, Timothy M; Stevenson, Jennifer C; Thuma, Philip E; Moss, William J; For The Southern Africa International Centers Of Excellence For Malaria Research

2018-05-01

To improve malaria surveillance and achieve elimination, the Zambian National Malaria Elimination Program implemented a reactive test-and-treat program in Southern Province in 2013 in which individuals with rapid diagnostic test (RDT)-confirmed malaria are followed-up at their home within 1 week of diagnosis. Individuals present at the index case household and those residing within 140 m of the index case are tested with an RDT and treated with artemether-lumefantrine if positive. This study evaluated the efficiency of this reactive test-and-treat strategy by characterizing infected individuals missed by the RDT and the current screening radius. The radius was expanded to 250 m, and a quantitative polymerase chain reaction (qPCR) test was performed on dried blood spot specimens. From January 2015 through March 2016, 145 index cases were identified at health centers and health posts. A total of 3,333 individuals residing in 525 households were screened. Excluding index cases, the parasite prevalence was 1.1% by RDT (33 positives of 3,016 participants) and 2.4% by qPCR (73 positives of 3,016 participants). Of the qPCR-positive cases, 62% of 73 individuals tested negative by RDT. Approximately half of the infected individuals resided within the index case household (58% of RDT-positive individuals and 48% of qPCR-positive individuals). The low sensitivity of the RDT and the high proportion of secondary cases within the index case household decreased the efficiency of this reactive test-and-treat strategy. Reactive focal drug administration in index case households would be a more efficient approach to treating infected individuals associated with a symptomatic case.

Ana o 2, a major cashew (Anacardium occidentale L.) nut allergen of the legumin family.

PubMed

Wang, Fang; Robotham, Jason M; Teuber, Suzanne S; Sathe, Shridhar K; Roux, Kenneth H

2003-09-01

We recently cloned and described a vicilin and showed it to be a major cashew allergen. Additional IgE-reactive cashew peptides of the legumin group and 2S albumin families have also been reported. Here, we attempt to clone, express and characterize a second major cashew allergen. A cashew cDNA library was screened with human IgE and rabbit IgG anti-cashew extract antisera, and a reactive nonvicilin clone was sequenced and expressed as a fusion protein in Escherichia coli. Immunoblotting was used to screen for reactivity with patients' sera, and inhibition of immunoblotting was used to identify the corresponding native peptides in cashew nut extract. The identified allergen was subjected to linear epitope mapping using SPOTs solid-phase synthetic peptide technology. Sequence analysis showed the selected clone, designated Ana o 2, to encode for a member of the legumin family (an 11S globulin) of seed storage proteins. By IgE immunoblotting, 13 of 21 sera (62%) from cashew-allergic patients were reactive. Immunoblot inhibition data showed that the native Ana o 2 constitutes a major band at approximately 33 kD and a minor band at approximately 53 kD. Probing of overlapping synthetic peptides with pooled human cashew-allergic sera identified 22 reactive peptides, 7 of which gave strong signals. Several Ana o 2 epitopes were shown to overlap those of the peanut legumin group allergen, Ara h 3, in position but with little sequence similarity. Greater positional overlap and identity was observed between Ana o 2 and soybean glycinin epitopes. We conclude that this legumin-like protein is a major allergen in cashew nut. Copyright 2003 S. Karger AG, Basel

Target discovery of cytotoxic withanolides from Physalis angulata var. villosa via reactivity-based screening.

PubMed

Zhang, Yi; Chen, Chen; Zhang, Ya-Long; Kong, Ling-Yi; Luo, Jian-Guang

2018-03-20

The reactivity-based screening (RBS) was developed for directed discovery of cytotoxic withanolides. In this study, a thiol probe, 4-chlorobenzenethiol, was used to selectively attack cytotoxic withanolides containing potential pharmacophore, 2(3)-en-1-one in ring A (AEO) and 5β,6β-epoxy in ring B (BE), from the plant extract of Physalis angulata var. villosa. The screening was performed based on the potential mechanism of 4-chlorobenzenethiol nucleophilic addition to AEO, followed by detection of adducts using liquid chromatography quadrupole-time-of-flight mass spectrometry (LC-Q-TOF-MS). Guided by RBS, eleven target withanolides, including five new compounds, physagulides R-V (10-14) and six known ones (2, 7-9, 15, 16) were discovered. All of them exhibited cytotoxicity against the both tested cell lines, especially, compounds 2, 7, 8 and 14 showed potent activities with IC 50 values of 1.57-6.29 μM. The results suggested that RBS was efficient and accurate for rapid identification of cytotoxic withanolides and could guide isolation of target components from the complex medicinal plant extract. Copyright © 2018 Elsevier B.V. All rights reserved.

Insight into infection-mediated prostate damage: Contrasting patterns of C-reactive protein and prostate-specific antigen levels during infection.

PubMed

Milbrandt, Melissa; Winter, Anke C; Nevin, Remington L; Pakpahan, Ratna; Bradwin, Gary; De Marzo, Angelo M; Elliott, Debra J; Gaydos, Charlotte A; Isaacs, William B; Nelson, William G; Rifai, Nader; Sokoll, Lori J; Zenilman, Jonathan M; Platz, Elizabeth A; Sutcliffe, Siobhan

2017-05-01

To investigate mechanisms underlying our previous observation of a large rise in serum prostate-specific antigen, a marker of prostate pathology, during both sexually transmitted and systemic infections, we measured serum high-sensitivity C-reactive protein (hsCRP), a marker of systemic inflammation, in our previous case-control study of young, male US military members and compared our findings to those for PSA. We measured hsCRP before and during infection for 299 chlamydia, 112 gonorrhea, and 59 non-chlamydial, non-gonococcal urethritis (NCNGU) cases; before and after infection for 55 infectious mononucleosis (IM) and 90 other systemic/non-genitourinary cases; and for 220-256 controls. Only gonorrhea cases were significantly more likely to have a large hsCRP rise (≥1.40 mg/L or ≥239%) during infection than controls (P < 0.01). However, gonorrhea, IM, and other systemic/non-genitourinary cases were more likely to have a rise of any magnitude up to one year post-diagnosis than controls (p = 0.038-0.077). These findings, which differ from those for PSA, suggest distinct mechanisms of elevation for hsCRP and PSA, and support both direct (eg, prostate infection) and indirect (eg, systemic inflammation-mediated prostate cell damage) mechanisms for PSA elevation. Future studies should explore our PSA findings further for their relevance to both prostate cancer screening and risk. © 2017 Wiley Periodicals, Inc.

Detection of Total Phenol in Green and Black Teas by Flow Injection System and Unmodified Screen Printed Electrode

PubMed Central

de Mattos, Ivanildo Luiz; Zagal, José Heraclito

2010-01-01

A flow injection system using an unmodified gold screen-printed electrode was employed for total phenol determination in black and green teas. In order to avoid passivation of the electrode surface due to the redox reaction, preoxidation of the sample was realized by hexacyanoferrate(III) followed by addition of an EDTA solution. The complex formed in the presence of EDTA minimizes or avoids polymerization of the oxidized phenols. The previously filtered tea sample and hexacyanoferrate(III) reagent were introduced simultaneously into two-carrier streams producing two reproducible zones. At confluence point, the pre-oxidation of the phenolic compounds occurs while this zone flows through the coiled reactor and receives the EDTA solution before phenol detection. The consumption of ferricyanide was monitorized at 360 mV versus Ag/AgCl and reflected the total amount of phenolic compounds present in the sample. Results were reported as gallic acid equivalents (GAEs). The proposed system is robust, versatile, environmentally-friendly (since the reactive is used only in the presence of the sample), and allows the analysis of about 35–40 samples per hour with detection limit = 1 mg/L without the necessity for surface cleaning after each measurement. Precise results are in agreement with those obtained by the Folin-Ciocalteu method. PMID:21461407

Reactive trace gas emissions from stressed plants: a poorly characterized major source of atmospheric volatiles

NASA Astrophysics Data System (ADS)

Niinemets, Ülo

2017-04-01

Vegetation constitutes the greatest source of reactive volatile organic compounds in the atmosphere. The current emission estimates primarily rely on constitutive emissions that are present only in some plant species. However, all plant species can be induced to emit reactive volatiles by different abiotic and biotic stresses, but the stress-dependent emissions have been largely neglected in emission measurements and models. This presentation provides an overview of systematic screening of stress-dependent volatile emissions from a broad range of structurally and physiologically divergent plant species from temperate to tropical ecosystems. Ozone, heat, drought and wounding stress were the abiotic stresses considered in the screening, while biotic stress included herbivory, chemical elicitors simulating herbivory and fungal infections. The data suggest that any moderate to severe stress leads to significant emissions of a rich blend of volatiles, including methanol, green leaf volatiles (the lipoxygenase pathway volatiles, dominated by C6 aldehydes, alcohols and derivatives), different mono- and sesquiterpenes and benzenoids. The release of volatiles occurs in stress severity-dependent manner, although the emission responses are often non-linear with more severe stresses resulting in disproportionately greater emissions. Stress volatile release is induced in both non-constitutive and constitutive volatile emitters, whereas the rate of constitutive volatile emissions in constitutive emitters is often reduced under environmental and biotic stresses. Given that plants in natural conditions often experience stress, this analysis suggests that global volatile emissions have been significantly underestimated. Furthermore, in globally changing hotter climates, the frequency and severity of both abiotic and biotic stresses is expected to increase. Thus, the stress-induced volatile emissions are predicted to play a dominant role in plant-atmosphere interactions in near future. Quantitative models that link stress severity, plant volatile emissions and climatic feedbacks are currently being developed, and this presentation argues that incorporating stress-dependent feedbacks in Earth system models in inevitable to simulate future climates.

The association between C-reactive protein levels and the risk for chronic kidney disease hospitalizations in adults of a remote Indigenous Australian community - A prospective cohort study.

PubMed

Arnold, Luke W; Hoy, Wendy E; Wang, Zhiqiang

2017-09-01

Indigenous Australians are significantly burdened by chronic kidney disease (CKD). Elevated levels of C-reactive protein (CRP) have been associated with diabetes and cardiovascular incidence in previous studies. Elevated CRP has been associated with albuminuria and reduced eGFR in cross-sectional studies. This study investigated the long-term predictive association between CRP measured at a baseline exam and the incidence of a CKD-related hospitalization. Health screening examinations were conducted in individuals of a remote indigenous Australian community between 1992 and 1998. The risk of subsequent CKD hospitalisations, documented through Northern Territory hospital records up to 2010, was estimated with Cox proportional hazard models in people aged over 18 years at the baseline screen and who had albumin-creatinine ratios (ACRs) less than 34g/mol. 546 participants were eligible for our study. Individuals in the highest CRP tertile at baseline had increased levels of traditional cardiovascular risk factors. They also had almost 4 times the risk of a CKD-related hospitalisation compared with participants in the lowest CRP tertile (HR=3.91, 95%CI 1.01-15.20, P=0.049) after adjustment for potential confounding factors. Participants with CRP concentrations greater than 3mg/L had almost 3 times the risk of CKD hospitalisations than those ≤3mg/L (HR=2.84, 95%CI 1.00-8.00, P=0.049). Furthermore, risk of CKD hospitalisations increased 34% per doubling of baseline CRP (HR=1.34, 95%CI 1.04-1.74, P=0.024). In individuals in this remote indigenous community without overt albuminuria at baseline the risk for incident CKD related hospitalisations was predicted by elevated C-reactive protein levels almost a decade earlier. Further research is needed to understand the roles that CRP and systemic inflammation play in CKD risk. © 2016 Asian Pacific Society of Nephrology.

Syphilis in adults

PubMed Central

Goh, B

2005-01-01

Syphilis is a sexually transmitted disease with protean manifestations resulting from infection by Treponema pallidum. It is systemic early from the outset, the primary pathology being vasculitis. Acquired syphilis can be divided into primary, secondary, latent, and tertiary stages. The infection can also be transmitted vertically resulting in congenital syphilis, and occasionally by blood transfusion and non-sexual contact. Diagnosis is mainly by dark field microscopy in early syphilis and by serological tests. The management in the tropics depends on the diagnostic facilities available: in resource poor countries, primary syphilis is managed syndromically as for anogenital ulcer. The introduction of rapid "desktop" serological tests may simplify and promote widespread screening for syphilis. The mainstay of treatment is with long acting penicillin. Syphilis promotes the transmission of HIV and both infections can simulate and interact with each other. Treponemes may persist despite effective treatment and may have a role in reactivation in immunosuppressed patients. Partner notification, health education, and screening in high risk populations and pregnant women to prevent congenital syphilis are essential aspects in controlling the infection. PMID:16326843

A screening tool to prioritize public health risk associated with accidental or deliberate release of chemicals into the atmosphere

PubMed Central

2013-01-01

The Chemical Events Working Group of the Global Health Security Initiative has developed a flexible screening tool for chemicals that present a risk when accidentally or deliberately released into the atmosphere. The tool is generic, semi-quantitative, independent of site, situation and scenario, encompasses all chemical hazards (toxicity, flammability and reactivity), and can be easily and quickly implemented by non-subject matter experts using freely available, authoritative information. Public health practitioners and planners can use the screening tool to assist them in directing their activities in each of the five stages of the disaster management cycle. PMID:23517410

Cross-Reactivity of Pantoprazole with Three Commercial Cannabinoids Immunoassays in Urine.

PubMed

Gomila, Isabel; Barceló, Bernardino; Rosell, Antonio; Avella, Sonia; Sahuquillo, Laura; Dastis, Macarena

2017-11-01

Pantoprazole is a frequently prescribed proton pump inhibitor (PPI) commonly utilized in the management of gastrointestinal symptoms. Few substances have proved to cause a false-positive cannabinoid urine screen. However, a case of false-positive urine cannabinoid screen in a patient who received a pantoprazole dose has been recently published. The purpose of this study was to determine the potential cross-reactivity of pantoprazole in the cannabinoid immunoassays: Alere Triage® TOX Drug Screen, KIMS® Cannabinoids II and DRI® Cannabinoids Assay. Drug-free urine to which pantoprazole was added up to 12,000 μg/mL produced negative results in the DRI® Cannabinoids and KIMS® Cannabinoids II. Alere Triage® TOX Drug Screen assay gave positive results at pantoprazole concentrations higher than 1,000 μg/mL. Urine samples from 8 pediatric patients were collected at the beginning of their pantoprazole treatment. Alere Triage® TOX Drug Screen assay produced positive test results in all patient samples and KIMS® Cannabinoids II immunoassay produced positive test results in one patient sample. None patient sample gave a false-positive result when analyzed by the DRI® Cannabinoids Assay. Our findings demonstrate that some cannabinoids immunoassays are susceptible to cross-reaction errors resulting from the presence in urine of pantoprazole and the resulting metabolism of the parent drug. Clinicians should be aware of the possibility of false-positive results for cannabinoids after a pantoprazole treatment. © The Author 2017. Published by Oxford University Press. All rights reserved. For Permissions, please email: journals.permissions@oup.com.

Mono-oxime bisquaternary acetylcholinesterase reactivators with prop-1,3-diyl linkage-Preparation, in vitro screening and molecular docking.

PubMed

Musilek, Kamil; Komloova, Marketa; Holas, Ondrej; Horova, Anna; Pohanka, Miroslav; Gunn-Moore, Frank; Dohnal, Vlastimil; Dolezal, Martin; Kuca, Kamil

2011-01-15

The treatment of organophosphorus (OP) poisoning consists of the administration of a parasympatholytic agent (e.g., atropine), an anticonvulsant (e.g., diazepam) and an acetylcholinesterase (AChE) reactivator (e.g., obidoxime). The AChE reactivator is the causal treatment of OP exposure, because it cleaves the OP moiety covalently bound to the AChE active site. In this paper, fourteen novel AChE reactivators are described. Their design originated from a former promising compound K027. These compounds were synthesized, evaluated in vitro on human AChE (hAChE) inhibited by tabun, paraoxon, methylparaoxon and DFP and then compared to commercial hAChE reactivators (pralidoxime, HI-6, trimedoxime, obidoxime, methoxime) or previously prepared compounds (K027, K203). Three of these novel compounds showed a promising ability to reactivate hAChE comparable or better than the used standards. Consequently, a molecular docking study was performed for three of these promising novel compounds. The docking results confirmed the apparent influence of π-π or cation-π interactions and hydrogen bonding for reactivator binding within the hAChE active site cleft. The SAR features concerning the non-oxime part of the reactivator molecule are also discussed. Copyright © 2010 Elsevier Ltd. All rights reserved.

A pilot study on screening blood donors with individual-donation nucleic acid testing in China

PubMed Central

Dong, Jie; Wu, Yaling; Zhu, Hong; Li, Gan; Lv, Mengen; Wu, Daxiao; Li, Xiaotao; Zhu, Faming; Lv, Hangjun

2014-01-01

Background Nucleic acid amplification testing (NAT) is not yet obligatory in China for blood donor screening and the risk of enzyme immunoassay (EIA)-negative, NAT-reactive donations in Chinese blood donors has rarely been reported. The aim of this study was to screen a population of Chinese blood donors using a triplex individual-donation (ID)-NAT assay and assess the safety benefits of implementing NAT. Materials and methods Between 1st August, 2010 and 31st December, 2011 all donations at a Chinese blood centre were screened individually using the Procleix® Ultrio® assay, a multiplex NAT assay for the detection of hepatitis B virus (HBV) DNA, hepatitis C virus (HCV) RNA and human immunodeficiency virus-1 (HIV-1) RNA. All donations were also screened for HBsAg, anti-HIV and anti-HCV using two different EIA for each marker. Samples with discordant results between NAT and EIA were further tested with an alternative NAT assay (Cobas® TaqMan®). Potential yield cases (serologically negative/NAT-reactive donors) were further evaluated when possible. Results During the study period a total of 178,447 donations were screened by NAT and EIA, among which 169 HBV NAT yield cases (0.095%) were detected. No N AT yield cases were found for HIV-1 or HCV. For the HBV NAT yield cases, follow-up results showed that 11 (6.51%) were probable or confirmed HBV window period infections, 5 (2.96%) were chronic HBV carriers and 153 (90.53%) were probable or confirmed occult HBV infections. There was a statistically significant difference between the NAT-positive rates for first-time vs repeat donations (0.472% vs 0.146%, respectively; P<0.001). Discussion Our data demonstrate that the potential HBV yield rate was 1:1,056 for blood donations in the Zhejiang province of China. Implementation of NAT will provide a significant increment in safety relative to serological screening alone. PMID:24333061

Investigational Testing for Zika Virus among U.S. Blood Donors.

PubMed

Saá, Paula; Proctor, Melanie; Foster, Gregory; Krysztof, David; Winton, Colleen; Linnen, Jeffrey M; Gao, Kui; Brodsky, Jaye P; Limberger, Ronald J; Dodd, Roger Y; Stramer, Susan L

2018-05-10

Because of the potential severe clinical consequences of Zika virus (ZIKV) infection, the large numbers of asymptomatic travelers returning from ZIKV-active areas, the detection of ZIKV nucleic acid in blood, and reports of transmission of ZIKV through transfusion, in 2016 the Food and Drug Administration released recommendations for individual-unit nucleic acid testing to minimize the risk of transmission of ZIKV through blood transfusions. The American Red Cross implemented investigational screening of donated blood for ZIKV RNA by means of transcription-mediated amplification (TMA). Confirmatory testing of reactive donations involved repeat TMA, TMA testing in exploratory minipools, real-time reverse-transcriptase polymerase chain reaction, IgM serologic testing, and red-cell TMA. Viral loads in plasma and red cells were estimated by means of end-point TMA. The costs of interdicting a donation that was confirmed to be positive were calculated for the 15-month period between June 2016 and September 2017. Of the 4,325,889 donations that were screened, 393,713 (9%) were initially tested in 24,611 minipools, and no reactive donations were found. Of the 3,932,176 donations that were subsequently tested individually, 160 were initially reactive and 9 were confirmed positive (a 1:480,654 confirmed-positive rate overall; positive predictive value, 5.6%; specificity, 99.997%). Six (67%) of the confirmed-positive donations were reactive on repeat TMA, of which 4 were IgM-negative; of these 4, all 3 that could be tested were reactive on minipool TMA. Two confirmed-positive donors had infections that had been transmitted locally (in Florida), 6 had traveled to ZIKV-active areas, and 1 had received an experimental ZIKV vaccine. ZIKV RNA levels in red cells ranged from 40 to 800,000 copies per milliliter and were detected up to 154 days after donation, as compared with 80 days of detection in plasma at levels of 12 to 20,000 copies per milliliter. On the basis of industry-reported costs of testing and the yield of the tests in our study, the cost of identifying 8 mosquito-borne ZIKV infections through individual-unit nucleic acid testing was $5.3 million per ZIKV RNA-positive donation. Screening of U.S. blood donations for ZIKV by individual-donation TMA was costly and had a low yield. Among the 9 confirmed ZIKV-positive donations, only 4 were IgM-negative; of these donations, all 3 that were tested were reactive on minipool TMA. (Funded by the American Red Cross and Grifols Diagnostic Solutions.).

[From the "screen" society to concern for future generations].

PubMed

Le Coz, Pierre

2015-01-01

The youth of today is evolving in an unprecedented sociocultural context marked by the rapid development of new virtual technologies. Young people are constantly looking at screens, big and small, tactile and digital, which have invaded their social sphere. Connected, logged on, overstimulated, the new generation lives surrounded by reactivity and electronic interactions. It is adults' responsibility to expand the range of their cultural and outdoor activities in order to avoid the risk of their capacity for personal expression wasting away.

SUBCELLULAR PHARMACOKINETICS AND ITS POTENTIAL FOR LIBRARY FOCUSING (R826652)

EPA Science Inventory

Abstract

Subcellular pharmacokinetics (SP) optimizes biology-related factors in the design of libraries for high throughput screening by defining comparatively narrow ranges of properties (lipophilicity, amphiphilicity, acidity, reactivity, 3D-structural features) of t...

Chemical Safety Alert: Identifying Chemical Reactivity Hazards Preliminary Screening Method

EPA Pesticide Factsheets

Introduces small-to-medium-sized facilities to a method developed by Center for Chemical Process Safety (CCPS), based on a series of twelve yes-or-no questions to help determine hazards in warehousing, repackaging, blending, mixing, and processing.

Quantitative data on the magnitude of the systemic inflammatory response and its effect on micronutrient status based on plasma measurements.

PubMed

Duncan, Andrew; Talwar, Dinesh; McMillan, Donald C; Stefanowicz, Fiona; O'Reilly, Denis St J

2012-01-01

Plasma concentrations of several trace elements and vitamins decrease because of the systemic inflammatory response. Thus, low values do not necessarily indicate deficiency. The magnitude of this effect on plasma micronutrient concentrations was investigated to provide guidance on the interpretation of routine clinical results. Between 2001 and 2011, the results (2217 blood samples from 1303 patients) of routine micronutrient screens (plasma zinc, copper, selenium, and vitamins A, B-6, C, and E) and all vitamin D results (4327 blood samples from 3677 patients) were extracted from the laboratory database. C-reactive protein concentrations were measured as a marker of the severity of inflammation and categorized into 6 groups; for each group, plasma micronutrient concentrations and percentage changes were calculated. Except for copper and vitamin E, all plasma micronutrient concentrations decreased with increasing severities of the acute inflammatory response. For selenium and vitamins B-6 and C, this occurred with only slightly increased C-reactive protein concentrations of 5 to 10 mg/L. For each micronutrient, the change in plasma concentrations varied markedly from patient to patient. The magnitude of the effect was greatest for selenium and vitamins A, B-6, C, and D, for which the median plasma concentrations decreased by >40%. The clinical interpretation of plasma micronutrients can be made only with knowledge of the degree of inflammatory response. A reliable clinical interpretation can be made only if the C-reactive protein is <20 mg/L (plasma zinc), <10 mg/L (plasma selenium and vitamins A and D), or <5 mg/L (vitamins B-6 and C).

Characterization of Francisella tularensis Schu S4 mutants identified from a transposon library screened for O-antigen and capsule deficiencies

PubMed Central

Rasmussen, Jed A.; Fletcher, Joshua R.; Long, Matthew E.; Allen, Lee-Ann H.; Jones, Bradley D.

2015-01-01

The lipopolysaccharide (LPS) and O-antigen polysaccharide capsule structures of Francisella tularensis play significant roles in helping these highly virulent bacteria avoid detection within a host. We previously created pools of F. tularensis mutants that we screened to identify strains that were not reactive to a monoclonal antibody to the O-antigen capsule. To follow up previously published work, we characterize further seven of the F. tularensis Schu S4 mutant strains identified by our screen. These F. tularensis strains carry the following transposon mutations: FTT0846::Tn5, hemH::Tn5, wbtA::Tn5, wzy::Tn5, FTT0673p/prsA::Tn5, manB::Tn5, or dnaJ::Tn5. Each of these strains displayed sensitivity to human serum, to varying degrees, when compared to wild-type F. tularensis Schu S4. By Western blot, only FTT0846::Tn5, wbtA::Tn5, wzy::Tn5, and manB::Tn5 strains did not react to the capsule and LPS O-antigen antibody 11B7, although the wzy::Tn5 strain did have a single O-antigen reactive band that was detected by the FB11 monoclonal antibody. Of these strains, manB::Tn5 and FTT0846 appear to have LPS core truncations, whereas wbtA::Tn5 and wzy::Tn5 had LPS core structures that are similar to the parent F. tularensis Schu S4. These strains were also shown to have poor growth within human monocyte derived macrophages (MDMs) and bone marrow derived macrophages (BMDMs). We examined the virulence of these strains in mice, following intranasal challenge, and found that each was attenuated compared to wild type Schu S4. Our results provide additional strong evidence that LPS and/or capsule are F. tularensis virulence factors that most likely function by providing a stealth shield that prevents the host immune system from detecting this potent pathogen. PMID:25999917

Serodiagnosis of Echinococcus spp. Infection: Explorative Selection of Diagnostic Antigens by Peptide Microarray

PubMed Central

List, Claudia; Qi, Weihong; Maag, Eva; Gottstein, Bruno; Müller, Norbert; Felger, Ingrid

2010-01-01

Background Production of native antigens for serodiagnosis of helminthic infections is laborious and hampered by batch-to-batch variation. For serodiagnosis of echinococcosis, especially cystic disease, most screening tests rely on crude or purified Echinococcus granulosus hydatid cyst fluid. To resolve limitations associated with native antigens in serological tests, the use of standardized and highly pure antigens produced by chemical synthesis offers considerable advantages, provided appropriate diagnostic sensitivity and specificity is achieved. Methodology/Principal Findings Making use of the growing collection of genomic and proteomic data, we applied a set of bioinformatic selection criteria to a collection of protein sequences including conceptually translated nucleotide sequence data of two related tapeworms, Echinococcus multilocularis and Echinococcus granulosus. Our approach targeted alpha-helical coiled-coils and intrinsically unstructured regions of parasite proteins potentially exposed to the host immune system. From 6 proteins of E. multilocularis and 5 proteins of E. granulosus, 45 peptides between 24 and 30 amino acids in length were designed. These peptides were chemically synthesized, spotted on microarrays and screened for reactivity with sera from infected humans. Peptides reacting above the cut-off were validated in enzyme-linked immunosorbent assays (ELISA). Peptides identified failed to differentiate between E. multilocularis and E. granulosus infection. The peptide performing best reached 57% sensitivity and 94% specificity. This candidate derived from Echinococcus multilocularis antigen B8/1 and showed strong reactivity to sera from patients infected either with E. multilocularis or E. granulosus. Conclusions/Significance This study provides proof of principle for the discovery of diagnostically relevant peptides by bioinformatic selection complemented with screening on a high-throughput microarray platform. Our data showed that a single peptide cannot provide sufficient diagnostic sensitivity whereas pooling several peptide antigens improved sensitivity; thus combinations of several peptides may lead the way to new diagnostic tests that replace, or at least complement conventional immunodiagnosis of echinococcosis. Our strategy could prove useful for diagnostic developments in other pathogens. PMID:20689813

Novel cell-based assay for detection of thyroid receptor beta-interacting environmental contaminants.

PubMed

Stavreva, Diana A; Varticovski, Lyuba; Levkova, Ludmila; George, Anuja A; Davis, Luke; Pegoraro, Gianluca; Blazer, Vicki; Iwanowicz, Luke; Hager, Gordon L

2016-08-10

Even though the presence of endocrine disrupting chemicals (EDCs) with thyroid hormone (TH)-like activities in the environment is a major health concern, the methods for their efficient detection and monitoring are still limited. Here we describe a novel cell assay, based on the translocation of a green fluorescent protein (GFP)-tagged chimeric molecule of glucocorticoid receptor (GR) and the thyroid receptor beta (TRβ) from the cytoplasm to the nucleus in the presence of TR ligands. Unlike the constitutively nuclear TRβ, this GFP-GR-TRβ chimera is cytoplasmic in the absence of hormone while translocating to the nucleus in a time- and concentration-dependent manner upon stimulation with triiodothyronine (T3) and thyroid hormone analogue, TRIAC, while the reverse triiodothyronine (3,3',5'-triiodothyronine, or rT3) was inactive. Moreover, GFP-GR-TRβ chimera does not show any cross-reactivity with the GR-activating hormones, thus providing a clean system for the screening of TR beta-interacting EDCs. Using this assay, we demonstrated that Bisphenol A (BPA) and 3,3',5,5'-Tetrabromobisphenol (TBBPA) induced GFP-GR-TRβ translocation at micro molar concentrations. We screened over 100 concentrated water samples from different geographic locations in the United States and detected a low, but reproducible contamination in 53% of the samples. This system provides a novel high-throughput approach for screening for endocrine disrupting chemicals (EDCs) interacting with TR beta. Published by Elsevier Ireland Ltd.

Novel cell-based assay for detection of thyroid receptor beta-interacting environmental contaminants

USGS Publications Warehouse

Stavreva, Diana A.; Varticovski, Lyuba; Levkova, Ludmila; George, Anuja A.; Davis, Luke; Pegoraro, Gianluca; Blazer, Vicki S.; Iwanowicz, Luke R.; Hager, Gordon L.

2016-01-01

Even though the presence of endocrine disrupting chemicals (EDCs) with thyroid hormone (TH)-like activities in the environment is a major health concern, the methods for their efficient detection and monitoring are still limited. Here we describe a novel cell assay, based on the translocation of a green fluorescent protein (GFP)—tagged chimeric molecule of glucocorticoid receptor (GR) and the thyroid receptor beta (TRβ) from the cytoplasm to the nucleus in the presence of TR ligands. Unlike the constitutively nuclear TRβ, this GFP-GR-TRβ chimera is cytoplasmic in the absence of hormone while translocating to the nucleus in a time- and concentration-dependent manner upon stimulation with triiodothyronine (T3) and thyroid hormone analogue, TRIAC, while the reverse triiodothyronine (3,3′,5′-triiodothyronine, or rT3) was inactive. Moreover, GFP-GR-TRβ chimera does not show any cross-reactivity with the GR-activating hormones, thus providing a clean system for the screening of TR beta-interacting EDCs. Using this assay, we demonstrated that Bisphenol A (BPA) and 3,3′,5,5′-Tetrabromobisphenol (TBBPA) induced GFP-GR-TRβ translocation at micro molar concentrations. We screened over 100 concentrated water samples from different geographic locations in the United States and detected a low, but reproducible contamination in 53% of the samples. This system provides a novel high-throughput approach for screening for endocrine disrupting chemicals (EDCs) interacting with TR beta.

Novel cell-based assay for detection of thyroid receptor beta-interacting environmental contaminants

PubMed Central

Stavreva, Diana A.; Varticovski, Lyuba; Levkova, Ludmila; George, Anuja A.; Davis, Luke; Pegoraro, Gianluca; Blazer, Vicki; Iwanowicz, Luke; Hager, Gordon L.

2016-01-01

Even though the presence of endocrine disrupting chemicals (EDCs) with thyroid hormone (TH)-like activities in the environment is a major health concern, the methods for their efficient detection and monitoring are still limited. Here we describe a novel cell assay, based on the translocation of a green fluorescent protein (GFP) - tagged chimeric molecule of glucocorticoid receptor (GR) and the thyroid receptor beta (TRβ) from the cytoplasm to the nucleus in the presence of TR ligands. Unlike the constitutively nuclear TRβ, this GFP-GR-TRβ chimera is cytoplasmic in the absence of hormone while translocating to the nucleus in a time- and concentration-dependent manner upon stimulation with triiodothyronine (T3) and thyroid hormone analogue, TRIAC, while the reverse triiodothyronine (3,3′,5′-triiodothyronine, or rT3) was inactive. Moreover, GFP-GR-TRβ chimera does not show any cross-reactivity with the GR-activating hormones, thus providing a clean system for the screening of TR beta -interacting EDCs. Using this assay, we demonstrated that Bisphenol A (BPA) and 3,3′,5,5′-Tetrabromobisphenol (TBBPA) induced GFP-GR-TRβ translocation at micro molar concentrations. We screened over 100 concentrated water samples from different geographic locations in the United States and detected a low, but reproducible contamination in 53 % of the samples. This system provides a novel high-throughput approach for screening for endocrine disrupting chemicals (EDCs) interacting with TR beta. PMID:27528272

Discovery of host-targeted covalent inhibitors of dengue virus

PubMed Central

de Wispelaere, Mélissanne; Carocci, Margot; Liang, Yanke; Liu, Qingsong; Sun, Eileen; Vetter, Michael L.; Wang, Jinhua; Gray, Nathanael S.; Yang, Priscilla L.

2017-01-01

We report here on an approach targeting the host reactive cysteinome to identify inhibitors of host factors required for the infectious cycle of Flaviviruses and other viruses. We used two parallel cellular phenotypic screens to identify a series of covalent inhibitors, exemplified by QL-XII-47, that are active against dengue virus. We show that the compounds effectively block viral protein expression and that this inhibition is associated with repression of downstream processes of the infectious cycle, and thus significantly contributes to the potent antiviral activity of these compounds. We demonstrate that QL-XII-47’s antiviral activity requires selective, covalent modification of a host target by showing that the compound's antiviral activity is recapitulated when cells are preincubated with QL-XII-47 and then washed prior to viral infection and by showing that QL-XII-47R, a non-reactive analog, lacks antiviral activity at concentrations more than 20-fold higher than QL-XII-47's IC90. QL-XII-47’s inhibition of Zika virus, West Nile virus, hepatitis C virus, and poliovirus further suggests that it acts via a target mediating inhibition of these other medically relevant viruses. These results demonstrate the utility of screens targeting the host reactive cysteinome for rapid identification of compounds with potent antiviral activity. PMID:28034743

Differences in tuberculin reactivity as determined in a veterans administration employee health screening program.

PubMed

Mehta, Sanjay R; MacGruder, Cathy; Looney, David; Johns, Scott; Smith, Davey M

2009-04-01

In response to a difference in pricing, the San Diego Veterans Administration Medical Center changed its tuberculin preparation from Tubersol to Aplisol in the fall of 2006. Following the change, an increased number of employee skin test conversions was noted. Employee tuberculin skin test converters from 2006 were screened with the QuantiFERON Gold (QFT-G) gamma interferon release assay. Those employees who tested negative by QFT-G were asked to repeat their skin test with both Tubersol and Aplisol tuberculin preparations. Of the new purified protein derivative converters, 12 of 14 returned for repeat testing with QFT-G, and the assay was negative for 83% (10/12), positive for 8% (1/12), and indeterminate for 8% (1/12) of the individuals. Nine of the individuals who were QFT-G negative agreed to repeat skin testing with both tuberculin preparations, and 7/8 (87.5%) demonstrated reactivity with the Aplisol preparation, while 0/8 (0%) reacted to the Tubersol preparation. A change from Tubersol to Aplisol resulted in elevated tuberculin skin test conversion rates that may be due to false-positive reactions. The differences in skin test reactivity between preparations support CDC guidelines that recommend that institutions should not change tuberculin preparations, as doing so may falsely increase the number of positive reactions.

21 CFR 610.41 - Donor deferral.

Code of Federal Regulations, 2012 CFR

2012-04-01

... §§ 610.46 and 610.47 when a donor tests reactive by a screening test for HIV or HCV required under § 610... evidence of HIV or HCV infection. [66 FR 31164, June 11, 2001, as amended at 72 FR 48798, Aug. 24, 2007] ...

21 CFR 610.41 - Donor deferral.

Code of Federal Regulations, 2014 CFR

2014-04-01

... §§ 610.46 and 610.47 when a donor tests reactive by a screening test for HIV or HCV required under § 610... evidence of HIV or HCV infection. [66 FR 31164, June 11, 2001, as amended at 72 FR 48798, Aug. 24, 2007] ...

21 CFR 610.41 - Donor deferral.

Code of Federal Regulations, 2011 CFR

2011-04-01

... §§ 610.46 and 610.47 when a donor tests reactive by a screening test for HIV or HCV required under § 610... evidence of HIV or HCV infection. [66 FR 31164, June 11, 2001, as amended at 72 FR 48798, Aug. 24, 2007] ...

21 CFR 610.41 - Donor deferral.

Code of Federal Regulations, 2013 CFR

2013-04-01

... §§ 610.46 and 610.47 when a donor tests reactive by a screening test for HIV or HCV required under § 610... evidence of HIV or HCV infection. [66 FR 31164, June 11, 2001, as amended at 72 FR 48798, Aug. 24, 2007] ...

ToxAlerts: a Web server of structural alerts for toxic chemicals and compounds with potential adverse reactions.

PubMed

Sushko, Iurii; Salmina, Elena; Potemkin, Vladimir A; Poda, Gennadiy; Tetko, Igor V

2012-08-27

The article presents a Web-based platform for collecting and storing toxicological structural alerts from literature and for virtual screening of chemical libraries to flag potentially toxic chemicals and compounds that can cause adverse side effects. An alert is uniquely identified by a SMARTS template, a toxicological endpoint, and a publication where the alert was described. Additionally, the system allows storing complementary information such as name, comments, and mechanism of action, as well as other data. Most importantly, the platform can be easily used for fast virtual screening of large chemical datasets, focused libraries, or newly designed compounds against the toxicological alerts, providing a detailed profile of the chemicals grouped by structural alerts and endpoints. Such a facility can be used for decision making regarding whether a compound should be tested experimentally, validated with available QSAR models, or eliminated from consideration altogether. The alert-based screening can also be helpful for an easier interpretation of more complex QSAR models. The system is publicly accessible and tightly integrated with the Online Chemical Modeling Environment (OCHEM, http://ochem.eu). The system is open and expandable: any registered OCHEM user can introduce new alerts, browse, edit alerts introduced by other users, and virtually screen his/her data sets against all or selected alerts. The user sets being passed through the structural alerts can be used at OCHEM for other typical tasks: exporting in a wide variety of formats, development of QSAR models, additional filtering by other criteria, etc. The database already contains almost 600 structural alerts for such endpoints as mutagenicity, carcinogenicity, skin sensitization, compounds that undergo metabolic activation, and compounds that form reactive metabolites and, thus, can cause adverse reactions. The ToxAlerts platform is accessible on the Web at http://ochem.eu/alerts, and it is constantly growing.

ToxAlerts: A Web Server of Structural Alerts for Toxic Chemicals and Compounds with Potential Adverse Reactions

PubMed Central

2012-01-01

The article presents a Web-based platform for collecting and storing toxicological structural alerts from literature and for virtual screening of chemical libraries to flag potentially toxic chemicals and compounds that can cause adverse side effects. An alert is uniquely identified by a SMARTS template, a toxicological endpoint, and a publication where the alert was described. Additionally, the system allows storing complementary information such as name, comments, and mechanism of action, as well as other data. Most importantly, the platform can be easily used for fast virtual screening of large chemical datasets, focused libraries, or newly designed compounds against the toxicological alerts, providing a detailed profile of the chemicals grouped by structural alerts and endpoints. Such a facility can be used for decision making regarding whether a compound should be tested experimentally, validated with available QSAR models, or eliminated from consideration altogether. The alert-based screening can also be helpful for an easier interpretation of more complex QSAR models. The system is publicly accessible and tightly integrated with the Online Chemical Modeling Environment (OCHEM, http://ochem.eu). The system is open and expandable: any registered OCHEM user can introduce new alerts, browse, edit alerts introduced by other users, and virtually screen his/her data sets against all or selected alerts. The user sets being passed through the structural alerts can be used at OCHEM for other typical tasks: exporting in a wide variety of formats, development of QSAR models, additional filtering by other criteria, etc. The database already contains almost 600 structural alerts for such endpoints as mutagenicity, carcinogenicity, skin sensitization, compounds that undergo metabolic activation, and compounds that form reactive metabolites and, thus, can cause adverse reactions. The ToxAlerts platform is accessible on the Web at http://ochem.eu/alerts, and it is constantly growing. PMID:22876798

Application of synthetic peptides for detection of anti-citrullinated peptide antibodies.

PubMed

Trier, Nicole Hartwig; Holm, Bettina Eide; Slot, Ole; Locht, Henning; Lindegaard, Hanne; Svendsen, Anders; Nielsen, Christoffer Tandrup; Jacobsen, Søren; Theander, Elke; Houen, Gunnar

2016-02-01

Anti-citrullinated protein antibodies (ACPAs) are a hallmark of rheumatoid arthritis (RA) and represent an important tool for the serological diagnosis of RA. In this study, we describe ACPA reactivity to overlapping citrullinated Epstein-Barr virus nuclear antigen-1 (EBNA-1)-derived peptides and analyze their potential as substrates for ACPA detection by streptavidin capture enzyme-linked immunosorbent assay. Using systematically overlapping peptides, containing a 10 amino acid overlap, labelled with biotin C-terminally or N-terminally, sera from 160 individuals (RA sera (n=60), healthy controls (n=40), systemic lupus erythematosus (n=20), Sjögren's syndrome (n=40)) were screened for antibody reactivity. Antibodies to a panel of five citrullinated EBNA-1 peptides were found in 67% of RA sera, exclusively of the IgG isotype, while 53% of the patient sera reacted with a single peptide, ARGGSRERARGRGRG-Cit-GEKR, accounting for more than half of the ACPA reactivity alone. Moreover, these antibodies were detected in 10% of CCP2-negative RA sera. In addition, 47% of the RA sera reacted with two or three citrullinated EBNA-1 peptides from the selected peptide panel. Furthermore, a negative correlation between the biotin attachment site and the location of citrulline in the peptides was found, i.e. the closer the citrulline was located to biotin, the lower the antibody reactivity. Our data suggest that citrullinated EBNA-1 peptides may be considered a substrate for the detection of ACPAs and that the presence of Epstein-Barr virus may play a role in the induction of these autoantibodies. Copyright © 2016 Elsevier Inc. All rights reserved.

Synthesis and characterization of a novel inhibitor of C-reactive protein-mediated proinflammatory effects.

PubMed

Kumaresan, Pappanaicken R; Devaraj, Sridevi; Huang, Wenzhe; Lau, Edmond Y; Liu, Ruiwu; Lam, Kit S; Jialal, Ishwarlal

2013-06-01

Numerous studies have shown that high C-reactive protein (CRP) levels predict cardiovascular disease and augur a poor prognosis in patients with acute coronary syndromes. Much in vitro and in vivo data support of a role for CRP in atherogenesis. There is an urgent need to develop inhibitors that specifically block the biological effects of CRP in vivo. The one-bead-one-compound (OBOC) combinatorial library method has been used to discover ligands against several biological targets. In this study, we use a novel fluorescence-based screening method to screen an OBOC combinatorial library for the discovery of peptides against human CRP. Human CRP was labeled with fluorescein isothiocyanate (FITC) and human serum albumin (HuSA) was labeled with phycoerythrin (PE) and used for screening. The OBOC library LWH-01 was synthesized on TentaGel resin beads using a standard solid-phase "split/mix" approach. By subtraction screening, eight peptides that bind specifically to CRP and not to HuSA were identified. In human aortic endothelial cells (HAECs) incubated with CRP, inhibitors CRPi-2, CRPi-3, and CRPi-6 significantly inhibited CRP-induced superoxide, cytokine release, and nuclear factor-κB (NFκB) activity. Molecular docking studies demonstrate that CRPi-2 interacts with the two Ca(2+) ions in the single subunit of CRP. The binding of CRPi-2 is reminiscent of choline binding. Future studies will examine the utility of this inhibitor in animal models and clinical trials.

Evaluation of the Recombinant Protein TpF1 of Treponema pallidum for Serodiagnosis of Syphilis

PubMed Central

Jiang, Chuanhao; Zhao, Feijun; Xiao, Jinhong; Zeng, Tiebing; Yu, Jian; Ma, Xiaohua; Wu, Haiying

2013-01-01

Syphilis is a chronic infection caused by Treponema pallidum subsp. pallidum, and diagnosis with sensitive and specific methods is a challenging process that is important for its prevention and treatment. In the present study, we established a recombinant protein TpF1-based indirect immunoglobulin G (IgG) enzyme-linked immunosorbent assay (ELISA) and a Western blot assay for human and rabbit sera. The 20-kDa recombinant protein TpF1 was detected by Western blotting performed with sera from rabbits immunized with recombinant TpF1 and infected with the T. pallidum Nichols strain and T. pallidum clinical isolates but was not detected by Western blotting with sera from uninfected rabbits. The sensitivity of the recombinant protein was determined by screening sera from individuals with primary, secondary, latent, and congenital syphilis (n = 82). The specificity of the recombinant protein was determined by screening sera from uninfected controls (n = 30) and individuals with potentially cross-reactive infections, including Lyme disease (n = 30) and leptospirosis (n = 5). The sensitivities of TpF1-based ELISAs were 93.3%, 100%, 100%, and 100% for primary, secondary, latent, and congenital syphilis, respectively, and the specificities were all 100% for sera from uninfected controls and individuals with potentially cross-reactive infections. In Western blot assays, the sensitivities and specificities of TpF1 for human sera were all 100%. The reactivities of TpF1 with syphilitic sera were proportional to the titers of the T. pallidum particle agglutination (TPPA) assay. These data indicate that the recombinant protein TpF1 is a highly immunogenic protein in human and rabbit infections and a promising marker for the screening of syphilis. PMID:23945159

High-resolution chromatography/time-of-flight MSE with in silico data mining is an information-rich approach to reactive metabolite screening.

PubMed

Barbara, Joanna E; Castro-Perez, Jose M

2011-10-30

Electrophilic reactive metabolite screening by liquid chromatography/mass spectrometry (LC/MS) is commonly performed during drug discovery and early-stage drug development. Accurate mass spectrometry has excellent utility in this application, but sophisticated data processing strategies are essential to extract useful information. Herein, a unified approach to glutathione (GSH) trapped reactive metabolite screening with high-resolution LC/TOF MS(E) analysis and drug-conjugate-specific in silico data processing was applied to rapid analysis of test compounds without the need for stable- or radio-isotope-labeled trapping agents. Accurate mass defect filtering (MDF) with a C-heteroatom dealkylation algorithm dynamic with mass range was compared to linear MDF and shown to minimize false positive results. MS(E) data-filtering, time-alignment and data mining post-acquisition enabled detection of 53 GSH conjugates overall formed from 5 drugs. Automated comparison of sample and control data in conjunction with the mass defect filter enabled detection of several conjugates that were not evident with mass defect filtering alone. High- and low-energy MS(E) data were time-aligned to generate in silico product ion spectra which were successfully applied to structural elucidation of detected GSH conjugates. Pseudo neutral loss and precursor ion chromatograms derived post-acquisition demonstrated 50.9% potential coverage, at best, of the detected conjugates by any individual precursor or neutral loss scan type. In contrast with commonly applied neutral loss and precursor-based techniques, the unified method has the advantage of applicability across different classes of GSH conjugates. The unified method was also successfully applied to cyanide trapping analysis and has potential for application to alternate trapping agents. Copyright © 2011 John Wiley & Sons, Ltd.

Isolation and characterization of a novel human scFv inhibiting EGFR vIII expressing cancers.

PubMed

Rahbarnia, Leila; Farajnia, Safar; Babaei, Hossein; Majidi, Jafar; Dariushnejad, Hassan; Hosseini, Mohammad Kazem

2016-12-01

EGFRvIII, a mutant form of epidermal growth factor receptor is highly expressed in glioblastoma, carcinoma of the breast, ovary, and lung but not in normal cells. This tumor specific antigen has emerged as a promising candidate for antibody based therapy of several cancers. The aim of the present study was isolation and characterization of a human single chain antibody against EGFRvIII as a promising target for cancer therapy. For this, a synthetic peptide corresponding to EGFRvIII protein was used for screening the naive human scFv phage library. Selection was performed using a novel screening strategy for enrichment of rare specific clones. After five rounds of screening, six positive scFv clones against EGFRvIII were selected using monoclonal phage ELISA, among them, a clone with an amber mutation in VH CDR2 coding sequence showed higher reactivity. The mutation was corrected through site directed mutagenesis and then scFv fragment was expressed after subcloning into the bacterial expression vector. Expression in BL21 pLysS resulted in a highly soluble scFv appeared in soluble fraction of E. coli lysate. Bioinformatic in silico analysis between scFv and EGFRvIII sequences confirmed specific binding of desired scFv to EGFRvIII in CDR regions. The specific reactivity of the purified scFv with native EGFRvIII was confirmed by cell based ELISA and western blot. In conclusion, human anti- EGFRvIII scFv isolated from a scFv phage library displayed high reactivity with EGFRvIII. The scFv isolated in this study can be the groundwork for developing more effective diagnostic and therapeutic agents against EGFRvIII expressing cancers. Copyright © 2016 European Federation of Immunological Societies. Published by Elsevier B.V. All rights reserved.

A comprehensive approach to reactive power scheduling in restructured power systems

NASA Astrophysics Data System (ADS)

Shukla, Meera

Financial constraints, regulatory pressure, and need for more economical power transfers have increased the loading of interconnected transmission systems. As a consequence, power systems have been operated close to their maximum power transfer capability limits, making the system more vulnerable to voltage instability events. The problem of voltage collapse characterized by a severe local voltage depression is generally believed to be associated with inadequate VAr support at key buses. The goal of reactive power planning is to maintain a high level of voltage security, through installation of properly sized and located reactive sources and their optimal scheduling. In case of vertically-operated power systems, the reactive requirement of the system is normally satisfied by using all of its reactive sources. But in case of different scenarios of restructured power systems, one may consider a fixed amount of exchange of reactive power through tie lines. Reviewed literature suggests a need for optimal scheduling of reactive power generation for fixed inter area reactive power exchange. The present work proposed a novel approach for reactive power source placement and a novel approach for its scheduling. The VAr source placement technique was based on the property of system connectivity. This is followed by development of optimal reactive power dispatch formulation which facilitated fixed inter area tie line reactive power exchange. This formulation used a Line Flow-Based (LFB) model of power flow analysis. The formulation determined the generation schedule for fixed inter area tie line reactive power exchange. Different operating scenarios were studied to analyze the impact of VAr management approach for vertically operated and restructured power systems. The system loadability, losses, generation and the cost of generation were the performance measures to study the impact of VAr management strategy. The novel approach was demonstrated on IEEE 30 bus system.

Reactive oxygen species generated by a heat shock protein (Hsp) inducing product contributes to Hsp70 production and Hsp70-mediated protective immunity in Artemia franciscana against pathogenic vibrios.

PubMed

Baruah, Kartik; Norouzitallab, Parisa; Linayati, Linayati; Sorgeloos, Patrick; Bossier, Peter

2014-10-01

The cytoprotective role of heat shock protein (Hsp70) described in a variety of animal disease models, including vibriosis in farmed aquatic animals, suggests that new protective strategies relying upon the use of compounds that selectively turn on Hsp genes could be developed. The product Tex-OE® (hereafter referred to as Hspi), an extract from the skin of the prickly pear fruit, Opuntia ficus indica, was previously shown to trigger Hsp70 synthesis in a non-stressful situation in a variety of animals, including in a gnotobiotically (germ-free) cultured brine shrimp Artemia franciscana model system. This model system offers great potential for carrying out high-throughput, live-animal screens of compounds that have health benefit effects. By using this model system, we aimed to disclose the underlying cause behind the induction of Hsp70 by Hspi in the shrimp host, and to determine whether the product affects the shrimp in inducing resistance towards pathogenic vibrios. We provide unequivocal evidences indicating that during the pretreatment period with Hspi, there is an initial release of reactive oxygen species (hydrogen peroxide and/or superoxide anion), generated by the added product, in the rearing water and associated with the host. The reactive molecules generated are the triggering factors responsible for causing Hsp70 induction within Artemia. We have also shown that Hspi acts prophylactically at an optimum dose regimen to confer protection against pathogenic vibrios. This salutary effect was associated with upregulation of two important immune genes, prophenoloxidase and transglutaminase of the innate immune system. These findings suggest that inducers of stress protein (e.g. Hsp70) are potentially important modulator of immune responses and might be exploited to confer protection to cultured shrimp against Vibrio infection. Copyright © 2014 Elsevier Ltd. All rights reserved.

Chemical probes for competitive profiling of the quorum sensing signal synthase PqsD of Pseudomonas aeruginosa

PubMed Central

Prothiwa, Michaela; Szamosvári, Dávid; Glasmacher, Sandra

2016-01-01

The human pathogen Pseudomonas aeruginosa uses the pqs quorum sensing system to coordinate the production of its broad spectrum of virulence factors to facilitate colonization and infection of its host. Hereby, the enzyme PqsD is a virulence related quorum sensing signal synthase that catalyzes the central step in the biosynthesis of the Pseudomonas quinolone signals HHQ and PQS. We developed a library of cysteine reactive chemical probes with an alkyne handle for fluorescence tagging and report the selective and highly sensitive in vitro labelling of the active site cysteine of this important enzyme. Interestingly, only one type of probe, with a reactive α-chloroacetamide was capable of covalently reacting with the active site. We demonstrated the potential of our probes in a competitive labelling platform where we screened a library of synthetic HHQ and PQS analogues with heteroatom replacements and found several inhibitors of probe binding that may represent promising scaffolds for the development of customized PqsD inhibitors as well as a chemical toolbox to investigate the activity and active site specificity of the enzyme. PMID:28144351

Screening reactive oxygen species scavenging properties of platinum nanoparticles on a microfluidic chip.

PubMed

Zheng, Wenfu; Jiang, Bo; Hao, Yi; Zhao, Yuyun; Zhang, Wei; Jiang, Xingyu

2014-09-12

Hyperglycemia, hyperlipidemia and inflammation are key risk factors for atherosclerosis and can lead to overproduction of reactive oxygen species (ROS), which plays a critical role in vascular endothelial dysfunction and subsequent progress of atherosclerosis. However, there is currently a lack of effective drugs that deal with ROS. Platinum nanoparticles (Pt-NPs) have proven to be promising antioxidant drugs in vitro and in vivo. To optimize the efficacy of Pt-NP based drugs, we synthesized and characterized the ROS scavenging properties of three kinds of small molecules that capped Pt-NPs (Pt-AMP-NPs, Pt-ATT-NPs, Pt-MI-NPs) on a blood vessel-mimicking microfluidic chip. The Pt-NPs showed superior superoxide dismutase (SOD)-like functions and can scavenge ROS and recover compromised cell-cell junctions under hyperglycemic, hyperlipidemic and proinflammatory conditions. Amongst these NPs, Pt-AMP-NPs showed the most superior antioxidant properties, suggesting its potency to serve as a novel drug to treat vascular diseases such as atherosclerosis. Our microfluidic chip, providing physiological hemodynamic conditions for the experiments, is potentially a promising tool for a wide range of biological research on the vascular system.

An efficient route to selective bio-oxidation catalysts: an iterative approach comprising modeling, diversification, and screening, based on CYP102A1.

PubMed

Seifert, Alexander; Antonovici, Mihaela; Hauer, Bernhard; Pleiss, Jürgen

2011-06-14

Perillyl alcohol is the terminal hydroxylation product of the cheap and readily available terpene, limonene. It has high potential as an anti-tumor substance, but is of limited availability. In principle, cytochrome P450 monooxygenases, such as the self-sufficient CYP102A1, are promising catalysts for the oxidation of limonene or other inert hydrocarbons. The wild-type enzyme converts (4R)-limonene to four different oxidation products; however, terminal hydroxylation at the allylic C7 is not observed. Here we describe a generic strategy to engineer this widely used enzyme to hydroxylate exclusively the exposed, but chemically less reactive, primary C7 in the presence of other reactive positions. The approach presented here turns CYP102A1 into a highly selective catalyst with a shifted product spectra by successive rounds of modeling, the design of small focused libraries, and screening. In the first round a minimal CYP102A1 mutant library was rationally designed. It contained variants with improved or strongly shifted regio-, stereo- and chemoselectivity, compared to wild-type. From this library the variant with the highest perillyl alcohol ratio was fine-tuned by two additional rounds of molecular modeling, diversification, and screening. In total only 29 variants needed to be screened to identify the triple mutant A264V/A238V/L437F that converts (4R)-limonene to perillyl alcohol with a selectivity of 97 %. Focusing mutagenesis on a small number of relevant positions identified by computational approaches is the key for efficient screening for enzyme selectivity. Copyright © 2011 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

Hepatitis C virus infection in the 1945-1965 birth cohort (baby boomers) in a large urban ED.

PubMed

Allison, Waridibo E; Chiang, William; Rubin, Ada; O'Donnell, Lauren; Saldivar, Miguel A; Maurantonio, Michael; Dela Cruz, Jeffrey; Duvidovich, Svetlana; Carmody, Ellie

2016-04-01

The US Preventive Services Task Force recommends one-time screening of the 1945-1965 birth cohort (baby boomers) for hepatitis C (HCV) infection. New York State legislation mandates screening of baby boomers for HCV in most patient care settings except the emergency department (ED). This cross-sectional study explores baby boomer knowledge of HCV, prevalence of HCV infection, and linkage to care from a large urban ED. Patients participated in a researcher-administered structured interview and were offered an HCV screening test. If HCV antibody reactive, a follow-up clinic appointment was made within 6 weeks. Reminder telephone calls were made a week before the appointment. Attendance at the follow-up appointment was considered successful linkage to care. A total of 915 eligible patients were approached between October 21, 2014, and July 13, 2015. A total of 427 patients participated in the structured interview; 383 agreed to an HCV rapid test. Prevalence of HCV antibody reactivity was 7.3%. Four patients were successfully linked to care. General knowledge about HCV was fair. Misconceptions about transmission were apparent. Beliefs that "if someone is infected with HCV they will most likely carry the virus all their lives unless treated" and that "someone with hepatitis can look and feel fine" were significantly associated with agreement to testing. Better linkage to care is needed to justify HCV screening in the 1945-1965 birth cohort in this particular ED setting. Linkage to care from the ED is challenging but can potentially be improved with specific measures including simplified screening algorithms and supportive resources. Copyright © 2015 Elsevier Inc. All rights reserved.

Do work-related stress and reactivity to stress predict dementia more than 30 years later?

PubMed

Crowe, Michael; Andel, Ross; Pedersen, Nancy L; Gatz, Margaret

2007-01-01

The purpose of this study was to examine associations for work-related stress, reactivity to stress, and subsequent risk of dementia. The sample consisted of members of the population-based Swedish Twin Registry who were participants in the HARMONY study (n=2,049). We used case control and cotwin control designs, with information on work-related stress and reactivity to stress collected as part of a questionnaire completed in 1967. Dementia was diagnosed approximately 30 years later using a 2-stage procedure-screening for cognitive impairment followed by full clinical evaluation. We found that measures of work-related stress (job dissatisfaction and high job demands) were not associated with dementia risk. Greater reactivity to stress predicted higher risk of dementia controlling for age, education, sex, occupational status, alcohol use, and smoking status (odds ratio=1.57, 95% confidence interval 1.08-2.31). Cotwin control analyses also showed that dementia probands were more likely to report high reactivity to stress than their nondemented cotwins. We did not find evidence of an interaction between work stress and reactivity in predicting dementia. Overall, indicators of stress due to environment (ie, work) were not associated with dementia, whereas the individual characteristic of reactivity to stress predicted dementia risk.

Comprehensive Mechanistic Analysis of Hits from High-Throughput and Docking Screens against β-Lactamase

PubMed Central

Babaoglu, Kerim; Simeonov, Anton; Irwin, John J.; Nelson, Michael E.; Feng, Brian; Thomas, Craig J.; Cancian, Laura; Costi, M. Paola; Maltby, David A.; Jadhav, Ajit; Inglese, James; Austin, Christopher P.; Shoichet, Brian K.

2009-01-01

High-throughput screening (HTS) is widely used in drug discovery. Especially for screens of unbiased libraries, false positives can dominate “hit lists”; their origins are much debated. Here we determine the mechanism of every active hit from a screen of 70,563 unbiased molecules against β-lactamase using quantitative HTS (qHTS). Of the 1274 initial inhibitors, 95% were detergent-sensitive and were classified as aggregators. Among the 70 remaining were 25 potent, covalent-acting β-lactams. Mass spectra, counter-screens, and crystallography identified 12 as promiscuous covalent inhibitors. The remaining 33 were either aggregators or irreproducible. No specific reversible inhibitors were found. We turned to molecular docking to prioritize molecules from the same library for testing at higher concentrations. Of 16 tested, 2 were modest inhibitors. Subsequent X-ray structures corresponded to the docking prediction. Analog synthesis improved affinity to 8 µM. These results suggest that it may be the physical behavior of organic molecules, not their reactivity, that accounts for most screening artifacts. Structure-based methods may prioritize weak-but-novel chemotypes in unbiased library screens. PMID:18333608

21 CFR 866.5270 - C-reactive protein immuno-logical test system.

Code of Federal Regulations, 2010 CFR

2010-04-01

... SERVICES (CONTINUED) MEDICAL DEVICES IMMUNOLOGY AND MICROBIOLOGY DEVICES Immunological Test Systems § 866.5270 C-reactive protein immuno-logical test system. (a) Identification. A C-reactive protein... 21 Food and Drugs 8 2010-04-01 2010-04-01 false C-reactive protein immuno-logical test system. 866...

In vitro P-glycoprotein activity does not completely explain in vivo efficacy of novel centrally effective oxime acetylcholinesterase reactivators.

PubMed

Dail, Mary Beth; Meek, Edward Caldwell; Chambers, Howard Wayne; Chambers, Janice Elaine

2018-05-03

Novel-substituted phenoxyalkyl pyridinium oxime acetylcholinesterase (AChE) reactivators (US patent 9,227,937) that showed convincing evidence of penetration into the brains of intact rats were developed by our laboratories. The oximes separated into three groups based on their levels of brain AChE reactivation following exposure of rats to the sarin surrogate nitrophenyl isopropyl methylphosphonate (NIMP). P-glycoprotein (P-gp) is a major blood-brain barrier (BBB) transporter and requires ATP for efflux. To determine if P-gp affinity screening could be used to reduce animal use, we measured in vitro oxime-stimulated ATPase activity to see if the in vivo reactivation efficacies related to the oximes' functions as P-gp substrates. High efficacy oximes were expected to be poor P-gp substrates, thus remaining in the brain longer. The high efficacy oximes (24-35% brain AChE reactivation) were worse P-gp substrates than the low efficacy oximes (0-7% brain AChE reactivation). However, the oxime group with medium in vivo reactivation of 10-17% were even worse P-gp substrates than the high efficacy group so their reactivation ability was not reflected by P-gp export. The results suggest that in vitro P-gp ATPase activity can remove the low efficacy oximes from in vivo testing, but is not sufficient to differentiate between the top two tiers.

Metabolite screening of aromatic amine hair dyes using in vitro hepatic models.

PubMed

Skare, J A; Hewitt, N J; Doyle, E; Powrie, R; Elcombe, C

2009-11-01

Aromatic amines and heterocyclic amines are widely used ingredients in permanent hair dyes. However, little has been published on their potential for oxidation via hepatic cytochrome P450s. Therefore, the authors screened nine such compounds for their potential to undergo oxidative metabolism in human liver microsomes. Toluene-2,5-diamine (TDA), p-aminophenol, m-aminophenol, p-methylaminophenol, N,N'-bis(2-hydroxyethyl)-p-phenylenediamine, and 1-hydroxyethyl-4,5-diaminopyrazole showed no evidence of oxidative metabolism. Oxidized metabolites of 4-amino-2-hydroxytoluene (AHT), 2-methyl-5- hydroxyethylaminophenol (MHEAP), and phenyl methyl pyrazolone (PMP) were detected, but there was no evidence of beta-nicotinamide adenine dinucleotide phosphate (NADPH)-dependent covalent binding to microsomal protein, suggesting that these are not reactive metabolites. Metabolism of AHT, MHEAP, PMP, and TDA was further studied in human hepatocytes. All these compounds underwent conjugation, but no oxidative metabolites were found. The results suggest that none of the hair dye ingredients tested showed evidence of hepatic metabolism to potentially biologically reactive oxidized metabolites.

Screening for antibody to HTLV-III in blood donors of Liguria. Ligurian Committee for the Study of Infections Transmitted through Blood and Blood Products.

PubMed

1985-01-01

Anti-HTLV III had been detected in 12,689 serum samples collected within August 1985 from 12 Transfusion Centres of Liguria. In the course of the first test, carried out by ELISA using disrupted virions as antigen, 12,666 samples (99.81%) resulted non reactive; 14 (0.1%) belonged to the grey-zone and 9 (0.08%) were clearly reactive. The samples of the last two classes were tested again in the same way and, whenever the cases were suspect as positive, by Western-blot technique. All positive cases, but three, were linked with risk factors such as intravenous drug use or drug addicts partners. Even if the prevalence of blood donors anti-HTLV III positive resulted, on the whole, very low (0.063%), the investigations carried out prove the importance of regular screening of blood units for the prevention of HTLV III infection.

AllerML: markup language for allergens.

PubMed

Ivanciuc, Ovidiu; Gendel, Steven M; Power, Trevor D; Schein, Catherine H; Braun, Werner

2011-06-01

Many concerns have been raised about the potential allergenicity of novel, recombinant proteins into food crops. Guidelines, proposed by WHO/FAO and EFSA, include the use of bioinformatics screening to assess the risk of potential allergenicity or cross-reactivities of all proteins introduced, for example, to improve nutritional value or promote crop resistance. However, there are no universally accepted standards that can be used to encode data on the biology of allergens to facilitate using data from multiple databases in this screening. Therefore, we developed AllerML a markup language for allergens to assist in the automated exchange of information between databases and in the integration of the bioinformatics tools that are used to investigate allergenicity and cross-reactivity. As proof of concept, AllerML was implemented using the Structural Database of Allergenic Proteins (SDAP; http://fermi.utmb.edu/SDAP/) database. General implementation of AllerML will promote automatic flow of validated data that will aid in allergy research and regulatory analysis. Copyright © 2011 Elsevier Inc. All rights reserved.

AllerML: Markup Language for Allergens

PubMed Central

Ivanciuc, Ovidiu; Gendel, Steven M.; Power, Trevor D.; Schein, Catherine H.; Braun, Werner

2011-01-01

Many concerns have been raised about the potential allergenicity of novel, recombinant proteins into food crops. Guidelines, proposed by WHO/FAO and EFSA, include the use of bioinformatics screening to assess the risk of potential allergenicity or cross-reactivities of all proteins introduced, for example, to improve nutritional value or promote crop resistance. However, there are no universally accepted standards that can be used to encode data on the biology of allergens to facilitate using data from multiple databases in this screening. Therefore, we developed AllerML a markup language for allergens to assist in the automated exchange of information between databases and in the integration of the bioinformatics tools that are used to investigate allergenicity and cross-reactivity. As proof of concept, AllerML was implemented using the Structural Database of Allergenic Proteins (SDAP; http://fermi.utmb.edu/SDAP/) database. General implementation of AllerML will promote automatic flow of validated data that will aid in allergy research and regulatory analysis. PMID:21420460

Computational diagnosis of canine lymphoma

NASA Astrophysics Data System (ADS)

Mirkes, E. M.; Alexandrakis, I.; Slater, K.; Tuli, R.; Gorban, A. N.

2014-03-01

One out of four dogs will develop cancer in their lifetime and 20% of those will be lymphoma cases. PetScreen developed a lymphoma blood test using serum samples collected from several veterinary practices. The samples were fractionated and analysed by mass spectrometry. Two protein peaks, with the highest diagnostic power, were selected and further identified as acute phase proteins, C-Reactive Protein and Haptoglobin. Data mining methods were then applied to the collected data for the development of an online computer-assisted veterinary diagnostic tool. The generated software can be used as a diagnostic, monitoring and screening tool. Initially, the diagnosis of lymphoma was formulated as a classification problem and then later refined as a lymphoma risk estimation. Three methods, decision trees, kNN and probability density evaluation, were used for classification and risk estimation and several preprocessing approaches were implemented to create the diagnostic system. For the differential diagnosis the best solution gave a sensitivity and specificity of 83.5% and 77%, respectively (using three input features, CRP, Haptoglobin and standard clinical symptom). For the screening task, the decision tree method provided the best result, with sensitivity and specificity of 81.4% and >99%, respectively (using the same input features). Furthermore, the development and application of new techniques for the generation of risk maps allowed their user-friendly visualization.

Engineering of Pyranose Dehydrogenase for Increased Oxygen Reactivity

PubMed Central

Krondorfer, Iris; Lipp, Katharina; Brugger, Dagmar; Staudigl, Petra; Sygmund, Christoph; Haltrich, Dietmar; Peterbauer, Clemens K.

2014-01-01

Pyranose dehydrogenase (PDH), a member of the GMC family of flavoproteins, shows a very broad sugar substrate specificity but is limited to a narrow range of electron acceptors and reacts extremely slowly with dioxygen as acceptor. The use of substituted quinones or (organo)metals as electron acceptors is undesirable for many production processes, especially of food ingredients. To improve the oxygen reactivity, site-saturation mutagenesis libraries of twelve amino acids around the active site of Agaricus meleagris PDH were expressed in Saccharomyces cerevisiae. We established high-throughput screening assays for oxygen reactivity and standard dehydrogenase activity using an indirect Amplex Red/horseradish peroxidase and a DCIP/D-glucose based approach. The low number of active clones confirmed the catalytic role of H512 and H556. Only one position was found to display increased oxygen reactivity. Histidine 103, carrying the covalently linked FAD cofactor in the wild-type, was substituted by tyrosine, phenylalanine, tryptophan and methionine. Variant H103Y was produced in Pichia pastoris and characterized and revealed a five-fold increase of the oxygen reactivity. PMID:24614932

HLA-B*1502 allele is associated with a cross-reactivity pattern of cutaneous adverse reactions to antiepileptic drugs.

PubMed

Wang, J; Zhang, J; Wu, X; Yu, P; Hong, Z

2012-01-01

The US Food and Drug Administration has recommended genetic screening for the human leucocyte antigen-B (HLA-B)*1502 allele in patients of Asian ethnicity before starting carbamazepine therapy, to avoid the fatal adverse treatment-related events associated with this drug. The association between cross-reactivity to antiepileptic drugs (AEDs) and the HLA-B*1502 allele has been only rarely reported. Here, two cases of cross-reactivity to AEDs, where cutaneous adverse drug reactions (cADRs) developed in female Han Chinese patients with epilepsy who tested positive for the HLA-B*1502 allele, are described. If the genetic association could be confirmed in larger studies, the HLA-B*1502 allele should be tested for in any patient experiencing cADRs, to avoid crossreactivity to AEDs.

Real-time polymerase chain reaction detection of cauliflower mosaic virus to complement the 35S screening assay for genetically modified organisms.

PubMed

Cankar, Katarina; Ravnikar, Maja; Zel, Jana; Gruden, Kristina; Toplak, Natasa

2005-01-01

Labeling of genetically modified organisms (GMOs) is now in place in many countries, including the European Union, in order to guarantee the consumer's choice between GM and non-GM products. Screening of samples is performed by polymerase chain reaction (PCR) amplification of regulatory sequences frequently introduced into genetically modified plants. Primers for the 35S promoter from Cauliflower mosaic virus (CaMV) are those most frequently used. In virus-infected plants or in samples contaminated with plant material carrying the virus, false-positive results can consequently occur. A system for real-time PCR using a TaqMan minor groove binder probe was designed that allows recognition of virus coat protein in the sample, thus allowing differentiation between transgenic and virus-infected samples. We measured the efficiency of PCR amplification, limits of detection and quantification, range of linearity, and repeatability of the assay in order to assess the applicability of the assay for routine analysis. The specificity of the detection system was tested on various virus isolates and plant species. All 8 CaMV isolates were successfully amplified using the designed system. No cross-reactivity was detected with DNA from 3 isolates of the closely related Carnation etched ring virus. Primers do not amplify plant DNA from available genetically modified maize and soybean lines or from different species of Brassicaceae or Solanaceae that are natural hosts for CaMV. We evaluated the assay for different food matrixes by spiking CaMV DNA into DNA from food samples and have successfully amplified CaMV from all samples. The assay was tested on rapeseed samples from routine GMO testing that were positive in the 35S screening assay, and the presence of the virus was confirmed.

Making real-time reactive systems reliable

NASA Technical Reports Server (NTRS)

Marzullo, Keith; Wood, Mark

1990-01-01

A reactive system is characterized by a control program that interacts with an environment (or controlled program). The control program monitors the environment and reacts to significant events by sending commands to the environment. This structure is quite general. Not only are most embedded real time systems reactive systems, but so are monitoring and debugging systems and distributed application management systems. Since reactive systems are usually long running and may control physical equipment, fault tolerance is vital. The research tries to understand the principal issues of fault tolerance in real time reactive systems and to build tools that allow a programmer to design reliable, real time reactive systems. In order to make real time reactive systems reliable, several issues must be addressed: (1) How can a control program be built to tolerate failures of sensors and actuators. To achieve this, a methodology was developed for transforming a control program that references physical value into one that tolerates sensors that can fail and can return inaccurate values; (2) How can the real time reactive system be built to tolerate failures of the control program. Towards this goal, whether the techniques presented can be extended to real time reactive systems is investigated; and (3) How can the environment be specified in a way that is useful for writing a control program. Towards this goal, whether a system with real time constraints can be expressed as an equivalent system without such constraints is also investigated.

Prevalence of HIV in pregnant women identified with a risk factor at a tertiary care hospital.

PubMed

Mahmud, Ghazala; Abbas, Shazra

2009-01-01

HIV is an epidemic quite unlike any other, combining the problems of a lifelong medical disease with immense social, psychological, economic and public health consequences. Since we are living in a global village where human interactions has become fast and frequent, diseases like HIV are no more alien to us. HIV/AIDS in Pakistan is slowly gaining recognition as a public health issue of great importance. Objectives of this study were to determine the prevalence of HIV in pregnant women identified with a high risk factor/behaviour at a tertiary care hospital. It is a Descriptive study. All pregnant women attending antenatal booking clinic were assessed via a pre-designed 'Risk assessment questionnaire'. Women identified with a risk factor were offered HIV Rapid screening test (Capillus HIV1/2). Positive (reactive) results on screening test were confirmed with ELISA. During the study period (March 2007-May 2008), out of 5263 antenatal bookings 785 (14%) women were identified with a risk factor. HIV screening test was done in 779 (99%), and 6 women refused testing. Three women (0.3%) were found positive (reactive) on screening. Two out of 3 women were confirmed positive (0.2%) on ELISA. Husbands of both women were tested and one found positive (migrant from Dubai). Second women had history of blood transfusion. Her husband was HIV negative. During the study period, in addition to 2 pregnant women diagnosed as HIV positive through ANC risk screening, 6 confirmed HIV positive women, found pregnant were referred from 'HIV Treatment Centre', Pakistan Institute of Medical Sciences (PIMS) to Prevention of Parent to Child Transmission (PPTCT) centre for obstetric care. Spouses of 5 out of 6 had history of working abroad and extramarital sexual relationships. All positive (8) women were referred to PPTCT centre for further management. A simple 'Risk Assessment Questionnaire' can help us in identifying women who need HIV screening. Sexual transmission still remains the commonest cause of HIV transmission.

The Insulin-Like Growth Factor System and Nutritional Assessment

PubMed Central

Livingstone, Callum

2012-01-01

Over recent years there has been considerable interest in the role of the insulin-like growth factor (IGF) system in health and disease. It has long been known to be dysregulated in states of under- and overnutrition, serum IGF-I levels falling in malnourished patients and responding promptly to nutritional support. More recently, other proteins in this system have been observed to be dysregulated in both malnutrition and obesity. Currently no biochemical marker is sufficiently specific for use in screening for malnutrition, but levels may be valuable in providing information on nutritional status and in monitoring of nutritional support. All have limitations as nutritional markers in that their serum levels are influenced by factors other than nutritional status, most importantly the acute phase response (APR). Levels should be interpreted along with clinical findings and the results of other investigations such as C-reactive protein (CRP). This paper reviews data supporting the use of proteins of the IGF system as nutritional markers. PMID:24278739

A REACTIVITY PATTERN OF DISCRIMINATION OF ER AGONISM AND ANTAGONISM BASED ON 3-D MOLECULAR ATTRIBUTES

EPA Science Inventory

Various models have been developed to predict the relative binding affinity (RBA) of chemicals to estrogen receptors (ER). These models are important for prioritizing chemicals for screening in biological assays assessing the potential for endocrine disruption. One shortcoming of...

Practice Patterns in Hepatitis B Virus Screening Before Cancer Chemotherapy in a Major US Hospital Network.

PubMed

Kwak, Ye Eun; Stein, Stacy M; Lim, Joseph K

2018-01-01

Cancer patients receiving chemotherapy face an increased risk of reactivation of chronic hepatitis B virus infection. To determine the HBV screening rate in patients receiving cancer chemotherapy in various clinical settings. We identified 11,959 adult cancer patients (age ≥ 18 years) receiving parenteral chemotherapy between 2012 and 2015 within a major US hospital network, including a large university hospital, community teaching hospitals, and community oncology clinics. Two thousand and forty-five patients (17.1%) were screened for either HBV surface antigen (HBsAg) or HBV core antibody (HBcAb) before chemotherapy, and 1850 patients (15.5%) had both HBsAg and HBcAb tested before chemotherapy. 8.4% were exposed to HBV, and 0.9% had chronic HBV infection (both HBsAg/HBcAb positive). Patients with hematologic tumor were more often screened than with solid tumor (55.6 vs. 8.3%, p < 0.001). Patients receiving chemotherapy with higher HBV reactivation risk had higher yet suboptimal HBV screening rate (41.1% B-depleting agents, 21.5% anthracycline, 14.9% steroid, 64.7% anti-TNF alpha and 18.6% other chemotherapy, p < 0.001). Patients with age ≥ 50 years (old 16.2% vs. young 23.9%, p < 0.001) and Asian ethnicity (Asian 13.6 vs. Caucasian 16.6%, p < 0.001) were screened less for HBV despite higher prevalence of HBV exposure (old 9.3% vs. young 4.3%, p < 0.001 and Asian 27.8% vs. Caucasian 6.4%, p < 0.001). Patients receiving chemotherapy in community oncology clinics were less screened versus community teaching hospitals or university hospital (12.7 vs. 19.1 vs. 19.7%, p < 0.001), despite similar prevalence of HBV infection. On multivariate analysis, receiving chemotherapy at a community oncology clinic [odds ratio (OR) 0.57, 95% confidence interval (CI) 0.45-0.72, p < 0.001] was independently associated with less HBV screening compared to receiving chemotherapy at a university or community teaching hospital. HBV screening among patients undergoing cancer chemotherapy was suboptimal and less commonly performed in community oncology clinics compared to teaching hospitals.

An approach to evaluating reactive airborne wind shear systems

NASA Technical Reports Server (NTRS)

Gibson, Joseph P., Jr.

1992-01-01

An approach to evaluating reactive airborne windshear detection systems was developed to support a deployment study for future FAA ground-based windshear detection systems. The deployment study methodology assesses potential future safety enhancements beyond planned capabilities. The reactive airborne systems will be an integral part of planned windshear safety enhancements. The approach to evaluating reactive airborne systems involves separate analyses for both landing and take-off scenario. The analysis estimates the probability of effective warning considering several factors including NASA energy height loss characteristics, reactive alert timing, and a probability distribution for microburst strength.

The state of the art of conventional flow visualization techniques for wind tunnel testing

NASA Technical Reports Server (NTRS)

Settles, G. S.

1982-01-01

Conventional wind tunnel flow visualization techniques which consist of surface flow methods, tracers, and optical methods are presented. Different surface flow methods are outlined: (1) liquid films (oil and fluorescent dye and UV lighting, renewable film via porous dispenser in model, volatile carrier fluid, cryogenic colored oil dots, oil film interferometry); (2) reactive surface treatment (reactive gas injection, reversible dye); (3) transition and heat transfer detectors (evaporation, sublimation, liquid crystals, phase change paints, IR thermography); and (4) tufts (fluorescent mini tufts, cryogenic suitability). Other methods are smoke wire techniques, vapor screens, and optical methods.

Reactive system verification case study: Fault-tolerant transputer communication

NASA Technical Reports Server (NTRS)

Crane, D. Francis; Hamory, Philip J.

1993-01-01

A reactive program is one which engages in an ongoing interaction with its environment. A system which is controlled by an embedded reactive program is called a reactive system. Examples of reactive systems are aircraft flight management systems, bank automatic teller machine (ATM) networks, airline reservation systems, and computer operating systems. Reactive systems are often naturally modeled (for logical design purposes) as a composition of autonomous processes which progress concurrently and which communicate to share information and/or to coordinate activities. Formal (i.e., mathematical) frameworks for system verification are tools used to increase the users' confidence that a system design satisfies its specification. A framework for reactive system verification includes formal languages for system modeling and for behavior specification and decision procedures and/or proof-systems for verifying that the system model satisfies the system specifications. Using the Ostroff framework for reactive system verification, an approach to achieving fault-tolerant communication between transputers was shown to be effective. The key components of the design, the decoupler processes, may be viewed as discrete-event-controllers introduced to constrain system behavior such that system specifications are satisfied. The Ostroff framework was also effective. The expressiveness of the modeling language permitted construction of a faithful model of the transputer network. The relevant specifications were readily expressed in the specification language. The set of decision procedures provided was adequate to verify the specifications of interest. The need for improved support for system behavior visualization is emphasized.

Elimination of falsely reactive results in a commercially-available West Nile virus IgM capture enzyme-linked immunosorbent assay by heterophilic antibody blocking reagents.

PubMed

Prince, Harry E; Lapé-Nixon, Mary; Givens, Tara S; Bradshaw, Tiffany; Nowicki, Marek J

2017-05-01

All sera initially reactive in the Focus Diagnostics West Nile virus IgM capture enzyme-linked immunosorbent assay (WNV IgM ELISA) must be retested with background subtraction to identify falsely-reactive (FR) samples due to antibodies that bind to immunoglobulins of other animal species (heterophilic antibodies). In some settings, such as pre-transplant testing of organ donors, the reporting delay associated with retesting can have an adverse impact on donor procurement and organ placement. We sought to determine if inclusion of heterophilic antibody blockers in assay conjugate could eliminate the nonspecific reactivity of FR samples. Of 6 blocking reagents evaluated using a well-characterized FR sample, immunoglobulin inhibiting reagent from Bioreclamation (IIR) and blocker from Fitzgerald Industries (BFI) were superior in their ability to inhibit false reactivity; these 2 blockers were then used to evaluate 20 additional FR and 21 truly-reactive (TR) samples. Both blockers eliminated the reactivity of 20/21 FR samples, whereas all 21 TR samples remained reactive; further, all 13 truly non-reactive (NR) samples evaluated remained non-reactive when using blocker-containing conjugate. A subset of 22 samples were tested in parallel using the initial lot and a second lot of IIR and BFI; with one exception, all samples showed the same qualitative result using both lots of a given blocker. These findings demonstrate that modification of the Focus WNV IgM screening ELISA to include heterophilic antibody blocker IIR or BFI in assay conjugate eliminates the reactivity of most FR samples, markedly reducing the number of samples requiring further testing by background subtraction. Copyright © 2017 Elsevier B.V. All rights reserved.

Identification of a B cell-dependent subpopulation of multiple sclerosis by measurements of brain-reactive B cells in the blood.

PubMed

Kuerten, Stefanie; Pommerschein, Giovanna; Barth, Stefanie K; Hohmann, Christopher; Milles, Bianca; Sammer, Fabian W; Duffy, Cathrina E; Wunsch, Marie; Rovituso, Damiano M; Schroeter, Michael; Addicks, Klaus; Kaiser, Claudia C; Lehmann, Paul V

2014-01-01

B cells are increasingly coming into play in the pathogenesis of multiple sclerosis (MS). Here, we screened peripheral blood mononuclear cells (PBMC) from patients with clinically isolated syndrome (CIS), MS, other non-inflammatory neurological, inflammatory neurological or autoimmune diseases, and healthy donors for their B cell reactivity to CNS antigen using the enzyme-linked immunospot technique (ELISPOT) after 96 h of polyclonal stimulation. Our data show that nine of 15 patients with CIS (60.0%) and 53 of 67 patients with definite MS (79.1%) displayed CNS-reactive B cells, compared to none of the control donors. The presence of CNS-reactive B cells in the blood of the majority of patients with MS or at risk to develop MS along with their absence in control subjects suggests that they might be indicative of a B cell-dependent subpopulation of the disease. Copyright © 2014. Published by Elsevier Inc.

BEARKIMPE-2: A VBA Excel program for characterizing granular iron in treatability studies

NASA Astrophysics Data System (ADS)

Firdous, R.; Devlin, J. F.

2014-02-01

The selection of a suitable kinetic model to investigate the reaction rate of a contaminant with granular iron (GI) is essential to optimize the permeable reactive barrier (PRB) performance in terms of its reactivity. The newly developed Kinetic Iron Model (KIM) determines the surface rate constant (k) and sorption parameters (Cmax &J) which were not possible to uniquely identify previously. The code was written in Visual Basic (VBA), within Microsoft Excel, was adapted from earlier command line FORTRAN codes, BEARPE and KIMPE. The program is organized with several user interface screens (UserForms) that guide the user step by step through the analysis. BEARKIMPE-2 uses a non-linear optimization algorithm to calculate transport and chemical kinetic parameters. Both reactive and non-reactive sites are considered. A demonstration of the functionality of BEARKIMPE-2, with three nitroaromatic compounds showed that the differences in reaction rates for these compounds could be attributed to differences in their sorption behavior rather than their propensities to accept electrons in the reduction process.

Generation of Antigen Microarrays to Screen for Autoantibodies in Heart Failure and Heart Transplantation.

PubMed

Chruscinski, Andrzej; Huang, Flora Y Y; Nguyen, Albert; Lioe, Jocelyn; Tumiati, Laura C; Kozuszko, Stella; Tinckam, Kathryn J; Rao, Vivek; Dunn, Shannon E; Persinger, Michael A; Levy, Gary A; Ross, Heather J

2016-01-01

Autoantibodies directed against endogenous proteins including contractile proteins and endothelial antigens are frequently detected in patients with heart failure and after heart transplantation. There is evidence that these autoantibodies contribute to cardiac dysfunction and correlate with clinical outcomes. Currently, autoantibodies are detected in patient sera using individual ELISA assays (one for each antigen). Thus, screening for many individual autoantibodies is laborious and consumes a large amount of patient sample. To better capture the broad-scale antibody reactivities that occur in heart failure and post-transplant, we developed a custom antigen microarray technique that can simultaneously measure IgM and IgG reactivities against 64 unique antigens using just five microliters of patient serum. We first demonstrated that our antigen microarray technique displayed enhanced sensitivity to detect autoantibodies compared to the traditional ELISA method. We then piloted this technique using two sets of samples that were obtained at our institution. In the first retrospective study, we profiled pre-transplant sera from 24 heart failure patients who subsequently received heart transplants. We identified 8 antibody reactivities that were higher in patients who developed cellular rejection (2 or more episodes of grade 2R rejection in first year after transplant as defined by revised criteria from the International Society for Heart and Lung Transplantation) compared with those who did have not have rejection episodes. In a second retrospective study with 31 patients, we identified 7 IgM reactivities that were higher in heart transplant recipients who developed antibody-mediated rejection (AMR) compared with control recipients, and in time course studies, these reactivities appeared prior to overt graft dysfunction. In conclusion, we demonstrated that the autoantibody microarray technique outperforms traditional ELISAs as it uses less patient sample, has increased sensitivity, and can detect autoantibodies in a multiplex fashion. Furthermore, our results suggest that this autoantibody array technology may help to identify patients at risk of rejection following heart transplantation and identify heart transplant recipients with AMR.

Generation of Antigen Microarrays to Screen for Autoantibodies in Heart Failure and Heart Transplantation

PubMed Central

Chruscinski, Andrzej; Huang, Flora Y. Y.; Nguyen, Albert; Lioe, Jocelyn; Tumiati, Laura C.; Kozuszko, Stella; Tinckam, Kathryn J.; Rao, Vivek; Dunn, Shannon E.; Persinger, Michael A.; Levy, Gary A.; Ross, Heather J.

2016-01-01

Autoantibodies directed against endogenous proteins including contractile proteins and endothelial antigens are frequently detected in patients with heart failure and after heart transplantation. There is evidence that these autoantibodies contribute to cardiac dysfunction and correlate with clinical outcomes. Currently, autoantibodies are detected in patient sera using individual ELISA assays (one for each antigen). Thus, screening for many individual autoantibodies is laborious and consumes a large amount of patient sample. To better capture the broad-scale antibody reactivities that occur in heart failure and post-transplant, we developed a custom antigen microarray technique that can simultaneously measure IgM and IgG reactivities against 64 unique antigens using just five microliters of patient serum. We first demonstrated that our antigen microarray technique displayed enhanced sensitivity to detect autoantibodies compared to the traditional ELISA method. We then piloted this technique using two sets of samples that were obtained at our institution. In the first retrospective study, we profiled pre-transplant sera from 24 heart failure patients who subsequently received heart transplants. We identified 8 antibody reactivities that were higher in patients who developed cellular rejection (2 or more episodes of grade 2R rejection in first year after transplant as defined by revised criteria from the International Society for Heart and Lung Transplantation) compared with those who did have not have rejection episodes. In a second retrospective study with 31 patients, we identified 7 IgM reactivities that were higher in heart transplant recipients who developed antibody-mediated rejection (AMR) compared with control recipients, and in time course studies, these reactivities appeared prior to overt graft dysfunction. In conclusion, we demonstrated that the autoantibody microarray technique outperforms traditional ELISAs as it uses less patient sample, has increased sensitivity, and can detect autoantibodies in a multiplex fashion. Furthermore, our results suggest that this autoantibody array technology may help to identify patients at risk of rejection following heart transplantation and identify heart transplant recipients with AMR. PMID:26967734

Reactive low temperature plasma ionization mass spectrometry for the determination of organic UV filters in personal care products.

PubMed

Ding, Xuelu; Gerbig, Stefanie; Spengler, Bernhard; Schulz, Sabine

2018-02-01

Organic UV filters in personal care products (PCPs) have been persistently reported as a potential threat to human health. In order to guarantee consumers ' safety, the dose of these compounds in PCPs needs to be monitored. Here, a methodology based on reactive low temperature plasma ionization (LTP) mass spectrometry (MS) has been developed for the determination of common organic UV filters in PCPs including benzophenone-3, ethylhexyl dimethyl p-aminobenzoic acid, ethylhexyl methoxycinnamate, 4-methylbenzylidene camphor, octocrylene, and ethylhexyl salicylate. The experiments were carried out in transmission geometry where the LTP ion source, samples loaded on a stainless steel mesh, and the MS inlet were aligned coaxially. Four chemicals, ammonia, ammonium formate, aniline, and methylamine were considered as reactive additives allowing reactions with the UV filters through different mechanisms. Methylamine-induced reactive LTP-MS showed the most prominent improvement on the detection of UV filter compounds. Compared to direct LTP-MS, the developed method improved the detection limits of UV filters more than 10 fold. Moreover, the method enabled fast semi-quantitative screening of UV filters in authentic PCPs. Concentrations of active ingredients in eight authentic PCPs as determined with reactive LTP-MS were found comparable to values offered by the cosmetic companies and corresponding HPLC data. The methodology provides high throughput analysis (70s per sample) and sensitive identification of organic UV filters. Lowest detectable concentrations ranged from 0.13µg/g for 4-methylbenzylidene camphor to 7.67µg/g for octocrylene in spiked cream. In addition, it shows the potential to be used as a screening tool for legal authentications of these chemicals in the future due to its semi-quantitative determination of UV filters in PCPs without tedious sample preparation and time-consuming chromatographic separation. Copyright © 2017 Elsevier B.V. All rights reserved.

Approach to the vadose zone monitoring in hazardous and solid waste disposal facilities

NASA Astrophysics Data System (ADS)

Twardowska, Irena

2004-03-01

In the solid waste (SW)disposal sites, in particular at the unlined facilities, at the remediated or newly-constructed units equipped with novel protective/reactive permeable barriers or at lined facilities with leachate collection systems that are prone to failure, the vadose zone monitoring should comprise besides the natural soil layer beneath the landfill, also the anthropogenic vadose zone, i.e. the waste layer and pore solutions in the landfill. The vadose zone screening along the vertical profile of SW facilities with use of direct invasive soil-core and soil-pore liquid techniques shows vertical downward redistribution of inorganic (macroconstituents and heavy metals) and organic (PAHs) contaminant loads in water infiltrating through the waste layer. These loads can make ground water down-gradient of the dump unfit for any use. To avoid damage of protective/reactive permeable barriers and liners, an installation of stationary monitoring systems along the waste layer profile during the construction of a landfill, which are amenable to generate accurate data and information in a near-real time should be considered including:(i) permanent samplers of pore solution, with a periodic pump-induced transport of collected solution to the surface, preferably with instant field measurements;(ii)chemical sensors with continuous registration of critical parameters. These techniques would definitely provide an early alert in case when the chemical composition of pore solution percolating downward the waste profile shows unfavorable transformations, which indicate an excessive contaminant load approaching ground water. The problems concerning invasive and stationary monitoring of the vadose zone in SW disposal facilities will be discussed at the background of results of monitoring data and properties of permeable protective/reactive barriers considered for use.

Nucleic acid testing: Is it the only answer for safe Blood in India?

PubMed Central

Naidu, N. K.; Bharucha, Z. S.; Sonawane, Vandana; Ahmed, Imran

2016-01-01

Background: With the implementation of NAT in countries around the world, there is a growing pressure on the transfusion services in India to adopt NAT testing. India has about 2545 licensed Blood Centres. The Transfusion Services in India are fragmented, poorly regulated and the quality standards are poorly implemented. Blood Centres are still dependent on replacement/family donors and in most places laboratory testing for Transfusion transmitted infections is not quality assured, laboratory equipment are not calibrated and maintained, and validation of results is not carried out. Against the current scenario introducing NAT for screening of blood donors in India would pose a challenge. Aim: To study the prudence of universal NAT testing in India. Materials and Methods: A retrospective study of 5 years from 2008-2012 was undertaken to study the true reactivity of donors using WHO strategy II and III and therefore the true seroprevalence of TTI infections in the donor populations. Results: The true reactivity of the donors was much less as compared to the initially reactive donors due to the use of a well designed testing algorithm. In addition having a total voluntary blood collection along with good pre-donation counseling program also reduces the transmission of infections. Conclusions: What India essentially needs to do is religiously implement the strategies outlined in the WHO Aide-memoire. The blood should be collected only from voluntary non remunerative and repeat donors, there should be stringent donor selection with pre-donation counseling instituted. Strict implementation of quality management system, development of well defined testing startegies and strong haemovigilance system could take us a step in the right direction. PMID:27011677

A multipumping flow system for in vitro screening of peroxynitrite scavengers.

PubMed

Ribeiro, Marta F T; Dias, Ana C B; Santos, João L M; Fernandes, Eduarda; Lima, José L F C; Zagatto, Elias A G

2007-09-01

Peroxynitrite anion is a reactive nitrogen species formed in vivo by the rapid, controlled diffusion reaction between nitric oxide and superoxide radicals. By reacting with several biological molecules, peroxynitrite may cause important cellular and tissue deleterious effects, which have been associated with many diseases. In this work, an automated flow-based procedure for the in vitro generation of peroxynitrite and subsequent screening of the scavenging activity of selected compounds is developed. This procedure involves a multipumping flow system (MPFS) and exploits the ability of compounds such as lipoic acid, dihydrolipoic acid, cysteine, reduced glutathione, oxidized glutathione, sulindac, and sulindac sulfone to inhibit the chemiluminescent reaction of luminol with peroxynitrite under physiological simulated conditions. Peroxynitrite was generated in the MPFS by the online reaction of acidified hydrogen peroxide with nitrite, followed by a subsequent stabilization by merging with a sodium hydroxide solution to rapidly quench the developing reaction. The pulsed flow and the timed synchronized insertion of sample and reagent solutions provided by the MPFS ensure the establishment of the reaction zone only inside the flow cell, thus allowing maximum chemiluminescence emission detection. The results obtained for the assayed compounds show that, with the exception of oxidized glutathione, all are highly potent scavengers of peroxynitrite at the studied concentrations.

HIV‑2 antibody detection after indeterminate or negative HIV‑1 Western blot in Cuba, 2005-2008.

PubMed

Díaz, Dervel F; Ortiz, Eva; Martín, Dayamí; Nibot, Carmen; Rizo, Adis; Silva, Eladio

2012-01-01

INTRODUCTION Differentiating between HIV-1 and HIV-2 infection is the first step to understanding HIV transmission, epidemiology and pathogenesis in geographical areas where both viruses circulate. In Cuba, positive results in mixed HIV-1/2 screening assays are confirmed by HIV-1 Western blot. Indeterminate results constitute the main limitation of this test and HIV-2 infection is among their possible causes; hence the importance of second-stage screening and confirmatory tests for HIV-2 infection. OBJECTIVE Investigate the contribution of HIV-2 antibodies to negative or indeterminate HIV-1 Western blot results in serum samples from 2005 through 2008 in Cuba. METHODS HIV-2 reactivity was studied using the ELISA DAVIH-VIH-2 diagnostic kit (Cuba) in 1723 serum samples with negative or indeterminate results for HIV-1 Western blot from January 2005 through December 2008. Duplicate sera reactive by ELISA were confirmed by HIV-2 Western blot, results interpreted according to WHO criteria. The epidemiological interview established by Cuba's National Program for Prevention and Control Sexually-Transmitted Diseases and HIV/AIDS was applied to HIV-2 Western blot-positive patients. RESULTS Among all sera studied, HIV-2 ELISA identified 12 reactive serum samples (0.70%) and 1711 non-reactive (99.30%). Western blot analysis of the 12 ELISA-reactive samples confirmed two positive samples (16.67%), 4 negative (33.33%) and 6 indeterminate (50%). Positive samples reacted against the p16, p26, gp36, p53, p56, p68 and gp105 proteins. All 12 ELISA-reactive samples belonged to the HIV-1 Western blot indeterminate group. The two HIV-2-positive samples showed well defined reactivity to gp160, p53, p55 and p34 of HIV-1. HIV-1 seroconversion was observed in all 10 remaining samples during serological followup. CONCLUSIONS Two new HIV-2 seropositive cases were diagnosed using DAVIH-VIH-2 and HIV-2 Western blot in indeterminate HIV-1 Western blot samples. Results support the recommendation that HIV-2 Western blot be included in the diagnostic algorithm for HIV-1/2 to followup negative or indeterminate HIV-1 Western blot results. KEYWORDS Diagnosis, laboratory techniques and procedures, antibodies, HIV-2, Western blot, enzyme-linked immunosorbent assay, algorithm, Cuba.

A fluorescence high throughput screening method for the detection of reactive electrophiles as potential skin sensitizers

USDA-ARS?s Scientific Manuscript database

Skin sensitization is an important toxicological end-point in the risk assessment of chemical allergens. Because of the complexity of the biological mechanisms associated with skin sensitization integrated approaches combining different chemical, biological and in silico methods are recommended to r...

21 CFR 640.70 - Labeling.

Code of Federal Regulations, 2010 CFR

2010-04-01

... STANDARDS FOR HUMAN BLOOD AND BLOOD PRODUCTS Source Plasma § 640.70 Labeling. (a) In addition to the... container of Source Plasma: (1) The proper name of the product. (2) The statement “Caution: For... size and type of print as the proper name. If the Source Plasma has a reactive screening test for...

21 CFR 640.70 - Labeling.

Code of Federal Regulations, 2011 CFR

2011-04-01

... STANDARDS FOR HUMAN BLOOD AND BLOOD PRODUCTS Source Plasma § 640.70 Labeling. (a) In addition to the... container of Source Plasma: (1) The proper name of the product. (2) The statement “Caution: For... size and type of print as the proper name. If the Source Plasma has a reactive screening test for...

Progress in plant protoplast research.

PubMed

Eeckhaut, Tom; Lakshmanan, Prabhu Shankar; Deryckere, Dieter; Van Bockstaele, Erik; Van Huylenbroeck, Johan

2013-12-01

In this review we focus on recent progress in protoplast regeneration, symmetric and asymmetric hybridization and novel technology developments. Regeneration of new species and improved culture techniques opened new horizons for practical breeding in a number of crops. The importance of protoplast sources and embedding systems is discussed. The study of reactive oxygen species effects and DNA (de)condensation, along with thorough phytohormone monitoring, are in our opinion the most promising research topics in the further strive for rationalization of protoplast regeneration. Following, fusion and fragmentation progress is summarized. Genomic, transcriptomic and proteomic studies have led to better insights in fundamental processes such as cell wall formation, cell development and chromosome rearrangements in fusion products, whether or not obtained after irradiation. Advanced molecular screening methods of both genome and cytoplasmome facilitate efficient screening of both symmetric and asymmetric fusion products. We expect that emerging technologies as GISH, high resolution melting and next generation sequencing will pay major contributions to our insights of genome creation and stabilization, mainly after asymmetric hybridization. Finally, we demonstrate agricultural valorization of somatic hybridization through enumerating recent introgression of diverse traits in a number of commercial crops.

Matrix effect and cross-reactivity of select amphetamine-type substances, designer analogues, and putrefactive amines using the Bio-Quant direct ELISA presumptive assays for amphetamine and methamphetamine.

PubMed

Apollonio, Luigino G; Whittall, Ian R; Pianca, Dennis J; Kyd, Jennelle M; Maher, William A

2007-05-01

The aim of this study was to evaluate the Bio-Quant Direct ELISA assays for amphetamine and methamphetamine in the routine presumptive screening of biological fluids. Standard concentration curves of the target analytes were assayed to assess sensitivity, and known concentrations of common amphetamine-type substances (ephedrine, pseudoephedrine, phentermine), designer analogues (MDA, MDMA, MDEA, MBDB, PMA, 4-MTA, 2CB), and putrefactive amines (phenylethylamine, putrescine, tryptamine, tyramine) were analyzed to determine cross-reactivity. Results of the standard curve studies show the capacity of both Direct ELISA kits to confidently detect down to 3 ng/mL interday (PBS matrix; CVs 6.3-15.5%). Cross-reactivity relative to that of 50 ng/mL preparations of the target compounds demonstrated that the Direct ELISA kit for amphetamine also detected MDA (282%), PMA (265%), 4-MTA (280%), and phentermine (61%), and the Direct ELISA for methamphetamine also assayed positive for MDMA (73%), MDEA (18%), pseudoephedrine (19%), MBDB (8%), and ephedrine (9%). Matrix studies demonstrated that both ELISA kits could be applied to screening of blood, urine, and saliva to a concentration of 6 ng/mL or lower. In conclusion, the Bio-Quant Direct ELISA kits for amphetamine and methamphetamine are fast and accurate and have demonstrated themselves to be useful tools in routine toxicological testing.

Non-animal photosafety assessment approaches for cosmetics based on the photochemical and photobiochemical properties.

PubMed

Onoue, Satomi; Suzuki, Gen; Kato, Masashi; Hirota, Morihiko; Nishida, Hayato; Kitagaki, Masato; Kouzuki, Hirokazu; Yamada, Shizuo

2013-12-01

The main purpose of the present study was to establish a non-animal photosafety assessment approach for cosmetics using in vitro photochemical and photobiochemical screening systems. Fifty-one cosmetics, pharmaceutics and other chemicals were selected as model chemicals on the basis of animal and/or clinical photosafety information. The model chemicals were assessed in terms of photochemical properties by UV/VIS spectral analysis, reactive oxygen species (ROS) assay and 3T3 neutral red uptake phototoxicity testing (3T3 NRU PT). Most phototoxins exhibited potent UV/VIS absorption with molar extinction coefficients of over 1000M(-1)cm(-1), although false-negative prediction occurred for 2 cosmetic phototoxins owing to weak UV/VIS absorption. Among all the cosmetic ingredients, ca. 42% of tested chemicals were non-testable in the ROS assay because of low water solubility; thereby, micellar ROS (mROS) assay using a solubilizing surfactant was employed for follow-up screening. Upon combination use of ROS and mROS assays, the individual specificity was 88.2%, and the positive and negative predictivities were estimated to be 94.4% and 100%, respectively. In the 3T3 NRU PT, 3 cosmetics and 4 drugs were incorrectly predicted not to be phototoxic, although some of them were typical photoallergens. Thus, these in vitro screening systems individually provide false predictions; however, a systematic tiered approach using these assays could provide reliable photosafety assessment without any false-negatives. The combined use of in vitro assays might enable simple and fast non-animal photosafety evaluation of cosmetic ingredients. Copyright © 2013 Elsevier Ltd. All rights reserved.

Procyanidin trimer C1 derived from Theobroma cacao reactivates latent human immunodeficiency virus type 1 provirus.

PubMed

Hori, Takanori; Barnor, Jacob; Huu, Tung Nguyen; Morinaga, Osamu; Hamano, Akiko; Ndzinu, Jerry; Frimpong, Angela; Minta-Asare, Keren; Amoa-Bosompem, Mildred; Brandful, James; Odoom, John; Bonney, Joseph; Tuffour, Isaac; Owusu, Baffour-Awuah; Ofosuhene, Mark; Atchoglo, Philip; Sakyiamah, Maxwell; Adegle, Richard; Appiah-Opong, Regina; Ampofo, William; Koram, Kwadwo; Nyarko, Alexander; Okine, Laud; Edoh, Dominic; Appiah, Alfred; Uto, Takuhiro; Yoshinaka, Yoshiyuki; Uota, Shin; Shoyama, Yukihiro; Yamaoka, Shoji

2015-04-03

Despite remarkable advances in combination antiretroviral therapy (cART), human immunodeficiency virus type 1 (HIV-1) infection remains incurable due to the incomplete elimination of the replication-competent virus, which persists in latent reservoirs. Strategies for targeting HIV reservoirs for eradication that involves reactivation of latent proviruses while protecting uninfected cells by cART are urgently needed for cure of HIV infection. We screened medicinal plant extracts for compounds that could reactivate the latent HIV-1 provirus and identified a procyanidin trimer C1 derived from Theobroma cacao as a potent activator of the provirus in human T cells latently infected with HIV-1. This reactivation largely depends on the NF-κB and MAPK signaling pathways because either overexpression of a super-repressor form of IκBα or pretreatment with a MEK inhibitor U0126 diminished provirus reactivation by C1. A pan-PKC inhibitor significantly blocked the phorbol ester-induced but not the C1-induced HIV-1 reactivation. Although C1-induced viral gene expression persisted for as long as 48 h post-stimulation, NF-κB-dependent transcription peaked at 12 h post-stimulation and then quickly declined, suggesting Tat-mediated self-sustainment of HIV-1 expression. These results suggest that procyanidin C1 trimer is a potential compound for reactivation of latent HIV-1 reservoirs. Copyright © 2015 Elsevier Inc. All rights reserved.

Reactivation of Herpesvirus in Patients With Hepatitis C Treated With Direct-Acting Antiviral Agents.

PubMed

Perelló M, Christie; Fernández-Carrillo, Carlos; Londoño, María-Carlota; Arias-Loste, Teresa; Hernández-Conde, Marta; Llerena, Susana; Crespo, Javier; Forns, Xavier; Calleja, José Luis

2016-11-01

We performed a case-series analysis of reactivation of herpesvirus in patients with hepatitis C virus (HCV) infection treated with direct-acting antiviral (DAA) agents. We collected data from 576 patients with HCV infection treated with DAA combinations at 3 hospitals in Spain, from November 2014 through November 2015. We also collected data from a control population (230 HCV-infected patients, matched for sex and age; 23 untreated and 213 treated with interferon-based regimens). Herpesvirus was reactivated in 10 patients who received DAA therapy (7 patients had cirrhosis and 3 patients had received liver transplants), a median of 8 weeks after the therapy was initiated. None of the controls had herpesvirus reactivation. Patients with herpesvirus reactivation were receiving the DAA agents sofosbuvir with ledipasvir (with or without ribavirin, 7/10), ombitasvir with paritaprevir and ritonavir plus dasabuvir (with or without ribavirin, 2/10), or sofosbuvir with simeprevir plus ribavirin (1/10). Two of the 10 patients developed postherpetic neuralgia and 1 patient developed kerato-uveitis. All 10 patients with herpesvirus reactivation achieved a sustained virologic response. Immune changes that follow clearance of HCV might lead to reactivation of other viruses, such as herpesvirus. Patients with HCV infection suspected of having herpesvirus infection should be treated immediately. Some groups also might be screened for herpesvirus infection. Copyright © 2016 AGA Institute. Published by Elsevier Inc. All rights reserved.

Maternal prenatal stress and infant emotional reactivity six months postpartum.

PubMed

Nolvi, Saara; Karlsson, Linnea; Bridgett, David J; Korja, Riikka; Huizink, Anja C; Kataja, Eeva-Leena; Karlsson, Hasse

2016-07-15

Maternal prenatal stress has been related to infant negative affect. However, it is still unclear how different sources of maternal prenatal stress such as depressive, anxiety and pregnancy-specific anxiety symptoms are associated with reactivity outcomes. This study aimed to test the associations between different sources of maternal prenatal stress and the aspects of infant emotional reactivity at six months. Our study population (n=282) was drawn from the FinnBrain Birth Cohort Study. Prenatal stress was measured by questionnaires on maternal depression, general anxiety and pregnancy-specific anxiety at three time points across pregnancy (gwk 14, 24, 34). Based on the symptom scores, the sample was divided into mothers with high stress during pregnancy (n=110) and mothers with low stress during pregnancy (n=172). Mother-reported infant emotional reactivity and its subscales were measured six months postpartum. After controlling for background variables and maternal postnatal symptoms, overall negative emotional reactivity (β=0.20, p<0.01), and its aspects fearfulness (β=0.15, p=.057) and falling reactivity (β=-0.22, p<0.01), were predicted by only pregnancy-specific anxiety. No significant predictors were found for infant positive reactivity after adjusting for confounders. Mother reports of both maternal symptoms and infant reactivity were used, which might increase the risk of reporting bias. The findings suggest that mothers experiencing stress should be provided intervention during pregnancy, and that screening should have a particular focus on pregnancy-related worries. Copyright © 2016 Elsevier B.V. All rights reserved.

Software Development Technologies for Reactive, Real-Time, and Hybrid Systems: Summary of Research

NASA Technical Reports Server (NTRS)

Manna, Zohar

1998-01-01

This research is directed towards the implementation of a comprehensive deductive-algorithmic environment (toolkit) for the development and verification of high assurance reactive systems, especially concurrent, real-time, and hybrid systems. For this, we have designed and implemented the STCP (Stanford Temporal Prover) verification system. Reactive systems have an ongoing interaction with their environment, and their computations are infinite sequences of states. A large number of systems can be seen as reactive systems, including hardware, concurrent programs, network protocols, and embedded systems. Temporal logic provides a convenient language for expressing properties of reactive systems. A temporal verification methodology provides procedures for proving that a given system satisfies a given temporal property. The research covered necessary theoretical foundations as well as implementation and application issues.

Reliability of techniques used in the diagnosis of canine visceral leishmaniasis by the national control program in Brazil: A survey in an area of recent transmission.

PubMed

Belo, Vinícius Silva; Gregório, Eliana Aparecida; Teixeira-Neto, Rafael Gonçalves; da Rocha Lima, Ana Cristina Vianna Mariano; Pereira, Agnes Antônia Sampaio; Marcelino, Andreza Pain; Paz, Gustavo Fontes; da Silva, Eduardo Sérgio

2017-10-01

One of the key components of the Brazilian Program for the Control of Visceral Leishmaniasis (PCLV) is the euthanasia of Leishmania-infected canine reservoirs, the detection of which depends on a screening procedure involving a Dual Path Platform ® (DPP) immunoassay and a confirmatory enzyme-linked immunosorbent assay (ELISA). The aims of the present study were to evaluate the reliability of these techniques in a region of recent transmission of canine VL, to follow up the seroconversion 3-4 months after the initial diagnosis of DPP reactive but ELISA indeterminate or non-reactive dogs, and to identify the species of Leishmania in circulation in the area. Each animal was submitted to DPP under field conditions, performed by municipal health workers using peripheral blood (DPP-field), to DPP under laboratory conditions using serum (DPP-lab) and to ELISA using serum. The agreements between the tests were determined using McNemar's χ 2 test, Cohen's kappa coefficient (k) at the 95% confidence interval and prevalence-adjusted bias-adjusted kappa (PABAK). Of the 1130 dogs examined, 74.2% were non-reactive in all three tests applied. Based on the PCLV positive-infection criterion, seroprevalence was 8.9% (101/1130) with 83.2% (84/101) of infected animals showing reactivity in all three tests while 7.8% (8/101) were reactive in DPP-field and ELISA and 8.9% (9/101) in DPP-lab and ELISA. The proportions of disagreements were substantial in all comparisons. Inter-rater reliability between DPP-field and ELISA (k=0.55; PABAK=0.78) and DPP-lab and ELISA (k=0.59; PABAK=0.81) were considered moderate, while that between DPP-field and DPP-lab (k=0.61; PABAK=0.79) was classified as marginally good. The proportion of seroconversions in DPP reactive animals that were initially ELISA indeterminate was significantly higher than in those that were DPP reactive but initially ELISA non-reactive. Restriction fragment length polymorphism analysis revealed the presence of Leishmania infantum, the etiologic agent of VL, in bone marrow samples from VL-infected animals. Our data showed that the techniques and protocols currently employed in the PCLV screening approach are not entirely reliable. Further consideration should be given to monitoring dogs with undetermined results in ELISA and a better training should be provided for health workers responsible for performing DPP tests applied under field conditions. Copyright © 2017 Elsevier B.V. All rights reserved.

Validity of the Enzyme-linked Immunoelectrotransfer Blot (EITB) for naturally acquired porcine cysticercosis

PubMed Central

Jayashi, César M.; Gonzalez, Armando E.; Neyra, Ricardo Castillo; Rodríguez, Silvia; García, Hector H.; Lightowlers, Marshall W.

2017-01-01

The Enzyme-linked Immunoelectrotransfer Blot (EITB) has been used widely as a screening test for Taenia solium cysticercosis in swine. However, the relation between seropositivity and infection in pig populations from endemic areas has not been well defined. The aim of this study is to relate EITB seropositivity with infection and infection burden, analyse the trade-off between sensitivity and specificity with various cut-off points for the EITB assay, and finally describe the serology changes in a cohort of rural pigs raised under natural conditions. A group of 107 pigs that were used as controls during a vaccination field trial in Peru was our study population. The prevalence of porcine cysticercosis determined by necropsy examination was 16.82% (18/107) in these animals. Using EITB reactivity to ≥ 1 band as a cut-off point for the assay, the sensitivity was 88.89% (65.29-98.62, 95% CI) and the specificity was 48.31% (37.59-59.16, 95% CI). Comparing other cut-off points, involving up to as many as 7 reactive bands, a reactivity of ≥ 3 bands provided the best trade-offs in sensitivity and specificity. Using this cut-off point for the assay, the sensitivity was 77.77% (52.36 - 93.59, 95% CI) and the specificity was 76.40% (66.22 - 84.76, 95% CI). A significant association was found between cyst counts over 100 cysts and reactivity to ≥ 3 bands in the EITB assay (Fisher’s exact test, p<0.05). The results of this study suggest that the use of the EITB assay to study porcine cysticercosis may require setting different cut-offs under field and experimental conditions, and depending upon the objective of the screening process. PMID:24183647

Detection of toxoplasma-specific immunoglobulin G in human sera: performance comparison of in house Dot-ELISA with ECLIA and ELISA.

PubMed

Teimouri, Aref; Modarressi, Mohammad Hossein; Shojaee, Saeedeh; Mohebali, Mehdi; Zouei, Nima; Rezaian, Mostafa; Keshavarz, Hossein

2018-05-08

In the current study, performance of electrochemiluminescence immunoassay (ECLIA) in detection of anti-toxoplasma IgG in human sera was compared with that of enzyme-linked immunosorbent assay (ELISA). Furthermore, performance of an in house Dot-ELISA in detection of anti-toxoplasma IgG was compared with that of ECLIA and ELISA. In total, 219 human sera were tested to detect anti-toxoplasma IgG using Dynex DS2® and Roche Cobas® e411 Automated Analyzers. Discordant results rechecked using immunofluorescence assay (IFA). Then, sera were used in an in house Dot-ELISA to assess toxoplasma-specific IgG. Of the 219 samples, two samples were found undetermined using ECLIA but reactive using ELISA. Using IFA, the two sera were reported unreactive. Furthermore, two samples were found reactive using ECLIA and unreactive using ELISA. These samples were reported reactive using IFA. The overall agreement for the two former methods was 98% (rZ0.98.1; P < 0.001). The intrinsic parameters calculated for in house Dot-ELISA included sensitivity of 79.5, specificity of 78.2, and accuracy of 78.9%, compared to ECLIA and ELISA. Positive and negative predictive values included 82.9 and 74.2%, respectively. A 100% sensitivity was found in in house Dot-ELISA for highly reactive sera in ECLIA and ELISA. ECLIA is appropriate for the first-line serological screening tests and can replace ELISA due to high speed, sensitivity, and specificity, particularly in large laboratories. Dot-ELISA is a rapid, sensitive, specific, cost-effective, user-friendly, and field-portable technique and hence can be used for screening toxoplasmosis, especially in rural fields or less equipped laboratories.

Photographic Combustion Characterization of LOX/Hydrocarbon Type Propellants

NASA Technical Reports Server (NTRS)

Judd, D. C.

1980-01-01

The advantages and limitations of using high speed photography to identify potential combustion anomalies (pops, fuel freezing, reactive stream separation (RSS), carbon formation) were demonstrated. Combustion evaluation criteria were developed for evaluating, characterizing, and screening promising low cost propellant combination(s) and injector element(s) for long life, reusable engine systems. Carbon formation and RSS mechanisms and trends were identified by using high speed color photography at speeds up to 6000 frames/sec. Single element injectors were tested with LOX/RP-1, LOX/Propane, LOX/Methane and LOX/Ammonia propellants. Tests were conducted using seven separate injector elements. Five different conventionally machined elements were tested: OFO Triplet; Rectangular Unlike Doublet (RUD); Unlike Doublet (UD); Like on Lke Doublet (LOL-EDM); and Slit Triplet.

Construction of High Activity Titanium Dioxide Crystal Surface Heterostructures and Characterization of Its Basic Properties

NASA Astrophysics Data System (ADS)

Wang, Chunxiao; Li, DanQi; Shen, Tingting; Lu, Cheng; Sun, Jing; Wang, Xikui

2018-01-01

Heterogeneous photocatalytic materials, which combine the advantages of photocatalytic materials and heterojunction, have been developed rapidly in the field of environmental pollution control. In this paper, TiO2 surface heterojunction catalysts with different catalytic activity were prepared by controlling the amount of HF, and their XRD characterization was also carried out. In addition, the optimum amount of HF was determined by photocatalytic degradation of simulated dye wastewater by methylene blue solution. And the optimal amount of catalyst and the optimal pH reaction conditions for degradation experiments were used to screen the highly reactive titania surface heterojunction system and its optimum application conditions. It provides the possibility of application in the degradation of industrial wastewater and environmental treatment.

Persistent latent tuberculosis reactivation risk in United States immigrants.

PubMed

Walter, Nicholas D; Painter, John; Parker, Matthew; Lowenthal, Phillip; Flood, Jennifer; Fu, Yunxin; Asis, Redentor; Reves, Randall

2014-01-01

Current guidelines limit latent tuberculosis infection (LTBI) evaluation to persons in the United States less than or equal to 5 years based on the assumption that high TB rates among recent entrants are attributable to high LTBI reactivation risk, which declines over time. We hypothesized that high postarrival TB rates may instead be caused by imported active TB. Estimate reactivation and imported TB in an immigrant cohort. We linked preimmigration records from a cohort of California-bound Filipino immigrants during 2001-2010 with subsequent TB reports. TB was likely LTBI reactivation if the immigrant had no evidence of active TB at preimmigration examination, likely imported if preimmigration radiograph was abnormal and TB was reported less than or equal to 6 months after arrival, and likely reactivation of inactive TB if radiograph was abnormal but TB was reported more than 6 months after arrival. Among 123,114 immigrants, 793 TB cases were reported. Within 1 year of preimmigration examination, 85% of TB was imported; 6 and 9% were reactivation of LTBI and inactive TB, respectively. Conversely, during Years 2-9 after U.S. entry, 76 and 24% were reactivation of LTBI and inactive TB, respectively. The rate of LTBI reactivation (32 per 100,000) did not decline during Years 1-9. High postarrival TB rates were caused by detection of imported TB through active postarrival surveillance. Among immigrants without active TB at baseline, reported TB did not decline over 9 years, indicating sustained high risk of LTBI reactivation. Revised guidelines should support LTBI screening and treatment more than 5 years after U.S. arrival.

Atypical angioimmunoblastic T-cell lymphomas masquerading as systemic polyclonal B-immunoblastic proliferation.

PubMed

Papadi, Bhavesh; Polski, Jacek M; Clarkson, David R; Liu-Dumlao, Theresa O

2012-09-01

Angioimmunoblastic T cell lymphoma (AITL) is a relatively rare peripheral T cell lymphoma derived from follicular T helper cells. AITL has a varied presentation, both clinically and morphologically. AITL can pose a diagnostic challenge as it may be difficult to identify and characterize the neoplastic cells among the polymorphous infiltrates composed of polyclonal B immunoblasts and plasma cells. In AITL, the reactive B cell and plasma cell proliferation is secondary to dysregulated secretion of cytokines such as interleukin-6 by the neoplastic follicular T helper cells. SPBIP is a condition of unknown etiopathogenesis characterized by systemic involvement by polyclonal B immunoblasts and plasma cells. We report two cases of AITL, which are presented with atypical findings making it difficult to diagnose. The cases had features similar to SPBIP. Our cases highlight the importance of screening cases of polyclonal plasmacytosis and SPBIP like cases for underlying AITL.

Application of the Firefly and Luus-Jaakola algorithms in the calculation of a double reactive azeotrope

NASA Astrophysics Data System (ADS)

Mendes Platt, Gustavo; Pinheiro Domingos, Roberto; Oliveira de Andrade, Matheus

2014-01-01

The calculation of reactive azeotropes is an important task in the preliminary design and simulation of reactive distillation columns. Classically, homogeneous nonreactive azeotropes are vapor-liquid coexistence conditions where phase compositions are equal. For homogeneous reactive azeotropes, simultaneous phase and chemical equilibria occur concomitantly with equality of compositions (in the Ung-Doherty transformed space). The modeling of reactive azeotrope calculation is represented by a nonlinear algebraic system with phase equilibrium, chemical equilibrium and azeotropy equations. This nonlinear system can exhibit more than one solution, corresponding to a double reactive azeotrope. In a previous paper (Platt et al 2013 J. Phys.: Conf. Ser. 410 012020), we investigated some numerical aspects of the calculation of reactive azeotropes in the isobutene + methanol + methyl-tert-butyl-ether (with two reactive azeotropes) system using two metaheuristics: the Luus-Jaakola adaptive random search and the Firefly algorithm. Here, we use a hybrid structure (stochastic + deterministic) in order to produce accurate results for both azeotropes. After identifying the neighborhood of the reactive azeotrope, the nonlinear algebraic system is solved using Newton's method. The results indicate that using metaheuristics and some techniques devoted to the calculation of multiple minima allows both azeotropic coordinates in this reactive system to be obtains. In this sense, we provide a comprehensive analysis of a useful framework devoted to solving nonlinear systems, particularly in phase equilibrium problems.

Screen-based entertainment time, all-cause mortality, and cardiovascular events: population-based study with ongoing mortality and hospital events follow-up.

PubMed

Stamatakis, Emmanuel; Hamer, Mark; Dunstan, David W

2011-01-18

The aim of this study was to examine the independent relationships of television viewing or other screen-based entertainment ("screen time") with all-cause mortality and clinically confirmed cardiovascular disease (CVD) events. A secondary objective was to examine the extent to which metabolic (body mass index, high-density lipoprotein and total cholesterol) and inflammatory (C-reactive protein) markers mediate the relationship between screen time and CVD events. Although some evidence suggests that prolonged sitting is linked to CVD risk factor development regardless of physical activity participation, studies with hard outcomes are scarce. A population sample of 4,512 (1,945 men) Scottish Health Survey 2003 respondents (≥35 years) were followed up to 2007 for all-cause mortality and CVD events (fatal and nonfatal combined). Main exposures were interviewer-assessed screen time (<2 h/day; 2 to <4 h/day; and ≥4 h/day) and moderate to vigorous intensity physical activity. Two hundred fifteen CVD events and 325 any-cause deaths occurred during 19,364 follow-up person-years. The covariable (age, sex, ethnicity, obesity, smoking, social class, long-standing illness, marital status, diabetes, hypertension)-adjusted hazard ratio (HR) for all-cause mortality was 1.52 (95% confidence interval [CI]: 1.06 to 2.16) and for CVD events was 2.30 (95% CI: 1.33 to 3.96) for participants engaging in ≥4 h/day of screen time relative to <2 h/day. Adjusting for physical activity attenuated these associations only slightly (all-cause mortality: HR: 1.48, 95% CI: 1.04 to 2.13; CVD events: HR: 2.25, 95% CI: 1.30 to 3.89). Exclusion of participants with CVD events in the first 2 years of follow-up and previous cancer registrations did not change these results appreciably. Approximately 25% of the association between screen time and CVD events was explained collectively by C-reactive protein, body mass index, and high-density lipoprotein cholesterol. Recreational sitting, as reflected by television/screen viewing time, is related to raised mortality and CVD risk regardless of physical activity participation. Inflammatory and metabolic risk factors partly explain this relationship. Copyright © 2011 American College of Cardiology Foundation. Published by Elsevier Inc. All rights reserved.

Specific Nongluten Proteins of Wheat Are Novel Target Antigens in Celiac Disease Humoral Response

PubMed Central

2014-01-01

While the antigenic specificity and pathogenic relevance of immunologic reactivity to gluten in celiac disease have been extensively researched, the immune response to nongluten proteins of wheat has not been characterized. We aimed to investigate the level and molecular specificity of antibody response to wheat nongluten proteins in celiac disease. Serum samples from patients and controls were screened for IgG and IgA antibody reactivity to a nongluten protein extract from the wheat cultivar Triticum aestivum Butte 86. Antibodies were further analyzed for reactivity to specific nongluten proteins by two-dimensional gel electrophoresis and immunoblotting. Immunoreactive molecules were identified by tandem mass spectrometry. Compared with healthy controls, patients exhibited significantly higher levels of antibody reactivity to nongluten proteins. The main immunoreactive nongluten antibody target proteins were identified as serpins, purinins, α-amylase/protease inhibitors, globulins, and farinins. Assessment of reactivity toward purified recombinant proteins further confirmed the presence of antibody response to specific antigens. The results demonstrate that, in addition to the well-recognized immune reaction to gluten, celiac disease is associated with a robust humoral response directed at a specific subset of the nongluten proteins of wheat. PMID:25329597

Bond Strength and Reactivity Scales for Lewis Superacid Adducts: A Comparative Study with In(OTf)3 and Al(OTf)3.

PubMed

Compain, Guillaume; Sikk, Lauri; Massi, Lionel; Gal, Jean-François; Duñach, Elisabet

2017-03-17

Metal triflates, often called Lewis superacids, are potent catalysts for organic synthesis. However, the reactivity of a given Lewis superacid toward a given base is difficult to anticipate. A systematic screening of catalysts is often necessary when developing synthetic methodologies. Presented herein is the development of quantitative reactivity and bond strength scales by using mass spectrometry (MS). By applying a collision-induced dissociation (CID) technique to the adducts formed between Lewis superacids Al(OTf) 3 or In(OTf) 3 with a series of amides bases, including monodentate and bidentate ligands, different dissociation pathways were observed. Quantitative relative energy scales were established by performing energy-resolved mass spectrometry (ERMS) analysis on the adducts. ERMS of the adducts affords a bond strength scale when the fragmentation leads to the loss of a ligand, and reactivity scales when the dissociation leads to the C-F bond activation of one triflate anion or the deprotonation of the ligand. Al(OTf) 3 was found to bind stronger to amides than In(OTf) 3 and to provide the most reactive adducts. © 2017 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim.

Cap-n-Collar Promotes Tissue Regeneration by Regulating ROS and JNK Signaling in the Drosophila melanogaster Wing Imaginal Disc.

PubMed

Brock, Amanda R; Seto, Mabel; Smith-Bolton, Rachel K

2017-07-01

Regeneration is a complex process that requires an organism to recognize and repair tissue damage, as well as grow and pattern new tissue. Here, we describe a genetic screen to identify novel regulators of regeneration. We ablated the Drosophila melanogaster larval wing primordium by inducing apoptosis in a spatially and temporally controlled manner and allowed the tissue to regenerate and repattern. To identify genes that regulate regeneration, we carried out a dominant-modifier screen by assessing the amount and quality of regeneration in adult wings heterozygous for isogenic deficiencies. We have identified 31 regions on the right arm of the third chromosome that modify the regenerative response. Interestingly, we observed several distinct phenotypes: mutants that regenerated poorly, mutants that regenerated faster or better than wild-type, and mutants that regenerated imperfectly and had patterning defects. We mapped one deficiency region to cap-n-collar ( cnc ), the Drosophila Nrf2 ortholog, which is required for regeneration. Cnc regulates reactive oxygen species levels in the regenerating epithelium, and affects c-Jun N-terminal protein kinase (JNK) signaling, growth, debris localization, and pupariation timing. Here, we present the results of our screen and propose a model wherein Cnc regulates regeneration by maintaining an optimal level of reactive oxygen species to promote JNK signaling. Copyright © 2017 by the Genetics Society of America.

Cost-effectiveness of post-landing latent tuberculosis infection control strategies in new migrants to Canada.

PubMed

Campbell, Jonathon R; Johnston, James C; Sadatsafavi, Mohsen; Cook, Victoria J; Elwood, R Kevin; Marra, Fawziah

2017-01-01

The majority of tuberculosis in migrants to Canada occurs due to reactivation of latent TB infection. Risk of tuberculosis in those with latent tuberculosis infection can be significantly reduced with treatment. Presently, only 2.4% of new migrants are flagged for post-landing surveillance, which may include latent tuberculosis infection screening; no other migrants receive routine latent tuberculosis infection screening. To aid in reducing the tuberculosis burden in new migrants to Canada, we determined the cost-effectiveness of using different latent tuberculosis infection interventions in migrants under post-arrival surveillance and in all new migrants. A discrete event simulation model was developed that focused on a Canadian permanent resident cohort after arrival in Canada, utilizing a ten-year time horizon, healthcare system perspective, and 1.5% discount rate. Latent tuberculosis infection interventions were evaluated in the population under surveillance (N = 6100) and the total cohort (N = 260,600). In all evaluations, six different screening and treatment combinations were compared to the base case of tuberculin skin test screening followed by isoniazid treatment only in the population under surveillance. Quality adjusted life years, incident tuberculosis cases, and costs were recorded for each intervention and incremental cost-effectiveness ratios were calculated in relation to the base case. In the population under surveillance (N = 6100), using an interferon-gamma release assay followed by rifampin was dominant compared to the base case, preventing 4.90 cases of tuberculosis, a 4.9% reduction, adding 4.0 quality adjusted life years, and saving $353,013 over the ensuing ten-years. Latent tuberculosis infection screening in the total population (N = 260,600) was not cost-effective when compared to the base case, however could potentially prevent 21.8% of incident tuberculosis cases. Screening new migrants under surveillance with an interferon-gamma release assay and treating with rifampin is cost saving, but will not significantly impact TB incidence. Universal latent tuberculosis infection screening and treatment is cost-prohibitive. Research into using risk factors to target screening post-landing may provide alternate solutions.

Color adaptation induced from linguistic description of color

PubMed Central

Zheng, Liling; Huang, Ping; Zhong, Xiao; Li, Tianfeng; Mo, Lei

2017-01-01

Recent theories propose that language comprehension can influence perception at the low level of perceptual system. Here, we used an adaptation paradigm to test whether processing language caused color adaptation in the visual system. After prolonged exposure to a color linguistic context, which depicted red, green, or non-specific color scenes, participants immediately performed a color detection task, indicating whether they saw a green color square in the middle of a white screen or not. We found that participants were more likely to perceive the green color square after listening to discourses denoting red compared to discourses denoting green or conveying non-specific color information, revealing that language comprehension caused an adaptation aftereffect at the perceptual level. Therefore, semantic representation of color may have a common neural substrate with color perception. These results are in line with the simulation view of embodied language comprehension theory, which predicts that processing language reactivates the sensorimotor systems that are engaged during real experience. PMID:28358807

Color adaptation induced from linguistic description of color.

PubMed

Zheng, Liling; Huang, Ping; Zhong, Xiao; Li, Tianfeng; Mo, Lei

2017-01-01

Recent theories propose that language comprehension can influence perception at the low level of perceptual system. Here, we used an adaptation paradigm to test whether processing language caused color adaptation in the visual system. After prolonged exposure to a color linguistic context, which depicted red, green, or non-specific color scenes, participants immediately performed a color detection task, indicating whether they saw a green color square in the middle of a white screen or not. We found that participants were more likely to perceive the green color square after listening to discourses denoting red compared to discourses denoting green or conveying non-specific color information, revealing that language comprehension caused an adaptation aftereffect at the perceptual level. Therefore, semantic representation of color may have a common neural substrate with color perception. These results are in line with the simulation view of embodied language comprehension theory, which predicts that processing language reactivates the sensorimotor systems that are engaged during real experience.

Construction of helper plasmid-mediated dual-display phage for autoantibody screening in serum.

PubMed

Rajaram, Kaushik; Vermeeren, Veronique; Somers, Klaartje; Somers, Veerle; Michiels, Luc

2014-01-01

M13 filamentous bacteriophage has been used in displaying disease-specific antibodies, biomarkers, and peptides. One of the major drawbacks of using phage in diagnostic assays is the aspecific adsorption of proteins leading to a high background signal and decreasing sensitivity. To deal with this, we developed a genetically pure, exchangeable dual-display phage system in which biomarkers and streptavidin-binding protein (SBP) are displayed at opposite ends of the phage. This approach allows for sample purification, using streptavidin-coated magnetic beads resulting in a higher sensitivity of signal detection assays. Our dual-display cassette system approach also allows for easy exchange of both the anchor protein (SBP) and the displayed biomarker. The presented principle is applied for the detection of antibody reactivity against UH-RA.21 which is a good candidate biomarker for rheumatoid arthritis (RA). The applicability of dual-display phage preparation using a helper plasmid system is demonstrated, and its increased sensitivity in phage ELISA assays using patient serum samples is shown.

Reaction of formaldehyde at the ortho- and para-positions of phenol: exploration of mechanisms using computational chemistry.

Treesearch

Anthony H. Conner; Melissa S. Reeves

2001-01-01

Computational chemistry methods can be used to explore the theoretical chemistry behind reactive systems, to compare the relative chemical reactivity of different systems, and, by extension, to predict the reactivity of new systems. Ongoing research has focused on the reactivity of a wide variety of phenolic compounds with formaldehyde using semi-empirical and ab...

The analysis of false prolongation of the activated partial thromboplastin time (activator: silica): Interference of C-reactive protein.

PubMed

Liu, Jie; Li, Fanfan; Shu, Kuangyi; Chen, Tao; Wang, Xiaoou; Xie, Yaoqi; Li, Shanshan; Zhang, Zhaohua; Jin, Susu; Jiang, Minghua

2018-05-13

To investigate the effect of C-reactive protein on the activated partial thromboplastin time (APTT) (different activators) in different detecting systems. The C-reactive protein and coagulation test of 112 patients with the infectious disease were determined by automation protein analyzer IMMAG 800 and automation coagulation analyzer STA-R Evolution, respectively. The pooled plasma APTT with different concentrations of C-reactive protein was measured by different detecting system: STA-R Evolution (activator: silica, kaolin), Sysmex CS-2000i (activator: ellagic acid), and ACL TOP 700 (activator: colloidal silica). In addition, the self-made platelet lysate (phospholipid) was added to correct the APTT prolonged by C-reactive protein (150 mg/L) on STA-R Evolution (activator: silica) system. The good correlation between C-reactive protein and APTT was found on the STA-R Evolution (activator: silica) system. The APTT on the STA-R Evolution (activator: silica) system was prolonged by 24.6 second, along with increasing C-reactive protein concentration. And the APTT of plasma containing 150 mg/L C-reactive protein was shortened by 3.4-6.9 second when the plasma was mixed with self-made platelet lysate. However, the APTT was prolonged unobviously on other detecting systems including STA-R Evolution (activator: kaolin), Sysmex CS-2000i, and ACL TOP 700. C-reactive protein interferes with the detection of APTT, especially in STA-R Evolution (activator: silica) system. The increasing in C-reactive protein results in a false prolongation of the APTT (activator: silica), and it is most likely that C-reactive protein interferes the coagulable factor binding of phospholipid. © 2018 Wiley Periodicals, Inc.

Survey of citrus tristeza virus populations in Central California that react with MCA13 monoclonal antibody

USDA-ARS?s Scientific Manuscript database

The Citrus Pest Detection Program (CPDP) of the Central California Tristeza Eradication Agency monitors Citrus tristeza virus (CTV) in Central California. MCA13 is a severe strain discriminating monoclonal antibody used to screen for potentially virulent CTV isolates. MCA13-reactive CTV isolates are...

Informatics approach using metabolic reactivity classifiers to link in vitro to in vivo data in application to the ToxCast Phase I dataset

EPA Science Inventory

Strategic combinations and tiered application of alternative testing methods to replace or minimize the use of animal models is attracting much attention. With the advancement of high throughput screening (HTS) assays and legacy databases providing in vivo testing results, suffic...

Central insulin administration improves odor-cued reactivation of spatial memory in young men.

PubMed

Brünner, Yvonne F; Kofoet, Anja; Benedict, Christian; Freiherr, Jessica

2015-01-01

Insulin receptors are ubiquitously found in the human brain, comprising the olfactory bulb, essential for odor processing, and the hippocampus, important for spatial memory processing. The present study aimed at examining if intranasal insulin, which is known to transiently increase brain insulin levels in humans, would improve odor-cued reactivation of spatial memory in young men. We applied a double-blind, placebo-controlled, counterbalanced within-subject design. The study was conducted at the research unit of a university hospital. Interventions/Participants/Main Outcome Measures: Following intranasal administration of either insulin (40 I.U.) or placebo, male subjects (n = 18) were exposed to eight odors. During each odor exposure, a green-colored field was presented on a 17-in. computer screen. During immediate recall (comprising 3 runs), the participants were re-exposed to each odor cue, and were asked to select the corresponding field (with visual feedback after each response). The delayed recall was scheduled ∼10 min later (without feedback). To test if insulin's putative effect on odor-place memory would be domain-specific, participants also performed a separate place and odor recognition task. Intranasal insulin improved the delayed but not immediate odor-cued recall of spatial memory. This effect was independent of odor type and in the absence of systemic side effects (eg, fasting plasma glucose levels remained unaltered). Place and odor recognition were unaffected by the insulin treatment. These findings suggest that acute intranasal insulin improves odor-cued reactivation of spatial memory in young men.

Transcriptional Inhibition of the Human Papilloma Virus Reactivates Tumor Suppressor p53 in Cervical Carcinoma Cells

PubMed Central

Kochetkov, D. V.; Ilyinskaya, G. V.; Komarov, P. G.; Strom, E.; Agapova, L. S.; Ivanov, A. V.; Budanov, A. V.; Frolova, E. I.; Chumakov, P. M.

2009-01-01

Inactivation of tumor suppressor p53 accompanies the majority of human malignancies. Restoration of p53 function causes death of tumor cells and is potentially suitable for gene therapy of cancer. In cervical carcinoma, human papilloma virus (HPV) E6 facilitates proteasomal degradation of p53. Hence, a possible approach to p53 reactivation is the use of small molecules suppressing the function of viral proteins. HeLa cervical carcinoma cells (HPV-18) with a reporter construct containing the b-galactosidase gene under the control of a p53-responsive promoter were used as a test system to screen a library of small molecules for restoration of the transcriptional activity of p53. The effect of the two most active compounds was studied with cell lines differing in the state of p53-dependent signaling pathways. The compounds each specifically activated p53 in cells expressing HPV-18 and, to a lesser extent, HPV-16 and exerted no effect on control p53-negative cells or cells with the intact p53-dependent pathways. Activation of p53 in cervical carcinoma cells was accompanied by induction of p53-dependent CDKN1 (p21), inhibition of cell proliferation, and induction of apoptosis. In addition, the two compounds dramatically decreased transcription of the HPV genome, which was assumed to cause p53 reactivation. The compounds were low-toxic for normal cells and can be considered as prototypes of new anticancer drugs. PMID:17685229

Pubertal changes in emotional information processing: pupillary, behavioral, and subjective evidence during emotional word identification.

PubMed

Silk, Jennifer S; Siegle, Greg J; Whalen, Diana J; Ostapenko, Laura J; Ladouceur, Cecile D; Dahl, Ronald E

2009-01-01

This study investigated pupillary and behavioral responses to an emotional word valence identification paradigm among 32 pre-/early pubertal and 34 mid-/late pubertal typically developing children and adolescents. Participants were asked to identify the valence of positive, negative, and neutral words while pupil dilation was assessed using an eyetracker. Mid-/late pubertal children showed greater peak pupillary reactivity to words presented during the emotional word identification task than pre-/early pubertal children, regardless of word valence. Mid-/late pubertal children also showed smaller sustained pupil dilation than pre-/early pubertal children after the word was no longer on screen. These findings were replicated controlling for participants' age. In addition, mid-/late pubertal children had faster reaction times to all words, and rated themselves as more emotional during their laboratory visit compared to pre-/early pubertal children. Greater recall of emotional words following the task was associated with mid-/late pubertal status, and greater recall of emotional words was also associated with higher peak pupil dilation. These results provide physiological, behavioral, and subjective evidence consistent with a model of puberty-specific changes in neurobehavioral systems underpinning emotional reactivity.

Pubertal Changes in Emotional Information Processing: Pupillary, Behavioral, and Subjective Evidence during Emotional Word Identification

PubMed Central

Silk, Jennifer S.; Siegle, Greg J.; Whalen, Diana J.; Ostapenko, Laura J.; Ladouceur, Cecile D.; Dahl, Ronald E.

2008-01-01

This study investigated pupillary and behavioral responses to an emotional word valence identification paradigm among 32 pre/early and 34 mid/late pubertal typically developing children and adolescents. Participants were asked to identify the valence of positive, negative, and neutral words while pupil dilation was assessed using an eye-tracker. Mid-to-late pubertal children showed greater peak pupillary reactivity to words presented during the emotional word identification task than pre-to-early pubertal children, regardless of word valence. Mid-to-late pubertal children also showed smaller sustained pupil dilation than pre-to-early pubertal children after the word was no longer on screen. These findings were replicated controlling for participants’ age. Additionally, mid-to-late pubertal children had faster reaction times to all words, and rated themselves as more emotional during their laboratory visit compared to pre-to-early pubertal children. Greater recall of emotional words following the task was associated with mid-to-late pubertal status, and greater recall of emotional words was also associated with higher peak pupil dilation. These results provide physiological, behavioral, and subjective evidence consistent with a model of puberty-specific changes in neurobehavioral systems underpinning emotional reactivity. PMID:19144220

Secure provision of reactive power ancillary services in competitive electricity markets

NASA Astrophysics Data System (ADS)

El-Samahy, Ismael

The research work presented in this thesis discusses various complex issues associated with reactive power management and pricing in the context of new operating paradigms in deregulated power systems, proposing appropriate policy solutions. An integrated two-level framework for reactive power management is set forth, which is both suitable for a competitive market and ensures a secure and reliable operation of the associated power system. The framework is generic in nature and can be adopted for any electricity market structure. The proposed hierarchical reactive power market structure comprises two stages: procurement of reactive power resources on a seasonal basis, and real-time reactive power dispatch. The main objective of the proposed framework is to provide appropriate reactive power support from service providers at least cost, while ensuring a secure operation of the power system. The proposed procurement procedure is based on a two-step optimization model. First, the marginal benefits of reactive power supply from each provider, with respect to system security, are obtained by solving a loadability-maximization problem subject to transmission security constraints imposed by voltage and thermal limits. Second, the selected set of generators is determined by solving an optimal power flow (OPF)-based auction. This auction maximizes a societal advantage function comprising generators' offers and their corresponding marginal benefits with respect to system security, and considering all transmission system constraints. The proposed procedure yields the selected set of generators and zonal price components, which would form the basis for seasonal contracts between the system operator and the selected reactive power service providers. The main objective of the proposed reactive power dispatch model is to minimize the total payment burden on the Independent System Operator (ISO), which is associated with reactive power dispatch. The real power generation is decoupled and assumed to be fixed during the reactive power dispatch procedures; however, the effect of reactive power on real power is considered in the model by calculating the required reduction in real power output of a generator due to an increase in its reactive power supply. In this case, real power generation is allowed to be rescheduled, within given limits, from the already dispatched levels obtained from the energy market clearing process. The proposed dispatch model achieves the main objective of an ISO in a competitive electricity market, which is to provide the required reactive power support from generators at least cost while ensuring a secure operation of the power system. The proposed reactive power procurement and dispatch models capture both the technical and economic aspects of power system operation in competitive electricity markets; however, from an optimization point of view, these models represent non-convex mixed integer non-linear programming (MINLP) problems due to the presence of binary variables associated with the different regions of reactive power operation in a synchronous generator. Such MINLP optimization problems are difficult to solve, especially for an actual power system. A novel Generator Reactive Power Classification (GRPC) algorithm is proposed in this thesis to address this issue, with the advantage of iteratively solving the optimization models as a series of non-linear programming (NLP) sub-problems. The proposed reactive power procurement and dispatch models are implemented and tested on the CIGRE 32-bus system, with several case studies that represent different practical operating scenarios. The developed models are also compared with other approaches for reactive power provision, and the results demonstrate the robustness and effectiveness of the proposed model. The results clearly reveal the main features of the proposed models for optimal provision of reactive power ancillary service, in order to suit the requirements of an ISO under today's stressed system conditions in a competitive market environment.

Optimizing screening for tuberculosis and hepatitis B prior to starting tumor necrosis factor-α inhibitors in Crohn's disease.

PubMed

van der Have, Mike; Oldenburg, Bas; Fidder, Herma H; Belderbos, Tim D G; Siersema, Peter D; van Oijen, Martijn G H

2014-03-01

Treatment with tumor necrosis factor-α (TNF-α) inhibitors in patients with Crohn's disease (CD) is associated with potentially serious infections, including tuberculosis (TB) and hepatitis B virus (HBV). We assessed the cost-effectiveness of extensive TB screening and HBV screening prior to initiating TNF-α inhibitors in CD. We constructed two Markov models: (1) comparing tuberculin skin test (TST) combined with chest X-ray (conventional TB screening) versus TST and chest X-ray followed by the interferon-gamma release assay (extensive TB screening) in diagnosing TB; and (2) HBV screening versus no HBV screening. Our base-case included an adult CD patient starting with infliximab treatment. Input parameters were extracted from the literature. Direct medical costs were assessed and discounted following a third-party payer perspective. The main outcome was the incremental cost-effectiveness ratio (ICER). Sensitivity and Monte Carlo analyses were performed over wide ranges of probability and cost estimates. At base-case, the ICERs of extensive screening and HBV screening were €64,340 and €75,760 respectively to gain one quality-adjusted life year. Sensitivity analyses concluded that extensive TB screening was a cost-effective strategy if the latent TB prevalence is more than 12 % or if the false positivity rate of TST is more than 20 %. HBV screening became cost-effective if HBV reactivation or HBV-related mortality is higher than 37 and 62 %, respectively. Extensive TB screening and HBV screening are not cost-effective compared with conventional TB screening and no HBV screening, respectively. However, when targeted at high-risk patient groups, these screening strategies are likely to become cost-effective.

RAADS-14 Screen: validity of a screening tool for autism spectrum disorder in an adult psychiatric population

PubMed Central

2013-01-01

Background Autism spectrum disorder (ASD) can be difficult to distinguish from other psychiatric disorders. The clinical assessment of ASD is lengthy, and has to be performed by a specialized clinician. Therefore, a screening instrument to aid in the identification of patients who may have undiagnosed ASD should be useful. The purpose of this study was to develop such a screening instrument. Methods Based on the 80 item Ritvo Autism and Asperger Diagnostic Scale-Revised (RAADS-R), we developed a 14 item self-evaluation questionnaire, the RAADS-14 Screen. In total, 135 adults with ASD and 508 psychiatric controls completed the abridged version of the RAADS-R. Results The RAADS-14 Screen score was significantly higher in the ASD group than in the control samples, with a median score of 32 for ASD, 15 for attention deficit hyperactivity disorder, and 11 for other psychiatric disorders (P < 0.001). A cut-off score of 14 or above reached a sensitivity of 97% and a specificity of 46 to 64%. A factor analysis identified three factors consistent with mentalizing deficits, social anxiety, and sensory reactivity relevant for the diagnosis of ASD. The psychometric properties of RAADS-14 Screen were shown to be satisfactory. Conclusions The results of this study indicate that RAADS-14 Screen is a promising measure in screening for ASD in adult psychiatric outpatients. PMID:24321513

Point-of-care screening, prevalence, and risk factors for hepatitis B infection among 3,728 mainly undocumented migrants from non-EU countries in northern Italy.

PubMed

El-Hamad, Issa; Pezzoli, Maria Chiara; Chiari, Erika; Scarcella, Carmelo; Vassallo, Francesco; Puoti, Massimo; Ciccaglione, Anna; Ciccozzi, Massimo; Scalzini, Alfredo; Castelli, Francesco

2015-01-01

Screening migrants from areas where hepatitis B virus (HBV) infection is endemic is important to implement preventive measures in Europe. The aim of our study was to assess (1) the feasibility of point-of-care screening in a primary care clinic and (2) hepatitis B surface antigen (HBsAg) prevalence, associated risk factors, and its clinical and epidemiological implications in undocumented migrants in Brescia, northern Italy. A longitudinal prospective study was conducted from January 2006 to April 2010 to assess HBsAg reactivity and associated risk factors among consenting undocumented migrants who accessed the Service of International Medicine of Brescia's Local Health Authority. Genotyping assay was also performed in HBV DNA-positive patients. Screening was accepted by 3,728/4,078 (91.4%) subjects consecutively observed during the study period, 224 (6%) of whom were found to be HBsAg-positive. HBsAg reactivity was independently associated with the prevalence of HBsAg carriers in the geographical area of provenance (p < 0.001). On the contrary, current or past sexual risk behaviors (despite being common in our sample) were not associated with HBV infection. Half of the HBsAg patients (111/224) had either hepatitis B e-antigen (HBeAg)-positive or -negative chronic HBV infection with a possible indication for treatment. HBV genotypes were identified in 45 of 167 HBV-infected patients as follows: genotype D, 27 subjects; genotype A, 8; genotype B, 5; and genotype C, 5. The geographical distribution of genotypes reflected the geographic provenance. Our results suggest that point-of-care screening is feasible in undocumented migrants and should be targeted according to provenance. Case detection of HBV infection among migrants could potentially reduce HBV incidence in migrants' contacts and in the general population by prompting vaccination of susceptible individuals and care of eligible infected patients. © 2014 International Society of Travel Medicine.

Comparison of alkaline industrial wastes for aqueous mineral carbon sequestration through a parallel reactivity study.

PubMed

Noack, Clinton W; Dzombak, David A; Nakles, David V; Hawthorne, Steven B; Heebink, Loreal V; Dando, Neal; Gershenzon, Michael; Ghosh, Rajat S

2014-10-01

Thirty-one alkaline industrial wastes from a wide range of industrial processes were acquired and screened for application in an aqueous carbon sequestration process. The wastes were evaluated for their potential to leach polyvalent cations and base species. Following mixing with a simple sodium bicarbonate solution, chemistries of the aqueous and solid phases were analyzed. Experimental results indicated that the most reactive materials were capable of sequestering between 77% and 93% of the available carbon under experimental conditions in four hours. These materials - cement kiln dust, spray dryer absorber ash, and circulating dry scrubber ash - are thus good candidates for detailed, process-oriented studies. Chemical equilibrium modeling indicated that amorphous calcium carbonate is likely responsible for the observed sequestration. High variability and low reactive fractions render many other materials less attractive for further pursuit without considering preprocessing or activation techniques. Copyright © 2014 Elsevier Ltd. All rights reserved.

Increasing procaspase 8 expression using repurposed drugs to induce HIV infected cell death in ex vivo patient cells

PubMed Central

Sampath, Rahul; Cummins, Nathan W.; Natesampillai, Sekar; Bren, Gary D.; Chung, Thomas D.; Baker, Jason; Henry, Keith; Pagliuzza, Amélie; Badley, Andrew D.

2017-01-01

HIV persists because a reservoir of latently infected CD4 T cells do not express viral proteins and are indistinguishable from uninfected cells. One approach to HIV cure suggests that reactivating HIV will activate cytotoxic pathways; yet when tested in vivo, reactivating cells do not die sufficiently to reduce cell-associated HIV DNA levels. We recently showed that following reactivation from latency, HIV infected cells generate the HIV specific cytotoxic protein Casp8p41 which is produced by HIV protease cleaving procaspase 8. However, cell death is prevented, possibly due to low procaspase 8 expression. Here, we tested whether increasing procaspase 8 levels in CD4 T cells will produce more Casp8p41 following HIV reactivation, causing more reactivated cells to die. Screening 1277 FDA approved drugs identified 168 that increased procaspase 8 expression by at least 1.7-fold. Of these 30 were tested for anti-HIV effects in an acute HIVIIIb infection model, and 9 drugs at physiologic relevant levels significantly reduced cell-associated HIV DNA. Primary CD4 T cells from ART suppressed HIV patients were treated with one of these 9 drugs and reactivated with αCD3/αCD28. Four drugs significantly increased Casp8p41 levels following HIV reactivation, and decreased total cell associated HIV DNA levels (flurbiprofen: p = 0.014; doxycycline: p = 0.044; indomethacin: p = 0.025; bezafibrate: P = 0.018) without effecting the viability of uninfected cells. Thus procaspase 8 levels can be increased pharmacologically and, in the context of HIV reactivation, increase Casp8p41 causing death of reactivating cells and decreased HIV DNA levels. Future studies will be required to define the clinical utility of this or similar approaches. PMID:28628632

Persistent Latent Tuberculosis Reactivation Risk in United States Immigrants

PubMed Central

Painter, John; Parker, Matthew; Lowenthal, Phillip; Flood, Jennifer; Fu, Yunxin; Asis, Redentor; Reves, Randall

2014-01-01

Rationale: Current guidelines limit latent tuberculosis infection (LTBI) evaluation to persons in the United States less than or equal to 5 years based on the assumption that high TB rates among recent entrants are attributable to high LTBI reactivation risk, which declines over time. We hypothesized that high postarrival TB rates may instead be caused by imported active TB. Objectives: Estimate reactivation and imported TB in an immigrant cohort. Methods: We linked preimmigration records from a cohort of California-bound Filipino immigrants during 2001–2010 with subsequent TB reports. TB was likely LTBI reactivation if the immigrant had no evidence of active TB at preimmigration examination, likely imported if preimmigration radiograph was abnormal and TB was reported less than or equal to 6 months after arrival, and likely reactivation of inactive TB if radiograph was abnormal but TB was reported more than 6 months after arrival. Measurements and Main Results: Among 123,114 immigrants, 793 TB cases were reported. Within 1 year of preimmigration examination, 85% of TB was imported; 6 and 9% were reactivation of LTBI and inactive TB, respectively. Conversely, during Years 2–9 after U.S. entry, 76 and 24% were reactivation of LTBI and inactive TB, respectively. The rate of LTBI reactivation (32 per 100,000) did not decline during Years 1–9. Conclusions: High postarrival TB rates were caused by detection of imported TB through active postarrival surveillance. Among immigrants without active TB at baseline, reported TB did not decline over 9 years, indicating sustained high risk of LTBI reactivation. Revised guidelines should support LTBI screening and treatment more than 5 years after U.S. arrival. PMID:24308495

A Spectrum of Monoclonal Antibodies Reactive with Human Mammary Tumor Cells

NASA Astrophysics Data System (ADS)

Colcher, D.; Horan Hand, P.; Nuti, M.; Schlom, J.

1981-05-01

Splenic lymphocytes of mice, immunized with membrane-enriched fractions of metastatic human mammary carcinoma tissues, were fused with the NS-1 non-immunoglobulin-secreting murine myeloma cell line. This resulted in the generation of hybridoma cultures secreting immunoglobulins reactive in solid-phase radioimmunoassays with extracts of metastatic mammary carcinoma cells from involved livers, but not with extracts of apparently normal human liver. As a result of further screening of immunoglobulin reactivities and double cloning of cultures, 11 monoclonal antibodies were chosen that demonstrated reactivities with human mammary tumor cells and not with apparently normal human tissues. These monoclonal antibodies could be placed into at least five major groups on the basis of their differential binding to the surface of various live human mammary tumor cells in culture, to extracts of mammary tumor tissues, or to tissue sections of mammary tumor cells studied by the immunoperoxidase technique. Whereas a spectrum of reactivities to mammary tumors was observed with the 11 monoclonal antibodies, no reactivity was observed to apparently normal cells of the following human tissues: breast, lymph node, lung, skin, testis, kidney, thymus, bone marrow, spleen, uterus, thyroid, intestine, liver, bladder, tonsils, stomach, prostate, and salivary gland. Several of the antibodies also demonstrated a ``pancarcinoma'' reactivity, showing binding to selected non-breast carcinomas. None of the monoclonal antibodies showed binding to purified ferritin or carcinoembryonic antigen. Monoclonal antibodies of all five major groups, however, demonstrated binding to human metastatic mammary carcinoma cells both in axillary lymph nodes and at distal sites.

Development and pilot validation of a sensory reactivity scale for adults with high functioning autism spectrum conditions: Sensory Reactivity in Autism Spectrum (SR-AS).

PubMed

Elwin, Marie; Schröder, Agneta; Ek, Lena; Kjellin, Lars

2016-01-01

Unusual reactions to sensory stimuli are experienced by 90-95% of people with an autism spectrum condition (ASC). Self-reported sensory reactivity in ASC has mainly been measured with generic questionnaires developed and validated on data from the general population. Interest in sensory reactivity in ASC increased after the inclusion of hyper- and hypo-reactivity together with unusual sensory interest as diagnostic markers of ASC in the DSM-5. To develop and pilot validate a self-report questionnaire designed from first-hand descriptions of the target group of adults diagnosed with high functioning ASC. Psychometric properties of the questionnaire were evaluated on a sample of participants with ASC diagnoses (N = 71) and a random sample from the general population (N = 162). The Sensory Reactivity in Autism Spectrum (SR-AS is intended to be used as a screening tool in diagnostic processes with adults and for support in adapting compensating strategies and environmental adjustments. The internal consistency was high for both the SR-AS and its subscales. The total scale Cronbach's alpha was 0.96 and the subscales alphas were ≥ 0.80. Confirmatory factor analysis (CFA) showed best fit for a four-factor model of inter-correlated factors: hyper and hypo-reactivity, strong sensory interest and a sensory/motor factor. The questionnaire discriminated well between ASC-diagnosed participants and participants from the general population. The SR-AS displayed good internal consistency and discriminatory power and promising factorial validity.

Validation of an Enzyme Immunoassay for Detection and Semiquantification of Cannabinoids in Oral Fluid

PubMed Central

Schwope, David M.; Milman, Garry; Huestis, Marilyn A.

2011-01-01

BACKGROUND Oral fluid (OF) is gaining prominence as an alternative matrix for monitoring drugs of abuse in the workplace, criminal justice, and driving under the influence of drugs programs. It is important to characterize assay performance and limitations of screening techniques for Δ9-tetrahydrocannabinol (THC) in OF. METHODS We collected OF specimens by use of the Quantisal™ OF collection device from 13 daily cannabis users after controlled oral cannabinoid administration. All specimens were tested with the Immunalysis Sweat/OF THC Direct ELISA and confirmed by 2-dimensional GC-MS. RESULTS The limit of detection was <1 µg/L THC equivalent, and the assay demonstrated linearity from 1 to 50 µg/L, with semiquantification to 200 µg/L. Intraplate imprecision (n = 7) ranged from 2.9% to 7.7% CV, and interplate imprecision (n = 20) was 3.0%–9.1%. Cross-reactivities at 4 µg/L were as follows: 11-hydroxy-THC, 198%; Δ8-tetrahydrocannabinol (Δ8-THC), 128%; 11-nor-9-carboxy-THC (THCCOOH), 121%; THC (target), 98%; cannabinol, 87%; THCCOOH-glucuronide, 11%; THC-glucuronide, 10%; and cannabidiol, 2.4%. Of 499 tested OF specimens, 52 confirmed positive (THC 2.0–290 µg/L), with 100% diagnostic sensitivity at the proposed Substance Abuse and Mental Health Services Administration screening cutoff of 4 µg/L cannabinoids and GC-MS cutoff of 2 µg/L THC. Forty-seven specimens screened positive but were not confirmed by 2D-GC-MS, yielding 89.5% diagnostic specificity and 90.6% diagnostic efficiency. Thirty-one of 47 unconfirmed immunoassay positive specimens were from 1 individual and contained >400 ng/L THCCOOH, potentially contributing to cross-reactivity. CONCLUSIONS The Immunalysis Sweat/OF THC Direct ELISA is an effective screening procedure for detecting cannabinoids in OF. PMID:20360126

Clinical and Laboratory Associations with Persistent Hyperferritinemia in 373 Black Hemochromatosis and Iron Overload Screening Study Participants.

PubMed

Barton, James C; Barton, J Clayborn; Adams, Paul C

2017-01-01

373 black participants had elevated screening and post-screening serum ferritin (SF) (> 300 μg/L men; > 200 μg/L women). We retrospectively studied SF and post-screening age; sex; body mass index; transferrin saturation (TS); ALT; AST; GGT; elevated C-reactive protein; ß-thalassemia; neutrophils; lymphocytes; monocytes; platelets; metacarpophalangeal joint hypertrophy; hepatomegaly; splenomegaly; diabetes; HFE H63D positivity; iron/alcohol intakes; and blood/erythrocyte transfusion units. Liver disease was defined as elevated ALT or AST. We computed correlations of SF and TS with: age; body mass index; ALT; AST; GGT; C-reactive protein; blood cell counts; and iron/alcohol. We compared participants with SF > 1,000 and ≤ 1,000 μg/L and performed regressions on SF. There were 237 men (63.5%). Mean age was 55 ± 13 (SD) y. 143 participants had liver disease (62 hepatitis B or C). There were significant correlations of SF: TS, ALT, AST, GGT, and monocytes (positive); and SF and TS with platelets (negative). 22 participants with SF > 1,000 μg/L had significantly higher median TS, ALT, and AST, and prevalences of anemia and transfusion > 10 units; and lower median platelets. Regression on SF revealed significant associations: TS; male sex; age; GGT; transfusion units (positive); and splenomegaly (negative) (p < 0.0001, 0.0016, 0.0281, 0.0025, 0.0001, and 0.0096, respectively). Five men with SF > 1,000 μg/L and elevated TS had presumed primary iron overload (hemochromatosis). Four participants had transfusion iron overload. Persistent hyperferritinemia in 373 black adults was associated with male sex, age, TS, GGT, and transfusion. 2.4% had primary iron overload (hemochromatosis) or transfusion iron overload.

LC-MS/MS screening strategy for unknown adducts to N-terminal valine in hemoglobin applied to smokers and nonsmokers.

PubMed

Carlsson, Henrik; von Stedingk, Hans; Nilsson, Ulrika; Törnqvist, Margareta

2014-12-15

Electrophilically reactive compounds have the ability to form adducts with nucleophilic sites in DNA and proteins, constituting a risk for toxic effects. Mass spectrometric detection of adducts to N-terminal valine in hemoglobin (Hb) after detachment by modified Edman degradation procedures is one approach for in vivo monitoring of exposure to electrophilic compounds/metabolites. So far, applications have been limited to one or a few selected reactive species, such as acrylamide and its metabolite glycidamide. This article presents a novel screening strategy for unknown Hb adducts to be used as a basis for an adductomic approach. The method is based on a modified Edman procedure, FIRE, specifically developed for LC-MS/MS analysis of N-terminal valine adducts in Hb detached as fluorescein thiohydantoin (FTH) derivatives. The aim is to detect and identify a priori unknown Hb adducts in human blood samples. Screening of valine adducts was performed by stepwise scanning of precursor ions in small mass increments, monitoring four fragments common for the FTH derivative of valine with different N-substitutions in the multiple-reaction mode, covering a mass range of 135 Da (m/z 503-638). Samples from six smokers and six nonsmokers were analyzed. Control experiments were performed to compare these results with known adducts and to check for artifactual formation of adducts. In all samples of smokers and nonsmokers, seven adducts were identified, of which six have previously been studied. Nineteen unknown adducts were observed, and 14 of those exhibited fragmentation patterns similar to earlier studied FTH derivatives of adducts to valine. Identification of the unknown adducts will be the focus of future work. The presented methodology is a promising screening tool using Hb adducts to indicate exposure to potentially toxic electrophilic compounds and metabolites.

Evaluation of the Cross-reactivity of Antidrug Antibodies to CT-P13 and Infliximab Reference Product (Remicade): An Analysis Using Immunoassays Tagged with Both Agents.

PubMed

Reinisch, Walter; Jahnsen, Jørgen; Schreiber, Stefan; Danese, Silvio; Panés, Julián; Balsa, Alejandro; Park, Won; Kim, JiSoo; Lee, Jee Un; Yoo, Dae Hyun

2017-06-01

During two pivotal clinical trials of the infliximab biosimilar CT-P13 (PLANETAS and PLANETRA), antidrug antibodies (ADAs) and neutralising antibodies (NAbs) were detected in the sera of patients treated with CT-P13 and the reference product (RP; Remicade). The aim was to assess the comparability of Remicade- and CT-P13-tagged immunoassays for the detection of ADAs and NAbs using data from these trials, in order to determine the cross-reactivity of CT-P13 and RP ADAs. Sera from patients with rheumatoid arthritis and ankylosing spondylitis were analysed using an electrochemiluminescence (ECL) bridging assay or Gyros immunoassay, tagged with Remicade or CT-P13 at screening, weeks 14, 30 and 54, and the end of study visit. NAb titre was compared at screening and weeks 14 and 30. The proportion of cross-reactive samples was determined and an inter-rater agreement analysis performed to assess the concordance of results between assays. In PLANETAS, 93.1% (94/101) of RP ADA-positive samples and 93.0% (93/100) of RP NAb-positive samples cross-reacted with CT-P13; 99.0% (103/104) of CT-P13 ADA-positive and 98.0% (98/100) of CT-P13 NAb-positive samples cross-reacted with the RP. In PLANETRA, 94.7% (426/450) of RP ADA-positive samples and 94.3% (415/440) of RP NAb-positive samples cross-reacted with CT-P13, and 96.6% (458/474) of CT-P13 ADA-positive and 96.4% (452/469) of CT-P13 NAb-positive samples cross-reacted with the RP. In both studies, there was strong agreement in outcome between assays at all post-screening time points (PLANETAS: Cohen's κ 0.89-0.98 for ADA, 0.86-0.98 for NAb; PLANETRA: 0.92-0.94 for both ADA and NAb, all p < 0.001). Significant concordance between assays was observed for NAb titre at weeks 14 and 30 (PLANETAS: Spearman's ρ 0.73 and 0.74, respectively; PLANETRA: 0.61 and 0.72, respectively; all p < 0.001). This study has demonstrated that ADAs and NAbs against CT-P13 and RP are cross-reactive, indicating that CT-P13 and RP share immunodominant epitopes.

Electrical engineering unit for the reactive power control of the load bus at the voltage instability

NASA Astrophysics Data System (ADS)

Kotenev, A. V.; Kotenev, V. I.; Kochetkov, V. V.; Elkin, D. A.

2018-01-01

For the purpose of reactive power control error reduction and decrease of the voltage sags in the electric power system caused by the asynchronous motors started the mathematical model of the load bus was developed. The model was built up of the sub-models of the following elements: a transformer, a transmission line, a synchronous and an asynchronous loads and a capacitor bank load, and represents the automatic reactive power control system taking into account electromagnetic processes of the asynchronous motors started and reactive power changing of the electric power system elements caused by the voltage fluctuation. The active power/time and reactive power/time characteristics based on the recommended procedure of the equivalent electric circuit parameters calculation were obtained. The derived automatic reactive power control system was shown to eliminate the voltage sags in the electric power system caused by the asynchronous motors started.

[Cold auto- and alloantibodies considered "benign"--do they have some pathological significance?].

PubMed

Serrano, J

1990-12-01

In our Blood Bank the screening for irregular antibodies is performed on blood bags and patient's serum and is done at 37 degrees C as well as 22 degrees C even when we are conscious that the test at 22 degrees C is devoid of any practical value as far as transfusional haemolytic reactions are concerned. A total of 23,021 patients and 91,021 blood bags have been studied in the last 10 years. The results have been analyzed in order to find out any possible association of cold autoanti-I antibodies, or cold alloantibodies, mainly anti-P1, anti-Leb, anti-Lea and anti-Lex, with certain diseases. The cold antibodies looked for in the present study are neither "natural" antibodies reactive only at 4-10 degrees C, since they were not investigated at such low temperatures, nor pathological antibodies, reactive up to 37 degrees C and/or endowed with haemolytic activity. They are instead antibodies, reactive at 22 degrees C, that interfere with compatibility tests and with screening for irregular antibodies, when the assay is performed at room temperature. In our experience, by far the most prominent antibody in this category is auto-anti-I, amounting to over two thirds of the positive findings. This autoantibodies, as well as allo-anti-P1, appear much more frequently in patients that in donors, whereas significant differences are not found with anti-Lewis antibodies.(ABSTRACT TRUNCATED AT 250 WORDS)

Airway hyperreactivity in asymptomatic military personnel.

PubMed

Morris, Michael J; Schwartz, Darin S; Nohrenberg, Jana L; Dooley, Sean N

2007-11-01

Asthma is frequently diagnosed in military personnel despite strict guidelines that disqualify persons with active disease or a recent history of asthma. It is generally considered incompatible with military service, because of the regular physical training, outdoor training exercises, and deployments to remote locations. The objective of this study was to determine the prevalence of airway hyperreactivity in asymptomatic military personnel, as an estimate of subclinical reactive airway disease. A prospective study of healthy, asymptomatic, military personnel with no previous history of asthma and <1 year on active duty status was conducted. After completion of a screening questionnaire, personnel underwent baseline spirometry with a portable spirometer. Personnel with obstructive indices (based on published guidelines) and matched control subjects participated in an exercise test (1.5-mile run), with pre- and postexercise spirometry. A total of 222 asymptomatic military personnel completed baseline spirometry, and 31 (14%) were found have airway obstruction. A normal matched control group of 31 military personnel and 26 personnel with obstruction performed exercise spirometry. Twenty-three percent of the participants with obstruction demonstrated increased airway hyper-reactivity after exercise, based on a reduction in forced expiratory volume at 1 second, compared with 19% of control subjects. Asymptomatic airway obstruction has a prevalence of 14% in young military personnel. A significant percentage of individuals also have evidence of worsening obstruction during exercise. These data suggest that screening spirometry may identify early reactive airway disease in asymptomatic individuals and should be considered as a method to identify persons predisposed to developing symptomatic asthma.

Diagnosis of Allergy to Mammals and Fish: Cross-Reactive vs. Specific Markers.

PubMed

Hilger, Christiane; van Hage, Marianne; Kuehn, Annette

2017-08-22

Allergen extracts are still widely used in allergy diagnosis as they are regarded as sensitive screening tools despite the fact that they may lack some minor allergens. Another drawback of extracts is their low specificity, which is due to the presence of cross-reactive allergens. Progress in allergen identification has disclosed a number of allergenic molecules of homologous sequence and structure which are present in different animal species. This review summarizes recent advances in mammalian and fish allergen identification and focuses on their clinical relevance. Serum albumins and parvalbumins are well-known animal panallergens. More recently several members of the lipocalin family were found to be cross-reactive between furry animals whereas in fish, additional allergens, enolase, aldolase and collagen, were found to be important and cross-reactive allergens. New epidemiological studies have analysed the prevalence and clinical relevance of mammalian and fish components. Primary sensitization can be distinguished from cross-sensitization by using marker allergens. Although substantial progress has been made in allergen identification, only few markers are commercially available for routine clinical practice.

Cross-reactivity between pollen extracts from six artemisia species.

PubMed

Brandys, J; Grimsøen, A; Nilsen, B M; Paulsen, B S; Park, H S; Hong, C S

1993-06-01

Pollen extracts of six different ARTEMISIA species, A. VULGARIS, A. SCOPARIA, A. PRINCEPS, A. TRIDENTATA, A. ANNUA, and A. CAMPESTRIS were compared using SDS-PAGE, IEF, immunoblotting, and immunoelectrophoretic methods. The band patterns obtained after SDS-PAGE and IEF showed a large degree of similarity between the extracts. Immunoblotting of these gels using a pool of sera from patients allergic to A. VULGARIS gave essentially the same IgE-binding band pattern with all the extracts, demonstrating an extensive degree of cross-reactivity between A. VULGARIS and the other ARTEMISIA species. FRIE using a polyspecific antiserum against A. VULGARIS showed that all the extracts contained several antigens that were immunologically identical to antigens in A. VULGARIS extract. Antigens showing immunological identity to the important A. VULGARIS allergens Ag 12 and ART V II were present in all the extracts. The cross-reactivity between A. VULGARIS and A. PRINCEPS was further verified by screening of ten Korean and nine Norwegian individual patient sera against extracts of both species in SDS-PAGE or IEF immunoblotting. Both groups of patients had essentially the same pattern of reactivity towards both pollen extracts.

Calculation of a double reactive azeotrope using stochastic optimization approaches

NASA Astrophysics Data System (ADS)

Mendes Platt, Gustavo; Pinheiro Domingos, Roberto; Oliveira de Andrade, Matheus

2013-02-01

An homogeneous reactive azeotrope is a thermodynamic coexistence condition of two phases under chemical and phase equilibrium, where compositions of both phases (in the Ung-Doherty sense) are equal. This kind of nonlinear phenomenon arises from real world situations and has applications in chemical and petrochemical industries. The modeling of reactive azeotrope calculation is represented by a nonlinear algebraic system with phase equilibrium, chemical equilibrium and azeotropy equations. This nonlinear system can exhibit more than one solution, corresponding to a double reactive azeotrope. The robust calculation of reactive azeotropes can be conducted by several approaches, such as interval-Newton/generalized bisection algorithms and hybrid stochastic-deterministic frameworks. In this paper, we investigate the numerical aspects of the calculation of reactive azeotropes using two metaheuristics: the Luus-Jaakola adaptive random search and the Firefly algorithm. Moreover, we present results for a system (with industrial interest) with more than one azeotrope, the system isobutene/methanol/methyl-tert-butyl-ether (MTBE). We present convergence patterns for both algorithms, illustrating - in a bidimensional subdomain - the identification of reactive azeotropes. A strategy for calculation of multiple roots in nonlinear systems is also applied. The results indicate that both algorithms are suitable and robust when applied to reactive azeotrope calculations for this "challenging" nonlinear system.

Creating and virtually screening databases of fluorescently-labelled compounds for the discovery of target-specific molecular probes

NASA Astrophysics Data System (ADS)

Kamstra, Rhiannon L.; Dadgar, Saedeh; Wigg, John; Chowdhury, Morshed A.; Phenix, Christopher P.; Floriano, Wely B.

2014-11-01

Our group has recently demonstrated that virtual screening is a useful technique for the identification of target-specific molecular probes. In this paper, we discuss some of our proof-of-concept results involving two biologically relevant target proteins, and report the development of a computational script to generate large databases of fluorescence-labelled compounds for computer-assisted molecular design. The virtual screening of a small library of 1,153 fluorescently-labelled compounds against two targets, and the experimental testing of selected hits reveal that this approach is efficient at identifying molecular probes, and that the screening of a labelled library is preferred over the screening of base compounds followed by conjugation of confirmed hits. The automated script for library generation explores the known reactivity of commercially available dyes, such as NHS-esters, to create large virtual databases of fluorescence-tagged small molecules that can be easily synthesized in a laboratory. A database of 14,862 compounds, each tagged with the ATTO680 fluorophore was generated with the automated script reported here. This library is available for downloading and it is suitable for virtual ligand screening aiming at the identification of target-specific fluorescent molecular probes.

Metabolic Toxicity Screening Using Electrochemiluminescence Arrays Coupled with Enzyme-DNA Biocolloid Reactors and Liquid Chromatography-Mass Spectrometry

NASA Astrophysics Data System (ADS)

Hvastkovs, Eli, G.; Schenkman, John B.; Rusling, James, F.

2012-07-01

New chemicals or drugs must be guaranteed safe before they can be marketed. Despite widespread use of bioassay panels for toxicity prediction, products that are toxic to a subset of the population often are not identified until clinical trials. This article reviews new array methodologies based on enzyme/DNA films that form and identify DNA-reactive metabolites that are indicators of potentially genotoxic species. This molecularly based methodology is designed in a rapid screening array that utilizes electrochemiluminescence (ECL) to detect metabolite-DNA reactions, as well as biocolloid reactors that provide the DNA adducts and metabolites for liquid chromatography-mass spectrometry (LC-MS) analysis. ECL arrays provide rapid toxicity screening, and the biocolloid reactor LC-MS approach provides a valuable follow-up on structure, identification, and formation rates of DNA adducts for toxicity hits from the ECL array screening. Specific examples using this strategy are discussed. Integration of high-throughput versions of these toxicity-screening methods with existing drug toxicity bioassays should allow for better human toxicity prediction as well as more informed decision making regarding new chemical and drug candidates.

The symphonic structure of childhood stress reactivity: Patterns of sympathetic, parasympathetic, and adrenocortical responses to psychological challenge

PubMed Central

Quas, Jodi A.; Yim, Ilona S.; Oberlander, Tim F.; Nordstokke, David; Essex, Marilyn J.; Armstrong, Jeffrey M.; Bush, Nicole; Obradović, Jelena; Boyce, W. Thomas

2015-01-01

Despite widespread recognition that the physiological systems underlying stress reactivity are well coordinated at a neurobiological level, surprisingly little empirical attention has been given to delineating precisely how the systems actually interact with one another when confronted with stress. We examined cross-system response proclivities in anticipation of and following standardized laboratory challenges in 664 4- to 14-year-olds from four independent studies. In each study, measures of stress reactivity within both the locus coeruleus-norepinephrine system (i.e., the sympathetic and parasympathetic branches of the autonomic nervous system) and the corticotrophin releasing hormone system (i.e., the hypothalamic-pituitary-adrenal axis) were collected. Latent profile analyses revealed six distinctive patterns that recurred across the samples: moderate reactivity (average cross-system activation; 52%-80% of children across samples), parasympathetic-specific reactivity (2%-36%), anticipatory arousal (4%-9%), multisystem reactivity (7%—14%), hypothalamic-pituitary-adrenal axis specific reactivity (6%-7%), and underarousal (0%-2%). Groups meaningfully differed in socioeconomic status, family adversity, and age. Results highlight the sample-level reliability of children’s neuroendocrine responses to stress and suggest important cross-system regularities that are linked to development and prior experiences and may have implications for subsequent physical and mental morbidity. PMID:24909883

Platelet reactivity in response to loading dose of atorvastatin or rosuvastatin in patients with stable coronary disease before percutaneous coronary intervention: The STATIPLAT randomized study.

PubMed

Godino, Cosmo; Pavon, Anna Giulia; Mangieri, Antonio; Salerno, Anna; Cera, Michela; Monello, Alberto; Chieffo, Alaide; Magni, Valeria; Cappelletti, Alberto; Margonato, Alberto; Colombo, Antonio

2017-08-01

The acute effects of statin loading dose (LD) on platelet reactivity in patients with chronic stable angina (CSA) are not completely clear. We hypothesized that LDs of atorvastatin and rosuvastatin have different pharmacodynamic acute effects on platelet aggregability in CSA patients with baseline normal platelet reactivity while on dual antiplatelet therapy (DAPT). From September 2011 to February 2014, all consecutive CSA patients on chronic DAPT (aspirin and clopidogrel) were evaluated before elective percutaneous coronary intervention (PCI). An initial assessment of platelet reactivity in response to thrombin receptor agonist, ADP, and ASP (respectively, indicative of the response to clopidogrel and aspirin) was performed with impedance aggregometry. Patients with high platelet reactivity to ADP test (area under the curve >47) were excluded. The remaining patients were randomized into 3 treatment groups: Group A, atorvastatin LD 80 mg; Group B, rosuvastatin LD 40 mg; and Group C, no statin LD (control group). A second assessment of platelet reactivity was performed ≥12 hours after statin LD. 682 patients were screened and 145 were randomized into the 3 groups. At baseline and after statin LD, no significant difference was found in platelet reactivity in response to 3 different agonists between the 3 groups. Subgroup analysis showed that platelet reactivity to ADP test was significantly lower in patients chronically treated with low-dose statins (n = 94) compared with statin-naïve patients (n = 51; 15.32 ± 1.50 vs 18.59 ± 1.30; P = 0.007). Loading dose of atorvastatin (80 mg) or rosuvastatin (40 mg) did not induce significant variation in platelet reactivity in CSA patients with baseline reduced platelet reactivity as in chronic DAPT. Our data confirm that chronic concomitant treatment with low-dose statins and clopidogrel resulted in significantly lower platelet reactivity compared with clopidogrel alone. © 2017 Wiley Periodicals, Inc.

System for reactivating catalysts

DOEpatents

Ginosar, Daniel M.; Thompson, David N.; Anderson, Raymond P.

2010-03-02

A method of reactivating a catalyst, such as a solid catalyst or a liquid catalyst is provided. The method comprises providing a catalyst that is at least partially deactivated by fouling agents. The catalyst is contacted with a fluid reactivating agent that is at or above a critical point of the fluid reactivating agent and is of sufficient density to dissolve impurities. The fluid reactivating agent reacts with at least one fouling agent, releasing the at least one fouling agent from the catalyst. The at least one fouling agent becomes dissolved in the fluid reactivating agent and is subsequently separated or removed from the fluid reactivating agent so that the fluid reactivating agent may be reused. A system for reactivating a catalyst is also disclosed.

Establishing Assay Cutoffs for HLA Antibody Screening of Apheresis Donors

PubMed Central

Carrick, Danielle M.; Norris, Philip J.; Endres, Robert O.; Pandey, Suchitra; Kleinman, Steven H.; Wright, David; Sun, Yu; Busch, Michael P.

2011-01-01

BACKGROUND TRALI is the leading cause of transfusion-related deaths. Donor HLA antibodies have been implicated in TRALI cases. Blood centers are implementing TRALI risk reduction strategies based on HLA antibody screening of some subpopulations of ever-pregnant apheresis platelet donors. However, if screening assay cutoffs are too sensitive, donation loss may adversely impact blood availability. STUDY DESIGN Pregnancy history and HLA antibody screening and single antigen bead (SAB) data from blood donors in the REDS-II Leukocyte Antibody Prevalence Study (LAPS) were evaluated for correlations between assay screening values, HLA antibody titer, and number of HLA antigen specificities. The probabilities of matching a cognate antigen in a recipient were calculated and examined in association with total number of specificities observed and screening values. The relative impact of imposing various screening assay cutoffs or pregnancy stratification was examined in relation to detection of HLA antibody reactive donations and loss of donors and donations. RESULTS We provide evidence that higher HLA Ab screening assay values are associated with maintaining higher screening signals upon dilution and an increased breadth of specificities compared with lower screening values; the latter correlated with an increased risk of a cognate antigen match in potential recipients. Depending upon the TRALI risk reduction strategy used, the potential loss of donations ranged between 0.9 and 6.0%. CONCLUSION This analysis should enable blood centers to decide upon a TRALI risk reduction strategy for apheresis platelets that is consistent with how much donation loss the blood center can tolerate. PMID:21332726

Sepsis biomarkers in neutropaenic systemic inflammatory response syndrome patients on standard care wards.

PubMed

Ratzinger, Franz; Haslacher, Helmuth; Perkmann, Thomas; Schmetterer, Klaus G; Poeppl, Wolfgang; Mitteregger, Dieter; Dorffner, Georg; Burgmann, Heinz

2015-08-01

Neutropaenic patients are at a high risk of contracting severe infections. In particular, in these patients, parameters with a high negative predictive value are desirable for excluding infection or bacteraemia. This study evaluated sepsis biomarkers in neutropaenic patients suffering from systemic inflammatory response syndrome (SIRS). Further, the predictive capacities of evaluated biomarkers in neutropaenic SIRS patients were compared to non-neutropaenic SIRS patients. In this prospective observational cohort study, patients with clinically suspected sepsis were screened. The predictive capacities of procalcitonin (PCT), C-reactive protein and lipopolysaccharide-binding protein (LBP) in neutropaenic SIRS patients were evaluated in terms of their potential to identify infection or bacteraemia and were compared to results for non-neutropaenic SIRS patients. To select an appropriate control cohort, propensity score matching was applied, balancing confounding factors between neutropaenic and non-neutropaenic SIRS patients. Of 3370 prospectively screened patients with suspected infection, 51 patients suffered from neutropaenic SIRS. For the identification of infection, none of the assessed biomarkers presented a clinically relevant discriminatory potency. Lipopolysaccharide-binding protein and PCT demonstrated discriminatory capacity to discriminate between nonbacteraemic and bacteraemic SIRS in patients with neutropaenia [receiver-operating characteristics-area under the curves (ROC-AUCs): 0.860, 0.818]. In neutropaenic SIRS patients, LBP had a significantly better ROC-AUC than in a comparable non-neutropaenic patient cohort for identifying bacteraemia (P = 0.01). In neutropaenic SIRS patients, none of the evaluated biomarkers was able to adequately identify infection. LBP and PCT presented a good performance in identifying bacteraemia. Therefore, these markers could be used for screening purposes to increase the pretest probability of blood culture analysis. © 2015 Stichting European Society for Clinical Investigation Journal Foundation.

The first Korean case report of anti-Gerbich.

PubMed

Jeon, You La; Park, Tae Sung; Cho, Sun Young; Oh, Seung Hwan; Kim, Myeong Hee; Kang, So Young; Lee, Woo-In

2012-11-01

In this study, we report the first Korean case of an anti-Gerbich (Ge) alloantibody to a high-incidence antigen that belongs to the Ge blood group system. The alloantibody was detected in a middle-aged Korean woman who did not have a history of transfusion. Her blood type was B+, and findings from the antibody screening test revealed 1+ reactivity in all panels except the autocontrol. The cross-matching test showed incompatible results with all 5 packed red blood cells. Additional blood type antigen and antibody tests confirmed the anti-Ge alloantibody. While rare, cases of hemolytic transfusion reaction or hemolytic disease in newborns due to anti-Ge have been recently reported in the literature. Therefore, additional further studies on alloantibodies to high-incidence antigens, including anti-Ge, are necessary in the future.

Autophagy Genes Enhance Murine Gammaherpesvirus 68 Reactivation From Latency by Preventing Virus-induced Systemic Inflammation

PubMed Central

Park, Sunmin; Buck, Michael D.; Desai, Chandni; Zhang, Xin; Loginicheva, Ekaterina; Martinez, Jennifer; Freeman, Michael L.; Saitoh, Tatsuya; Akira, Shizuo; Guan, Jun-Lin; He, You-Wen; Blackman, Marcia A.; Handley, Scott A.; Levine, Beth; Green, Douglas R.; Reese, Tiffany A.; Artyomov, Maxim N.; Virgin, Herbert W.

2016-01-01

SUMMARY Host genes that regulate systemic inflammation upon chronic viral infection are incompletely understood. Murine γ-herpesvirus 68 (MHV68) infection is characterized by latency in macrophages, and reactivation is inhibited by Interferon-γ (IFN-γ). Using a Lysozyme-M-cre (LysMcre) expression system, we show that deletion of autophagy-related (Atg) genes Fip200, beclin 1, Atg14, Atg16L1, Atg7, Atg3, and Atg5, in the myeloid compartment, inhibited MHV68 reactivation in macrophages. Atg5-deficiency did not alter reactivation from B cells, and effects on reactivation from macrophages were not explained by alterations in productive viral replication or the establishment of latency. Rather, chronic MHV68 infection triggered increased systemic inflammation, increased T cell production of IFN-γ and an IFN-γ-induced transcriptional signature in macrophages from Atg gene-deficient mice. The Atg5-related reactivation defect was partially reversed by neutralization of IFN-γ. Thus Atg genes in myeloid cells dampen virus-induced systemic inflammation, creating an environment that fosters efficient MHV68 reactivation from latency. PMID:26764599

Optimal reactive planning with security constraints

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

Thomas, W.R.; Cheng, D.T.Y.; Dixon, A.M.

1995-12-31

The National Grid Company (NGC) of England and Wales has developed a computer program, SCORPION, to help system planners optimize the location and size of new reactive compensation plant on the transmission system. The reactive power requirements of the NGC system have risen as a result of increased power flows and the shorter timescale on which power stations are commissioned and withdrawn from service. In view of the high costs involved, it is important that reactive compensation be installed as economically as possible, without compromising security. Traditional methods based on iterative use of a load flow program are labor intensivemore » and subjective. SCORPION determines a near-optimal pattern of new reactive sources which are required to satisfy voltage constraints for normal and contingent states of operation of the transmission system. The algorithm processes the system states sequentially, instead of optimizing all of them simultaneously. This allows a large number of system states to be considered with an acceptable run time and computer memory requirement. Installed reactive sources are treated as continuous, rather than discrete, variables. However, the program has a restart facility which enables the user to add realistically sized reactive sources explicitly and thereby work towards a realizable solution to the planning problem.« less

Proteome-wide covalent ligand discovery in native biological systems

PubMed Central

Backus, Keriann M.; Correia, Bruno E.; Lum, Kenneth M.; Forli, Stefano; Horning, Benjamin D.; González-Páez, Gonzalo E.; Chatterjee, Sandip; Lanning, Bryan R.; Teijaro, John R.; Olson, Arthur J.; Wolan, Dennis W.; Cravatt, Benjamin F.

2016-01-01

Small molecules are powerful tools for investigating protein function and can serve as leads for new therapeutics. Most human proteins, however, lack small-molecule ligands, and entire protein classes are considered “undruggable” 1,2. Fragment-based ligand discovery (FBLD) can identify small-molecule probes for proteins that have proven difficult to target using high-throughput screening of complex compound libraries 1,3. Although reversibly binding ligands are commonly pursued, covalent fragments provide an alternative route to small-molecule probes 4–10, including those that can access regions of proteins that are difficult to access through binding affinity alone 5,10,11. In this manuscript, we report a quantitative analysis of cysteine-reactive small-molecule fragments screened against thousands of proteins. Covalent ligands were identified for >700 cysteines found in both druggable proteins and proteins deficient in chemical probes, including transcription factors, adaptor/scaffolding proteins, and uncharacterized proteins. Among the atypical ligand-protein interactions discovered were compounds that react preferentially with pro- (inactive) caspases. We used these ligands to distinguish extrinsic apoptosis pathways in human cell lines versus primary human T-cells, showing that the former is largely mediated by caspase-8 while the latter depends on both caspase-8 and −10. Fragment-based covalent ligand discovery provides a greatly expanded portrait of the ligandable proteome and furnishes compounds that can illuminate protein functions in native biological systems. PMID:27309814

Cutaneous challenge with chemical warfare agents in the SKH-1 hairless mouse (II): effects of some currently used skin decontaminants (RSDL and Fuller's earth) against liquid sulphur mustard and VX exposure.

PubMed

Taysse, L; Dorandeu, F; Daulon, S; Foquin, A; Perrier, N; Lallement, G; Breton, P

2011-06-01

Using the hairless mouse screening model presented in the companion paper(1) the aim of this study was to assess two skin decontaminating systems: Fuller's earth (FE) and Reactive Skin Decontamination Lotion (RSDL) against two extremely toxic chemical warfare agents that represent a special percutaneous hazard, sulphur mustard (SM) and O-ethyl-S-(2[di-isopropylamino]ethyl)methyl-phosphonothioate (VX). Five minutes after being exposed on the back to either 2 µL of neat sulphur mustard or 50 µg.kg(-1) of diluted VX, mice were decontaminated. Both systems were able to reduce blisters 3 days after SM exposure. However, RSDL was found to be more efficient than FE in reducing the necrosis of the epidermis and erosion. In the case of VX exposure, RSDL, whatever the ratio of decontaminant to toxicant used (RSDL 10, 20, 50), was not able to sufficiently prevent the inhibition of plasma cholinesterases taken as a surrogate marker of exposure and toxicity. Only FE reduced significantly the ChE inhibition. Some of these observations are different from our previous results obtained in domestic swine and these changes are thus discussed in the perspective of using SKH-1 hairless mice for the initial in vivo screening of decontaminants.

Immunohistochemistry for the detection of neural and inflammatory cells in equine brain tissue

PubMed Central

Liu, Junjie; Herrington, Jenna M.; Vallario, Kelsey

2016-01-01

Phenotypic characterization of cellular responses in equine infectious encephalitides has had limited description of both peripheral and resident cell populations in central nervous system (CNS) tissues due to limited species-specific reagents that react with formalin-fixed, paraffin embedded tissue (FFPE). This study identified a set of antibodies for investigating the immunopathology of infectious CNS diseases in horses. Multiple commercially available staining reagents and antibodies derived from antigens of various species for manual immunohistochemistry (IHC) were screened. Several techniques and reagents for heat-induced antigen retrieval, non-specific protein blocking, endogenous peroxidase blocking, and visualization-detection systems were tested during IHC protocol development. Boiling of slides in a low pH, citrate-based buffer solution in a double-boiler system was most consistent for epitope retrieval. Pressure-cooking, microwaving, high pH buffers, and proteinase K solutions often resulted in tissue disruption or no reactivity. Optimal blocking reagents and concentrations of each working antibody were determined. Ultimately, a set of monoclonal (mAb) and polyclonal antibodies (pAb) were identified for CD3+ (pAb A0452, Dako) T-lymphocytes, CD79αcy+ B-lymphocytes (mAb HM57, Dako), macrophages (mAb MAC387, Leica), NF-H+ neurons (mAb NAP4, EnCor Biotechnology), microglia/macrophage (pAb Iba-1, Wako), and GFAP+ astrocytes (mAb 5C10, EnCor Biotechnology). In paraffin embedded tissues, mAbs and pAbs derived from human and swine antigens were very successful at binding equine tissue targets. Individual, optimized protocols are provided for each positively reactive antibody for analyzing equine neuroinflammatory disease histopathology. PMID:26855862

Stress-induced cortisol secretion impairs detection performance in x-ray baggage screening for hidden weapons by screening novices.

PubMed

Thomas, Livia; Schwaninger, Adrian; Heimgartner, Nadja; Hedinger, Patrik; Hofer, Franziska; Ehlert, Ulrike; Wirtz, Petra H

2014-09-01

Aviation security strongly depends on screeners' performance in the detection of threat objects in x-ray images of passenger bags. We examined for the first time the effects of stress and stress-induced cortisol increases on detection performance of hidden weapons in an x-ray baggage screening task. We randomly assigned 48 participants either to a stress or a nonstress group. The stress group was exposed to a standardized psychosocial stress test (TSST). Before and after stress/nonstress, participants had to detect threat objects in a computer-based object recognition test (X-ray ORT). We repeatedly measured salivary cortisol and X-ray ORT performance before and after stress/nonstress. Cortisol increases in reaction to psychosocial stress induction but not to nonstress independently impaired x-ray detection performance. Our results suggest that stress-induced cortisol increases at peak reactivity impair x-ray screening performance. Copyright © 2014 Society for Psychophysiological Research.

Photoluminescence and cathodoluminescence properties of green emitting SrGa2{S}4 : Eu2+ thin film

NASA Astrophysics Data System (ADS)

Chartier, Céline; Benalloul, Paul; Barthou, Charles; Frigerio, Jean-Marc; Mueller, Gerd O.; Mueller-Mach, Regina; Trottier, Troy

2002-02-01

Photoluminescence and cathodoluminescence properties of SrGa2S4 : Eu2+ thin films prepared by reactive RF magnetron sputtering are investigated. Luminescence performances of the phosphor in the thin film form are compared to those of powder samples: the brightness efficiency of thin films is found to be about 30% of the efficiency of powder at low current density. A ratio higher than 40% is expected at higher current density. Thin film screens for FEDs will become a positive alternative to powder screens provided that film quality and light extraction could be improved by optimization of thickness and deposition parameters.

Thermodynamically based solvent design for enzymatic saccharide acylation with hydroxycinnamic acids in non-conventional media.

PubMed

Zeuner, Birgitte; Kontogeorgis, Georgios M; Riisager, Anders; Meyer, Anne S

2012-02-15

Enzyme-catalyzed synthesis has been widely studied with lipases (EC 3.1.1.3), but feruloyl esterases (FAEs; EC 3.1.1.73) may provide advantages such as higher substrate affinity and regioselectivity in the synthesis of hydroxycinnamate saccharide esters. These compounds are interesting because of their amphiphilicity and antioxidative potential. Synthetic reactions using mono- or disaccharides as one of the substrates may moreover direct new routes for biomass upgrading in the biorefinery. The paper reviews the available data for enzymatic hydroxycinnamate saccharide ester synthesis in organic solvent systems as well as other enzymatic hydroxycinnamate acylations in ionic liquid systems. The choice of solvent system is highly decisive for enzyme stability, selectivity, and reaction yields in these synthesis reactions. To increase the understanding of the reaction environment and to facilitate solvent screening as a crucial part of the reaction design, the review explores the use of activity coefficient models for describing these systems and - more importantly - the use of group contribution model UNIFAC and quantum chemistry based COSMO-RS for thermodynamic predictions and preliminary solvent screening. Surfactant-free microemulsions of a hydrocarbon, a polar alcohol, and water are interesting solvent systems because they accommodate different substrate and product solubilities and maintain enzyme stability. Ionic liquids may provide advantages as solvents in terms of increased substrate and product solubility, higher reactivity and selectivity, as well as tunable physicochemical properties, but their design should be carefully considered in relation to enzyme stability. The treatise shows that thermodynamic modeling tools for solvent design provide a new toolbox to design enzyme-catalyzed synthetic reactions from biomass sources. Copyright © 2011 Elsevier B.V. All rights reserved.

Cue reactivity towards shopping cues in female participants.

PubMed

Starcke, Katrin; Schlereth, Berenike; Domass, Debora; Schöler, Tobias; Brand, Matthias

2013-03-01

Background and aims It is currently under debate whether pathological buying can be considered as a behavioural addiction. Addictions have often been investigated with cue-reactivity paradigms to assess subjective, physiological and neural craving reactions. The current study aims at testing whether cue reactivity towards shopping cues is related to pathological buying tendencies. Methods A sample of 66 non-clinical female participants rated shopping related pictures concerning valence, arousal, and subjective craving. In a subgroup of 26 participants, electrodermal reactions towards those pictures were additionally assessed. Furthermore, all participants were screened concerning pathological buying tendencies and baseline craving for shopping. Results Results indicate a relationship between the subjective ratings of the shopping cues and pathological buying tendencies, even if baseline craving for shopping was controlled for. Electrodermal reactions were partly related to the subjective ratings of the cues. Conclusions Cue reactivity may be a potential correlate of pathological buying tendencies. Thus, pathological buying may be accompanied by craving reactions towards shopping cues. Results support the assumption that pathological buying can be considered as a behavioural addiction. From a methodological point of view, results support the view that the cue-reactivity paradigm is suited for the investigation of craving reactions in pathological buying and future studies should implement this paradigm in clinical samples.

Canadian Public Health Laboratory Network laboratory guidelines for congenital syphilis and syphilis screening in pregnant women in Canada.

PubMed

Singh, Ameeta E; Levett, Paul N; Fonseca, Kevin; Jayaraman, Gayatri C; Lee, Bonita E

2015-01-01

Despite universal access to screening for syphilis in all pregnant women in Canada, cases of congenital syphilis have been reported in recent years in areas experiencing a resurgence of infectious syphilis in heterosexual partnerships. Antenatal screening in the first trimester continues to be important and should be repeated at 28 to 32 weeks and again at delivery in women at high risk of acquiring syphilis. The diagnosis of congenital syphilis is complex and is based on a combination of maternal history and clinical and laboratory criteria in both mother and infant. Serologic tests for syphilis remain important in the diagnosis of congenital syphilis and are complicated by the passive transfer of maternal antibodies which can affect the interpretation of reactive serologic tests in the infant. All infants born to mothers with reactive syphilis tests should have nontreponemal tests (NTT) and treponemal tests (TT) performed in parallel with the mother's tests. A fourfold or higher titre in the NTT in the infant at delivery is strongly suggestive of congenital infection but the absence of a fourfold or greater NTT titre does not exclude congenital infection. IgM tests for syphilis are not currently available in Canada and are not recommended due to poor performance. Other evaluation in the newborn infant may include long bone radiographs and cerebrospinal fluid tests but all suspect cases should be managed in conjunction with sexually transmitted infection and/or pediatric experts.

Canadian Public Health Laboratory Network laboratory guidelines for congenital syphilis and syphilis screening in pregnant women in Canada

PubMed Central

Singh, Ameeta E; Levett, Paul N; Fonseca, Kevin; Jayaraman, Gayatri C; Lee, Bonita E

2015-01-01

Despite universal access to screening for syphilis in all pregnant women in Canada, cases of congenital syphilis have been reported in recent years in areas experiencing a resurgence of infectious syphilis in heterosexual partnerships. Antenatal screening in the first trimester continues to be important and should be repeated at 28 to 32 weeks and again at delivery in women at high risk of acquiring syphilis. The diagnosis of congenital syphilis is complex and is based on a combination of maternal history and clinical and laboratory criteria in both mother and infant. Serologic tests for syphilis remain important in the diagnosis of congenital syphilis and are complicated by the passive transfer of maternal antibodies which can affect the interpretation of reactive serologic tests in the infant. All infants born to mothers with reactive syphilis tests should have nontreponemal tests (NTT) and treponemal tests (TT) performed in parallel with the mother’s tests. A fourfold or higher titre in the NTT in the infant at delivery is strongly suggestive of congenital infection but the absence of a fourfold or greater NTT titre does not exclude congenital infection. IgM tests for syphilis are not currently available in Canada and are not recommended due to poor performance. Other evaluation in the newborn infant may include long bone radiographs and cerebrospinal fluid tests but all suspect cases should be managed in conjunction with sexually transmitted infection and/or pediatric experts. PMID:25798162

Immigrant screening for latent tuberculosis in Norway: a cost-effectiveness analysis.

PubMed

Haukaas, Fredrik Salvesen; Arnesen, Trude Margrete; Winje, Brita Askeland; Aas, Eline

2017-05-01

The incidence of tuberculosis (TB) disease has increased in Norway since the mid-1990s. Immigrants are screened, and some are treated, for latent TB infection (LTBI) to prevent TB disease (reactivation). In this study, we estimated the costs of both treating and screening for LTBI and TB disease, which has not been done previously in Norway. We developed a model to indicate the cost-effectiveness of four different screening algorithms for LTBI using avoided TB disease cases as the health outcome. Further, we calculated the expected value of perfect information (EVPI), and indicated areas of LTBI screening that could be changed to improve cost-effectiveness. The costs of treating LTBI and TB disease were estimated to be €1938 and €15,489 per case, respectively. The model evaluates four algorithms, and suggests three cost-effective algorithms depending on the cost-effectiveness threshold. Screening all immigrants with interferon-gamma release assays (IGRA) requires the highest threshold (€28,400), followed by the algorithms "IGRA on immigrants with risk factors" and "no LTBI screening." EVPI is approximately €5 per screened immigrant. The costs for a cohort of 20,000 immigrants followed through 10 years range from €12.2 million for the algorithm "screening and treatment for TB disease but no LTBI screening," to €14 million for "screening all immigrants for both TB disease and LTBI with IGRA." The results suggest that the cost of TB disease screening and treatment is the largest contributor to total costs, while LTBI screening and treatment costs are relatively small. Increasing the proportion of IGRA-positive immigrants who are treated decreases the costs per avoided case substantially.

Quality assurance in the HIV/AIDS laboratory network of China.

PubMed

Jiang, Yan; Qiu, Maofeng; Zhang, Guiyun; Xing, Wenge; Xiao, Yao; Pan, Pinliang; Yao, Jun; Ou, Chin-Yih; Su, Xueli

2010-12-01

In 2009, there were 8273 local screening laboratories, 254 confirmatory laboratories, 35 provincial confirmatory central laboratories and 1 National AIDS Reference Laboratory (NARL) in China. These laboratories were located in Center for Disease Control and Prevention (CDC) facilities, hospitals, blood donation clinics, maternal and child health (MCH) hospitals and border health quarantine health-care facilities. The NARL and provincial laboratories provide quality assurance through technical, bio-safety and managerial training; periodic proficiency testing; on-site supervisory inspections; and commercial serologic kit evaluations. From 2002 to 2009, more than 220 million HIV antibody tests were performed at screening laboratories, and all reactive and indeterminate samples were confirmed at confirmatory laboratories. The use of highly technically complex tests, including CD4 cell enumeration, viral load, dried blood spot (DBS)-based early infant diagnosis (EID), drug resistance (DR) genotyping, HIV-1 subtyping and incidence assays, have increased in recent years and their performance quality is closely monitored. China has made significant progress in establishing a well-coordinated HIV laboratory network and QA systems. However, the coverage and intensity of HIV testing and quality assurance programmes need to be strengthened so as to ensure that more infected persons are diagnosed and that they receive timely prevention and treatment services.

A natural basis for efficient brain-actuated control

NASA Technical Reports Server (NTRS)

Makeig, S.; Enghoff, S.; Jung, T. P.; Sejnowski, T. J.

2000-01-01

The prospect of noninvasive brain-actuated control of computerized screen displays or locomotive devices is of interest to many and of crucial importance to a few 'locked-in' subjects who experience near total motor paralysis while retaining sensory and mental faculties. Currently several groups are attempting to achieve brain-actuated control of screen displays using operant conditioning of particular features of the spontaneous scalp electroencephalogram (EEG) including central mu-rhythms (9-12 Hz). A new EEG decomposition technique, independent component analysis (ICA), appears to be a foundation for new research in the design of systems for detection and operant control of endogenous EEG rhythms to achieve flexible EEG-based communication. ICA separates multichannel EEG data into spatially static and temporally independent components including separate components accounting for posterior alpha rhythms and central mu activities. We demonstrate using data from a visual selective attention task that ICA-derived mu-components can show much stronger spectral reactivity to motor events than activity measures for single scalp channels. ICA decompositions of spontaneous EEG would thus appear to form a natural basis for operant conditioning to achieve efficient and multidimensional brain-actuated control in motor-limited and locked-in subjects.

Developing an Apicomplexan DNA Barcoding System to Detect Blood Parasites of Small Coral Reef Fishes.

PubMed

Renoux, Lance P; Dolan, Maureen C; Cook, Courtney A; Smit, Nico J; Sikkel, Paul C

2017-08-01

Apicomplexan parasites are obligate parasites of many species of vertebrates. To date, there is very limited understanding of these parasites in the most-diverse group of vertebrates, actinopterygian fishes. While DNA barcoding targeting the eukaryotic 18S small subunit rRNA gene sequence has been useful in identifying apicomplexans in tetrapods, identification of apicomplexans infecting fishes has relied solely on morphological identification by microscopy. In this study, a DNA barcoding method was developed that targets the 18S rRNA gene primers for identifying apicomplexans parasitizing certain actinopterygian fishes. A lead primer set was selected showing no cross-reactivity to the overwhelming abundant host DNA and successfully confirmed 37 of the 41 (90.2%) microscopically verified parasitized fish blood samples analyzed in this study. Furthermore, this DNA barcoding method identified 4 additional samples that screened negative for parasitemia, suggesting this molecular method may provide improved sensitivity over morphological characterization by microscopy. In addition, this PCR screening method for fish apicomplexans, using Whatman FTA preserved DNA, was tested in efforts leading to a more simplified field collection, transport, and sample storage method as well as a streamlining sample processing important for DNA barcoding of large sample sets.

Trajectories of Social Anxiety in Children: Influence of Child Cortisol Reactivity and Parental Social Anxiety.

PubMed

Poole, Kristie L; Van Lieshout, Ryan J; McHolm, Angela E; Cunningham, Charles E; Schmidt, Louis A

2017-12-19

Few studies have examined the interactive effect of intra- and extra-individual vulnerability factors on the trajectory of social anxiety in children. In this study, we examined the joint influence of familial vulnerability (i.e., parental social anxiety) and child biological stress vulnerability (i.e., cortisol reactivity) on trajectories of social anxiety. Children (N = 112 (57 males), M age  = 8.14 years, S.D. = 2.25) were followed over three visits spanning approximately three years. Parental social anxiety was assessed using the Social Phobia and Anxiety Inventory, children's behavior and salivary cortisol reactivity were measured in response to a speech task, and children's social anxiety was assessed at all three visits using the Screen for Child Related Emotional Disorders (SCARED; Parent-report). A growth curve analysis was used to examine trajectories of child social anxiety as predicted by children's cortisol reactivity and parental social anxiety, adjusting for covariates. We found a significant interaction between parental social anxiety and child cortisol reactivity in predicting child social anxiety across time. Having a socially anxious parent coupled with heightened cortisol reactivity predicted the highest levels of child social anxiety, with scores that remained above clinically significant levels for social anxiety across all visits. Children with familial risk for social anxiety and who also exhibit high stress-reactivity appear to be at risk for persistent, clinically significant social anxiety. This highlights the importance of considering the interaction between both biological and contextual factors when considering the development, maintenance, and treatment of social anxiety in children across time.

A Multi-agent Based Cooperative Voltage and Reactive Power Control

NASA Astrophysics Data System (ADS)

Ishida, Masato; Nagata, Takeshi; Saiki, Hiroshi; Shimada, Ikuhiko; Hatano, Ryousuke

In order to maintain system voltage within the optimal range and prevent voltage instability phenomena before they occur, a variety of phase modifying equipment is installed in optimal locations throughout the power system network and a variety of methods of voltage reactive control are employed. The proposed system divided the traditional method to control voltage and reactive power into two sub problems; “voltage control” to adjust the secondary bus voltage of substations, and “reactive power control” to adjust the primary bus voltage. In this system, two types of agents are installed in substations in order to cooperate “voltage control” and “reactive power control”. In order to verify the performance of the proposed method, it has been applied to the model network system. The results confirm that our proposed method is able to control violent fluctuations in load.

Human endogenous retrovirus K(HML-2) Gag and Env specific T-cell responses are not detected in HTLV-I-infected subjects using standard peptide screening methods.

PubMed

Jones, R Brad; Leal, Fabio E; Hasenkrug, Aaron M; Segurado, Aluisio C; Nixon, Douglas F; Ostrowski, Mario A; Kallas, Esper G

2013-01-10

An estimated 10-20 million individuals are infected with the retrovirus human T-cell leukemia virus type 1 (HTLV-1). While the majority of these individuals remain asymptomatic, 0.3-4% develop a neurodegenerative inflammatory disease, termed HTLV-1-associated myelopathy/tropical spastic paraparesis (HAM/TSP). HAM/TSP results in the progressive demyelination of the central nervous system and is a differential diagnosis of multiple sclerosis (MS). The etiology of HAM/TSP is unclear, but evidence points to a role for CNS-inflitrating T-cells in pathogenesis. Recently, the HTLV-1-Tax protein has been shown to induce transcription of the human endogenous retrovirus (HERV) families W, H and K. Intriguingly, numerous studies have implicated these same HERV families in MS, though this association remains controversial. Here, we explore the hypothesis that HTLV-1-infection results in the induction of HERV antigen expression and the elicitation of HERV-specific T-cells responses which, in turn, may be reactive against neurons and other tissues. PBMC from 15 HTLV-1-infected subjects, 5 of whom presented with HAM/TSP, were comprehensively screened for T-cell responses to overlapping peptides spanning HERV-K(HML-2) Gag and Env. In addition, we screened for responses to peptides derived from diverse HERV families, selected based on predicted binding to predicted optimal epitopes. We observed a lack of responses to each of these peptide sets. Thus, although the limited scope of our screening prevents us from conclusively disproving our hypothesis, the current study does not provide data supporting a role for HERV-specific T-cell responses in HTLV-1 associated immunopathology.

Electroanalytical Evaluation of Nanoparticles by Nano-impact Electrochemistry

NASA Astrophysics Data System (ADS)

Karimi, Anahita

Applications of engineered nanoparticles in electronics, catalysis, solid oxide fuel cells, medicine and sensing continue to increase. Traditionally, nanoparticle systems are characterized by spectroscopic and microscopic techniques. These methods are cumbersome and expensive, which limit their routine use for screening purposes. Electrochemistry is a powerful, yet underutilized tool, for the detection and classification of nanoparticles. The first part of this dissertation investigates a recently developed electrochemical method -- nanoparticle collision electrochemistry -- for detection and characterization of nanoparticles. Three independent projects have been described to evaluate the use of this technique for characterizing nanoparticle based systems including: conjugation with biomolecules, interaction with environmental contaminants and fundamental investigation of conformational changes of nanoparticle capping ligands. The thesis reports the first use of nano-impact electrochemistry to quantitatively investigate bioconjugation and biomolecular recognition at conductive nanoparticles. Furthermore, we also demonstrate the potential of this method as a single step, reagentless and label-free technique for the ultra-sensitive detection of biomolecular targets. A fundamental study of biorecognition is important for the development of therapeutics and molecular diagnosis probes in the biomedical, biosensing and biotechnology fields. The second project describes the use of this method as a screening tool of particle reactivity. We study the interaction and adsorption of a toxic environmental metalloid (Arsenic) with metal oxide nanoparticles to extract mechanistic, speciation and loading information. We discuss the potential of this approach to complement or replace costly characterization techniques and enable routine study of nanoparticles and their reactivity. In the third project, we use the nano-impact method to study the pH-dependent conformational changes of polymeric capping agents on the surface of silver nanoparticles. Nano-impact elecrochemistry has demonstrated promising results for studying functionality, stability and conformational changes of stabilizing agents. The second part of this thesis explores the use of carbon nanomaterials such as graphene and Pt-doped CeO2 for the rational design of enzyme-conjugated nanostructures for biosensing applications. The dissertation reports fabrication, characterization and properties of hybrid CeO2-based bioelectrocatalytic nanostructure material with PEDOT:PSS [poly(3,4ethylenedioxythiophene):poly-styrene-sulfonic acid] on porous carbon materials as novel materials for designing high performance laccase (Lac) biocathodes and biofuel cells.

To Evaluate and Compare Periodontal Disease and Smoking as a Parallel Risk Factor for Systemic Health by Gauging the Serum C-Reactive Protein Levels.

PubMed

Raval, Ruchi Dinesh; Sharma, Payal; Chandran, Sarath; Vasavada, Dharmesh; Nadig, Priyadarshini; Bakutra, Gaurav

2017-03-01

Physiologic and metabolic changes that occur immediately after a damage or disease are known as Acute Phase Reaction (APR). Acute Phase Proteins (APP) are blood proteins secreted by hepatocytes during APR C-Reactive Protein (CRP) being the important one. Present study was designed to estimate and compare the levels of the serum CRP in current smokers, former smokers and non-smokers, with and without periodontitis. An experimental study was planned on 165 subjects who were divided into four groups. Group 1- nonsmokers with periodontitis. Group 2- smokers without periodontitis. Group 3- smokers with periodontitis. Group 4- former smokers without periodontitis. Healthy controls were not included in the study as the normal range of CRP in health is already established. Periodontal examination was done and serum CRP was measured. After getting the acceptance to be a part of the study, written informed consent was taken from each participant. Data analysis was done by ANOVA and post-hoc tests. Highest level of CRP was found in smokers with periodontitis followed by non-smokers with periodontitis and smokers without periodontitis. Former smokers had minimum CRP compared to the other groups (p-value=0.03). Periodontitis alone and in combination with smoking increases the systemic inflammatory burden and associated cardiovascular risk. This fact should be communicated thoroughly to the general population, general dentist, physicians and cardiovascular specialist to enhance early screening and multidisciplinary treatment.

To Evaluate and Compare Periodontal Disease and Smoking as a Parallel Risk Factor for Systemic Health by Gauging the Serum C-Reactive Protein Levels

PubMed Central

Sharma, Payal; Chandran, Sarath; Vasavada, Dharmesh; Nadig, Priyadarshini; Bakutra, Gaurav

2017-01-01

Introduction Physiologic and metabolic changes that occur immediately after a damage or disease are known as Acute Phase Reaction (APR). Acute Phase Proteins (APP) are blood proteins secreted by hepatocytes during APR C-Reactive Protein (CRP) being the important one. Aim Present study was designed to estimate and compare the levels of the serum CRP in current smokers, former smokers and non-smokers, with and without periodontitis. Materials and Methods An experimental study was planned on 165 subjects who were divided into four groups. Group 1- nonsmokers with periodontitis. Group 2- smokers without periodontitis. Group 3- smokers with periodontitis. Group 4- former smokers without periodontitis. Healthy controls were not included in the study as the normal range of CRP in health is already established. Periodontal examination was done and serum CRP was measured. After getting the acceptance to be a part of the study, written informed consent was taken from each participant. Data analysis was done by ANOVA and post-hoc tests. Results Highest level of CRP was found in smokers with periodontitis followed by non-smokers with periodontitis and smokers without periodontitis. Former smokers had minimum CRP compared to the other groups (p-value=0.03). Conclusion Periodontitis alone and in combination with smoking increases the systemic inflammatory burden and associated cardiovascular risk. This fact should be communicated thoroughly to the general population, general dentist, physicians and cardiovascular specialist to enhance early screening and multidisciplinary treatment. PMID:28511516

A novel trapping system for the detection of reactive drug metabolites using the fungus Cunninghamella elegans and high resolution mass spectrometry.

PubMed

Rydevik, Axel; Hansson, Annelie; Hellqvist, Anna; Bondesson, Ulf; Hedeland, Mikael

2015-07-01

A new model is presented that can be used to screen for bioactivation of drugs. The evaluation of toxicity is an important step in the development of new drugs. One way to detect possible toxic metabolites is to use trapping agents such as glutathione. Often human liver microsomes are used as a metabolic model in initial studies. However, there is a need for alternatives that are easy to handle, cheap, and can produce large amounts of metabolites. In the presented study, paracetamol, mefenamic acid, and diclofenac, all known to form reactive metabolites in humans, were incubated with the fungus Cunninghamella elegans and the metabolites formed were characterized with ultra high performance liquid chromatography coupled to a quadrupole time of flight mass spectrometer. Interestingly, glutathione conjugates formed by the fungus were observed for all three drugs and their retention times and MS/MS spectra matched those obtained in a comparative experiment with human liver microsomes. These findings clearly demonstrated that the fungus is a suitable trapping model for toxic biotransformation products. Cysteine conjugates of all three test drugs were also observed with high signal intensities in the fungal incubates, giving the model a further indicator of drug bioactivation. To our knowledge, this is the first demonstration of the use of a fungal model for the formation and trapping of reactive drug metabolites. The investigated model is cheap, easy to handle, it does not involve experimental animals and it can be scaled up to produce large amounts of metabolites. Copyright © 2014 John Wiley & Sons, Ltd.

Screening of the chemical reactivity of three different graphite sources using the formation of reductively alkylated graphene as a model reaction.

PubMed

Knirsch, Kathrin C; Englert, Jan M; Dotzer, Christoph; Hauke, Frank; Hirsch, Andreas

2013-11-28

Reductive alkylation of three graphite starting materials G(flake), G(powder), and G(spherical) reveals pronounced differences in the obtained covalently functionalized graphene with respect to the degree of functionalization, exfoliation efficiency and product homogeneity, as demonstrated by statistical Raman microscopy (SRM), TGA/MS, IR-spectroscopy and solubility behavior.

Tuberculosis among elderly Chinese in residential homes: tuberculin reactivity and estimated prevalence.

PubMed

Woo, J; Chan, H S; Hazlett, C B; Ho, S C; Chan, R; Sham, A; Davies, P D

1996-01-01

Objectives of this study were to determine the prevalence of positive tuberculin reactivity and associated factors among elderly nursing home residents in a population with a relatively high tuberculosis notification rate, to estimate the prevalence of active tuberculosis, and to assess tuberculin reactivity as a screening tool. A stratified, disproportional, randomized cluster sample of residents was selected and the Mantoux test (using 0.1 ml of 5 tuberculin units of purified protein derivative of tuberculin) carried out. All subjects with a positive test had a chest X-ray followed by sputum smear and culture if the X-ray was abnormal. Sputum examination was also carried out in a random sample of controls, matched for age and gender, drawn from subjects with a negative Mantoux test. Information regarding medical history, tobacco smoking habits, symptoms related to tuberculosis, and communal eating habits were gathered. Also anthropometric data were collected. Sixteen nursing homes in the catchment area of a major district hospital in Hong Kong comprising 587 residents (136 men, 451 women, mean age 80 +/- 8 years) participated in this study. The weighted prevalence of tuberculin reactivity was 43.8%. It was higher in men, among those who took their meals in a common area, in the younger age group, and in those with no previous history of hospitalization. No association was found between prevalence and duration of residence, smoking, skinfold thickness, past medical history, or any relevant symptoms. Following radiological and sputum examination, the estimated prevalence of active tuberculosis ranged from 1.2 to 2.6%. The sensitivity of the tuberculin test was 86, the specificity 30%. The prevalence of active tuberculosis in nursing homes in Hong Kong is high, but it is unclear whether cross-infection or poor health of the residents is the major contributing factor. Tuberculin skin testing does not appear to be a useful screening method in this population.

A new method for total OH reactivity measurements using a fast Gas Chromatographic Photo-Ionization Detector (GC-PID)

NASA Astrophysics Data System (ADS)

Nölscher, A. C.; Sinha, V.; Bockisch, S.; Klüpfel, T.; Williams, J.

2012-05-01

The primary and most important oxidant in the atmosphere is the hydroxyl radical (OH). Currently OH sinks, particularly gas phase reactions, are poorly constrained. One way to characterize the overall sink of OH is to measure directly the ambient loss rate of OH, the total OH reactivity. To date direct measurements of total OH reactivity have been either performed using a Laser Induced Fluorescence (LIF) system ("pump-and-probe" or "flow reactor") or the Comparative Reactivity Method (CRM) with a Proton Transfer Reaction Mass Spectrometer (PTR-MS). Both techniques require large, complex and expensive detection systems. This study presents a feasibility assessment for CRM total OH reactivity measurements using a new detector, a Gas Chromatographic Photo-Ionization Detector (GC-PID). Such a system is smaller, more portable, less power consuming and less expensive than other total OH reactivity measurement techniques. Total OH reactivity is measured by the CRM using a competitive reaction between a reagent (here pyrrole) with OH alone and in the presence of atmospheric reactive molecules. The new CRM method for total OH reactivity has been tested with parallel measurements of the GC-PID and the previously validated PTR-MS as detector for the reagent pyrrole during laboratory experiments, plant chamber and boreal field studies. Excellent agreement of both detectors was found when the GC-PID was operated under optimum conditions. Time resolution (60-70 s), sensitivity (LOD 3-6 s-1) and overall uncertainty (25% in optimum conditions) for total OH reactivity were equivalent to PTR-MS based total OH reactivity measurements. One drawback of the GC-PID system was the steady loss of sensitivity and accuracy during intensive measurements lasting several weeks, and a possible toluene interference. Generally, the GC-PID system has been shown to produce closely comparable results to the PTR-MS and thus in suitable environments (e.g. forests) it presents a viably economical alternative for groups interested in total OH reactivity observations.

Total OH reactivity measurements using a new fast Gas Chromatographic Photo-Ionization Detector (GC-PID)

NASA Astrophysics Data System (ADS)

Nölscher, A. C.; Sinha, V.; Bockisch, S.; Klüpfel, T.; Williams, J.

2012-12-01

The primary and most important oxidant in the atmosphere is the hydroxyl radical (OH). Currently OH sinks, particularly gas phase reactions, are poorly constrained. One way to characterize the overall sink of OH is to measure directly the ambient loss rate of OH, the total OH reactivity. To date, direct measurements of total OH reactivity have been either performed using a Laser-Induced Fluorescence (LIF) system ("pump-and-probe" or "flow reactor") or the Comparative Reactivity Method (CRM) with a Proton-Transfer-Reaction Mass Spectrometer (PTR-MS). Both techniques require large, complex and expensive detection systems. This study presents a feasibility assessment for CRM total OH reactivity measurements using a new detector, a Gas Chromatographic Photoionization Detector (GC-PID). Such a system is smaller, more portable, less power consuming and less expensive than other total OH reactivity measurement techniques. Total OH reactivity is measured by the CRM using a competitive reaction between a reagent (here pyrrole) with OH alone and in the presence of atmospheric reactive molecules. The new CRM method for total OH reactivity has been tested with parallel measurements of the GC-PID and the previously validated PTR-MS as detector for the reagent pyrrole during laboratory experiments, plant chamber and boreal field studies. Excellent agreement of both detectors was found when the GC-PID was operated under optimum conditions. Time resolution (60-70 s), sensitivity (LOD 3-6 s-1) and overall uncertainty (25% in optimum conditions) for total OH reactivity were similar to PTR-MS based total OH reactivity measurements. One drawback of the GC-PID system was the steady loss of sensitivity and accuracy during intensive measurements lasting several weeks, and a possible toluene interference. Generally, the GC-PID system has been shown to produce closely comparable results to the PTR-MS and thus in suitable environments (e.g. forests) it presents a viably economical alternative for groups interested in total OH reactivity observations.

Effects of intranasal oxytocin on amygdala reactivity to emotional faces in recently trauma-exposed individuals.

PubMed

Frijling, Jessie L; van Zuiden, Mirjam; Koch, Saskia B J; Nawijn, Laura; Veltman, Dick J; Olff, Miranda

2016-02-01

There is a need for effective, early post-trauma preventive interventions for post-traumatic stress disorder (PTSD). Attenuating amygdala hyperreactivity early post-trauma, a likely PTSD vulnerability factor, may decrease PTSD risk. Since oxytocin modulates amygdala reactivity to emotional stimuli, oxytocin administration early post-trauma may be a promising candidate for PTSD prevention. In a randomized double-blind placebo-controlled fMRI study, we investigated effects of a single intranasal oxytocin administration (40 IU) on amygdala reactivity to happy, neutral and fearful faces in 41 recently trauma-exposed men and women showing moderate to high distress after initial post-trauma screening. We explored treatment interactions with sex. Participants were scanned within 11 days post-trauma. Compared with placebo, oxytocin significantly increased right amygdala reactivity to fearful faces. There was a significant treatment by sex interaction on amygdala reactivity to neutral faces, with women showing increased left amygdala reactivity after oxytocin. These findings indicate that a single oxytocin administration may enhance fearful faces processing in recently trauma-exposed individuals and neutral faces processing in recently trauma-exposed women. These observations may be explained by oxytocin-induced increased salience processing. Clinical implications of these findings for PTSD prevention should be further investigated. Netherlands Trial Registry; Boosting Oxytocin after trauma: Neurobiology and the Development of Stress-related psychopathology (BONDS); NTR3190; http://www.trialregister.nl/trialreg/admin/rctview.asp?TC = 3190. © The Author (2015). Published by Oxford University Press. For Permissions, please email: journals.permissions@oup.com.

C-reactive protein as a prognostic indicator for rebleeding in patients with nonvariceal upper gastrointestinal bleeding.

PubMed

Lee, Han Hee; Park, Jae Myung; Lee, Soon-Wook; Kang, Seung Hun; Lim, Chul-Hyun; Cho, Yu Kyung; Lee, Bo-In; Lee, In Seok; Kim, Sang Woo; Choi, Myung-Gyu

2015-05-01

In patients with acute nonvariceal upper gastrointestinal bleeding, rebleeding after an initial treatment is observed in 10-20% and is associated with mortality. To investigate whether the initial serum C-reactive protein level could predict the risk of rebleeding in patients with acute nonvariceal upper gastrointestinal bleeding. This was a retrospective study using prospectively collected data for upper gastrointestinal bleeding. Initial clinical characteristics, endoscopic features, and C-reactive protein levels were compared between those with and without 30-day rebleeding. A total of 453 patients were included (mean age, 62 years; male, 70.9%). The incidence of 30-day rebleeding was 15.9%. The mean serum C-reactive protein level was significantly higher in these patients than in those without rebleeding (P<0.001). The area under the receiver operating characteristics curve with a cutoff value of 0.5mg/dL was 0.689 (P<0.001). High serum C-reactive protein level (odds ratio, 2.98; confidence interval, 1.65-5.40) was independently associated with the 30-day rebleeding risk after adjustment for the main confounding risk factors, including age, blood pressure, and initial haemoglobin level. The serum C-reactive protein was an independent risk factor for 30-day rebleeding in patients with acute nonvariceal upper gastrointestinal bleeding, indicating a possible role as a useful screening indicator for predicting the risk of rebleeding. Copyright © 2015 Editrice Gastroenterologica Italiana S.r.l. Published by Elsevier Ltd. All rights reserved.

Abacavir induced T cell reactivity from drug naïve individuals shares features of allo-immune responses.

PubMed

Adam, Jacqueline; Wuillemin, Natascha; Watkins, Stephan; Jamin, Heidi; Eriksson, Klara K; Villiger, Peter; Fontana, Stefano; Pichler, Werner J; Yerly, Daniel

2014-01-01

Abacavir hypersensitivity is a severe hypersensitivity reaction which occurs exclusively in carriers of the HLA-B*57∶01 allele. In vitro culture of PBMC with abacavir results in the outgrowth of abacavir-reacting CD8+ T cells, which release IFNγ and are cytotoxic. How this immune response is induced and what is recognized by these T cells is still a matter of debate. We analyzed the conditions required to develop an abacavir-dependent T cell response in vitro. The abacavir reactivity was independent of co-stimulatory signals, as neither DC maturation nor release of inflammatory cytokines were observed upon abacavir exposure. Abacavir induced T cells arose in the absence of professional APC and stemmed from naïve and memory compartments. These features are reminiscent of allo-reactivity. Screening for allo-reactivity revealed that about 5% of generated T cell clones (n = 136) from three donors were allo-reactive exclusively to the related HLA-B*58∶01. The addition of peptides which can bind to the HLA-B*57∶01-abacavir complex and to HLA-B*58∶01 during the induction phase increased the proportion of HLA-B*58∶01 allo-reactive T cell clones from 5% to 42%. In conclusion, abacavir can alter the HLA-B*57∶01-peptide complex in a way that mimics an allo-allele ('altered self-allele') and create the potential for robust T cell responses.

Abacavir Induced T Cell Reactivity from Drug Naïve Individuals Shares Features of Allo-Immune Responses

PubMed Central

Adam, Jacqueline; Wuillemin, Natascha; Watkins, Stephan; Jamin, Heidi; Eriksson, Klara K.; Villiger, Peter; Fontana, Stefano; Pichler, Werner J.; Yerly, Daniel

2014-01-01

Abacavir hypersensitivity is a severe hypersensitivity reaction which occurs exclusively in carriers of the HLA-B*57∶01 allele. In vitro culture of PBMC with abacavir results in the outgrowth of abacavir-reacting CD8+ T cells, which release IFNγ and are cytotoxic. How this immune response is induced and what is recognized by these T cells is still a matter of debate. We analyzed the conditions required to develop an abacavir-dependent T cell response in vitro. The abacavir reactivity was independent of co-stimulatory signals, as neither DC maturation nor release of inflammatory cytokines were observed upon abacavir exposure. Abacavir induced T cells arose in the absence of professional APC and stemmed from naïve and memory compartments. These features are reminiscent of allo-reactivity. Screening for allo-reactivity revealed that about 5% of generated T cell clones (n = 136) from three donors were allo-reactive exclusively to the related HLA-B*58∶01. The addition of peptides which can bind to the HLA-B*57∶01-abacavir complex and to HLA-B*58∶01 during the induction phase increased the proportion of HLA-B*58∶01 allo-reactive T cell clones from 5% to 42%. In conclusion, abacavir can alter the HLA-B*57∶01-peptide complex in a way that mimics an allo-allele (‘altered self-allele’) and create the potential for robust T cell responses. PMID:24751900

Full-scale demonstration of in situ cometabolic biodegradation of trichloroethylene in groundwater 2. Comprehensive analysis of field data using reactive transport modeling

NASA Astrophysics Data System (ADS)

Gandhi, Rahul K.; Hopkins, Gary D.; Goltz, Mark N.; Gorelick, Steven M.; McCarty, Perry L.

2002-04-01

We present an analysis of an extensively monitored full-scale field demonstration of in situ treatment of trichloroethylene (TCE) contamination by aerobic cometabolic biodegradation. The demonstration was conducted at Edwards Air Force Base in southern California. There are two TCE-contaminated aquifers at the site, separated from one another by a clay aquitard. The treatment system consisted of two recirculating wells located 10 m apart. Each well was screened in both of the contaminated aquifers. Toluene, oxygen, and hydrogen peroxide were added to the water in both wells. At one well, water was pumped from the upper aquifer to the lower aquifer. In the other well, pumping was from the lower to the upper aquifer. This resulted in a ``conveyor belt'' flow system with recirculation between the two aquifers. The treatment system was successfully operated for a 410 day period. We explore how well a finite element reactive transport model can describe the key processes in an engineered field system. Our model simulates TCE, toluene, oxygen, hydrogen peroxide, and microbial growth/death. Simulated processes include advective-dispersive transport, biodegradation, the inhibitory effect of hydrogen peroxide on biomass growth, and oxygen degassing. Several parameter values were fixed to laboratory values or values from previous modeling studies. The remaining six parameter values were obtained by calibrating the model to 7213 TCE concentration data and 6997 dissolved oxygen concentration data collected during the demonstration using a simulation-regression procedure. In this complex flow field involving reactive transport, TCE and dissolved oxygen concentration histories are matched very well by the calibrated model. Both simulated and observed toluene concentrations display similar high-frequency oscillations due to pulsed toluene injection approximately one half hour during each 8 hour period. Simulation results indicate that over the course of the demonstration, 6.9 kg of TCE was degraded and that in the upper aquifer a region 40 m wide extending 25 m down gradient of the treatment system was cleaned up to less than 100 μg L-1 from initial concentrations of approximately 700 μg L-1. A smaller region was cleaned up to less than 30 μg L-1. Simulations indicate that the cleaned up area in the upper aquifer would continue to expand for as long as treatment was continued.

Ex vivo screening for immunodominant viral epitopes by quantitative real time polymerase chain reaction (qRT-PCR)

PubMed Central

Provenzano, Maurizio; Mocellin, Simone; Bonginelli, Paola; Nagorsen, Dirk; Kwon, Seog-Woon; Stroncek, David

2003-01-01

The identification and characterization of viral epitopes across the Human Leukocyte Antigen (HLA) polymorphism is critical for the development of actives-specific or adoptive immunotherapy of virally-mediated diseases. This work investigates whether cytokine mRNA transcripts could be used to identify epitope-specific HLA-restricted memory T lymphocytes reactivity directly in fresh peripheral blood mononuclear cells (PBMCs) from viral-seropositive individuals in response to ex vivo antigen recall. PBMCs from HLA-A*0201 healthy donors, seropositive for Cytomegalovirus (CMV) and Influenza (Flu), were exposed for different periods and at different cell concentrations to the HLA-A*0201-restricted viral FluM158–66 and CMVpp65495–503 peptides. Quantitative real time PCR (qRT-PCR) was employed to evaluate memory T lymphocyte immune reactivation by measuring the production of mRNA encoding four cytokines: Interferon-γ (IFN-γ), Interleukin-2 (IL-2), Interleukin-4 (IL-4), and Interleukin-10 (IL-10). We could characterize cytokine expression kinetics that illustrated how cytokine mRNA levels could be used as ex vivo indicators of T cell reactivity. Particularly, IFN-γ mRNA transcripts could be consistently detected within 3 to 12 hours of short-term stimulation in levels sufficient to screen for HLA-restricted viral immune responses in seropositive subjects. This strategy will enhance the efficiency of the identification of viral epitopes independently of the individual HLA phenotype and could be used to follow the intensity of immune responses during disease progression or in response to in vivo antigen-specific immunization. PMID:14675481

A fluorescence high throughput screening method for the detection of reactive electrophiles as potential skin sensitizers.

PubMed

Avonto, Cristina; Chittiboyina, Amar G; Rua, Diego; Khan, Ikhlas A

2015-12-01

Skin sensitization is an important toxicological end-point in the risk assessment of chemical allergens. Because of the complexity of the biological mechanisms associated with skin sensitization, integrated approaches combining different chemical, biological and in silico methods are recommended to replace conventional animal tests. Chemical methods are intended to characterize the potential of a sensitizer to induce earlier molecular initiating events. The presence of an electrophilic mechanistic domain is considered one of the essential chemical features to covalently bind to the biological target and induce further haptenation processes. Current in chemico assays rely on the quantification of unreacted model nucleophiles after incubation with the candidate sensitizer. In the current study, a new fluorescence-based method, 'HTS-DCYA assay', is proposed. The assay aims at the identification of reactive electrophiles based on their chemical reactivity toward a model fluorescent thiol. The reaction workflow enabled the development of a High Throughput Screening (HTS) method to directly quantify the reaction adducts. The reaction conditions have been optimized to minimize solubility issues, oxidative side reactions and increase the throughput of the assay while minimizing the reaction time, which are common issues with existing methods. Thirty-six chemicals previously classified with LLNA, DPRA or KeratinoSens™ were tested as a proof of concept. Preliminary results gave an estimated 82% accuracy, 78% sensitivity, 90% specificity, comparable to other in chemico methods such as Cys-DPRA. In addition to validated chemicals, six natural products were analyzed and a prediction of their sensitization potential is presented for the first time. Copyright © 2015 Elsevier Inc. All rights reserved.

Aqueous photodegradation of antibiotic florfenicol: kinetics and degradation pathway studies.

PubMed

Zhang, Ya; Li, Jianhua; Zhou, Lei; Wang, Guoqing; Feng, Yanhong; Wang, Zunyao; Yang, Xi

2016-04-01

The occurrence of antibacterial agents in natural environment was of scientific concern in recent years. As endocrine disrupting chemicals, they had potential risk on ecology system and human beings. In the present study, the photodegradation kinetics and pathways of florfenicol were investigated under solar and xenon lamp irradiation in aquatic systems. Direct photolysis half-lives of florfenicol were determined as 187.29 h under solar irradiation and 22.43 h under xenon lamp irradiation, respectively. Reactive oxygen species (ROS), such as hydroxyl radical (·OH) and singlet oxygen ((1)O2) were found to play an important role in indirect photolysis process. The presence of nitrate and dissolved organic matters (DOMs) could affect photolysis of florfenicol in solutions through light screening effect, quenching effect, and photoinduced oxidization process. Photoproducts of florfenicol in DOMs solutions were identified by solid phase extraction-liquid chromatography-mass spectrometry (SPE-LC-MS) analysis techniques, and degradation pathways were proposed, including photoinduced hydrolysis, oxidation by (1)O2 and ·OH, dechlorination, and cleavage of the side chain.

Inhibition of oxidative stress in cholinergic projection neurons fully rescues aging-associated olfactory circuit degeneration in Drosophila

PubMed Central

Loschek, Laura F; La Fortezza, Marco; Friedrich, Anja B; Blais, Catherine-Marie; Üçpunar, Habibe K; Yépez, Vicente A; Lehmann, Martin; Gompel, Nicolas; Gagneur, Julien; Sigrist, Stephan J

2018-01-01

Loss of the sense of smell is among the first signs of natural aging and neurodegenerative diseases such as Alzheimer’s and Parkinson’s. Cellular and molecular mechanisms promoting this smell loss are not understood. Here, we show that Drosophila melanogaster also loses olfaction before vision with age. Within the olfactory circuit, cholinergic projection neurons show a reduced odor response accompanied by a defect in axonal integrity and reduction in synaptic marker proteins. Using behavioral functional screening, we pinpoint that expression of the mitochondrial reactive oxygen scavenger SOD2 in cholinergic projection neurons is necessary and sufficient to prevent smell degeneration in aging flies. Together, our data suggest that oxidative stress induced axonal degeneration in a single class of neurons drives the functional decline of an entire neural network and the behavior it controls. Given the important role of the cholinergic system in neurodegeneration, the fly olfactory system could be a useful model for the identification of drug targets. PMID:29345616

Combining structure-based pharmacophore modeling, virtual screening, and in silico ADMET analysis to discover novel tetrahydro-quinoline based pyruvate kinase isozyme M2 activators with antitumor activity

PubMed Central

Chen, Can; Wang, Ting; Wu, Fengbo; Huang, Wei; He, Gu; Ouyang, Liang; Xiang, Mingli; Peng, Cheng; Jiang, Qinglin

2014-01-01

Compared with normal differentiated cells, cancer cells upregulate the expression of pyruvate kinase isozyme M2 (PKM2) to support glycolytic intermediates for anabolic processes, including the synthesis of nucleic acids, amino acids, and lipids. In this study, a combination of the structure-based pharmacophore modeling and a hybrid protocol of virtual screening methods comprised of pharmacophore model-based virtual screening, docking-based virtual screening, and in silico ADMET (absorption, distribution, metabolism, excretion and toxicity) analysis were used to retrieve novel PKM2 activators from commercially available chemical databases. Tetrahydroquinoline derivatives were identified as potential scaffolds of PKM2 activators. Thus, the hybrid virtual screening approach was applied to screen the focused tetrahydroquinoline derivatives embedded in the ZINC database. Six hit compounds were selected from the final hits and experimental studies were then performed. Compound 8 displayed a potent inhibitory effect on human lung cancer cells. Following treatment with Compound 8, cell viability, apoptosis, and reactive oxygen species (ROS) production were examined in A549 cells. Finally, we evaluated the effects of Compound 8 on mice xenograft tumor models in vivo. These results may provide important information for further research on novel PKM2 activators as antitumor agents. PMID:25214764

Occupational methacrylate and acrylate allergy--cross-reactions and possible screening allergens.

PubMed

Aalto-Korte, Kristiina; Henriks-Eckerman, Maj-Len; Kuuliala, Outi; Jolanki, Riitta

2010-12-01

Acrylic resin monomers, especially acrylates and methacrylates, are important occupational allergens. To analyse patterns of concomitant patch test reactions to acrylic monomers in relation to exposure, and to suggest possible screening allergens. We reviewed the patch test files for the years 1994-2009 at the Finnish Institute of Occupational Health for allergic reactions to acrylic monomers, and analysed the clinical records of sensitized patients. In a group of 66 patients allergic to an acrylic monomer, the most commonly positive allergens were three methacrylates, namely ethyleneglycol dimethacrylate (EGDMA), 2-hydroxyethyl methacrylate (2-HEMA) and 2-hydroxypropyl methacrylate (2-HPMA), and an acrylate, namely diethyleneglycol diacrylate (DEGDA). The patterns of concomitant reactions imply that exposure to methacrylates may induce cross-reactivity to acrylates, whereas exposure to acrylates usually does not lead to cross-allergy to methacrylates. Screening for triethyleneglycol diacrylate (TREGDA) in the baseline series was found to be useful, as 3 of 8 patients with diagnosed occupational acrylate allergy might have been missed without the screening. A short screening series of four allergens, EGDMA, DEGDA, 2-HPMA and pentaerythritol triacrylate (PETA), would have screened 93% of our 66 patients; each of the remaining 5 patients reacted to different acrylic monomer(s). © 2010 John Wiley & Sons A/S.

A high-throughput screen of the GTPase activity of Escherichia coli EngA to find an inhibitor of bacterial ribosome biogenesis

PubMed Central

Bharat, Amrita; Blanchard, Jan E.; Brown, Eric D.

2014-01-01

The synthesis of ribosomes is an essential process, which is aided by a variety of transacting factors in bacteria. Among these is a group of GTPases essential for bacterial viability and emerging as promising targets for new antibacterial agents. Herein, we describe a robust high-throughput screening process for inhibitors of one such GTPase, the Escherichia coli EngA protein. The primary screen employed an assay of phosphate production in 384-well density. Reaction conditions were chosen to maximize sensitivity for the discovery of competitive inhibitors while maintaining a strong signal amplitude and low noise. In a pilot screen of 31,800 chemical compounds, 44 active compounds were identified. Further, we describe the elimination of non-specific inhibitors that were detergent-sensitive or reactive as well as those that interfered with the high-throughput phosphate assay. Four inhibitors survived these common counter-screens for non-specificity but these chemicals were also inhibitors of the unrelated enzyme dihydrofolate reductase, suggesting that they too were promiscuously active. The high-throughput screen of the EngA protein described here provides a meticulous pilot study in the search for specific inhibitors of GTPases involved in ribosome biogenesis. PMID:23606650

Evaluation of a malarial antibody assay for use in the screening of blood and tissue products for clinical use.

PubMed

Kitchen, A D; Lowe, P H J; Lalloo, K; Chiodini, P L

2004-10-01

A new recombinant Plasmodium antigen enzyme immunoassay (EIA) for the detection of malarial antibodies was evaluated for the screening of 'malaria-risk' blood and tissue donations. A total of 13,269 donor and patient samples were tested by both the EIA and the standard diagnostic antibody immunofluorescence test (IFAT). A total of 114/138 (82.6%) samples from patients with P. falciparum and 11/13 (84.6%) samples from patients with P. vivax tested positive. A total of 714/13,053 (5.47%) samples from donors identified as 'malaria risk', owing to residency or travel, were reactive in the EIA. The assay is more sensitive than a previously implemented malarial antibody EIA (73% in acute P. falciparum and 56% in acute P. vivax infections). The sensitivity of this new EIA is comparable to that of the IFAT, and the specificity is sufficient to screen 'malaria-risk' donors.

A comparison of the absorbed fluorescent treponemal antibody (FTA-ABS) test and other screening tests for treponemal disease in patients attending a venereal disease clinic.

PubMed

Wilkinson, A E; Scrimgeour, G; Rodin, P

1972-05-01

Screening tests-absorbed fluorescent treponemal (FTA-ABS), the Reiter protein complement-fixation (RPCFT), VDRL slide test, automated reagin-and cardiolipin Wassermann reaction-were carried out on 1922 consecutive new patients attending the Whitechapel Clinic over a three-month period.Taking the FTA-ABS test results as an index, the most efficient combination of conventional tests was found to be the RPCFT and automated reagin test. The cardiolipin WR proved to be under-sensitive and of little value compared with the other tests.Forty-two per cent of the 107 sera reactive in the FTA-ABS test were not detected by the RPCFT or ART tests. An assessment based on the TPI test results and clinical findings in these patients is presented. The scope and limitations of the FTA-ABS test as a screening procedure are discussed.

Mitigation of NADPH Oxidase 2 Activity as a Strategy to Inhibit Peroxynitrite Formation*

PubMed Central

Zielonka, Jacek; Zielonka, Monika; VerPlank, Lynn; Cheng, Gang; Hardy, Micael; Ouari, Olivier; Ayhan, Mehmet Menaf; Podsiadły, Radosław; Sikora, Adam; Lambeth, J. David; Kalyanaraman, Balaraman

2016-01-01

Using high throughput screening-compatible assays for superoxide and hydrogen peroxide, we identified potential inhibitors of the NADPH oxidase (Nox2) isoform from a small library of bioactive compounds. By using multiple probes (hydroethidine, hydropropidine, Amplex Red, and coumarin boronate) with well defined redox chemistry that form highly diagnostic marker products upon reaction with superoxide (O2˙̄), hydrogen peroxide (H2O2), and peroxynitrite (ONOO−), the number of false positives was greatly decreased. Selected hits for Nox2 were further screened for their ability to inhibit ONOO− formation in activated macrophages. A new diagnostic marker product for ONOO− is reported. We conclude that the newly developed high throughput screening/reactive oxygen species assays could also be used to identify potential inhibitors of ONOO− formed from Nox2-derived O2˙̄ and nitric oxide synthase-derived nitric oxide. PMID:26839313

High-Throughput Screening Using iPSC-Derived Neuronal Progenitors to Identify Compounds Counteracting Epigenetic Gene Silencing in Fragile X Syndrome.

PubMed

Kaufmann, Markus; Schuffenhauer, Ansgar; Fruh, Isabelle; Klein, Jessica; Thiemeyer, Anke; Rigo, Pierre; Gomez-Mancilla, Baltazar; Heidinger-Millot, Valerie; Bouwmeester, Tewis; Schopfer, Ulrich; Mueller, Matthias; Fodor, Barna D; Cobos-Correa, Amanda

2015-10-01

Fragile X syndrome (FXS) is the most common form of inherited mental retardation, and it is caused in most of cases by epigenetic silencing of the Fmr1 gene. Today, no specific therapy exists for FXS, and current treatments are only directed to improve behavioral symptoms. Neuronal progenitors derived from FXS patient induced pluripotent stem cells (iPSCs) represent a unique model to study the disease and develop assays for large-scale drug discovery screens since they conserve the Fmr1 gene silenced within the disease context. We have established a high-content imaging assay to run a large-scale phenotypic screen aimed to identify compounds that reactivate the silenced Fmr1 gene. A set of 50,000 compounds was tested, including modulators of several epigenetic targets. We describe an integrated drug discovery model comprising iPSC generation, culture scale-up, and quality control and screening with a very sensitive high-content imaging assay assisted by single-cell image analysis and multiparametric data analysis based on machine learning algorithms. The screening identified several compounds that induced a weak expression of fragile X mental retardation protein (FMRP) and thus sets the basis for further large-scale screens to find candidate drugs or targets tackling the underlying mechanism of FXS with potential for therapeutic intervention. © 2015 Society for Laboratory Automation and Screening.

Drug-like properties and the causes of poor solubility and poor permeability.

PubMed

Lipinski, C A

2000-01-01

There are currently about 10000 drug-like compounds. These are sparsely, rather than uniformly, distributed through chemistry space. True diversity does not exist in experimental combinatorial chemistry screening libraries. Absorption, distribution, metabolism, and excretion (ADME) and chemical reactivity-related toxicity is low, while biological receptor activity is higher dimensional in chemistry space, and this is partly explainable by evolutionary pressures on ADME to deal with endobiotics and exobiotics. ADME is hard to predict for large data sets because current ADME experimental screens are multi-mechanisms, and predictions get worse as more data accumulates. Currently, screening for biological receptor activity precedes or is concurrent with screening for properties related to "drugability." In the future, "drugability" screening may precede biological receptor activity screening. The level of permeability or solubility needed for oral absorption is related to potency. The relative importance of poor solubility and poor permeability towards the problem of poor oral absorption depends on the research approach used for lead generation. A "rational drug design" approach as exemplified by Merck advanced clinical candidates leads to time-dependent higher molecular weight, higher H-bonding properties, unchanged lipophilicity, and, hence, poorer permeability. A high throughput screening (HTS)-based approach as exemplified by unpublished data on Pfizer (Groton, CT) early candidates leads to higher molecular weight, unchanged H-bonding properties, higher lipophilicity, and, hence, poorer aqueous solubility.

The usefulness of ozone treatment in spinal pain

PubMed Central

Bocci, Velio; Borrelli, Emma; Zanardi, Iacopo; Travagli, Valter

2015-01-01

Objective The aim of this review is to elucidate the biochemical, molecular, immunological, and pharmaceutical mechanisms of action of ozone dissolved in biological fluids. Studies performed during the last two decades allow the drawing of a comprehensive framework for understanding and recommending the integration of ozone therapy for spinal pain. Methods An in-depth screening of primary sources of information online – via SciFinder Scholar, Google Scholar, and Scopus databases as well as Embase, PubMed, and the Cochrane Database of Systemic Reviews – was performed. In this review, the most significant papers of the last 25 years are presented and their proposals critically evaluated, regardless of the bibliometric impact of the journals. Results The efficacy of standard treatments combined with the unique capacity of ozone therapy to reactivate the innate antioxidant system is the key to correcting the oxidative stress typical of chronic inflammatory diseases. Pain pathways and control systems of algesic signals after ozone administration are described. Conclusion This paper finds favors the full insertion of ozone therapy into pharmaceutical sciences, rather than as either an alternative or an esoteric approach. PMID:26028964

Syphilis in immigrants and the Canadian immigration medical examination.

PubMed

MacPherson, Douglas W; Gushulak, Brian D

2008-02-01

Immigrants to Canada must undergo screening for syphilis. This study presents the results of syphilis screening from 2000 to 2004 and describes its impact on Canadian syphilis reporting and epidemiology. The study identifies migrant groups at risk of syphilis disease. All permanent resident applicants 15 years of age or older; younger individuals who have syphilis risk factors, and long-term temporary resident applicants are required to have non-treponemal syphilis screening done. Reactive results were confirmed. Immigration-related syphilis screening results were analyzed for year, migrant origin, migrant age and classification. A total of 2,209 individuals were found with positive syphilis serology from the screening of 2,001,417 applicants. The sex ratio of positive cases was M:F = 1.4. Rates per 100,000 applicants were: refugees 286, refugee claimants 267, family class 187, temporary residents 85, and economic class 63. Age and geographic distribution reflected sexual transmission, known international prevalence, and the Canadian processes of immigration. Certain immigration class applicants from syphilis high-prevalence source countries are a significant source of syphilis notifications in Canada. Identifiable populations and the immigration application medical processes represent global public health policy and program opportunities at the national level.

Metabolic Toxicity Screening Using Electrochemiluminescence Arrays Coupled with Enzyme-DNA Biocolloid Reactors and Liquid Chromatography–Mass Spectrometry

PubMed Central

Hvastkovs, Eli G.; Schenkman, John B.; Rusling, James F.

2012-01-01

New chemicals or drugs must be guaranteed safe before they can be marketed. Despite widespread use of bioassay panels for toxicity prediction, products that are toxic to a subset of the population often are not identified until clinical trials. This article reviews new array methodologies based on enzyme/DNA films that form and identify DNA-reactive metabolites that are indicators of potentially genotoxic species. This molecularly based methodology is designed in a rapid screening array that utilizes electrochemiluminescence (ECL) to detect metabolite-DNA reactions, as well as biocolloid reactors that provide the DNA adducts and metabolites for liquid chromatography–mass spectrometry (LC-MS) analysis. ECL arrays provide rapid toxicity screening, and the biocolloid reactor LC-MS approach provides a valuable follow-up on structure, identification, and formation rates of DNA adducts for toxicity hits from the ECL array screening. Specific examples using this strategy are discussed. Integration of high-throughput versions of these toxicity-screening methods with existing drug toxicity bioassays should allow for better human toxicity prediction as well as more informed decision making regarding new chemical and drug candidates. PMID:22482786

Human tyrosinase produced in insect cells: a landmark for the screening of new drugs addressing its activity.

PubMed

Fogal, Stefano; Carotti, Marcello; Giaretta, Laura; Lanciai, Federico; Nogara, Leonardo; Bubacco, Luigi; Bergantino, Elisabetta

2015-01-01

Human tyrosinase is the first enzyme of the multistep process of melanogenesis. It catalyzes the hydroxylation of L-tyrosine to L-dihydroxyphenylalanine and the following oxidation of o-diphenol to the corresponding quinone, L-dopaquinone. In spite of its biomedical relevance, its reactivity is far from being fully understood, mostly because of the lack of a suitable expression system. Indeed, until now, studies on substrates and inhibitors of tyrosinases have been performed in vitro almost exclusively using mushroom or bacterial enzymes. We report on the production of a recombinant human tyrosinase in insect cells (Sf9 line). Engineering the protein, improving cell culture conditions, and setting a suitable purification protocol optimized product yield. The obtained active enzyme was truthfully characterized with a number of substrate and inhibitor molecules. These results were compared to those gained from a parallel analysis of the bacterial (Streptomyces antibioticus) enzyme and those acquired from the literature for mushroom tyrosinase, showing that the reactivity of the human enzyme appears unique and pointing out the great bias introduced when using non-human tyrosinases to measure the inhibitory efficacy of new molecules. The described enzyme is therefore an indispensable paradigm in testing pharmaceutical or cosmetic agents addressing tyrosinase activity.

Direct Analysis and Quantification of Metaldehyde in Water using Reactive Paper Spray Mass Spectrometry

PubMed Central

Maher, Simon; Jjunju, Fred P. M.; Damon, Deidre E.; Gorton, Hannah; Maher, Yosef S.; Syed, Safaraz U.; Heeren, Ron M. A.; Young, Iain S.; Taylor, Stephen; Badu-Tawiah, Abraham K.

2016-01-01

Metaldehyde is extensively used worldwide as a contact and systemic molluscicide for controlling slugs and snails in a wide range of agricultural and horticultural crops. Contamination of surface waters due to run-off, coupled with its moderate solubility in water, has led to increased concentration of the pesticide in the environment. In this study, for the first time, rapid analysis (<~1 minute) of metaldehyde residues in water is demonstrated using paper spray mass spectrometry (PS-MS). The observed precursor molecular ions of metaldehyde were confirmed from tandem mass spectrometry (MS/MS) experiments by studying the fragmentation patterns produced via collision-induced dissociation. The signal intensity ratios of the most abundant MS/MS transitions for metaldehyde (177 → 149 for protonated ion) and atrazine (221 → 179) were found to be linear in the range 0.01 to 5 ng/mL. Metaldehyde residues were detectable in environmental water samples at low concentration (LOD < 0.1 ng/mL using reactive PS-MS), with a relative standard deviation <10% and an R2 value >0.99, without any pre-concentration/separation steps. This result is of particular importance for environmental monitoring and water quality analysis providing a potential means of rapid screening to ensure safe drinking water. PMID:27767044

Mobile detection system to evaluate reactive hyperemia using radionuclide plethysmography.

PubMed

Harel, François; Ngo, Quam; Finnerty, Vincent; Hernandez, Edgar; Khairy, Paul; Dupuis, Jocelyn

2007-08-01

We validated a novel mobile detection system to evaluate reactive hyperemia using the radionuclide plethysmography technique. Twenty-six subjects underwent simultaneously radionuclide plethysmography with strain gauge plethysmography. Strain gauge and radionuclide methods showed excellent reproducibility with intraclass correlation coefficients of 0.96 and 0.89 respectively. There was also a good correlation of flows between the two methods during reactive hyperemia (r = 0.87). We conclude that radionuclide plethysmography using this mobile detection system is a non-invasive alternative to assess forearm blood flow and its dynamic variations during reactive hyperemia.

Clinical features and subjective/physiological responses to emotional stimuli in the presence of emotion dysregulation in attention-deficit hyperactivity disorder.

PubMed

Taskiran, Candan; Karaismailoglu, Serkan; Cak Esen, Halime Tuna; Tuzun, Zeynep; Erdem, Aysen; Balkanci, Zeynep Dicle; Dolgun, Anil Barak; Cengel Kultur, Sadriye Ebru

2018-05-01

Emotion dysregulation (ED) has long been recognized in clinical descriptions of attention-deficit hyperactivity disorder (ADHD), but a renewed interest in ED has advanced research on the overlap between the two entities. Autonomic reactivity (AR) is a neurobiological correlate of emotion regulation; however, the association between ADHD and AR remains unclear. Our aim was to explore the clinical differences, AR, and subjective emotional responses to visual emotional stimuli in ADHD children with and without ED. School-aged ADHD children with (n = 28) and without (n = 20) ED, according to the definition of deficiency in emotional self-regulation (DESR), and healthy controls (n = 22) were interviewed by using the Schedule for Affective Disorders and Schizophrenia for School Aged Children-Present and Lifetime version (K-SADS-PL) to screen frequent psychopathologies for these ages. All subjects were evaluated with Child Behavior Checklist 6-18 (CBCL), the Strengths and Difficulties Questionnaire (SDQ), the McMaster Family Assessment Device (FAD), the School-Age Temperament Inventory (SATI), and Conners' Parent Rating Scale (CPRS-48), which were completed by parents. To evaluate emotional responses, the International Affective Picture System (IAPS) and the subjective and physiological responses (electrodermal activity and heart rate reactivity) to selected pictures were examined. Regarding clinically distinctive features, the ADHD+ED group differed from the ADHD-ED and the control groups in terms of having higher temperamental negative reactivity, more oppositional/conduct problems, and lower prosocial behaviors. In the AR measures, children in the ADHD+ED group rated unpleasant stimuli as more negative, but they still had lower heart rate reactivity (HRR) than the ADHD-ED and control groups; moreover, unlike the two other groups, the ADHD+ED group showed no differences in HRR between different emotional stimuli. The presented findings are unique in terms of their ability to clinically and physiologically differentiate between ADHD children with and without ED.

A fragile bond: adoptive parents' experiences of caring for children with a diagnosis of reactive attachment disorder.

PubMed

Follan, Michael; McNamara, Martin

2014-04-01

To understand how adoptive parents caring for children with a diagnosis of reactive attachment disorder (RAD) make sense of their life-worlds by establishing the meanings that underlie and structure their experiences of their everyday lives. Reactive attachment disorder is a serious psychosocial disorder of childhood that causes short- and long-term relationship, health and social consequences for children. It is more likely to be observed in children being cared for by foster carers, kinship carers or adoptive parents. Exploration of adoption from parents' perspectives is not well documented, and no previous work has been undertaken to understand the challenges of caring for children with a diagnosis of reactive attachment disorder. The study was guided by Husserl's phenomenology, which aims to uncover the underlying essential meanings intrinsic to a phenomenon. Three concepts are central to this approach: essences, intuiting and eidetic reduction. Semi-structured interviews were conducted with eight adoptive parents. Data were analysed using an adaptation of Colaizzi's method. Four essential elements fundamental to participants' lived experiences of caring for a child with a diagnosis of RAD were uncovered: being profoundly unprepared, being insecure, being assailed by unexpected emotions and being committed. The parent-child relationship is a fragile bond developed at an unexpectedly high personal cost; it is a committed relationship but vulnerable to continual destabilisation. The involvement in the preparation of adoptive parents of child and adolescent mental health (CAMH) staff with expertise in the impact of early neglect or separation on children should be considered. The development of systems to prepare, screen and identify potential challenges and problems prior to adoption might help adoptive parents. Access to a CAMH professional in the pre and postadoption phases might assist potential adoptive parents in making informed decisions around the choice of a child for adoption. © 2013 John Wiley & Sons Ltd.

Coincident filarial, intestinal helminth, and mycobacterial infection: helminths fail to influence tuberculin reactivity, but BCG influences hookworm prevalence.

PubMed

Lipner, Ettie M; Gopi, P G; Subramani, R; Kolappan, C; Sadacharam, K; Kumaran, Paul; Prevots, D Rebecca; Narayanan, P R; Nutman, Thomas B; Kumaraswami, V

2006-05-01

The prevalence of helminth and tuberculosis infections is high in South India, whereas Bacille-Calmette-Guerin (BCG) vaccine efficacy is low. Our aim was to determine whether concurrent helminth infection alters the ability to mount a delayed-type hypersensitivity response to tuberculin. In a cross-sectional study in southern India, individuals 6-65 years of age were screened for intestinal helminths, circulating filarial antigenemia, tuberculin reactivity, active tuberculosis, and history of BCG vaccination; 54% were purified protein derivative (PPD) positive, 32% had intestinal helminth infection, 9% were circulating filarial antigen positive, and 0.5% had culture-confirmed active tuberculosis. Only age and BCG vaccination were significantly associated with PPD reactivity; however, BCG vaccination was associated with a lower prevalence of hookworm infection relative to those without prior BCG vaccination. Neither intestinal helminth infection nor filarial infection was associated with diminished frequencies of PPD positivity. Our findings suggest that preceding helminth infection does not influence significantly the delayed-type hypersensitivity response to tuberculin.

Linking Fearfulness and Coping Styles in Fish

PubMed Central

Martins, Catarina I. M.; Silva, Patricia I. M.; Conceição, Luis E. C.; Costas, Benjamin; Höglund, Erik; Øverli, Øyvind; Schrama, Johan W.

2011-01-01

Consistent individual differences in cognitive appraisal and emotional reactivity, including fearfulness, are important personality traits in humans, non-human mammals, and birds. Comparative studies on teleost fishes support the existence of coping styles and behavioral syndromes also in poikilothermic animals. The functionalist approach to emotions hold that emotions have evolved to ensure appropriate behavioral responses to dangerous or rewarding stimuli. Little information is however available on how evolutionary widespread these putative links between personality and the expression of emotional or affective states such as fear are. Here we disclose that individual variation in coping style predicts fear responses in Nile tilapia Oreochromis niloticus, using the principle of avoidance learning. Fish previously screened for coping style were given the possibility to escape a signalled aversive stimulus. Fearful individuals showed a range of typically reactive traits such as slow recovery of feed intake in a novel environment, neophobia, and high post-stress cortisol levels. Hence, emotional reactivity and appraisal would appear to be an essential component of animal personality in species distributed throughout the vertebrate subphylum. PMID:22140511

Feasibility of Using Convalescent Plasma Immunotherapy for MERS-CoV Infection, Saudi Arabia.

PubMed

Arabi, Yaseen M; Hajeer, Ali H; Luke, Thomas; Raviprakash, Kanakatte; Balkhy, Hanan; Johani, Sameera; Al-Dawood, Abdulaziz; Al-Qahtani, Saad; Al-Omari, Awad; Al-Hameed, Fahad; Hayden, Frederick G; Fowler, Robert; Bouchama, Abderrezak; Shindo, Nahoko; Al-Khairy, Khalid; Carson, Gail; Taha, Yusri; Sadat, Musharaf; Alahmadi, Mashail

2016-09-01

We explored the feasibility of collecting convalescent plasma for passive immunotherapy of Middle East respiratory syndrome coronavirus (MERS-CoV) infection by using ELISA to screen serum samples from 443 potential plasma donors: 196 patients with suspected or laboratory-confirmed MERS-CoV infection, 230 healthcare workers, and 17 household contacts exposed to MERS-CoV. ELISA-reactive samples were further tested by indirect fluorescent antibody and microneutralization assays. Of the 443 tested samples, 12 (2.7%) had a reactive ELISA result, and 9 of the 12 had reactive indirect fluorescent antibody and microneutralization assay titers. Undertaking clinical trials of convalescent plasma for passive immunotherapy of MERS-CoV infection may be feasible, but such trials would be challenging because of the small pool of potential donors with sufficiently high antibody titers. Alternative strategies to identify convalescent plasma donors with adequate antibody titers should be explored, including the sampling of serum from patients with more severe disease and sampling at earlier points during illness.

A novel acute HIV infection staging system based on 4th generation immunoassay.

PubMed

Ananworanich, Jintanat; Fletcher, James L K; Pinyakorn, Suteeraporn; van Griensven, Frits; Vandergeeten, Claire; Schuetz, Alexandra; Pankam, Tippawan; Trichavaroj, Rapee; Akapirat, Siriwat; Chomchey, Nitiya; Phanuphak, Praphan; Chomont, Nicolas; Michael, Nelson L; Kim, Jerome H; de Souza, Mark

2013-05-29

Fourth generation (4thG) immunoassay (IA) is becoming the standard HIV screening method but was not available when the Fiebig acute HIV infection (AHI) staging system was proposed. Here we evaluated AHI staging based on a 4thG IA (4thG staging). Screening for AHI was performed in real-time by pooled nucleic acid testing (NAT, n=48,828 samples) and sequential enzyme immunoassay (EIA, n=3,939 samples) identifying 63 subjects with non-reactive 2nd generation EIA (Fiebig stages I (n=25), II (n=7), III (n=29), IV (n=2)). The majority of samples tested (n=53) were subtype CRF_01AE (77%). NAT+ subjects were re-staged into three 4thG stages: stage 1 (n=20; 4th gen EIA-, 3rd gen EIA-), stage 2 (n=12; 4th gen EIA+, 3rd gen EIA-), stage 3 (n=31; 4th gen EIA+, 3rd gen EIA+, Western blot-/indeterminate). 4thG staging distinguishes groups of AHI subjects by time since presumed HIV exposure, pattern of CD8+ T, B and natural killer cell absolute numbers, and HIV RNA and DNA levels. This staging system further stratified Fiebig I subjects: 18 subjects in 4thG stage 1 had lower HIV RNA and DNA levels than 7 subjects in 4thG stage 2. Using 4th generation IA as part of AHI staging distinguishes groups of patients by time since exposure to HIV, lymphocyte numbers and HIV viral burden. It identifies two groups of Fiebig stage I subjects who display different levels of HIV RNA and DNA, which may have implication for HIV cure. 4th generation IA should be incorporated into AHI staging systems.

Using stable isotopes to monitor forms of sulfur during desulfurization processes: A quick screening method

USGS Publications Warehouse

Liu, Chao-Li; Hackley, Keith C.; Coleman, D.D.; Kruse, C.W.

1987-01-01

A method using stable isotope ratio analysis to monitor the reactivity of sulfur forms in coal during thermal and chemical desulfurization processes has been developed at the Illinois State Geological Survey. The method is based upon the fact that a significant difference exists in some coals between the 34S/32S ratios of the pyritic and organic sulfur. A screening method for determining the suitability of coal samples for use in isotope ratio analysis is described. Making these special coals available from coal sample programs would assist research groups in sorting out the complex sulfur chemistry which accompanies thermal and chemical processing of high sulfur coals. ?? 1987.

Systems and methods for forming defects on graphitic materials and curing radiation-damaged graphitic materials

DOEpatents

Ryu, Sunmin; Brus, Louis E.; Steigerwald, Michael L.; Liu, Haitao

2012-09-25

Systems and methods are disclosed herein for forming defects on graphitic materials. The methods for forming defects include applying a radiation reactive material on a graphitic material, irradiating the applied radiation reactive material to produce a reactive species, and permitting the reactive species to react with the graphitic material to form defects. Additionally, disclosed are methods for removing defects on graphitic materials.

Lymphocyte and neuronal antigens in neuropsychiatric lupus: presence of an elutable, immunoprecipitable lymphocyte/neuronal 52 kd reactivity.

PubMed Central

Denburg, J A; Behmann, S A

1994-01-01

OBJECTIVE--To examine specific lymphocyte or neuronal antigens immuno-precipitated by systemic lupus erythematosus (SLE) sera. METHOD--SLE sera were screened for the presence of antibodies binding to surface antigens of CD4(+) HUT-78 or SK-N-SH and IMR-6 neuroblastoma cells using Western blotting or radioimmunoprecipitation. RESULTS--IgG eluates from both lymphocytes and neuroblastoma cells recognised a 52 kd band in HUT 78 cell lysates. Eight sera studied further using radioimmunoprecipitation also demonstrated binding to a 52 kd antigen (4/8 on HUT-78, 8/8 on SK-N-SH cells), partially depleted by absorption with viable HUT-78. CONCLUSION--A 52 kd antigen recognised by SLE sera on lymphocytes and neuronal cells may play a role in the pathogenesis of neuropsychiatric-SLE. Images PMID:8017983

The First Korean Case Report of Anti-Gerbich

PubMed Central

Jeon, You La; Park, Tae Sung; Cho, Sun Young; Oh, Seung Hwan; Kim, Myeong Hee; Kang, So Young

2012-01-01

In this study, we report the first Korean case of an anti-Gerbich (Ge) alloantibody to a high-incidence antigen that belongs to the Ge blood group system. The alloantibody was detected in a middle-aged Korean woman who did not have a history of transfusion. Her blood type was B+, and findings from the antibody screening test revealed 1+ reactivity in all panels except the autocontrol. The cross-matching test showed incompatible results with all 5 packed red blood cells. Additional blood type antigen and antibody tests confirmed the anti-Ge alloantibody. While rare, cases of hemolytic transfusion reaction or hemolytic disease in newborns due to anti-Ge have been recently reported in the literature. Therefore, additional further studies on alloantibodies to high-incidence antigens, including anti-Ge, are necessary in the future. PMID:23130346

Learning to integrate reactivity and deliberation in uncertain planning and scheduling problems

NASA Technical Reports Server (NTRS)

Chien, Steve A.; Gervasio, Melinda T.; Dejong, Gerald F.

1992-01-01

This paper describes an approach to planning and scheduling in uncertain domains. In this approach, a system divides a task on a goal by goal basis into reactive and deliberative components. Initially, a task is handled entirely reactively. When failures occur, the system changes the reactive/deliverative goal division by moving goals into the deliberative component. Because our approach attempts to minimize the number of deliberative goals, we call our approach Minimal Deliberation (MD). Because MD allows goals to be treated reactively, it gains some of the advantages of reactive systems: computational efficiency, the ability to deal with noise and non-deterministic effects, and the ability to take advantage of unforseen opportunities. However, because MD can fall back upon deliberation, it can also provide some of the guarantees of classical planning, such as the ability to deal with complex goal interactions. This paper describes the Minimal Deliberation approach to integrating reactivity and deliberation and describe an ongoing application of the approach to an uncertain planning and scheduling domain.

Hybrid Plasma Reactor/Filter for Transportable Collective Protection Systems

DTIC Science & Technology

2011-03-01

protection. The key premise of the hybrid system is to couple a nonthermal plasma (NTP) reactor with reactive adsorption to provide a broader envelope of...conventional methods for collective protection. The key premise of the hybrid system is to couple a nonthermal plasma (NTP) reactor with reactive adsorption to...protection. The key premise of the hybrid system is to couple a nonthermal plasma (NTP) reactor with reactive adsorption to provide a broader

Child Maltreatment and Autonomic Nervous System Reactivity: Identifying Dysregulated Stress Reactivity Patterns using the Biopsychosocial Model of Challenge and Threat

PubMed Central

McLaughlin, Katie A.; Sheridan, Margaret A.; Alves, Sonia; Mendes, Wendy Berry

2014-01-01

OBJECTIVE Disruptions in stress response system development have been posited as mechanisms linking child maltreatment (CM) to psychopathology. Existing theories predict elevated sympathetic nervous system (SNS) reactivity following CM, but evidence for this is inconsistent. We present a novel framework for conceptualizing stress reactivity following CM using the biopsychosocial model of challenge and threat. We predicted that in the context of a social-evaluative stressor, maltreated adolescents would exhibit a threat pattern of reactivity, involving SNS activation paired with elevated vascular resistance and blunted cardiac output (CO) reactivity. METHODS A sample of 168 adolescents (mean age=14.9 years) participated. Recruitment targeted maltreated adolescents; 38.2% qualified as maltreated. Electrocardiogram, impedance cardiography, and blood pressure were acquired at rest and during an evaluated social stressor (Trier Social Stress Test). Pre-ejection period (PEP), CO, and total peripheral resistance (TPR) reactivity were computed during task preparation, speech-delivery, and verbal mental-arithmetic. Internalizing and externalizing symptoms were assessed. RESULTS Maltreatment was unrelated to PEP reactivity during preparation or speech, but maltreated adolescents had reduced PEP reactivity during math. Maltreatment exposure (F(1,145)=3.8-9.4, p=.053-<.001) and severity (β=−.10-.12, p=.030-.007) were associated with significantly reduced CO reactivity during all components of the stress-task and marginally associated with elevated TPR reactivity (F(1,145)=3.8-9.4, p=.053-<.001; β=.07-.11, p=.11-.009, respectively). Threat reactivity was negatively associated with externalizing symptoms. CONCLUSIONS Child maltreatment is associated with a dysregulated pattern of physiological reactivity consistent with theoretical conceptualizations of threat but not previously examined in relation to maltreatment, suggesting a more nuanced pattern of stress reactivity than predicted by current theoretical models. PMID:25170753

Interference in diagnostic tests for brucellosis in cattle recently vaccinated against leptospirosis.

PubMed

Naves, Joao Helder Frederico de Faria; Rezende, Lais M; Ramos, Gabriel C; Soares, Pollyanna M; Tavares, Tatiane C F; França, Andre M S; Neves, Saira M N; Silva, Natascha A M; Lima-Ribeiro, Anna M C

2012-03-01

The aim of the current study was to verify if cattle vaccinated against leptospirosis may react in diagnostic tests for brucellosis. Sixty cows were divided into 5 groups, each comprising 12 animals. Four groups were given different vaccines against leptospirosis, while the control group received only saline. Two doses of vaccine were given, as recommended by the manufacturers. Serum samples were collected on the first day of immunization (day 0) and on postvaccination days 7, 14, 21, 28, 35, 42, 49, 56, 96, and 126. All the serum samples were tested for brucellosis and leptospirosis. Twenty animals were reactive at least once to the Rose Bengal test, but by day 96, no further reactions were elicited by this test. Twenty-six samples were reactive to the Rose Bengal test, but only 7 remained positive in confirmatory tests: 1 to the 2-mercaptoethanol test, 2 to the fluorescence polarization assay, and 6 to indirect enzyme-linked immunosorbent assays. None of the samples was reactive in the complement fixation test. None of the animals in the control group was reactive. A significant difference was found between the control group and the groups vaccinated against leptospirosis, according to Fisher exact test. However, the groups were found to respond independently of the vaccine brand. The results indicate that cattle vaccinated against leptospirosis may show reactivity on screening tests for brucellosis.

Tuberculin reactivity and tuberculosis epidemiology in the Pakaanóva (Wari') Indians of Rondônia, south-western Brazilian Amazon.

PubMed

Escobar, A L; Coimbra, C E A; Camacho, L A B; Santos, R V

2004-01-01

To investigate the characteristics of tuberculin skin test reactivity in the Pakaanóva Indians, in Amazonia, Brazil, after revaccination of all study participants with bacille Calmette-Guerin (BCG). The investigation was designed as a post-BCG vaccination purified protein derivative (PPD) survey. Data included PPD readings, age, sex, nutritional status, place of residence, previous tuberculosis, physical examinations and BCG status. Bivariate and multivariate logistic regression analyses were conducted. About 90% (n = 505) of the total population participated. One third (32.1%) of the subjects presented induration > or = 10 mm at 72 h. Induration sizes showed weak linear correlation with age; differences between sexes were not observed. Skin reaction was not associated with nutritional status. Individuals with a history of tuberculosis were six times more likely to test positive. History of tuberculosis, age, and previous BCG vaccination were significantly associated with PPD reactivity in the multivariate analyses. The Pakaanóva showed a high proportion (58.4%) of non-reactors, even with a recent BCG booster. Sex differences in PPD reactivity were either not present or could not be demonstrated. The association between age and PPD reactivity resembles that observed in other Amazonian populations. The authors discuss the potential of PPD testing as a screening tool to enhance tuberculosis detection, especially in indigenous populations in Amazonia with limited access to health services.

Point-of-care C-reactive protein-based tuberculosis screening for people living with HIV: a diagnostic accuracy study.

PubMed

Yoon, Christina; Semitala, Fred C; Atuhumuza, Elly; Katende, Jane; Mwebe, Sandra; Asege, Lucy; Armstrong, Derek T; Andama, Alfred O; Dowdy, David W; Davis, J Luke; Huang, Laurence; Kamya, Moses; Cattamanchi, Adithya

2017-12-01

Symptom-based screening for tuberculosis is recommended for all people living with HIV. This recommendation results in unnecessary Xpert MTB/RIF testing in many individuals living in tuberculosis-endemic areas and thus poor implementation of intensified case finding and tuberculosis preventive therapy. Novel approaches to tuberculosis screening are needed to help achieve global targets for tuberculosis elimination. We assessed the performance of C-reactive protein (CRP) measured with a point-of-care assay as a screening tool for active pulmonary tuberculosis. For this prospective study, we enrolled adults (aged ≥18 years) living with HIV with CD4 cell count less than or equal to 350 cells per μL who were initiating antiretroviral therapy (ART) from two HIV/AIDS clinics in Uganda. CRP concentrations were measured at study entry with a point-of-care assay using whole blood obtained by fingerprick (concentration ≥10 mg/L defined as screen positive for tuberculosis). Sputum samples were collected for Xpert MTB/RIF testing and culture. We calculated the sensitivity and specificity of point-of-care CRP and WHO symptom-based screening in reference to culture results. We repeated the sensitivity analysis with Xpert MTB/RIF as the reference standard. Between July 8, 2013, and Dec 15, 2015, 1237 HIV-infected adults were enrolled and underwent point-of-care CRP testing. 60 (5%) patients with incomplete or contaminated cultures were excluded from the analysis. Of the remaining 1177 patients (median CD4 count 165 cells per μL [IQR 75-271]), 163 (14%) had culture-confirmed tuberculosis. Point-of-care CRP testing had 89% sensitivity (145 of 163, 95% CI 83-93) and 72% specificity (731 of 1014, 95% CI 69-75) for culture-confirmed tuberculosis. Compared with WHO symptom-based screening, point-of-care CRP testing had lower sensitivity (difference -7%, 95% CI -12 to -2; p=0·002) but substantially higher specificity (difference 58%, 95% CI 55 to 61; p<0·0001). When Xpert MTB/RIF results were used as the reference standard, sensitivity of point-of-care CRP and WHO symptom-based screening were similar (94% [79 of 84] vs 99% [83 of 84], respectively; difference -5%, 95% CI -12 to 2; p=0·10). The performance characteristics of CRP support its use as a tuberculosis screening test for people living with HIV with CD4 count less than or equal to 350 cells per μL who are initiating ART. HIV/AIDS programmes should consider point-of-care CRP-based tuberculosis screening to improve the efficiency of intensified case finding and increase uptake of tuberculosis preventive therapy. National Institutes of Health; President's Emergency Plan for AIDS Relief; University of California, San Francisco, Nina Ireland Program for Lung Health. Copyright © 2017 Elsevier Ltd. All rights reserved.

Novel High-Fidelity Screening of Environmental Chemicals and Carcinogens and Mechanisms in Colorectal Cancer.

DTIC Science & Technology

2016-09-01

Chemical Promiscuity, Pharmacokinetics, Colorectal Cancer, N , N ’-disalicylidene-1,2-diaminopropane, Pyraclostrobin, Paclobutrazol, Vitamin D Receptor, Wnt...Environmental Chemicals, TOX-TMFS, CPTM, Cancer Cellular Network Model, Chemical Reactivity, Chemical Promiscuity, Pharmacokinetics, Colorectal Cancer, N , N ...network models were further enriched with oncologic disease OMIM profiles to create cancer-specific networks. The ECs N , N ’-disalicylidene- 1,2

Rapid screening method to study the reactivity of UV filter substances towards skin proteins by high-performance thin-layer chromatography.

PubMed

Stiefel, C; Schwack, W

2013-12-01

Most UV filters used in sunscreens and other cosmetic products contain carbonyl groups, which generally are able to react with peptides or free amino acids of the human skin. To estimate their reactivity, we studied different prominent UV filter substances, octocrylene, ethylhexyl salicylate, 4-t-butyl-4'-methoxydibenzoylmethane, ethylhexyl methoxycinnamate, benzophenone-3, hydroxymethylbenzoyl sulphonic acid, octyldimethyl p-aminobenzoic acid, 3-benzylidene camphor, 4-methylbenzylidene camphor, diethylhexyl butamido triazone and ethylhexyl triazone. A simple screening method using an amino HPTLC plate as protein model was established. The influence of different reaction conditions like heating and irradiation was determined. The ketones BP-3, HMBS and BM-DBM revealed the highest binding rates after both irradiation and heating. After 1 h of irradiation, 82%, 28% and 96%, respectively, were bonded to the amino phase, while heating resulted in values of 52%, 36% and 16%. For BP-3 and HMBS, even storage in the dark at room temperature resulted in a low binding. Contrarily, for the two camphor derivatives 3-BC and 4-MBC, only irradiation led to a slightly turnover. UV filters with ester groups also showed a different behaviour depending on their main skeleton. While OCR especially reacted under heating with the amino phase, resulting in 36% of bound species after one hour, UV irradiation particularly encouraged a reaction of the other esters. After 1 h irradiation, 15% of EHMC, 38% of EHS and 48% of OD-PABA were bonded to the amino groups of the HPTLC plate, whereas the reactivity of the two triazones, EHT and DEBT, was comparatively low. Especially the UV filters BP-3, BM-DBM, HMBS, EHMC or OCR, which are commonly known to cause contact dermatitis, showed a high tendency to form adducts with the amino layer. Thus, the amino plate seems to be a proper tool to screen for skin sensitizers. © 2013 Society of Cosmetic Scientists and the Société Française de Cosmétologie.

Fracture Characterization in Reactive Fluid-Fractured Rock Systems Using Tracer Transport Data

NASA Astrophysics Data System (ADS)

Mukhopadhyay, S.

2014-12-01

Fractures, whether natural or engineered, exert significant controls over resource exploitation from contemporary energy sources including enhanced geothermal systems and unconventional oil and gas reserves. Consequently, fracture characterization, i.e., estimating the permeability, connectivity, and spacing of the fractures is of critical importance for determining the viability of any energy recovery program. While some progress has recently been made towards estimating these critical fracture parameters, significant uncertainties still remain. A review of tracer technology, which has a long history in fracture characterization, reveals that uncertainties exist in the estimated parameters not only because of paucity of scale-specific data but also because of knowledge gaps in the interpretation methods, particularly in interpretation of tracer data in reactive fluid-rock systems. We have recently demonstrated that the transient tracer evolution signatures in reactive fluid-rock systems are significantly different from those in non-reactive systems (Mukhopadhyay et al., 2013, 2014). For example, the tracer breakthrough curves in reactive fluid-fractured rock systems are expected to exhibit a long pseudo-state condition, during which tracer concentration does not change by any appreciable amount with passage of time. Such a pseudo-steady state condition is not observed in a non-reactive system. In this paper, we show that the presence of this pseudo-steady state condition in tracer breakthrough patterns in reactive fluid-rock systems can have important connotations for fracture characterization. We show that the time of onset of the pseudo-steady state condition and the value of tracer concentration in the pseudo-state condition can be used to reliably estimate fracture spacing and fracture-matrix interface areas.

Immunoassay screening in urine for synthetic cannabinoids - an evaluation of the diagnostic efficiency.

PubMed

Franz, Florian; Angerer, Verena; Jechle, Hanna; Pegoro, Melanie; Ertl, Harald; Weinfurtner, Georg; Janele, David; Schlögl, Christian; Friedl, Matthias; Gerl, Stefan; Mielke, Reinhard; Zehnle, Ralf; Wagner, Matthias; Moosmann, Bjoern; Auwärter, Volker

2017-08-28

The abuse of synthetic cannabinoids (SCs) as presumed legal alternative to cannabis poses a great risk to public health. For economic reasons many laboratories use immunoassays (IAs) to screen for these substances in urine. However, the structural diversity and high potency of these designer drugs places high demands on IAs regarding cross-reactivity of the antibodies used and detection limits. Two retrospective studies were carried out in order to evaluate the capability of two homogenous enzyme IAs for the detection of currently prevalent SCs in authentic urine samples. Urine samples were analyzed utilizing a 'JWH-018' kit and a 'UR-144' kit. The IA results were confirmed by an up-to-date liquid chromatography-electrospray ionization-tandem mass spectrometry (LC-ESI-MS/MS) screening method covering metabolites of 45 SCs. The first study (n=549) showed an 8% prevalence of SCs use (LC-MS/MS analysis) among inpatients of forensic-psychiatric clinics, whereas all samples were tested negative by the IAs. In a second study (n=200) the combined application of both IAs led to a sensitivity of 2% and a diagnostic accuracy of 51% when applying the recommended IA cut-offs. Overall, 10 different currently prevalent SCs were detected in this population. The results can be explained by an insufficient cross-reactivity of the antibodies towards current SCs in combination with relatively high detection limits of the IAs. In light of the presented study data it is strongly recommended not to rely on the evaluated IA tests for SCs in clinical or forensic settings. For IA kits of other providers similar results can be expected.

VERifyNow in DIabetes high-on-treatment platelet reactivity: a pharmacodynamic study on switching from clopidogrel to prasugrel.

PubMed

Cubero Gómez, José M; Acosta Martínez, Juan; Mendias Benítez, Crsitina; Díaz De La Llera, Luis S; Fernández-Quero, Mónica; Guisado Rasco, Agustí; Villa Gil-Ortega, Manuel; Sánchez González, Ángel

2015-12-01

Diabetic patients with an acute coronary syndrome undergoing percutaneous coronary intervention frequently exhibit high platelet reactivity while on clopidogrel. We hypothesized that in diabetic patients undergoing percutaneous coronary intervention, who exhibit high-platelet-reactivity after standard treatment with clopidogrel, a 60-mg prasugrel loading dose is superior to standard treatment with clopidogrel for optimal P2Y12 inhibition within the first 24-36 h post-angioplasty. VERDI was a prospective, randomized, single-centre, single-blind, parallel-design study (NCT01684813). Consecutive diabetic patients with an non-ST-segment elevation acute coronary syndrome undergoing percutaneous coronary intervention and loaded with clopidogrel were considered for platelet reactivity assessment immediately before angioplasty with the VerifyNow assay measured in P2Y12 reaction units (PRU). Fifty of 63 screened patients (79.4%) had high platelet reactivity (PRU ≥ 208) and were randomized to receive a 60-mg prasugrel loading dose (n = 25) versus clopidogrel standard dose (n = 25). Platelet function was assessed again 24 hours post-angioplasty. Prasugrel achieved greater platelet inhibition than clopidogrel 24 hours post-angioplasty (median [interquartile range], 38 [9-72] vs 285 [240-337], respectively; P < 0.001). The non-high-platelet-reactivity rate (PRU < 208) at 24 h post-angioplasty (primary end point) was higher with prasugrel; 25 patients (100%) in the prasugrel group achieved optimal antiaggregation vs 4 patients (16%) in the clopidogrel group (P < 0.001). No significant acute bleeding was documented in either group. Among type 2 diabetic patients suffering an acute coronary syndrome with high-platelet-reactivity undergoing percutaneous coronary intervention, switching from clopidogrel to prasugrel was superior to standard treatment with clopidogrel for the achievement of optimal antiaggregation within the first 24 hours post-angioplasty.

Hit-and-run stimulation: a novel concept to reactivate latent HIV-1 infection without cytokine gene induction.

PubMed

Wolschendorf, Frank; Duverger, Alexandra; Jones, Jennifer; Wagner, Frederic H; Huff, Jason; Benjamin, William H; Saag, Michael S; Niederweis, Michael; Kutsch, Olaf

2010-09-01

Current antiretroviral therapy (ART) efficiently controls HIV-1 replication but fails to eradicate the virus. Even after years of successful ART, HIV-1 can conceal itself in a latent state in long-lived CD4(+) memory T cells. From this latent reservoir, HIV-1 rebounds during treatment interruptions. Attempts to therapeutically eradicate this viral reservoir have yielded disappointing results. A major problem with previously utilized activating agents is that at the concentrations required for efficient HIV-1 reactivation, these stimuli trigger high-level cytokine gene expression (hypercytokinemia). Therapeutically relevant HIV-1-reactivating agents will have to trigger HIV-1 reactivation without the induction of cytokine expression. We present here a proof-of-principle study showing that this is a possibility. In a high-throughput screening effort, we identified an HIV-1-reactivating protein factor (HRF) secreted by the nonpathogenic bacterium Massilia timonae. In primary T cells and T-cell lines, HRF triggered a high but nonsustained peak of nuclear factor kappa B (NF-kappaB) activity. While this short NF-kappaB peak potently reactivated latent HIV-1 infection, it failed to induce gene expression of several proinflammatory NF-kappaB-dependent cellular genes, such as those for tumor necrosis factor alpha (TNF-alpha), interleukin-8 (IL-8), and gamma interferon (IFN-gamma). Dissociation of cellular and viral gene induction was achievable, as minimum amounts of Tat protein, synthesized following application of a short NF-kappaB pulse, triggered HIV-1 transactivation and subsequent self-perpetuated HIV-1 expression. In the absence of such a positive feedback mechanism, cellular gene expression was not sustained, suggesting that strategies modulating the NF-kappaB activity profile could be used to selectively trigger HIV-1 reactivation.

Association of CMV-Specific T Cell-Mediated Immunity with CMV DNAemia and Development of CMV Disease in HIV-1-Infected Individuals.

PubMed

Aichelburg, Maximilian C; Weseslindtner, Lukas; Mandorfer, Mattias; Strassl, Robert; Rieger, Armin; Reiberger, Thomas; Puchhammer-Stöckl, Elisabeth; Grabmeier-Pfistershammer, Katharina

2015-01-01

Among HIV-1-infected individuals, cytomegalovirus (CMV) reactivation and disease occur in the setting of advanced immunosuppression. The value of a standardized assessment of CMV-specific T-cell mediated immunity by the CMV QuantiFERON assay (CMV-QFT) has not yet been thoroughly investigated in HIV-1-infected subjects. Prospective, longitudinal study in 153 HIV-1-infected subjects with a CD4+ T cell count < 350/μL who simultaneously underwent CMV-QFT, CMV serology testing and CMV-DNA quantification. Factors associated with CMV-QFT were evaluated. Clinical screening for CMV manifestations was then performed every 3 months. Among the 141 CMV IgG-seropositive individuals the CMV-QFT assay yielded reactive results in 84% (118/141), negative results in 15% (21/141) and indeterminate (negative mitogen IFN-gamma response) results in 1% (2/141) of subjects. The mean actual CD4+ T cell count was significantly higher in CMV-QFT reactive subjects, when compared to CMV-QFT non-reactive individuals (183 ± 102 vs. 126 ± 104 cells/μL, P = 0.015). A significantly lower proportion of CMV-QFT reactive vs. non-reactive patients displayed CMV DNAemia > 100 copies/mL (23% (27/118) vs. 48% (11/23), P = 0.02). Furthermore, a statistically significant inverse association between mitogen IFN-gamma response and CMV-DNAemia > 1000 copies/mL was observed (P < 0.001). During the observational period, 5 CMV end-organ manifestations were observed. In three of the CMV cases the CMV-QFT yielded indeterminate results. While CMV-QFT reactivity indicates CMV-specific immunity, indeterminate results due to negative mitogen IFN-gamma response might reflect HIV-1-induced immunodeficiency. Thus, dependency upon CD4+ T cell count should be considered when interpreting CMV-QFT results.

Why screening rates vary between Korea and Japan--differences between two national healthcare systems.

PubMed

Goto, Rei; Hamashima, Chisato; Mun, Sunghyun; Lee, Won-Chul

2015-01-01

Both Japan and Korea provide population-based screening programs. However, screening rates are much higher in Korea than in Japan. To clarify the possible factors explaining the differences between these two countries, we analyzed the current status of the cancer screening and background healthcare systems. Population- based cancer screening in Korea is coordinated well with social health insurance under a unified insurer system. In Japan, there are over 3,000 insurers and coordinating a comprehensive strategy for cancer screening promotion has been very difficult. The public healthcare system also has influence over cancer screening. In Korea, public healthcare does not cover a wide range of services. Almost free cancer screening and subsidization for medical cost for cancers detected in population-screening provides high incentive to participation. In Japan, on the other hand, a larger coverage of medical services, low co-payment, and a lenient medical audit enables people to have cancer screening under public health insurance as well as the broad range of cancer screening. The implementation of evidence-based cancer screening programs may be largely dependent on the background healthcare system. It is important to understand the impacts of each healthcare system as a whole and to match the characteristics of a particular health system when designing an efficient cancer screening system.

An autonomous organic reaction search engine for chemical reactivity.

PubMed

Dragone, Vincenza; Sans, Victor; Henson, Alon B; Granda, Jaroslaw M; Cronin, Leroy

2017-06-09

The exploration of chemical space for new reactivity, reactions and molecules is limited by the need for separate work-up-separation steps searching for molecules rather than reactivity. Herein we present a system that can autonomously evaluate chemical reactivity within a network of 64 possible reaction combinations and aims for new reactivity, rather than a predefined set of targets. The robotic system combines chemical handling, in-line spectroscopy and real-time feedback and analysis with an algorithm that is able to distinguish and select the most reactive pathways, generating a reaction selection index (RSI) without need for separate work-up or purification steps. This allows the automatic navigation of a chemical network, leading to previously unreported molecules while needing only to do a fraction of the total possible reactions without any prior knowledge of the chemistry. We show the RSI correlates with reactivity and is able to search chemical space using the most reactive pathways.

An autonomous organic reaction search engine for chemical reactivity

NASA Astrophysics Data System (ADS)

Dragone, Vincenza; Sans, Victor; Henson, Alon B.; Granda, Jaroslaw M.; Cronin, Leroy

2017-06-01

The exploration of chemical space for new reactivity, reactions and molecules is limited by the need for separate work-up-separation steps searching for molecules rather than reactivity. Herein we present a system that can autonomously evaluate chemical reactivity within a network of 64 possible reaction combinations and aims for new reactivity, rather than a predefined set of targets. The robotic system combines chemical handling, in-line spectroscopy and real-time feedback and analysis with an algorithm that is able to distinguish and select the most reactive pathways, generating a reaction selection index (RSI) without need for separate work-up or purification steps. This allows the automatic navigation of a chemical network, leading to previously unreported molecules while needing only to do a fraction of the total possible reactions without any prior knowledge of the chemistry. We show the RSI correlates with reactivity and is able to search chemical space using the most reactive pathways.

An autonomous organic reaction search engine for chemical reactivity

PubMed Central

Dragone, Vincenza; Sans, Victor; Henson, Alon B.; Granda, Jaroslaw M.; Cronin, Leroy

2017-01-01

The exploration of chemical space for new reactivity, reactions and molecules is limited by the need for separate work-up-separation steps searching for molecules rather than reactivity. Herein we present a system that can autonomously evaluate chemical reactivity within a network of 64 possible reaction combinations and aims for new reactivity, rather than a predefined set of targets. The robotic system combines chemical handling, in-line spectroscopy and real-time feedback and analysis with an algorithm that is able to distinguish and select the most reactive pathways, generating a reaction selection index (RSI) without need for separate work-up or purification steps. This allows the automatic navigation of a chemical network, leading to previously unreported molecules while needing only to do a fraction of the total possible reactions without any prior knowledge of the chemistry. We show the RSI correlates with reactivity and is able to search chemical space using the most reactive pathways. PMID:28598440

[Screening of malnutrition risk versus indicators of nutritional status and systemic inflammatory response in newly diagnosed lung cancer patients].

PubMed

Illa, P; Tomíšková, M; Skřičková, J

2014-01-01

Most lung cancers are already advanced at the time of dia-gnosis. In these patients, a frequent symptom is protein energy malnutrition, often diagnosed prior to oncological treatment. Malnutrition results in poor tolerance of treatment and increased morbidity and mortality. Nutritional Risk Screening (NRS) 2002 adapted for oncological patients was used to assess the risk of undernutrition in a group of 188 lung cancer patients. The risk was evaluated on a 6- point scale according to common signs of nutritional status and tumor and its treatment risk factors. A score of 3 and more (called "nutritional risk") means a significant risk of malnutrition. Furthermore, pretreatment nutritional characteristics were evaluated in patients (including the value of BMI) and laboratory values indicating malnutrition/ acute phase response (albumin/ C reactive protein - CRP). Acceptable NRS score was found in 50.6%, while in 45.3% was suggested into risk of malnutrition ("nutritional risk"). Only 6.6% of our patients had a BMI less than 20 kg/ m2. Significant differences in albumin and CRP values in various categories of NRS were confirmed. Initial signs of cancer malnutrition may be overlooked in patients who fall within or above the range of BMI for adequate weight, although these patients may be at significant risk of malnutrition. The indicators of nutritional status and systemic inflammatory responses were significantly associated with resulting values NRS score.

Evolution of carbon isotope signatures during reactive transport of hydrocarbons in heterogeneous aquifers.

PubMed

Höyng, Dominik; Prommer, Henning; Blum, Philipp; Grathwohl, Peter; D'Affonseca, Fernando Mazo

2015-03-01

Compound-specific isotope analysis (CSIA) of organic pollutants has become a well-established tool for assessing the occurrence and extent of biodegradation processes in contaminated aquifers. However, the precision of CSIA is influenced by the degree to which assumptions underlying CSIA data interpretation hold under realistic field-scale conditions. For the first time this study demonstrates how aquifer analogs combined with reactive transport models offer an underexplored way to develop generic process understanding, evaluate monitoring and quantification strategies in highly heterogeneous subsurface settings. Data from high-resolution aquifer analogs were used in numerical experiments to track the propagation of a representative oxidizable organic compound (toluene) within a variety of realistic heterogeneous aquifers and to investigate its detailed fate. The simulations were used to analyze (1) the effects of physical aquifer heterogeneities on spatiotemporal patterns of contaminant concentrations and isotope signatures, (2) the performance of the commonly applied Rayleigh equation and (3) the applicability of an extension of the Rayleigh equation for complex hydrogeological conditions. The results indicate that if field-derived enrichment factors are applied without corrections for dilution, the conventional Rayleigh equation is inaccurate and estimates for biodegradation are typically overestimated and unreliable in heterogeneous aquifers. Underestimations can occur due to the partial source zone depletion. In contrast, if dilution can be accurately accounted for, field-derived enrichment factors comprise a suitable alternative to laboratory-derived and redox-specific enrichment factors. The study also examines to what extent variations in monitoring/sampling strategies influence the obtained results. Especially measurements from long-screened wells (>1 m) reveal to be inappropriate for the application of the Rayleigh equation in the investigated aquifer analogs, as low resolution data sampled from the simulated scenarios only enable a qualitative assessment of biodegradation. Measurements from both long- and short-screened wells employing the Rayleigh equation streamline approach are only partly viable for in situ biodegradation measurements in heterogeneous systems. Copyright © 2015 Elsevier B.V. All rights reserved.

C-reactive Protein is a Useful Marker for Early Prediction of Anastomotic Leakage after Esophageal Reconstruction.

PubMed

Edagawa, Eijiro; Matsuda, Yasunori; Gyobu, Ken; Lee, Shigeru; Kishida, Satoru; Fujiwara, Yushi; Hashiba, Ryoya; Osugi, Harushi; Suehiro, Shigefumi

2015-06-01

Esophageal anastomotic leakage is one of the most fatal complications after esophagectomy and increases the hospitalization length. We aimed to identify a convenient clinical marker of anastomotic leakage in the early postoperative period. In total, 108 patients who underwent esophagectomy were retrospectively screened, and 96 were used to validate the overall results. All 108 patients underwent physical examinations and determination of their white blood cell count, C-reactive protein level, platelet count, fibrinogen level, fibrin degradation product level, and antithrombin III level until postoperative day 6. Anastomotic leakage occurred in 21 of the 108 patients (median detection, 8 days). The C-reactive protein level on postoperative day 3 and fibrinogen level on postoperative day 4 in the leakage group were significantly higher than those in the nonleakage group. Receiver operating characteristic curves for detection of anastomotic leakage were constructed; the cutoff value of C-reactive protein on postoperative day 3 was 8.62 mg/dL, and that of fibrinogen on postoperative day 4 was 712 mg/dL. Anastomotic leakage occurred in 23 of the 96 patients in the validation group. There was a significant difference between the leakage and nonleakage groups when the C-reactive protein threshold on postoperative day 3 was set at 8.62 mg/dL. However, there was no difference between the groups when the fibrinogen threshold on postoperative day 4 was set at 712 mg/dL. The C-reactive protein level on postoperative day 3 is a valuable predictor of anastomotic leakage after esophagectomy and might allow for earlier management of this complication.

Comparison of techniques of detecting immunoglobulin-binding protein reactivity to immunoglobulin produced by different avian and mammalian species.

PubMed

Justiz-Vaillant, A A; Akpaka, P E; McFarlane-Anderson, N; Smikle, M F

2013-01-01

The rationale of this study was to use several immunological assays to investigate the reactivity of immunoglobulin binding protein (IBP) to immunoglobulins from various avian and mammalian species. The IBP studied were Staphylococcal protein A (SpA), Streptococcal protein G (SpG), Peptostreptococcal protein L (SpL) and recombinant protein LA (SpLA). The various immunological techniques used were double immunodiffusion (Ouchterlony technique) that tested positive high protein reactivities, direct and competitive enzyme-linked immunosorbent assays (ELISAs) that tested moderate and low positive protein binding capacities, respectively. In addition to sandwich ELISAs, immunoblot analyses and Ig-purification by SpA-affinity chromatography, which were sensitive tests and helpful in the screening and confirmatory tests were also used. The Ouchterlony technique showed that compared to the other proteins, SpLA had the highest range of reactivity with animal sera and purified immunoglobulins while SpL was least reactive. With the direct ELISA, SpL reacted with the raccoon sera, rabbit IgG and with IgY from bantam hens and pigeons. While with the direct ELISA, SpA reacted with sera from skunk, coyote, raccoon, mule, donkey and human. The sandwich ELISA revealed high reactivity of both SpG and SpLA with mammalian sera titres ranging from 1:32 (raccoon serum) to 1:1024 (mule and donkey sera). These results suggest that IBP can be used for the detection of immunoglobulin using various immunological assays and this is important for the diagnosis of infectious diseases in animal and bird populations studied and in the purification of immunoglobulins.

Using cheminformatics to predict cross reactivity of “designer drugs” to their currently available immunoassays

PubMed Central

2014-01-01

Background A challenge for drug of abuse testing is presented by ‘designer drugs’, compounds typically discovered by modifications of existing clinical drug classes such as amphetamines and cannabinoids. Drug of abuse screening immunoassays directed at amphetamine or methamphetamine only detect a small subset of designer amphetamine-like drugs, and those immunoassays designed for tetrahydrocannabinol metabolites generally do not cross-react with synthetic cannabinoids lacking the classic cannabinoid chemical backbone. This suggests complexity in understanding how to detect and identify whether a patient has taken a molecule of one class or another, impacting clinical care. Methods Cross-reactivity data from immunoassays specifically targeting designer amphetamine-like and synthetic cannabinoid drugs was collected from multiple published sources, and virtual chemical libraries for molecular similarity analysis were built. The virtual library for synthetic cannabinoid analysis contained a total of 169 structures, while the virtual library for amphetamine-type stimulants contained 288 compounds. Two-dimensional (2D) similarity for each test compound was compared to the target molecule of the immunoassay undergoing analysis. Results 2D similarity differentiated between cross-reactive and non-cross-reactive compounds for immunoassays targeting mephedrone/methcathinone, 3,4-methylenedioxypyrovalerone, benzylpiperazine, mephentermine, and synthetic cannabinoids. Conclusions In this study, we applied 2D molecular similarity analysis to the designer amphetamine-type stimulants and synthetic cannabinoids. Similarity calculations can be used to more efficiently decide which drugs and metabolites should be tested in cross-reactivity studies, as well as to design experiments and potentially predict antigens that would lead to immunoassays with cross reactivity for a broader array of designer drugs. PMID:24851137

Evaluation of a homogenous enzyme immunoassay for the detection of synthetic cannabinoids in urine

PubMed Central

Barnes, Allan J.; Young, Sheena; Spinelli, Eliani; Martin, Thomas M.; Klette, Kevin L.; Huestis, Marilyn A.

2014-01-01

Introduction The recent emergence and widespread availability of many new synthetic cannabinoids support the need for an accurate and high-throughput urine screen for these new designer drugs. We evaluated performance of the immunalysis homogeneous enzyme immunoassay (HEIA) to sensitively, selectively, and rapidly identify urinary synthetic cannabinoids. Methods 2443 authentic urine samples were analyzed with the HEIA that targets JWH-018 N-pentanoic acid, and a validated LC-MS/MS method for 29 synthetic cannabinoids and metabolites. Semiquantitative HEIA results were obtained, permitting performance evaluation at and around three cutoffs (5, 10 and 20 μg/L), and diagnostic sensitivity, specificity and efficiency determination. Performance challenges at ±25 and ±50% of each cutoff level, cross-reactivity and interferences also were evaluated. Results Sensitivity, specificity, and efficiency of the immunalysis HEIA K2 Spice kit with the manufacturer's recommended 10 μg/L cutoff were 75.6%, 99.6% and 96.8%, respectively, as compared to the reference LC-MS/MS method with limits of detection of 0.1 -10 μg/L. Performance at 5 μg/L was 92.2%, 98.1% and 97.4%, and for the 20 μg/L cutoff were 62.9%, 99.7% and 95.4%. Semi-quantitative results for in-house prepared standards were obtained from 2.5-30 μg/L, and documented acceptable linearity from 5-25 μg/L, with inter-day imprecision <30% (n = 17). Thirteen of 74 synthetic cannabinoids evaluated were classified as highly cross-reactive (≥50% at 10 μg/L); 4 showed moderate cross-reactivity (10–50% at 10 μg/L), 30 low cross-reactivity (<10% at 500 μg/L), and 27 <1% cross-reactivity at 500 μg/L. There was no interference from 102 investigated compounds. Only a mixture containing 1000 μg/L each of buprenorphine/norbuprenorphine produced a positive result above our proposed cutoff (5 μg/L) but below the manufacturer's recommended cutoff concentration (10 μg/L). Conclusion The Immunalysis HEIA K2 Spice kit required no sample preparation, had a high-throughput, and acceptable sensitivity, specificity and efficiency, offering a viable method for screening synthetic cannabinoids in urine that cross-react with JWH-018 N-pentanoic acid antibodies. PMID:24845968

Pistachio vicilin, Pis v 3, is immunoglobulin E-reactive and cross-reacts with the homologous cashew allergen, Ana o 1.

PubMed

Willison, L N; Tawde, P; Robotham, J M; Penney, R M; Teuber, S S; Sathe, S K; Roux, K H

2008-07-01

Patients allergic to cashew nuts often report allergy to pistachio, which could be a result of cross-reactivity between the two as both are members of the Anacardiaceae family. Because cashew 7S globulin (vicilin, Ana o 1) is a recognized major allergen, we cloned the pistachio homologue and assayed it for IgE reactivity and cross-reactivity with Ana o 1. Degenerate primers for 7S globulin were used in PCR to amplify DNA from a pistachio cDNA library. An isolate was sequenced, cloned and expressed in Escherichia coli. Reactivity to the allergen was screened by dot blot using 19 pistachio and/or cashew-allergic patients' sera. Cross-reactivity was investigated by inhibition dot- and Western immunoblot assays using pistachio/cashew-allergic patients' sera, and monoclonal antibodies (MAbs) raised against recombinant Ana o 1 (rAna o 1). An isolate was found that coded for a 7S vicilin-like protein, designated Pis v 3. IgE reactivity to Pis v 3 was found in the serum of seven of the 19 (37%) patients with histories of allergy to both pistachio and cashew or who were allergic to cashew but had never eaten pistachio. The seven patients with IgE that recognized rPis v 3 also recognized rAna o 1. Six of nine anti-rAna o 1 MAbs also showed reactivity to rPis v 3 on dot blots. Of the 37% of pistachio/cashew-allergic patients' sera that recognized the pistachio allergen, rPis v 3, all showed complete cross-reactivity with rAna o 1. The data does not identify the primary sensitizing agent but suggests that IgE reactivity to rPis v 3 and rAna o 1 is focused on the most conserved regions of the proteins. Clinical histories suggest that in some cases, cashew was the sensitizing agent. rPis v 3 is a likely contributor to the observed co-sensitivity to pistachio and cashew in some patients.

Detection of multiple retroviral infections in cattle and cross-reactivity of bovine immunodeficiency-like virus and human immunodeficiency virus type 1 proteins using bovine and human sera in a western blot assay.

PubMed Central

Jacobs, R M; Smith, H E; Gregory, B; Valli, V E; Whetstone, C A

1992-01-01

Bovine antibovine immunodeficiency-like virus (BIV) antibodies were detected by Western blot analysis (WBA) using a chemiluminescence protocol. Bovine sera with anti-BIV activity, obtained from cows in two dairy herds, had antibodies directed against a variety of BIV-specific antigens indicating chronic infections. These sera were also tested for serological reactivity against bovine leukemia virus (BLV) and bovine syncytial virus (BSV). Cows most commonly had anti-BSV antibodies (12 of 39). Evidence for infection with BSV and BIV or BSV and BLV occurred with almost equal frequency (5 of 39 and 4 of 39, respectively) while only one instance of BIV and BLV coseropositivity was detected. The high prevalence of BSV seropositivity is consistent with a relatively infectious virus, which, as is known, may be transferred congenitally. Similar rates of coseropositivity of BIV or BLV with BSV in this population suggest that BIV is no more infectious than BLV and probably requires prolonged close contact for transmission. Seven of nine cows with anti-BIV antibodies detected primarily human immunodeficiency virus type 1 (HIV-1) p51 and p63 antigens by WBA using an alkaline phosphatase detection system, suggesting that HIV-1 proteins have potential usefulness in screening cattle for BIV seropositivity. Six human sera that showed strong reactivity against multiple HIV-1 proteins and the serum from one of three patients considered to be an "indeterminate" HIV-1 reactor, cross-reacted primarily with BIV p26. This is the first report of human sera with antibody to BIV-specific proteins.(ABSTRACT TRUNCATED AT 250 WORDS) Images Fig. 1. Fig. 2. Fig. 3. PMID:1335835

Chemical structure-based predictive model for the oxidation of trace organic contaminants by sulfate radical.

PubMed

Ye, Tiantian; Wei, Zongsu; Spinney, Richard; Tang, Chong-Jian; Luo, Shuang; Xiao, Ruiyang; Dionysiou, Dionysios D

2017-06-01

Second-order rate constants [Formula: see text] for the reaction of sulfate radical anion (SO 4 •- ) with trace organic contaminants (TrOCs) are of scientific and practical importance for assessing their environmental fate and removal efficiency in water treatment systems. Here, we developed a chemical structure-based model for predicting [Formula: see text] using 32 molecular fragment descriptors, as this type of model provides a quick estimate at low computational cost. The model was constructed using the multiple linear regression (MLR) and artificial neural network (ANN) methods. The MLR method yielded adequate fit for the training set (R training 2 =0.88,n=75) and reasonable predictability for the validation set (R validation 2 =0.62,n=38). In contrast, the ANN method produced a more statistical robustness but rather poor predictability (R training 2 =0.99andR validation 2 =0.42). The reaction mechanisms of SO 4 •- reactivity with TrOCs were elucidated. Our result shows that the coefficients of functional groups reflect their electron donating/withdrawing characters. For example, electron donating groups typically exhibit positive coefficients, indicating enhanced SO 4 •- reactivity. Electron withdrawing groups exhibit negative values, indicating reduced reactivity. With its quick and accurate features, we applied this structure-based model to 55 discrete TrOCs culled from the Contaminant Candidate List 4, and quantitatively compared their removal efficiency with SO 4 •- and OH in the presence of environmental matrices. This high-throughput model helps prioritize TrOCs that are persistent to SO 4 •- based oxidation technologies at the screening level, and provide diagnostics of SO 4 •- reaction mechanisms. Copyright © 2017 Elsevier Ltd. All rights reserved.

New markers of pancreatic cancer identified through differential gene expression analyses: claudin 18 and annexin A8.

PubMed

Karanjawala, Zarir E; Illei, Peter B; Ashfaq, Raheela; Infante, Jeffrey R; Murphy, Kathleen; Pandey, Akhilesh; Schulick, Richard; Winter, Jordan; Sharma, Rajni; Maitra, Anirban; Goggins, Michael; Hruban, Ralph H

2008-02-01

New markers to distinguish benign reactive glands from infiltrating ductal adenocarcinoma of the pancreas are needed. The gene expression patterns of 24 surgically resected primary infiltrating ductal adenocarcinomas of the pancreas were compared with 18 non-neoplastic samples using the Affymetrix U133 Plus 2.0 Arrays and the Gene Logic GeneExpress Software System. Gene fragments from 4 genes (annexin A8, claudin 18, CXCL5, and S100 A2) were selected from the fragments found to be highly expressed in infiltrating adenocarcinomas when compared with normal tissues. The protein expression of these genes was examined using immunohistochemical labeling of tissue microarrays. Claudin 18 labeled infiltrating carcinomas in a membranous pattern. When compared with normal and reactive ducts, claudin 18 was overexpressed, at least focally, in 159 of 166 evaluable carcinomas (96%). Strong and diffuse claudin 18 overexpression was most often seen in well-differentiated carcinomas (P=0.02). Claudin 18 was overexpressed in 51 of 52 cases (98%) of pancreatic intraepithelial neoplasia. Annexin A8 was at least focally overexpressed in 149 of 154 evaluable infiltrating carcinomas (97%). S100 A2 was at least focally overexpressed in 118 of 154 evaluable infiltrating carcinomas (77%). Non-neoplastic glands also frequently expressed S100 A2 diminishing its potential diagnostic utility. Immunolabeling with antibodies directed against CXCL5 did not reveal any significant differences in protein expression between infiltrating adenocarcinomas and normal pancreatic ducts. Claudin 18 and annexin A8 are frequently highly overexpressed in infiltrating ductal adenocarcinomas when compared with normal reactive ducts, suggesting a role for these molecules in pancreatic ductal adenocarcinomas. Furthermore, these may serve as diagnostic markers, as screening tests and as therapeutic targets.

Is Cerebrospinal Fluid C-reactive Protein a Better Tool than Blood C-reactive Protein in Laboratory Diagnosis of Meningitis in Children?

PubMed Central

Malla, Kalpana K.; Malla, Tejesh; Rao, K. Seshagiri; Basnet, Sahisnuta; Shah, Ravi

2013-01-01

Objectives: This study aimed to test whether C-reactive protein (CRP) measurement could differentiate between different types of meningitis and become a routine test. Methods: A prospective study included 140 children admitted to Manipal Teaching Hospital, Pokhara, Nepal, between July 2009 and June 2011. The subjects had a blood test and detailed cerebrospinal fluid (CSF) analysis, including blood and CSF CRP levels. Results: Of those admitted, 31.1% had pyogenic meningitis (PM), 26.2% partially treated meningitis (PPM), 33% viral meningitis (VM), and 9.7% tubercular meningitis (TBM), with 26.4% controls. Organisms were isolated in 12.5% of the cases by blood culture and 25% of cases through CSF culture. Blood CRP was positive in all groups, with the highest values in PM (53.12 ± 28.88 mg/dl) and PPM (47.55 ± 34.34 mg/dl); this was not statistically significant (P = 0.08). The CSF CRP levels were significantly higher (P <0.001) in PM (45.75 ± 28.50 mg/dl) and PPM (23.11 ± 23.98 mg/dl). The sensitivity and specificity of blood CRP was 90.62%, 88.88%, 64.7%, 70% and 32.4%, 30.97%, 24.52%, 26.12% and that of CSF CRP was 96.87%, 66.66%, 20.58%, 10% and 74.73%, 63.71%, 50.94%, 55.35% for PM, PPM, VM and TBM, respectively. Conclusion: Because of its high sensitivity, both CSF CRP and blood CRP can be used to screen for bacterial meningitis (both PM and PPM). CSF CRP screening yielded results with a higher specificity than blood CRP; hence, it can be a supportive test along with CSF cytology, biochemistry, and microbiology for diagnosing meningitis. PMID:23573388

A new bead-based human platelet antigen antibodies detection assay versus the monoclonal antibody immobilization of platelet antigens assay.

PubMed

Porcelijn, Leendert; Huiskes, Elly; Comijs-van Osselen, Ilona; Chhatta, Aniska; Rathore, Vipul; Meyers, Matthew; de Haas, Masja

2014-06-01

The performance of a newly developed Luminex bead-based platelet (PLT) antibody detection method (PAKLx) was compared with the monoclonal antibody immobilization of PLT antigens (MAIPA) assay and the LifeScreen Deluxe Luminex bead-based HLA Class I antibody detection method (LMX). Six sera containing anti-human PLT antigen (HPA)-1a (n=2), HPA-1b, HPA-2b, HPA-3a, or HPA-5b were tested in titration. A total of 194 sera, including HPA-1a, -1b, -2a, -2b, -3a, -5a, and -5b antibodies with or without HLA antibodies (n=63); glycoprotein (GP) IV antibodies (n=1); PLT autoantibodies (n=3); HLA antibodies (n=45); and samples with no PLT-reactive antibodies (n=82), were tested in both assays. Comparable levels of sensitivity were obtained for the MAIPA and PAKLx. The PAKLx showed four (6%) false-negative results in 67 sera with HPA or GP-reactive antibodies: anti-HPA-3a (n=1) or anti-HPA-5b (n=3). The PAKLx showed in 10 of the total 194 samples (5%) the presence of antibodies not detected by the MAIPA. This concerned broadly GP-reactive antibodies (n=7), anti-GPIIb/IIIa combined with anti-HPA-3a (n=1), anti-HPA-1a (borderline, n=1), and anti-GPIV (n=1). Testing 175 sera for anti-HLA Class I antibodies in the PAKLx and LMX showed four discrepant results: PAKLx negative and LMX positive, n=3 and n=1, respectively. For the vast majority of the specimens tested (93%) the results of the PAKLx were in concordance with the MAIPA. The PAKLx is a fast, easy to perform, and sensitive PLT antibody screening method. © 2013 AABB.

Defining the origins of electron transfer at screen-printed graphene-like and graphite electrodes: MoO2 nanowire fabrication on edge plane sites reveals electrochemical insights.

PubMed

Rowley-Neale, Samuel J; Brownson, Dale A C; Banks, Craig E

2016-08-18

Molybdenum (di)oxide (MoO2) nanowires are fabricated onto graphene-like and graphite screen-printed electrodes (SPEs) for the first time, revealing crucial insights into the electrochemical properties of carbon/graphitic based materials. Distinctive patterns observed in the electrochemical process of nanowire decoration show that electron transfer occurs predominantly on edge plane sites when utilising SPEs fabricated/comprised of graphitic materials. Nanowire fabrication along the edge plane sites (and on edge plane like-sites/defects) of graphene/graphite is confirmed with Cyclic Voltammetry, Scanning Electron Microscopy (SEM) and Raman Spectroscopy. Comparison of the heterogeneous electron transfer (HET) rate constants (k°) at unmodified and nanowire coated SPEs show a reduction in the electrochemical reactivity of SPEs when the edge plane sites are effectively blocked/coated with MoO2. Throughout the process, the basal plane sites of the graphene/graphite electrodes remain relatively uncovered; except when the available edge plane sites have been utilised, in which case MoO2 deposition grows from the edge sites covering the entire surface of the electrode. This work clearly illustrates the distinct electron transfer properties of edge and basal plane sites on graphitic materials, indicating favourable electrochemical reactivity at the edge planes in contrast to limited reactivity at the basal plane sites. In addition to providing fundamental insights into the electron transfer properties of graphite and graphene-like SPEs, the reported simple, scalable, and cost effective formation of unique and intriguing MoO2 nanowires realised herein is of significant interest for use in both academic and commercial applications.

Development of scanning holographic display using MEMS SLM

NASA Astrophysics Data System (ADS)

Takaki, Yasuhiro

2016-10-01

Holography is an ideal three-dimensional (3D) display technique, because it produces 3D images that naturally satisfy human 3D perception including physiological and psychological factors. However, its electronic implementation is quite challenging because ultra-high resolution is required for display devices to provide sufficient screen size and viewing zone. We have developed holographic display techniques to enlarge the screen size and the viewing zone by use of microelectromechanical systems spatial light modulators (MEMS-SLMs). Because MEMS-SLMs can generate hologram patterns at a high frame rate, the time-multiplexing technique is utilized to virtually increase the resolution. Three kinds of scanning systems have been combined with MEMS-SLMs; the screen scanning system, the viewing-zone scanning system, and the 360-degree scanning system. The screen scanning system reduces the hologram size to enlarge the viewing zone and the reduced hologram patterns are scanned on the screen to increase the screen size: the color display system with a screen size of 6.2 in. and a viewing zone angle of 11° was demonstrated. The viewing-zone scanning system increases the screen size and the reduced viewing zone is scanned to enlarge the viewing zone: a screen size of 2.0 in. and a viewing zone angle of 40° were achieved. The two-channel system increased the screen size to 7.4 in. The 360-degree scanning increases the screen size and the reduced viewing zone is scanned circularly: the display system having a flat screen with a diameter of 100 mm was demonstrated, which generates 3D images viewed from any direction around the flat screen.

Native Human Monoclonal Antibodies with Potent Cross-Lineage Neutralization of Influenza B Viruses

PubMed Central

Vigil, Adam; Estélles, Angeles; Kauvar, Lawrence M.; Johnson, Scott K.

2018-01-01

ABSTRACT Although antibodies that effectively neutralize a broad set of influenza viruses exist in the human antibody repertoire, they are rare. We used a single-cell screening technology to identify rare monoclonal antibodies (MAbs) that recognized a broad set of influenza B viruses (IBV). The screen yielded 23 MAbs with diverse germ line origins that recognized hemagglutinins (HAs) derived from influenza strains of both the Yamagata and Victoria lineages of IBV. Of the 23 MAbs, 3 exhibited low expression in a transient-transfection system, 4 were neutralizers that bound to the HA head region, 11 were stalk-binding nonneutralizers, and 5 were stalk-binding neutralizers, with 4 of these 5 having unique antibody sequences. Of these four unique stalk-binding neutralizing MAbs, all were broadly reactive and neutralizing against a panel of multiple strains spanning both IBV lineages as well as highly effective in treating lethal IBV infections in mice at both 24 and 72 h postinfection. The MAbs in this group were thermostable and bound different epitopes in the highly conserved HA stalk region. These characteristics suggest that these MAbs are suitable for consideration as candidates for clinical studies to address their effectiveness in the treatment of IBV-infected patients. PMID:29507069

Gastroprotective effects of several H2RAs on ibuprofen-induced gastric ulcer in rats.

PubMed

Liu, Jing; Sun, Dan; He, Jinfeng; Yang, Chengli; Hu, Tingting; Zhang, Lijing; Cao, Hua; Tong, Ai-Ping; Song, Xiangrong; Xie, Yongmei; He, Gu; Guo, Gang; Luo, Youfu; Cheng, Ping; Zheng, Yu

2016-03-15

Ibuprofen is the first line of treatment for osteoarthritis and arthritis. The main side effects of ibuprofen especially in long-term treatment include gastric ulcer, duodenal ulcer and indigestion etc. Therefore, screening drugs with effective gastric protective effects and low toxicity for combination therapy with ibuprofen is necessary. The mechanism of gastric damage induced by ibuprofen is still unclear, however, cell damage caused by reactive oxygen species (ROS) is considered as the main reason. Preliminary screening of literature with the criteria of low toxicity led to four histamine-2 receptor antagonists (H2RAs): nizatidine, famotidine, lafutidine, and roxatidine acetate, which were selected for further investigation. These drugs were evaluated systemically by examining the gastric ulcer index, lipid peroxidation (LPO), membrane permeability, toxicity to main organs, and the influence on the activity of antioxidant enzymes, and myeloperoxidase (MPO). Nizatidine was found to be the best gastric protective agent. It exhibited excellent protective effect by increasing antioxidant enzyme activity, decreasing MPO activity, reducing LPO, and membrane permeability. Combination treatment with nizatidine and ibuprofen did not show any significant toxicity. Nizatidine was considered as a good option for combination therapy with ibuprofen especially for diseases that require long-term treatment such as arthritis and osteoarthritis. Copyright © 2016 Elsevier Inc. All rights reserved.

Rapid screening, separation, and detection of hydroxyl radical scavengers from total flavonoids of Ginkgo biloba leaves by chromatography combined with molecular devices.

PubMed

Wang, Jing; Zheng, Meizhu; Chen, Lina; Liu, Zhiqiang; Zhang, Yuchi; Liu, Chun-Ming; Liu, Shu

2016-11-01

Hydroxyl radicals are the most reactive free radical of human body, a strong contributor to tissue damage. In this study, liquid chromatography coupled to electrospray ionization mass spectrometry was applied to screen and identify hydroxyl radical scavengers from the total flavonoids of Ginkgo biloba leaves, and high-performance counter current chromatography was used to separate and isolate the active compounds. Furthermore, molecular devices were used to determine hydroxyl radical scavenging activities of the obtained hydroxyl radical scavengers and other flavonoids from G. biloba leaves. As a result, six compounds were screened as hydroxyl radical scavengers, but only three flavonoids, namely, rutin, cosmos glycosides and apigenin-7-O-Glu-4'-O-Rha, were isolated successfully from total flavonoids by high-performance counter current chromatography. The purities of the three obtained compounds were over 90%, respectively, as determined by liquid chromatography. Molecular devices with 96-well microplates evaluation indicated that the 50% scavenging concentration values of screened compounds were lower than that of other flavonoids, they performed greater hydroxyl radical scavenging activity, and the evaluation effects were consistent with the liquid chromatography with mass spectrometry screening results. Therefore, chromatography combined with molecular devices is a feasible and an efficient method for systematic screening, identification, isolation, and evaluation of bioactive components in mixture of botanical medicines. © 2016 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

Cost-effectiveness analysis of strategies using new immunological diagnostic tests of latent tuberculosis infection before TNF-blockers therapy.

PubMed

Freund, Romain; Granger, Benjamin; Francois, Cécile; Carcelain, Guislaine; Ravaud, Philippe; Mariette, Xavier; Fautrel, Bruno

2018-02-01

Several tests have been proposed to detect latent tuberculosis (LTB). To evaluate the cost-effectiveness of different interferon-gamma release assays based strategies used to screen LTB before tumour necrosis factor (TNF) blockers initiation. Consecutive patients with rheumatoid arthritis, spondyloarthritis or Crohn's disease for whom TNF-blockers were considered, were recruited in 15 tertiary care centres. All were screened for LTB with tuberculin skin test (TST), QuantiFERON TB Gold ® in tube (QFT) and T-SPOT.TB ® (TSpot) on the same day. Cost-minimization and cost-effectiveness analysis, testing 8 screening test combinations, were conducted. Effectiveness was defined as the percentage of LTB treatment avoided and compared with TST alone. Cost were elicited in the payer perspective, included all the costs related to the screening procedure. No tuberculosis reactivation was observed after TNF-blocker initiation. TST followed by QFT if TST was positive was found as the best screening strategy, i.e. the less costly (-54€ compared to reference) and most effective (effectiveness 0.93), resulting in an incremental cost-effectiveness ratio of -192€ per treatment avoided. A probabilistic sensitivity analysis confirmed this result in 72.3% of simulations. TST followed by QFT if TST was positive is the most cost-effective strategy in screening for LTB in patients before starting anti-TNF therapy. NCT00811343. Copyright © 2018 Elsevier Masson SAS. All rights reserved.

Reactive Oxygen Species Produced by Prostate Cancer Cells Cause Castrate-Resistant Cell Growth by Inducing B-cell Lymphotoxin Release

DTIC Science & Technology

2013-06-01

data sources, gathering and maintaining the data needed, and completing and reviewing this collection of information. Send comments regarding this...Gaussia luciferase reconstitution, high throughput screen, small molecule inhibitors, human prostate carcinoma cells, pharmacokinetcs, prostate cancer...cells. The increase in ROS levels is probably due to an induction of a polyamine oxidation pathway and specific small molecule inhibitors of this

Chalcogenide Glass for Active and Passive Mid-IR Applications

DTIC Science & Technology

2010-09-01

Reactive gas conversion • Chemical vapour deposition What is a Chalcogenide? – From Greek sulphur-loving for elements that frequently bond to sulphur...Predominately As or Se based (toxic!) ORC Research Focussed On – Gallium Lanthanum Sulphides (non-toxic) – Germanium Sulphides (non-toxic) – Capability to...770 2 hours Primary Screening 2 - 3 days Time Scale: one week Pioneering Technology: High Throughput Physical Vapour Deposition Material Discovery

Short Time Exposure (STE) test in conjunction with Bovine Corneal Opacity and Permeability (BCOP) assay including histopathology to evaluate correspondence with the Globally Harmonized System (GHS) eye irritation classification of textile dyes.

PubMed

Oliveira, Gisele Augusto Rodrigues; Ducas, Rafael do Nascimento; Teixeira, Gabriel Campos; Batista, Aline Carvalho; Oliveira, Danielle Palma; Valadares, Marize Campos

2015-09-01

Eye irritation evaluation is mandatory for predicting health risks in consumers exposed to textile dyes. The two dyes, Reactive Orange 16 (RO16) and Reactive Green 19 (RG19) are classified as Category 2A (irritating to eyes) based on the UN Globally Harmonized System for classification (UN GHS), according to the Draize test. On the other hand, animal welfare considerations and the enforcement of a new regulation in the EU are drawing much attention in reducing or replacing animal experiments with alternative methods. This study evaluated the eye irritation of the two dyes RO16 and RG19 by combining the Short Time Exposure (STE) and the Bovine Corneal Opacity and Permeability (BCOP) assays and then comparing them with in vivo data from the GHS classification. The STE test (first level screening) categorized both dyes as GHS Category 1 (severe irritant). In the BCOP, dye RG19 was also classified as GHS Category 1 while dye RO16 was classified as GHS no prediction can be made. Both dyes caused damage to the corneal tissue as confirmed by histopathological analysis. Our findings demonstrated that the STE test did not contribute to arriving at a better conclusion about the eye irritation potential of the dyes when used in conjunction with the BCOP test. Adding the histopathology to the BCOP test could be an appropriate tool for a more meaningful prediction of the eye irritation potential of dyes. Copyright © 2015 Elsevier Ltd. All rights reserved.

Macroprolactin, big-prolactin and potential effects on the misdiagnosis of hyperprolactinemia using the Beckman Coulter Access Prolactin assay.

PubMed

Ellis, M Jane; Livesey, John H; Soule, Steven G

2006-10-01

To examine whether use of the Beckman Coulter Access Prolactin (PRL) assay, which has low reactivity with macro-PRL, obviates the need for screening hyperprolactinemic samples. Samples from 1020 hyperprolactinemic individuals and 401 healthy volunteers were treated with polyethylene glycol (PEG). Macro-PRL was assessed from (1) percent PRL recovery, using cut-off values derived by gel filtration chromatography (GFC) and (2) significant (p<0.05) normalisation of PRL following PEG. PRL recovery was similar in volunteer and hyperprolactinemic samples (mean+/-SD 101+/-13% and 101+/-19%, respectively). In hyperprolactinemic samples, macro-PRL was identified from PRL recovery in 9.7%, although levels were moderate to high in only 3.9%. The total PRL normalised following PEG in 7.4%. Correlations of PRL recovery with the proportions of macro-, big- and monomeric PRL following GFC (n=30 samples, range of PRL and macro-PRL levels) were -0.89, -0.20 and 0.92, respectively. The big-PRL content was 0-28%. Regression analysis suggested that PEG precipitated both macro-PRL and big-PRL. Using the Access assay, macro-PRL can cause apparent hyperprolactinemia and big-PRL may cause misclassification of individuals. Screening using PEG is applicable to assays with low macro-PRL reactivity provided specific reference values are derived.

Issues encountered in development of enzyme-linked immunosorbent assay for use in detecting Influenza A virus subtype H5N1 exposure in swine.

PubMed

Buehler, Jason; Lager, Kelly; Vincent, Amy; Miller, Cathy; Thacker, Eileen; Janke, Bruce

2014-03-01

A potential mechanism by which highly pathogenic avian Influenza A virus subtype H5N1 could more readily infect human beings is through the infection of and adaptation in pigs. To detect the occurrence of such infection, monitoring of pig populations through serological screening would be highly desirable. In the current study, hemagglutination inhibition assays were able to detect antibodies against H5N1 developed in pigs, but because of antigenic variation between clades, the use of multiple virus strains were required. Whole recombinant virus and recombinant hemagglutinin antigen enzyme-linked immunosorbent assays (ELISAs) were generated that could detect antibody against multiple H5N1 strains, but which also detected antibody against endemic swine influenza viruses. A recombinant hemagglutinin antigen-based ELISA was as effective as the whole virus antigen ELISAs in detecting antibody against the H5N1 virus strains used and eliminated nearly all of the cross-reactivity with non-H5N1 virus antibody. The current study also highlighted the difficulty in establishing a decision (cutoff) value that would effectively counterbalance nonspecific reactivity against sensitivity. The results provide important information and considerations for the development of serological screening assays for highly pathogenic avian H5N1 viruses.

Factors associated with the development of atrial fibrillation in patients with rheumatic mitral stenosis.

PubMed

Ozaydin, Mehmet; Turker, Yasin; Varol, Ercan; Alaca, Sule; Erdogan, Dogan; Yilmaz, Nigar; Dogan, Abdullah

2010-06-01

The aim of this study was to evaluate the factors associated with the development of atrial fibrillation (AF) in patients with rheumatic mitral stenosis (MS). A total of 146 consecutive patients with rheumatic MS were screened. They were accepted to be in AF group and sinus rhythm group according to their rhythm in the baseline ECG. After screening, 38 patients were excluded due to hyperthyroidism (n = 13), chronic obstructive pulmonary disease (n = 22), malignancy (n = 2) and rheumatoid arthritis (n = 1). Therefore, remaining 108 patients, 74 of whom in sinus rhythm (MS-SR) and 34 of whom in AF (MS-AF) constituted study population. Fourty age- and gender-matched patients constituted control group. Factors associated with development of AF in multivariable analysis included High sensitivity C reactive protein (P = 0.005; odds ratio, 3.44; 95% confidence interval, 1.44-8.22), N-terminal of brain natriuretic peptide precursor (P < 0.0001; odds ratio, 1.03; 95% confidence interval, 1.02-1.06) and left atrial diameter (P < 0.0001; odds ratio, 1.68; 95% confidence interval, 1.32-2.14). Present study suggests that High sensitivity C reactive protein, N-terminal of brain natriuretic peptide precursor and left atrial diameter are associated with development AF in patients with MS.

Discordant HIV Test Results: Implications on Perinatal and Haemotransfusion Screening for HIV Infection, Cape Coast, Ghana.

PubMed

Tetteh, Ato Kwamena; Agyarko, Edward

2017-01-01

Screening results of 488 pregnant women aged 15-44 years whose blood samples had been tested on-site, using First Response® HIV 1/2, and confirmed with INNO-LIA™ HIV I/II Score were used. Of this total, 178 were reactive (HIV I, 154; HIV II, 2; and HIV I and HIV II, 22). Of the 154 HIV I-reactive samples, 104 were confirmed to be HIV I-positive and 2 were confirmed to be HIV II-positive, while 48 were confirmed to be negative [false positive rate = 17.44% (13.56-21.32)]. The two HIV II samples submitted were confirmed to be negative with the confirmatory test. For the 22 HIV I and HIV II samples, 7 were confirmed to be HIV I-positive and 1 was confirmed to be HIV I- and HIV II-positive, while 14 were confirmed to be negative. Of the 310 nonreactive samples, 6 were confirmed to be HIV I-positive and 1 was confirmed to be HIV II-positive [false negative rate = 5.79% (1.63-8.38)], while 303 were negative. False negative outcomes will remain unconfirmed, with no management options for the client. False negative rate of 5.79% requires attention, as its resultant implications on control of HIV/AIDS could be dire.

Prevalence of Chagas Disease among Solid Organ-Transplanted Patients in a Nonendemic Country.

PubMed

Salvador, Fernando; Sánchez-Montalvá, Adrián; Sulleiro, Elena; Moreso, Francesc; Berastegui, Cristina; Caralt, Mireia; Pinazo, María-Jesús; Moure, Zaira; Los-Arcos, Ibai; Len, Oscar; Gavaldà, Joan; Molina, Israel

2018-03-01

Reactivation of Chagas disease in the chronic phase may occur after solid organ transplantation, which may result in high parasitemia and severe clinical manifestations such as myocarditis and meningoencephalitis. The aim of the present study is to describe the prevalence of Chagas disease among solid organ-transplanted patients in a tertiary hospital from a nonendemic country. A cross-sectional study was performed at Vall d'Hebron University Hospital (Barcelona, Spain) from April to September 2016. Chagas disease screening was performed through serological tests in adult patients coming from endemic areas that had received solid organ transplantation and were being controlled in our hospital during the study period. Overall, 42 patients were included, 20 (47.6%) were male and median age was 50.5 (23-73) years. Transplanted organs were as follows: 18 kidneys, 17 lungs, and 7 livers. Three patients had Chagas disease, corresponding to a prevalence among this group of solid organ-transplanted patients of 7.1%. All three patients were born in Bolivia, had been diagnosed with Chagas disease and received specific treatment before the organ transplantation. We highly recommend providing screening tests for Chagas disease in patients with or candidates for solid organ transplantation coming from endemic areas, early treatment with benznidazole, and close follow-up to prevent clinical reactivations.

Immunodiagnosis of Echinococcus Infections: Confirmatory Testing and Species Differentiation by a New Commercial Western Blot

PubMed Central

Liance, Martine; Janin, Veronique; Bresson-Hadni, Solange; Vuitton, Dominique-Angele; Houin, Rene; Piarroux, Renaud

2000-01-01

The Echinococcus Western Blot IgG (LDBIO Diagnostics, Lyon, France), using a whole larval antigen from Echinococcus multilocularis, was evaluated for serodiagnosis and differentiation between two human parasitic infections of worldwide importance: cystic echinococcosis, due to Echinococcus granulosus, and alveolar echinococcosis, due to E. multilocularis. Fifty and 61 serum samples from patients with cystic and alveolar echinococcosis, respectively, were used for assessing diagnostic sensitivity. The sensitivity of the assay was compared with those of screening tests used for these applications. Sera used for assessing cross-reactivities were from 154 patients with other diseases, either parasitic or not. The assay allowed the detection of serum immunoglobulin G antibodies in 97% of Echinococcus-infected patients. It had a higher sensitivity than screening assays for the detection for each echinococcosis. The assay allowed us to correctly distinguish between E. granulosus- and E. multilocularis-infected patients in 76% of cases. It did not allow us to distinguish active from inactive forms of both echinococcoses. The occurrence of cross-reactivities with neurocysticercosis indicates the necessity for retesting sera with species-specific antigens, for rare patients with neurologic disorders. This study shows the usefulness of the commercially available Echinococcus Western Blot IgG for the serological confirmation of human echinococcosis. PMID:11015390

Rapid Screening for Potential Epitopes Reactive with a Polycolonal Antibody by Solution-Phase H/D Exchange Monitored by FT-ICR Mass Spectrometry

NASA Astrophysics Data System (ADS)

Zhang, Qian; Noble, Kyle A.; Mao, Yuan; Young, Nicolas L.; Sathe, Shridhar K.; Roux, Kenneth H.; Marshall, Alan G.

2013-07-01

The potential epitopes of a recombinant food allergen protein, cashew Ana o 2, reactive to polyclonal antibodies, were mapped by solution-phase amide backbone H/D exchange (HDX) coupled with Fourier transform ion cyclotron resonance mass spectrometry (FT-ICR MS). Ana o 2 polyclonal antibodies were purified in the serum from a goat immunized with cashew nut extract. Antibodies were incubated with recombinant Ana o 2 (rAna o 2) to form antigen:polyclonal antibody (Ag:pAb) complexes. Complexed and uncomplexed (free) rAna o 2 were then subjected to HDX-MS analysis. Four regions protected from H/D exchange upon pAb binding are identified as potential epitopes and mapped onto a homologous model.

Label-assisted mass spectrometry for the acceleration of reaction discovery and optimization

NASA Astrophysics Data System (ADS)

Cabrera-Pardo, Jaime R.; Chai, David I.; Liu, Song; Mrksich, Milan; Kozmin, Sergey A.

2013-05-01

The identification of new reactions expands our knowledge of chemical reactivity and enables new synthetic applications. Accelerating the pace of this discovery process remains challenging. We describe a highly effective and simple platform for screening a large number of potential chemical reactions in order to discover and optimize previously unknown catalytic transformations, thereby revealing new chemical reactivity. Our strategy is based on labelling one of the reactants with a polyaromatic chemical tag, which selectively undergoes a photoionization/desorption process upon laser irradiation, without the assistance of an external matrix, and enables rapid mass spectrometric detection of any products originating from such labelled reactants in complex reaction mixtures without any chromatographic separation. This method was successfully used for high-throughput discovery and subsequent optimization of two previously unknown benzannulation reactions.

Acute seronegative polyarthritis associated with lymphogranuloma venereum infection in a patient with prevalent HIV infection.

PubMed

Kober, C; Richardson, D; Bell, C; Walker-Bone, K

2011-01-01

A 44-year-old man who has sex with men presented with a three-month asymmetrical polyarthropathy. He had a positive HIV-1 antibody test consistent with infection acquired more than six months previously. Lymphogranuloma venereum (LGV)-associated DNA was detected from a rectal swab. Following successful treatment for LGV his arthritis resolved completely. Infection with HIV-1 has been hypothesized to cause reactive arthritis but this has been disputed. The most likely diagnosis in this patient was sexually acquired reactive arthritis secondary to LGV infection. As LGV can be asymptomatic and treatment differs from that of the other serovars, screening should be considered in all men who have sex with men (MSM) presenting with acute arthritis, particularly if they are HIV infected.

Anti-enrofloxacin antibody production by using enrofloxacin-screened HSA as an immunogen

NASA Astrophysics Data System (ADS)

Liu, Chune; Lin, Hong; Cao, Limin; Jiang, Jie

2005-07-01

A two-step zero-length cross-linking procedure using active esters was successfully adopted for conjugating enrofloxacin (EF) to human serum albumin (HSA). The derived conjugate was characterized by UV spectrum and then used for immunization of BALB/C mice. In enzyme-linked immunosorbent assay (ELISA) and competitive inhibition ELISA experiments, the derived antiserum exhibited high antibody titer (greater than 1:250 000) as well as varied cross-reactivity (from 97.8% to 161.7%) to three analogs of EF belonging to fluoroquinolones family. But over the concentration range studied, no significant cross-reactivity was observed to other group of antibiotics (chloramphenicol, oxytetracycline, sulphamethoxazole and nysfungin). It was confirmed that the synthesized immunogen was highly antigenic and elicited specific antibody responses in BALB/C mice against EF.

Lunar Dust Chemical, Electrical, and Mechanical Reactivity: Simulation and Characterization

NASA Technical Reports Server (NTRS)

VanderWal, Randy L.

2008-01-01

Lunar dust is recognized to be a highly reactive material in its native state. Many, if not all Constellation systems will be affected by its adhesion, abrasion, and reactivity. A critical requirement to develop successful strategies for dealing with lunar dust and designing tolerant systems will be to produce similar material for ground-based testing.

Spatial imaging of carbon reactivity centers in Pd/C catalytic systems† †Electronic supplementary information (ESI) available: Detailed experimental procedures and FE-SEM images. See DOI: 10.1039/c5sc00802f

PubMed Central

Pentsak, E. O.; Kashin, A. S.; Polynski, M. V.; Kvashnina, K. O.; Glatzel, P.

2015-01-01

Gaining insight into Pd/C catalytic systems aimed at locating reactive centers on carbon surfaces, revealing their properties and estimating the number of reactive centers presents a challenging problem. In the present study state-of-the-art experimental techniques involving ultra high resolution SEM/STEM microscopy (1 Å resolution), high brilliance X-ray absorption spectroscopy and theoretical calculations on truly nanoscale systems were utilized to reveal the role of carbon centers in the formation and nature of Pd/C catalytic materials. Generation of Pd clusters in solution from the easily available Pd2dba3 precursor and the unique reactivity of the Pd clusters opened an excellent opportunity to develop an efficient procedure for the imaging of a carbon surface. Defect sites and reactivity centers of a carbon surface were mapped in three-dimensional space with high resolution and excellent contrast using a user-friendly nanoscale imaging procedure. The proposed imaging approach takes advantage of the specific interactions of reactive carbon centers with Pd clusters, which allows spatial information about chemical reactivity across the Pd/C system to be obtained using a microscopy technique. Mapping the reactivity centers with Pd markers provided unique information about the reactivity of the graphene layers and showed that >2000 reactive centers can be located per 1 μm2 of the surface area of the carbon material. A computational study at a PBE-D3-GPW level differentiated the relative affinity of the Pd2 species to the reactive centers of graphene. These findings emphasized the spatial complexity of the carbon material at the nanoscale and indicated the importance of the surface defect nature, which exhibited substantial gradients and variations across the surface area. The findings show the crucial role of the structure of the carbon support, which governs the formation of Pd/C systems and their catalytic activity. PMID:29511504

Chemiluminescence analysis of antioxidant capacity for serum albumin isolated from healthy or uremic volunteers.

PubMed

Huang, Chih-Yang; Liou, Show-Yih; Kuo, Wei-Wen; Wu, Hsi-Chin; Chang, Yen-Lin; Chen, Tung-Sheng

2016-12-01

Regular hemodialysis treatment induces an elevation in oxidative stress in patients with end-stage renal failure, resulting in oxidative damage of the most abundant serum protein, albumin. Oxidation of serum albumin causes depletion of albumin reactive thiols, leading to oxidative modification of serum albumin. The aim of this study was to screen the antioxidant capacity of albumins isolated from uremic patients (HD-ALB) or healthy volunteers (N-ALB). From high-performance liquid chromatography spectra, we observed that one uremic solute binds to HD-ALB via the formation of disulfide bonds between HD-ALB and the uremic solute. Furthermore, we found using chemiluminescent analysis that the antioxidant capacities for N-ALB to scavenge reactive oxygen species including singlet oxygen, hypochlorite and hydrogen peroxide were higher than HD-ALB. Our results suggest that protein-bound uremic solute binds to albumin via formation of disulfide bonds, resulting in the depletion of albumin reactive thiols. The depletion of albumin reactive thiols leads to a reduced antioxidant capacity of HD-ALB, implying postmodification of albumin. This situation may reduce the antioxidant capacity of albumin and increase oxidative stress, resulting in increase in complications related to oxidative damage in uremic patients. Copyright © 2016 John Wiley & Sons, Ltd. Copyright © 2016 John Wiley & Sons, Ltd.

Assay to detect lipid peroxidation upon exposure to nanoparticles.

PubMed

Potter, Timothy M; Neun, Barry W; Stern, Stephan T

2011-01-01

This chapter describes a method for the analysis of human hepatocarcinoma cells (HEP G2) for lipid peroxidation products, such as malondialdehyde (MDA), following treatment with nanoparticle formulations. Oxidative stress has been identified as a likely mechanism of nanoparticle toxicity, and cell-based in vitro systems for evaluation of nanoparticle-induced oxidative stress are widely considered to be an important component of biocompatibility screens. The products of lipid peroxidation, lipid hydroperoxides, and aldehydes, such as MDA, can be measured via a thiobarbituric acid reactive substances (TBARS) assay. In this assay, which can be performed in cell culture or in cell lysate, MDA combines with thiobarbituric acid (TBA) to form a fluorescent adduct that can be detected at an excitation wavelength of 530 nm and an emission wavelength of 550 nm. The results are then expressed as MDA equivalents, normalized to total cellular protein (determined by Bradford assay).

Identification of proteins interacting with Toxoplasma SRCAP by yeast two-hybrid screening.

PubMed

Nallani, Karuna C; Sullivan, William J

2005-03-01

Toxoplasma gondii is an opportunistic protozoan parasite that differentiates into latent cysts (bradyzoite) that can be reactivated during immunosuppression. TgSRCAP (Toxoplasma gondii Snf2-related CBP activator protein) is a SWI2/SNF2 family chromatin remodeler whose expression increases during cyst development. Identifying the proteins associating with TgSRCAP during the pre-cyst stage (tachyzoite) will increase our understanding of how parasite differentiation is initiated. We employed the yeast two-hybrid system to identify proteins that may interact directly with TgSRCAP. A stretch of 1,060 amino acids between ATPase subdomains IV and V of TgSRCAP was chosen as "bait" since the corresponding region in human SRCAP interacts with other proteins, including CREB binding protein. We have identified several novel parasite-specific transcription factors predicted to be in the T. gondii genome. Metabolic enzymes that may participate in cyst development were also identified as interacting with TgSRCAP.

Thermal decomposition hazard evaluation of hydroxylamine nitrate.

PubMed

Wei, Chunyang; Rogers, William J; Mannan, M Sam

2006-03-17

Hydroxylamine nitrate (HAN) is an important member of the hydroxylamine family and it is a liquid propellant when combined with alkylammonium nitrate fuel in an aqueous solution. Low concentrations of HAN are used primarily in the nuclear industry as a reductant in nuclear material processing and for decontamination of equipment. Also, HAN has been involved in several incidents because of its instability and autocatalytic decomposition behavior. This paper presents calorimetric measurement for the thermal decomposition of 24 mass% HAN/water. Gas phase enthalpy of formation of HAN is calculated using both semi-empirical methods with MOPAC and high-level quantum chemical methods of Gaussian 03. CHETAH is used to estimate the energy release potential of HAN. A Reactive System Screening Tool (RSST) and an Automatic Pressure Tracking Adiabatic Calorimeter (APTAC) are used to characterize thermal decomposition of HAN and to provide guidance about safe conditions for handling and storing of HAN.

In situ Generated Ruthenium Catalyst Systems Bearing Diverse N-Heterocyclic Carbene Precursors for Atom-Economic Amide Synthesis from Alcohols and Amines.

PubMed

Cheng, Hua; Xiong, Mao-Qian; Cheng, Chuan-Xiang; Wang, Hua-Jing; Lu, Qiang; Liu, Hong-Fu; Yao, Fu-Bin; Chen, Cheng; Verpoort, Francis

2018-02-16

The transition-metal-catalyzed direct synthesis of amides from alcohols and amines is herein demonstrated as a highly environmentally benign and atom-economic process. Among various catalyst systems, in situ generated N-heterocyclic carbene (NHC)-based ruthenium (Ru) halide catalyst systems have been proven to be active for this transformation. However, these existing catalyst systems usually require an additional ligand to achieve satisfactory results. In this work, through extensive screening of a diverse variety of NHC precursors, we discovered an active in situ catalyst system for efficient amide synthesis without any additional ligand. Notably, this catalyst system was found to be insensitive to the electronic effects of the substrates, and various electron-deficient substrates, which were not highly reactive with our previous catalyst systems, could be employed to afford the corresponding amides efficiently. Furthermore, mechanistic investigations were performed to provide a rationale for the high activity of the optimized catalyst system. NMR-scale reactions indicated that the rapid formation of a Ru hydride intermediate (signal at δ=-7.8 ppm in the 1 H NMR spectrum) after the addition of the alcohol substrate should be pivotal in establishing the high catalyst activity. Besides, HRMS analysis provided possible structures of the in situ generated catalyst system. © 2018 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim.

Gold silver alloy nanoparticles (GSAN): an imaging probe for breast cancer screening with dual-energy mammography or computed tomography

NASA Astrophysics Data System (ADS)

Naha, Pratap C.; Lau, Kristen C.; Hsu, Jessica C.; Hajfathalian, Maryam; Mian, Shaameen; Chhour, Peter; Uppuluri, Lahari; McDonald, Elizabeth S.; Maidment, Andrew D. A.; Cormode, David P.

2016-07-01

Earlier detection of breast cancer reduces mortality from this disease. As a result, the development of better screening techniques is a topic of intense interest. Contrast-enhanced dual-energy mammography (DEM) is a novel technique that has improved sensitivity for cancer detection. However, the development of contrast agents for this technique is in its infancy. We herein report gold-silver alloy nanoparticles (GSAN) that have potent DEM contrast properties and improved biocompatibility. GSAN formulations containing a range of gold : silver ratios and capped with m-PEG were synthesized and characterized using various analytical methods. DEM and computed tomography (CT) phantom imaging showed that GSAN produced robust contrast that was comparable to silver alone. Cell viability, reactive oxygen species generation and DNA damage results revealed that the formulations with 30% or higher gold content are cytocompatible to Hep G2 and J774A.1 cells. In vivo imaging was performed in mice with and without breast tumors. The results showed that GSAN produce strong DEM and CT contrast and accumulated in tumors. Furthermore, both in vivo imaging and ex vivo analysis indicated the excretion of GSAN via both urine and feces. In summary, GSAN produce strong DEM and CT contrast, and has potential for both blood pool imaging and for breast cancer screening.Earlier detection of breast cancer reduces mortality from this disease. As a result, the development of better screening techniques is a topic of intense interest. Contrast-enhanced dual-energy mammography (DEM) is a novel technique that has improved sensitivity for cancer detection. However, the development of contrast agents for this technique is in its infancy. We herein report gold-silver alloy nanoparticles (GSAN) that have potent DEM contrast properties and improved biocompatibility. GSAN formulations containing a range of gold : silver ratios and capped with m-PEG were synthesized and characterized using various analytical methods. DEM and computed tomography (CT) phantom imaging showed that GSAN produced robust contrast that was comparable to silver alone. Cell viability, reactive oxygen species generation and DNA damage results revealed that the formulations with 30% or higher gold content are cytocompatible to Hep G2 and J774A.1 cells. In vivo imaging was performed in mice with and without breast tumors. The results showed that GSAN produce strong DEM and CT contrast and accumulated in tumors. Furthermore, both in vivo imaging and ex vivo analysis indicated the excretion of GSAN via both urine and feces. In summary, GSAN produce strong DEM and CT contrast, and has potential for both blood pool imaging and for breast cancer screening. Electronic supplementary information (ESI) available: Reactive oxygen species generation and DNA damage methods, stability of GSAN in PBS, step phantom images and a DEM image of a gold nanoparticle phantom, GSAN CT phantom results. See DOI: 10.1039/c6nr02618d

Enhanced systemic immune reactivity to a Basal cell carcinoma associated antigen following photodynamic therapy.

PubMed

Kabingu, Edith; Oseroff, Allan R; Wilding, Gregory E; Gollnick, Sandra O

2009-07-01

Numerous preclinical studies have shown that local photodynamic therapy (PDT) of tumors enhances systemic antitumor immunity. However, other than single-case and anecdotal reports, this phenomenon has not been examined following clinical PDT. To determine whether PDT in a clinical setting enhances systemic recognition of tumor cells, we examined whether PDT of basal cell carcinoma resulted in an increased systemic immune response to Hip1, a tumor antigen associated with basal cell carcinoma. Basal cell carcinoma lesions were either treated with PDT or surgically removed. Blood was collected from patients immediately before or 7 to 10 days following treatment. Peripheral blood leukocytes were isolated from HLA-A2-expressing patients and reactivity to a HLA-A2-restricted Hip1 peptide was measured by INF-gamma ELISpot assay. Immune recognition of Hip1 increased in patients whose basal cell carcinoma lesions were treated with PDT. This increase in reactivity was significantly greater than reactivity observed in patients whose lesions were surgically removed. Patients with superficial lesions exhibited greater enhancement of reactivity compared with patients with nodular lesions. Immune reactivity following PDT was inversely correlated with treatment area and light dose. These findings show for the first time that local tumor PDT can enhance systemic immune responses to tumors in patients, and validate previous preclinical findings.

Evidence for an Inducible Repair-Recombination System in the Female Germ Line of Drosophila Melanogaster. III. Correlation between Reactivity Levels, Crossover Frequency and Repair Efficiency

PubMed Central

Laurencon, A.; Gay, F.; Ducau, J.; Bregliano, J. C.

1997-01-01

We previously reported evidence that the so-called reactivity level, a peculiar cellular state of oocytes that regulates the frequency of transposition of I factor, a LINE element-like retrotransposon, might be one manifestation of a DNA repair system. In this article, we report data showing that the reactivity level is correlated with the frequency of crossing over, at least on the X chromosome and on the pericentromeric region of the third chromosome. Moreover, a check for X-chromosome losses and recessive lethals produced after gamma irradiation in flies with different reactivity levels, but common genetic backgrounds, brings more precise evidence for the relationship between reactivity levels and DNA repair. Those results support the existence of a repair-recombination system whose efficiency is modulated by endogenous and environmental factors. The implications of this biological system in connecting genomic variability and environment may shed new lights on adaptative mechanisms. We propose to call it VAMOS for variability modulation system. PMID:9258678

Validation of an in vitro exposure system for toxicity assessment of air-delivered nanomaterials

PubMed Central

Kim, Jong Sung; Peters, Thomas M.; O’Shaughnessy, Patrick T.; Adamcakova-Dodd, Andrea; Thorne, Peter S.

2013-01-01

To overcome the limitations of in vitro exposure of submerged lung cells to nanoparticles (NPs), we validated an integrated low flow system capable of generating and depositing airborne NPs directly onto cells at an air–liquid interface (ALI). The in vitro exposure system was shown to provide uniform and controlled dosing of particles with 70.3% efficiency to epithelial cells grown on transwells. This system delivered a continuous airborne exposure of NPs to lung cells without loss of cell viability in repeated 4 h exposure periods. We sequentially exposed cells to air-delivered copper (Cu) NPs in vitro to compare toxicity results to our prior in vivo inhalation studies. The evaluation of cellular dosimetry indicated that a large amount of Cu was taken up, dissolved and released into the basolateral medium (62% of total mass). Exposure to Cu NPs decreased cell viability to 73% (p < 0.01) and significantly (p < 0.05) elevated levels of lactate dehydrogenase, intracellular reactive oxygen species and interleukin-8 that mirrored our findings from subacute in vivo inhalation studies in mice. Our results show that this exposure system is useful for screening of NP toxicity in a manner that represents cellular responses of the pulmonary epithelium in vivo. PMID:22981796

Newborn screening healthcare information system based on service-oriented architecture.

PubMed

Hsieh, Sung-Huai; Hsieh, Sheau-Ling; Chien, Yin-Hsiu; Weng, Yung-Ching; Hsu, Kai-Ping; Chen, Chi-Huang; Tu, Chien-Ming; Wang, Zhenyu; Lai, Feipei

2010-08-01

In this paper, we established a newborn screening system under the HL7/Web Services frameworks. We rebuilt the NTUH Newborn Screening Laboratory's original standalone architecture, having various heterogeneous systems operating individually, and restructured it into a Service-Oriented Architecture (SOA), distributed platform for further integrity and enhancements of sample collections, testing, diagnoses, evaluations, treatments or follow-up services, screening database management, as well as collaboration, communication among hospitals; decision supports and improving screening accuracy over the Taiwan neonatal systems are also addressed. In addition, the new system not only integrates the newborn screening procedures among phlebotomy clinics, referral hospitals, as well as the newborn screening center in Taiwan, but also introduces new models of screening procedures for the associated, medical practitioners. Furthermore, it reduces the burden of manual operations, especially the reporting services, those were heavily dependent upon previously. The new system can accelerate the whole procedures effectively and efficiently. It improves the accuracy and the reliability of the screening by ensuring the quality control during the processing as well.

Effect of transient liquid flow on retention characteristics of screen acquisition systems. [design of Space Shuttle feed system

NASA Technical Reports Server (NTRS)

Cady, E. C.

1977-01-01

A design analysis, is developed based on experimental data, to predict the effects of transient flow and pressure surges (caused either by valve or pump operation, or by boiling of liquids in warm lines) on the retention performance of screen acquisition systems. A survey of screen liquid acquisition system applications was performed to determine appropriate system environment and classification. A screen model was developed which assumed that the screen device was a uniformly distributed composite orthotropic structure, and which accounted for liquid inflow/outflow, gas ingestion quality, screen stress, and liquid spill. A series of 177 tests using 13 specimens (5 screen meshes, 4 screen device construction/backup methods, and 2 orientations) with three test fluids (isopropyl alcohol, Freon 114, and LH2) provided data which verified important features of the screen model and resulted in a design tool which could accurately predict the transient startup performance acquisition devices.

Efficiency of the strong satisfiability checking procedure for reactive system specifications

NASA Astrophysics Data System (ADS)

Shimakawa, Masaya; Hagihara, Shigeki; Yonezaki, Naoki

2018-04-01

Reactive systems are those that interact with their environment. To develop reactive systems without defects, it is important to describe behavior specifications in a formal language, such as linear temporal logic, and to verify the specification. Specifically, it is important to check whether specifications satisfy the property called realizability. In previous studies, we have proposed the concept of strong satisfiability as a necessary condition for realizability. Although this property of reactive system specifications is a necessary condition, many practical unrealizable specifications are also strongly unsatisfiable. Moreover, we have previously shown the theoretical complexity of the strong satisfiability problem. In the current study, we investigate the practical efficiency of the strong satisfiability checking procedure and demonstrate that strong satisfiability can be checked more efficiently than realizability.

Covalent Docking of Large Libraries for the Discovery of Chemical Probes

PubMed Central

London, Nir; Miller, Rand M.; Krishnan, Shyam; Uchida, Kenji; Irwin, John J.; Eidam, Oliv; Gibold, Lucie; Cimermančič, Peter; Bonnet, Richard; Shoichet, Brian K.; Taunton, Jack

2014-01-01

Chemical probes that form a covalent bond with a protein target often show enhanced selectivity, potency, and utility for biological studies. Despite these advantages, protein-reactive compounds are usually avoided in high-throughput screening campaigns. Here we describe a general method (DOCKovalent) for screening large virtual libraries of electrophilic small molecules. We apply this method prospectively to discover reversible covalent fragments that target distinct protein nucleophiles, including the catalytic serine of AmpC β-lactamase and noncatalytic cysteines in RSK2, MSK1, and JAK3 kinases. We identify submicromolar to low-nanomolar hits with high ligand efficiency, cellular activity and selectivity, including the first reported reversible covalent inhibitors of JAK3. Crystal structures of inhibitor complexes with AmpC and RSK2 confirm the docking predictions and guide further optimization. As covalent virtual screening may have broad utility for the rapid discovery of chemical probes, we have made the method freely available through an automated web server (http://covalent.docking.org). PMID:25344815

PAINS in the Assay: Chemical Mechanisms of Assay Interference and Promiscuous Enzymatic Inhibition Observed during a Sulfhydryl-Scavenging HTS

PubMed Central

2015-01-01

Significant resources in early drug discovery are spent unknowingly pursuing artifacts and promiscuous bioactive compounds, while understanding the chemical basis for these adverse behaviors often goes unexplored in pursuit of lead compounds. Nearly all the hits from our recent sulfhydryl-scavenging high-throughput screen (HTS) targeting the histone acetyltransferase Rtt109 were such compounds. Herein, we characterize the chemical basis for assay interference and promiscuous enzymatic inhibition for several prominent chemotypes identified by this HTS, including some pan-assay interference compounds (PAINS). Protein mass spectrometry and ALARM NMR confirmed these compounds react covalently with cysteines on multiple proteins. Unfortunately, compounds containing these chemotypes have been published as screening actives in reputable journals and even touted as chemical probes or preclinical candidates. Our detailed characterization and identification of such thiol-reactive chemotypes should accelerate triage of nuisance compounds, guide screening library design, and prevent follow-up on undesirable chemical matter. PMID:25634295

Covalent docking of large libraries for the discovery of chemical probes.

PubMed

London, Nir; Miller, Rand M; Krishnan, Shyam; Uchida, Kenji; Irwin, John J; Eidam, Oliv; Gibold, Lucie; Cimermančič, Peter; Bonnet, Richard; Shoichet, Brian K; Taunton, Jack

2014-12-01

Chemical probes that form a covalent bond with a protein target often show enhanced selectivity, potency and utility for biological studies. Despite these advantages, protein-reactive compounds are usually avoided in high-throughput screening campaigns. Here we describe a general method (DOCKovalent) for screening large virtual libraries of electrophilic small molecules. We apply this method prospectively to discover reversible covalent fragments that target distinct protein nucleophiles, including the catalytic serine of AmpC β-lactamase and noncatalytic cysteines in RSK2, MSK1 and JAK3 kinases. We identify submicromolar to low-nanomolar hits with high ligand efficiency, cellular activity and selectivity, including what are to our knowledge the first reported reversible covalent inhibitors of JAK3. Crystal structures of inhibitor complexes with AmpC and RSK2 confirm the docking predictions and guide further optimization. As covalent virtual screening may have broad utility for the rapid discovery of chemical probes, we have made the method freely available through an automated web server (http://covalent.docking.org/).

Tropical diseases screening in immigrant patients with human immunodeficiency virus infection in Spain.

PubMed

Salvador, Fernando; Molina, Israel; Sulleiro, Elena; Burgos, Joaquín; Curran, Adrián; Van den Eynde, Eva; Villar del Saz, Sara; Navarro, Jordi; Crespo, Manuel; Ocaña, Inma; Ribera, Esteve; Falcó, Vicenç; Pahissa, Albert

2013-06-01

Latent parasitic infections can reactivate because of immunosuppression. We conducted a prospective observational study of all human immunodeficiency virus (HIV)-infected immigrants who visited the Infectious Diseases Department of the Hospital Universitari Vall d'Hebron, Barcelona, Spain, during June 2010-May 2011. Screening of the most prevalent tropical diseases (intestinal parasitosis, Chagas disease, leishmaniasis, malaria, schistosomiasis, and strongyloidiasis) was performed according to geographic origin. A total of 190 patients were included: 141 (74.2%) from Latin America, 41 (21.6%) from sub-Saharan Africa, and 8 (4.2%) from northern Africa. Overall, 36.8% (70 of 190) of the patients had at least one positive result for any parasitic disease: 5 patients with positive Trypanosoma cruzi serology, 11 patients with positive Schistosoma mansoni serology, 35 patients with positive Strongyloides stercoralis serology, 7 patients with positive Leishmania infantum serology, intestinal parasitosis were detected in 37 patients, malaria was diagnosed in one symptomatic patient. We propose a screening and management strategy of latent parasitic infections in immigrant patients infected with HIV.

[HCV and HBV seropositivity in university students of the State of Nuevo Leòn, Mexico].

PubMed

Flores-Castañeda, M S; García-Méndez, B L; Tijerina-Menchaca, R

1996-01-01

Viral hepatitis is a contagious disease. Patients infected with hepatitis B virus (HBV) or hepatitis C virus (HCV), may be either chronically symptomatic or asymptomatic, and suffer cirrhosis and high risk of hepatic carcinoma. Asymptomatic carriers of HBV surface antigen (HBs-Ag) or with anti-HCV antibodies are potentially infectious, and therefore a risk to public health. This work seeks to establish the frequency of seropositivity for HBs-Ag and anti-HCV antibodies in a population of 774 newly accepted students of the Medical School of the Autonomous University of Nuevo Leon, whose average age was 18 years. Second generation ELISA test were used to screen for HBs-Ag and anti-HCV antibodies. HBs-Ag was confirmed by a neutralization test and anti-HCV antibodies were confirmed by a RIBA test. Three sera were positive for HBs-Ag by ELISA and only one serum (0.13% of analyzed samples) was confirmed by the neutralization technique. On the other hand 12 sera were positive for anti-HCV antibodies by ELISA, and eight of these were confirmed by RIBA (1.03% of the analyzed samples). Intensive reactivity bands were found in two sera, and weak reactivity bands were found in six sera. ELISA screening for anti-HCV antibodies showed 0.5% of false positives. This study shows that the frequency of anti-HCV antibodies is 7.95% times higher than that found for HBs-Ag. All seropositive patients were asymptomatic and potentially infective. This demonstrates the need to routinely screen for HBs-Ag and anti-HCV antibodies to establish the prevalence of these diseases in our area.

Thermal preference predicts animal personality in Nile tilapia Oreochromis niloticus.

PubMed

Cerqueira, Marco; Rey, Sonia; Silva, Tome; Featherstone, Zoe; Crumlish, Margaret; MacKenzie, Simon

2016-09-01

Environmental temperature gradients provide habitat structure in which fish orientate and individual thermal choice may reflect an essential integrated response to the environment. The use of subtle thermal gradients likely impacts upon specific physiological and behavioural processes reflected as a suite of traits described by animal personality. In this study, we examine the relationship between thermal choice, animal personality and the impact of infection upon this interaction. We predicted that thermal choice in Nile tilapia Oreochromis niloticus reflects distinct personality traits and that under a challenge individuals exhibit differential thermal distribution. Nile tilapia were screened following two different protocols: 1) a suite of individual behavioural tests to screen for personality and 2) thermal choice in a custom-built tank with a thermal gradient (TCH tank) ranging from 21 to 33 °C. A first set of fish were screened for behaviour and then thermal preference, and a second set were tested in the opposite fashion: thermal then behaviour. The final thermal distribution of the fish after 48 h was assessed reflecting final thermal preferendum. Additionally, fish were then challenged using a bacterial Streptococcus iniae model infection to assess the behavioural fever response of proactive and reactive fish. Results showed that individuals with preference for higher temperatures were also classified as proactive with behavioural tests and reactive contemporaries chose significantly lower water temperatures. All groups exhibited behavioural fever recovering personality-specific thermal preferences after 5 days. Our results show that thermal preference can be used as a proxy to assess personality traits in Nile tilapia and it is a central factor to understand the adaptive meaning of animal personality within a population. Importantly, response to infection by expressing behavioural fever overrides personality-related thermal choice. © 2016 The Authors. Journal of Animal Ecology © 2016 British Ecological Society.

Audit of antenatal screening for syphilis and HIV in migrant and refugee women on the Thai-Myanmar border: a descriptive study

PubMed Central

McGready, Rose; Kang, Joy; Watts, Isabella; Tyrosvoutis, Mary Ellen G; Torchinsky, Miriam B.; Htut, Aung Myo; Tun, Nay Win; Keereecharoen, Lily; Wangsing, Chirapat; Hanboonkunupakarn, Borimas; Nosten, François H.

2015-01-01

Objective: The antenatal prevalence of syphilis and HIV/AIDS in migrants and refugees is poorly documented. The aim of this study was to audit the first year of routine syphilis screening in the same population and reassess the trends in HIV rates. Methods: From August 2012 to July 2013, 3600 pregnant women were screened for HIV (ELISA) and syphilis (VDRL with TPHA confirmation) at clinics along the Thai-Myanmar border. Results: Seroprevalence for HIV 0.47% (95% CI 0.30-0.76) (17/3,599), and syphilis 0.39% (95% CI 0.23-0.65) (14/3,592), were low. Syphilis was significantly lower in refugees (0.07% 95% CI 0.01-0.38) (1/1,469), than in migrants (0.61% 95% CI 0.36-1.04) (13/2,123). The three active (VDRL≥1:8 and TPHA reactive) syphilis cases with VDRL titres of 1:32 were easy to counsel and treat. Women with low VDRL titres (>75% were < 1:8) and TPHA reactive results, in the absence of symptoms and both the woman and her husband having only one sexual partner in their lifetime, and the inability to determine the true cause of the positive results presented ethical difficulties for counsellors. Conclusion: As HIV and syphilis testing becomes available in more and more settings, the potential impact of false positive results should be considered, especially in populations with low prevalence for these diseases. This uncertainty must be considered in order to counsel patients and partners accurately and safely about the results of these tests, without exposing women to increased risk for abuse or abandonment. Our findings highlight the complexities of counselling patients about these tests and the global need for more conclusive syphilis testing strategies. PMID:26664698

Optimization of protease-inhibitor interactions by randomizing adventitious contacts

PubMed Central

Komiyama, Tomoko; VanderLugt, Bryan; Fugère, Martin; Day, Robert; Kaufman, Randal J.; Fuller, Robert S.

2003-01-01

Polypeptide protease inhibitors are often found to inhibit targets with which they did not coevolve, as in the case of high-affinity inhibition of bacterial subtilisin by the leech inhibitor eglin c. Two kinds of contacts exist in such complexes: (i) reactive site loop-active site contacts and (ii) interactions outside of these that form the broader enzyme-inhibitor interface. We hypothesized that the second class of “adventitious” contacts could be optimized to generate significant increases in affinity for a target enzyme or discrimination of an inhibitor for closely related target proteases. We began with a modified eglin c, Arg-42–Arg-45–eglin, in which the reactive site loop had been optimized for subtilisin-related processing proteases of the Kex2/furin family. We randomized 10 potential adventitious contact residues and screened for inhibition of soluble human furin. Substitutions at one of these sites, Y49, were also screened against yeast Kex2 and human PC7. These screens identified not only variants that exhibited increased affinity (up to 20-fold), but also species that exhibited enhanced selectivity, that is, increased discrimination between the target enzymes (up to 41-fold for furin versus PC7 and 20-fold for PC7 versus furin). One variant, Asp-49–Arg-42–Arg-45–eglin, exhibited a Ki of 310 pM for furin and blocked furin-dependent processing of von Willebrand factor in COS-1 cells when added to the culture medium of the cells. The exploitation of adventitious contact sites may provide a versatile technique for developing potent, selective inhibitors for newly discovered proteases and could in principle be applied to optimize numerous protein–protein interactions. PMID:12832612

Syphilis screening in out-of-hospital care.

PubMed

Marvez-Valls, E; Weiss, S J; Ernst, A A; Johnson, W D

1995-07-01

To estimate the rates of syphilis infection in inner-city patients managed by prehospital providers, a convenience sampling of prehospital patients who had intravenous lines initiated was screened for syphilis over a nine-month study period from February 1992 through October 1992. In a university-affiliated inner-city emergency department served by a city ambulance company, patients 18 years of age or older transported via ambulance who had had intravenous lines initiated at the scene or en route had a Venereal Disease Research Laboratory (VDRL) and microhemagglutination-Treponema pallidum (MHA-TP) drawn and performed by the state laboratory as a routine serological test. If the results were reactive with no previous history of syphilis recorded in the state registry, the state health department and/or one of the authors of this study contacted the patient for follow-up treatment. Age, race, sex, and diagnostic category (medical, surgical/obstetric, or neuropsychiatric) were recorded. Results were checked with the state syphilis registry. Latent syphilis was defined as a reactive VDRL and MHA-TP with no prior history of infection or record of infection in the state syphilis registry. Chi-squared test was used in statistical analysis for comparisons among ages, races, and sexes, with P > .05 considered significant. Three hundred two subjects 18 years of age and older consenting to a screening VDRL and MHA-TP had serum drawn. Two hundred seventy-nine patients were enrolled in the study after 23 patients were excluded because of improper data collection or insufficient serum collection. There were 174 men (63%) and 105 women (37%), with 73 white (26%) and 199 African-Americans (71%).(ABSTRACT TRUNCATED AT 250 WORDS)

Executive Functioning, Cortisol Reactivity, and Symptoms of Psychopathology in Girls with Premature Adrenarche

PubMed Central

Sontag-Padilla, Lisa M.; Dorn, Lorah D.; Tissot, Abbigail; Susman, Elizabeth J.; Beers, Sue R.; Rose, Susan R.

2012-01-01

The study examined the interaction between early maturational timing [as measured by premature adrenarche (PA)] and executive functioning and cortisol reactivity on symptoms of psychopathology. The study included 76 girls aged 6 through 8 years (mean = 7.50; SD = .85) with PA (n = 40) and on-time adrenarche (n = 36). Girls completed a battery of psychological and neuropsychological tests and blood sampling for cortisol. Parents completed the Child Behavior Checklist. Results demonstrated that girls with PA with lower levels of executive functioning had higher externalizing and anxious symptoms compared to other girls. Additionally, girls with PA who demonstrated increases in serum cortisol had higher externalizing symptoms than those with stable patterns. Finally, girls with PA who demonstrated decreases in cortisol reported higher depressive symptoms. Findings from this study provide important information concerning the impact of cognitive functioning and stress reactivity on adjustment to early maturation in girls with PA. Results of this research may inform screening and intervention efforts for girls who may be at greatest risk for emotional and behavioral problems as a result of early maturation. PMID:22293005

Serologic evidence for human hantavirus infection in Peru.

PubMed

Castillo Oré, Roger M; Forshey, Brett M; Huaman, Alfredo; Villaran, Manuel V; Long, Kanya C; Kochel, Tadeusz J; Guevara, Carolina; Montgomery, Joel M; Alvarez, Carlos A; Vilcarromero, Stalin; Morrison, Amy C; Halsey, Eric S

2012-08-01

While human illness associated with hantavirus infection has been documented in many countries of South America, evidence for hantavirus transmission in Peru has been limited to the isolation of Rio Mamore virus from a pigmy mouse rat (Oligoryzomys microtis) in the Amazon city of Iquitos. To address the possibility of human hantavirus exposure in the region, we screened febrile patients reporting to health clinics in Iquitos from 2007 to 2010 for serological evidence of recent hantavirus infection. In addition, we conducted a serological survey for hantavirus-reactive IgG among healthy participants residing in Iquitos and rural areas surrounding the city. Through the febrile surveillance study, we identified 15 participants (0.3%; 15/5174) with IgM reactive to hantavirus (Andes virus) antigen, all with relatively mild, self-limited illness. From the cross-sectional serosurvey we found that 1.7% (36/2063) of residents of the Iquitos area had serum IgG reactive to one or more hantaviruses, with a higher prevalence in the urban population (2.2%, compared to 1.1% in rural areas). These results suggest that human infection with hantavirus has occurred in Peru.

Applicability of DFT model in reactive distillation

NASA Astrophysics Data System (ADS)

Staszak, Maciej

2017-11-01

The density functional theory (DFT) applicability to reactive distillation is discussed. Brief modeling techniques description of distillation and rectification with chemical reaction is provided as a background for quantum method usage description. The equilibrium and nonequilibrium distillation models are described for that purpose. The DFT quantum theory is concisely described. The usage of DFT in the modeling of reactive distillation is described in two parts. One of the fundamental and very important component of distillation modeling is vapor-liquid equilibrium description for which the DFT quantum approach can be used. The representative DFT models, namely COSMO-RS (Conductor like Screening Model for Real Solvents), COSMOSPACE (COSMO Surface Pair Activity Coefficient) and COSMO-SAC (SAC - segment activity coefficient) approaches are described. The second part treats the way in which the chemical reaction is described by means of quantum DFT method. The intrinsic reaction coordinate (IRC) method is described which is used to find minimum energy path of substrates to products transition. The DFT is one of the methods which can be used for that purpose. The literature data examples are provided which proves that IRC method is applicable for chemical reaction kinetics description.

A Comparison of the effectiveness of Mammographic Film-Screen and Standard Film-Screen in the Detection of Small Bone Fractures

PubMed Central

Sani, Karim Ghazikhanlou; Jafari, Mahmoodreza; Rostampoor, Nima

2011-01-01

The use of mammography film-screen is limited in general radiography. The purpose of this study was to compare the effectiveness of mammographic film-screen and standard film-screen systems in the detection of small bone fractures. Radiographs were taken from patients' extremities and neck areas using mammography film-screen and standard film-screen (n=57 each). Fourteen other radiographs were taken from other views (predominantly oblique views), making a total number of 128 radiographs. Paired radiographs, taken from the same areas, were compared by two radiologists in terms of image visual sharpness, presence of bony fractures, and soft tissue injuries. The surface dose received by patients in the two systems was also compared. The radiographs taken by mammography film-screen had a statistically better visual sharpness compared to those taken by the standard film-screen system. However, there was no statistically significant difference between the diagnostic accuracy of the two systems. Mammography film-screen was able to detect only one out of 57 lesions, whereas standard film-screen system did not detec any lesion. The surface dose received by patients in mammography film-screen was higher than that in standard film-screen system. The findings of the present study suggest that mammography film-screen may be recommended as a diagnostic tool for the detection of small fractures of tinny parts of body such as fingers, hand or foot. They also suggest that mammography film-screen has no advantage over standard film-screen for radiography of thick body parts such as neck and knee. PMID:23115417

Improved sugar yields from biomass sorghum feedstocks: comparing low-lignin mutants and pretreatment chemistries.

PubMed

Godin, Bruno; Nagle, Nick; Sattler, Scott; Agneessens, Richard; Delcarte, Jérôme; Wolfrum, Edward

2016-01-01

For biofuel production processes to be economically efficient, it is essential to maximize the production of monomeric carbohydrates from the structural carbohydrates of feedstocks. One strategy for maximizing carbohydrate production is to identify less recalcitrant feedstock cultivars by performing some type of experimental screening on a large and diverse set of candidate materials, or by identifying genetic modifications (random or directed mutations or transgenic plants) that provide decreased recalcitrance. Economic efficiency can also be increased using additional pretreatment processes such as deacetylation, which uses dilute NaOH to remove the acetyl groups of hemicellulose prior to dilute acid pretreatment. In this work, we used a laboratory-scale screening tool that mimics relevant thermochemical pretreatment conditions to compare the total sugar yield of three near-isogenic brown midrib ( bmr ) mutant lines and the wild-type (WT) sorghum cultivar. We then compared results obtained from the laboratory-scale screening pretreatment assay to a large-scale pretreatment system. After pretreatment and enzymatic hydrolysis, the bmr mutants had higher total sugar yields than the WT sorghum cultivar. Increased pretreatment temperatures increased reactivity for all sorghum samples reducing the differences observed at lower reaction temperatures. Deacetylation prior to dilute acid pretreatment increased the total sugar yield for all four sorghum samples, and reduced the differences in total sugar yields among them, but solubilized a sizable fraction of the non-structural carbohydrates. The general trends of increased total sugar yield in the bmr mutant compared to the WT seen at the laboratory scale were observed at the large-scale system. However, in the larger reactor system, the measured total sugar yields were lower and the difference in total sugar yield between the WT and bmr sorghum was larger. Sorghum bmr mutants, which have a reduced lignin content showed higher total sugar yields than the WT cultivar after dilute acid pretreatment and enzymatic hydrolysis. Deacetylation prior to dilute acid pretreatment increased the total sugar yield for all four sorghum samples. However, since deacetylation also solubilizes a large fraction of the non-structural carbohydrates, the ability to derive value from these solubilized sugars will depend greatly on the proposed conversion process.

Improved sugar yields from biomass sorghum feedstocks: comparing low-lignin mutants and pretreatment chemistries

DOE PAGES

Godin, Bruno; Nagle, Nick; Sattler, Scott; ...

2016-11-21

For biofuel production processes to be economically efficient, it is essential to maximize the production of monomeric carbohydrates from the structural carbohydrates of feedstocks. One strategy for maximizing carbohydrate production is to identify less recalcitrant feedstock cultivars by performing some type of experimental screening on a large and diverse set of candidate materials, or by identifying genetic modifications (random or directed mutations or transgenic plants) that provide decreased recalcitrance. Economic efficiency can also be increased using additional pretreatment processes such as deacetylation, which uses dilute NaOH to remove the acetyl groups of hemicellulose prior to dilute acid pretreatment. In thismore » work, we used a laboratory-scale screening tool that mimics relevant thermochemical pretreatment conditions to compare the total sugar yield of three near-isogenic brown midrib (bmr) mutant lines and the wild-type (WT) sorghum cultivar. We then compared results obtained from the laboratory-scale screening pretreatment assay to a large-scale pretreatment system. After pretreatment and enzymatic hydrolysis, the bmr mutants had higher total sugar yields than the WT sorghum cultivar. Increased pretreatment temperatures increased reactivity for all sorghum samples reducing the differences observed at lower reaction temperatures. Deacetylation prior to dilute acid pretreatment increased the total sugar yield for all four sorghum samples, and reduced the differences in total sugar yields among them, but solubilized a sizable fraction of the non-structural carbohydrates. The general trends of increased total sugar yield in the bmr mutant compared to the WT seen at the laboratory scale were observed at the large-scale system. However, in the larger reactor system, the measured total sugar yields were lower and the difference in total sugar yield between the WT and bmr sorghum was larger. Sorghum bmr mutants, which have a reduced lignin content showed higher total sugar yields than the WT cultivar after dilute acid pretreatment and enzymatic hydrolysis. In conclusion, deacetylation prior to dilute acid pretreatment increased the total sugar yield for all four sorghum samples. However, since deacetylation also solubilizes a large fraction of the non-structural carbohydrates, the ability to derive value from these solubilized sugars will depend greatly on the proposed conversion process.« less

Improved sugar yields from biomass sorghum feedstocks: comparing low-lignin mutants and pretreatment chemistries

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

Godin, Bruno; Nagle, Nick; Sattler, Scott

For biofuel production processes to be economically efficient, it is essential to maximize the production of monomeric carbohydrates from the structural carbohydrates of feedstocks. One strategy for maximizing carbohydrate production is to identify less recalcitrant feedstock cultivars by performing some type of experimental screening on a large and diverse set of candidate materials, or by identifying genetic modifications (random or directed mutations or transgenic plants) that provide decreased recalcitrance. Economic efficiency can also be increased using additional pretreatment processes such as deacetylation, which uses dilute NaOH to remove the acetyl groups of hemicellulose prior to dilute acid pretreatment. In thismore » work, we used a laboratory-scale screening tool that mimics relevant thermochemical pretreatment conditions to compare the total sugar yield of three near-isogenic brown midrib (bmr) mutant lines and the wild-type (WT) sorghum cultivar. We then compared results obtained from the laboratory-scale screening pretreatment assay to a large-scale pretreatment system. After pretreatment and enzymatic hydrolysis, the bmr mutants had higher total sugar yields than the WT sorghum cultivar. Increased pretreatment temperatures increased reactivity for all sorghum samples reducing the differences observed at lower reaction temperatures. Deacetylation prior to dilute acid pretreatment increased the total sugar yield for all four sorghum samples, and reduced the differences in total sugar yields among them, but solubilized a sizable fraction of the non-structural carbohydrates. The general trends of increased total sugar yield in the bmr mutant compared to the WT seen at the laboratory scale were observed at the large-scale system. However, in the larger reactor system, the measured total sugar yields were lower and the difference in total sugar yield between the WT and bmr sorghum was larger. Sorghum bmr mutants, which have a reduced lignin content showed higher total sugar yields than the WT cultivar after dilute acid pretreatment and enzymatic hydrolysis. In conclusion, deacetylation prior to dilute acid pretreatment increased the total sugar yield for all four sorghum samples. However, since deacetylation also solubilizes a large fraction of the non-structural carbohydrates, the ability to derive value from these solubilized sugars will depend greatly on the proposed conversion process.« less

A Proposal for a Subcritical Reactivity Meter based on Gandini and Salvatores' point kinetics equations for Multiplying Subcritical Systems

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

Pinto, Leticia N.; Dos Santos, Adimir

2015-07-01

Multiplying Subcritical Systems were for a long time poorly studied and its theoretical description remains with plenty open questions. Great interest on such systems arose partly due to the improvement of hybrid concepts, such as the Accelerator-Driven Systems (ADS). Along with the need for new technologies to be developed, further study and understanding of subcritical systems are essential also in more practical situations, such as in the case of a PWR criticalization in their physical startup tests. Point kinetics equations are fundamental to continuously monitor the reactivity behavior to a possible variation of external sources intensity. In this case, quicklymore » and accurately predicting power transients and reactivity becomes crucial. It is known that conventional Reactivity Meters cannot operate in subcritical levels nor describe the dynamics of multiplying systems in these conditions, by the very structure of the classical kinetic equations. Several theoretical models have been proposed to characterize the kinetics of such systems with special regard to the reactivity, as the one developed by Gandini and Salvatores among others. This work presents a discussion about the derivation of point kinetics equations for subcritical systems and the importance of considering the external source. From the point of view of the Gandini and Salvatores' point kinetics model and based on the experimental results provided by Lee and dos Santos, it was possible to develop an innovative approach. This article proposes an algorithm that describes the subcritical reactivity with external source, contributing to the advancement of studies in the field. (authors)« less

The effect of the systemic inflammatory response on plasma zinc and selenium adjusted for albumin.

PubMed

Ghashut, Rawia A; McMillan, Donald C; Kinsella, John; Vasilaki, Aikaterini T; Talwar, Dinesh; Duncan, Andrew

2016-04-01

The magnitude of systemic inflammatory response, as evidenced by C-reactive protein (CRP), is a major factor associated with lower zinc and selenium. They may also be influenced by their binding proteins, such as albumin. The aim of the present study was to examine the relationships between plasma zinc, selenium and the systemic inflammatory response in a large cohort of patients referred for nutritional screen and also to examine these relationships in patients with critical illness. Patients referred for nutritional assessment of zinc (n = 743) and selenium (n = 833) and 114 patients with critical illness were examined. Intra-assay imprecision was <10% for these analytes. In the nutritional screen cohort, plasma zinc was significantly associated with CRP (rs = -0.404, p < 0.001) and albumin (rs = 0.588, p < 0.001). For each CRP category (≤10, 11-80, >80 mg/l) the zinc/albumin ratio x100 was similar (31, 33 and 32 respectively, p = 0.029). Plasma selenium was significantly associated with CRP (rs = -0.489, p < 0.001) and albumin (rs = 0.600, p < 0.001). With increasing CRP category (≤10, 11-80, >80 mg/l) the selenium/albumin ratio ×100 was lower (2.3, 2.1 and 1.8 respectively, p < 0.001). Similar relationships were also observed in the cohort of patients with critical illness. Plasma zinc was associated with both CRP and albumin. The impact of the systemic inflammatory response could be largely adjusted by albumin concentrations. Plasma selenium was associated with both CRP and albumin. The impact of the systemic inflammatory response on plasma selenium concentrations could not be reasonably adjusted by albumin concentrations. Copyright © 2015 Elsevier Ltd and European Society for Clinical Nutrition and Metabolism. All rights reserved.

Drug-induced idiosyncratic hepatotoxicity: prevention strategy developed after the troglitazone case.

PubMed

Ikeda, Toshihiko

2011-01-01

Troglitazone induced an idiosyncratic, hepatocellular injury-type hepatotoxicity in humans. Statistically, double null genotype of glutathione S-transferase isoforms, GSTT1 and GSTM1, was a risk factor, indicating a low activity of the susceptible patients in scavenging chemically reactive metabolites. CYP3A4 and CYP2C8 were involved in the metabolic activation and CYP3A4 was inducible by repeated administrations of troglitazone. The genotype analysis, however, indicated that the metabolic idiosyncrasy resides in the degradation of but not in the production of the toxic metabolites of troglitazone. Antibody against hepatic aldolase B was detected in the case patients, suggesting involvement of immune reaction in the toxic mechanism. Troglitazone induced apoptotic cell death in human hepatocytes at a high concentration, and this property may have served as the immunological danger signal, which is thought to play an important role in activating immune reactions. Hypothesis is proposed in analogy to the virus-induced hepatitis. After the troglitazone-case, pharmaceutical companies implemented screening systems for chemically reactive metabolites at early stage of drug development, taking both the amount of covalent binding to the proteins in vitro and the assumed clinical dose level into consideration. At the post-marketing stage, gene analyses of the case patients, if any, to find pharmacogenetic biomarkers could be a powerful tool for contraindicating to the risky patients.

A systematic review and meta-analyses on C-reactive protein in relation to periodontitis.

PubMed

Paraskevas, Spiros; Huizinga, John D; Loos, Bruno G

2008-04-01

Elevated plasma C-reactive protein (CRP) is regarded as a risk predictor for cardiovascular diseases. This systematic review explored the robustness of observations that CRP is elevated in periodontitis. Similarly, the effect of periodontal therapy on CRP levels was investigated. Selection of publications was based on: (1) cross-sectional (case-control) studies; (2) longitudinal (treatment) studies; (3) high-sensitivity CRP measurement; (4) median and/or mean (+/-SD) values presented; and (5) subjects with no systemic disorders. Screening of the initially 448 identified studies and reference checking resulted in 18 suitable papers. The majority of the studies showed that CRP levels are higher in patients than in controls. Often, studies showed that patients had CRP levels >2.1 mg/l. A meta-analysis of 10 cross-sectional studies showed that the weighted mean difference (WMD) of CRP between patients and controls was 1.56 mg/l (p<0.00001). Evidence from available treatment studies (n=6) showed lower levels of CRP after periodontal therapy. Eligible treatment studies in a meta-analysis demonstrated a WMD of reductions of CRP after therapy of 0.50 mg/L (95% CI 0.08-0.93) (p=0.02). There is strong evidence from cross-sectional studies that plasma CRP in periodontitis is elevated compared with controls. There is modest evidence on the effect of periodontal therapy in lowering the levels of CRP.

Human anti-HIV IgM detection by the OraQuick ADVANCE® Rapid HIV 1/2 Antibody Test.

PubMed

Guillon, Geraldine; Yearwood, Graham; Snipes, Casey; Boschi, Daniel; Reed, Michael R

2018-01-01

The Centers for Disease Control and Prevention (CDC) and many public health jurisdictions continue to advocate for the most sensitive rapid HIV test that is available. Currently, the recommendation is to utilize tests that can detect HIV infection biomarkers within 30 days of infection, when initial immune responses are mounted. The infected patient's IgM response is often used to detect acute infection within a 20-25 days window after infection. This requirement applies to lab-based testing with automated analyzers and rapid, point of care (POC) testing used for screening in a non-clinical setting. A recent study has demonstrated that POC tests using a Protein A-based detection system can detect samples with predominantly HIV-1 IgM reactivity (Moshgabadi et al., 2015). The OraQuick ADVANCE ® Rapid HIV-1/2 Antibody Test (OraQuick ADVANCE ®) also uses Protein A as the detection protein in the antibody-binding colloidal gold conjugate, so it is expected that the OraQuick ADVANCE ® Test will also detect samples with predominantly IgM reactivity. This report definitively demonstrates that the OraQuick ADVANCE ® Test can detect IgM antibodies during an acute infection window period of approximately 20-25 days after infection, and is therefore suitable for use in testing environments requiring adherence to current CDC recommendations.

Delayed tuberculin reactivity in persons of Indochinese origin: implications for preventive therapy.

PubMed

Robertson, J M; Burtt, D S; Edmonds, K L; Molina, P L; Kiefe, C I; Ellner, J J

1996-05-01

To 1) study a variant delayed reaction to tuberculin testing as a way to enhance screening for tuberculosis among high-risk persons and 2) correlate the delayed reaction with lymphocyte blastogenesis. Cross-sectional study. 2 public health department clinics in North Carolina. 121 adults who had recently emigrated from Vietnam to North Carolina and who were ethnic Vietnamese and ethnic Dega, a minority population group from the central highlands region of Vietnam. Medical history, physical examination, laboratory evaluation, and standard purified protein derivative (PPD) testing (Mantoux method). Skin test results were read at 72 hours and again at 6 days. Variant reactivity was defined as induration of less than 10 mm at 72 hours that, when reassessed at 6 days, had increased in size to 10 mm or greater. Persons with negative (n=54) and variant (n=32) PPD results also had booster testing at 10 to 12 weeks. Serum samples were obtained from 57 participants for lymphocyte blastogenesis studies. 26% of participants had variant tuberculin reactivity. Variant reactivity was strongly associated with booster positivity: Sixty-five percent of persons with variant PPD results had booster positivity compared with 16% of persons with negative PPD results (P<0.001). The lymphocyte blastogenesis response of persons with variant PPD results was between the response of persons with negative PPD results and that of persons with positive PPD results. Variant reactivity in this high-risk group was a predictor of booster positivity. Together with the blastogenic response pattern, this association strongly suggests that variant reactivity has a high positive predictive value for tuberculous infection. Clinicians should incorporate these findings into their approach for choosing candidates for preventive therapy.

Inflammation and psychotropic drugs: the relationship between C-reactive protein and antipsychotic drug levels.

PubMed

Hefner, Gudrun; Shams, Mohamed E E; Unterecker, Stefan; Falter, Tanja; Hiemke, Christoph

2016-05-01

In psychiatric clinical practice, there is a need to identify psychotropic drugs whose metabolisms are prone to be altered with increased inflammatory activity in an individual patient. The aim of this study was to find out whether elevated serum levels (≥5 mg/l) of C-reactive protein (CRP), an established laboratory marker of infection and inflammation, are associated with increased serum concentrations of the atypical antipsychotic drugs clozapine, quetiapine, and risperidone. Therapeutic drug monitoring request forms of patients whose antipsychotic drug concentrations had been measured under conditions of normal (<5 mg/l) and pathological (>5 mg/l) levels of C-reactive protein were retrospectively screened. The serum concentrations in relation to the daily doses [concentration per dose (C/D) (ng/mL/mg)] and the metabolic ratios [ratio of concentrations (metabolite/drug)] were compared intraindividually by the Wilcoxon signed rank test. To the study effects of the intensity of infections on drug concentrations, C-reactive protein and C/D levels were submitted to Spearman's correlation analysis. Elevated levels of C-reactive protein were found in 105 patients. They were significantly associated with elevated values in C/D for clozapine (n = 33, P < 0.01) and risperidone (n = 40, P < 0.01). A trend for an increase was found for quetiapine (n = 32, P = 0.05). Median increases were 48.0 % (clozapine), 11.9 % (quetiapine), and 24.2 % (active moiety of risperidone), respectively. In patients who exhibit signs of inflammation or infection with increased C-reactive protein values during psychopharmacological treatment, especially under clozapine and risperidone, therapeutic drug monitoring is recommendable in order to minimize the risk of intoxications due to elevated drug concentrations.

Detection of Virus-Specific CD8+ T Cells With Cross-Reactivity Against Alloantigens: Potency and Flaws of Present Experimental Methods

PubMed Central

van den Heuvel, Heleen; Heutinck, Kirstin M.; van der Meer-Prins, Ellen P.M.W.; Yong, Si La; Claas, Frans H.J.; ten Berge, Ineke J.M.

2015-01-01

Background Virus-specific T cells have the intrinsic capacity to cross-react against allogeneic HLA antigens, a phenomenon known as heterologous immunity. In transplantation, these cells may contribute to the alloimmune response and negatively impact graft outcome. This study describes the various techniques that can be used to detect heterologous immune responses of virus-specific CD8+ T cells against allogeneic HLA antigens. The strengths and weaknesses of the different approaches are discussed and illustrated by experimental data. Methods Mixed-lymphocyte reactions (MLRs) were performed to detect allo-HLA cross-reactivity of virus-specific CD8+ T cells in total peripheral blood mononuclear cells. T-cell lines and clones were generated to confirm allo-HLA cross-reactivity by IFNγ production and cytotoxicity. In addition, the conventional MLR protocol was adjusted by introducing a 3-day resting phase and subsequent short restimulation with alloantigen or viral peptide, whereupon the expression of IFNγ, IL-2, CD107a, and CD137 was determined. Results The accuracy of conventional MLR is challenged by potential bystander activation. T-cell lines and clones can circumvent this issue, yet their generation is laborious and time-consuming. Using the adjusted MLR and restimulation protocol, we found that only truly cross-reactive T cells responded to re-encounter of alloantigen and viral peptide, whereas bystander-activated cells did not. Conclusions The introduction of a restimulation phase improved the accuracy of the MLR as a screening tool for the detection of allo-HLA cross-reactivity by virus-specific CD8+ T cells at bulk level. For detailed characterization of cross-reactive cells, T-cell lines and clones remain the golden standard. PMID:27500209

Screening strategies for tubal factor subfertility.

PubMed

den Hartog, J E; Lardenoije, C M J G; Severens, J L; Land, J A; Evers, J L H; Kessels, A G H

2008-08-01

Different screening strategies exist to estimate the risk of tubal factor subfertility, preceding laparoscopy. Three screening strategies, comprising Chlamydia trachomatis IgG antibody testing (CAT), high-sensitivity C-reactive protein (hs-CRP) testing and hysterosalpingography (HSG), were explored using laparoscopy as reference standard and the occurrence of a spontaneous pregnancy as a surrogate marker for the absence of tubal pathology. In this observational study, 642 subfertile women, who underwent tubal testing, participated. Data on serological testing, HSG, laparoscopy and interval conception were collected. Multiple imputations were used to compensate for missing data. Strategy A (HSG) has limited value in estimating the risk of tubal pathology. Strategy B (CAT-->HSG) shows that CAT significantly discerns patients with a high versus low risk of tubal pathology, whereas HSG following CAT has no additional value. Strategy C (CAT-->hs-CRP-->HSG) demonstrates that hs-CRP may be valuable in CAT-positive patients only and HSG has no additional value. CAT is proposed as first screening test for tubal factor subfertility. In CAT-negative women, HSG may be performed because of its high specificity and fertility-enhancing effect. In CAT-positive women, hs-CRP seems promising, whereas HSG has no additional value. The position and timing of laparoscopy deserves critical reappraisal.

Towards medicinal mechanochemistry: evolution of milling from pharmaceutical solid form screening to the synthesis of active pharmaceutical ingredients (APIs).

PubMed

Tan, Davin; Loots, Leigh; Friščić, Tomislav

2016-06-14

This overview highlights the emergent area of mechanochemical reactions for making active pharmaceutical ingredients (APIs), and covers the latest advances in the recently established area of mechanochemical screening and synthesis of pharmaceutical solid forms, specifically polymorphs, cocrystals, salts and salt cocrystals. We also provide an overview of the most recent developments in pharmaceutical uses of mechanochemistry, including real-time reaction monitoring, techniques for polymorph control and approaches for continuous manufacture using twin screw extrusion, and more. Most importantly, we show how the overlap of previously unrelated areas of mechanochemical screening for API solid forms, organic synthesis by milling, and mechanochemical screening for molecular recognition, enables the emergence of a new research discipline in which different aspects of pharmaceutical and medicinal chemistry are addressed through mechanochemistry rather than through conventional solution-based routes. The emergence of such medicinal mechanochemistry is likely to have a strong impact on future pharmaceutical and medicinal chemistry, as it offers not only access to materials and reactivity that are sometimes difficult or even impossible to access from solution, but can also provide a general answer to the demands of the pharmaceutical industry for cleaner, safer and efficient synthetic solutions.

Screening for latent and active tuberculosis infection in the elderly at admission to residential care homes: A cost-effectiveness analysis in an intermediate disease burden area.

PubMed

Li, Jun; Yip, Benjamin H K; Leung, Chichiu; Chung, Wankyo; Kwok, Kin On; Chan, Emily Y Y; Yeoh, Engkiong; Chung, Puihong

2018-01-01

Tuberculosis (TB) in the elderly remains a challenge in intermediate disease burden areas like Hong Kong. Given a higher TB burden in the elderly and limited impact of current case-finding strategy by patient-initiated pathway, proactive screening approaches for the high-risk group could be optimal and increasingly need targeted economic evaluations. In this study, we examined whether and under what circumstance the screening strategies are cost-effective compared with no screening strategy for the elderly at admission to residential care homes. A decision analytic process based on Markov model was adopted to evaluate the cost-effectiveness of four strategies: (i) no screening, (ii) TB screening (CXR) and (iii) TB screening (Xpert) represent screening for TB in symptomatic elderly by chest X-ray and Xpert® MTB/RIF respectively, and (iv) LTBI/TB screening represents screening for latent and active TB infection by QuantiFERON®-TB Gold In-Tube and chest X-ray. The target population was a hypothetical cohort of 65-year-old people, using a health service provider perspective and a time horizon of 20 years. The outcomes were direct medical costs, life-years and quality-adjusted life-years (QALYs) measured by incremental cost-effectiveness ratio (ICER). In the base-case analysis, no screening was the most cost-saving; TB screening (CXR) was dominated by TB screening (Xpert); LTBI/TB screening resulted in more life-years and QALYs accrued. The ICERs of LTBI/TB screening were US$19,712 and US$29,951 per QALY gained compared with no screening and TB screening (Xpert), respectively. At the willingness-to-pay threshold of US$50,000 per QALY gained, LTBI/TB screening was the most cost-effective when the probability of annual LTBI reactivation was greater than 0.155% and acceptability of LTBI/TB screening was greater than 38%. In 1,000 iterations of Monte Carlo simulation, the probabilities of no screening, TB screening (CXR), TB screening (Xpert), and LTBI/TB screening to be cost-effective were 0, 1.3%, 20.1%, and 78.6% respectively. Screening for latent and active TB infection in Hong Kong elderly people at admission to residential care homes appears to be highly effective and cost-effective. The key findings may be the next key factor to bring down TB endemic in the elderly population among intermediate TB burden areas.

Sex differences in physiological reactivity to acute psychosocial stress in adolescence.

PubMed

Ordaz, Sarah; Luna, Beatriz

2012-08-01

Females begin to demonstrate greater negative affective responses to stress than males in adolescence. This may reflect the concurrent emergence of underlying differences in physiological response systems, including corticolimbic circuitries, the hypothalamic-pituitary-adrenal axis (HPAA), and the autonomic nervous system (ANS). This review examines when sex differences in physiological reactivity to acute psychosocial stress emerge and the directionality of these differences over development. Indeed, the literature indicates that sex differences emerge during adolescence and persist into adulthood for all three physiological response systems. However, the directionality of the differences varies by system. The emerging corticolimbic reactivity literature suggests greater female reactivity, particularly in limbic regions densely innervated by gonadal hormone receptors. In contrast, males generally show higher levels of HPAA and ANS reactivity. We argue that the contrasting directionality of corticolimbic and peripheral physiological responses may reflect specific effects of gonadal hormones on distinct systems and also sex differences in evolved behavioral responses that demand different levels of peripheral physiological activation. Studies that examine both subjective reports of negative affect and physiological responses indicate that beginning in adolescence, females respond to acute stressors with more intense negative affect than males despite their comparatively lower peripheral physiological responses. This dissociation is not clearly explained by sex differences in the strength of the relationship between physiological and subjective responses. We suggest that females' greater subjective responsivity may instead arise from a greater activity in brain regions that translate stress responses to subjective awareness in adolescence. Future research directions include investigations of the role of pubertal hormones in physiological reactivity across all systems, examining the relationship of corticolimbic reactivity and negative affect, and sex differences in emotion regulation processes. Copyright © 2012 Elsevier Ltd. All rights reserved.

Sex differences in physiological reactivity to acute psychosocial stress in adolescence

PubMed Central

Ordaz, Sarah; Luna, Beatriz

2012-01-01

Summary Females begin to demonstrate greater negative affective responses to stress than males in adolescence. This may reflect the concurrent emergence of underlying differences in physiological response systems, including corticolimbic circuitries, the hypothalamic—pituitary— adrenal axis (HPAA), and the autonomic nervous system (ANS). This review examines when sex differences in physiological reactivity to acute psychosocial stress emerge and the directionality of these differences over development. Indeed, the literature indicates that sex differences emerge during adolescence and persist into adulthood for all three physiological response systems. However, the directionality of the differences varies by system. The emerging corti-colimbic reactivity literature suggests greater female reactivity, particularly in limbic regions densely innervated by gonadal hormone receptors. In contrast, males generally show higher levels of HPAA and ANS reactivity. We argue that the contrasting directionality of corticolimbic and peripheral physiological responses may reflect specific effects of gonadal hormones on distinct systems and also sex differences in evolved behavioral responses that demand different levels of peripheral physiological activation. Studies that examine both subjective reports of negative affect and physiological responses indicate that beginning in adolescence, females respond to acute stressors with more intense negative affect than males despite their comparatively lower peripheral physiological responses. This dissociation is not clearly explained by sex differences in the strength of the relationship between physiological and subjective responses. We suggest that females' greater subjective responsivity may instead arise from a greater activity in brain regions that translate stress responses to subjective awareness in adolescence. Future research directions include investigations of the role of pubertal hormones in physiological reactivity across all systems, examining the relationship of corticolimbic reactivity and negative affect, and sex differences in emotion regulation processes. PMID:22281210

Children's biological responsivity to acute stress predicts concurrent cognitive performance.

PubMed

Roos, Leslie E; Beauchamp, Kathryn G; Giuliano, Ryan; Zalewski, Maureen; Kim, Hyoun K; Fisher, Philip A

2018-04-10

Although prior research has characterized stress system reactivity (i.e. hypothalamic-pituitary-adrenal axis, HPAA; autonomic nervous system, ANS) in children, it has yet to examine the extent to which biological reactivity predicts concurrent goal-directed behavior. Here, we employed a stressor paradigm that allowed concurrent assessment of both stress system reactivity and performance on a speeded-response task to investigate the links between biological reactivity and cognitive function under stress. We further investigated gender as a moderator given previous research suggesting that the ANS may be particularly predictive of behavior in males due to gender differences in socialization. In a sociodemographically diverse sample of young children (N = 58, M age = 5.38 yrs; 44% male), individual differences in sociodemographic covariates (age, household income), HPAA (i.e. cortisol), and ANS (i.e. respiratory sinus arrhythmia, RSA, indexing the parasympathetic branch; pre-ejection period, PEP, indexing the sympathetic branch) function were assessed as predictors of cognitive performance under stress. We hypothesized that higher income, older age, and greater cortisol reactivity would be associated with better performance overall, and flexible ANS responsivity (i.e. RSA withdrawal, PEP shortening) would be predictive of performance for males. Overall, females performed better than males. Two-group SEM analyses suggest that, for males, greater RSA withdrawal to the stressor was associated with better performance, while for females, older age, higher income, and greater cortisol reactivity were associated with better performance. Results highlight the relevance of stress system reactivity to cognitive performance under stress. Future research is needed to further elucidate for whom and in what situations biological reactivity predicts goal-directed behavior.

A pathogenesis assay using Saccharomyces cerevisiae and Caenorhabditis elegans reveals novel roles for yeast AP-1, Yap1, and host dual oxidase BLI-3 in fungal pathogenesis.

PubMed

Jain, Charu; Yun, Meijiang; Politz, Samuel M; Rao, Reeta Prusty

2009-08-01

Treatment of systemic fungal infections is difficult because of the limited number of antimycotic drugs available. Thus, there is an immediate need for simple and innovative systems to assay the contribution of individual genes to fungal pathogenesis. We have developed a pathogenesis assay using Caenorhabditis elegans, an established model host, with Saccharomyces cerevisiae as the invading fungus. We have found that yeast infects nematodes, causing disease and death. Our data indicate that the host produces reactive oxygen species (ROS) in response to fungal infection. Yeast mutants sod1Delta and yap1Delta, which cannot withstand ROS, fail to cause disease, except in bli-3 worms, which carry a mutation in a dual oxidase gene. Chemical inhibition of the NADPH oxidase activity abolishes ROS production in worms exposed to yeast. This pathogenesis assay is useful for conducting systematic, whole-genome screens to identify fungal virulence factors as alternative targets for drug development and exploration of host responses to fungal infections.

Evaluation of an enzyme immunoassay system for measuring herpes simplex virus (HSV) type 1-specific and HSV type 2-specific IgG antibodies.

PubMed

Prince, H E; Ernst, C E; Hogrefe, W R

2000-01-01

MRL Diagnostics has developed a dual enzyme immunoassay (EIA) system that employs the recombinant Herpes Simplex Virus (HSV) type-specific glycoproteins G1 (HSV1) and G2 (HSV2) to detect HSV type-specific IgG antibodies. This system was evaluated using 155 consecutive sera previously tested in a conventional dual EIA system (Zeus) that employs multiple HSV1 and HSV2 proteins to detect type-common as well as type-specific antibodies. Sera were also analyzed by Western blot to determine the true HSV type-specific IgG reactivity pattern. Of 110 sera giving concordant reactivity patterns in the MRL and Zeus EIA systems, 108 (98%) also displayed concordant Western blot patterns; two sera gave false positive HSV2 reactivity in both EIA systems. Of 45 sera giving discordant MRL and Zeus EIA reactivity patterns, 41 (91%) displayed a Western blot reactivity pattern that matched the MRL reactivity pattern. Both the HSV1 IgG component and the HSV2 IgG component of the MRL EIA system were 100% sensitive and > 95% specific. In contrast, the Zeus HSV1 IgG EIA was 98% sensitive and 79% specific, and the Zeus HSV2 IgG EIA was 85% sensitive and 79% specific. An analysis of the distribution of index values in the MRL EIA system showed that low-positive values (1.0-3.0) were rare, but, when detected, often represented false positive results; only 11 MRL low-positive results were observed, but all 6 MRL false positive results were found within this low-positive subgroup. These findings show that the MRL dual EIA system effectively detects HSV type-specific IgG antibodies. Copyright 2000 Wiley-Liss, Inc.

Acute HIV Discovered During Routine HIV Screening With HIV Antigen-Antibody Combination Tests in 9 US Emergency Departments.

PubMed

White, Douglas A E; Giordano, Thomas P; Pasalar, Siavash; Jacobson, Kathleen R; Glick, Nancy R; Sha, Beverly E; Mammen, Priya E; Hunt, Bijou R; Todorovic, Tamara; Moreno-Walton, Lisa; Adomolga, Vincent; Feaster, Daniel J; Branson, Bernard M

2018-01-05

Newer combination HIV antigen-antibody tests allow detection of HIV sooner after infection than previous antibody-only immunoassays because, in addition to HIV-1 and -2 antibodies, they detect the HIV-1 p24 antigen, which appears before antibodies develop. We determine the yield of screening with HIV antigen-antibody tests and clinical presentations for new diagnoses of acute and established HIV infection across US emergency departments (EDs). This was a retrospective study of 9 EDs in 6 cities with HIV screening programs that integrated laboratory-based antigen-antibody tests between November 1, 2012, and December 31, 2015. Unique patients with newly diagnosed HIV infection were identified and classified as having either acute HIV infection or established HIV infection. Acute HIV infection was defined as a repeatedly reactive antigen-antibody test result, a negative HIV-1/HIV-2 antibody differentiation assay, or Western blot result, but detectable HIV ribonucleic acid (RNA); established HIV infection was defined as a repeatedly reactive antigen-antibody test result and a positive HIV-1/HIV-2 antibody differentiation assay or Western blot result. The primary outcomes were the number of new HIV diagnoses and proportion of patients with laboratory-defined acute HIV infection. Secondary outcomes compared reason for visit and the clinical presentation of acute HIV infection. In total, 214,524 patients were screened for HIV and 839 (0.4%) received a new diagnosis, of which 122 (14.5%) were acute HIV infection and 717 (85.5%) were established HIV infection. Compared with patients with established HIV infection, those with acute HIV infection were younger, had higher RNA and CD4 counts, and were more likely to have viral syndrome (41.8% versus 6.5%) or fever (14.3% versus 3.4%) as their reason for visit. Most patients with acute HIV infection displayed symptoms attributable to acute infection (median symptom count 5 [interquartile range 3 to 6]), with fever often accompanied by greater than or equal to 3 other symptoms (60.7%). ED screening using antigen-antibody tests identifies previously undiagnosed HIV infection at proportions that exceed the Centers for Disease Control and Prevention's screening threshold, with the added yield of identifying acute HIV infection in approximately 15% of patients with a new diagnosis. Patients with acute HIV infection often seek ED care for symptoms related to seroconversion. Copyright © 2017 American College of Emergency Physicians. Published by Elsevier Inc. All rights reserved.

Viewing-zone scanning holographic display using a MEMS spatial light modulator.

PubMed

Takaki, Yasuhiro; Fujii, Keisuke

2014-10-06

Horizontally scanning holography using a spatial light modulator based on microelectromechanical system, which we previously proposed for enlarging both the screen size and the viewing zone, utilized a screen scanning system with elementary holograms being scanned horizontally on the screen. In this study, to enlarge the screen size and the viewing zone, we propose a viewing-zone scanning system with enlarged hologram screen and horizontally scanned reduced viewing zone. The reduced viewing zone is localized using converging light emitted from the screen, and the entire screen can be viewed from the localized viewing zone. An experimental system was constructed, and we demonstrated the generation of reconstructed images with a screen size of 2.0 in, a viewing zone width of 437 mm at a distance of 600 mm from the screen, and a frame rate of 60 Hz.

Relational victimization and depressive symptoms: The role of autonomic nervous system reactivity in emerging adults.

PubMed

Holterman, Leigh Ann; Murray-Close, Dianna K; Breslend, Nicole L

2016-12-01

The goal of the current study was to investigate the association between relational victimization, defined as being the target of aggressive acts that damage relationships (e.g., gossip, social exclusion) and depressive symptoms during the relatively understudied developmental period of emerging adulthood. In addition, as individual differences in stress reactivity may influence the outcomes associated with victimization by peers, the moderating roles of sympathetic nervous system (SNS; as measured by skin conductance reactivity) and parasympathetic nervous system (PNS; as measured by respiratory sinus arrhythmia) reactivity to social and non-social stressors were examined. Findings indicated that relational victimization was positively related to depressive symptoms in individuals demonstrating coactivation (i.e., high SNS and PNS reactivity) and coinhibition (blunted SNS and PNS reactivity) to both social and non-social stressor tasks. These patterns may reflect a breakdown of regulation in the body's physiological response to stress, thus increasing risk for depressive symptoms in the context of peer stress. Findings highlight potential areas for future interventions. Copyright © 2016 Elsevier B.V. All rights reserved.

Developmental origins of infant stress reactivity profiles: A multi-system approach.

PubMed

Rash, Joshua A; Thomas, Jenna C; Campbell, Tavis S; Letourneau, Nicole; Granger, Douglas A; Giesbrecht, Gerald F

2016-07-01

This study tested the hypothesis that maternal physiological and psychological variables during pregnancy discriminate between theoretically informed infant stress reactivity profiles. The sample comprised 254 women and their infants. Maternal mood, salivary cortisol, respiratory sinus arrhythmia (RSA), and salivary α-amylase (sAA) were assessed at 15 and 32 weeks gestational age. Infant salivary cortisol, RSA, and sAA reactivity were assessed in response to a structured laboratory frustration task at 6 months of age. Infant responses were used to classify them into stress reactivity profiles using three different classification schemes: hypothalamic-pituitary-adrenal (HPA)-axis, autonomic, and multi-system. Discriminant function analyses evaluated the prenatal variables that best discriminated infant reactivity profiles within each classification scheme. Maternal stress biomarkers, along with self-reported psychological distress during pregnancy, discriminated between infant stress reactivity profiles. These results suggest that maternal psychological and physiological states during pregnancy have broad effects on the development of the infant stress response systems. © 2016 Wiley Periodicals, Inc. Dev Psychobiol 58: 578-599, 2016. © 2016 Wiley Periodicals, Inc.

The Reactive Species Interactome: Evolutionary Emergence, Biological Significance, and Opportunities for Redox Metabolomics and Personalized Medicine.

PubMed

Cortese-Krott, Miriam M; Koning, Anne; Kuhnle, Gunter G C; Nagy, Peter; Bianco, Christopher L; Pasch, Andreas; Wink, David A; Fukuto, Jon M; Jackson, Alan A; van Goor, Harry; Olson, Kenneth R; Feelisch, Martin

2017-10-01

Oxidative stress is thought to account for aberrant redox homeostasis and contribute to aging and disease. However, more often than not, administration of antioxidants is ineffective, suggesting that our current understanding of the underlying regulatory processes is incomplete. Recent Advances: Similar to reactive oxygen species and reactive nitrogen species, reactive sulfur species are now emerging as important signaling molecules, targeting regulatory cysteine redox switches in proteins, affecting gene regulation, ion transport, intermediary metabolism, and mitochondrial function. To rationalize the complexity of chemical interactions of reactive species with themselves and their targets and help define their role in systemic metabolic control, we here introduce a novel integrative concept defined as the reactive species interactome (RSI). The RSI is a primeval multilevel redox regulatory system whose architecture, together with the physicochemical characteristics of its constituents, allows efficient sensing and rapid adaptation to environmental changes and various other stressors to enhance fitness and resilience at the local and whole-organism level. To better characterize the RSI-related processes that determine fluxes through specific pathways and enable integration, it is necessary to disentangle the chemical biology and activity of reactive species (including precursors and reaction products), their targets, communication systems, and effects on cellular, organ, and whole-organism bioenergetics using system-level/network analyses. Understanding the mechanisms through which the RSI operates will enable a better appreciation of the possibilities to modulate the entire biological system; moreover, unveiling molecular signatures that characterize specific environmental challenges or other forms of stress will provide new prevention/intervention opportunities for personalized medicine. Antioxid. Redox Signal. 00, 000-000.

Quantitative High-Throughput Screen Identifies Inhibitors of the Schistosoma mansoni Redox Cascade

PubMed Central

Simeonov, Anton; Jadhav, Ajit; Sayed, Ahmed A.; Wang, Yuhong; Nelson, Michael E.; Thomas, Craig J.; Inglese, James; Williams, David L.; Austin, Christopher P.

2008-01-01

Schistosomiasis is a tropical disease associated with high morbidity and mortality, currently affecting over 200 million people worldwide. Praziquantel is the only drug used to treat the disease, and with its increased use the probability of developing drug resistance has grown significantly. The Schistosoma parasites can survive for up to decades in the human host due in part to a unique set of antioxidant enzymes that continuously degrade the reactive oxygen species produced by the host's innate immune response. Two principal components of this defense system have been recently identified in S. mansoni as thioredoxin/glutathione reductase (TGR) and peroxiredoxin (Prx) and as such these enzymes present attractive new targets for anti-schistosomiasis drug development. Inhibition of TGR/Prx activity was screened in a dual-enzyme format with reducing equivalents being transferred from NADPH to glutathione via a TGR-catalyzed reaction and then to hydrogen peroxide via a Prx-catalyzed step. A fully automated quantitative high-throughput (qHTS) experiment was performed against a collection of 71,028 compounds tested as 7- to 15-point concentration series at 5 µL reaction volume in 1536-well plate format. In order to generate a robust data set and to minimize the effect of compound autofluorescence, apparent reaction rates derived from a kinetic read were utilized instead of end-point measurements. Actives identified from the screen, along with previously untested analogues, were subjected to confirmatory experiments using the screening assay and subsequently against the individual targets in secondary assays. Several novel active series were identified which inhibited TGR at a range of potencies, with IC50s ranging from micromolar to the assay response limit (∼25 nM). This is, to our knowledge, the first report of a large-scale HTS to identify lead compounds for a helminthic disease, and provides a paradigm that can be used to jump-start development of novel therapeutics for other neglected tropical diseases. PMID:18235848

Qualification of serological infectious disease assays for the screening of samples from deceased tissue donors.

PubMed

Kitchen, A D; Newham, J A

2011-05-01

Whilst some of the assays used for serological screening of post-mortem blood samples from deceased tissue donors in some countries have been specifically validated by the manufacturer for this purpose, a significant number of those currently in use globally have not. Although specificity has previously been considered a problem in the screening of such samples, we believe that ensuring sensitivity is more important. The aim of this study was to validate a broader range of assays for the screening of post-mortem blood samples from deceased tissue donors. Six microplate immunoassays currently in use within National Health Service Blood and Transplant (NHSBT) for the screening of blood, tissue and stem cell donations were included. Representative samples from confirmed positive donors were titrated in screen negative post-mortem samples in parallel with normal pooled negative serum to determine if there was any inhibition with the post-mortem samples. There were no significant differences seen (P < 0.005) between the dilution curves obtained for the positive samples diluted in post-mortem samples and normal pooled sera. Although small numbers of samples were studied, it can be surmised that the post-mortem blood samples from deceased tissue donors, collected according to United Kingdom guidelines, are a suitable substrate for the assays evaluated. No diminution of reactivity was seen when dilution with sera from deceased donors was compared to dilution using pooled serum from live donors. In the absence of genuine low titre positive post-mortem samples, the use of samples spiked with various levels of target material provides a means of qualifying serological screening assays used by NHSBT for the screening of post-mortem blood samples from deceased tissue donors.

Description of 15 DNA-positive and antibody-negative "window-period" blood donations identified during prospective screening for Babesia microti.

PubMed

Moritz, Erin D; Tonnetti, Laura; Hewins, Mary Ellen; Berardi, Victor P; Dodd, Roger Y; Stramer, Susan L

2017-07-01

Blood donation screening detecting only antibodies fails to identify donors in the earliest stage of infection, before a detectable immunologic response, that is, the "window period" (WP). We present data on WP donations identified during prospective screening for Babesia microti, a transfusion-transmissible parasite of increasing concern in the United States. Blood donations collected in Connecticut, Massachusetts, Minnesota, and Wisconsin were screened using polymerase chain reaction (PCR) and arrayed fluorescence immunoassay (AFIA) to detect B. microti DNA and antibodies, respectively. Parasite loads were estimated using quantitative PCR. Red blood cell (RBC) samples were inoculated into hamsters to assess infectivity. Donors screening reactive were indefinitely deferred, tested by supplemental methods, and followed to assess DNA and antibody clearance. Demographic data from WP donors (i.e., those screening PCR positive and AFIA negative) were compared to data from other positive donors. Of 220,479 donations screened from June 2012 to August 2016, a total of 700 were positive, of which 15 (2% of positive donations or 1 per 14,699 screened donations) were confirmed WP donations. The median estimated parasite load in WP donations was 350 parasites/mL, no different than AFIA-positive and PCR-positive donors. Parasite loads in RBC samples from WP units ranged from 14 to 11,022 parasites/mL; RBC samples from three of 10 (30%) WP donations infected hamsters. The mean age of WP donors was 48 years (range, 17-75 years); three (20%) were female. WP donor demographics did not differ significantly from demographics of other donors. We report one per 15,000 B. microti WP infections in blood donors in endemic areas, demonstrating the importance of nucleic acid testing to mitigate the risk of transfusion-transmitted babesiosis. © 2017 AABB.

Monoclonal antibodies specific to sailfish serum albumin: development of an assay for the identification of fish species in the field.

PubMed

Rossi, E A; Shepard, S R; Poyer, J C; Hartmann, J X

1992-06-01

Balb/c mice were immunized with albumin purified from sailfish (Istiophorus albicans) serum. Hybridomas were produced and screened by ELISA for reactivity with the purified albumins of sailfish, blue marlin (Makaira nigricans) and white marlin (Tetrapturus albidus). Monoclonal antibodies (MAbs) from 16 different clones exhibited activity against sailfish albumin. Thirteen of the MAbs showed cross-reactivity with the marlin species. Three MAbs exhibited distinct specificity for sailfish albumin. One of these species specific MAbs (M2D1) was conjugated to horseradish peroxidase (HRP) in order to construct an ELISA for identification of sailfish from serum. The ELISA for sailfish correctly identified eight sailfish from 26 billfish serum samples. The MAb-peroxidase conjugate was highly specific toward sailfish in that no reaction against heterologous species was detected.

Prediction and characterization of heat-affected zone formation due to neighboring nickel-aluminum multilayer foil reaction

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

Adams, David P.; Hirschfeld, Deidre A.; Hooper, Ryan J.

2015-09-01

Reactive multilayer foils have the potential to be used as local high intensity heat sources for a variety of applications. Much of the past research effort concerning these materials have focused on understanding the structure-property relationships of the foils that govern the energy released during a reaction. To enhance the ability of researchers to more rapidly develop technologies based on reactive multilayer foils, a deeper and more predictive understanding of the relationship between the heat released from the foil and microstructural evolution in the neighboring materials is needed. This work describes the development of a numerical model for the purposemore » of evaluating new foil-substrate combinations for screening and optimization. The model is experimentally validated using a commercially available Ni-Al multilayer foils and different alloys.« less

Unique system of photoreceptors in sea urchin tube feet

PubMed Central

Ullrich-Lüter, Esther M; Dupont, Sam; Arboleda, Enrique; Hausen, Harald; Arnone, Maria Ina

2011-01-01

Different sea urchin species show a vast variety of responses to variations in light intensity; however, despite this behavioral evidence for photosensitivity, light sensing in these animals has remained an enigma. Genome information of the recently sequenced purple sea urchin (Strongylocentrotus purpuratus) allowed us to address this question from a previously unexplored molecular perspective by localizing expression of the rhabdomeric opsin Sp-opsin4 and Sp-pax6, two genes essential for photoreceptor function and development, respectively. Using a specifically designed antibody against Sp-Opsin4 and in situ hybridization for both genes, we detected expression in two distinct groups of photoreceptor cells (PRCs) located in the animal's numerous tube feet. Specific reactivity of the Sp-Opsin4 antibody with sea star optic cushions, which regulate phototaxis, suggests a similar visual function in sea urchins. Ultrastructural characterization of the sea urchin PRCs revealed them to be of a microvillar receptor type. Our data suggest that echinoderms, in contrast to chordates, deploy a microvillar, r-opsin–expressing PRC type for vision, a feature that has been so far documented only in protostome animals. Surprisingly, sea urchin PRCs lack any associated screening pigment. Indeed, one of the tube foot PRC clusters may account for directional vision by being shaded through the opaque calcite skeleton. The PRC axons connect to the animal internal nervous system, suggesting an integrative function beyond local short circuits. Because juveniles display no phototaxis until skeleton completion, we suggest a model in which the entire sea urchin, deploying its skeleton as PRC screening device, functions as a huge compound eye. PMID:21536888

A Method of Dynamic Extended Reactive Power Optimization in Distribution Network Containing Photovoltaic-Storage System

NASA Astrophysics Data System (ADS)

Wang, Wu; Huang, Wei; Zhang, Yongjun

2018-03-01

The grid-integration of Photovoltaic-Storage System brings some undefined factors to the network. In order to make full use of the adjusting ability of Photovoltaic-Storage System (PSS), this paper puts forward a reactive power optimization model, which are used to construct the objective function based on power loss and the device adjusting cost, including energy storage adjusting cost. By using Cataclysmic Genetic Algorithm to solve this optimization problem, and comparing with other optimization method, the result proved that: the method of dynamic extended reactive power optimization this article puts forward, can enhance the effect of reactive power optimization, including reducing power loss and device adjusting cost, meanwhile, it gives consideration to the safety of voltage.

ReaCog, a Minimal Cognitive Controller Based on Recruitment of Reactive Systems.

PubMed

Schilling, Malte; Cruse, Holk

2017-01-01

It has often been stated that for a neuronal system to become a cognitive one, it has to be large enough. In contrast, we argue that a basic property of a cognitive system, namely the ability to plan ahead, can already be fulfilled by small neuronal systems. As a proof of concept, we propose an artificial neural network, termed reaCog, that, first, is able to deal with a specific domain of behavior (six-legged-walking). Second, we show how a minor expansion of this system enables the system to plan ahead and deploy existing behavioral elements in novel contexts in order to solve current problems. To this end, the system invents new solutions that are not possible for the reactive network. Rather these solutions result from new combinations of given memory elements. This faculty does not rely on a dedicated system being more or less independent of the reactive basis, but results from exploitation of the reactive basis by recruiting the lower-level control structures in a way that motor planning becomes possible as an internal simulation relying on internal representation being grounded in embodied experiences.

Rapid screening for human-pathogenic Mucorales using rolling circle amplification.

PubMed

Dolatabadi, S; Najafzadeh, M J; de Hoog, G S

2014-12-01

Mucormycosis has emerged as a relatively common severe mycosis in patients with haematological and allogeneic stem cell transplantation. Source of transmission is from unidentified sources in the environment. Early diagnosis of infection and its source of contamination are paramount for rapid and appropriate therapy. In this study, rolling circle amplification (RCA) is introduced as a sensitive, specific and reproducible isothermal DNA amplification technique for rapid molecular identification of six of the most virulent species (Rhizopus microsporus, R. arrhizus var. arrhizus, R. arrhizus var. delemar, Mucor irregularis, Mucor circinelloides, Lichtheimia ramosa, Lichtheimia corymbifera). DNAs of target species were successfully amplified, with no cross reactivity between species. RCA can be considered as a rapid detection method with high specificity and sensitivity, suitable for large screening. © 2014 Blackwell Verlag GmbH.

Antiplatelet and anticancer isothiocyanates in Japanese domestic horseradish, wasabi.

PubMed

Morimitsu, Y; Hayashi, K; Nakagawa, Y; Horio, F; Uchida, K; Osawa, T

2000-01-01

6-Methylsulfinylhexyl isothiocyanate (MS-ITC) was isolated from wasabi (Wasabia japonica, Japanese domestic horseradish) as a potential inhibitor of human platelet aggregation in vitro through our extensive screening of vegetables and fruits. In the course of another screening for the induction of glutathione S-transferase (GST) activity in RL34 cells. MS-ITC was inadvertently isolated from wasabi as a potential inducer of GST. MS-ITC administered to rats or mice also showed both activities in vivo. As a result from elucidation of the platelet aggregation inhibition and the GST induction mechanisms of MS-ITC, the isothiocyanate moiety of MS-ITC plays an important role for antiplatelet and anticancer activities because of its highly reactivity with sulfhydryl (-SH) groups in biomolecules (GSH, cysteine residue in a certain protein, etc.).

Antiplatelet and anticancer isothiocyanates in Japanese domestic horseradish, Wasabi.

PubMed

Morimitsu, Y; Hayashi, K; Nakagawa, Y; Fujii, H; Horio, F; Uchida, K; Osawa, T

2000-07-31

6-Methylsulfinylhexyl isothiocyanate (MS-ITC) was isolated from wasabi (Wasabia japonica, Japanese domestic horseradish) as a potential inhibitor of human platelet aggregation in vitro through our extensive screening of vegetables and fruits. In the course of an another screening for the induction of glutathione S-transferase (GST) activity in RL34 cells, MS-ITC was inadvertently isolated from wasabi as a potential inducer of GST. MS-ITC administered to rats or mice also showed both activities in vivo. As a result from elucidation of the platelet aggregation inhibition and the GST induction mechanisms of MS-ITC, the isothiocyanate moiety of MS-ITC plays an important role for antiplatelet and anticancer activities because of its high reactivity with sulfhydryl (RSH) groups in biomolecules (GSH, cysteine residue in a certain protein, etc.).

Evaluation of a time efficient immunization strategy for anti-PAH antibody development

PubMed Central

Li, Xin; Kaattari, Stephen L.; Vogelbein, Mary Ann; Unger, Michael A.

2016-01-01

The development of monoclonal antibodies (mAb) with affinity to small molecules can be a time-consuming process. To evaluate shortening the time for mAb production, we examined mouse antisera at different time points post-immunization to measure titer and to evaluate the affinity to the immunogen PBA (pyrene butyric acid). Fusions were also conducted temporally to evaluate antibody production success at various time periods. We produced anti-PBA antibodies 7 weeks post-immunization and selected for anti-PAH reactivity during the hybridoma screening process. Moreover, there were no obvious sensitivity differences relative to antibodies screened from a more traditional 18 week schedule. Our results demonstrate a more time efficient immunization strategy for anti-PAH antibody development that may be applied to other small molecules. PMID:27282486

Survey of rheumatologists on the use of the Philippine Guidelines on the Screening for Tuberculosis prior to use of Biologic Agents.

PubMed

Aquino-Villamin, Melissa; Tankeh-Torres, Sandra; Lichauco, Juan Javier

2016-11-01

The use of biologic agents has become an important option in treating patients with rheumatoid arthritis. However, these drugs have been associated with an increased risk of tuberculosis (TB) reactivation. Local guidelines for TB screening prior to the use of biologic agents were developed to address this issue. This study is a survey describing the compliance of Filipino rheumatologists to these guidelines. Eighty-seven rheumatologists in the Philippines were given the questionnaire and responses from 61 rheumatologists were included in the analysis. All respondents agree that patients should be screened prior to giving the biologic agents. Local guidelines recommend screening with tuberculin skin test (TST) and chest radiograph. However, cut-off values considered for a positive TST and timing of initiation of biologic agents after starting TB prophylaxis and treatment varied among respondents. In addition, screening of close household contacts were only performed by 41 (69.5%) respondents. There were 11 respondents who reported 16 patients developing TB during or after receiving biologic agents, despite adherence to the guidelines. This survey describes the compliance rate of Filipino rheumatologists in applying current local recommendations for TB screening prior to initiating biologic agents. The incidence of new TB cases despite the current guidelines emphasizes the importance of compliance and the need to revise the guidelines based on updated existing literature. © 2015 Asia Pacific League of Associations for Rheumatology and Wiley Publishing Asia Pty Ltd.

Autoantibodies to MUC1 glycopeptides cannot be used as a screening assay for early detection of breast, ovarian, lung or pancreatic cancer

PubMed Central

Burford, B; Gentry-Maharaj, A; Graham, R; Allen, D; Pedersen, J W; Nudelman, A S; Blixt, O; Fourkala, E O; Bueti, D; Dawnay, A; Ford, J; Desai, R; David, L; Trinder, P; Acres, B; Schwientek, T; Gammerman, A; Reis, C A; Silva, L; Osório, H; Hallett, R; Wandall, H H; Mandel, U; Hollingsworth, M A; Jacobs, I; Fentiman, I; Clausen, H; Taylor-Papadimitriou, J; Menon, U; Burchell, J M

2013-01-01

Background: Autoantibodies have been detected in sera before diagnosis of cancer leading to interest in their potential as screening/early detection biomarkers. As we have found autoantibodies to MUC1 glycopeptides to be elevated in early-stage breast cancer patients, in this study we analysed these autoantibodies in large population cohorts of sera taken before cancer diagnosis. Methods: Serum samples from women who subsequently developed breast cancer, and aged-matched controls, were identified from UK Collaborative Trial of Ovarian Cancer Screening (UKCTOCS) and Guernsey serum banks to formed discovery and validation sets. These were screened on a microarray platform of 60mer MUC1 glycopeptides and recombinant MUC1 containing 16 tandem repeats. Additional case–control sets comprised of women who subsequently developed ovarian, pancreatic and lung cancer were also screened on the arrays. Results: In the discovery (273 cases, 273 controls) and the two validation sets (UKCTOCS 426 cases, 426 controls; Guernsey 303 cases and 606 controls), no differences were found in autoantibody reactivity to MUC1 tandem repeat peptide or glycoforms between cases and controls. Furthermore, no differences were observed between ovarian, pancreatic and lung cancer cases and controls. Conclusion: This robust, validated study shows autoantibodies to MUC1 peptide or glycopeptides cannot be used for breast, ovarian, lung or pancreatic cancer screening. This has significant implications for research on the use of MUC1 in cancer detection. PMID:23652307

21 CFR 862.1055 - Newborn screening test system for amino acids, free carnitine, and acylcarnitines using tandem...

Code of Federal Regulations, 2011 CFR

2011-04-01

... 21 Food and Drugs 8 2011-04-01 2011-04-01 false Newborn screening test system for amino acids... screening test system for amino acids, free carnitine, and acylcarnitines using tandem mass spectrometry. (a) Identification. A newborn screening test system for amino acids, free carnitine, and acylcarnitines using tandem...

21 CFR 862.1055 - Newborn screening test system for amino acids, free carnitine, and acylcarnitines using tandem...

Code of Federal Regulations, 2010 CFR

2010-04-01

... 21 Food and Drugs 8 2010-04-01 2010-04-01 false Newborn screening test system for amino acids... screening test system for amino acids, free carnitine, and acylcarnitines using tandem mass spectrometry. (a) Identification. A newborn screening test system for amino acids, free carnitine, and acylcarnitines using tandem...

Evaluation of Contribution for Voltage Control Ancillary Services Based on Social Surplus

NASA Astrophysics Data System (ADS)

Ueki, Yuji; Hara, Ryoichi; Kita, Hiroyuki; Hasegawa, Jun

Reactive power supply plays an important role in active power supply with adequate system voltages. Various pricing mechanism for reactive power supply have been developed and some of them are adopted in some power systems, however they are in a trial stage. The authors also focus on development of a pricing method for reactive power ancillary services. This problem involves two technical issues: rational estimation of the cost associated with reactive power supply and fair and transparent allocation of the estimated cost among the market participants. This paper proposes methods for evaluating the contribution of generators and demands.

Screening for Syphilis: Updated Evidence Report and Systematic Review for the US Preventive Services Task Force.

PubMed

Cantor, Amy G; Pappas, Miranda; Daeges, Monica; Nelson, Heidi D

2016-06-07

Screening for syphilis infection is currently recommended for high-risk individuals, including those with previous syphilis infection, an infected sexual partner, HIV infection, or more than 4 sex partners in the preceding year. To update a 2004 systematic review of studies of syphilis screening effectiveness, test accuracy, and screening harms in nonpregnant adults and adolescents. Cochrane Central Register of Controlled Trials and Cochrane Database of Systematic Reviews through October 2015 and Ovid MEDLINE (January 2004 to October 2015), with updated search through March 2016. English-language trials and observational studies of screening effectiveness, test accuracy, and screening harms in nonpregnant adults and adolescents. One investigator abstracted data, a second checked data for accuracy, and 2 investigators independently assessed study quality using predefined criteria. Transmission of disease, including HIV; complications of syphilis; diagnostic accuracy; and harms of screening. No evidence was identified regarding the effectiveness of screening on clinical outcomes or the effectiveness of risk assessment instruments; the harms of screening; or the effectiveness of screening in average-risk, nonpregnant adolescents or adults or high-risk individuals other than men who have sex with men (MSM) or men who are HIV positive. Four non-US studies indicated higher rates of syphilis detection with screening every 3 months vs 6 or 12 months for early syphilis in HIV-positive men or MSM. For example, there was an increased proportion of asymptomatic, higher-risk MSM in Australia (n = 6789 consultations) receiving a diagnosis of early syphilis when tested every 3 months vs annually (53% vs 16%, P = .001), but no difference among low-risk MSM. Treponemal and nontreponemal tests were accurate in asymptomatic individuals (sensitivity >85%, specificity >91%) in 3 studies but required confirmatory testing. Reverse sequence testing with an initial automated treponemal test yielded more false reactive test results than with rapid plasma reagin in 2 studies, one with a low-prevalence US population (0.6% vs 0.0%, P = .03) and another in a higher-prevalence Canadian population (0.26% vs 0.13%). Screening HIV-positive men or MSM for syphilis every 3 months is associated with improved syphilis detection. Treponemal or nontreponemal tests are accurate screening tests but require confirmation. Research is needed on the effect of screening on clinical outcomes; effective screening strategies, including reverse sequence screening, in various patient populations; and harms of screening.

Association of CMV-Specific T Cell-Mediated Immunity with CMV DNAemia and Development of CMV Disease in HIV-1–Infected Individuals

PubMed Central

Aichelburg, Maximilian C.; Weseslindtner, Lukas; Mandorfer, Mattias; Strassl, Robert; Rieger, Armin; Reiberger, Thomas; Puchhammer-Stöckl, Elisabeth; Grabmeier-Pfistershammer, Katharina

2015-01-01

Background Among HIV-1–infected individuals, cytomegalovirus (CMV) reactivation and disease occur in the setting of advanced immunosuppression. The value of a standardized assessment of CMV-specific T-cell mediated immunity by the CMV QuantiFERON assay (CMV-QFT) has not yet been thoroughly investigated in HIV-1–infected subjects. Methods Prospective, longitudinal study in 153 HIV-1–infected subjects with a CD4+ T cell count < 350/μL who simultaneously underwent CMV-QFT, CMV serology testing and CMV-DNA quantification. Factors associated with CMV-QFT were evaluated. Clinical screening for CMV manifestations was then performed every 3 months. Results Among the 141 CMV IgG-seropositive individuals the CMV-QFT assay yielded reactive results in 84% (118/141), negative results in 15% (21/141) and indeterminate (negative mitogen IFN-gamma response) results in 1% (2/141) of subjects. The mean actual CD4+ T cell count was significantly higher in CMV-QFT reactive subjects, when compared to CMV-QFT non-reactive individuals (183 ± 102 vs. 126 ± 104 cells/μL, P = 0.015). A significantly lower proportion of CMV-QFT reactive vs. non-reactive patients displayed CMV DNAemia > 100 copies/mL (23% (27/118) vs. 48% (11/23), P = 0.02). Furthermore, a statistically significant inverse association between mitogen IFN-gamma response and CMV-DNAemia > 1000 copies/mL was observed (P < 0.001). During the observational period, 5 CMV end-organ manifestations were observed. In three of the CMV cases the CMV-QFT yielded indeterminate results. Conclusions While CMV-QFT reactivity indicates CMV-specific immunity, indeterminate results due to negative mitogen IFN-gamma response might reflect HIV-1-induced immunodeficiency. Thus, dependency upon CD4+ T cell count should be considered when interpreting CMV-QFT results. PMID:26322514

Sensitization prevalence, antibody cross-reactivity and immunogenic peptide profile of Api g 2, the non-specific lipid transfer protein 1 of celery.

PubMed

Gadermaier, Gabriele; Hauser, Michael; Egger, Matthias; Ferrara, Rosetta; Briza, Peter; Santos, Keity Souza; Zennaro, Danila; Girbl, Tamara; Zuidmeer-Jongejan, Laurian; Mari, Adriano; Ferreira, Fatima

2011-01-01

Celery (Apium graveolens) represents a relevant allergen source that can elicit severe reactions in the adult population. To investigate the sensitization prevalence and cross-reactivity of Api g 2 from celery stalks in a Mediterranean population and in a mouse model. 786 non-randomized subjects from Italy were screened for IgE reactivity to rApi g 2, rArt v 3 (mugwort pollen LTP) and nPru p 3 (peach LTP) using an allergen microarray. Clinical data of 32 selected patients with reactivity to LTP under investigation were evaluated. Specific IgE titers and cross-inhibitions were performed in ELISA and allergen microarray. Balb/c mice were immunized with purified LTPs; IgG titers were determined in ELISA and mediator release was examined using RBL-2H3 cells. Simulated endolysosomal digestion was performed using microsomes obtained from human DCs. IgE testing showed a sensitization prevalence of 25.6% to Api g 2, 18.6% to Art v 3, and 28.6% to Pru p 3 and frequent co-sensitization and correlating IgE-reactivity was observed. 10/32 patients suffering from LTP-related allergy reported symptoms upon consumption of celery stalks which mainly presented as OAS. Considerable IgE cross-reactivity was observed between Api g 2, Art v 3, and Pru p 3 with varying inhibition degrees of individual patients' sera. Simulating LTP mono-sensitization in a mouse model showed development of more congruent antibody specificities between Api g 2 and Art v 3. Notably, biologically relevant murine IgE cross-reactivity was restricted to the latter and diverse from Pru p 3 epitopes. Endolysosomal processing of LTP showed generation of similar clusters, which presumably represent T-cell peptides. Api g 2 represents a relevant celery stalk allergen in the LTP-sensitized population. The molecule displays common B cell epitopes and endolysosomal peptides that encompass T cell epitopes with pollen and plant-food derived LTP.

Development of Metal Cluster-Based Energetic Materials at NSWC-IHD

DTIC Science & Technology

2011-01-01

reactivity of NixAly + clusters with nitromethane was investigated using a gas-phase molecular beam system. Results indicate that nitromethane is highly...clusters make up the subunit of a molecular metal-based energetic material. The reactivity of NixAly+ clusters with nitromethane was investigated using...a gas-phase molecular beam system. Results indicate that nitromethane is highly reactive toward the NixAly+ clusters and suggests it would not make

Children's patterns of emotional reactivity to conflict as explanatory mechanisms in links between interpartner aggression and child physiological functioning.

PubMed

Davies, Patrick T; Sturge-Apple, Melissa L; Cicchetti, Dante; Manning, Liviah G; Zale, Emily

2009-11-01

This paper examined children's fearful, sad, and angry reactivity to interparental conflict as mediators of associations between their exposure to interparental aggression and physiological functioning. Participants included 200 toddlers and their mothers. Assessments of interparental aggression and children's emotional reactivity were derived from maternal surveys and a semi-structured interview. Cortisol levels and cardiac indices of sympathetic nervous system (SNS) and parasympathetic nervous system (PNS) activity were used to assess toddler physiological functioning. Results indicated that toddler exposure to interparental aggression was associated with greater cortisol levels and PNS activity and diminished SNS activity. Toddler angry emotional reactivity mediated associations between interparental aggression and cortisol and PNS functioning. Fearful emotional reactivity was a mediator of the link between interparental aggression and SNS functioning. The results are interpreted within conceptualizations of how exposure and reactivity to family risk organize individual differences in physiological functioning.

Method for reactivating catalysts and a method for recycling supercritical fluids used to reactivate the catalysts

DOEpatents

Ginosar, Daniel M.; Thompson, David N.; Anderson, Raymond P.

2008-08-05

A method of reactivating a catalyst, such as a solid catalyst or a liquid catalyst. The method comprises providing a catalyst that is at least partially deactivated by fouling agents. The catalyst is contacted with a fluid reactivating agent that is at or above a critical point of the fluid reactivating agent and is of sufficient density to dissolve impurities. The fluid reactivating agent reacts with at least one fouling agent, releasing the at least one fouling agent from the catalyst. The at least one fouling agent becomes dissolved in the fluid reactivating agent and is subsequently separated or removed from the fluid reactivating agent so that the fluid reactivating agent may be reused. A system for reactivating a catalyst is also disclosed.

Sleep System Sensitization: Evidence for Changing Roles of Etiological Factors in Insomnia

PubMed Central

Kalmbach, David A.; Pillai, Vivek; Arnedt, J. Todd; Anderson, Jason R.; Drake, Christopher L.

2016-01-01

Objectives To test for sensitization of the sleep system in response to insomnia development and major life stress. In addition, to evaluate the impact on depression and anxiety associated with sleep system sensitization. Methods A longitudinal study with three annual assessments. The community-based sample included 262 adults with no history of insomnia or depression who developed insomnia 1 year after baseline (67.6% female; 44.0±13.4y). Measures included the Ford Insomnia Response to Stress Test to assess sleep reactivity, Quick Inventory of Depressive Symptomatology, and Beck Anxiety Inventory. Insomnia classification was based on DSM-IV criteria. Sleep system sensitization was operationally defined as significant increases in sleep reactivity. Results Sensitization of the sleep system was observed from baseline to insomnia onset at 1-y follow-up among insomniacs with low premorbid vulnerability (p<.001), resulting in 68.3% of these individuals re-classified as highly sleep reactive. Major life stress was associated with greater sleep system sensitization (p=.02). Results showed that sleep reactivity at 2-y follow-up remained elevated among those with low premorbid vulnerability, even after insomnia remission (p<.01). Finally, analyses revealed that increases in sleep reactivity predicted greater depression (p<.001) and anxiety (p<.001) at insomnia onset. The impact of sensitization on depression was stable at 2-y follow-up (p=.01). Conclusions Evidence supports sensitization of the sleep system as consequence of insomnia development and major life stress among individuals with low premorbid sleep reactivity. Sleep system sensitization may serve as a mechanism by which insomnia is perpetuated. Harmful effects of the sensitization process may increase risk for insomnia-related depression and anxiety. PMID:27448474

Sleep system sensitization: evidence for changing roles of etiological factors in insomnia.

PubMed

Kalmbach, David A; Pillai, Vivek; Arnedt, J Todd; Anderson, Jason R; Drake, Christopher L

2016-05-01

To test for sensitization of the sleep system in response to insomnia development and major life stress. In addition, to evaluate the impact on depression and anxiety associated with sleep system sensitization. A longitudinal study with three annual assessments. The community-based sample included 262 adults with no history of insomnia or depression who developed insomnia one year after baseline (67.6% female; 44.0 ± 13.4 yr). Measures included the Ford Insomnia Response to Stress Test to assess sleep reactivity, Quick Inventory of Depressive Symptomatology, and Beck Anxiety Inventory. Insomnia classification was based on DSM-IV criteria. Sleep system sensitization was operationally defined as significant increases in sleep reactivity. Sensitization of the sleep system was observed from baseline to insomnia onset at 1-yr follow-up among insomniacs with low premorbid vulnerability (p < 0.001), resulting in 68.3% of these individuals re-classified as highly sleep reactive. Major life stress was associated with greater sleep system sensitization (p = 0.02). Results showed that sleep reactivity at 2-yr follow-up remained elevated among those with low premorbid vulnerability, even after insomnia remission (p < 0.01). Finally, analyses revealed that increases in sleep reactivity predicted greater depression (p < 0.001) and anxiety (p < 0.001) at insomnia onset. The impact of sensitization on depression was stable at 2-yr follow-up (p = 0.01). Evidence supports sensitization of the sleep system as a consequence of insomnia development and major life stress among individuals with low premorbid sleep reactivity. Sleep system sensitization may serve as a mechanism by which insomnia is perpetuated. Harmful effects of the sensitization process may increase risk for insomnia-related depression and anxiety. Copyright © 2016 Elsevier B.V. All rights reserved.

Design, Control, and Modeling of a New Voltage Source Converter for HVDC System

NASA Astrophysics Data System (ADS)

Mohan, Madhan; Singh, Bhim; Ketan Panigrahi, Bijaya

2013-05-01

Abstract: A New Voltage Source Converter (VSC) based on neutral clamped three-level circuit is proposed for High Voltage DC (HVDC) system. The proposed VSC is designed in a multipulse configuration. The converter is operated by Fundamental Frequency Switching (FFS). A new control method is developed for achieving all the necessary control aspects of HVDC system such as independent real and reactive power control, bidirectional real and reactive power control. The basic of the control method is varying the pulse width and by keeping the dc link voltage constant. The steady state and dynamic performances of HVDC system interconnecting two different frequencies network are demonstrated for active and reactive power control. Total number of transformers used in this system are reduced to half in comparison with the two-level VSCs for both active and reactive power control. The performance of the HVDC system is improved in terms of reduced harmonics level even at fundamental frequency switching. The harmonic performance of the designed converter is also studied for different value of the dead angle (β), and the optimized range of the dead angle is achieved for varying reactive power requirement. Simulation results are presented for the designed three level multipulse voltage source converters with the proposed control algorithm.

[High-contrast resolution of film-screen systems in oral and maxillofacial radiology].

PubMed

Kaeppler, G; Reinert, S

2007-11-01

The aim was to determine differences in high-contrast resolution of film-screen systems used in dental panoramic and cephalometric radiography by calculating the modulation transfer function (MTF). The radiographs used to determine the MTF should be taken by the same x-ray units as those used for patient radiographs. The MTF was determined using a lead grid and according to DIN 6867-2 for 11 film-screen systems (speed 250, speed class 200 and 400) used in dental radiographic diagnostics. The optical density was measured using a microdensitometer developed by PTB. With 10% of the modulation transfer factor, newly developed film-screen systems (speed class 200 and 400) demonstrated a resolution of 4.9 to 6 line pairs per mm (panoramic radiography). In cephalometric radiography a film-screen system (speed class 400 and green-sensitive film) had a resolution of 4.2 line pairs per mm and surpassed two film-screen systems (speed class 400, resolution of 3 line pairs per mm, blue-sensitive films). The relevance of this study is underlined by the diagnostic reference doses defined in the German X-ray Ordinance (RöV) which are also intended for dentistry. Film-screen systems (speed 250, speed class 200) previously used in dental panoramic and cephalometric radiography can be replaced by newly developed film-screen systems (speed class 400). In dental radiography dose reductions are possible with film-screen systems (speed class 400) without impairing diagnostic accuracy. The introduction of newly developed film-screen systems (speed class 400) requires lower milliampere-seconds and therefore an adjustment of the x-ray units to lower milliampere settings.

Diversifying Homogenous Au(I)-Catalysis through New Reaction Discovery

NASA Astrophysics Data System (ADS)

Motika, Stephen

Homogenous Au(I)-catalysis has become a valuable synthetic tool to activate a host of unsaturated carbon functional groups towards nucleophilic addition. Over the course of the past two decades, many have embarked on new journeys within this field. Notably, the advancements in this field hinge on the development of new ligand systems that impart novel reactivity at the metal. Our group has focused on this area, as we have successfully demonstrated the utility of 1,2,3-triazoles as ligands for gold and a host of other transition metals and Lewis acids. With respect to gold catalysis, these ligands enhance the stability of the metal center, thus inhibiting typical reductive decomposition pathways that have plagued this field. The enhanced stability comes with a price though as higher temperatures can be required. We've addressed this challenge by discovering an interesting synergy between triazole-gold and Lewis acids, allowing us to overcome the lower reactivity of these catalysts. During my time as a graduate student, I have focused heavily on enlisting these catalytic systems for new reaction discovery. In my first experimental chapter, I was able to develop an interesting reaction cascade in which triazole-gold and secondary amine catalysts were used. I started with a well-known gold-catalyzed Claisen rearrangement of propargyl vinyl ether, yielding functionalized allenes. The identical oxidation state between these allenes and synthetically appealing dienals was an impetus to develop a new isomerization strategy. After screening various conditions, I was able to successfully execute this design. Most of the work I have been involved in over the past two years has surrounded a gold-catalyzed hydroboration to yield interesting hetercocycles containing a N-B bond. The N-B bond offers some unique properties as it is isoelectronic to a C-C double bond. Despite the simplicity in this design, it would become apparent early on in this research that mitigating the reducing strength of the starting materials was absolutely critical. Starting materials that were too strongly reducing led to rapid catalyst decomposition. Through thorough reaction screening, we have been able to identify a catalytic system that performs extremely well in this context. Ultimately, our goal in this work is to access 1,2-azaborines, which are isosteres of benzene. This compound exhibits aromaticity, as determined through structural and quantitative analyses by several groups. However, subtle differences in properties between the azaborine and benzene, such as its polarity, have intrigued many researchers across various disciplines. Moreover, the ubiquity of its carbonaceous parent in biological systems has prompted many to pursue new synthetic routes to access 1,2-azaborines.

Software Development Technologies for Reactive, Real-Time, and Hybrid Systems

NASA Technical Reports Server (NTRS)

Manna, Zohar

1996-01-01

The research is directed towards the design and implementation of a comprehensive deductive environment for the development of high-assurance systems, especially reactive (concurrent, real-time, and hybrid) systems. Reactive systems maintain an ongoing interaction with their environment, and are among the most difficult to design and verify. The project aims to provide engineers with a wide variety of tools within a single, general, formal framework in which the tools will be most effective. The entire development process is considered, including the construction, transformation, validation, verification, debugging, and maintenance of computer systems. The goal is to automate the process as much as possible and reduce the errors that pervade hardware and software development.

Online Assessment of Voltage Stability in Power Systems with PMUs

NASA Astrophysics Data System (ADS)

Chitare, Prasad Bhagwat; Murthy Balijepalli, V. S. K.; Khaparde, S. A.

2013-05-01

Abstract: For the assessment of voltage instability which comprises the detection of voltage instability and identification of critical buses, two indices namely, system wide Qtax, and bus-specific qtax, are proposed. The Qtax, based on the sensitivity of the reactive power injections to the loading in the system provides early detection of impending voltage instability. The computed qtax indices identify the critcal buses among the load buses in the system. The identified critical buses provided optimal lacations for the corrective control actions for averting voltage instability. Additionally, for voltage stability monitoring, determining the poing of exhaustion of the reactive reserves in system is also crucial. This is addressed by proposed Q-Monitoring Index (QMI), which is the ratio of the reactive component of the source current to the sink current that flows through the adjacent transmission line. These proposed indices together can provide early indication to impending voltage instability. This has been illustrated on IEEE-39 bus system. The reactive support on identified critical buses results in maximum increase in the loadability of the system.

Acellular assessments of engineered-manufactured nanoparticle biological surface reactivity

EPA Science Inventory

It is critical to assess the surface properties and reactivity of engineered-manufactured nanoparticles (NPs) as these will influence their interactions with biological systems, biokinetics and toxicity. We examined the physicochemical properties and surface reactivity of metal o...

Annual Report to Congress - Fiscal Year 1996. A Report by the Council of the Strategic Environmental Research and Development Program

DTIC Science & Technology

1997-03-01

volatile organic compounds (VOCs), dense non-aqueous phase liquids (DNAPLs), and permeable reactive walls for chlorinated solvents The GRFL is the only... compounds , solvents, and heavy metals. SCAPS technology has been demonstrated to reduce the costs of traditional site screening by up to 90 percent; it...styphnate and volatile organic compounds (VOCs). Hazardous wastes also are generated during demilitarization. Under partial sponsorship of SERDP, the US Army

Utilizing the Cross-Reactivity of MIPs.

PubMed

Yilmaz, Ecevit; Billing, Johan; Nilsson, Carina; Boyd, Brian; Kecili, Rüstem; Nivhede, David; Axelsson, Sara; Rees, Anthony

2015-01-01

The crossreactivity of molecularly imprinted polymers (MIPs) and its practical implications are discussed. Screening of MIP libraries is presented as a fasttrack route to discovery of resins selective towards new targets, exploiting the fact that MIPs imprinted with one type of template molecule also show recognition to related and sometimes also to apparently unrelated molecules. Several examples from our own and others' studies are presented that illustrate this crossreactivity and the pattern of recognition is discussed for selected examples.

Clinical Investigation Program Report Control Symbol MED 300.

DTIC Science & Technology

1982-10-01

Preeclampsia as an Aid to Further Management. (C) (PR) 41 1961 Use of C-Reactive Protein in Prediction of ARD Prog- nosiS, (C) (PR) 42 1981 The Assessment...37 Status: Completed * Title: Routine Use of Serum Uric Acid Levels at 36 Weeks Gestation as Screening Test for Preeclampsia as an Aid to Further...nvestigators: .amily Pr-&ctiU. CPT Ellis M. Knight, MC Key Words: Serum Uric Acid Preeclampsia Accumulative MZDCASI Eat Accumulative Periodic Mar 82 Cost: ]A

An Alternative Thiol-Reactive Dye to Analyze Ligand Interactions with the Chemokine Receptor CXCR2 Using a New Thermal Shift Assay Format.

PubMed

Bergsdorf, Christian; Fiez-Vandal, Cédric; Sykes, David A; Bernet, Pascal; Aussenac, Sonia; Charlton, Steven J; Schopfer, Ulrich; Ottl, Johannes; Duckely, Myriam

2016-03-01

Integral membrane proteins (IMPs) play an important role in many cellular events and are involved in numerous pathological processes. Therefore, understanding the structure and function of IMPs is a crucial prerequisite to enable successful targeting of these proteins with low molecular weight (LMW) ligands early on in the discovery process. To optimize IMP purification/crystallization and to identify/characterize LMW ligand-target interactions, robust, reliable, high-throughput, and sensitive biophysical methods are needed. Here, we describe a differential scanning fluorimetry (DSF) screening method using the thiol-reactive BODIPY FL-cystine dye to monitor thermal unfolding of the G-protein-coupled receptor (GPCR), CXCR2. To validate this method, the seven-transmembrane protein CXCR2 was analyzed with a set of well-characterized antagonists. This study showed that the new DSF assay assessed reliably the stability of CXCR2 in a 384-well format. The analysis of 14 ligands with a potency range over 4 log units demonstrated the detection/characterization of LMW ligands binding to the membrane protein target. Furthermore, DSF results cross-validated with the label-free differential static light scattering (DSLS) thermal denaturation method. These results underline the potential of the BODIPY assay format as a general tool to investigate membrane proteins and their interaction partners. © 2015 Society for Laboratory Automation and Screening.

The utility of direct agglutination (DAT) and fast agglutination screening (FAST) tests in serodiagnosis of experimental microsporidiosis.

PubMed

Abou El Naga, Iman F; Gaafar, Maha R; El-Zawawy, Lobna A; El-Said, Doaa; Mossallam, Sherin F

2008-12-01

The present study was designed to evaluate the efficiency of two serodiagnostic tests; the direct agglutination test (DAT) and the fast agglutination screening test (FAST) in the diagnosis of Microsporidia in experimentally infected mice and to differentiate between different species of the parasite. The swiss albino mice were divided into non infected control and infected experimental groups which were further subdivided into ten subgroups. Ten samples of microsporidial spores were isolated from ten human stools and each one was used to infect each subgroup of mice. Stool and sera were collected weekly from each subgroup from the 1st to the 4th week post infection (PI). DAT & FAST tests, using antigen prepared from the different species of microsporidial spores were used to detect antibodies in sera of different mice subgroups. The cross reactivity of microsporidial spores with the antibodies of Cyclospora cyatenensis and Cryptosporidium parvum was investigated by DAT & FAST. The results proved that DAT & FAST were effective in detecting microsporidial antibodies in sera of experimentally infected mice from the 2nd week PI till the end of the study, without cross reactivity with C. cyatenensis or C. parvum. They failed to differentiate between different Microspoiridia species used but, they gave good interpretation and they were specific and sensitive, and did not need sophisticated equipments.

Recognition of Naegleriae ameba surface protein epitopes by anti-human CD45 antibodies.

PubMed

Ravine, Terrence J; Polski, Jacek M; Jenkins, James

2010-04-01

Phagocytosis is a highly conserved mechanism exhibited by both free-living amebas and mammalian blood cells. Similarities demonstrated by either cell type during engulfment of the same bacterial species may imply analogous surface proteins involved in receptor-mediated endocytosis. The increased availability of anti-human leukocyte antibodies or clusters of differentiation (CD) markers used in conjunction with flow cytometric (FCM) and/or immunohistochemical (IHC) analysis provides investigators with a relatively easy method to screen different cell populations for comparable plasma membrane proteins. In this study, we incubated Naegleria and Acanthamoeba amebas with several directly conjugated anti-human leukocyte monoclonal antibodies (mAb) for similarly recognized amebic epitopes. CD marker selection was based upon a recognized role of each mAb in phagocyte activation and/or uptake of bacteria. These included CD14, CD45, and CD206. In FCM, only one CD45 antibody demonstrated strong reactivity with both Naegleria fowleri and Naegleria gruberi that was not expressed in similarly tested Acanthamoeba species. Additional testing of N. gruberi by IHC demonstrated reactivity to a different CD45 antibody. Our results suggest a possible utility of using anti-human leukocyte antibodies to screen amebic cells for similarly expressed protein epitopes. In doing so, several important items must be considered when selecting potential mAbs for testing to increase the probability of a positive result.

Saliva C-reactive protein as a biomarker of metabolic syndrome in diabetic patients.

PubMed

Dezayee, Zhian Mahmood Ibrahim; Al-Nimer, Marwan Salih Mohamad

2016-01-01

Human C-reactive protein (CRP) has been used in the risk assessment of coronary events. Human saliva mirrors the body's health and well-being and is noninvasive, easy to collect, and ideal for third-world countries as well as for large patient screening. This study aimed to screen the saliva CRP qualitatively in patients with diabetes (Type 1 and 2) taking in considerations, the diagnostic criteria of metabolic syndrome. Center for diabetes mellitus, prospective study. A total number of 50 Type 2 diabetes (T2D) patients, 25 Type 1 diabetes (T1D) patients, and 25 healthy subjects were recruited from the center for diabetes mellitus. Each patient was assessed clinically, and the anthropometric measures, glycemic status, and lipid profiles were determined. Stimulated salivary flow rate and saliva CRP were determined. All calculations analysis was made using Excel 2003 program for Windows. The results showed that the salivary flow rate in T1D was less than healthy subjects and T2D and CRP was found positive (6 mg/L) in 36% and 56% of patients with T1D and T2D, respectively. Saliva CRP was found to be related to the anthropometric measurement, blood pressure, and glycemic control. We conclude that saliva CRP may be used as a biomarker for metabolic syndrome and its value is obvious in T2D rather than in T1D.

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

Grabaskas, David; Brunett, Acacia J.; Passerini, Stefano

GE Hitachi Nuclear Energy (GEH) and Argonne National Laboratory (Argonne) participated in a two year collaboration to modernize and update the probabilistic risk assessment (PRA) for the PRISM sodium fast reactor. At a high level, the primary outcome of the project was the development of a next-generation PRA that is intended to enable risk-informed prioritization of safety- and reliability-focused research and development. A central Argonne task during this project was a reliability assessment of passive safety systems, which included the Reactor Vessel Auxiliary Cooling System (RVACS) and the inherent reactivity feedbacks of the metal fuel core. Both systems were examinedmore » utilizing a methodology derived from the Reliability Method for Passive Safety Functions (RMPS), with an emphasis on developing success criteria based on mechanistic system modeling while also maintaining consistency with the Fuel Damage Categories (FDCs) of the mechanistic source term assessment. This paper provides an overview of the reliability analyses of both systems, including highlights of the FMEAs, the construction of best-estimate models, uncertain parameter screening and propagation, and the quantification of system failure probability. In particular, special focus is given to the methodologies to perform the analysis of uncertainty propagation and the determination of the likelihood of violating FDC limits. Additionally, important lessons learned are also reviewed, such as optimal sampling methodologies for the discovery of low likelihood failure events and strategies for the combined treatment of aleatory and epistemic uncertainties.« less

Table screen 360-degree holographic display using circular viewing-zone scanning.

PubMed

Inoue, Tatsuaki; Takaki, Yasuhiro

2015-03-09

A table screen 360-degree holographic display is proposed, with an increased screen size, having an expanded viewing zone over all horizontal directions around the table screen. It consists of a microelectromechanical systems spatial light modulator (MEMS SLM), a magnifying imaging system, and a rotating screen. The MEMS SLM generates hologram patterns at a high frame rate, the magnifying imaging system increases the screen of the MEMS SLM, and the reduced viewing zones are scanned circularly by the rotating screen. The viewing zones are localized to practically realize wavefront reconstruction. An experimental system has been constructed. The generation of 360-degree three-dimensional (3D) images was achieved by scanning 800 reduced and localized viewing zones circularly. The table screen had a diameter of 100 mm, and the frame rate of 3D image generation was 28.4 Hz.

Cloning and characterization of 2S albumin, Car i 1, a major allergen in pecan.

PubMed

Sharma, Girdhari M; Irsigler, Andre; Dhanarajan, Pushparani; Ayuso, Rosalia; Bardina, Luda; Sampson, Hugh A; Roux, Kenneth H; Sathe, Shridhar K

2011-04-27

Although pecans are associated with IgE-mediated food allergies, the allergens responsible remain to be identified and characterized. The 2S albumin gene was amplified from the pecan cDNA library. Dot-blots were used to screen the recombinant protein with pecan allergic patients' serum. The affinity purified native protein was analyzed by Edman sequencing and mass spectrometry/mass spectrometry (MS/MS) analysis. Cross-reactivity with walnut was determined by inhibition enzyme-linked immunosorbent assay (ELISA). Sequential epitopes were determined by probing the overlapping peptides with three different patients' serum pool. The 3-dimensional homology model was generated, and the locations of the pecan epitopes were compared with those of known sequential epitopes on other allergenic tree nut homologues. Of 28 patients tested by dot-blot, 22 (79%) bound to 2S albumin, designated as Car i 1. Edman sequencing and the MS/MS sequencing of native 2S albumin confirmed the identity of recombinant (r) Car i 1. Both pecan and walnut protein extracts inhibited the IgE-binding to rCar i 1. Sequential epitope mapping indicated weak, moderate, and strong reactivity against 12, 7, and 5 peptides, respectively. Of the 11 peptides recognized by all serum pools, 5 peptides were strongly reactive and located in 3 discrete regions of the Car i 1 (amino acids 43-57, 67-78, and 106-120). Three-dimensional modeling revealed IgE-reactive epitopes to be solvent accessible and share significant homology with other tree nuts providing a possible basis for previously observed cross-reactivity.

High-sensitive factor I and C-reactive protein based biomarkers for coronary artery disease.

PubMed

Zhao, Qing; Du, Jian-Shi; Han, Dong-Mei; Ma, Ying

2014-01-01

An analysis of high-sensitive factor I and C-reactive proteins as biomarkers for coronary artery disease has been performed from 19 anticipated cohort studies that included 21,567 participants having no information about coronary artery disease. Besides, the clinical implications of statin therapy initiated due to assessment of factor I and C-reactive proteins have also been modeled during studies. The measure of risk discrimination (C-index) was increased (by 0.0101) as per the prognostic model for coronary artery disease with respect to sex, smoking status, age, blood pressure, total cholesterol level along with diabetic history characteristic parameters. The C-index was further raised by 0.0045 and 0.0053 when factor I and C-reactive proteins based information were added, respectively which finally predicted 10-year risk categories as: high (> 20%), medium (10% to < 20%), and low (< 10%) risks. We found 2,254 persons (among 15,000 adults (age ≥ 45 years)) would initially be classified as being at medium risk for coronary artery disease when only conventional risk factors were used as calculated risk. Besides, persons with a predicted risk of more than 20% as well as for persons suffering from other risk factors (i.e. diabetes), statin therapy was initiated (irrespective of their decade old predicted risk). We conclude that under current treatment guidelines assessment of factor I and C-reactive proteins levels (as biomarker) in people at medium risk for coronary artery disease could prevent one additional coronary artery disease risk over a period a decade for every 390-500 people screened.

Solutions to a reduced Poisson–Nernst–Planck system and determination of reaction rates

PubMed Central

Li, Bo; Lu, Benzhuo; Wang, Zhongming; McCammon, J. Andrew

2010-01-01

We study a reduced Poisson–Nernst–Planck (PNP) system for a charged spherical solute immersed in a solvent with multiple ionic or molecular species that are electrostatically neutralized in the far field. Some of these species are assumed to be in equilibrium. The concentrations of such species are described by the Boltzmann distributions that are further linearized. Others are assumed to be reactive, meaning that their concentrations vanish when in contact with the charged solute. We present both semi-analytical solutions and numerical iterative solutions to the underlying reduced PNP system, and calculate the reaction rate for the reactive species. We give a rigorous analysis on the convergence of our simple iteration algorithm. Our numerical results show the strong dependence of the reaction rates of the reactive species on the magnitude of its far field concentration as well as on the ionic strength of all the chemical species. We also find non-monotonicity of electrostatic potential in certain parameter regimes. The results for the reactive system and those for the non-reactive system are compared to show the significant differences between the two cases. Our approach provides a means of solving a PNP system which in general does not have a closed-form solution even with a special geometrical symmetry. Our findings can also be used to test other numerical methods in large-scale computational modeling of electro-diffusion in biological systems. PMID:20228879

Reactivation of wild-type and mutant p53 by tryptophanolderived oxazoloisoindolinone SLMP53-1, a novel anticancer small-molecule

PubMed Central

Soares, Joana; Raimundo, Liliana; Pereira, Nuno A.L.; Monteiro, Ângelo; Gomes, Sara; Bessa, Cláudia; Pereira, Clara; Queiroz, Glória; Bisio, Alessandra; Fernandes, João; Gomes, Célia; Reis, Flávio; Gonçalves, Jorge; Inga, Alberto; Santos, Maria M.M.; Saraiva, Lucília

2016-01-01

Restoration of the p53 pathway, namely by reactivation of mutant (mut) p53, represents a valuable anticancer strategy. Herein, we report the identification of the enantiopure tryptophanol-derived oxazoloisoindolinone SLMP53-1 as a novel reactivator of wild-type (wt) and mut p53, using a yeast-based screening strategy. SLMP53-1 has a p53-dependent anti-proliferative activity in human wt and mut p53R280K-expressing tumor cells. Additionally, SLMP53-1 enhances p53 transcriptional activity and restores wt-like DNA binding ability to mut p53R280K. In wt/mut p53-expressing tumor cells, SLMP53-1 triggers p53 transcription-dependent and mitochondrial apoptotic pathways involving BAX, and wt/mut p53 mitochondrial translocation. SLMP53-1 inhibits the migration of wt/mut p53-expressing tumor cells, and it shows promising p53-dependent synergistic effects with conventional chemotherapeutics. In xenograft mice models, SLMP53-1 inhibits the growth of wt/mut p53-expressing tumors, but not of p53-null tumors, without apparent toxicity. Collectively, besides the potential use of SLMP53-1 as anticancer drug, the tryptophanol-derived oxazoloisoindolinone scaffold represents a promissing starting point for the development of effective p53-reactivating drugs. PMID:26735173

Evaluation of an automated connective tissue disease screening assay in Korean patients with systemic rheumatic diseases

PubMed Central

Jeong, Seri; Yang, Heeyoung; Hwang, Hyunyong

2017-01-01

This study aimed to evaluate the diagnostic utilities of the automated connective tissues disease screening assay, CTD screen, in patients with systemic rheumatic diseases. A total of 1093 serum samples were assayed using CTD screen and indirect immunofluorescent (IIF) methods. Among them, 162 were diagnosed with systemic rheumatic disease, including rheumatoid arthritis (RA), systemic lupus erythematosus (SLE), and mixed connective tissue disease (MCT). The remaining 931 with non-systemic rheumatic disease were assigned to the control group. The median ratios of CTD screen tests were significantly higher in the systemic rheumatic disease group than in the control group. The positive likelihood ratios of the CTD screen were higher than those of IIF in patients with total rheumatic diseases (4.1 vs. 1.6), including SLE (24.3 vs. 10.7). The areas under the receiver operating characteristic curves (ROC-AUCs) of the CTD screen for discriminating total rheumatic diseases, RA, SLE, and MCT from controls were 0.68, 0.56, 0.92 and 0.80, respectively. The ROC-AUCs of the combinations with IIF were significantly higher in patients with total rheumatic diseases (0.72) and MCT (0.85) than in those of the CTD screen alone. Multivariate analysis indicated that both the CTD screen and IIF were independent variables for predicting systemic rheumatic disease. CTD screen alone and in combination with IIF were a valuable diagnostic tool for predicting systemic rheumatic diseases, particularly for SLE. PMID:28273146

Evaluation of an automated connective tissue disease screening assay in Korean patients with systemic rheumatic diseases.

PubMed

Jeong, Seri; Yang, Heeyoung; Hwang, Hyunyong

2017-01-01

This study aimed to evaluate the diagnostic utilities of the automated connective tissues disease screening assay, CTD screen, in patients with systemic rheumatic diseases. A total of 1093 serum samples were assayed using CTD screen and indirect immunofluorescent (IIF) methods. Among them, 162 were diagnosed with systemic rheumatic disease, including rheumatoid arthritis (RA), systemic lupus erythematosus (SLE), and mixed connective tissue disease (MCT). The remaining 931 with non-systemic rheumatic disease were assigned to the control group. The median ratios of CTD screen tests were significantly higher in the systemic rheumatic disease group than in the control group. The positive likelihood ratios of the CTD screen were higher than those of IIF in patients with total rheumatic diseases (4.1 vs. 1.6), including SLE (24.3 vs. 10.7). The areas under the receiver operating characteristic curves (ROC-AUCs) of the CTD screen for discriminating total rheumatic diseases, RA, SLE, and MCT from controls were 0.68, 0.56, 0.92 and 0.80, respectively. The ROC-AUCs of the combinations with IIF were significantly higher in patients with total rheumatic diseases (0.72) and MCT (0.85) than in those of the CTD screen alone. Multivariate analysis indicated that both the CTD screen and IIF were independent variables for predicting systemic rheumatic disease. CTD screen alone and in combination with IIF were a valuable diagnostic tool for predicting systemic rheumatic diseases, particularly for SLE.

Ru-decorated Pt surfaces as model fuel cell electrocatalysts for CO electrooxidation.

PubMed

Maillard, F; Lu, G-Q; Wieckowski, A; Stimming, U

2005-09-01

This feature article concerns Pt surfaces modified (decorated) by ruthenium as model fuel cell electrocatalysts for electrooxidation processes. This work reveals the role of ruthenium promoters in enhancing electrocatalytic activity toward organic fuels for fuel cells, and it particularly concerns the methanol decomposition product, surface CO. A special focus is on surface mobility of the CO as it is catalytically oxidized to CO(2). Different methods used to prepare Ru-decorated Pt single crystal surfaces as well as Ru-decorated Pt nanoparticles are reviewed, and the methods of characterization and testing of their activity are discussed. The focus is on the origin of peak splitting involved in the voltammetric electrooxidation of CO on Ru-decorated Pt surfaces, and on the interpretative consequences of the splitting for single crystal and nanoparticle Pt/Ru bimetallic surfaces. Apparently, screening through the literature allows formulating several models of the CO stripping reaction, and the validity of these models is discussed. Major efforts are made in this article to compare the results reported by the Urbana-Champaign group and the Munich group, but also by other groups. As electrocatalysis is progressively more and more driven by theory, our review of the experimental findings may serve to summarize the state of the art and clarify the roads ahead. Future studies will deal with highly dispersed and reactive nanoscale surfaces and other more advanced catalytic materials for fuel cell catalysis and related energy applications. It is expected that the metal/metal and metal/substrate interactions will be increasingly investigated on atomic and electronic levels, with likewise increasing participation of theory, and the structure and reactivity of various monolayer catalytic systems involving more than two metals (that is ternary and quaternary systems) will be interrogated.

Impact of mixing chemically heterogeneous groundwaters on the sustainability of an open-loop groundwater heat pump

NASA Astrophysics Data System (ADS)

Burté, L.; Farasin, J.; Cravotta, C., III; Gerard, M. F.; Cotiche Baranger, C.; Aquilina, L.; Le Borgne, T.

2017-12-01

Geothermal systems using shallow aquifers are commonly used for heating and cooling. The sustainability of these systems can be severely impacted by the occurrence of clogging process. The geothermal loop operation (including pumping of groundwater, filtering and heat extraction through exchangers and cooled water injection) can lead to an unexpected biogeochemical reactivity and scaling formation that can ultimately lead to the shutdown of the geothermal doublet. Here, we report the results of investigations carried out on a shallow geothermal doublet (< 40 m depth) affected by rapid clogging processes linked to iron and manganese oxidation. Using a reactive transport model, we determine the parameters controlling clogging. To characterize the biogeochemical processes induced by the operation of the production well, we combined hydrodynamic measurements by flowmeter and in-situ chemical depth profiles. We thus investigated the chemical heterogeneity into the pumping well as a function of the operating conditions (static or dynamic). Hydrochemical data collected at the pumping well showed that groundwater was chemically heterogeneous long the 11 meters well screen. While the aquifer was dominantly oxic, a localized inflow of anoxic water was detected and evaluated to produce about 40% of the total flow . The mixture of chemically heterogeneous water induced by pumping lead to the oxidation of reductive species and thus to the formation of biogenic precipitates responsible for clogging. The impact of pumping waters of different redox potential and chemical characteristics was quantified by numerical modeling using PHREEQC. These results shows that natural chemical heterogeneity can occur at a small scale in heterogeneous aquifers and highlight the importance of their characterization during the production well testing and the geothermal loop operation in order to take preventive measures to avoid clogging.

High-throughput drug screen identifies chelerythrine as a selective inducer of death in a TSC2-null setting.

PubMed

Medvetz, Doug; Sun, Yang; Li, Chenggang; Khabibullin, Damir; Balan, Murugabaskar; Parkhitko, Andrey; Priolo, Carmen; Asara, John M; Pal, Soumitro; Yu, Jane; Henske, Elizabeth P

2015-01-01

Tuberous sclerosis complex (TSC) is an autosomal dominant syndrome associated with tumors of the brain, heart, kidney, and lung. The TSC protein complex inhibits the mammalian or mechanistic target of rapamycin complex 1 (mTORC1). Inhibitors of mTORC1, including rapamycin, induce a cytostatic response in TSC tumors, resulting in temporary disease stabilization and prompt regrowth when treatment is stopped. The lack of TSC-specific cytotoxic therapies represents an important unmet clinical need. Using a high-throughput chemical screen in TSC2-deficient, patient-derived cells, we identified a series of molecules antagonized by rapamycin and therefore selective for cells with mTORC1 hyperactivity. In particular, the cell-permeable alkaloid chelerythrine induced reactive oxygen species (ROS) and depleted glutathione (GSH) selectively in TSC2-null cells based on metabolic profiling. N-acetylcysteine or GSH cotreatment protected TSC2-null cells from chelerythrine's effects, indicating that chelerythrine-induced cell death is ROS dependent. Induction of heme-oxygenase-1 (HMOX1/HO-1) with hemin also blocked chelerythrine-induced cell death. In vivo, chelerythrine inhibited the growth of TSC2-null xenograft tumors with no evidence of systemic toxicity with daily treatment over an extended period of time. This study reports the results of a bioactive compound screen and the identification of a potential lead candidate that acts via a novel oxidative stress-dependent mechanism to selectively induce necroptosis in TSC2-deficient tumors. This study demonstrates that TSC2-deficient tumor cells are hypersensitive to oxidative stress-dependent cell death, and provide critical proof of concept that TSC2-deficient cells can be therapeutically targeted without the use of a rapalog to induce a cell death response. ©2014 American Association for Cancer Research.

System Strategies for Colorectal Cancer Screening at Federally Qualified Health Centers

PubMed Central

Levy, Barcey T.; Moss, Carol A.; Bay, Camden P.

2015-01-01

Objectives. We assessed the protocols and system processes for colorectal cancer (CRC) screening at federally qualified health centers (FQHCs) in 4 midwestern states. Methods. We identified 49 FQHCs in 4 states. In January 2013, we mailed their medical directors a 49-item questionnaire about policies on CRC screening, use of electronic medical records, types of CRC screening recommended, clinic tracking systems, referrals for colonoscopy, and barriers to providing CRC. Results. Forty-four questionnaires (90%) were returned. Thirty-three of the respondents (75%) estimated the proportion of their patients up-to-date with CRC screening, with a mean of 35%. One major barrier to screening was inability to provide colonoscopy for patients with a positive fecal occult blood test (59%). The correlation of system strategies and estimated percentage of patients up-to-date with CRC screening was 0.43 (P = .01). Conclusions. CRC system strategies were associated with higher CRC screening rates. Implementing system strategies for CRC screening takes time and effort and is important to maintain, to help prevent, or to cure many cases of CRC, the second leading cause of cancer in the United States. PMID:24832146

Unified Behavior Framework for Discrete Event Simulation Systems

DTIC Science & Technology

2015-03-26

I would like to thank Dr. Hodson for his guidance and direction throughout the AFIT program. I also would like to thank my thesis committee members...SPA Sense-Plan-Act SSL System Service Layer TCA Task Control Architecture TRP Teleo-Reactive Program UAV Unmanned Aerial Vehicle UBF Unified Behavior...a teleo-reactive architecture [11]. Teleo-Reactive Programs ( TRPs ) are composed of a list of rules, where each has a condition and an action. When the

Screening for cardiac disease in potential recruits to the British Army.

PubMed

Cox, Andrew T; Cameron-Smith, M; Folkes, F; Sharma, S; Boos, C

2015-09-01

The British Army screens potential recruits for disease, including cardiovascular disease, at the pre-employment medical assessment in the Army Selection Centres. The epidemiology of cardiovascular disease in the Armed Forces coupled with the high physical demand placed on the cardiovascular system, often in remote locations make screening desirable. This is particularly pertinent as servicemen and women die from cardiovascular disease each year. To evaluate this particular screening system it is essential to understand the aim of the system, how it is designed and how screening systems in general are evaluated. The efficacy of a screening test is quantified using the measurements of sensitivity, specificity and likelihood ratios. These measurements are defined and the pitfalls associated with evaluating a screening system are described. The different screening tests used to identify cardiac disease and their individual strengths and weaknesses, are illustrated. Finally the article reviews the previous British Army recruit cardiac screening system, that used a stereotyped history and physical examination and the newer system that replaced it, which includes the incorporation of the 12-lead ECG and on site echocardiography in individuals revealing abnormalities on history, examination or ECG. Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to http://group.bmj.com/group/rights-licensing/permissions.

The Reactive Species Interactome: Evolutionary Emergence, Biological Significance, and Opportunities for Redox Metabolomics and Personalized Medicine

PubMed Central

Koning, Anne; Kuhnle, Gunter G.C.; Nagy, Peter; Bianco, Christopher L.; Pasch, Andreas; Wink, David A.; Fukuto, Jon M.; Jackson, Alan A.; van Goor, Harry; Olson, Kenneth R.

2017-01-01

Abstract Significance: Oxidative stress is thought to account for aberrant redox homeostasis and contribute to aging and disease. However, more often than not, administration of antioxidants is ineffective, suggesting that our current understanding of the underlying regulatory processes is incomplete. Recent Advances: Similar to reactive oxygen species and reactive nitrogen species, reactive sulfur species are now emerging as important signaling molecules, targeting regulatory cysteine redox switches in proteins, affecting gene regulation, ion transport, intermediary metabolism, and mitochondrial function. To rationalize the complexity of chemical interactions of reactive species with themselves and their targets and help define their role in systemic metabolic control, we here introduce a novel integrative concept defined as the reactive species interactome (RSI). The RSI is a primeval multilevel redox regulatory system whose architecture, together with the physicochemical characteristics of its constituents, allows efficient sensing and rapid adaptation to environmental changes and various other stressors to enhance fitness and resilience at the local and whole-organism level. Critical Issues: To better characterize the RSI-related processes that determine fluxes through specific pathways and enable integration, it is necessary to disentangle the chemical biology and activity of reactive species (including precursors and reaction products), their targets, communication systems, and effects on cellular, organ, and whole-organism bioenergetics using system-level/network analyses. Future Directions: Understanding the mechanisms through which the RSI operates will enable a better appreciation of the possibilities to modulate the entire biological system; moreover, unveiling molecular signatures that characterize specific environmental challenges or other forms of stress will provide new prevention/intervention opportunities for personalized medicine. Antioxid. Redox Signal. 27, 684–712. PMID:28398072

Reactive multi-particle collision dynamics with reactive boundary conditions

NASA Astrophysics Data System (ADS)

Sayyidmousavi, Alireza; Rohlf, Katrin

2018-07-01

In the present study, an off-lattice particle-based method called the reactive multi-particle collision (RMPC) dynamics is extended to model reaction-diffusion systems with reactive boundary conditions in which the a priori diffusion coefficient of the particles needs to be maintained throughout the simulation. To this end, the authors have made use of the so-called bath particles whose purpose is only to ensure proper diffusion of the main particles in the system. In order to model partial adsorption by a reactive boundary in the RMPC, the probability of a particle being adsorbed, once it hits the boundary, is calculated by drawing an analogy between the RMPC and Brownian Dynamics. The main advantages of the RMPC compared to other molecular based methods are less computational cost as well as conservation of mass, energy and momentum in the collision and free streaming steps. The proposed approach is tested on three reaction-diffusion systems and very good agreement with the solutions to their corresponding partial differential equations is observed.

Sensitivity analysis of reactive ecological dynamics.

PubMed

Verdy, Ariane; Caswell, Hal

2008-08-01

Ecological systems with asymptotically stable equilibria may exhibit significant transient dynamics following perturbations. In some cases, these transient dynamics include the possibility of excursions away from the equilibrium before the eventual return; systems that exhibit such amplification of perturbations are called reactive. Reactivity is a common property of ecological systems, and the amplification can be large and long-lasting. The transient response of a reactive ecosystem depends on the parameters of the underlying model. To investigate this dependence, we develop sensitivity analyses for indices of transient dynamics (reactivity, the amplification envelope, and the optimal perturbation) in both continuous- and discrete-time models written in matrix form. The sensitivity calculations require expressions, some of them new, for the derivatives of equilibria, eigenvalues, singular values, and singular vectors, obtained using matrix calculus. Sensitivity analysis provides a quantitative framework for investigating the mechanisms leading to transient growth. We apply the methodology to a predator-prey model and a size-structured food web model. The results suggest predator-driven and prey-driven mechanisms for transient amplification resulting from multispecies interactions.

Startup of RAPID-L Lunar Base Reactor by Lithium Release Module

NASA Astrophysics Data System (ADS)

Kambe, Mitsuru

The 200 kWe uranium-nitride fueled lithium cooled fast reactor concept RAPID-L to be combined with thermoelectric power conversion system for lunar base power system is demonstrated. Unique challenges in reactivity control systems design have been attempted in RAPID-L concept. The reactor involves the following innovative reactivity control systems: Lithium Expansion Modules (LEM) for inherent reactivity feedback, Lithium Injection Modules (LIM) for inherent ultimate shutdown, and Lithium Release Modules (LRM) for automated reactor startup. All these systems adopt lithium-6 as a liquid poison instead of conventional B4C rods or Be reflectors. These systems are effective independent of the magnitude and direction of the gravity force. In 2006, however, the following design amendment has been made. 1) B4C poison rods were added to ensure criticality safety in unintended positive reactivity insertion by LRMs due to fire in the launch phase accident; because LRM freeze seal melts at 800°C which result in positive reactivity insertion. 2) Lower hot standby temperature of 200°C was adopted instead of conventional 800°C to reduce the external power at the startup. In this paper, development of the LRM orifice which dominates the startup transient of RAPID-L is discussed. An attention was focused how to achieve sufficiently small flow rate of 6Li in the orifice because it enables moderate positive reactivity insertion rate. The LRM orifice performance has been confirmed using 0.5 mm diameter SUS316 orifice/lithium flow test setup in the glove box.

Design and evaluation of thermodynamic vent/screen baffle cryogenic storage system. [for space shuttles, space tugs, and spacelab

NASA Technical Reports Server (NTRS)

Cady, E. C.

1975-01-01

A comprehensive analytical program was performed to compare an integrated thermodynamic vent/screen baffle orbital cryogenic propellant storage and transfer system with other concepts. The screen systems were found to be 20% to 29% lighter in weight than a propulsively accelerated Tug-scale LH2/LO2 resupply module. The screen systems were compared with small-scale supercritical storage systems for the space shuttle fuel cell reactant and life support system fluid supply and were lighter by up to 556 kg (1225 lb) for the extended 30-day mission. When compared with high-pressure gas storage for the spacelab atmosphere supply, the screen system saved 79% of the inert system weight for the 30-day mission. An experimental program found that heat flux rates up to 9,450 watts/sq m (3,000 Btu/hr-sq ft) degraded the LH2 bubble point performance of eight screens by a maximum of 12.5%. No effects of helium pressurant, screen material, or LH2 superheat were observed.

Antibodies elicited during natural infection in a predominantly Plasmodium falciparum transmission area cross-react with sexual stage-specific antigen in P. vivax.

PubMed

Bansal, Geetha P; Vengesai, Arthur; Cao, Yi; Mduluza, Takafira; Kumar, Nirbhay

2017-06-01

Infections caused by Plasmodium falciparum and P. vivax account for more than 90% of global malaria burden. Exposure to malaria parasite elicits immune responses during natural infection and it is generally believed that the immunity is not only stage specific but also species specific. However, partial genomic similarity for various antigens in different Plasmodium spp. raises the possibility of immunological cross-reactivity at the level of specific antigens. Serum samples collected from children who were permanent residents of a P. falciparum transmission area in Zimbabwe were screened for antibody reactivity against Pfs48/45, a P. falciparum gametocyte antigen and Pvs48/45, a P. vivax homolog of Pfs48/45 using ELISA. Western blotting was used to further confirm identity of the specific antibody reactivity to the Pfs48/45 and Pvs48/45 proteins. Pan Plasmodium PCR and nested PCR were used to confirm infection with the Plasmodium species. Twenty-seven percent (49/181) of the participants were found to be sero-positive for Pfs48/45 and 73% (n=36) of these Pfs48/45 positive sera also showed reactivity with Pvs48/45. Immune cross-reactivity revealed by ELISA was also confirmed by Western blot analysis using a panel of randomly selected 23 Pfs48/45 and Pvs48/45 ELISA positive samples. Nested PCR analysis of 27 blood samples randomly selected from the 36 that showed positive ELISA reactivity to both Pfs48/45 and Pvs48/45 antigens confirmed infection with P. falciparum and generalized absence of P. vivax except for a single sample which revealed PCR positivity for both P. vivax and P. falciparum. Our studies with sera samples from a predominantly P. falciparum transmission area in Zimbabwe suggest immunological cross-reactivity with Pvs48/45, thus raising the possibility of partial species cross-reactive immunity and possible cross-boosting of immunity during co-infection with P. falciparum and P. vivax. Copyright © 2017 Elsevier B.V. All rights reserved.

[Visual–manual tracking after long spaceflight].

PubMed

2016-01-01

This study presents the results of the pre- and postflight clinical and physiological examination (CPE) and scientific experiment “Sensory Adaptation-2” carried out in Yu.A. Gagarin Research & Test Cosmonaut Training Center. There were examined 14 Russian cosmonauts, crewmembers of long-term international spaceflights ISS-28/29 to ISS 36/37, who were in microgravity from 159 to 195 days. Age of the cosmonauts was 35–50 years. Studies were conducted twice before space flight (baseline), and on days R+1(2), R+4(5), and R+8(9) after landing. In the study of visual–manual tracking (VMT), eye movements were recorded by the electrooculography method (EOG), hand movements - by a joystick using biological visual feedback (on the screen represented the current angle/position of a joystick). Examinations were conducted using computerized stimulation programs, which were presented on the screen of the hardware-software complex "Sensomotor". Examinations of the VMT took place in the dialog mode and included the following sections: a) EOG-calibration; b) visual-manual tracking within ±10° on the screen with blank background (smooth linear and sinusoidal movement of a point target with a frequency of 0.16 Hz in the vertical and horizontal directions). There were evaluated time, amplitude, and velocity characteristics of visual and manual tracking (VT and MT), including the effectiveness (EC) and gain (GC) coefficients which were calculated respectively, as the ratio of amplitude and velocity of the visual stimulus (target). A study of the vestibular function (VF) was performed before and after space flight using videooculography. There were assessed static torsion otolith–cervical–ocular reflex, dynamic vestibular–cervical–ocular reactions, vestibular reactivity, spontaneous eye movements. Study of VF in the first postflight has shown a sharp decrease (up to its complete absence) of static vestibular excitability (otolith reflex) accompanied by the increased dynamic reactivity of the vestibular system. Study of VTM has shown a significant decrease of gain and effectiveness/amplitud of VT in the first days postflight, as well as correlation between the parameters of VF and MT, between the VF and VT, and no found correlation between parameters of VF and MT. It was found that the conditions of space flight (microgravity) have a greater impact on the accuracy of the VT than the accuracy of MT. Full return of characteristics of the VMT and VF to the baseline was observed on R+8(9) days after space flight.

ReaCog, a Minimal Cognitive Controller Based on Recruitment of Reactive Systems

PubMed Central

Schilling, Malte; Cruse, Holk

2017-01-01

It has often been stated that for a neuronal system to become a cognitive one, it has to be large enough. In contrast, we argue that a basic property of a cognitive system, namely the ability to plan ahead, can already be fulfilled by small neuronal systems. As a proof of concept, we propose an artificial neural network, termed reaCog, that, first, is able to deal with a specific domain of behavior (six-legged-walking). Second, we show how a minor expansion of this system enables the system to plan ahead and deploy existing behavioral elements in novel contexts in order to solve current problems. To this end, the system invents new solutions that are not possible for the reactive network. Rather these solutions result from new combinations of given memory elements. This faculty does not rely on a dedicated system being more or less independent of the reactive basis, but results from exploitation of the reactive basis by recruiting the lower-level control structures in a way that motor planning becomes possible as an internal simulation relying on internal representation being grounded in embodied experiences. PMID:28194106

Young Investigator Proposal, Research Area 7.4 Reactive Chemical Systems: Multifunctional, Bimetallic Nanomaterials Prepared by Atomic Layer Electroless Deposition

DTIC Science & Technology

2017-09-30

Report: Young Investigator Proposal, Research Area 7.4 Reactive Chemical Systems: Multifunctional, Bimetallic Nanomaterials Prepared by Atomic Layer...ES) U.S. Army Research Office P.O. Box 12211 Research Triangle Park, NC 27709-2211 REPORT DOCUMENTATION PAGE 11. SPONSOR/MONITOR’S REPORT NUMBER...Number: W911NF-16-1-0438 Organization: University of Massachusetts - North Dartmouth Title: Young Investigator Proposal, Research Area 7.4 Reactive

Screening Systems and Decision Making at the Preschool Level: Application of a Comprehensive Validity Framework

ERIC Educational Resources Information Center

Kettler, Ryan J.; Feeney-Kettler, Kelly A.

2011-01-01

Universal screening is designed to be an efficient method for identifying preschool students with mental health problems, but prior to use, screening systems must be evaluated to determine their appropriateness within a specific setting. In this article, an evidence-based validity framework is applied to four screening systems for identifying…

Proceedings of radiological health symposium

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

Doi, K.; Holje, G.; Loo, L.N.

Resolution (or sharpness) of radiographic screen-film systems influences the physical image quality of radiographs, and thereby the diagnositc accuracy and patient exposure. We use the modulation transfer function (MTF) to quantify the resolution property of screen-film systems. In our laboratory, the slit method and the digital Fourier transformation are used for measurements of the MTFs of screen-film systems. Recent measurements indicate that the MTFs of Detail, Par Speed, and Hi-Plus screens with XRP film are significantly lower than the MTFs of the same screens with Blue Brand film. This result underscores the need to evaluate the resolution property of screen-filmmore » systems with close attention to the x-ray film used.« less

Thermodynamic responses of electronic systems.

PubMed

Franco-Pérez, Marco; Ayers, Paul W; Gázquez, José L; Vela, Alberto

2017-09-07

We present how the framework of the temperature-dependent chemical reactivity theory can describe the panorama of different types of interactions between an electronic system and external reagents. The key reactivity indicators are responses of an appropriate state function (like the energy or grand potential) to the variables that determine the state of the system (like the number of electrons/chemical potential, external potential, and temperature). We also consider the response of the average electron density to appropriate perturbations. We present computable formulas for these reactivity indicators and discuss their chemical utility for describing electronic, electrostatic, and thermal changes associated with chemical processes.

Thermodynamic responses of electronic systems

NASA Astrophysics Data System (ADS)

Franco-Pérez, Marco; Ayers, Paul W.; Gázquez, José L.; Vela, Alberto

2017-09-01

We present how the framework of the temperature-dependent chemical reactivity theory can describe the panorama of different types of interactions between an electronic system and external reagents. The key reactivity indicators are responses of an appropriate state function (like the energy or grand potential) to the variables that determine the state of the system (like the number of electrons/chemical potential, external potential, and temperature). We also consider the response of the average electron density to appropriate perturbations. We present computable formulas for these reactivity indicators and discuss their chemical utility for describing electronic, electrostatic, and thermal changes associated with chemical processes.

Prototype Systems Containing Human Cytochrome P450 for High-Throughput Real-Time Detection of DNA Damage by Compounds That Form DNA-Reactive Metabolites.

PubMed

Brito Palma, Bernardo; Fisher, Charles W; Rueff, José; Kranendonk, Michel

2016-05-16

The formation of reactive metabolites through biotransformation is the suspected cause of many adverse drug reactions. Testing for the propensity of a drug to form reactive metabolites has increasingly become an integral part of lead-optimization strategy in drug discovery. DNA reactivity is one undesirable facet of a drug or its metabolites and can lead to increased risk of cancer and reproductive toxicity. Many drugs are metabolized by cytochromes P450 in the liver and other tissues, and these reactions can generate hard electrophiles. These hard electrophilic reactive metabolites may react with DNA and may be detected in standard in vitro genotoxicity assays; however, the majority of these assays fall short due to the use of animal-derived organ extracts that inadequately represent human metabolism. The current study describes the development of bacterial systems that efficiently detect DNA-damaging electrophilic reactive metabolites generated by human P450 biotransformation. These assays use a GFP reporter system that detects DNA damage through induction of the SOS response and a GFP reporter to control for cytotoxicity. Two human CYP1A2-competent prototypes presented here have appropriate characteristics for the detection of DNA-damaging reactive metabolites in a high-throughput manner. The advantages of this approach include a short assay time (120-180 min) with real-time measurement, sensitivity to small amounts of compound, and adaptability to a microplate format. These systems are suitable for high-throughput assays and can serve as prototypes for the development of future enhanced versions.