77 FR 20648 - Certain Digital Models, Digital Data, and Treatment Plans for Use in Making Incremental Dental...

Federal Register 2010, 2011, 2012, 2013, 2014

2012-04-05

... which the complaint is to be served: ClearCorrect Pakistan (Private), Ltd., Azia Cottage, 9-Kanal Park, Gulberg II, Lahore, Pakistan. ClearCorrect Operating, LLC, 15151 Sommermeyer Street, Houston, TX 77041...

Young donor-graft assisted endothelial keratoplasty (PDEK/DMEK) with epithelial debridement for chronic pseudophakic bullous keratopathy.

PubMed

Agarwal, Amar; Narang, Priya; Kumar, Dhivya A; Agarwal, Ashvin

2017-10-01

The aim of this study was to describe the applicability and report visual outcomes for the treatment of subepithelial fibrosis and anterior stromal scarring in cases of chronic pseudophakic bullous keratopathy (PBK) with epithelial debridement and endothelial keratoplasty (EK) (pre-Descemet endothelial keratoplasty [PDEK]; Descemet membrane endothelial keratoplasty [(DMEK]) using young donor tissue. Prospective, single-centre, interventional study. 6 cases with chronic PBK (> 1 year duration). Case 1 underwent PDEK with glued intraocular lens (IOL) as a single-stage procedure, whereas cases 2 and 3 underwent glued IOL followed by DMEK and PDEK, respectively, as a second-stage procedure. Cases 4 and 6 underwent PDEK, whereas case 5 underwent DMEK. Epithelial debridement was performed in all cases at the time of EK, and young donor grafts were used. The main outcome measures were best spectacle-corrected visual acuity, clearance of corneal scar and haze, central corneal thickness (CCT), specular microscopy, and endothelial cell count (ECC). Postoperatively, all cases demonstrated significant improvement in visual acuity. The mean value of depth of subepithelial haze was 121±71.7 µm and 25.3 ± 19.8 µm in the preoperative and postoperative periods, respectively (p = 0.028). At the 1-month follow-up, the mean preoperative CCT of 676 ± 92.7 µm was reduced to 534.6 ± 21.1µm. At the 6-month follow-up, the mean ECC loss resulting from the procedure was 36.5 ± 10.4%. EK with epithelial debridement performed for the treatment of chronic PBK resulted in significantly improved visual acuity to a functional level, with the clearance of subepithelial fibrosis and anterior stromal scar, in most patients. Copyright © 2017 Canadian Ophthalmological Society. Published by Elsevier Inc. All rights reserved.

Changing Practice Patterns and Long-term Outcomes of Endothelial Versus Penetrating Keratoplasty: A Prospective Dutch Registry Study.

PubMed

Dickman, Mor M; Peeters, Jean Marie P W U; van den Biggelaar, Frank J H M; Ambergen, Ton A W; van Dongen, Martin C J M; Kruit, Pieter Jan; Nuijts, Rudy M M A

2016-10-01

To compare graft survival, best-corrected visual acuity (BCVA), endothelial cell density (ECD), and refraction following penetrating keratoplasty (PK) vs endothelial keratoplasty (EK) for Fuchs endothelial dystrophy (FED) and pseudophakic bullous keratopathy (PBK). Nonrandomized treatment comparison with national registry data. All consecutive patients undergoing first keratoplasty for FED and PBK between 1998 and 2014 were analyzed, with a maximum follow-up of 5 years (mean ± SD follow-up 39 ± 20 months, range 0-60 months). Graft survival was analyzed using Kaplan-Meier survival curves and Cox regression analysis. BCVA, ECD, and refractive error were compared using linear mixed models. Main outcome measures were graft survival, BCVA, refraction, and ECD. A total of 5115 keratoplasties (PK = 2390; EK = 2725) were identified. Two-year graft survival following EK was lower compared with PK (94.5% vs 96.3%, HR = 1.56, P = .001). Five-year survival was comparable for EK and PK (93.4% vs 89.7%, HR = 0.89, P = .261). EK graft survival improved significantly over time while remaining stable for PK. One-year BCVA was better following EK vs PK (0.34 vs 0.47 logMAR, P < .001). Astigmatism was lower 1 year after EK vs PK (-1.69 vs -3.52 D, P < .001). One-year ECD was lower after EK vs PK (1472 vs 1859 cells/mm 2 , P < .001). At 3 years, ECD did not differ between EK and PK. Long-term graft survival after EK and PK is high and comparable despite lower short-term survival for EK. EK graft survival improved over time, suggesting a learning curve. EK results in better BCVA, lower astigmatism, and similar long-term ECD compared with PK for FED and PBK. Copyright © 2016 Elsevier Inc. All rights reserved.

Automated workflows for modelling chemical fate, kinetics and toxicity.

PubMed

Sala Benito, J V; Paini, Alicia; Richarz, Andrea-Nicole; Meinl, Thorsten; Berthold, Michael R; Cronin, Mark T D; Worth, Andrew P

2017-12-01

Automation is universal in today's society, from operating equipment such as machinery, in factory processes, to self-parking automobile systems. While these examples show the efficiency and effectiveness of automated mechanical processes, automated procedures that support the chemical risk assessment process are still in their infancy. Future human safety assessments will rely increasingly on the use of automated models, such as physiologically based kinetic (PBK) and dynamic models and the virtual cell based assay (VCBA). These biologically-based models will be coupled with chemistry-based prediction models that also automate the generation of key input parameters such as physicochemical properties. The development of automated software tools is an important step in harmonising and expediting the chemical safety assessment process. In this study, we illustrate how the KNIME Analytics Platform can be used to provide a user-friendly graphical interface for these biokinetic models, such as PBK models and VCBA, which simulates the fate of chemicals in vivo within the body and in vitro test systems respectively. Copyright © 2017 The Authors. Published by Elsevier Ltd.. All rights reserved.

Tuning the overlap and the cross-layer correlations in two-layer networks: Application to a susceptible-infectious-recovered model with awareness dissemination

NASA Astrophysics Data System (ADS)

Juher, David; Saldaña, Joan

2018-03-01

We study the properties of the potential overlap between two networks A ,B sharing the same set of N nodes (a two-layer network) whose respective degree distributions pA(k ) ,pB(k ) are given. Defining the overlap coefficient α as the Jaccard index, we prove that α is very close to 0 when A and B are random and independently generated. We derive an upper bound αM for the maximum overlap coefficient permitted in terms of pA(k ) , pB(k ) , and N . Then we present an algorithm based on cross rewiring of links to obtain a two-layer network with any prescribed α inside the range (0 ,αM) . A refined version of the algorithm allows us to minimize the cross-layer correlations that unavoidably appear for values of α beyond a critical overlap αc<αM . Finally, we present a very simple example of a susceptible-infectious-recovered epidemic model with information dissemination and use the algorithms to determine the impact of the overlap on the final outbreak size predicted by the model.

Building Partner Capabilities for Coalition Operations

DTIC Science & Technology

2007-01-01

HEALTH CARE INTERNATIONAL AFFAIRS NATIONAL SECURITY POPULATION AND AGING PUBLIC SAFETY SCIENCE AND TECHNOLOGY SUBSTANCE ABUSE TERRORISM AND HOMELAND...distribution unlimited Jennifer D. P. Moroney • Nancy E. Blacker Renee Buhr • James McFadden Cathryn Quantic Thurston • Anny Wong The RAND...4211-8 (pbk. : alk. paper) 1. Combined operations (Military science ) 2. United States. Army— Organization. 3. Multinational armed forces—Organization

International Cooperation with Partner Air Forces

DTIC Science & Technology

2009-01-01

AND HEALTH CARE INTERNATIONAL AFFAIRS NATIONAL SECURITY POPULATION AND AGING PUBLIC SAFETY SCIENCE AND TECHNOLOGY SUBSTANCE ABUSE TERRORISM AND...bibliographical references. “MG-203.” ISBN 978-0-8330-4571-3 (pbk. : alk. paper) 1. Combined operations (Military science ) 2. United States. Air Force. 3...Military relations—Foreign countries. 7. Military art and science —International cooperation. I. Moroney, Jennifer D. P., 1973– U260.I53 2009

Methodology for Constructing a Modernization Roadmap for Air Force Automatic Test Systems

DTIC Science & Technology

2012-01-01

Constructing a Modernization Roadmap for Air Force Automatic Test Systems Lionel A. Galway , Rachel Rue, James M. Masters, Ben D. Van Roo, Manuel...constructing a modernization roadmap for Air Force automatic test systems / Lionel A. Galway ... [et al.]. p. cm. Includes bibliographical...references. ISBN 978-0-8330-5899-7 (pbk. : alk. paper) 1. United States. Air Force—Weapons systems—Testing. I. Galway , Lionel A., 1950- UG633.M3445

Methods Development for the Isolation and Culture of Primary Corneal Endothelial Cells

DTIC Science & Technology

2017-02-01

are collectively referred to as mustard gas keratopathy (MGK). Prevailing evidence suggests that late onset MGK may result from a deficit in corneal...and PBK is similar to that seen in mustard gas keratopathy (MGK).3,6,7 MGK can occur years after ocular sulfur mustard (SM) exposure. Treatment...component into the stage component such that the O-ring creates a liquid -tight seal. The final assembled device is shown in panel D. A primary

North Korean Paradoxes. Circumstances, Costs, and Consequences of Korean Unification

DTIC Science & Technology

2005-01-01

consequences of Korean unification / Charles Wolf, Jr., Kamil Akramov. p. cm. "MG-333." Includes bibliographical references. ISBN 0-8330-3762-5 (pbk. : alk ...Institute of Technology NBER National Bureau for Economic Research OECD Organization for Economic Cooperation and Develoment OSD Office of the Secretary of...opment ( OECD ) with a per capita income over $10,000 and the other a "lights-out" but nuclear-capable dynastic state-is the riddle; how to link economic

Improving the Composability of Department of Defense Models and Simulations

DTIC Science & Technology

2003-01-01

Simulations 5a. CONTRACT NUMBER 5b. GRANT NUMBER 5c. PROGRAM ELEMENT NUMBER 6. AUTHOR(S) 5d. PROJECT NUMBER 5e. TASK NUMBER 5f. WORK UNIT NUMBER 7...bibliographical references. “MG-101.” ISBN 0-8330-3525-8 (pbk. : alk. paper) 1. Military art and science— United States—Mathematical models. 2...Military art and science— United States—Simulation methods. 3. Operations research. 4. Military research— United States. 5. Military planning— United States

China and India, 2025: A Comparative Assessment

DTIC Science & Technology

2011-01-01

Charles Wolf ... [et al.]. p. cm. Includes bibliographical references. ISBN 978-0-8330-5042-7 (pbk. : alk. paper ) 1. Economic development...http://www.rand.org/nsrd/about/isdp.html or contact the director (contact information is provided on the web page). v Contents Preface...2010. Year B ir th s p er 1 ,0 00 p o p u la ti o n 30 25 20 15 10 5 0 2030202520202015201020052000 2035 China India 2010 2020–2025 Figure 2.3 Total

Support Air and Space Expeditionary Forces. Analysis of Combat Support Basing Options

DTIC Science & Technology

2004-01-01

Mahyar A . Amouzegar, Robert S. Tripp, Ronald G. McGarve Edward W Chan C. Robert Roll, Jr. _77 Ap L_ L; Reý PROJECT AIR FORCE - Supporting Air and Space...Expeditionary Forces Analysis of Combat Support Basing Options Mahyar A . Amouzegar Robert S. Tripp Ronald G. McGarvey Edward W. Chan C. Robert Roll...support basing options / Mahyar A . Amouzegar ... [et al. p. cm. "’MG-261." Indudes bibliographical references. ISBN 0-8330-3675-0 (pbk.) 1. Air bases

Acoustically-Evoked Auditory Change Complex in Children with Auditory Neuropathy Spectrum Disorder: A Potential Objective Tool for Identifying Cochlear Implant Candidates

PubMed Central

He, Shuman; Grose, John H.; Teagle, Holly F.B.; Woodard, Jennifer; Park, Lisa R.; Hatch, Debora R.; Roush, Patricia; Buchman, Craig A.

2014-01-01

Objective: The overall aim of the study was to evaluate the feasibility of using electrophysiological measures of the auditory change complex (ACC) to identify candidates for cochlear implantation in children with auditory neuropathy spectrum disorder (ANSD). In order to achieve this overall aim, this study 1) assessed the feasibility of measuring the ACC evoked by temporal gaps in a group of children with ANSD across a wide age range; and 2) investigated the association between gap detection thresholds (GDTs) measured by the ACC recordings and open-set speech-perception performance in these subjects. Design: Nineteen children with bilateral ANSD ranging in age between 1.9 to 14.9 yrs (mean: 7.8 yrs) participated in this study. Electrophysiological recordings of the auditory event-related potential (ERP), including the onset ERP response and the ACC, were completed in all subjects and open-set speech perception was evaluated for a subgroup of sixteen subjects. For the ERP recordings, the stimulus was a Gaussian noise presented through ER-3A insert earphones to the test ear. Two stimulation conditions were used. In the “control condition,” the stimulus was an 800-ms Gaussian noise. In the “gapped condition”, the stimuli were two noise segments, each being 400 ms in duration, separated by one of five gaps (i.e. 5, 10, 20, 50, or 100 ms). The inter-stimulation interval was 1200 ms. The aided open-set speech perception ability was assessed using the Phonetically Balanced Kindergarten (PBK) word lists presented at 60 dB SPL using recorded testing material in a sound booth. For speech perception tests, subjects wore their hearing aids at the settings recommended by their clinical audiologists. For a subgroup of five subjects, psychophysical gap detection thresholds for the Gaussian noise were also assessed using a three-interval, three-alternative forced-choice procedure. Results: Responses evoked by the onset of the Gaussian noise (i.e. onset responses) were

Combined expressional analysis, bioinformatics and targeted proteomics identify new potential therapeutic targets in glioblastoma stem cells.

PubMed

Stangeland, Biljana; Mughal, Awais A; Grieg, Zanina; Sandberg, Cecilie Jonsgar; Joel, Mrinal; Nygård, Ståle; Meling, Torstein; Murrell, Wayne; Vik Mo, Einar O; Langmoen, Iver A

2015-09-22

Glioblastoma (GBM) is both the most common and the most lethal primary brain tumor. It is thought that GBM stem cells (GSCs) are critically important in resistance to therapy. Therefore, there is a strong rationale to target these cells in order to develop new molecular therapies.To identify molecular targets in GSCs, we compared gene expression in GSCs to that in neural stem cells (NSCs) from the adult human brain, using microarrays. Bioinformatic filtering identified 20 genes (PBK/TOPK, CENPA, KIF15, DEPDC1, CDC6, DLG7/DLGAP5/HURP, KIF18A, EZH2, HMMR/RHAMM/CD168, NOL4, MPP6, MDM1, RAPGEF4, RHBDD1, FNDC3B, FILIP1L, MCC, ATXN7L4/ATXN7L1, P2RY5/LPAR6 and FAM118A) that were consistently expressed in GSC cultures and consistently not expressed in NSC cultures. The expression of these genes was confirmed in clinical samples (TCGA and REMBRANDT). The first nine genes were highly co-expressed in all GBM subtypes and were part of the same protein-protein interaction network. Furthermore, their combined up-regulation correlated negatively with patient survival in the mesenchymal GBM subtype. Using targeted proteomics and the COGNOSCENTE database we linked these genes to GBM signalling pathways.Nine genes: PBK, CENPA, KIF15, DEPDC1, CDC6, DLG7, KIF18A, EZH2 and HMMR should be further explored as targets for treatment of GBM.

The Evolution of NATO with Four Plausible Threat Scenarios

DTIC Science & Technology

1987-08-01

were political changes as well. The evolution of British political institutions, and especially the widening of the franchise by electoral reform, had...countries. King Edward, in particular, excited the French imagination. In his con- tact with French statesmen, Edward made clear his desire for an...such as the Mitteland Kanal, British lines of communication and the Teuto- burger Wald before making contact. With Soviet air forces alert against

Gap detection measured with electrically evoked auditory event-related potentials and speech-perception abilities in children with auditory neuropathy spectrum disorder.

PubMed

He, Shuman; Grose, John H; Teagle, Holly F B; Woodard, Jennifer; Park, Lisa R; Hatch, Debora R; Buchman, Craig A

2013-01-01

This study aimed (1) to investigate the feasibility of recording the electrically evoked auditory event-related potential (eERP), including the onset P1-N1-P2 complex and the electrically evoked auditory change complex (EACC) in response to temporal gaps, in children with auditory neuropathy spectrum disorder (ANSD); and (2) to evaluate the relationship between these measures and speech-perception abilities in these subjects. Fifteen ANSD children who are Cochlear Nucleus device users participated in this study. For each subject, the speech-processor microphone was bypassed and the eERPs were elicited by direct stimulation of one mid-array electrode (electrode 12). The stimulus was a train of biphasic current pulses 800 msec in duration. Two basic stimulation conditions were used to elicit the eERP. In the no-gap condition, the entire pulse train was delivered uninterrupted to electrode 12, and the onset P1-N1-P2 complex was measured relative to the stimulus onset. In the gapped condition, the stimulus consisted of two pulse train bursts, each being 400 msec in duration, presented sequentially on the same electrode and separated by one of five gaps (i.e., 5, 10, 20, 50, and 100 msec). Open-set speech-perception ability of these subjects with ANSD was assessed using the phonetically balanced kindergarten (PBK) word lists presented at 60 dB SPL, using monitored live voice in a sound booth. The eERPs were recorded from all subjects with ANSD who participated in this study. There were no significant differences in test-retest reliability, root mean square amplitude or P1 latency for the onset P1-N1-P2 complex between subjects with good (>70% correct on PBK words) and poorer speech-perception performance. In general, the EACC showed less mature morphological characteristics than the onset P1-N1-P2 response recorded from the same subject. There was a robust correlation between the PBK word scores and the EACC thresholds for gap detection. Subjects with poorer speech

Knowledge-Based Image Analysis.

DTIC Science & Technology

1981-04-01

UNCLASSIF1 ED ETL-025s N IIp ETL-0258 AL Ai01319 S"Knowledge-based image analysis u George C. Stockman Barbara A. Lambird I David Lavine Laveen N. Kanal...extraction, verification, region classification, pattern recognition, image analysis . 3 20. A. CT (Continue on rever.. d. It necessary and Identify by...UNCLgSTFTF n In f SECURITY CLASSIFICATION OF THIS PAGE (When Date Entered) .L1 - I Table of Contents Knowledge Based Image Analysis I Preface

Screening for genes and subnetworks associated with pancreatic cancer based on the gene expression profile.

PubMed

Long, Jin; Liu, Zhe; Wu, Xingda; Xu, Yuanhong; Ge, Chunlin

2016-05-01

The present study aimed to screen for potential genes and subnetworks associated with pancreatic cancer (PC) using the gene expression profile. The expression profile GSE 16515 was downloaded from the Gene Expression Omnibus database, which included 36 PC tissue samples and 16 normal samples. Limma package in R language was used to screen differentially expressed genes (DEGs), which were grouped as up‑ and downregulated genes. Then, PFSNet was applied to perform subnetwork analysis for all the DEGs. Moreover, Gene Ontology (GO) and REACTOME pathway enrichment analysis of up‑ and downregulated genes was performed, followed by protein‑protein interaction (PPI) network construction using Search Tool for the Retrieval of Interacting Genes Search Tool for the Retrieval of Interacting Genes. In total, 1,989 DEGs including 1,461 up‑ and 528 downregulated genes were screened out. Subnetworks including pancreatic cancer in PC tissue samples and intercellular adhesion in normal samples were identified, respectively. A total of 8 significant REACTOME pathways for upregulated DEGs, such as hemostasis and cell cycle, mitotic were identified. Moreover, 4 significant REACTOME pathways for downregulated DEGs, including regulation of β‑cell development and transmembrane transport of small molecules were screened out. Additionally, DEGs with high connectivity degrees, such as CCNA2 (cyclin A2) and PBK (PDZ binding kinase), of the module in the protein‑protein interaction network were mainly enriched with cell‑division cycle. CCNA2 and PBK of the module and their relative pathway cell‑division cycle, and two subnetworks (pancreatic cancer and intercellular adhesion subnetworks) may be pivotal for further understanding of the molecular mechanism of PC.

Evaluation of Interindividual Human Variation in Bioactivation and DNA Adduct Formation of Estragole in Liver Predicted by Physiologically Based Kinetic/Dynamic and Monte Carlo Modeling.

PubMed

Punt, Ans; Paini, Alicia; Spenkelink, Albertus; Scholz, Gabriele; Schilter, Benoit; van Bladeren, Peter J; Rietjens, Ivonne M C M

2016-04-18

Estragole is a known hepatocarcinogen in rodents at high doses following metabolic conversion to the DNA-reactive metabolite 1'-sulfooxyestragole. The aim of the present study was to model possible levels of DNA adduct formation in (individual) humans upon exposure to estragole. This was done by extending a previously defined PBK model for estragole in humans to include (i) new data on interindividual variation in the kinetics for the major PBK model parameters influencing the formation of 1'-sulfooxyestragole, (ii) an equation describing the relationship between 1'-sulfooxyestragole and DNA adduct formation, (iii) Monte Carlo modeling to simulate interindividual human variation in DNA adduct formation in the population, and (iv) a comparison of the predictions made to human data on DNA adduct formation for the related alkenylbenzene methyleugenol. Adequate model predictions could be made, with the predicted DNA adduct levels at the estimated daily intake of estragole of 0.01 mg/kg bw ranging between 1.6 and 8.8 adducts in 10(8) nucleotides (nts) (50th and 99th percentiles, respectively). This is somewhat lower than values reported in the literature for the related alkenylbenzene methyleugenol in surgical human liver samples. The predicted levels seem to be below DNA adduct levels that are linked with tumor formation by alkenylbenzenes in rodents, which were estimated to amount to 188-500 adducts per 10(8) nts at the BMD10 values of estragole and methyleugenol. Although this does not seem to point to a significant health concern for human dietary exposure, drawing firm conclusions may have to await further validation of the model's predictions.

Effect of coexisting Al(III) ions on Pb(II) sorption on biochars: Role of pH buffer and competition.

PubMed

Yang, Yuxi; Zhang, Weihua; Qiu, Hao; Tsang, Daniel C W; Morel, Jean-Louis; Qiu, Rongliang

2016-10-01

Biochar is being widely considered as a promising amendment agent for immobilizing heavy metals in contaminated acidic soils, where plenty of soluble Al(III) ions exist. In view of uncertain significance of the effects of coexisting Al(III) on Pb(II) sorption by biochars, this study used kenaf core biochar (KB550; high carbon, low ash) and sewage sludge biochar (SB550; low carbon, high ash) pyrolyzed at 550 °C to elucidate the influence of coexisting Al(III) species and biochars' mineral components on Pb(II) immobilization conducted in aqueous solution with initial pHs of 3.0-4.5. Results showed that Al(III) reduced Pb(II) sorption on KB550 primarily via pH buffering against biochar alkalinity, thus inhibiting lead carbonate formation. In contrast, the reduction on SB550 mainly resulted from direct competition for sorption sites, especially on Fe-rich phengite 2M1 and metakaolinite. Because of Pb-P precipitation and Pb-K interlayer exchange, the residual Pb(II) adsorption capacity resistant to coexisting Al(III) was 3-5 times higher on SB550 than on KB550. The Pb-K interlayer exchange was enhanced by lower pH and coexisting Al(III), while Pb-P precipitation was the dominant Pb(II) sorption mechanism on SB550 resistant to Al(III) buffering and competition at higher pH. Application of these two biochars as amendments confirmed that the mineral-rich SB550 was more suitable for Pb(II) immobilization in acidic soils with high levels of extractable Al(III). Copyright © 2016 Elsevier Ltd. All rights reserved.

CORRELATIONS IN HORIZONTAL BRANCH OSCILLATIONS AND BREAK COMPONENTS IN XTE J1701-462 AND GX 17+2

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

Bu, Qing-cui; Chen, Li; Zhang, Liang

2015-01-20

We studied the horizontal branch oscillations (HBO) and the band-limited components observed in the power spectra of the transient neutron star low-mass X-ray binary XTE J1701-462 and the persistent ''Sco-like'' Z source GX 17+2. These two components were studied based on the state-resolved spectra. We found that the frequencies of XTE J1701-462 lie on the known correlations (WK and PBK), showing consistency with other types of X-ray binaries (black holes, atoll sources, and millisecond X-ray pulsars). However, GX 17+2 is shifted from the WK correlation like other typical Z sources. We suggest that the WK/PBK main track forms a boundarymore » that separates persistent sources from transient sources. The characteristic frequencies of break and HBO are independent of accretion rate in both sources, though it depends on spectral models. We also report the energy dependence of the HBO and break frequencies in XTE J1701-462 and how the temporal properties change with spectral state in XTE J1701-462 and GX 17+2. We studied the correlation between rms at the break and the HBO frequency. We suggest that HBO and break components for both sources probably arise from a similar physical mechanism: Comptonization emission from the corona. These two components could be caused by the same kind of oscillation in a corona with uneven density, and they could be generated from different areas of the corona. We further suggest that different proportions of the Comptonization component in the total flux cause the different distribution between GX 17+2 and XTE J1701-462 in the rms{sub break}-rms{sub HBO} diagram.« less

A physiologically based in silico model for trans-2-hexenal detoxification and DNA adduct formation in human including interindividual variation indicates efficient detoxification and a negligible genotoxicity risk.

PubMed

Kiwamoto, R; Spenkelink, A; Rietjens, I M C M; Punt, A

2013-09-01

A number of α,β-unsaturated aldehydes are present in food both as natural constituents and as flavouring agents. Their reaction with DNA due to their electrophilic α,β-unsaturated aldehyde moiety may result in genotoxicity as observed in some in vitro models, thereby raising a safety concern. A question that remains is whether in vivo detoxification would be efficient enough to prevent DNA adduct formation and genotoxicity. In this study, a human physiologically based kinetic/dynamic (PBK/D) model of trans-2-hexenal (2-hexenal), a selected model α,β-unsaturated aldehyde, was developed to examine dose-dependent detoxification and DNA adduct formation in humans upon dietary exposure. The kinetic model parameters for detoxification were quantified using relevant pooled human tissue fractions as well as tissue fractions from 11 different individual subjects. In addition, a Monte Carlo simulation was performed so that the impact of interindividual variation in 2-hexenal detoxification on the DNA adduct formation in the population as a whole could be examined. The PBK/D model revealed that DNA adduct formation due to 2-hexenal exposure was 0.039 adducts/10⁸ nucleotides (nt) at the estimated average 2-hexenal dietary intake (0.04 mg 2-hexenal/kg bw) and 0.18 adducts/10⁸ nt at the 95th percentile of the dietary intake (0.178 mg 2-hexenal/kg bw) in the most sensitive people. These levels are three orders of magnitude lower than natural background DNA adduct levels that have been reported in disease-free humans (6.8-110 adducts/10⁸ nt), suggesting that the genotoxicity risk for the human population at realistic dietary daily intakes of 2-hexenal may be negligible.

Exposure assessment of process-related contaminants in food by biomarker monitoring

DOE PAGES

Rietjens, Ivonne M. C. M.; Dussort, P.; Gunther, Helmut; ...

2018-01-04

Exposure assessment is a fundamental part of the risk assessment paradigm, but can often present a number of challenges and uncertainties. This is especially the case for process contaminants formed during the processing, e.g. heating of food, since they are in part highly reactive and/or volatile, thus making exposure assessment by analysing contents in food unreliable. New approaches are therefore required to accurately assess consumer exposure and thus better inform the risk assessment. Such novel approaches may include the use of biomarkers, physiologically based kinetic (PBK) modelling-facilitated reverse dosimetry, and/or duplicate diet studies. This review focuses on the state ofmore » the art with respect to the use of biomarkers of exposure for the process contaminants acrylamide, 3-MCPD esters, glycidyl esters, furan and acrolein. From the overview presented, it becomes clear that the field of assessing human exposure to process-related contaminants in food by biomarker monitoring is promising and strongly developing. The current state of the art as well as the existing data gaps and challenges for the future were defined. They include (1) using PBK modelling and duplicate diet studies to establish, preferably in humans, correlations between external exposure and biomarkers; (2) elucidation of the possible endogenous formation of the process-related contaminants and the resulting biomarker levels; (3) the influence of inter-individual variations and how to include that in the biomarker-based exposure predictions; (4) the correction for confounding factors; (5) the value of the different biomarkers in relation to exposure scenario’s and risk assessment, and (6) the possibilities of novel methodologies. Here, in spite of these challenges it can be concluded that biomarker-based exposure assessment provides a unique opportunity to more accurately assess consumer exposure to process-related contaminants in food and thus to better inform risk assessment.« less

Exposure assessment of process-related contaminants in food by biomarker monitoring

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

Rietjens, Ivonne M. C. M.; Dussort, P.; Gunther, Helmut

Exposure assessment is a fundamental part of the risk assessment paradigm, but can often present a number of challenges and uncertainties. This is especially the case for process contaminants formed during the processing, e.g. heating of food, since they are in part highly reactive and/or volatile, thus making exposure assessment by analysing contents in food unreliable. New approaches are therefore required to accurately assess consumer exposure and thus better inform the risk assessment. Such novel approaches may include the use of biomarkers, physiologically based kinetic (PBK) modelling-facilitated reverse dosimetry, and/or duplicate diet studies. This review focuses on the state ofmore » the art with respect to the use of biomarkers of exposure for the process contaminants acrylamide, 3-MCPD esters, glycidyl esters, furan and acrolein. From the overview presented, it becomes clear that the field of assessing human exposure to process-related contaminants in food by biomarker monitoring is promising and strongly developing. The current state of the art as well as the existing data gaps and challenges for the future were defined. They include (1) using PBK modelling and duplicate diet studies to establish, preferably in humans, correlations between external exposure and biomarkers; (2) elucidation of the possible endogenous formation of the process-related contaminants and the resulting biomarker levels; (3) the influence of inter-individual variations and how to include that in the biomarker-based exposure predictions; (4) the correction for confounding factors; (5) the value of the different biomarkers in relation to exposure scenario’s and risk assessment, and (6) the possibilities of novel methodologies. Here, in spite of these challenges it can be concluded that biomarker-based exposure assessment provides a unique opportunity to more accurately assess consumer exposure to process-related contaminants in food and thus to better inform risk assessment.« less

Exposure assessment of process-related contaminants in food by biomarker monitoring.

PubMed

Rietjens, Ivonne M C M; Dussort, P; Günther, Helmut; Hanlon, Paul; Honda, Hiroshi; Mally, Angela; O'Hagan, Sue; Scholz, Gabriele; Seidel, Albrecht; Swenberg, James; Teeguarden, Justin; Eisenbrand, Gerhard

2018-01-01

Exposure assessment is a fundamental part of the risk assessment paradigm, but can often present a number of challenges and uncertainties. This is especially the case for process contaminants formed during the processing, e.g. heating of food, since they are in part highly reactive and/or volatile, thus making exposure assessment by analysing contents in food unreliable. New approaches are therefore required to accurately assess consumer exposure and thus better inform the risk assessment. Such novel approaches may include the use of biomarkers, physiologically based kinetic (PBK) modelling-facilitated reverse dosimetry, and/or duplicate diet studies. This review focuses on the state of the art with respect to the use of biomarkers of exposure for the process contaminants acrylamide, 3-MCPD esters, glycidyl esters, furan and acrolein. From the overview presented, it becomes clear that the field of assessing human exposure to process-related contaminants in food by biomarker monitoring is promising and strongly developing. The current state of the art as well as the existing data gaps and challenges for the future were defined. They include (1) using PBK modelling and duplicate diet studies to establish, preferably in humans, correlations between external exposure and biomarkers; (2) elucidation of the possible endogenous formation of the process-related contaminants and the resulting biomarker levels; (3) the influence of inter-individual variations and how to include that in the biomarker-based exposure predictions; (4) the correction for confounding factors; (5) the value of the different biomarkers in relation to exposure scenario's and risk assessment, and (6) the possibilities of novel methodologies. In spite of these challenges it can be concluded that biomarker-based exposure assessment provides a unique opportunity to more accurately assess consumer exposure to process-related contaminants in food and thus to better inform risk assessment.

Construction of fusion vectors of corynebacteria: expression of glutathione-S-transferase fusion protein in Corynebacterium acetoacidophilum ATCC 21476.

PubMed

Srivastava, Preeti; Deb, J K

2002-07-02

A series of fusion vectors containing glutathione-S-transferase (GST) were constructed by inserting GST fusion cassette of Escherichia coli vectors pGEX4T-1, -2 and -3 in corynebacterial vector pBK2. Efficient expression of GST driven by inducible tac promoter of E. coli was observed in Corynebacterium acetoacidophilum. Fusion of enhanced green fluorescent protein (EGFP) and streptokinase genes in this vector resulted in the synthesis of both the fusion proteins. The ability of this recombinant organism to produce several-fold more of the product in the extracellular medium than in the intracellular space would make this system quite attractive as far as the downstream processing of the product is concerned.

The River Danube: An Examination of Navigation on the River

NASA Astrophysics Data System (ADS)

Cooper, R. W.

One of the definitions of Navigation that gets little attention in this Institute is (Oxford English Dictionary), and which our French friends call La Navigation. I have always found this subject fascinating, and have previously navigated the Rivers Mekong, Irrawaddy, Hooghly, Indus, Shatt-al-Arab, Savannah and RhMainKanal (RMDK) and the River Danube, a distance of approximately 4000 km. This voyage has only recently become possible with the opening of the connecting RMDK at the end of 1992, but has been made little use of because of the civil war in the former Yugoslavia.

On p53 revival using system oriented drug dosage design.

PubMed

Haseeb, Muhammad; Azam, Shumaila; Bhatti, A I; Azam, Rizwan; Ullah, Mukhtar; Fazal, Sahar

2017-02-21

We propose a new paradigm in the drug design for the revival of the p53 pathway in cancer cells. It is shown that the current strategy of using small molecule based Mdm2 inhibitors is not enough to adequately revive p53 in cancerous cells, especially when it comes to the extracting pulsating behavior of p53. This fact has come to notice when a novel method for the drug dosage design is introduced using system oriented concepts. As a test case, small molecule drug Mdm2 repressor Nutlin 3a is considered. The proposed method determines the dose of Nutlin to revive p53 pathway functionality. For this purpose, PBK dynamics of Nutlin have also been integrated with p53 pathway model. The p53 pathway is the focus of researchers for the last thirty years for its pivotal role as a frontline cancer suppressant protein due to its effect on cell cycle checkpoints and cell apoptosis in response to a DNA strand break. That is the reason for finding p53 being absent in more than 50% of tumor cancers. Various drugs have been proposed to revive p53 in cancer cells. Small molecule based drugs are at the foremost and are the subject of advanced clinical trials. The dosage design of these drugs is an important issue. We use control systems concepts to develop the drug dosage so that the cancer cells can be treated in appropriate time. We investigate by using a computational model how p53 protein responds to drug Nutlin 3a, an agent that interferes with the MDM2-mediated p53 regulation. The proposed integrated model describes in some detail the regulation network of p53 including the negative feedback loop mediated by MDM2 and the positive feedback loop mediated by Mdm2 mRNA as well as the reversible represses of MDM2 caused by Nutlin. The reported PBK dynamics of Nutlin 3a are also incorporated to see the full effect. It has been reported that p53 response to stresses in two ways. Either it has a sustained (constant) p53 response, or there are oscillations in p53 concentration. The

Dose-dependent DNA adduct formation by cinnamaldehyde and other food-borne α,β-unsaturated aldehydes predicted by physiologically based in silico modelling.

PubMed

Kiwamoto, R; Ploeg, D; Rietjens, I M C M; Punt, A

2016-03-01

Genotoxicity of α,β-unsaturated aldehydes shown in vitro raises a concern for the use of the aldehydes as food flavourings, while at low dose exposures the formation of DNA adducts may be prevented by detoxification. Unlike many α,β-unsaturated aldehydes for which in vivo data are absent, cinnamaldehyde was shown to be not genotoxic or carcinogenic in vivo. The present study aimed at comparing dose-dependent DNA adduct formation by cinnamaldehyde and 18 acyclic food-borne α,β-unsaturated aldehydes using physiologically based kinetic/dynamic (PBK/D) modelling. In rats, cinnamaldehyde was predicted to induce higher DNA adducts levels than 6 out of the 18 α,β-unsaturated aldehydes, indicating that these 6 aldehydes may also test negative in vivo. At the highest cinnamaldehyde dose that tested negative in vivo, cinnamaldehyde was predicted to form at least three orders of magnitude higher levels of DNA adducts than the 18 aldehydes at their respective estimated daily intake. These results suggest that for all the 18 α,β-unsaturated aldehydes DNA adduct formation at doses relevant for human dietary exposure may not raise a concern. The present study illustrates a possible use of physiologically based in silico modelling to facilitate a science-based comparison and read-across on the possible risks posed by DNA reactive agents. Copyright © 2015 Elsevier B.V. All rights reserved.

Biotransformation and bioactivation reactions - 2015 literature highlights.

PubMed

Baillie, Thomas A; Dalvie, Deepak; Rietjens, Ivonne M C M; Cyrus Khojasteh, S

2016-05-01

Since 1972, Drug Metabolism Reviews has been recognized as one of the principal resources for researchers in pharmacological, pharmaceutical and toxicological fields to keep abreast of advances in drug metabolism science in academia and the pharmaceutical industry. With a distinguished list of authors and editors, the journal covers topics ranging from relatively mature fields, such as cytochrome P450 enzymes, to a variety of emerging fields. We hope to continue this tradition with the current compendium of mini-reviews that highlight novel biotransformation processes that were published during the past year. Each review begins with a summary of the article followed by our comments on novel aspects of the research and their biological implications. This collection of highlights is not intended to be exhaustive, but rather to be illustrative of recent research that provides new insights or approaches that advance the field of drug metabolism. Abbreviations NAPQI N-acetyl-p-benzoquinoneimine ALDH aldehyde dehydrogenase AO aldehyde oxidase AKR aldo-keto reductase CES carboxylesterase CSB cystathionine β-synthase CSE cystathionine γ-lyase P450 cytochrome P450 DHPO 2,3-dihydropyridin-4-one ESI electrospray FMO flavin monooxygenase GSH glutathione GSSG glutathione disulfide ICPMS inductively coupled plasma mass spectrometry i.p. intraperitoneal MDR multidrug-resistant NNAL 4-(methylnitrosamino)-1-(3-pyridyl)-1-butanol NNK 4-(methylnitrosamino)-1-(3-pyridyl)-1-butanone oaTOF orthogonal acceleration time-of-flight PBK physiologically based kinetic PCP pentachlorophenol SDR short-chain dehydrogenase/reductase SULT sulfotransferase TB tuberculosis.

The Assessment of Biological and Pollution Index of Estuaries Around Port of Tanjung Emas Semarang

NASA Astrophysics Data System (ADS)

Tjahjono, A.; Wahyuni, O.; Purwantini, S.

2018-02-01

Estuary is a place of accumulation of the population’s actitivites produced by domestic, industry or agriculture. This research was conducted to three of estuary of the rivers around the waters of Port of Tanjung Emas Semarang (PTES). They were estuaries of Baru river, Banjir Kanal Timur (BKT) and Siangker in west monsoon from October to December 2015. The purpose of this research was to analyze pollution index, the abundance of microorganisms either phytoplankton or zooplankton, the content of heavy metal in sediment and sea water, biological index that included diversity (H), uniformity (e), dominance (D), Saprobik Index (SI), and the Total of Saprobik Index (TSI) in the waters either HTL (High Tide Level) or LTL (Low Tide Level). The concentration of heavy metal in both sea water and sediments were analyzed by using Atomic Absorption Spectrophotometer (AAS). The result obtained from 12 parameters which were tested showed that the three waters can be categorized at heavily polluted condition at each value from 12.52 to 24.98. The concentration of heavy metal at sea water during HTW and LTW ranging from Cd is around 0.033 and 0. 048 mg/kg, Cu 0.047 and 0.07 mg/kg, Pb 0.48 and 0.71 mg/kg, and Zn 0.043 and 0.057 mg/kg. The saprobity value index based on the existence of phytoplankton or zooplankton was ranging of Oligosaprobik at low pollution or has not been polluted yet.

Numerical solutions of pulsating flow and heat transfer characteristics in a channel with a backward-facing step

NASA Astrophysics Data System (ADS)

Valencia, A.; Hinojosa, L.

The incompressible laminar flow of air and heat transfer in a channel with a backward-facing step is studied for steady cases and for pulsatile inlet conditions. For steady flows the influence of the inlet velocity profile, the height of the step and the Reynolds number on the reattachment length is investigated. A parabolic entrance profile was used for pulsatile flow. It was found with amplitude of oscillation of one by Re=100 that the primary vortex breakdown through one pulsatile cycle. The wall shear rate in the separation zone varied markedly with pulsatile flows and the wall heat transfer remained relatively constant. The time-average pulsatile heat transfer at the walls was greater as with steady flow with the same mean Reynolds number. Zusammenfassung Es wird eine zweidimensionale numerische Untersuchung des instationären Wärmeübergangs und Druckverlustes im laminar durchströmten Spaltkanal mit einer plötzlichen Kanalerweiterung dargelegt und zwar für stationäre und periodische Geschwindigkeitsprofile am Eintritt des Kanals. Für stationäre Strömungen wurden die Form des Eintrittsprofils, die Reynoldszahl und die Kanalerweiterung variiert. Als Lösung der Navier/Stokes-und der Energiegleichungen mit periodischen Randbedingungen resultiert eine oszillierende Strömung, die das Aufplatzen des Primärwirbels in einer Schwingungsperiode zur Folge hat. Der Einfluß dieser Oszillation auf den Wärmeübergang und den Strömungsverlust wurde für die maximale Amplitude und für Re=100 eingehend untersucht.

Lossless quantum data compression and secure direct communication

NASA Astrophysics Data System (ADS)

Boström, Kim

2004-07-01

of the message. Diese Dissertation behandelt die Kodierung und Verschickung von Information durch einen Quantenkanal. Ein Quantenkanal besteht aus einem quantenmechanischen System, welches vom Sender manipuliert und vom Empfänger ausgelesen werden kann. Dabei repräsentiert der individuelle Zustand des Kanals die Nachricht. Die zwei Themen der Dissertation umfassen 1) die Möglichkeit, eine Nachricht in einem Quantenkanal verlustfrei zu komprimieren und 2) die Möglichkeit eine Nachricht von einer Partei zu einer einer anderen direkt und auf sichere Weise zu übermitteln, d.h. ohne dass es einer dritte Partei möglich ist, die Nachricht abzuhören und dabei unerkannt zu bleiben. Die wesentlichen Ergebnisse der Dissertation sind die folgenden. Ein allgemeiner Formalismus für Quantencodes mit variabler Länge wird ausgearbeitet. Diese Codes sind notwendig um verlustfreie Kompression zu ermöglichen. Wegen der Quantennatur des Kanals sind die codierten Nachrichten allgemein in einer Superposition von verschiedenen Längen. Es zeigt sich, daß es unmöglich ist eine Quantennachricht verlustfrei zu komprimieren, wenn diese dem Sender nicht apriori bekannt ist. Im anderen Falle wird die Möglichkeit verlustfreier Quantenkompression gezeigt und eine untere Schranke für die Kompressionsrate abgeleitet. Des weiteren wird ein expliziter Kompressionsalgorithmus konstruiert, der für beliebig vorgegebene Ensembles aus Quantennachrichten funktioniert. Ein quantenkryptografisches Prokoll - das “Ping-Pong Protokoll” - wird vorgestellt, welches die sichere direkte übertragung von klassischen Nachrichten durch einen Quantenkanal ermöglicht. Die Sicherheit des Protokolls gegen beliebige Abhörangriffe wird bewiesen für den Fall eines idealen Quantenkanals. Im Gegensatz zu anderen quantenkryptografischen Verfahren ist das Ping-Pong Protokoll deterministisch und kann somit sowohl für die Übermittlung eines zufälligen Schlüssels als auch einer komponierten Nachricht

Modeling of the fate of radionuclides in urban sewer systems after contamination due to nuclear or radiological incidents.

PubMed

Urso, L; Kaiser, J C; Andersson, K G; Andorfer, H; Angermair, G; Gusel, C; Tandler, R

2013-04-01

After an accidental radioactive contamination by aerosols in inhabited areas, the radiation exposure to man is determined by complex interactions between different factors such as dry or wet deposition, different types of ground surfaces, chemical properties of the radionuclides involved and building development as well as dependence on bomb construction e.g. design and geometry. At short-term, the first rainfall is an important way of natural decontamination: deposited radionuclides are washed off from surfaces and in urban areas the resulting contaminated runoff enters the sewer system and is collected in a sewage plant. Up to now the potential exposure caused by this process has received little attention and is estimated here with simulation models. The commercial rainfall-runoff model for urban sewer systems KANAL++ has been extended to include transport of radionuclides from surfaces through the drainage to various discharge facilities. The flow from surfaces is modeled by unit hydrographs, which produce boundary conditions for a system of 1d coupled flow and transport equations in a tube system. Initial conditions are provided by a map of surface contamination which is produced by geo-statistical interpolation of γ-dose rate measurements taking into account the detector environment. The corresponding methodology is implemented in the Inhabited Area Monitoring Module (IAMM) software module as part of the European decision system JRODOS. A hypothetical scenario is considered where a Radiation Dispersal Device (RDD) with Cs-137 is detonated in a small inhabited area whose drainage system is realistically modeled. The transition of deposited radionuclides due to rainfall into the surface runoff is accounted for by different nuclide-specific entrainment coefficients for paved and unpaved surfaces. The concentration of Cs-137 in water is calculated at the nodes of the drainage system and at the sewage treatment plant. The external exposure to staff of the

Print, Web, And Podcast Tov Public Outreach

NASA Astrophysics Data System (ADS)

Pasachoff, Jay M.

2012-10-01

As part of alerting the general public to the subtly spectacular transit of Venus as an intellectual marvel not available to us from Earth until AD 2117/2125, in addition to our scientific plans (Pasachoff et al., this meeting), I provided: (1) an article in the children's magazine Odyssey (May/June 2011); (2) a discussion in National Geographic Society's BreakingOrbit blog (March 1, 2011); (3) and a year's advance notice as "June 5: Transit of Venus," 365daysofastronomy.org. (4) Nantes DPS: I participated in "Transits of Venus in Public Education and Contemporary Research" (http://transitofvenus.nl/wp/2011/10/16/four-giants-talk-about-transits). (5) 22-minute lecture on the Phi Beta Kappa website: http://www.pbk.org/home/playpodcast.aspx?id=772. (6) E/PO summary at Historical Astronomy Division News, #79, October. Closer to the event, I had a (7) Comment in Nature ("Transit of Venus: Last Chance to See," Nature 485, 303-304) and (8, 9) articles in Physics World, 25, 36-41; and Scientific American, http://www.scientificamerican.com/article.cfm?id=transit-venus-june-5). The day before the transit, (10) I had a radio/podcast Academic Minute (http://www.wamc.org/post/dr-jay-pasachoff-williams-college). (11) On transit day, I had an Op-Ed piece in The New York Times ("Learning from Celestial Beauty," http://www.nytimes.com/2012/06/05/opinion/learning-from-celestial-beauty.html) that was seen by largely a non-scientific audience. Subsequently, (12) I gave a Keck-Observatory-sponsored Waimea general-public lecture (http://keckobservatory.org/news/video_venus_transits_past_present_future), and (13) an invited public lecture at the AAS meeting in Anchorage (http://aas.org/meetings/aas220/video_session_127). I had a podcast on (14) 365daysofastronomy.org (June 29). (15) My article for Sky & Telescope appeared in its October issue. (16) My editorial "Syzygy x 3" will be in RASC Observer's Handbook 2013. (16) These efforts as well as links to history and science of transits

WE-FG-BRA-11: Theranostic Platinum Nanoparticle for Radiation Sensitization in Breast Cancer Radiotherapy

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

Yue, Y; Wagner, S; Medina-Kauwe, L

Purpose: We have developed a novel receptor-targeted theranostic platinum nanoparticle (HER-PtNP) for enhanced radiation sensitization in HER2-positive breast cancer radiation treatment. This study aims to evaluate receptor-targeting specificity, and radiation sensitization of the nanoparticle. Methods: The platinum nanoparticle (PtNP) was synthesized with the diameter of 2nm, and capped with cysteine. The nanoparticle was tagged with a fluorescent dye (cy5) for the fluoresence detection, and conjuated with HER2/3 targeted protein (HerPBK10) for HER2-targeting specificity. We evaluated the theranostic features using in vitro breast cancer cell models: HER2-positive BT-474, and HER2-negative MDA-MB-231. The HER2-targeting specificity was evaluated using immunofluorescence and confocal microscopy.more » For each cell line, three sets of samples, including non-stained control, fluorescence stained PtNP-cy5 treated, and HER-PtNP treated, were imaged by confocal microscopy. Two breast cancer cell lineages were incubated with PtNP and HER-PtNP at 10 µg/mL, and then irradiated with X-rays for 2 Gy dose at 50 kVp. A colonogenic assay was used to determine cellular survival fractions by immediately reseeding 300 cells after irradiation in growth media and allowing colonies to grow for 2 weeks. Results: The results of confocal images show that no apparent nanoparticle cellular uptake was observed in the HER2-(MDA-MB-231) cells with 1% for PtNP-cy5 and 0.5% for HER-PtNP. Similarly no apparent PtNP-cy5 uptake (<1%) for BT474 cells was observed. However, there was significant HER-PtNP uptake (73%) for the HER2+(BT474) cells. The clonogenic assay showed that BT474 cells treated with HER-PtNP had significantly lower survival compared to those treated with PtNP (32% vs 81%, p=0.01). However, no significant radiosensitivity enhancement was observed for MDA-MB-231 cell treated with PtNP and HER-PtNP (89% vs 92%, p=0.78). Conclusion: Our studies suggest that the HER2-targeted

Genomically Informed Surveillance for Carbapenem-Resistant Enterobacteriaceae in a Health Care System.

PubMed

Pecora, Nicole D; Li, Ning; Allard, Marc; Li, Cong; Albano, Esperanza; Delaney, Mary; Dubois, Andrea; Onderdonk, Andrew B; Bry, Lynn

2015-07-28

Carbapenem-resistant Enterobacteriaceae (CRE) are an urgent public health concern. Rapid identification of the resistance genes, their mobilization capacity, and strains carrying them is essential to direct hospital resources to prevent spread and improve patient outcomes. Whole-genome sequencing allows refined tracking of both chromosomal traits and associated mobile genetic elements that harbor resistance genes. To enhance surveillance of CREs, clinical isolates with phenotypic resistance to carbapenem antibiotics underwent whole-genome sequencing. Analysis of 41 isolates of Klebsiella pneumoniae and Enterobacter cloacae, collected over a 3-year period, identified K. pneumoniae carbapenemase (KPC) genes encoding KPC-2, -3, and -4 and OXA-48 carbapenemases. All occurred within transposons, including multiple Tn4401 transposon isoforms, embedded within more than 10 distinct plasmids representing incompatibility (Inc) groups IncR, -N, -A/C, -H, and -X. Using short-read sequencing, draft maps were generated of new KPC-carrying vectors, several of which were derivatives of the IncN plasmid pBK31551. Two strains also had Tn4401 chromosomal insertions. Integrated analyses of plasmid profiles and chromosomal single-nucleotide polymorphism (SNP) profiles refined the strain patterns and provided a baseline hospital mobilome to facilitate analysis of new isolates. When incorporated with patient epidemiological data, the findings identified limited outbreaks against a broader 3-year period of sporadic external entry of many different strains and resistance vectors into the hospital. These findings highlight the utility of genomic analyses in internal and external surveillance efforts to stem the transmission of drug-resistant strains within and across health care institutions. We demonstrate how detection of resistance genes within mobile elements and resistance-carrying strains furthers active surveillance efforts for drug resistance. Whole-genome sequencing is increasingly

Book Review: Conceptual mathematics: a first introduction to categories. F. William Lawvere and Stephen H. Schanuel, Cambridge University Press, Cambridge, 1997 (reprinted with corrections 1998), xvi+358 pp., index, hbk, ISBN 0-521-47249-0, pbk, ISBN 0-521-47817-0

NASA Astrophysics Data System (ADS)

Corfield, David

Casting scientific or mathematical research activity in the form of programmes with a view to gauging its progressiveness is no straightforward business, as Imre Lakatos discovered. The category theory "programme", now over half a century old, has certainly become too large to be judged as a united enterprise whose members share a common mission. Speaking about Bayesian statistics, Edwin Jaynes could imagine a time when its methods had become so pervasive that its practitioners found their common interests insufficiently extensive to cause them to gather together for conferences, just as the time when researchers could meet up to discuss the uses of Fourier transforms is long past. Well, category theory has already progressed a certain way towards this stage. Its penetration into the various branches of mathematics has been uneven, but in some cases it has been profound. For instance, any algebraic topologist or algebraic geometer just must use a considerable amount of category theory as part of their job. It has also made inroads into logic and, from there, to theoretical computer science (see e.g., Taylor, 1999). Its reach even extends to mathematical physics where, for example, we find topological quantum field theories defined in terms of functors between categories (Atiyah, 1988), and the intriguing prospect that higher-dimensional categories will feature in subsequent developments.

Volatilization, transport and sublimation of metallic and non-metallic elements in high temperature gases at Merapi Volcano, Indonesia

USGS Publications Warehouse

Symonds, R.B.; Rose, William I.; Reed, M.H.; Lichte, F.E.; Finnegan, David L.

1987-01-01

Condensates, silica tube sublimates and incrustations were sampled from 500-800??C fumaroles and lava samples were collected at Merapi Volcano, Indonesia in Jan.-Feb., 1984. With respect to the magma, Merapi gases are enriched by factors greater than 105 in Se, Re, Bi and Cd; 104-105 in Au, Br, In, Pb and W; 103-104 in Mo, Cl, Cs, S, Sn and Ag; 102-103 in As, Zn, F and Rb; and 1-102 in Cu, K, Na, Sb, Ni, Ga, V, Fe, Mn and Li. The fumaroles are transporting more than 106 grams/day ( g d) of S, Cl and F; 104-106 g/d of Al, Br, Zn, Fe, K and Mg; 103-104 g d of Pb, As, Mo, Mn, V, W and Sr; and less than 103 g d of Ni, Cu, Cr, Ga, Sb, Bi, Cd, Li, Co and U. With decreasing temperature (800-500??C) there were five sublimate zones found in silica tubes: 1) cristobalite and magnetite (first deposition of Si, Fe and Al); 2) K-Ca sulfate, acmite, halite, sylvite and pyrite (maximum deposition of Cl, Na, K, Si, S, Fe, Mo, Br, Al, Rb, Cs, Mn, W, P, Ca, Re, Ag, Au and Co); 3) aphthitalite (K-Na sulfate), sphalerite, galena and Cs-K. sulfate (maximum deposition of Zn, Bi, Cd, Se and In; higher deposition of Pb and Sn); 4) Pb-K chloride and Na-K-Fe sulfate (maximum deposition of Pb, Sn and Cu); and 5) Zn, Cu and K-Pb sulfates (maximum deposition of Pb, Sn, Ti, As and Sb). The incrustations surrounding the fumaroles are also chemically zoned. Bi, Cd, Pb, W, Mo, Zn, Cu, K, Na, V, Fe and Mn are concentrated most in or very close to the vent as expected with cooling, atmospheric contamination and dispersion. The highly volatile elements Br, Cl, As and Sb are transported primarily away from high temperature vents. Ba, Si, P, Al, Ca and Cr are derived from wall rock reactions. Incomplete degassing of shallow magma at 915??C is the origin of most of the elements in the Merapi volcanic gas, although it is partly contaminated by particles or wall rock reactions. The metals are transported predominantly as chloride species. As the gas cools in the fumarolic environment, it becomes saturated

Pb isotope systematics in volcanic river system: Constraints about weathering processes

NASA Astrophysics Data System (ADS)

Negrel, P. J.; Millot, R.; Petelet-Giraud, E.; Guerrot, C.

2012-12-01

lead content and depleted Si content - high lead content that bedrock. The comparison of 1000Pb/K versus Si/K ratio evidenced the evolution line from weathering processes and the lead enrichment from atmospheric deposition as a major contributor to explain the deviation of several points from this line. Lead isotopes decrease from bedrock to sediments-soils without any clear relationship when compared to lead contents. The use of Pb-isotopic compositions showed that most of the lead budget in sediments and soils result from bedrock weathering with an influence of gasoline additive-lead derived inputs and a lack of lead input from agricultural activities.