Sample records for deriving release criteria

  1. Update on US EPA's Revision to the 1985 Guidelines for ...

    EPA Pesticide Factsheets

    National Water Quality Criteria for the Protection of Aquatic Organisms and Their Uses (Stephan et al. 1985), to reflect the current state-of-the-science for aquatic effects assessments. Following a 2015 public meeting soliciting early input from the scientific community, EPA decided to undertake two overarching parallel tracks for this revision: 1) updating and refining methods for deriving state-of-the-science criteria through comprehensive analyses, and 2) developing criteria more rapidly for the broader protection of aquatic life from the potential adverse effects of the large number of chemicals released into the aquatic environment. The first track reflects that for a smaller group of chemicals, criteria development may be scientifically complex, and deriving robust criteria for these chemicals may require detailed investigation. The second track reflects the recognition that extensive testing of all chemicals is infeasible and there is a need to efficiently derive criteria using approaches that estimate safe environmental concentrations with limited empirical data. Based on these objectives, EPA will develop two criteria documents for this revision: 1) a Comprehensive Guidelines Document, intended to directly update and expand upon approaches presented in the 1985 Guidelines, and that will describe methods that provide criteria for chemicals requiring a more detailed level of evaluation, and 2) an Expedited Guidelines Document, which will focus on criteri

  2. Microsiemens or Milligrams: Measures of Ionic Mixtures

    EPA Science Inventory

    In December of 2016, EPA released the Draft Field-Based Methods for Developing Aquatic Life Criteria for Specific Conductivity for public comment. Once final, states and authorized tribes may use these methods to derive field-based ecoregional ambient Aquatic Life Ambient Water Q...

  3. Exposure Levels for Chemical Threat Compounds; Information to Facilitate Chemical Incident Response

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

    Hauschild, Veronique; Watson, Annetta Paule

    2013-01-01

    Exposure Standards, Limits and Guidelines for Chemical Threat Compunds ABSTRACT Exposure criteria for chemical warfare (CW) agents and certain toxic industrial chemicals (TICs) used as CW agents (such as chlorine fill in an improvised explosive device) have been developed for protection of the civilian general public, civilian employees in chemical agent processing facilities and deployed military populations. In addition, compound-specific concentrations have been developed to serve as how clean is clean enough clearance criteria guiding facility recovery following chemical terrorist or other hazardous release events. Such criteria are also useful to verify compound absence, identify containment boundaries and expedite facilitymore » recovery following chemical threat release. There is no single right value or concentration appropriate for all chemical hazard control applications. It is acknowledged that locating and comparing the many sources of CW agent and TIC exposure criteria has not been previously well-defined. This paper summarizes many of these estimates and assembles critical documentation regarding their derivation and use.« less

  4. Human HDAC isoform selectivity achieved via exploitation of the acetate release channel with structurally unique small molecule inhibitors

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

    Whitehead, Lewis; Dobler, Markus R.; Radetich, Branko

    2013-11-20

    Herein we report the discovery of a family of novel yet simple, amino-acid derived class I HDAC inhibitors that demonstrate isoform selectivity via access to the internal acetate release channel. Isoform selectivity criteria is discussed on the basis of X-ray crystallography and molecular modeling of these novel inhibitors bound to HDAC8, potentially revealing insights into the mechanism of enzymatic function through novel structural features revealed at the atomic level.

  5. Decontamination and management of human remains following incidents of hazardous chemical release.

    PubMed

    Hauschild, Veronique D; Watson, Annetta; Bock, Robert

    2012-01-01

    To provide specific guidance and resources for systematic and orderly decontamination of human remains resulting from a chemical terrorist attack or accidental chemical release. A detailed review and health-based decision criteria protocol is summarized. Protocol basis and logic are derived from analyses of compound-specific toxicological data and chemical/physical characteristics. Guidance is suitable for civilian or military settings where human remains potentially contaminated with hazardous chemicals may be present, such as sites of transportation accidents, terrorist operations, or medical examiner processing points. Guidance is developed from data-characterizing controlled experiments with laboratory animals, fabrics, and materiel. Logic and specific procedures for decontamination and management of remains, protection of mortuary affairs personnel, and decision criteria to determine when remains are sufficiently decontaminated are presented. Established procedures as well as existing materiel and available equipment for decontamination and verification provide reasonable means to mitigate chemical hazards from chemically exposed remains. Unique scenarios such as those involving supralethal concentrations of certain liquid chemical warfare agents may prove difficult to decontaminate but can be resolved in a timely manner by application of the characterized systematic approaches. Decision criteria and protocols to "clear" decontaminated remains for transport and processing are also provided. Once appropriate decontamination and verification have been accomplished, normal procedures for management of remains and release can be followed.

  6. Balancing Punishment and Compassion for Seriously Ill Prisoners

    PubMed Central

    Williams, Brie A.; Sudore, Rebecca L.; Greifinger, Robert; Morrison, R. Sean

    2011-01-01

    Compassionate release is a mechanism to allow some eligible, seriously ill prisoners to die outside of prison before sentence completion. It became a matter of federal statute in 1984 and currently has been adopted by the majority of U.S. prison jurisdictions. Incarceration is justified on 4 principles: retribution, rehabilitation, deterrence, and incapacitation. Compassionate release derives from the theory that changes in health status may affect these principles and thus alter justification for incarceration and sentence completion. The medical profession is intricately involved in this process because eligibility for consideration for compassionate release is generally based on medical evidence. Due to an aging prison population, overcrowding, rising deaths in custody, and soaring criminal justice medical costs, many policy experts are calling for broader use of compassionate release. Yet, the medical eligibility criteria of many compassionate release guidelines – which often assume a definitive prognosis – are clinically flawed and procedural barriers may further limit their rational application. We propose changes to address these flaws. PMID:21628351

  7. Identification and validation of multiple cell surface markers of clinical-grade adipose-derived mesenchymal stromal cells as novel release criteria for good manufacturing practice-compliant production.

    PubMed

    Camilleri, Emily T; Gustafson, Michael P; Dudakovic, Amel; Riester, Scott M; Garces, Catalina Galeano; Paradise, Christopher R; Takai, Hideki; Karperien, Marcel; Cool, Simon; Sampen, Hee-Jeong Im; Larson, A Noelle; Qu, Wenchun; Smith, Jay; Dietz, Allan B; van Wijnen, Andre J

    2016-08-11

    Clinical translation of mesenchymal stromal cells (MSCs) necessitates basic characterization of the cell product since variability in biological source and processing of MSCs may impact therapeutic outcomes. Although expression of classical cell surface markers (e.g., CD90, CD73, CD105, and CD44) is used to define MSCs, identification of functionally relevant cell surface markers would provide more robust release criteria and options for quality control. In addition, cell surface expression may distinguish between MSCs from different sources, including bone marrow-derived MSCs and clinical-grade adipose-derived MSCs (AMSCs) grown in human platelet lysate (hPL). In this work we utilized quantitative PCR, flow cytometry, and RNA-sequencing to characterize AMSCs grown in hPL and validated non-classical markers in 15 clinical-grade donors. We characterized the surface marker transcriptome of AMSCs, validated the expression of classical markers, and identified nine non-classical markers (i.e., CD36, CD163, CD271, CD200, CD273, CD274, CD146, CD248, and CD140B) that may potentially discriminate AMSCs from other cell types. More importantly, these markers exhibit variability in cell surface expression among different cell isolates from a diverse cohort of donors, including freshly prepared, previously frozen, or proliferative state AMSCs and may be informative when manufacturing cells. Our study establishes that clinical-grade AMSCs expanded in hPL represent a homogeneous cell culture population according to classical markers,. Additionally, we validated new biomarkers for further AMSC characterization that may provide novel information guiding the development of new release criteria. Use of Autologous Bone Marrow Aspirate Concentrate in Painful Knee Osteoarthritis (BMAC): Clinicaltrials.gov NCT01931007 . Registered August 26, 2013. MSC for Occlusive Disease of the Kidney: Clinicaltrials.gov NCT01840540 . Registered April 23, 2013. Mesenchymal Stem Cell Therapy in Multiple System Atrophy: Clinicaltrials.gov NCT02315027 . Registered October 31, 2014. Efficacy and Safety of Adult Human Mesenchymal Stem Cells to Treat Steroid Refractory Acute Graft Versus Host Disease. Clinicaltrials.gov NCT00366145 . Registered August 17, 2006. A Dose-escalation Safety Trial for Intrathecal Autologous Mesenchymal Stem Cell Therapy in Amyotrophic Lateral Sclerosis. Clinicaltrials.gov NCT01609283 . Registered May 18, 2012.

  8. Microsiemens or Milligrams: Measures of Ionic Mixtures ...

    EPA Pesticide Factsheets

    In December of 2016, EPA released the Draft Field-Based Methods for Developing Aquatic Life Criteria for Specific Conductivity for public comment. Once final, states and authorized tribes may use these methods to derive field-based ecoregional ambient Aquatic Life Ambient Water Quality Criteria (AWQC) for specific conductivity (SC) in flowing waters. The methods provide flexible approaches for developing science-based SC criteria that reflect ecoregional or state specific factors. The concentration of a dissolved salt mixture can be measured in a number of ways including measurement of total dissolved solids, freezing point depression, refractive index, density, or the sum of the concentrations of individually measured ions. For the draft method, SC was selected as the measure because SC is a measure of all ions in the mixture; the measurement technology is fast, inexpensive, and accurate, and it measures only dissolved ions. When developing water quality criteria for major ions, some stakeholders may prefer to identify the ionic constituents as a measure of exposure instead of SC. A field-based method was used to derive example chronic and acute water quality criteria for SC and two anions a common mixture of ions (bicarbonate plus sulfate, [HCO3−] + [SO42−] in mg/L) that represent common mixtures in streams. These two anions are sufficient to model the ion mixture and SC (R2 = 0.94). Using [HCO3−] + [SO42−] does not imply that these two anions are the

  9. Exponential synchronization of chaotic systems with time-varying delays and parameter mismatches via intermittent control.

    PubMed

    Cai, Shuiming; Hao, Junjun; Liu, Zengrong

    2011-06-01

    This paper studies the synchronization of coupled chaotic systems with time-varying delays in the presence of parameter mismatches by means of periodically intermittent control. Some novel and useful quasisynchronization criteria are obtained by using the methods which are different from the techniques employed in the existing works, and the derived results are less conservative. Especially, a strong constraint on the control width that the control width should be larger than the time delay imposed by the current references is released in this paper. Moreover, our results show that the synchronization criteria depend on the ratio of control width to control period, but not the control width or the control period. Finally, some numerical simulations are given to show the effectiveness of the theoretical results.

  10. Development of drug-loaded polymer microcapsules for treatment of epilepsy.

    PubMed

    Chen, Yu; Gu, Qi; Yue, Zhilian; Crook, Jeremy M; Moulton, Simon E; Cook, Mark J; Wallace, Gordon G

    2017-09-26

    Despite significant progress in developing new drugs for seizure control, epilepsy still affects 1% of the global population and is drug-resistant in more than 30% of cases. To improve the therapeutic efficacy of epilepsy medication, a promising approach is to deliver anti-epilepsy drugs directly to affected brain areas using local drug delivery systems. The drug delivery systems must meet a number of criteria, including high drug loading efficiency, biodegradability, neuro-cytocompatibility and predictable drug release profiles. Here we report the development of fibre- and sphere-based microcapsules that exhibit controllable uniform morphologies and drug release profiles as predicted by mathematical modelling. Importantly, both forms of fabricated microcapsules are compatible with human brain derived neural stem cells and differentiated neurons and neuroglia, indicating clinical compliance for neural implantation and therapeutic drug delivery.

  11. When Medical News Comes from Press Releases-A Case Study of Pancreatic Cancer and Processed Meat.

    PubMed

    Taylor, Joseph W; Long, Marie; Ashley, Elizabeth; Denning, Alex; Gout, Beatrice; Hansen, Kayleigh; Huws, Thomas; Jennings, Leifa; Quinn, Sinead; Sarkies, Patrick; Wojtowicz, Alex; Newton, Philip M

    2015-01-01

    The media have a key role in communicating advances in medicine to the general public, yet the accuracy of medical journalism is an under-researched area. This project adapted an established monitoring instrument to analyse all identified news reports (n = 312) on a single medical research paper: a meta-analysis published in the British Journal of Cancer which showed a modest link between processed meat consumption and pancreatic cancer. Our most significant finding was that three sources (the journal press release, a story on the BBC News website and a story appearing on the 'NHS Choices' website) appeared to account for the content of over 85% of the news stories which covered the meta analysis, with many of them being verbatim or moderately edited copies and most not citing their source. The quality of these 3 primary sources varied from excellent (NHS Choices, 10 of 11 criteria addressed) to weak (journal press release, 5 of 11 criteria addressed), and this variance was reflected in the accuracy of stories derived from them. Some of the methods used in the original meta-analysis, and a proposed mechanistic explanation for the findings, were challenged in a subsequent commentary also published in the British Journal of Cancer, but this discourse was poorly reflected in the media coverage of the story.

  12. Final Status Survey Report for Corrective Action Unit 117 - Pluto Disassembly Facility, Building 2201, Nevada National Security Site, Nevada

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

    Jeremy Gwin and Douglas Frenette

    This document contains the process knowledge, radiological data and subsequent statistical methodology and analysis to support approval for the radiological release of Corrective Action Unit (CAU) 117 – Pluto Disassembly Facility, Building 2201 located in Area 26 of the Nevada National Security Site (NNSS). Preparations for release of the building began in 2009 and followed the methodology described in the Multi-Agency Radiation Survey and Site Investigation Manual (MARSSIM). MARSSIM is the DOE approved process for release of Real Property (buildings and landmasses) to a set of established criteria or authorized limits. The pre-approved authorized limits for surface contamination values andmore » corresponding assumptions were established by DOE O 5400.5. The release criteria coincide with the acceptance criteria of the U10C landfill permit. The U10C landfill is the proposed location to dispose of the radiologically non-impacted, or “clean,” building rubble following demolition. However, other disposition options that include the building and/or waste remaining at the NNSS may be considered providing that the same release limits apply. The Final Status Survey was designed following MARSSIM guidance by reviewing historical documentation and radiological survey data. Following this review a formal radiological characterization survey was performed in two phases. The characterization revealed multiple areas of residual radioactivity above the release criteria. These locations were remediated (decontaminated) and then the surface activity was verified to be less than the release criteria. Once remediation efforts had been successfully completed, a Final Status Survey Plan (10-015, “Final Status Survey Plan for Corrective Action Unit 117 – Pluto Disassembly Facility, Building 2201”) was developed and implemented to complete the final step in the MARSSIM process, the Final Status Survey. The Final Status Survey Plan consisted of categorizing each individual room into one of three categories: Class 1, Class 2 or Class 3 (a fourth category is a “Non-Impacted Class” which in the case of Building 2201 only pertained to exterior surfaces of the building.) The majority of the rooms were determined to fall in the less restrictive Class 3 category, however, Rooms 102, 104, 106, and 107 were identified as containing Class 1 and 2 areas. Building 2201 was divided into “survey units” and surveyed following the requirements of the Final Status Survey Plan for each particular class. As each survey unit was completed and documented, the survey results were evaluated. Each sample (static measurement) with units of counts per minute (cpm) was corrected for the appropriate background and converted to a value with units of dpm/100 cm2. With a surface contamination value in the appropriate units, it was compared to the surface contamination limits, or in this case the derived concentration guideline level (DCGLw). The appropriate statistical test (sign test) was then performed. If the survey unit was statistically determined to be below the DCGLw, then the survey unit passed and the null hypothesis (that the survey unit is above limits) was rejected. If the survey unit was equal to or below the critical value in the sign test, the null hypothesis was not rejected. This process was performed for all survey units within Building 2201. A total of thirty-three “Class 1,” four “Class 2,” and one “Class 3” survey units were developed, surveyed, and evaluated. All survey units successfully passed the statistical test. Building 2201 meets the release criteria commensurate with the Waste Acceptance Criteria (for radiological purposes) of the U10C landfill permit residing within NNSS boundaries. Based on the thorough statistical sampling and scanning of the building’s interior, Building 2201 may be considered radiologically “clean,” or free of contamination.« less

  13. Enclosure fire hazard analysis using relative energy release criteria. [burning rate and combustion control

    NASA Technical Reports Server (NTRS)

    Coulbert, C. D.

    1978-01-01

    A method for predicting the probable course of fire development in an enclosure is presented. This fire modeling approach uses a graphic plot of five fire development constraints, the relative energy release criteria (RERC), to bound the heat release rates in an enclosure as a function of time. The five RERC are flame spread rate, fuel surface area, ventilation, enclosure volume, and total fuel load. They may be calculated versus time based on the specified or empirical conditions describing the specific enclosure, the fuel type and load, and the ventilation. The calculation of these five criteria, using the common basis of energy release rates versus time, provides a unifying framework for the utilization of available experimental data from all phases of fire development. The plot of these criteria reveals the probable fire development envelope and indicates which fire constraint will be controlling during a criteria time period. Examples of RERC application to fire characterization and control and to hazard analysis are presented along with recommendations for the further development of the concept.

  14. 21 CFR 211.165 - Testing and release for distribution.

    Code of Federal Regulations, 2010 CFR

    2010-04-01

    ... products meet each appropriate specification and appropriate statistical quality control criteria as a condition for their approval and release. The statistical quality control criteria shall include appropriate acceptance levels and/or appropriate rejection levels. (e) The accuracy, sensitivity, specificity, and...

  15. The nervus terminalis in amphibians: anatomy, chemistry and relationship with the hypothalamic gonadotropin-releasing hormone system.

    PubMed

    Muske, L E; Moore, F L

    1988-01-01

    The nervus terminalis (TN), a component of the olfactory system, is found in most vertebrates. The TN of some fishes and mammals contains neurons immunoreactive (ir) to gonadotropin-releasing hormone (LHRH), and to several other neuropeptides and neurotransmitter systems, but there is little information on TN chemistry in other vertebrate taxa. Using immunocytochemical techniques, we found LHRH-ir neurons in amphibian TNs. In anurans, but not in a urodele, the TN was also found to contain Phe-Met-Arg-Phe-NH2 (FMRFamide) immunoreactivity. LHRH-ir neurons of the TN and those of the septal-hypothalamic system are morphologically homogeneous and form a distinct anatomical continuum in amphibians. Based upon topographical and cytological criteria, we hypothesize that LHRH-ir systems in vertebrates might derive embryonically from the TN.

  16. 76 FR 15001 - Entergy Nuclear Operations, Inc,. Entergy Nuclear Vermont Yankee, LLC, Vermont Yankee Nuclear...

    Federal Register 2010, 2011, 2012, 2013, 2014

    2011-03-18

    ... understand VY's design, layout, and construction. This failure to comprehend and understand the layout... Facilities,'' and General Design Criteria 60, ``Control of Releases of Radioactive Materials to the Environment,'' and 64, ``Monitoring Radioactivity Releases,'' of Appendix A, ``General Design Criteria for...

  17. Cadmium risks to freshwater life: derivation and validation of low-effect criteria values using laboratory and field studies

    USGS Publications Warehouse

    Mebane, Christopher A.

    2006-01-01

    In 2001, the U.S. Environmental Protection Agency (EPA) released updated aquatic life criteria for cadmium. Since then, additional data on the effects of cadmium to aquatic life have become available from studies supported by the EPA, Idaho Department of Environmental Quality (IDEQ), and the U.S. Geological Survey, among other sources. Updated data on the effects of cadmium to aquatic life were compiled and reviewed and low-effect concentrations were estimated. Low-effect values were calculated using EPA's guidelines for deriving numerical national water-quality criteria for the protection of aquatic organisms and their uses. Data on the short-term (acute) effects of cadmium on North American freshwater species that were suitable for criteria derivation were located for 69 species representing 57 genera and 33 families. For longer-term (chronic) effects of cadmium on North American freshwater species, suitable data were located for 28 species representing 21 genera and 17 families. Both the acute and chronic toxicity of cadmium were dependent on the hardness of the test water. Hardness-toxicity regressions were developed for both acute and chronic datasets so that effects data from different tests could be adjusted to a common water hardness. Hardness-adjusted effects values were pooled to obtain species and genus mean acute and chronic values, which then were ranked by their sensitivity to cadmium. The four most sensitive genera to acute exposures were, in order of increasing cadmium resistance, Oncorhynchus (Pacific trout and salmon), Salvelinus ('char' trout), Salmo (Atlantic trout and salmon), and Cottus (sculpin). The four most sensitive genera to chronic exposures were Hyalella (amphipod), Cottus, Gammarus (amphipod), and Salvelinus. Using the updated datasets, hardness dependent criteria equations were calculated for acute and chronic exposures to cadmium. At a hardness of 50 mg/L as calcium carbonate, the criterion maximum concentration (CMC, or 'acute' criterion) was calculated as 0.75 mug/L cadmium using the hardness-dependent equation CMC = e(0.8403 ? ln(hardness)-3.572) where the 'ln hardness' is the natural logarithm of the water hardness. Likewise, the criterion continuous concentration (CCC, or 'chronic' criterion) was calculated as 0.37 mug/L cadmium using the hardness-dependent equation CCC = (e(0.6247 ? ln(hardness)-3.384)) ? (1.101672 - ((ln hardness) ? 0.041838))). Using data that were independent of those used to derive the criteria, the criteria concentrations were evaluated to estimate whether adverse effects were expected to the biological integrity of natural waters or to selected species listed as threatened or endangered. One species was identified that would not be fully protected by the derived CCC, the amphipod Hyalella azteca. Exposure to CCC conditions likely would lead to population decreases in Hyalella azteca, the food web consequences of which probably would be slight if macroinvertebrate communities were otherwise diverse. Some data also suggested adverse behavioral changes are possible in fish following long-term exposures to low levels of cadmium, particularly in char (genus Salvelinus). Although ambiguous, these data indicate a need to periodically review the literature on behavioral changes in fish following metals exposure as more information becomes available. Most data reviewed indicated that criteria conditions were unlikely to contribute to overt adverse effects to either biological integrity or listed species. If elevated cadmium concentrations that approach the chronic criterion values occur in ambient waters, careful biological monitoring of invertebrate and fish assemblages would be prudent to validate the prediction that the assemblages would not be adversely affected by cadmium at criterion concentrations.

  18. When Medical News Comes from Press Releases—A Case Study of Pancreatic Cancer and Processed Meat

    PubMed Central

    Taylor, Joseph W.; Long, Marie; Ashley, Elizabeth; Denning, Alex; Gout, Beatrice; Hansen, Kayleigh; Huws, Thomas; Jennings, Leifa; Quinn, Sinead; Sarkies, Patrick; Wojtowicz, Alex; Newton, Philip M.

    2015-01-01

    The media have a key role in communicating advances in medicine to the general public, yet the accuracy of medical journalism is an under-researched area. This project adapted an established monitoring instrument to analyse all identified news reports (n = 312) on a single medical research paper: a meta-analysis published in the British Journal of Cancer which showed a modest link between processed meat consumption and pancreatic cancer. Our most significant finding was that three sources (the journal press release, a story on the BBC News website and a story appearing on the ‘NHS Choices’ website) appeared to account for the content of over 85% of the news stories which covered the meta analysis, with many of them being verbatim or moderately edited copies and most not citing their source. The quality of these 3 primary sources varied from excellent (NHS Choices, 10 of 11 criteria addressed) to weak (journal press release, 5 of 11 criteria addressed), and this variance was reflected in the accuracy of stories derived from them. Some of the methods used in the original meta-analysis, and a proposed mechanistic explanation for the findings, were challenged in a subsequent commentary also published in the British Journal of Cancer, but this discourse was poorly reflected in the media coverage of the story. PMID:26083640

  19. Comparison of human platelet lysate alternatives using expired and freshly isolated platelet concentrates for adipose-derived stromal cell expansion.

    PubMed

    Dessels, Carla; Durandt, Chrisna; Pepper, Michael S

    2018-03-19

    Pooled human platelet lysate (pHPL) has been used to expand adipose-derived stromal cells (ASCs) and can be formulated using fresh or expired buffy coats (BCs) which are then resuspended in either plasma or an additive solution. Not much is known about the effects that expired products and additive solutions have on ASC expansion, and the need for quality control and release criteria has been expressed. This pilot study compared proliferation, cell size, morphology and immunophenotype of ASCs expanded in the different pHPL alternatives versus foetal bovine serum (FBS). Quality control criteria were assessed prior to and during the manufacture of the pHPL alternatives. ASCs were then expanded in 1%, 2.5%, 5% or 10% of the different pHPL alternatives or in 10% FBS. Cell size, morphology, cell number and immunophenotype were measured using microscopy and flow cytometry. The majority of the pHPL alternatives were within the recommended ranges for the quality control criteria. ASCs expanded in the pHPL alternatives were smaller in size, displayed a tighter spindle-shaped morphology, increased cell growth and had a similar immunophenotype (with the exception of CD34 and CD36) when compared to ASCs expanded in FBS. Here we report on the effects that expired BC products and additive solutions have on ASC expansion. When taken together, our findings indicate that all of the pHPL alternatives can be considered to be suitable replacements for FBS for ASC expansion, and that expired BC products can be used as an alternative to fresh BC products.

  20. DEVELOPMENT OF MARINE WATER QUALITY CRITERIA

    EPA Science Inventory

    The U.S. Environmental Protectional Agency has developed guidelines for deriving numerical national water quality criteria for the protection of aquatic organisms and their uses. These guidelines provide the method for deriving water quality criteria, including minimum data base...

  1. Criteria for Identifying and Evaluating Candidate Sites for Open-Field Trials of Genetically Engineered Mosquitoes

    PubMed Central

    Brown, David M.; Alphey, Luke S.; McKemey, Andrew; Beech, Camilla

    2014-01-01

    Abstract Recent laboratory successes in the development of genetically engineered mosquitoes for controlling pathogen transmission have fostered the need for standardized procedures for advancing the technical achievements to practical tools. It is incumbent in many cases for the same scientists doing the in-laboratory discovery research to also take on the initial challenges of developing the pathway that will move the technologies to the field. One of these challenges is having a set of criteria for selecting collaborators and sites for efficacy and safety field trials that combine rigorous science with good ethical and legal practices. Specific site-selection criteria were developed in four categories—Scientific, Regulatory, Community Engagement, and Resources—in anticipation of open-field releases of a transgenic mosquito strain designed to suppress populations of the dengue vector mosquito, Aedes aegypti. The criteria are derived from previous published material, discussions, and personal experiences with the expectation of providing guidance to laboratory scientists for addressing the conceptual and operational considerations for identifying partner researchers and countries with whom to collaborate. These criteria are not intended to be prescriptive nor can they be applied to every circumstance where genetic approaches are proposed for deployment. However, we encourage those involved in the discovery phase of research to consider each criterion during project planning activities, and where appropriate, incorporate them into a “go/no-go” decision-making process for further development and testing of the technologies. PMID:24689963

  2. Derivation of Xeno-Free and GMP-Grade Human Embryonic Stem Cells – Platforms for Future Clinical Applications

    PubMed Central

    Aizenman, Einat; Kirshberg, Sophie; Ilouz, Nili; Gil, Yaniv; Berman-Zaken, Yael; Perlman, Temima Schnitzer; Geva, Nitshia; Levy, Ora; Arbell, Daniel; Simon, Alex; Ben-Meir, Assaf; Shufaro, Yoel; Laufer, Neri; Reubinoff, Benjamin E.

    2012-01-01

    Clinically compliant human embryonic stem cells (hESCs) should be developed in adherence to ethical standards, without risk of contamination by adventitious agents. Here we developed for the first time animal-component free and good manufacturing practice (GMP)-compliant hESCs. After vendor and raw material qualification, we derived xeno-free, GMP-grade feeders from umbilical cord tissue, and utilized them within a novel, xeno-free hESC culture system. We derived and characterized three hESC lines in adherence to regulations for embryo procurement, and good tissue, manufacturing and laboratory practices. To minimize freezing and thawing, we continuously expanded the lines from initial outgrowths and samples were cryopreserved as early stocks and banks. Batch release criteria included DNA-fingerprinting and HLA-typing for identity, characterization of pluripotency-associated marker expression, proliferation, karyotyping and differentiation in-vitro and in-vivo. These hESCs may be valuable for regenerative therapy. The ethical, scientific and regulatory methodology presented here may serve for development of additional clinical-grade hESCs. PMID:22745653

  3. 2017 Draft Aquatic Life Criteria for Aluminum in Freshwater

    EPA Pesticide Factsheets

    EPA has released draft updated aluminum aquatic life ambient water quality criteria for freshwater under Section 304(a)(1) of the Clean Water Act. EPA will accept public comments on the draft criteria for 60 days upon publication in the Federal Register.

  4. Financial analysis of experimental releases conducted at Glen Canyon Dam during water years 1997 through 2005.

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

    Veselka, T. D.; Poch, L. A.; Palmer, C. S.

    2010-04-21

    Because of concerns about the impact that Glen Canyon Dam (GCD) operations were having on downstream ecosystems and endangered species, the Bureau of Reclamation (Reclamation) conducted an Environmental Impact Statement (EIS) on dam operations (DOE 1996). New operating rules and management goals for GCD that had been specified in the Record of Decision (ROD) (Reclamation 1996) were adopted in February 1997. In addition to issuing new operating criteria, the ROD mandated experimental releases for the purpose of conducting scientific studies. This paper examines the financial implications of the experimental flows that were conducted at the GCD from 1997 to 2005.more » An experimental release may have either a positive or negative impact on the financial value of energy production. This study estimates the financial costs of experimental releases, identifies the main factors that contribute to these costs, and compares the interdependencies among these factors. An integrated set of tools was used to compute the financial impacts of the experimental releases by simulating the operation of the GCD under two scenarios, namely, (1) a baseline scenario that assumes operations comply with the ROD operating criteria and experimental releases that actually took place during the study period, and (2) a ''without experiments'' scenario that is identical to the baseline scenario of operations that comply with the GCD ROD, except it assumes that experimental releases did not occur. The Generation and Transmission Maximization (GTMax) model was the main simulation tool used to dispatch GCD and other hydropower plants that comprise the Salt Lake City Area Integrated Projects (SLCA/IP). Extensive data sets and historical information on SLCA/IP power plant characteristics, hydrologic conditions, and Western Area Power Administration's (Western's) power purchase prices were used for the simulation. In addition to estimating the financial impact of experimental releases, the GTMax model was also used to gain insights into the interplay among ROD operating criteria, exceptions that were made to criteria to accommodate the experimental releases, and Western operating practices. Experimental releases in some water years resulted in financial benefits to Western while others resulted in financial costs. During the study period, the total financial costs of all experimental releases were $11.9 million.« less

  5. Revised financial analysis of experimental releases conducted at Glen Canyon Dam during water years 1997 through 2005.

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

    Veselka, T. D.; Poch, L. A.; Palmer, C. S.

    2011-01-11

    Because of concerns about the impact that Glen Canyon Dam (GCD) operations were having on downstream ecosystems and endangered species, the Bureau of Reclamation (Reclamation) conducted an Environmental Impact Statement (EIS) on dam operations (DOE 1996). New operating rules and management goals for GCD that had been specified in the Record of Decision (ROD) (Reclamation 1996) were adopted in February 1997. In addition to issuing new operating criteria, the ROD mandated experimental releases for the purpose of conducting scientific studies. This paper examines the financial implications of the experimental flows that were conducted at the GCD from 1997 to 2005.more » An experimental release may have either a positive or negative impact on the financial value of energy production. This study estimates the financial costs of experimental releases, identifies the main factors that contribute to these costs, and compares the interdependencies among these factors. An integrated set of tools was used to compute the financial impacts of the experimental releases by simulating the operation of the GCD under two scenarios, namely, (1) a baseline scenario that assumes operations comply with the ROD operating criteria and experimental releases that actually took place during the study period, and (2) a 'without experiments' scenario that is identical to the baseline scenario of operations that comply with the GCD ROD, except it assumes that experimental releases did not occur. The Generation and Transmission Maximization (GTMax) model was the main simulation tool used to dispatch GCD and other hydropower plants that comprise the Salt Lake City Area Integrated Projects (SLCA/IP). Extensive data sets and historical information on SLCA/IP power plant characteristics, hydrologic conditions, and Western Area Power Administration's (Western's) power purchase prices were used for the simulation. In addition to estimating the financial impact of experimental releases, the GTMax model was also used to gain insights into the interplay among ROD operating criteria, exceptions that were made to criteria to accommodate the experimental releases, and Western operating practices. Experimental releases in some water years resulted in financial benefits to Western whileothers resulted in financial costs. During the study period, the total financial costs of all experimental releases were more than $23 million.« less

  6. 76 FR 8735 - Release of Final Document Related to the Review of the Secondary National Ambient Air Quality...

    Federal Register 2010, 2011, 2012, 2013, 2014

    2011-02-15

    ... ``criteria pollutants.'' The air quality criteria are to ``accurately reflect the latest scientific knowledge... criteria. The revised air quality criteria reflect advances in scientific knowledge on the effects of the... Related to the Review of the Secondary National Ambient Air Quality Standards for Oxides of Nitrogen and...

  7. Effects of dantrolene and its derivatives on Ca2+ release from the sarcoplasmic reticulum of mouse skeletal muscle fibres

    PubMed Central

    Ikemoto, Takaaki; Hosoya, Takamitsu; Aoyama, Hiroshi; Kihara, Yasutaka; Suzuki, Masaaki; Endo, Makoto

    2001-01-01

    We analysed the effect of dantrolene (Dan) and five newly synthesized derivatives (GIFs) on Ca2+ release from the sarcoplasmic reticulum (SR) of mouse skeletal muscle.In intact muscles, GIF-0185 reduced the size of twitch contraction induced by electrical stimulation to the same extent as Dan. GIF-0082, an azido-functionalized Dan derivative, also inhibited twitch contraction, although the extent of inhibition was less than that of Dan and of GIF-0185.In skinned fibres, Dan inhibited Ca2+-induced Ca2+ release (CICR) under Mg2+-free conditions at room temperature. In contrast, GIF-0082 and GIF-0185 showed no inhibitory effect on CICR under the same conditions.Dan-induced inhibition of CICR was not affected by the presence of GIF-0082, whereas it was diminished in the presence of GIF-0185.GIF-0082 and GIF-0185 significantly inhibited clofibric acid (Clof)-induced Ca2+ release, as did Dan.Several Dan derivatives other than GIF-0082 and GIF-0185 showed an inhibitory effect on twitch tension but not on the CICR mechanism. All of these derivatives inhibited Clof-induced Ca2+ release.The magnitudes of inhibition of Clof-induced Ca2+ release by all Dan derivatives were well correlated with those of twitch inhibition. This supports the notion that the mode of Clof-induced opening of the RyR-Ca2+ release channel may be similar to that of physiological Ca2+ release (PCR).These results indicate that the difference in opening modes of the RyR-Ca2+ release channel is recognized by certain Dan derivatives. PMID:11606312

  8. Full GMP-Compliant Validation of Bone Marrow-Derived Human CD133+ Cells as Advanced Therapy Medicinal Product for Refractory Ischemic Cardiomyopathy

    PubMed Central

    Belotti, Daniela; Gaipa, Giuseppe; Bassetti, Beatrice; Cabiati, Benedetta; Spaltro, Gabriella; Biagi, Ettore; Parma, Matteo; Biondi, Andrea; Cavallotti, Laura; Gambini, Elisa; Pompilio, Giulio

    2015-01-01

    According to the European Medicine Agency (EMA) regulatory frameworks, Advanced Therapy Medicinal Products (ATMP) represent a new category of drugs in which the active ingredient consists of cells, genes, or tissues. ATMP-CD133 has been widely investigated in controlled clinical trials for cardiovascular diseases, making CD133+ cells one of the most well characterized cell-derived drugs in this field. To ensure high quality and safety standards for clinical use, the manufacturing process must be accomplished in certified facilities following standard operative procedures (SOPs). In the present work, we report the fully compliant GMP-grade production of ATMP-CD133 which aims to address the treatment of chronic refractory ischemic heart failure. Starting from bone marrow (BM), ATMP-CD133 manufacturing output yielded a median of 6.66 × 106 of CD133+ cells (range 2.85 × 106–30.84 × 106), with a viability ranged between 96,03% and 99,97% (median 99,87%) and a median purity of CD133+ cells of 90,60% (range 81,40%–96,20%). Based on these results we defined our final release criteria for ATMP-CD133: purity ≥ 70%, viability ≥ 80%, cellularity between 1 and 12 × 106 cells, sterile, and endotoxin-free. The abovementioned criteria are currently applied in our Phase I clinical trial (RECARDIO Trial). PMID:26495296

  9. Full GMP-compliant validation of bone marrow-derived human CD133(+) cells as advanced therapy medicinal product for refractory ischemic cardiomyopathy.

    PubMed

    Belotti, Daniela; Gaipa, Giuseppe; Bassetti, Beatrice; Cabiati, Benedetta; Spaltro, Gabriella; Biagi, Ettore; Parma, Matteo; Biondi, Andrea; Cavallotti, Laura; Gambini, Elisa; Pompilio, Giulio

    2015-01-01

    According to the European Medicine Agency (EMA) regulatory frameworks, Advanced Therapy Medicinal Products (ATMP) represent a new category of drugs in which the active ingredient consists of cells, genes, or tissues. ATMP-CD133 has been widely investigated in controlled clinical trials for cardiovascular diseases, making CD133(+) cells one of the most well characterized cell-derived drugs in this field. To ensure high quality and safety standards for clinical use, the manufacturing process must be accomplished in certified facilities following standard operative procedures (SOPs). In the present work, we report the fully compliant GMP-grade production of ATMP-CD133 which aims to address the treatment of chronic refractory ischemic heart failure. Starting from bone marrow (BM), ATMP-CD133 manufacturing output yielded a median of 6.66 × 10(6) of CD133(+) cells (range 2.85 × 10(6)-30.84 × 10(6)), with a viability ranged between 96,03% and 99,97% (median 99,87%) and a median purity of CD133(+) cells of 90,60% (range 81,40%-96,20%). Based on these results we defined our final release criteria for ATMP-CD133: purity ≥ 70%, viability ≥ 80%, cellularity between 1 and 12 × 10(6) cells, sterile, and endotoxin-free. The abovementioned criteria are currently applied in our Phase I clinical trial (RECARDIO Trial).

  10. Preparation and characterization of controlled-release fertilizers coated with marine polysaccharide derivatives

    NASA Astrophysics Data System (ADS)

    Wang, Jing; Liu, Song; Qin, Yukun; Chen, Xiaolin; Xing, Rong'e.; Yu, Huahua; Li, Kecheng; Li, Pengcheng

    2017-09-01

    Encapsulation of water-soluble nitrogen fertilizers by membranes can be used to control the release of nutrients to maximize the fertilization effect and reduce environmental pollution. In this research, we formulated a new double-coated controlled-release fertilizer (CRF) by using food-grade microcrystalline wax (MW) and marine polysaccharide derivatives (calcium alginate and chitosan-glutaraldehyde copolymer). The pellets of water-soluble nitrogen fertilizer were coated with the marine polysaccharide derivatives and MW. A convenient and eco-friendly method was used to prepare the CRF. Scanning electron microscopy (SEM) and Fourier transform infrared spectroscopy (FTIR) were used to characterize the morphology and composition of the products. The nitrogen-release properties were determined in water using UV-Vis spectrophotometry. The controlled-release properties of the fertilizer were improved dramatically after coating with MW and the marine polysaccharide derivatives. The results show that the double-coated CRFs can release nitrogen in a controlled manner, have excellent controlled-release features, and meet the European Standard for CRFs.

  11. Air Quality Criteria for Ozone and Related Photochemical Oxidants (First External Review Draft)

    EPA Science Inventory

    This first external review draft of the Air Quality Criteria for Ozone and Related Photochemical Oxidants (Ozone Criteria Document) is being released in January 2005 for public comment and for review by EPA's Clean A...

  12. Air Quality Criteria for Ozone and Related Photochemical Oxidants (Second External Review Draft)

    EPA Science Inventory

    This second external review draft of the Air Quality Criteria for Ozone and Related Photochemical Oxidants, Volumes I-III (Ozone Criteria Document) is being released for public comment and for review by EPA's Clean Air Scientific Advisory Committee (CASAC) r...

  13. Financial analysis of experimental releases conducted at Glen Canyon Dam during water years 2006 through 2010.

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

    Poch, L. A.; Veselka, T. D.; Palmer, C. S.

    2011-08-22

    Because of concerns about the impact that Glen Canyon Dam (GCD) operations were having on downstream ecosystems and endangered species, the Bureau of Reclamation (Reclamation) conducted an Environmental Impact Statement (EIS) on dam operations (DOE 1996). New operating rules and management goals for GCD that had been specified in the Record of Decision (ROD) (Reclamation 1996) were adopted in February 1997. In addition to issuing new operating criteria, the ROD mandated experimental releases for the purpose of conducting scientific studies. A report released in January 2011 examined the financial implications of the experimental flows that were conducted at the GCDmore » from 1997 to 2005. This report continues the analysis and examines the financial implications of the experimental flows conducted at the GCD from 2006 to 2010. An experimental release may have either a positive or negative impact on the financial value of energy production. This study estimates the financial costs of experimental releases, identifies the main factors that contribute to these costs, and compares the interdependencies among these factors. An integrated set of tools was used to compute the financial impacts of the experimental releases by simulating the operation of the GCD under two scenarios, namely, (1) a baseline scenario that assumes both that operations comply with the ROD operating criteria and the experimental releases that actually took place during the study period, and (2) a 'without experiments' scenario that is identical to the baseline scenario of operations that comply with the GCD ROD, except it assumes that experimental releases did not occur. The Generation and Transmission Maximization (GTMax) model was the main simulation tool used to dispatch GCD and other hydropower plants that comprise the Salt Lake City Area Integrated Projects (SLCA/IP). Extensive data sets and historical information on SLCA/IP powerplant characteristics, hydrologic conditions, and Western Area Power Administration's (Western's) power purchase prices were used for the simulation. In addition to estimating the financial impact of experimental releases, the GTMax model was also used to gain insights into the interplay among ROD operating criteria, exceptions that were made to criteria to accommodate the experimental releases, and Western operating practices. Experimental releases in some water years resulted in financial benefits to Western while others resulted in financial costs. During the study period, the total financial costs of all experimental releases were more than $4.8 million.« less

  14. r.randomwalk v1.0, a multi-functional conceptual tool for mass movement routing

    NASA Astrophysics Data System (ADS)

    Mergili, M.; Krenn, J.; Chu, H.-J.

    2015-09-01

    We introduce r.randomwalk, a flexible and multi-functional open source tool for backward- and forward-analyses of mass movement propagation. r.randomwalk builds on GRASS GIS, the R software for statistical computing and the programming languages Python and C. Using constrained random walks, mass points are routed from defined release pixels of one to many mass movements through a digital elevation model until a defined break criterion is reached. Compared to existing tools, the major innovative features of r.randomwalk are: (i) multiple break criteria can be combined to compute an impact indicator score, (ii) the uncertainties of break criteria can be included by performing multiple parallel computations with randomized parameter settings, resulting in an impact indicator index in the range 0-1, (iii) built-in functions for validation and visualization of the results are provided, (iv) observed landslides can be back-analyzed to derive the density distribution of the observed angles of reach. This distribution can be employed to compute impact probabilities for each pixel. Further, impact indicator scores and probabilities can be combined with release indicator scores or probabilities, and with exposure indicator scores. We demonstrate the key functionalities of r.randomwalk (i) for a single event, the Acheron Rock Avalanche in New Zealand, (ii) for landslides in a 61.5 km2 study area in the Kao Ping Watershed, Taiwan; and (iii) for lake outburst floods in a 2106 km2 area in the Gunt Valley, Tajikistan.

  15. r.randomwalk v1, a multi-functional conceptual tool for mass movement routing

    NASA Astrophysics Data System (ADS)

    Mergili, M.; Krenn, J.; Chu, H.-J.

    2015-12-01

    We introduce r.randomwalk, a flexible and multi-functional open-source tool for backward and forward analyses of mass movement propagation. r.randomwalk builds on GRASS GIS (Geographic Resources Analysis Support System - Geographic Information System), the R software for statistical computing and the programming languages Python and C. Using constrained random walks, mass points are routed from defined release pixels of one to many mass movements through a digital elevation model until a defined break criterion is reached. Compared to existing tools, the major innovative features of r.randomwalk are (i) multiple break criteria can be combined to compute an impact indicator score; (ii) the uncertainties of break criteria can be included by performing multiple parallel computations with randomized parameter sets, resulting in an impact indicator index in the range 0-1; (iii) built-in functions for validation and visualization of the results are provided; (iv) observed landslides can be back analysed to derive the density distribution of the observed angles of reach. This distribution can be employed to compute impact probabilities for each pixel. Further, impact indicator scores and probabilities can be combined with release indicator scores or probabilities, and with exposure indicator scores. We demonstrate the key functionalities of r.randomwalk for (i) a single event, the Acheron rock avalanche in New Zealand; (ii) landslides in a 61.5 km2 study area in the Kao Ping Watershed, Taiwan; and (iii) lake outburst floods in a 2106 km2 area in the Gunt Valley, Tajikistan.

  16. 14 CFR 417.227 - Toxic release hazard analysis.

    Code of Federal Regulations, 2010 CFR

    2010-01-01

    ... 14 Aeronautics and Space 4 2010-01-01 2010-01-01 false Toxic release hazard analysis. 417.227..., DEPARTMENT OF TRANSPORTATION LICENSING LAUNCH SAFETY Flight Safety Analysis § 417.227 Toxic release hazard analysis. A flight safety analysis must establish flight commit criteria that protect the public from any...

  17. Plasma treatment of air pollution control residues.

    PubMed

    Amutha Rani, D; Gomez, E; Boccaccini, A R; Hao, L; Deegan, D; Cheeseman, C R

    2008-01-01

    Air pollution control (APC) residues from waste incineration have been blended with silica and alumina and the mix melted using DC plasma arc technology. The chemical composition of the fully amorphous homogeneous glass formed has been determined. Waste acceptance criteria compliance leach testing demonstrates that the APC residue derived glass releases only trace levels of heavy metals (Pb (<0.007mg/kg) and Zn (0.02mg/kg)) and Cl(-) (0.2mg/kg). These are significantly below the limit values for disposal to inert landfill. It is concluded that plasma treatment of APC residues can produce an inert glass that may have potential to be used either in bulk civil engineering applications or in the production of higher value glass-ceramic products.

  18. FRAMEWORK FOR DEVELOPING AMBIENT WATER ...

    EPA Pesticide Factsheets

    Currently, Ambient Water Quality Criteria (AWQC) for aquatic life protection are derived according to the Guidelines for Derivation of Ambient Water Quality Criteria for the Protection of Aquatic Life and Their Uses, published in 1985. To ensure that AWQC are derived from the best available science, Office of Water assessed the need to update the Guidelines and identified issues that should be addressed in the revisions. In December 2002, EPA's Science Advisory Board concurred with EPA's assessment of the need to update the Guidelines as well as with the issues EPA identified to address. Updating the Guidelines is a Priority Strategic Action included in OST's Strategy for Water Quality Standards and Criteria (Next Priority Strategic Action #1). To revise existing methodology for deriving ambient water quality criteria for the protection of aquatic life.

  19. "Using Satellite Remote Sensing to Derive Numeric Criteria in Coastal and Inland Waters of the United States"

    NASA Astrophysics Data System (ADS)

    Crawford, T. N.; Schaeffer, B. A.

    2016-12-01

    Anthropogenic nutrient pollution is a major stressor of aquatic ecosystems around the world. In the United States, states and tribes can adopt numeric water quality values (i.e. criteria) into their water quality management standards to protect aquatic life from eutrophication impacts. However, budget and resource constraints have limited the ability of many states and tribes to collect the water quality monitoring data needed to derive numeric criteria. Over the last few decades, satellite technology has provided water quality measurements on a global scale over long time periods. Water quality managers are finding the data provided by satellite technology useful in managing eutrophication impacts in coastal waters, estuaries, lakes, and reservoirs. In recent years EPA has worked with states and tribes to derive remotely sensed numeric Chl-a criteria for coastal waters with limited field-based data. This approach is now being expanded and used to derive Chl-a criteria in freshwater systems across the United States. This presentation will cover EPA's approach to derive numeric Chl-a criteria using satellite remote sensing, recommendations to improve satellite sensors to expand applications, potential areas of interest, and the challenges of using remote sensing to establish water quality management goals, as well as provide a case in which this approach has been applied.

  20. Minimizing the cost of translocation failure with decision-tree models that predict species' behavioral response in translocation sites.

    PubMed

    Ebrahimi, Mehregan; Ebrahimie, Esmaeil; Bull, C Michael

    2015-08-01

    The high number of failures is one reason why translocation is often not recommended. Considering how behavior changes during translocations may improve translocation success. To derive decision-tree models for species' translocation, we used data on the short-term responses of an endangered Australian skink in 5 simulated translocations with different release conditions. We used 4 different decision-tree algorithms (decision tree, decision-tree parallel, decision stump, and random forest) with 4 different criteria (gain ratio, information gain, gini index, and accuracy) to investigate how environmental and behavioral parameters may affect the success of a translocation. We assumed behavioral changes that increased dispersal away from a release site would reduce translocation success. The trees became more complex when we included all behavioral parameters as attributes, but these trees yielded more detailed information about why and how dispersal occurred. According to these complex trees, there were positive associations between some behavioral parameters, such as fight and dispersal, that showed there was a higher chance, for example, of dispersal among lizards that fought than among those that did not fight. Decision trees based on parameters related to release conditions were easier to understand and could be used by managers to make translocation decisions under different circumstances. © 2015 Society for Conservation Biology.

  1. Financial analysis of experimental releases conducted at Glen Canyon Dam during water year 2011

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

    Poch, L. A.; Veselka, T. D.; Palmer, C. S.

    2012-07-16

    This report examines the financial implications of experimental flows conducted at the Glen Canyon Dam (GCD) in water year 2011. It is the third report in a series examining financial implications of experimental flows conducted since the Record of Decision (ROD) was adopted in February 1997 (Reclamation 1996). A report released in January 2011 examined water years 1997 to 2005 (Veselka et al. 2011), and a report released in August 2011 examined water years 2006 to 2010 (Poch et al. 2011). An experimental release may have either a positive or negative impact on the financial value of energy production. Thismore » study estimates the financial costs of experimental releases, identifies the main factors that contribute to these costs, and compares the interdependencies among these factors. An integrated set of tools was used to compute the financial impacts of the experimental releases by simulating the operation of the GCD under two scenarios, namely, (1) a baseline scenario that assumes both that operations comply with the ROD operating criteria and the experimental releases that actually took place during the study period, and (2) a 'without experiments' scenario that is identical to the baseline scenario of operations that comply with the GCD ROD, except it assumes that experimental releases did not occur. The Generation and Transmission Maximization (GTMax) model was the main simulation tool used to dispatch GCD and other hydropower plants that comprise the Salt Lake City Area Integrated Projects (SLCA/IP). Extensive data sets and historical information on SLCA/IP powerplant characteristics, hydrologic conditions, and Western Area Power Administration's (Western's) power purchase prices were used for the simulation. In addition to estimating the financial impact of experimental releases, the GTMax model was also used to gain insights into the interplay among ROD operating criteria, exceptions that were made to criteria to accommodate the experimental releases, and Western operating practices. Experimental releases conducted in water year 2011 resulted only in financial costs; the total cost of all experimental releases was about $622,000.« less

  2. Fisk-based criteria to support validation of detection methods for drinking water and air.

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

    MacDonell, M.; Bhattacharyya, M.; Finster, M.

    2009-02-18

    This report was prepared to support the validation of analytical methods for threat contaminants under the U.S. Environmental Protection Agency (EPA) National Homeland Security Research Center (NHSRC) program. It is designed to serve as a resource for certain applications of benchmark and fate information for homeland security threat contaminants. The report identifies risk-based criteria from existing health benchmarks for drinking water and air for potential use as validation targets. The focus is on benchmarks for chronic public exposures. The priority sources are standard EPA concentration limits for drinking water and air, along with oral and inhalation toxicity values. Many contaminantsmore » identified as homeland security threats to drinking water or air would convert to other chemicals within minutes to hours of being released. For this reason, a fate analysis has been performed to identify potential transformation products and removal half-lives in air and water so appropriate forms can be targeted for detection over time. The risk-based criteria presented in this report to frame method validation are expected to be lower than actual operational targets based on realistic exposures following a release. Note that many target criteria provided in this report are taken from available benchmarks without assessing the underlying toxicological details. That is, although the relevance of the chemical form and analogues are evaluated, the toxicological interpretations and extrapolations conducted by the authoring organizations are not. It is also important to emphasize that such targets in the current analysis are not health-based advisory levels to guide homeland security responses. This integrated evaluation of chronic public benchmarks and contaminant fate has identified more than 200 risk-based criteria as method validation targets across numerous contaminants and fate products in drinking water and air combined. The gap in directly applicable values is considerable across the full set of threat contaminants, so preliminary indicators were developed from other well-documented benchmarks to serve as a starting point for validation efforts. By this approach, at least preliminary context is available for water or air, and sometimes both, for all chemicals on the NHSRC list that was provided for this evaluation. This means that a number of concentrations presented in this report represent indirect measures derived from related benchmarks or surrogate chemicals, as described within the many results tables provided in this report.« less

  3. Evaluating multimedia chemical persistence: Classification and regression tree analysis

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

    Bennett, D.H.; McKone, T.E.; Kastenberg, W.E.

    2000-04-01

    For the thousands of chemicals continuously released into the environment, it is desirable to make prospective assessments of those likely to be persistent. Widely distributed persistent chemicals are impossible to remove from the environment and remediation by natural processes may take decades, which is problematic if adverse health or ecological effects are discovered after prolonged release into the environment. A tiered approach using a classification scheme and a multimedia model for determining persistence is presented. Using specific criteria for persistence, a classification tree is developed to classify a chemical as persistent or nonpersistent based on the chemical properties. In thismore » approach, the classification is derived from the results of a standardized unit world multimedia model. Thus, the classifications are more robust for multimedia pollutants than classifications using a single medium half-life. The method can be readily implemented and provides insight without requiring extensive and often unavailable data. This method can be used to classify chemicals when only a few properties are known and can be used to direct further data collection. Case studies are presented to demonstrate the advantages of the approach.« less

  4. Slow-release granisetron (APF530) versus palonosetron for chemotherapy-induced nausea/vomiting: analysis by American Society of Clinical Oncology emetogenicity criteria.

    PubMed

    Raftopoulos, Harry; Boccia, Ralph; Cooper, William; O'Boyle, Erin; Gralla, Richard J

    2015-09-01

    APF530 is a novel sustained-release formulation of granisetron. In a Phase III trial, APF530 500 mg was noninferior to palonosetron 0.25 mg in preventing acute chemotherapy-induced nausea and vomiting (CINV) after moderately (MEC) or highly emetogenic chemotherapy (HEC) and delayed CINV after MEC, but not superior in preventing delayed CINV after HEC. Emetogenicity was classified by Hesketh criteria; this reanalysis uses newer American Society of Clinical Oncology criteria. Complete responses (no emesis or rescue medication) after cycle one were reanalyzed after reclassification of MEC and HEC by American Society of Clinical Oncology criteria. APF530 maintained noninferiority to palonosetron. Single-dose APF530 is a promising alternative to palonosetron for preventing acute and delayed CINV after MEC or HEC. The Clinicaltrials.gov identifier for this study is NCT00343460.

  5. Release profile of synthesized coumarin derivatives as a novel antibacterial agent from glass ionomer cement (GIC)

    NASA Astrophysics Data System (ADS)

    Rahman, Fatimah Suhaily Abdul; Osman, Hasnah; Mohamad, Dasmawati

    2017-12-01

    Glass ionomer cements (GIC) are widely used as dental restorative materials due to their aesthetics features and fluoride content. However, a capability of fluoride content in GIC to inhibit bacteria growth in an oral environment was insufficient for a long term which may lead to secondary caries. Therefore, two types of synthesized coumarin derivatives were incorporated with GIC to act as new antibacterial agent. However prior to the antibacterial evaluation, this study investigated the release profile of GIC incorporated with 3-Acetylcoumarin (GIC-1) and hydrazinyl thiosemicarbazide of coumarin derivatives (GIC-2) at three different concentrations of 0.5, 1.0 and 1.5 wt% up to 30 days. At early incubation period, GIC-1 revealed a higher release profile at 0.5 % fabrication that reached almost 45 % of cumulative release for 8 hours observational. Meanwhile, a slightly different output was obtained for GIC-2 in which 1.0 % fabrication of coumarin gave a better release in the initial hour. However, the pattern was replaced by 0.5 % substitution after 4 hours incubation time. A substitution of 1.5 % coumarin seems to be low in releasing activity for all materials. Conversely, in a longer period 1.0 % fabrication was discovered to be the highest coumarin release among others fabrications for both materials. Filler particle size and porosity of the materials were considered to be the main factor that may affect the coumarin release. Nonetheless, both synthesized coumarin derivatives can be incorporated with GIC as their release profile look very promising. Ultimately, the coumarin derivatives could improve the properties of GIC.

  6. Framework for Derivation of Water Quality Criteria Using the Biotic Ligand Model: Copper as a Case Study.

    PubMed

    Gondek, John C; Gensemer, Robert W; Claytor, Carrie A; Canton, Steven P; Gorsuch, Joseph W

    2018-06-01

    Acceptance of the Biotic Ligand Model (BLM) to derive aquatic life criteria, for metals in general and copper in particular, is growing amongst regulatory agencies worldwide. Thus, it is important to ensure that water quality data are used appropriately and consistently in deriving such criteria. Here we present a suggested BLM implementation framework (hereafter referred to as "the Framework") to help guide the decision-making process when designing sampling and analysis programs for use of the BLM to derive water quality criteria applied on a site-specific basis. Such a framework will help inform stakeholders on the requirements needed to derive BLM-based criteria, and thus, ensure the appropriate types and amount of data are being collected and interpreted. The Framework was developed for calculating BLM-based criteria when data are available from multiple sampling locations on a stream. The Framework aspires to promote consistency when applying the BLM across datasets of disparate water quality, data quantity, and spatial and temporal representativeness, and is meant to be flexible to maximize applicability over a wide range of scenarios. Therefore, the Framework allows for a certain level of interpretation and adjustment to address the issues unique to each dataset. This article is protected by copyright. All rights reserved. This article is protected by copyright. All rights reserved.

  7. Chinese plasma-derived products supply under the lot release management system in 2007-2011.

    PubMed

    Zhang, Xuejun; Ye, Shengliang; Du, Xi; Yuan, Jing; Zhao, Chaoming; Li, Changqing

    2013-11-01

    In 2007, the Chinese State Food and Drug Administration (SFDA) implemented a management system for lot release of all plasma-derived products. Since then, there have been only a few systematic studies of the blood supply, which is a concern when considering the small amount of plasma collected per capita (approximately 3 L/1000 people). As a result, there may be a threat to the safety of the available blood supply. In this study, we examined the characteristics of the supply of Chinese plasma-derived products. We investigated the reports of lot-released biological products derived from all 8 national or regional regulatory authorities in China from 2007 to 2011. The market supply characteristics of Chinese plasma-derived products were analyzed by reviewing the changes in supply varieties, the batches of lot-released plasma-derived products and the actual supply. As a result, the national regulatory authorities can more accurately develop a specific understanding of the production and quality management information provided by Chinese plasma product manufacturers. The implementation of the lot release system further ensures the clinical validity of the plasma-derived products in China and improves the safety of using plasma-derived products. This work provides an assessment of the future Chinese market supply of plasma-derived products and can function as a theoretical basis for the establishment of hemovigilance. Copyright © 2013 The International Alliance for Biological Standardization. Published by Elsevier Ltd. All rights reserved.

  8. 75 FR 5589 - Science Advisory Board Staff Office; Request for Public Nominations of Experts To Conduct a Peer...

    Federal Register 2010, 2011, 2012, 2013, 2014

    2010-02-03

    ... Conductivity Using Field Data: An Adaptation of the U.S. EPA's Standard Methodology for Deriving Water Quality... Adaptation of the U.S. EPA's Standard Methodology for Deriving Water Quality Criteria'' DATES: Nominations... Deriving Water Quality Criteria'' should be directed to Dr. Michael Slimak, ORD's Associate Director of...

  9. Review: A Position Paper on Selenium in Ecotoxicology: A Procedure for Deriving Site-Specific Water Quality Criteria

    Treesearch

    A. Dennis Lemly

    1997-01-01

    This paper describes a method for deriving site-specific water quality criteria for selenium using a two-step process: (1) gather information on selenium residues and biological effects at the site and in down-gradient systems and (2) examine criteria based on the degree of bioaccumulation, the relationship between mea-sured residues and threshold concentrations for...

  10. Development of cultured Plasmodium falciparum blood-stage malaria cell banks for early phase in vivo clinical trial assessment of anti-malaria drugs and vaccines.

    PubMed

    Stanisic, Danielle I; Liu, Xue Q; De, Sai Lata; Batzloff, Michael R; Forbes, Tanya; Davis, Christopher B; Sekuloski, Silvana; Chavchich, Marina; Chung, Wendy; Trenholme, Katharine; McCarthy, James S; Li, Tao; Sim, B Kim Lee; Hoffman, Stephen L; Good, Michael F

    2015-04-07

    The ability to undertake controlled human malaria infection (CHMI) studies for preliminary evaluation of malaria vaccine candidates and anti-malaria drug efficacy has been limited by the need for access to sporozoite infected mosquitoes, aseptic, purified, cryopreserved sporozoites or blood-stage malaria parasites derived ex vivo from malaria infected individuals. Three different strategies are described for the manufacture of clinical grade cultured malaria cell banks suitable for use in CHMI studies. Good Manufacturing Practices (GMP)-grade Plasmodium falciparum NF54, clinically isolated 3D7, and research-grade P. falciparum 7G8 blood-stage malaria parasites were cultured separately in GMP-compliant facilities using screened blood components and then cryopreserved to produce three P. falciparum blood-stage malaria cell banks. These cell banks were evaluated according to specific criteria (parasitaemia, identity, viability, sterility, presence of endotoxin, presence of mycoplasma or other viral agents and in vitro anti-malarial drug sensitivity of the cell bank malaria parasites) to ensure they met the criteria to permit product release according to GMP requirements. The P. falciparum NF54, 3D7 and 7G8 cell banks consisted of >78% ring stage parasites with a ring stage parasitaemia of >1.4%. Parasites were viable in vitro following thawing. The cell banks were free from contamination with bacteria, mycoplasma and a broad panel of viruses. The P. falciparum NF54, 3D7 and 7G8 parasites exhibited differential anti-malarial drug susceptibilities. The P. falciparum NF54 and 3D7 parasites were susceptible to all anti-malaria compounds tested, whereas the P. falciparum 7G8 parasites were resistant/had decreased susceptibility to four compounds. Following testing, all defined release criteria were met and the P. falciparum cell banks were deemed suitable for release. Ethical approval has been obtained for administration to human volunteers. The production of cultured P. falciparum blood-stage malaria cell banks represents a suitable approach for the generation of material suitable for CHMI studies. A key feature of this culture-based approach is the ability to take research-grade material through to a product suitable for administration in clinical trials.

  11. Iron Release from Soybean Seed Ferritin Induced by Cinnamic Acid Derivatives.

    PubMed

    Sha, Xuejiao; Chen, Hai; Zhang, Jingsheng; Zhao, Guanghua

    2018-05-04

    Plant ferritin represents a novel class of iron supplement, which widely co-exists with phenolic acids in a plant diet. However, there are few reports on the effect of these phenolic acids on function of ferritin. In this study, we demonstrated that cinnamic acid derivatives, as widely occurring phenolic acids, can induce iron release from holo soybean seed ferritin (SSF) in a structure-dependent manner. The ability of the iron release from SSF by five cinnamic acids follows the sequence of Cinnamic acid > Chlorogenic acid > Ferulic acid > p -Coumaric acid > Trans -Cinnamic acid. Fluorescence titration in conjunction with dialysis results showed that all of these five compounds have a similar, weak ability to bind with protein, suggesting that their protein-binding ability is not related to their iron release activity. In contrast, both Fe 2+ -chelating activity and reducibility of these cinnamic acid derivatives are in good agreement with their ability to induce iron release from ferritin. These studies indicate that cinnamic acid and its derivatives could have a negative effect on iron stability of holo soybean seed ferritin in diet, and the Fe 2+ -chelating activity and reducibility of cinnamic acid and its derivatives have strong relations to the iron release of soybean seed ferritin.

  12. ASSESSING BIOACCUMULATION FOR DERIVING NATIONAL HUMAN HEALTH WATER QUALITY CRITERIA

    EPA Science Inventory

    The United States Environmental Protection Agency is revising its methodology for deriving national ambient water quality criteria (AWQC) to protect human health. A component of this guidance involves assessing the potential for chemical bioaccumulation in commonly consumed fish ...

  13. Setting radon-specific release criteria and demonstrating compliance for land affected by NORM.

    PubMed

    García-Talavera, M; Martínez, M; Matarranz, J L M; Ramos, L

    2008-11-01

    Residues from industrial activities involving naturally occurring radioactive materials (NORMs) may cause radiation exposures to members of the public, particularly when NORM-affected land is brought into residential use. To provide an adequate protection against radiation in such situations, the following limiting criteria are currently required in Spain for releasing NORM-affected land: (i) no more than a 300 microSv yr(-1) increase (excluding radon doses) over the natural background; (ii) (222)Rn concentrations in hypothetical future dwellings lower than 200 Bq m(-3); and (iii) reduction of all radiation exposures to as low as reasonable achievable. This paper addresses some of the problems encountered in translating the (222)Rn criterion into site-specific release limits and in demonstrating compliance with them.

  14. Deriving sediment Interstitial Water Remediation Goals ...

    EPA Pesticide Factsheets

    Background/Objectives. Passive sampling is becoming a frequently used measurement technique at Superfund sites with contaminated sediments. Passive sampling measures the concentrations of freely dissolved chemicals (Cfrees) in the sediment interstitial water. The freely dissolved chemical is a good surrogate for and a very practical means for estimating the concentrations of bioavailable chemical in the sediments. Building from this approach, a methodology is proposed to derive sediment Interstitial Water Remediation Goals (IWRGs) for the protection of benthic organisms from direct toxicity using Cfrees measured with passive sampling.Approach/Activities. In the early 2000s, EPA developed and released Equilibrium Partitioning Sediment Benchmarks (ESBs) for a series of chemicals. ESBs are intended to be chemical concentrations below which unacceptable toxicity to benthic organisms does not occur. The ESBs (expressed with the units of ug/g OC) were derived using the equations:ESB= K_OC×FCV where K_OC=0.00028+0.983K_OWThe KOC is the organic carbon normalized sediment-water chemical partition coefficient, FCV is the Final Chronic Value from EPA’s ambient water quality criteria for the protection of aquatic life, and KOW is the n-octanol/water partition coefficient for the chemical. At a specific site, the remedial goal (CS:ESB µg/kg-dw) in sediment are then derived using the site-specific fraction of organic carbon in the sediment (fOC:SS) at the site:C_

  15. Maximizing the accuracy of field-derived numeric nutrient criteria in water quality regulations.

    PubMed

    McLaughlin, Douglas B

    2014-01-01

    High levels of the nutrients nitrogen and phosphorus can cause unhealthy biological or ecological conditions in surface waters and prevent the attainment of their designated uses. Regulatory agencies are developing numeric criteria for these nutrients in an effort to ensure that the surface waters in their jurisdictions remain healthy and productive, and that water quality standards are met. These criteria are often derived using field measurements that relate nutrient concentrations and other water quality conditions to expected biological responses such as undesirable growth or changes in aquatic plant and animal communities. Ideally, these numeric criteria can be used to accurately "diagnose" ecosystem health and guide management decisions. However, the degree to which numeric nutrient criteria are useful for decision making depends on how accurately they reflect the status or risk of nutrient-related biological impairments. Numeric criteria that have little predictive value are not likely to be useful for managing nutrient concerns. This paper presents information on the role of numeric nutrient criteria as biological health indicators, and the potential benefits of sufficiently accurate criteria for nutrient management. In addition, it describes approaches being proposed or adopted in states such as Florida and Maine to improve the accuracy of numeric criteria and criteria-based decisions. This includes a preference for developing site-specific criteria in cases where sufficient data are available, and the use of nutrient concentration and biological response criteria together in a framework to support designated use attainment decisions. Together with systematic planning during criteria development, the accuracy of field-derived numeric nutrient criteria can be assessed and maximized as a part of an overall effort to manage nutrient water quality concerns. © 2013 SETAC.

  16. Considerations in the Derivation of Water Quality Criteria for Endocrine-disrupting Chemicals

    EPA Science Inventory

    When the USEPA’s 1985 guidelines for deriving numerical water quality criteria (WQC) for the protection of aquatic life were developed there was little anticipation that endocrine-disrupting chemicals (EDCs) would be come a widespread environmental issue. While the basic guidelin...

  17. On the Uniqueness Conditions and Bifurcation Criteria in Coupled Thermo-Elasto-Plasticity

    NASA Astrophysics Data System (ADS)

    Śloderbach, Z.

    2017-02-01

    The global and local conditions of uniqueness and the criteria excluding a possibility of bifurcation of the equilibrium state for small strains are derived. The conditions and criteria are derived analyzing the problem of uniqueness of solution of the basic incremental boundary problem of coupled generalized thermo-elasto-plasticity. This paper is a continuation of some previous works by the author, but contains new derivation of the global and local criteria excluding a possibility of bifurcation of the equilibrium state for a comparison body dependent on statically admissible fields of stress velocity. All the thermal elastoplastic coupling effects, non-associated laws of plastic flow and influence of plastic strains on thermoplastic properties of a body were taken into account in this work. Thus, the mathematical problem considered here is not a self-conjugated problem. The paper contains four Appendices A, B, C and D where the local necessery and sufficient conditions of uniqueness have been derived.

  18. Adipose-derived stem cell-derived microvesicle-released miR-210 promoted proliferation, migration and invasion of endothelial cells by regulating RUNX3.

    PubMed

    Zheng, Zeqi; Liu, Lijuan; Zhan, Yuliang; Yu, Songping; Kang, Ting

    2018-06-18

    To explore the potential mechanism of miRNA released from adipose-derived stem cell (ADSC)-derived micro vesicle (MV) on the modulation of proliferation, migration and invasion of endothelial cells. miR-210 level was detected by qT-PCR. Alix, VEGF and RUNX3 expressions were detected by Western blot. The proliferation, migration and invasion of human umbilical vein endothelial cells (HUVECs) were observed by MTT assay and Transwell assay. Luciferase reporter gene assay was conducted to validate the targeting activity of MVs-released miR-210 on RUNX3. Hypoxia significantly increased the expression of MVs-released miR-210. MVs released from ADSCs in hypoxic group significantly promoted the proliferation, migration and invasion of HUVECs. Overexpression of miR-210 significantly upregulated VEGF expression, and promoted the proliferation, migration and invasion of HUVECs. Besides, RUNX3 was identified as the direct of miR-210 in HUVECs. Overexpression of miR-210 decreased RUNX3 expression and promoted the proliferation, migration and invasion of HUVECs, while overexpression of RUNX3 inhibited these promotion effects. In vivo experiment showed that MVs derived from ADSCs under hypoxia increased miR-210 level and capillary density, and inhibition of miR-210 decreased capillary density. We also found MVs downregulated RUNX3 expression, and inhibition of miR-210 upregulated RUNX3 expression. miR-210 released from ADSCs-derived MVs promoted proliferation, migration and invasion of HUVECs by targeting RUNX3, which revealed one of the mechanisms of ADSCs-derived MVs on the promotion of proliferation, migration and invasion of HUVECs.

  19. Radiological criteria for underground nuclear tests

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

    Malik, J.S.; Brownlee, R.R.; Costa, C.F.

    1981-04-01

    The radiological criteria for the conduct of nuclear tests have undergone many revisions with the current criteria being 0.17 rad for uncontrolled populations and 0.5 rad for controllable populations. Their effect upon operations at the Nevada Test Site and the current off-site protective plans are reviewed for areas surrounding the Site. The few accidental releases that have occurred are used to establish estimates of probability of release and of hazard to the population. These are then put into context by comparing statistical data on other accidents and cataclysms. The guidelines established by DOE Manual Chapter MC-0524 have never been exceededmore » during the entire underground nuclear test program. The probability of real hazard to off-site populations appears to be sufficiently low as not to cause undue concern to the citizenry.« less

  20. Facilitating emergency hospital evacuation through uniform discharge criteria.

    PubMed

    Sandra, Keret; Meital, Nahari; Ofer, Merin; Limor, Aharonson-Daniel; Sara, Goldberg; Bruria, Adini

    2017-05-01

    Though hospitals' operational continuity is crucial, full institutional evacuation may at times be unavoidable. The study's objective was to establish criteria for discharge of patients during complete emergency evacuation and compare scope of patients suitable for discharge pre/post implementation of criteria. Standards for patient discharge during an evacuation were developed based on literature and disaster managers. The standards were reviewed in a two-round Delphi process. All hospitals in Israel were requested to identify inpatients' that could be released home during institutional evacuation. Potential discharges were compared in 2013-2014, before and after formulation of discharge criteria. Consensus exceeding 80% was obtained for four out of five criteria after two Delphi cycles. Average projected discharge rate before and after formulation of criteria was 34.2% and 42.9%, respectively (p<0.001). Variance in potential dischargeable patients was 31-fold less in 2014 than in 2013 (MST=8,452 versus MST=264,366, respectively; p<0.001). Differences were found between small, medium and large hospitals in mean rate of dischargeable patients: 52.1%, 41.5% and 42.2%, respectively (p=0.001). The study's findings enable to forecast the extent of patients that may be released home during full emergency evacuation of a hospital; thereby facilitating preparedness of contingency plans. Copyright © 2016 Elsevier Inc. All rights reserved.

  1. Generation of Requirements for Simulant Measurements. Revised, May 30, 2010

    NASA Technical Reports Server (NTRS)

    Rickman, Doug; Edmunson, Jennifer

    2010-01-01

    This document provides a formal, logical explanation of the parameters selected for the Figure of Merit algorithm used to evaluate lunar regolith simulant. The objectives, requirements, assumptions and analysis behind the parameters is provided. From NASA's objectives for lunar simulants a requirement is derived to verify and validate simulant performance versus lunar regolith. This requirement leads to a specification that comparative measurements be taken the same way on the regolith and the simulant. In turn this leads to a set of 9 criteria with which to evaluate comparative measurement. Many of the potential measurements of interest are not defensible under these criteria, for example many geotechnical properties of interest were not explicitly measured during Apollo and they can only be measured in situ on the Moon. A 2005 workshop identified 32 properties of major interest to users (Sibille Carpenter Schlagheck, and French, 2006). Virtually all of the properties are tightly constrained, though not predictable, if just four parameters are controlled. Three: composition, size and shape, are recognized as being definable at the particle level. The fourth, density, is a bulk property. In recent work a fifth parameter has been identified, which will need to be added to future releases of the Figure of Merit: spectroscopy.

  2. Generation of Requirements for Simulant Measurements

    NASA Technical Reports Server (NTRS)

    Rickman, D. L.; Schrader, C. M.; Edmunson, J. E.

    2010-01-01

    This TM presents a formal, logical explanation of the parameters selected for the figure of merit (FoM) algorithm. The FoM algorithm is used to evaluate lunar regolith simulant. The objectives, requirements, assumptions, and analysis behind the parameters are provided. A requirement is derived to verify and validate simulant performance versus lunar regolith from NASA s objectives for lunar simulants. This requirement leads to a specification that comparative measurements be taken the same way on the regolith and the simulant. In turn, this leads to a set of nine criteria with which to evaluate comparative measurements. Many of the potential measurements of interest are not defensible under these criteria. For example, many geotechnical properties of interest were not explicitly measured during Apollo and they can only be measured in situ on the Moon. A 2005 workshop identified 32 properties of major interest to users. Virtually all of the properties are tightly constrained, though not predictable, if just four parameters are controlled. Three parameters (composition, size, and shape) are recognized as being definable at the particle level. The fourth parameter (density) is a bulk property. In recent work, a fifth parameter (spectroscopy) has been identified, which will need to be added to future releases of the FoM.

  3. Air Quality Criteria for Ozone and Related Photochemical Oxidants (Final Report, 2006)

    EPA Science Inventory

    In February 2006, EPA released the final document, Air Quality Criteria for Ozone and Other Photochemical Oxidants. Tropospheric or surface-level ozone (O3) is one of six major air pollutants regulated by National Ambient Air Quality Standards (NAAQS) under the U.S...

  4. Environmental risk assessment in GMO analysis.

    PubMed

    Pirondini, Andrea; Marmiroli, Nelson

    2010-01-01

    Genetically modified or engineered organisms (GMOs, GEOs) are utilised in agriculture, expressing traits of interest, such as insect or herbicide resistance. Soybean, maize, cotton and oilseed rape are the GM crops with the largest acreage in the world. The distribution of GM acreage in the different countries is related with the different positions concerning labelling of GMO products: based on the principle of substantial equivalence, or rather based on the precautionary principle. The paper provides an overview on how the risks associated with release of GMO in the environments can be analysed and predicted, in view of a possible coexistence of GM and non-GM organisms in agriculture.Risk assessment procedures, both qualitative and quantitative, are compared in the context of application to GMOs considering also legislation requirements (Directive 2001/18/EC). Criteria and measurable properties to assess harm for human health and environmental safety are listed, and the possible consequences are evaluated in terms of significance.Finally, a mapping of the possible risks deriving from GMO release is reported, focusing on gene transfer to related species, horizontal gene transfer, direct and indirect effects on non target organisms, development of resistance in target organisms, and effects on biodiversity.

  5. Environmental risk assessment in GMO analysis.

    PubMed

    Pirondini, Andrea; Marmiroli, Nelson

    2008-01-01

    Genetically modified or engineered organisms (GMOs, GEOs) are utilised in agriculture, expressing traits of interest, such as insect or herbicide resistance. Soybean, maize, cotton and oilseed rape are the GM crops with the largest acreage in the world. The distribution of GM acreage in the different countries is related with the different positions concerning labelling of GMO products: based on the principle of substantial equivalence, or rather based on the precautionary principle. The paper provides an overview on how the risks associated with release of GMO in the environments can be analysed and predicted, in view of a possible coexistence of GM and non-GM organisms in agriculture.Risk assessment procedures, both qualitative and quantitative, are compared in the context of application to GMOs considering also legislation requirements (Directive 2001/18/EC). Criteria and measurable properties to assess harm for human health and environmental safety are listed, and the possible consequences are evaluated in terms of significance.Finally, a mapping of the possible risks deriving from GMO release is reported, focusing on gene transfer to related species, horizontal gene transfer, direct and indirect effects on non target organisms, development of resistance in target organisms, and effects on biodiversity.

  6. Northrop TRIGA facility decommissioning plan versus actual results

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

    Gardner, F.W.

    1986-01-01

    This paper compares the TRIGA facility decontamination and decommissioning (D and D) plan to the actual results and discusses key areas where operational activities were impacted by the final US Nuclear Regulatory Commission approved D and D plan. A discussion of fuel transport, release criteria, and release survey plans is included.

  7. Tumor necrosis factor alpha promotes the expression of immunosuppressive proteins and enhances the cell growth in a human bone marrow-derived stem cell culture

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

    Miettinen, Johanna A., E-mail: johanna.miettinen@oulu.fi; Pietilae, Mika; Salonen, Riikka J.

    Mesenchymal stem cells (MSCs) are widely used in experimental treatments for various conditions that involve normal tissue regeneration via inflammatory repair. It is known that MSCs can secrete multiple soluble factors and suppress inflammation. Even though the effect of MSCs on inflammation has been extensively studied, the effect of inflammation on MSCs is poorly understood. One of the major cytokines released at the site of inflammation is tumor necrosis factor alpha (TNF-{alpha}) which is known to induce MSC invasion and proliferation. Therefore, we wanted to test the effects of TNF-{alpha} exposure on MSCs derived from human bone marrow. We found,more » as expected, that cell proliferation was significantly enhanced during TNF-{alpha} exposure. However, according to the cell surface marker analysis, the intensity of several antigens in the minimum criteria panel for MSCs proposed by International Society of Cellular Therapy (ISCT) was decreased dramatically, and in certain cases, the criteria for MSCs were not fulfilled. In addition, TNF-{alpha} exposure resulted in a significant but transient increase in human leukocyte antigen and CD54 expression. Additional proteomic analysis by two-dimensional difference gel electrophoresis and mass spectrometry revealed three proteins whose expression levels decreased and 8 proteins whose expression levels increased significantly during TNF-{alpha} exposure. The majority of these proteins could be linked to immunosuppressive and signalling pathways. These results strongly support reactive and immunosuppressive activation of MSCs during TNF-{alpha} exposure, which might influence MSC differentiation stage and capacity.« less

  8. Installation Restoration Program. Phase II Stage I Study McGuire Air Force Base, Burlington County, New Jersey.

    DTIC Science & Technology

    1984-10-01

    risk level.derive human health criteria. Most evaluation and synthesis. Scientific SurmyofteJlrc &2criteria are based solely on exposure judg~~nt was...State drinking water and human health standards, criteria, and guidelines applica- ble in the State of New Jersey. On November 28, 1980, the U.S...established recommended maximum concentrations for acute and chronic exposure to these pollutants by both humans and aquatic life. The derivation of these

  9. The main beam correction term in kinetic energy release from metastable peaks.

    PubMed

    Petersen, Allan Christian

    2017-12-01

    The correction term for the precursor ion signal width in determination of kinetic energy release is reviewed, and the correction term is formally derived. The derived correction term differs from the traditionally applied term. An experimental finding substantiates the inaccuracy in the latter. The application of the "T-value" to study kinetic energy release is found preferable to kinetic energy release distributions when the metastable peaks are slim and simple Gaussians. For electronically predissociated systems, a "borderline zero" kinetic energy release can be directly interpreted in reaction dynamics with strong curvature in the reaction coordinate. Copyright © 2017 John Wiley & Sons, Ltd.

  10. REVISING EPA'S GUIDELINES FOR THE DERIVATIONS OF AQUATIC LIFE AMBIENT WATER QUALITY CRITERIA

    EPA Science Inventory

    Henry, T.R., H.E. Bell, C.G. Delos, R.J. Erickson, K.M. Kubena and F.L. Mayer. In press. Revising EPA's Guidelines for the Derivation of Aquatic Life Ambient Water Quality Criteria (Abstract). To be presented at the SETAC Fourth World Congress, 14-18 November 2004, Portland, OR. ...

  11. Electrocardiographic Criteria for Left Ventricular Hypertrophy in Asians Differs from Criteria Derived from Western Populations--Community-based Data from an Asian Population.

    PubMed

    Xu, Chang Fen; Tan, Eugene S J; Feng, Liang; Santhanakrishnan, Rajalakshmi; Chan, Michelle M Y; Nyunt, Shwe Zin; Ng, Tze Pin; Ling, Lieng Hsi; Richards, A Mark; Lam, Carolyn S P; Lim, Toon Wei

    2015-08-01

    Electrocardiographic (ECG) criteria for left ventricular hypertrophy (LVH), such as the Cornell and Sokolow-Lyon voltage criteria were derived from Western populations. However, their utility and accuracy for diagnosing echocardiographic LVH in Asian populations is unclear. The objective of this study was to assess the accuracy of ECG criteria for LVH in Asians and to determine if alternative gender-specific ECG cut-offs may improve its diagnostic accuracy. ECG and echocardiographic assessments were performed on 668 community-dwelling Asian adults (50.9% women; 57 ± 10 years) in Singapore. The accuracy of ECG voltage criteria was compared to echocardiographic LVH criteria based on the American Society of Echocardiography guidelines, and Asian ethnicity and gender-specific partition values. Echocardiographic LVH was present in 93 (13.6%) adults. Cornell criteria had low sensitivity (5.5%) and high specificity (98.9%) for diagnosing LVH. Modified gender specific cut-offs (18 mm in women, 22 mm in men) improved sensitivity (8.8% to 17.5%, 0% to 14.7%, respectively) whilst preserving specificity (98.2% to 94.2%, 100% to 95.8%). Similarly, Sokolow-Lyon criteria had poor sensitivity (7.7%) and high specificity (96.1%) for diagnosing LVH. Lowering the cut-off value from 35 mm to 31 mm improved the sensitivity in women from 3.5% to 14% while preserving specificity at 94.2%. A cut-off of 36 mm was optimal in men (sensitivity of 14.7%, specificity of 95.5%). Current ECG criteria for LVH derived in Western cohorts have limited sensitivity in Asian populations. Our data suggests that ethnicity- and gender-specific ECG criteria may be needed.

  12. Release Report for Building Debris for TA-21 Sewage Treatment Facility

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

    Whicker, Jeffrey Jay; Gillis, Jessica; Ruedig, Elizabeth

    2017-05-03

    ENV-ES finds that the materials associated with TA-21 Buildings 227 (superstructure only), and 229 (see Figure 1) meet the criteria for unrestricted release to the public for recycle or as sanitary/commercial waste. The interior and exterior of the metal shed, building 387, passed the release criteria collectively; however, results from the roof of the structure were above reference background measurements. Waste management should be consulted for waste disposition options for the roofing metal. These findings are consistent with the requirements of DOE Order 458.1 “Radiation Protection of the Public and the Environment” and LANL Policy 412 “Environmental Radiation Protection.” Samplingmore » and data analysis, as described in this report, were sufficient to meet measurement objectives under the Multi-Agency Radiation Survey and Assessment of Materials and Equipment (MARSAME) manual (2009).« less

  13. Reversible water uptake/release by thermoresponsive polyelectrolyte hydrogels derived from ionic liquids.

    PubMed

    Deguchi, Yuki; Kohno, Yuki; Ohno, Hiroyuki

    2015-06-07

    Thermoresponsive polyelectrolyte hydrogels, derived from tetra-n-alkylphosphonium 3-sulfopropyl methacrylate-type ionic liquid monomers, show reversible water uptake/release, in which the gels absorb/desorb water for at least ten cycles via a lower critical solution temperature-type phase transition.

  14. 78 FR 52192 - Final Aquatic Life Ambient Water Quality Criteria For Ammonia-Freshwater 2013

    Federal Register 2010, 2011, 2012, 2013, 2014

    2013-08-22

    ... ambient water quality criteria for the protection of aquatic life from effects of ammonia in freshwater... life criteria are developed based on EPA's Guidelines for Deriving Numerical National Water Quality... quality standards for protecting aquatic life and human health. EPA's recommended water quality criteria...

  15. 77 FR 30280 - Final National Recommended Ambient Water Quality Criteria for Carbaryl-2012

    Federal Register 2010, 2011, 2012, 2013, 2014

    2012-05-22

    ... national recommended water quality criteria for the protection of aquatic life from effects of carbaryl... developed the aquatic life criteria based on EPA's Guidelines for Deriving Numerical National Water Quality... quality standards for protecting aquatic life and human health. These criteria are intended to protect...

  16. 2014 Edition Release 2 Electronic Health Record (EHR) certification criteria and the ONC HIT Certification Program; regulatory flexibilities, improvements, and enhanced health information exchange. Final rule.

    PubMed

    2014-09-11

    This final rule introduces regulatory flexibilities and general improvements for certification to the 2014 Edition EHR certification criteria (2014 Edition). It also codifies a few revisions and updates to the ONC HIT Certification Program for certification to the 2014 Edition and future editions of certification criteria as well as makes administrative updates to the Code of Federal Regulations.

  17. Chitosan cross-linked with poly(ethylene glycol)dialdehyde via reductive amination as effective controlled release carriers for oral protein drug delivery.

    PubMed

    Jing, Zi-Wei; Ma, Zhi-Wei; Li, Chen; Jia, Yi-Yang; Luo, Min; Ma, Xi-Xi; Zhou, Si-Yuan; Zhang, Bang-Le

    2017-02-15

    The covalently cross-linked chitosan-poly(ethylene glycol) 1540 derivatives have been developed as a controlled release system with potential for the delivery of protein drug. The swelling characteristics of the hydrogels based on these derivatives as the function of different PEG content and the release profiles of a model protein (bovine serum albumin, BSA) from the hydrogels were evaluated in simulated gastric fluid with or without enzyme in order to simulate the gastrointestinal tract conditions. The derivatives cross-linked with difunctional PEG 1540 -dialdehyde via reductive amination can swell in alkaline pH and remain insoluble in acidic medium. The cumulative release amount of BSA was relatively low in the initial 2h and increased significantly at pH 7.4 with intestinal lysozyme for additional 12h. The results proved that the release-and-hold behavior of the cross-linked CS-PEG 1540 H-CS hydrogel provided a swell and intestinal enzyme controlled release carrier system, which is suitable for oral protein drug delivery. Copyright © 2016 Elsevier Ltd. All rights reserved.

  18. 77 FR 14843 - [Securities Act of 1933; Release No. 9300/March 7, 2012; Securities Exchange Act of 1934; Release...

    Federal Register 2010, 2011, 2012, 2013, 2014

    2012-03-13

    ..., as generally accepted for purposes of the securities laws, any accounting principles established by a... concluding that the Financial Accounting Standards Board (``FASB'') and its parent organization, the Financial Accounting Foundation (``FAF''), satisfied the criteria for an accounting standard-setting body...

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

    Garabedian, G.

    This document details the decontamination and decommissioning (D&D) process of Rooms 248 and 250 of Building 62 at the Ernest Orlando Lawrence Berkeley National Laboratory (LBNL). The document describes the D&D efforts for the rooms, their contents, and adjacent areas containing ancillary equipment. The rooms and equipment, before being released, were required to meet the unrestricted release criteria and requirements set forth in DOE orders 5400.5 and 5480.11, LBNL`s internal release-criteria procedure (EH&S Procedure 708), and the LBNL Radiological Control Manual. The radioactive material and items not meeting the release criteria were either sent to the Hazardous Waste Handling Facilitymore » (HWHF) for disposal or transferred to other locations approved for radioactive material. The D&D was undertaken by the Radiation Protection Group of LBNL`s Environment, Health and Safety (EH&S) Division at the request of the Materials Sciences Division. Current and past use of radioactive material in both Rooms 248 and 250 necessitated the D&D in order to release both rooms for nonradioactive work. (1) Room 248 was designated a {open_quotes}controlled area.{close_quotes} There was contained radioactive material in some of the equipment. The previous occupants of Room 248 had worked with radioactive materials. (2) Room 250 was designated a {open_quotes}Radioactive Materials Management Area{close_quotes} (RMMA) because the current occupants used potentially dispersible radioisotopes. Both laboratories, during the occupancy of U.C. Berkeley Professor Leo Brewer and Ms. Karen Krushwitz, were kept in excellent condition. There was a detailed inventory of all radioactive materials and chemicals. All work and self surveys were documented. The labs were kept extremely orderly, clean, and in compliance. In October 1993 Ms. Krushwitz received an award in recognition of her efforts in Environmental Protection, Health, and Safety at LBNL.« less

  20. Resin selection criteria for tough composite structures

    NASA Technical Reports Server (NTRS)

    Chamis, C. C.; Smith, G. T.

    1983-01-01

    Resin selection criteria are derived using a structured methodology consisting of an upward integrated mechanistic theory and its inverse (top-down structured theory). These criteria are expressed in a "criteria selection space" which are used to identify resin bulk properties for improved composite "toughness". The resin selection criteria correlate with a variety of experimental data including laminate strength, elevated temperature effects and impact resistance.

  1. Importance of being Nernst: Synaptic activity and functional relevance in stem cell-derived neurons

    PubMed Central

    Bradford, Aaron B; McNutt, Patrick M

    2015-01-01

    Functional synaptogenesis and network emergence are signature endpoints of neurogenesis. These behaviors provide higher-order confirmation that biochemical and cellular processes necessary for neurotransmitter release, post-synaptic detection and network propagation of neuronal activity have been properly expressed and coordinated among cells. The development of synaptic neurotransmission can therefore be considered a defining property of neurons. Although dissociated primary neuron cultures readily form functioning synapses and network behaviors in vitro, continuously cultured neurogenic cell lines have historically failed to meet these criteria. Therefore, in vitro-derived neuron models that develop synaptic transmission are critically needed for a wide array of studies, including molecular neuroscience, developmental neurogenesis, disease research and neurotoxicology. Over the last decade, neurons derived from various stem cell lines have shown varying ability to develop into functionally mature neurons. In this review, we will discuss the neurogenic potential of various stem cells populations, addressing strengths and weaknesses of each, with particular attention to the emergence of functional behaviors. We will propose methods to functionally characterize new stem cell-derived neuron (SCN) platforms to improve their reliability as physiological relevant models. Finally, we will review how synaptically active SCNs can be applied to accelerate research in a variety of areas. Ultimately, emphasizing the critical importance of synaptic activity and network responses as a marker of neuronal maturation is anticipated to result in in vitro findings that better translate to efficacious clinical treatments. PMID:26240679

  2. Cross-species evaluation of molecular target sequence and structural conservation as a line of evidence for identification of susceptible taxa to inform derivation of aquatic life criteria

    EPA Science Inventory

    The 1985 U.S. Environmental Protection Agency (EPA) Guidelines for Deriving Aquatic Life Criteria (ALC) require acute and chronic toxicity testing with a fixed list of taxa that cover aquatic organisms from vertebrates, invertebrates, and plants. In considering Guideline revision...

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

    Jeremy Gwin and Douglas Frenette

    This document contains process knowledge and radiological data and analysis to support approval for release of the 25-ton locomotive, Serial Number 21547, at the Area 25 Engine Maintenance, Assembly, and Disassembly (EMAD) Facility, located on the Nevada Test Site (NTS). The 25-ton locomotive is a small, one-of-a-kind locomotive used to move railcars in support of the Nuclear Engine for Rocket Vehicle Application project. This locomotive was identified as having significant historical value by the Nevada State Railroad Museum in Boulder City, Nevada, where it will be used as a display piece. A substantial effort to characterize the radiological conditions ofmore » the locomotive was undertaken by the NTS Management and Operations Contractor, National Security Technologies, LLC (NSTec). During this characterization process, seven small areas on the locomotive had contamination levels that exceeded the NTS release criteria (limits consistent with U.S. Department of Energy [DOE] Order DOE O 5400.5, “Radiation Protection of the Public and the Environment”). The decision was made to perform radiological decontamination of these known accessible impacted areas to further the release process. On February 9, 2010, NSTec personnel completed decontamination of these seven areas to within the NTS release criteria. Although all accessible areas of the locomotive had been successfully decontaminated to within NTS release criteria, it was plausible that inaccessible areas of the locomotive (i.e., those areas on the locomotive where it was not possible to perform radiological surveys) could potentially have contamination above unrestricted release limits. To access the majority of these inaccessible areas, the locomotive would have to be disassembled. A complete disassembly for a full radiological survey could have permanently destroyed parts and would have ruined the historical value of the locomotive. Complete disassembly would also add an unreasonable financial burden for the contractor. A decision was reached between the NTS regulator and NSTec, opting for alternative authorized limits from DOE Headquarters. In doing so, NSTec personnel performed a dose model using the DOE-approved modeling code RESRAD-BUILD v3.5 to evaluate scenarios. The parameters used in the dose model were conservative. NSTec’s Radiological Engineering Calculation, REC-2010-001, “Public Dose Estimate from the EMAD 25 Ton Locomotive,” concluded that the four scenarios evaluated were below the 25-millirem per year limit, the “likely” dose scenarios met the “few millirem in a year” criteria, and that the EMAD 25-ton locomotive met the radiological requirements to be released with residual radioactivity to the public.« less

  4. Evaluation and construction of diagnostic criteria for inclusion body myositis

    PubMed Central

    Mammen, Andrew L.; Amato, Anthony A.; Weiss, Michael D.; Needham, Merrilee

    2014-01-01

    Objective: To use patient data to evaluate and construct diagnostic criteria for inclusion body myositis (IBM), a progressive disease of skeletal muscle. Methods: The literature was reviewed to identify all previously proposed IBM diagnostic criteria. These criteria were applied through medical records review to 200 patients diagnosed as having IBM and 171 patients diagnosed as having a muscle disease other than IBM by neuromuscular specialists at 2 institutions, and to a validating set of 66 additional patients with IBM from 2 other institutions. Machine learning techniques were used for unbiased construction of diagnostic criteria. Results: Twenty-four previously proposed IBM diagnostic categories were identified. Twelve categories all performed with high (≥97%) specificity but varied substantially in their sensitivities (11%–84%). The best performing category was European Neuromuscular Centre 2013 probable (sensitivity of 84%). Specialized pathologic features and newly introduced strength criteria (comparative knee extension/hip flexion strength) performed poorly. Unbiased data-directed analysis of 20 features in 371 patients resulted in construction of higher-performing data-derived diagnostic criteria (90% sensitivity and 96% specificity). Conclusions: Published expert consensus–derived IBM diagnostic categories have uniformly high specificity but wide-ranging sensitivities. High-performing IBM diagnostic category criteria can be developed directly from principled unbiased analysis of patient data. Classification of evidence: This study provides Class II evidence that published expert consensus–derived IBM diagnostic categories accurately distinguish IBM from other muscle disease with high specificity but wide-ranging sensitivities. PMID:24975859

  5. Financial Analysis of Experimental Releases Conducted at Glen Canyon Dam during Water Year 2015

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

    Graziano, D. J.; Poch, L. A.; Veselka, T. D.

    This report examines the financial implications of experimental flows conducted at the Glen Canyon Dam (GCD) in water year (WY) 2015. It is the seventh report in a series examining the financial implications of experimental flows conducted since the Record of Decision (ROD) was adopted in February 1997 (Reclamation 1996). A report released in January 2011 examined WYs 1997 to 2005 (Veselka et al. 2011); a report released in August 2011 examined WYs 2006 to 2010 (Poch et al. 2011); a report released June 2012 examined WY 2011 (Poch et al. 2012); a report released April 2013 examined WY 2012more » (Poch et al. 2013); a report released June 2014 examined WY 2013 (Graziano et al. 2014); and a report released September 2015 examined WY 2014 (Graziano et al. 2015). An experimental release may have either a positive or negative impact on the financial value of energy production. Only one experimental release was conducted at GCD in WY 2015; specifically, a high flow experimental (HFE) release conducted in November 2014. For this experimental release, financial costs of approximately $2.1 million were incurred because the HFE required sustained water releases that exceeded the powerplant’s maximum flow rate. In addition, during the month of the experiment, operators were not allowed to shape GCD power production to either follow firm power customer loads or to respond to market prices. This study identifies the main factors that contribute to HFE costs and examines the interdependencies among these factors. It applies an integrated set of tools to estimate financial impacts by simulating the GCD operations under two scenarios: (1) a baseline scenario that mimics both HFE operations during the experiment and during the rest of the year when it complies with the 1996 ROD operating criteria, and (2) a “without experiments” scenario that is identical to the baseline except it assumes that the HFE did not occur. The Generation and Transmission Maximization (GTMax) model was the main simulation tool used to simulate the dispatch of hydropower plants at GCD and other plants that comprise the Salt Lake City Area Integrated Projects (SLCA/IP). The research team used extensive data sets and historical information on SLCA/IP powerplant characteristics, hydrologic conditions, and Western Area Power Administration’s (WAPA’s) power purchase prices in the modeling process. In addition to estimating the financial impact of the HFE, the team used the GTMax model to gain insights into the interplay among ROD operating criteria, exceptions that were made to criteria to accommodate the experimental releases, and WAPA operating practices.« less

  6. Deriving a water quality guideline for protection of aquatic communities exposed to triclosan in the Canadian environment.

    PubMed

    Hill, Katie L; Breton, Roger L; Manning, Gillian E; Teed, R Scott; Capdevielle, Marie; Slezak, Brian

    2018-07-01

    Triclosan is an antibacterial and antifungal chemical used in a variety of consumer products, including soaps, detergents, moisturizers, and cosmetics. Aquatic ecosystems may be exposed to triclosan following the release of remaining residues in wastewater effluents and biosolids. In December 2017, Environment and Climate Change Canada (ECCC) released a federal environmental quality guideline (FEQG) report that contained a federal water quality guideline (FWQG) for triclosan. This guideline will be used as an adjunct to the risk assessment and risk management of priority chemicals identified under the Government of Canada's Chemicals Management Plan (CMP). The FWQG value for triclosan (0.47 μg/L) was derived by ECCC using a hazardous concentration for 5% of species (HC5) from a species sensitivity distribution (SSD). We recalculated the FWQG after performing an independent analysis and evaluation of the available aquatic toxicity data for triclosan and compared our results with the ECCC FWQG value. Our independent analysis of the available aquatic toxicity data entailed conducting a literature search of all available and relevant studies, evaluating the quality and reliability of all studies considered using thorough and consistent study evaluation criteria, and thereby generating a data set of high-quality toxicity values. The selected data set includes 22 species spanning 5 taxonomic groups. An SSD was developed using this data set following the ECCC approaches. The HC5 from the SSD derived based on our validated data set is 0.76 μg/L. This HC5 value is slightly greater (i.e., less sensitive) than the value presented in ECCC's final FWQG. Integr Environ Assess Manag 2018;14:437-441. © 2018 The Authors. Integrated Environmental Assessment and Management published by Wiley Periodicals, Inc. on behalf of Society of Environmental Toxicology & Chemistry (SETAC). © 2018 The Authors. Integrated Environmental Assessment and Management Published by Wiley Periodicals, Inc. on behalf of Society of Environmental Toxicology & Chemistry (SETAC).

  7. Cardiac mast cell-derived renin promotes local angiotensin formation, norepinephrine release, and arrhythmias in ischemia/reperfusion.

    PubMed

    Mackins, Christina J; Kano, Seiichiro; Seyedi, Nahid; Schäfer, Ulrich; Reid, Alicia C; Machida, Takuji; Silver, Randi B; Levi, Roberto

    2006-04-01

    Having identified renin in cardiac mast cells, we assessed whether its release leads to cardiac dysfunction. In Langendorff-perfused guinea pig hearts, mast cell degranulation with compound 48/80 released Ang I-forming activity. This activity was blocked by the selective renin inhibitor BILA2157, indicating that renin was responsible for Ang I formation. Local generation of cardiac Ang II from mast cell-derived renin also elicited norepinephrine release from isolated sympathetic nerve terminals. This action was mediated by Ang II-type 1 (AT1) receptors. In 2 models of ischemia/reperfusion using Langendorff-perfused guinea pig and mouse hearts, a significant coronary spillover of renin and norepinephrine was observed. In both models, this was accompanied by ventricular fibrillation. Mast cell stabilization with cromolyn or lodoxamide markedly reduced active renin overflow and attenuated both norepinephrine release and arrhythmias. Similar cardioprotection was observed in guinea pig hearts treated with BILA2157 or the AT1 receptor antagonist EXP3174. Renin overflow and arrhythmias in ischemia/reperfusion were much less prominent in hearts of mast cell-deficient mice than in control hearts. Thus, mast cell-derived renin is pivotal for activating a cardiac renin-angiotensin system leading to excessive norepinephrine release in ischemia/reperfusion. Mast cell-derived renin may be a useful therapeutic target for hyperadrenergic dysfunctions, such as arrhythmias, sudden cardiac death, myocardial ischemia, and congestive heart failure.

  8. Generic Assessment Criteria for human health risk assessment of potentially contaminated land in China.

    PubMed

    Cheng, Yuanyuan; Nathanail, Paul C

    2009-12-20

    Generic Assessment Criteria (GAC) are derived using widely applicable assumptions about the characteristics and behaviour of contaminant sources, pathways and receptors. GAC provide nationally consistent guidance, thereby saving money and time. Currently, there are no human health based Generic Assessment Criteria (GAC) for contaminated sites in China. Protection of human health is therefore difficult to ensure and demonstrate; and the lack of GAC makes it difficult to tell if there is potential significant risk to human health unless site-specific criteria are derived. This paper derived Chinese GAC (GAC) for five inorganic and eight organic substances for three regions in China for three land uses: urban residential without plant uptake, Chinese cultivated land, and commercial/industrial using the SNIFFER model. The SNIFFER model has been further implemented with a dermal absorption algorithm and the model default input values have been changed to reflect the Chinese exposure scenarios. It is envisaged that the modified SNIFFER model could be used to derive GAC for more contaminants, more Regions, and more land uses. Further research to enhance the reliability and acceptability of the GAC is needed in regional/national surveys in diet and working patterns.

  9. Feasibility and application of a retronasal aroma-trapping device to study in vivo aroma release during the consumption of model wine-derived beverages

    PubMed Central

    Muñoz-González, Carolina; Rodríguez-Bencomo, Juan José; Moreno-Arribas, Maria Victoria; Pozo-Bayón, Maria Ángeles

    2014-01-01

    New types of wine-derived beverages are now in the market. However, little is known about the impact of ingredient formulation on aroma release during consumption, which is directly linked to consumer preferences and liking. In this study, the optimization and validation of a retronasal aroma-trapping device (RATD) for the in vivo monitoring of aroma release was carried out. This device was applied to assess the impact of two main ingredients (sugar and ethanol) in these types of beverages on in vivo aroma release. Two aroma-trapping materials (Lichrolut and Tenax) were firstly assayed. Tenax provided higher recovery and lower intra- and inter-trap variability. In in vivo conditions, RATD provided an adequate linear range (R2 > 0.91) between 0 and 50 mg L−1 of aroma compounds. Differences in the total aroma release were observed in equally trained panelists. It was proven that the addition of sugar (up to 150 mg kg−1) did not have effect on aroma release, while ethanol (up to 40 mg L−1) enhanced the aroma release during drinking. The RATD is a useful tool to collect real in vivo data to extract reliable conclusions about the effect of beverage components on aroma release during consumption. The concentration of ethanol should be taken into consideration for the formulation of wine-derived beverages. PMID:25473493

  10. A catalog of rules, variables, and definitions applied to accelerometer data in the National Health and Nutrition Examination Survey, 2003-2006.

    PubMed

    Tudor-Locke, Catrine; Camhi, Sarah M; Troiano, Richard P

    2012-01-01

    The National Health and Nutrition Examination Survey (NHANES) included accelerometry in the 2003-2006 data collection cycles. Researchers have used these data since their release in 2007, but the data have not been consistently treated, examined, or reported. The objective of this study was to aggregate data from studies using NHANES accelerometry data and to catalogue study decision rules, derived variables, and cut point definitions to facilitate a more uniform approach to these data. We conducted a PubMed search of English-language articles published (or indicated as forthcoming) from January 2007 through December 2011. Our initial search yielded 74 articles, plus 1 article that was not indexed in PubMed. After excluding 21 articles, we extracted and tabulated details on 54 studies to permit comparison among studies. The 54 articles represented various descriptive, methodological, and inferential analyses. Although some decision rules for treating data (eg, criteria for minimal wear-time) were consistently applied, cut point definitions used for accelerometer-derived variables (eg, time spent in various intensities of physical activity) were especially diverse. Unique research questions may require equally unique analytical approaches; some inconsistency in approaches must be tolerated if scientific discovery is to be encouraged. This catalog provides a starting point for researchers to consider relevant and/or comparable accelerometer decision rules, derived variables, and cut point definitions for their own research questions.

  11. Cross-linked high amylose starch derivatives for drug release III. Diffusion properties.

    PubMed

    Mulhbacher, Jérôme; Mateescu, Mircea Alexandru

    2005-06-13

    Acetate (Ac-), aminoethyl (AE-) and carboxymethyl (CM-) derivatives of cross-linked high amylose starch (HASCL-6) were previously shown to control the release of drugs over 20 h from highly loaded (up to 60% drug) monolithic tablets. This report presents a diffusion analysis, aimed to facilitate a better understanding of the mechanisms involved in the control of the drug release from these hydrogels. The diffusion was found to depend on the molecular weight of the diffusant, whereas the partition coefficient depended on the affinities of the diffusant for the polymers and for the dissolution media via attractive or repulsive ionic interactions. The diffusion was also affected by the swelling of CM-HASCL-6, which, unexpectedly, increased with the decrease of the ionic strength. This diffusion analysis completes the swelling studies of HASCL-6 and of its derivatives, allowing the prediction of release kinetics of various active agents.

  12. 76 FR 55237 - Use of Derivatives by Investment Companies Under the Investment Company Act of 1940

    Federal Register 2010, 2011, 2012, 2013, 2014

    2011-09-07

    ... years, the use of derivatives by mutual funds has soared.''), available at http://www.interactivedata... Companies, Investment Company Act Release No. 10666 (Apr. 18, 1979) (``Release 10666'') [44 FR 25128 (Apr. 27, 1979)], and Registered Investment Company Use of Senior Securities-Select Bibliography (``Senior...

  13. Designing adaptive operating rules for a large multi-purpose reservoir

    NASA Astrophysics Data System (ADS)

    Geressu, Robel; Rougé, Charles; Harou, Julien

    2017-04-01

    Reservoirs whose live storage capacity is large compared with annual inflow have "memory", i.e., their storage levels contain information about past inflows and reservoir operations. Such "long-memory" reservoirs can be found in basins in dry regions such as the Nile River Basin in Africa, the Colorado River Basin in the US, or river basins in Western and Central Asia. There the effects of a dry year have the potential to impact reservoir levels and downstream releases for several subsequent years, prompting tensions in transboundary basins. Yet, current reservoir operation rules in those reservoirs do not reflect this by integrating past climate history and release decisions among the factors that influence operating decisions. This work proposes and demonstrates an adaptive reservoir operating rule that explicitly accounts for the recent history of release decisions, and not only current storage level and near-term inflow forecasts. This implies adding long-term (e.g., multiyear) objectives to the existing short-term (e.g., annual) ones. We apply these operating rules to the Grand Ethiopian Renaissance Dam, a large reservoir under construction on the Blue Nile River. Energy generation has to be balanced with the imperative of releasing enough water in low flow years (e.g., the minimum 1, 2 or 3 year cumulative flow) to avoid tensions with downstream countries, Sudan and Egypt. Maximizing the minimum multi-year releases could be of interest for the Nile problem to minimize the impact on performance of the large High Aswan Dam in Egypt. Objectives include maximizing the average and minimum annual energy generation and maximizing the minimum annual, two year and three year cumulative releases. The system model is tested using 30 stochastically generated streamflow series. One can then derive adaptive release rules depending on the value of one- and two-year total releases with respect to thresholds. Then, there are 3 sets of release rules for the reservoir depending on whether one or both thresholds are not met, vs. only one with a non-adaptive rule. Multi-objective evolutionary algorithms (MOEAs) are used to obtain the Pareto front, i.e., non-dominated adaptive and non-adaptive operating rule sets. Implementing adaptive rules is found to improve the trade-offs between energy generation criteria and minimum release targets. Compared with non-adaptive operations, an adaptive operating policy shows an increase of around 3 and 10 Billion cubic meters in the minimum 1 and 3-year cumulative releases for a given value of the same average annual energy generation.

  14. Lateral patellar retinaculum reconstruction for medial patellar instability following lateral retinacular release: a case report.

    PubMed

    Udagawa, Kazuhiko; Niki, Yasuo; Matsumoto, Hiroaki; Matsumoto, Hideo; Enomoto, Hiroyuki; Toyama, Yoshiaki; Suda, Yasunori

    2014-01-01

    Lateral retinacular release is still being performed in patients with recurrent patellar dislocation as an additional procedure with distal realignment or medial patellofemoral ligament (MPFL) reconstruction. However, consensus remains lacking regarding suitable indications for lateral retinacular release. A 20-year-old woman presented with patellar instability in both medial and lateral directions after undergoing lateral retinacular release with MPFL reconstruction. She displayed inherent systemic joint laxity meeting all seven Carter-Wilkinson criteria. Simultaneous MPFL revision and lateral retinaculum reconstruction successfully improved patellar instability in both directions. This case provides an example of iatrogenic medial patellar instability after failed lateral retinacular release. Copyright © 2013 Elsevier B.V. All rights reserved.

  15. Patient release criteria following radioactive iodine-131 treatment in the light of international practice: where does South Africa fit in?

    PubMed

    Mongane, Modisenyane S; Rae, William I D

    2017-10-01

    The release from hospital of patients treated with radioactive iodine-131 (I) remains a controversial issue as a result of the range of guidelines implemented by national regulatory bodies responsible for radiation protection in various countries worldwide. The aim of this study was to review and analyse the literature on patient release criteria (PRC) applied internationally in an attempt to achieve a justifiable approach to setting equivalent criteria in South Africa. In 2016, the South African Department of Health, Directorate: Radiation Control added conditions (numbers 50 and 90), to licences to use radioactive nuclides. These conditions state that patients must be hospitalized when the dose rate at 1 m is above 25 μSv/h, or more than 555 MBq of iodine-131 was administered to the patient. However, these criteria do not consider patients' socioeconomic conditions. A literature survey was carried out of articles detailing PRC from high-income countries as well as those in the middle-income and lower-income groups. Socioeconomic conditions within countries were determined using the International Monetary Fund lists of gross domestic product. The results from the literature have shown that in setting PRC, several countries have considered the socioeconomic conditions prevailing in their countries to achieve harmony between public protection and cost associated with hospitalization. The South African authority conditions must be seen in the context of the approach followed by other countries. Considering the international context, a justifiable, and potentially implementable, guideline or policy for improving individualized and more caring patient management is advocated.

  16. Defining applied behavior analysis: An historical analogy

    PubMed Central

    Deitz, Samuel M.

    1982-01-01

    This article examines two criteria for a definition of applied behavior analysis. The criteria are derived from a 19th century attempt to establish medicine as a scientific field. The first criterion, experimental determinism, specifies the methodological boundaries of an experimental science. The second criterion, philosophic doubt, clarifies the tentative nature of facts and theories derived from those facts. Practices which will advance the science of behavior are commented upon within each criteria. To conclude, the problems of a 19th century form of empiricism in medicine are related to current practices in applied behavior analysis. PMID:22478557

  17. Sequestration of hydrophobic organic contaminants by geosorbents

    USGS Publications Warehouse

    Luthy, Richard G.; Aiken, George R.; Brusseau, Mark L.; Cunningham, Scott D.; Gschwend, Philip M.; Pignatello, Joseph J.; Reinhard, Martin; Traina, Samuel J.; Weber, Walter J.; Westall, John C.

    1997-01-01

    The chemical interactions of hydrophobic organic contaminants (HOCs) with soils and sediments (geosorbents) may result in strong binding and slow subsequent release rates that significantly affect remediation rates and endpoints. The underlying physical and chemical phenomena potentially responsible for this apparent sequestration of HOCs by geosorbents are not well understood. This challenges our concepts for assessing exposure and toxicity and for setting environmental quality criteria. Currently there are no direct observational data revealing the molecular-scale locations in which nonpolar organic compounds accumulate when associated with natural soils or sediments. Hence macroscopic observations are used to make inferences about sorption mechanisms and the chemical factors affecting the sequestration of HOCs by geosorbents. Recent observations suggest that HOC interactions with geosorbents comprise different inorganic and organic surfaces and matrices, and distinctions may be drawn along these lines, particularly with regard to the roles of inorganic micropores, natural sorbent organic matter components, combustion residue particulate carbon, and spilled organic liquids. Certain manipulations of sorbates or sorbent media may help reveal sorption mechanisms, but mixed sorption phenomena complicate the interpretation of macroscopic data regarding diffusion of HOCs into and out of different matrices and the hysteretic sorption and aging effects commonly observed for geosorbents. Analytical characterizations at the microscale, and mechanistic models derived therefrom, are needed to advance scientific knowledge of HOC sequestration, release, and environmental risk.

  18. GMP-based CD133+ cells isolation maintains progenitor angiogenic properties and enhances standardization in cardiovascular cell therapy

    PubMed Central

    Gaipa, Giuseppe; Tilenni, Manuela; Straino, Stefania; Burba, Ilaria; Zaccagnini, Germana; Belotti, Daniela; Biagi, Ettore; Valentini, Marco; Perseghin, Paolo; Parma, Matteo; Campli, Cristiana Di; Biondi, Andrea; Capogrossi, Maurizio C; Pompilio, Giulio; Pesce, Maurizio

    2010-01-01

    Abstract The aim of the present study was to develop and validate a good manufacturing practice (GMP) compliant procedure for the preparation of bone marrow (BM) derived CD133+ cells for cardiovascular repair. Starting from available laboratory protocols to purify CD133+ cells from human cord blood, we implemented these procedures in a GMP facility and applied quality control conditions defining purity, microbiological safety and vitality of CD133+ cells. Validation of CD133+ cells isolation and release process were performed according to a two-step experimental program comprising release quality checking (step 1) as well as ‘proofs of principle’ of their phenotypic integrity and biological function (step 2). This testing program was accomplished using in vitro culture assays and in vivo testing in an immunosuppressed mouse model of hindlimb ischemia. These criteria and procedures were successfully applied to GMP production of CD133+ cells from the BM for an ongoing clinical trial of autologous stem cells administration into patients with ischemic cardiomyopathy. Our results show that GMP implementation of currently available protocols for CD133+ cells selection is feasible and reproducible, and enables the production of cells having a full biological potential according to the most recent quality requirements by European Regulatory Agencies. PMID:19627397

  19. Regulating Drug Release Behavior and Kinetics from Matrix Tablets Based on Fine Particle-Sized Ethyl Cellulose Ether Derivatives: An In Vitro and In Vivo Evaluation

    PubMed Central

    Shah, Kifayat Ullah; Khan, Gul Majid

    2012-01-01

    The design and fabrication of sustained/controlled release dosage forms, employing new excipients capable of extending/controlling the release of drugs from the dosage forms over prolonged periods, has worked well in achieving optimally enhanced therapeutic levels of the drugs. In this sense, the objective of this study was to investigate the suitability of selected cellulose ether derivatives for use in direct compression (DC) and as efficient drug release controlling agents. Controlled release matrix tablets of ciprofloxacin were prepared at different drug-to-polymer (D : P) ratios by direct compression using a fine particle sized ethylcellulose ether derivative (ETHOCEL Standard Premium 7FP) as rate controlling polymer. The tablets obtained were evaluated for various physico-chemical characteristics and in-vitro drug release studies were conducted in phosphate buffer (pH 7.4) using PharmaTest dissolution apparatus at constant temperature of 37°C ± 0.1. Similarity factor f 2 was employed to the release profiles of test formulations and were compared with marketed ciprofloxacin conventional tablets. Drug release mechanism and the kinetics involved were investigated by fitting the release profile data to various kinetic models. It was found that with increasing the proportion of ethylcellulose ether derivative in the matrix, the drug release was significantly extended up to 24 hours. The tablets exhibited zero order or nearly zero order drug transport mechanism. In vivo drug release performance of the developed controlled release tablets and reference conventional tablets containing ciprofloxacin were determined in rabbit serum according to randomized two-way crossover study design using High Performance Liquid Chromatography. Several bioavailability parameters of both the test tablets and conventional tablets including C max⁡, T max⁡ and AUC0-t were compared which showed an optimized C max⁡ and T max⁡ (P < 0.05). A good correlation was obtained between in vitro drug release and in vivo drug absorption with correlation value (R 2 = 0.934). Relative bioavailability was found to be 93%. Reproducibility of manufacturing process and accelerated stability of the developed tablets were performed in stability chamber at 40 ± 2°C and 75 ± 5% relative humidity for a period of 6 months and were found to be stable throughout the stability period. PMID:22649325

  20. A comparison of video review and feedback device measurement of chest compressions quality during pediatric cardiopulmonary resuscitation.

    PubMed

    Hsieh, Ting-Chang; Wolfe, Heather; Sutton, Robert; Myers, Sage; Nadkarni, Vinay; Donoghue, Aaron

    2015-08-01

    To describe chest compression (CC) rate, depth, and leaning during pediatric cardiopulmonary resuscitation (CPR) as measured by two simultaneous methods, and to assess the accuracy and reliability of video review in measuring CC quality. Resuscitations in a pediatric emergency department are videorecorded for quality improvement. Patients aged 8-18 years receiving CPR under videorecording were eligible for inclusion. CPR was recorded by a pressure/accelerometer feedback device and tabulated in 30-s epochs of uninterrupted CC. Investigators reviewed videorecorded CPR and measured rate, depth, and release by observation. Raters categorized epochs as 'meeting criteria' if 80% of CCs in an epoch were done with appropriate depth (>45 mm) and/or release (<2.5 kg leaning). Comparison between device measurement and video was made by Spearman's ρ for rate and by κ statistic for depth and release. Interrater reliability for depth and release was measured by κ statistic. Five patients underwent videorecorded CPR using the feedback device. 97 30-s epochs of CCs were analyzed. CCs met criteria for rate in 74/97 (76%) of epochs; depth in 38/97 (39%); release in 82/97 (84%). Agreement between video and feedback device for rate was good (ρ = 0.77); agreement was poor for depth and release (κ 0.04-0.41). Interrater reliability for depth and release measured by video was poor (κ 0.04-0.49). Video review measured CC rate accurately; depth and release were not reliably or accurately assessed by video. Future research should focus on the optimal combination of methods for measuring CPR quality. Copyright © 2015 Elsevier Ireland Ltd. All rights reserved.

  1. Application of the relative energy release criteria to enclosure fire testing. [aircraft compartments

    NASA Technical Reports Server (NTRS)

    Roschke, E. J.; Coulbert, C. D.

    1979-01-01

    The five relative energy release criteria (RERC) which are a first step towards formulating a unified concept that can be applied to the development of fires in enclosures, place upper bounds on the rate and amount of energy released during a fire. They are independent, calculated readily, and may be applied generally to any enclosure regardless of size. They are useful in pretest planning and for interpreting experimental data. Data from several specific fire test programs were examined to evaluate the potential use of RERC to provide test planning guidelines. The RERC were compared with experimental data obtained in full-scale enclosures. These results confirm that in general the RERC do identify the proper limiting constraints on enclosure fire development and determine the bounds of the fire development envelope. Plotting actual fire data against the RERC reveals new valid insights into fire behavior and reveals the controlling constraints in fire development. The RERC were calculated and plotted for several descrpitions of full-scale fires in various aircraft compartments.

  2. Electrochemical Responsive Superhydrophilic Surfaces of Polythiophene Derivatives towards Cell Capture and Release.

    PubMed

    Hao, Yuwei; Li, Yingying; Zhang, Feilong; Cui, Haijun; Hu, Jinsong; Meng, Jingxin; Wang, Shutao

    2018-03-23

    Highly efficient cell capture and release with low background are urgently required for early diagnosis of diseases such as cancer. Herein, we report an electrochemical responsive superhydrophilic surface exhibiting specific cell capture and release with high yields and extremely low nonspecific adhesion. Through electrochemical deposition, 3-substituted thiophene derivatives are deposited onto indium tin oxide (ITO) nanowire arrays with 4-n-nonylbenzeneboronic acid (BA) as dopant, fabricating the electrochemical responsive superhydrophilic surfaces. The molecular recognition between sialic acids over-expressed on the cell membrane and doped BAs endows the electrochemical responsive surfaces with the ability to capture and release targeted cancer cells. By adjusting the substituent group of thiophene derivatives, the surface wettability can be readily regulated and further utilized for reducing nonspecific cell adhesion. Significantly, the released cells still maintain a high proliferation ability, which indicates that the applied potential does not significantly harm the cells. Therefore, these results may provide a new strategy to achieve advanced functions of biomedical materials, such as low nonspecific adhesion. © 2018 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim.

  3. Crop-tree release thinning in 65-year-old commercial cherry-maple stands (5-year results)

    Treesearch

    H. Clay Smith; Gary W. Miller; Neil I. Lamson

    1994-01-01

    Crop-tree release was applied to a 65-year-old cherry-maple stand in north central West Virginia. Criteria were developed for selecting crop trees for high quality sawtimber and veneer products. Five-year stand growth, mortality, and ingrowth using basal areas, volume, relative density, and number of trees were discussed for the treatments.

  4. State-of-Science Approaches to Determine Sensitive Taxa for Water Quality Criteria Derivation

    EPA Science Inventory

    Current Ambient Water Quality Criteria (AWQC) guidelines specify pre-defined taxa diversity requirements, which has limited chemical-specific criteria development in the U.S. to less than 100 chemicals. A priori knowledge of sensitive taxa to toxicologically similar groups of che...

  5. A novel mathematical model considering change of diffusion coefficient for predicting dissolution behavior of acetaminophen from wax matrix dosage form.

    PubMed

    Nitanai, Yuta; Agata, Yasuyoshi; Iwao, Yasunori; Itai, Shigeru

    2012-05-30

    From wax matrix dosage forms, drug and water-soluble polymer are released into the external solvent over time. As a consequence, the pore volume inside the wax matrix particles is increased and the diffusion coefficient of the drug is altered. In the present study, we attempted to derive a novel empirical mathematical model, namely, a time-dependent diffusivity (TDD) model, that assumes the change in the drug's diffusion coefficient can be used to predict the drug release from spherical wax matrix particles. Wax matrix particles were prepared by using acetaminophen (APAP), a model drug; glyceryl monostearate (GM), a wax base; and aminoalkyl methacrylate copolymer E (AMCE), a functional polymer that dissolves below pH 5.0 and swells over pH 5.0. A three-factor, three-level (3(3)) Box-Behnken design was used to evaluate the effects of several of the variables in the model formulation, and the release of APAP from wax matrix particles was evaluated by the paddle method at pH 4.0 and pH 6.5. When comparing the goodness of fit to the experimental data between the proposed TDD model and the conventional pure diffusion model, a better correspondence was observed for the TDD model in all cases. Multiple regression analysis revealed that an increase in AMCE loading enhanced the diffusion coefficient with time, and that this increase also had a significant effect on drug release behavior. Furthermore, from the results of the multiple regression analysis, a formulation with desired drug release behavior was found to satisfy the criteria of the bitter taste masking of APAP without lowering the bioavailability. That is to say, the amount of APAP released remains below 15% for 10 min at pH 6.5 and exceeds 90% within 30 min at pH 4.0. The predicted formulation was 15% APAP loading, 8.25% AMCE loading, and 400 μm mean particle diameter. When wax matrix dosage forms were prepared accordingly, the predicted drug release behavior agreed well with experimental values at each pH level. Therefore, the proposed model is feasible as a useful tool for predicting drug release behavior, as well as for designing the formulation of wax matrix dosage forms. Copyright © 2012 Elsevier B.V. All rights reserved.

  6. Air Quality Criteria for Ozone and Related Photochemical ...

    EPA Pesticide Factsheets

    In February 2006, EPA released the final document, Air Quality Criteria for Ozone and Other Photochemical Oxidants. Tropospheric or surface-level ozone (O3) is one of six major air pollutants regulated by National Ambient Air Quality Standards (NAAQS) under the U.S. Clean Air Act. As mandated by the Clean Air Act, the U.S. Environmental Protection Agency (EPA) must periodically review the scientific bases (or criteria) for the various NAAQS by assessing newly available scientific information on a given criteria air pollutant. This document, Air Quality Criteria for Ozone and Other Photochemical Oxidants, is an updated revision of the 1996 Ozone Air Quality Criteria Document (O3 AQCD) that provided scientific bases for the current O3 NAAQS set in 1997. The Clean Air Act mandates periodic review of the National Ambient Air Quality Standards (NAAQS) for six common air pollutants, also referred to as criteria pollutants, including ozone.

  7. 28 CFR 33.30 - Program criteria.

    Code of Federal Regulations, 2010 CFR

    2010-07-01

    ... prosecutorial and defender services, juvenile delinquency agencies, and pretrial service or release agencies... reduction of narcotic addiction and juvenile delinquency. Section 901(a)(1) of the Act. ...

  8. Derivation of site-specific surface water quality criteria for the protection of aquatic ecosystems near a Korean military training facility.

    PubMed

    Jeong, Seung-Woo; An, Youn-Joo

    2014-01-01

    This study suggested the first Korean site-specific ecological surface water quality criteria for the protection of ecosystems near an artillery range at a Korean military training facility. Surface water quality (SWQ) criteria in Korea address human health protection but do not encompass ecological criteria such as limits for metals and explosives. The first objective of this study was to derive site-specific SWQ criteria for the protection of aquatic ecosystems in Hantan River, Korea. The second objective was to establish discharge criteria for the artillery range to protect the aquatic ecosystems of Hantan River. In this study, we first identified aquatic organisms living in the Hantan River, including fishes, reptiles, invertebrates, phytoplankton, zooplankton, and amphibians. Second, we collected ecotoxicity data for these aquatic organisms and constructed an ecotoxicity database for Cd, Cu, Zn, TNT, and RDX. This study determined the ecological maximum permissible concentrations for metals and explosives based on the ecotoxicity database and suggested ecological surface water quality criteria for the Hantan River by considering analytical detection limits. Discharge limit criteria for the shooting range were determined based on the ecological surface water quality criteria suggested for Hantan River with further consideration of the dilution of the contaminants discharged into the river.

  9. Health technology prioritization: which criteria for prioritizing new technologies and what are their relative weights?

    PubMed

    Golan, Ofra; Hansen, Paul; Kaplan, Giora; Tal, Orna

    2011-10-01

    To review the criteria and 'other' considerations used internationally for prioritizing new health technologies, and to demonstrate a conjoint-analysis methodology (also known as discrete choice experiments) for deriving relative weights for the criteria. We searched the literature for criteria and other considerations for prioritizing new technologies. A convenience sample of 74 respondents completed a conjoint-analysis survey involving criteria related to technologies' 'benefits'. Encompassing 11 countries and the US state of Oregon, we were able to distinguish three main groups of criteria: (a) Need, appropriateness and clinical benefits; (b) Efficiency (including cost-effectiveness); and (c) Equality, solidarity and other ethical or social values. For several countries, the quality of the clinical and economic evidence and factors related to strategic issues and procedural justice respectively are also considered. The criteria and their weights from the conjoint-analysis survey are: 'Lives saved'=0.343, 'Life-prolongation benefits'=0.243, 'Quality-of-life gains'=0.217, a criterion representing the availability of alternative treatments=0.107, and 'Other important social/ethical benefits'=0.087. The criteria represent a pluralistic combination of needs-based, maximizing and egalitarian principles, and we demonstrated a methodology for deriving the weights for criteria related to technologies' 'benefits'. Copyright © 2010 Elsevier Ireland Ltd. All rights reserved.

  10. Criteria: waste tank isolation and stabilization

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

    Metz, W.P.; Ogren, W.E.

    1976-09-01

    The crystallized Hanford high-level wastes stored in single-shell underground tanks consist of sludges and salt cakes covered with supernatural liquor. Purpose of stabilization and isolation is to reduce the releases and losses as a result of a loss of tank integrity. The tanks will be modified so that no inadvertent liquid additions can be made. Criteria for the isolation and stabilization are given and discussed briefly. (DLC)

  11. Justification of disintegration testing beyond current FDA criteria using in vitro and in silico models.

    PubMed

    Uebbing, Lukas; Klumpp, Lukas; Webster, Gregory K; Löbenberg, Raimar

    2017-01-01

    Drug product performance testing is an important part of quality-by-design approaches, but this process often lacks the underlying mechanistic understanding of the complex interactions between the disintegration and dissolution processes involved. Whereas a recent draft guideline by the US Food and Drug Administration (FDA) has allowed the replacement of dissolution testing with disintegration testing, the mentioned criteria are not globally accepted. This study provides scientific justification for using disintegration testing rather than dissolution testing as a quality control method for certain immediate release (IR) formulations. A mechanistic approach, which is beyond the current FDA criteria, is presented. Dissolution testing via United States Pharmacopeial Convention Apparatus II at various paddle speeds was performed for immediate and extended release formulations of metronidazole. Dissolution profile fitting via DDSolver and dissolution profile predictions via DDDPlus™ were performed. The results showed that Fickian diffusion and drug particle properties (DPP) were responsible for the dissolution of the IR tablets, and that formulation factors (eg, coning) impacted dissolution only at lower rotation speeds. Dissolution was completely formulation controlled if extended release tablets were tested and DPP were not important. To demonstrate that disintegration is the most important dosage form attribute when dissolution is DPP controlled, disintegration, intrinsic dissolution and dissolution testing were performed in conventional and disintegration impacting media (DIM). Tablet disintegration was affected by DIM and model fitting to the Korsmeyer-Peppas equation showed a growing effect of the formulation in DIM. DDDPlus was able to predict tablet dissolution and the intrinsic dissolution profiles in conventional media and DIM. The study showed that disintegration has to occur before DPP-dependent dissolution can happen. The study suggests that disintegration can be used as performance test of rapidly disintegrating tablets beyond the FDA criteria. The scientific criteria and justification is that dissolution has to be DPP dependent, originated from active pharmaceutical ingredient characteristics and formulations factors have to be negligible.

  12. Justification of disintegration testing beyond current FDA criteria using in vitro and in silico models

    PubMed Central

    Uebbing, Lukas; Klumpp, Lukas; Webster, Gregory K; Löbenberg, Raimar

    2017-01-01

    Drug product performance testing is an important part of quality-by-design approaches, but this process often lacks the underlying mechanistic understanding of the complex interactions between the disintegration and dissolution processes involved. Whereas a recent draft guideline by the US Food and Drug Administration (FDA) has allowed the replacement of dissolution testing with disintegration testing, the mentioned criteria are not globally accepted. This study provides scientific justification for using disintegration testing rather than dissolution testing as a quality control method for certain immediate release (IR) formulations. A mechanistic approach, which is beyond the current FDA criteria, is presented. Dissolution testing via United States Pharmacopeial Convention Apparatus II at various paddle speeds was performed for immediate and extended release formulations of metronidazole. Dissolution profile fitting via DDSolver and dissolution profile predictions via DDDPlus™ were performed. The results showed that Fickian diffusion and drug particle properties (DPP) were responsible for the dissolution of the IR tablets, and that formulation factors (eg, coning) impacted dissolution only at lower rotation speeds. Dissolution was completely formulation controlled if extended release tablets were tested and DPP were not important. To demonstrate that disintegration is the most important dosage form attribute when dissolution is DPP controlled, disintegration, intrinsic dissolution and dissolution testing were performed in conventional and disintegration impacting media (DIM). Tablet disintegration was affected by DIM and model fitting to the Korsmeyer–Peppas equation showed a growing effect of the formulation in DIM. DDDPlus was able to predict tablet dissolution and the intrinsic dissolution profiles in conventional media and DIM. The study showed that disintegration has to occur before DPP-dependent dissolution can happen. The study suggests that disintegration can be used as performance test of rapidly disintegrating tablets beyond the FDA criteria. The scientific criteria and justification is that dissolution has to be DPP dependent, originated from active pharmaceutical ingredient characteristics and formulations factors have to be negligible. PMID:28442890

  13. International Heart Valve Bank Survey: A Review of Processing Practices and Activity Outcomes

    PubMed Central

    Albrecht, Helmi; Lim, Yeong Phang; Manning, Linda

    2013-01-01

    A survey of 24 international heart valve banks was conducted to acquire information on heart valve processing techniques used and outcomes achieved. The objective was to provide an overview of heart valve banking activities for tissue bankers, tissue banking associations, and regulatory bodies worldwide. Despite similarities found for basic manufacturing processes, distinct differences in procedural details were also identified. The similarities included (1) use of sterile culture media for procedures, (2) antibiotic decontamination, (3) use of dimethyl sulfoxide (DMSO) as a cryoprotectant, (4) controlled rate freezing for cryopreservation, and (5) storage at ultralow temperatures of below −135°C. Differences in procedures included (1) type of sterile media used, (2) antibiotics combination, (3) temperature and duration used for bioburden reduction, (4) concentration of DMSO used for cryopreservation, and (5) storage duration for released allografts. For most banks, the primary reasons why allografts failed to meet release criteria were positive microbiological culture and abnormal morphology. On average, 85% of allografts meeting release criteria were implanted, with valve size and type being the main reasons why released allografts were not used clinically. The wide variation in percentage of allografts meeting release requirements, despite undergoing validated manufacturing procedures, justifies the need for regular review of important outcomes as cited in this paper, in order to encourage comparison and improvements in the HVBs' processes. PMID:24163756

  14. Formulation and In-vitro Characterization of Sustained Release Matrix Type Ocular Timolol Maleate Mini-Tablet

    PubMed Central

    Mortazavi, Seyed Alireza; Jafariazar, Zahra; Ghadjahani, Yasaman; Mahmoodi, Hoda; Mehtarpour, Farzaneh

    2014-01-01

    The purpose of this study was preparation and evaluation of sustained release matrix type ocular mini-tablets of timolol maleate, as a potential formulation for the treatment of glaucoma. Following the initial studies on timolol maleate powder, it was formulated into ocular mini-tablets. The polymers investigated in this study included cellulose derivatives (HEC, CMC, EC) and Carbopol 971P. Mannitol was used as the solubilizing agent and magnesium stearate as the lubricant. Mini-tablets were prepared by through mixing of the ingredients, followed by direct compression. All the prepared formulations were evaluated in terms of physicochemical tests, including uniformity of weight, thickness, crushing strength, friability and in-vitro drug release. Four groups of formulations were prepared. The presence of different amounts of cellulose derivatives or Carbopol 971P, alone, was studied in group A formulations. In group B formulations, the effect of adding Carbopol 971P alongside different cellulose derivatives was investigated. Group C formulations were made by including mannitol as the solubilizing agent, alongside Carbopol 971P and a cellulose derivative. In group D formulations, mini-tablets were made using Carbopol 971P, alongside two different cellulose derivative. The selected formulation (C1) contained ethyl cellulose, Carbopol 971P, mannitol and magnesium stearate, which showed almost 100% drug release over 5 h. Based on kinetic studies, this formulation was found to best fit the zero-order model of drug release. However, the Higuchi and Hixson -Crowell models also showed a good fit. Hence, overall, formulation C1 was chosen as the best formulation. PMID:24734053

  15. Morphological changes in vesicles and release of an encapsulated compound triggered by a photoresponsive Malachite Green leuconitrile derivative.

    PubMed

    Uda, Ryoko M; Hiraishi, Eri; Ohnishi, Ryo; Nakahara, Yoshio; Kimura, Keiichi

    2010-04-20

    Photoinduced morphological changes in phosphatidylcholine vesicles are triggered by a Malachite Green leuconitrile derivative dissolved in the lipidic membrane, and are observed at Malachite Green derivative/lipid ratios <5 mol %. This Malachite Green derivative is a photoresponsive compound that undergoes ionization to afford a positive charge on the molecule by UV irradiation. The Malachite Green derivative exhibits amphiphilicity when ionized photochemically, whereas it behaves as a lipophilic compound under dark conditions. Cryo-transmission electron microscopy was used to determine vesicle morphology. The effects of the Malachite Green derivative on vesicles were studied by dynamic light scattering and fluorescence resonance energy transfer. Irradiation of vesicles containing the Malachite Green derivative induces nonspherical vesicle morphology, fusion of vesicles, and membrane solubilization, depending on conditions. Furthermore, irradiation of the Malachite Green derivative induces the release of a vesicle-encapsulated compound.

  16. Higuchi equation: derivation, applications, use and misuse.

    PubMed

    Siepmann, Juergen; Peppas, Nicholas A

    2011-10-10

    Fifty years ago, the legendary Professor Takeru Higuchi published the derivation of an equation that allowed for the quantification of drug release from thin ointment films, containing finely dispersed drug into a perfect sink. This became the famous Higuchi equation whose fiftieth anniversary we celebrate this year. Despite the complexity of the involved mass transport processes, Higuchi derived a very simple equation, which is easy to use. Based on a pseudo-steady-state approach, a direct proportionality between the cumulative amount of drug released and the square root of time can be demonstrated. In contrast to various other "square root of time" release kinetics, the constant of proportionality in the classical Higuchi equation has a specific, physically realistic meaning. The major benefits of this equation include the possibility to: (i) facilitate device optimization, and (ii) to better understand the underlying drug release mechanisms. The equation can also be applied to other types of drug delivery systems than thin ointment films, e.g., controlled release transdermal patches or films for oral controlled drug delivery. Later, the equation was extended to other geometries and related theories have been proposed. The aim of this review is to highlight the assumptions the derivation of the classical Higuchi equation is based on and to give an overview on the use and potential misuse of this equation as well as of related theories. Copyright © 2011 Elsevier B.V. All rights reserved.

  17. To What Extent Do Biology Textbooks Contribute to Scientific Literacy? Criteria for Analysing Science-Technology-Society-Environment Issues

    ERIC Educational Resources Information Center

    Calado, Florbela M.; Scharfenberg, Franz-Josef; Bogner, Franz X.

    2015-01-01

    Our article proposes a set of six criteria for analysing science-technology-society-environment (STSE) issues in regular textbooks as to how they are expected to contribute to students' scientific literacy. We chose genetics and gene technology as fields prolific in STSE issues. We derived our criteria (including 26 sub-criteria) from a literature…

  18. A potential-of-mean-force approach for fracture mechanics of heterogeneous materials using the lattice element method

    NASA Astrophysics Data System (ADS)

    Laubie, Hadrien; Radjaï, Farhang; Pellenq, Roland; Ulm, Franz-Josef

    2017-08-01

    Fracture of heterogeneous materials has emerged as a critical issue in many engineering applications, ranging from subsurface energy to biomedical applications, and requires a rational framework that allows linking local fracture processes with global fracture descriptors such as the energy release rate, fracture energy and fracture toughness. This is achieved here by means of a local and a global potential-of-mean-force (PMF) inspired Lattice Element Method (LEM) approach. In the local approach, fracture-strength criteria derived from the effective interaction potentials between mass points are shown to exhibit a scaling commensurable with the energy dissipation of fracture processes. In the global PMF-approach, fracture is considered as a sequence of equilibrium states associated with minimum potential energy states analogous to Griffith's approach. It is found that this global approach has much in common with a Grand Canonical Monte Carlo (GCMC) approach, in which mass points are randomly removed following a maximum dissipation criterion until the energy release rate reaches the fracture energy. The duality of the two approaches is illustrated through the application of the PMF-inspired LEM for fracture propagation in a homogeneous linear elastic solid using different means of evaluating the energy release rate. Finally, by application of the method to a textbook example of fracture propagation in a heterogeneous material, it is shown that the proposed PMF-inspired LEM approach captures some well-known toughening mechanisms related to fracture energy contrast, elasticity contrast and crack deflection in the considered two-phase layered composite material.

  19. 78 FR 38777 - Self-Regulatory Organizations; NASDAQ OMX PHLX LLC; Notice of Filing and Immediate Effectiveness...

    Federal Register 2010, 2011, 2012, 2013, 2014

    2013-06-27

    ... market and to protect investors (Rule 3100(a)(2)); a halt in a Derivative Securities Product (as defined... Release No. 67091 (May 31, 2012), 77 FR 33498 (June 6, 2012). a trading halt in a Derivative Security... SECURITIES AND EXCHANGE COMMISSION [Release No. 34-69817; File No. SR-Phlx-2013-66] Self...

  20. Developing Health-Based Pre-Planning Clearance Goals for Airport Remediation Following a Chemical Terrorist Attack: Decision Criteria for Multipathway Exposure Routes

    PubMed Central

    Watson, Annetta; Dolislager, Fredrick; Hall, Linda; Raber, Ellen; Hauschild, Veronique D.; Love, Adam H.

    2011-01-01

    In the event of a chemical terrorist attack on a transportation hub, post-event remediation and restoration activities necessary to attain unrestricted facility re-use and re-entry could require hours to multiple days. While timeframes are dependent on numerous variables, a primary controlling factor is the level of pre-planning and decision-making completed prior to chemical release. What follows is the second of a two-part analysis identifying key considerations, critical information and decision criteria to facilitate post-attack and post-decontamination consequence management activities. Decision criteria analysis presented here provides first-time, open-literature documentation of multi-pathway, health-based remediation exposure guidelines for selected toxic industrial compounds, chemical warfare agents, and agent degradation products for pre-planning application in anticipation of a chemical terrorist attack. Guideline values are provided for inhalation and direct ocular vapor exposure routes as well as percutaneous vapor, surface contact, and ingestion. Target populations include various employees as well as transit passengers. This work has been performed as a national case study conducted in partnership with the Los Angeles International Airport and The Bradley International Terminal. All recommended guidelines have been selected for consistency with airport scenario release parameters of a one-time, short-duration, finite airborne release from a single source followed by compound-specific decontamination. PMID:21399674

  1. Developing health-based pre-planning clearance goals for airport remediation following a chemical terrorist attack: Decision criteria for multipathway exposure routes

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

    Watson, Annetta Paule; Dolislager, Frederick; Hall, Dr. Linda

    2011-01-01

    In the event of a chemical terrorist attack on a transportation hub, post-event remediation and restoration activities necessary to attain unrestricted facility re-use and re-entry could require hours to multiple days. While timeframes are dependent on numerous variables, a primary controlling factor is the level of pre-planning and decision-making completed prior to chemical release. What follows is the second of a two-part analysis identifying key considerations, critical information and decision criteria to facilitate post-attack and post-decontamination consequence management activities. Decision criteria analysis presented here provides first-time, open-literature documentation of multi-pathway, health-based remediation exposure guidelines for selected toxic industrial compounds, chemicalmore » warfare agents, and agent degradation products for pre-planning application in anticipation of a chemical terrorist attack. Guideline values are provided for inhalation and direct ocular vapor exposure routes as well as percutaneous vapor, surface contact, and ingestion. Target populations include various employees as well as transit passengers. This work has been performed as a national case study conducted in partnership with the Los Angeles International Airport and The Bradley International Terminal. All recommended guidelines have been selected for consistency with airport scenario release parameters of a one-time, short-duration, finite airborne release from a single source followed by compound-specific decontamination.« less

  2. Clinical-scale expansion of mesenchymal stromal cells: a large banking experience.

    PubMed

    Lechanteur, Chantal; Briquet, Alexandra; Giet, Olivier; Delloye, Olivier; Baudoux, Etienne; Beguin, Yves

    2016-05-20

    Mesenchymal stromal cells (MSC) are largely investigated in clinical trials aiming to control inappropriate immune reactions (GVHD, Crohn's disease, solid organ transplantation). As the percentage of MSC precursors in bone marrow is very low, these must be expanded in vitro to obtain therapeutic cell doses. We describe here the constitution of an allogeneic human third-party MSC bank from screened healthy volunteer donors in compliance with quality specifications and ISCT-release criteria and report follow-up of different aspects of this activity since 2007. 68 clinical-grade large-scale MSC cultures were completed and analyzed. The whole process was described, including volunteer donor screening, bone marrow collection, mononuclear cell isolation and expansion over 4 weeks, harvesting, cryopreservation, release, administration and quality controls of the cells (including microbiology, phenotype, and potency assays). From 59 validated donors, 68 cultures were completed (mean of final yields: 886 × 10(6) cells/culture) and a total of 464 MSC aliquots have been produced and stored in liquid nitrogen (mean of 132.8 × 10(6) cells/bag). Each MSC batch underwent extensive testing to verify its conformity with EBMT and ISCT release criteria and was individually validated. As of June 1 2015, 314 bags have been released and infused to patients included in 6 different clinical protocols. All thawed MSC units satisfied to release criteria and no infusion-related toxicity was reported. In conclusion, despite low passage cultures, we have been able to create an allogeneic "off-the-shelf" MSC bank with a large number of frozen aliquots and report here an efficient clinical-grade MSC banking activity in place for more than 7 years. Our challenge now is to produce MSC in compliance with good manufacturing practices (GMP) as, in the meantime, MSC have become considered as advanced therapy medicinal products (ATMP). Another significant challenge remains the development of relevant potency assay.

  3. Examining DSM criteria for trichotillomania in a dimensional framework: implications for DSM-5 and diagnostic practice.

    PubMed

    Houghton, David C; Balsis, Steve; Stein, Dan J; Compton, Scott N; Twohig, Michael P; Saunders, Stephen M; Franklin, Martin E; Neal-Barnett, Angela M; Woods, Douglas W

    2015-07-01

    Diagnosis of trichotillomania (TTM) requires meeting several criteria that aim to embody the core pathology of the disorder. These criteria are traditionally interpreted monothetically, in that they are all equally necessary for diagnosis. Alternatively, a dimensional conceptualization of psychopathology allows for examination of the relatedness of each criterion to the TTM latent continuum. First, to examine the ability of recently removed criteria (B and C) to identify the latent dimensions of TTM psychopathology, such that they discriminate between individuals with low and high degrees of hair pulling severity. Second, to determine the impact of removing criteria B and C on the information content of remaining diagnostic criteria. Third, to determine the psychometric properties of remaining TTM diagnostic criteria that remain largely unchanged in DSM-5; that is, whether they measure distinct or overlapping levels of TTM psychopathology. Fourth, to determine whether information content derived from diagnostic criteria aid in the prediction of disease trajectory (i.e., can relapse propensity be predicted from criteria endorsement patterns). Statistics derived from item response theory were used to examine diagnostic criteria endorsement in 91 adults with TTM who underwent psychotherapy. The removal of two criteria in DSM-5 and psychometric validity of remaining criteria was supported. Additionally, individual trait parameters were used to predict treatment progress, uncovering predictive power where none previously existed. Diagnostic criteria for TTM should be examined in dimensional models, which allow for nuanced and sensitive measurement of core symptomology in treatment contexts. Copyright © 2015 Elsevier Inc. All rights reserved.

  4. TEDE per cumulated activity for family members exposed to adult patients treated with 131I.

    PubMed

    Han, Eun Young; Lee, Choonsik; Bolch, Wesley E

    2013-01-01

    In 1997, the United States Nuclear Regulatory Commission amended its criteria under which patients administered radioactive materials could be released from the hospital. The revised criteria ensures that the total effective dose equivalent (TEDE) to any individual exposed to the released patient will not likely exceed 5 mSv. Licensees are recommended to use one of the three options to release the patient in accordance with these regulatory requirements: administered activity, measured dose rate, or patient-specific dose calculation. The NRC's suggested calculation method is based on the assumption that the patient (source) and a family member (target) are each considered to be points in space. This point source/target assumption has been shown to be conservative in comparison to more realistic guidelines. In this present study, the effective doses to family members were calculated using a series of revised Oak Ridge National Laboratory stylised phantoms coupled with a Monte Carlo radiation transport code. A set of TEDE per cumulated activity values were calculated for three different distributions of (131)I (thyroid, abdomen and whole body), various separation distances and two exposure scenarios (face-to-face standing and side-by-side lying). The results indicate that an overestimation of TEDE per cumulated activity based on the point source/target method was >2-fold. The values for paediatric phantoms showed a strong age-dependency, which showed that dosimetry for children should be separately considered instead of using adult phantoms as a substitute. On the basis of the results of this study, a licensee may use less conservative patient-specific release criteria and provide the patient and the family members with more practical dose avoidance guidelines.

  5. In vitro dissolution of generic immediate-release solid oral dosage forms containing BCS class I drugs: comparative assessment of metronidazole, zidovudine, and amoxicillin versus relevant comparator pharmaceutical products in South Africa and India.

    PubMed

    Reddy, Nallagundla H S; Patnala, Srinivas; Löbenberg, Raimar; Kanfer, Isadore

    2014-10-01

    Biowaivers are recommended for immediate-release solid oral dosage forms using dissolution testing as a surrogate for in vivo bioequivalence studies. Several guidance are currently available (the World Health Organization (WHO), the US FDA, and the EMEA) where the conditions are described. In this study, definitions, criteria, and methodologies according to the WHO have been applied. The dissolution performances of immediate-release metronidazole, zidovudine, and amoxicillin products purchased in South African and Indian markets were compared to the relevant comparator pharmaceutical product (CPP)/reference product. The dissolution performances were studied using US Pharmacopeia (USP) apparatus 2 (paddle) set at 75 rpm in each of three dissolution media (pH1.2, 4.5, and 6.8). Concentrations of metronidazole, zidovudine, and amoxicillin in each dissolution media were determined by HPLC. Of the 11 metronidazole products tested, only 8 could be considered as very rapidly dissolving products as defined by the WHO, whereas 2 of those products could be considered as rapidly dissolving products but did not comply with the f 2 acceptance criteria in pH 6.8. All 11 zidovudine products were very rapidly dissolving, whereas in the case of the 14 amoxicillin products tested, none of those products met any of the WHO criteria. This study indicates that not all generic products containing the same biopharmaceutics classification system (BCS) I drug and in similar strength and dosage form are necessarily in vitro equivalent. Hence, there is a need for ongoing market surveillance to determine whether marketed generic products containing BCS I drugs meet the release requirements to confirm their in vitro bioequivalence to the respective reference product.

  6. Subsurface Contamination Control

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

    Y. Yuan

    There are two objectives of this report, ''Subsurface Contamination Control''. The first is to provide a technical basis for recommending limiting radioactive contamination levels (LRCL) on the external surfaces of waste packages (WP) for acceptance into the subsurface repository. The second is to provide an evaluation of the magnitude of potential releases from a defective WP and the detectability of the released contents. The technical basis for deriving LRCL has been established in ''Retrieval Equipment and Strategy for Wp on Pallet'' (CRWMS M and O 2000g, 6.3.1). This report updates the derivation by incorporating the latest design information of themore » subsurface repository for site recommendation. The derived LRCL on the external surface of WPs, therefore, supercede that described in CRWMS M and O 2000g. The derived LRCL represent the average concentrations of contamination on the external surfaces of each WP that must not be exceeded before the WP is to be transported to the subsurface facility for emplacement. The evaluation of potential releases is necessary to control the potential contamination of the subsurface repository and to detect prematurely failed WPs. The detection of failed WPs is required in order to provide reasonable assurance that the integrity of each WP is intact prior to MGR closure. An emplaced WP may become breached due to manufacturing defects or improper weld combined with failure to detect the defect, by corrosion, or by mechanical penetration due to accidents or rockfall conditions. The breached WP may release its gaseous and volatile radionuclide content to the subsurface environment and result in contaminating the subsurface facility. The scope of this analysis is limited to radioactive contaminants resulting from breached WPs during the preclosure period of the subsurface repository. This report: (1) documents a method for deriving LRCL on the external surfaces of WP for acceptance into the subsurface repository; (2) provides a table of derived LRCL for nuclides of radiological importance; (3) Provides an as low as is reasonably achievable (ALARA) evaluation of the derived LRCL by comparing potential onsite and offsite doses to documented ALARA requirements; (4) Provides a method for estimating potential releases from a defective WP; (5) Provides an evaluation of potential radioactive releases from a defective WP that may become airborne and result in contamination of the subsurface facility; and (6) Provides a preliminary analysis of the detectability of a potential WP leak to support the design of an airborne release monitoring system.« less

  7. Biological Activity Predictions and Hydrogen Bonding Analysis in Quinolines

    NASA Astrophysics Data System (ADS)

    Gupta, Palvi; Kamni

    The paper has been designed to make a comprehensive review of a particular series of organic molecular assembly in the form of compendium. An overview of general description of fifteen quinoline derivatives has been given. The biological activity spectra of quinoline derivatives have been correlated on structure activity relationships base which provides the different Pa (possibility of activity) and Pi (possibility of inactivity) values. Expositions of the role of intermolecular interactions in the identified derivatives have been discussed with the standard distance and angle cut-off criteria criteria as proposed by Desiraju and Steiner (1999) in an International monogram on crystallography. Distance-angle scatter plots for intermolecular interactions are presented for a better understanding of the packing interactions which exist in quinoline derivatives.

  8. A Standard-Setting Study to Establish College Success Criteria to Inform the SAT® College and Career Readiness Benchmark. Research Report 2012-3

    ERIC Educational Resources Information Center

    Kobrin, Jennifer L.; Patterson, Brian F.; Wiley, Andrew; Mattern, Krista D.

    2012-01-01

    In 2011, the College Board released its SAT college and career readiness benchmark, which represents the level of academic preparedness associated with a high likelihood of college success and completion. The goal of this study, which was conducted in 2008, was to establish college success criteria to inform the development of the benchmark. The…

  9. Redefining autism spectrum disorder using DSM-5: the implications of the proposed DSM-5 criteria for autism spectrum disorders.

    PubMed

    Young, Robyn L; Rodi, Melissa L

    2014-04-01

    A number of changes were made to pervasive developmental disorders (PDDs) in the recently released diagnostic and statistical manual of mental disorders (APA, Diagnostic and statistical manual of mental disorders, American Psychiatric Publishing, Arlington, VA, 2013). Of the 210 participants in the present study who met DSM-IV-TR criteria for a PDD [i.e., autistic disorder, Asperger's disorder and pervasive developmental disorder-not otherwise specified (PDD-NOS)], only 57.1% met DSM-5 criteria (specificity = 1.0) for autism spectrum disorder when criteria were applied concurrently during diagnostic assessment. High-functioning individuals (i.e., Asperger's disorder and PDD-NOS) were less likely to meet DSM-5 criteria than those with autistic disorder. A failure to satisfy all three criteria in the social-communication domain was the most common reason for exclusion (39%). The implications of these results are discussed.

  10. NK cell-released exosomes: Natural nanobullets against tumors.

    PubMed

    Fais, Stefano

    2013-01-01

    We have recently reported that human natural killer (NK) cells release exosomes that express both NK-cell markers and cytotoxic molecules. Similar results were obtained with circulating exosomes from human healthy donors. Both NK-cell derived and circulating exosomes exerted a full functional activity and killed both tumor and activated immune cells. These findings indicate that NK-cell derived exosomes might constitute a new promising therapeutic tool.

  11. NK cell-released exosomes

    PubMed Central

    Fais, Stefano

    2013-01-01

    We have recently reported that human natural killer (NK) cells release exosomes that express both NK-cell markers and cytotoxic molecules. Similar results were obtained with circulating exosomes from human healthy donors. Both NK-cell derived and circulating exosomes exerted a full functional activity and killed both tumor and activated immune cells. These findings indicate that NK-cell derived exosomes might constitute a new promising therapeutic tool. PMID:23482694

  12. Closed set of the uniqueness conditions and bifurcation criteria in generalized coupled thermoplasticity for small deformations

    NASA Astrophysics Data System (ADS)

    Śloderbach, Zdzisław

    2016-05-01

    This paper reports the results of a study into global and local conditions of uniqueness and the criteria excluding the possibility of bifurcation of the equilibrium state for small strains. The conditions and criteria are derived on the basis of an analysis of the problem of uniqueness of a solution involving the basic incremental boundary problem of coupled generalized thermo-elasto-plasticity. This work forms a follow-up of previous research (Śloderbach in Bifurcations criteria for equilibrium states in generalized thermoplasticity, IFTR Reports, 1980, Arch Mech 3(35):337-349, 351-367, 1983), but contains a new derivation of global and local criteria excluding a possibility of bifurcation of an equilibrium state regarding a comparison body dependent on the admissible fields of stress rate. The thermal elasto-plastic coupling effects, non-associated laws of plastic flow and influence of plastic strains on thermoplastic properties of a body were taken into account in this work. Thus, the mathematical problem considered here is not a self-conjugated problem.

  13. Injectable Biodegradable Polyurethane Scaffolds with Release of Platelet-derived Growth Factor for Tissue Repair and Regeneration

    PubMed Central

    Hafeman, Andrea E.; Li, Bing; Yoshii, Toshitaka; Zienkiewicz, Katarzyna; Davidson, Jeffrey M.; Guelcher, Scott A.

    2013-01-01

    Purpose The purpose of this work was to investigate the effects of triisocyanate composition on the biological and mechanical properties of biodegradable, injectable polyurethane scaffolds for bone and soft tissue engineering. Methods Scaffolds were synthesized using reactive liquid molding techniques, and were characterized in vivo in a rat subcutaneous model. Porosity, dynamic mechanical properties, degradation rate, and release of growth factors were also measured. Results Polyurethane scaffolds were elastomers with tunable damping properties and degradation rates, and they supported cellular infiltration and generation of new tissue. The scaffolds showed a two-stage release profile of platelet-derived growth factor, characterized by a 75% burst release within the first 24 h and slower release thereafter. Conclusions Biodegradable polyurethanes synthesized from triisocyanates exhibited tunable and superior mechanical properties compared to materials synthesized from lysine diisocyanates. Due to their injectability, biocompatibility, tunable degradation, and potential for release of growth factors, these materials are potentially promising therapies for tissue engineering. PMID:18516665

  14. The relationship between Q gamma and Ca release from the sarcoplasmic reticulum in skeletal muscle

    PubMed Central

    1991-01-01

    Asymmetric membrane currents and fluxes of Ca2+ release were determined in skeletal muscle fibers voltage clamped in a Vaseline-gap chamber. The conditioning pulse protocol 1 for suppressing Ca2+ release and the "hump" component of charge movement current (I gamma), described in the first paper of this series, was applied at different test pulse voltages. The amplitude of the current suppressed during the ON transient reached a maximum at slightly suprathreshold test voltages (- 50 to -40 mV) and decayed at higher voltages. The component of charge movement current suppressed by 20 microM tetracaine also went through a maximum at low pulse voltages. This anomalous voltage dependence is thus a property of I gamma, defined by either the conditioning protocol or the tetracaine effect. A negative (inward-going) phase was often observed in the asymmetric current during the ON of depolarizing pulses. This inward phase was shown to be an intramembranous charge movement based on (a) its presence in the records of total membrane current, (b) its voltage dependence, with a maximum at slightly suprathreshold voltages, (c) its association with a "hump" in the asymmetric current, (d) its inhibition by interventions that reduce the "hump", (e) equality of ON and OFF areas in the records of asymmetric current presenting this inward phase, and (f) its kinetic relationship with the time derivative of Ca release flux. The nonmonotonic voltage dependence of the amplitude of the hump and the possibility of an inward phase of intramembranous charge movement are used as the main criteria in the quantitative testing of a specific model. According to this model, released Ca2+ binds to negatively charged sites on the myoplasmic face of the voltage sensor and increases the local transmembrane potential, thus driving additional charge movement (the hump). This model successfully predicts the anomalous voltage dependence and all the kinetic properties of I gamma described in the previous papers. It also accounts for the inward phase in total asymmetric current and in the current suppressed by protocol 1. According to this model, I gamma accompanies activating transitions at the same set of voltage sensors as I beta. Therefore it should open additional release channels, which in turn should cause more I gamma, providing a positive feedback mechanism in the regulation of calcium release. PMID:1650812

  15. Controlled Release of Antigens for One Dose Immunization

    DTIC Science & Technology

    1983-01-01

    microencapsulation of antigen coated alum or by microencapsulating clusters of smaller (᝺ microns) microcapsules . Microcapsules under 10 microns in... microencapsulation were studied to determine what criteria must be satisfied to provide a protective immune response to hepatitis B surface antigen... microencapsulated in poly (DL-lactide-co- glycolide) in a form that was too large to be phagocytized and had an antigen release profile similar to that achieved with

  16. Islet oxygen consumption rate (OCR) dose predicts insulin independence for first clinical islet allotransplants

    PubMed Central

    Kitzmann, JP; O’Gorman, D; Kin, T; Gruessner, AC; Senior, P; Imes, S; Gruessner, RW; Shapiro, AMJ; Papas, KK

    2014-01-01

    Human islet allotransplant (ITx) for the treatment of type 1 diabetes is in phase III clinical registration trials in the US and standard of care in several other countries. Current islet product release criteria include viability based on cell membrane integrity stains, glucose stimulated insulin release (GSIR), and islet equivalent (IE) dose based on counts. However, only a fraction of patients transplanted with islets that meet or exceed these release criteria become insulin independent following one transplant. Measurements of islet oxygen consumption rate (OCR) have been reported as highly predictive of transplant outcome in many models. In this paper we report on the assessment of clinical islet allograft preparations using islet oxygen consumption rate (OCR) dose (or viable IE dose) and current product release assays in a series of 13 first transplant recipients. The predictive capability of each assay was examined and successful graft function was defined as 100% insulin independence within 45 days post-transplant. Results showed that OCR dose was most predictive of CTO. IE dose was also highly predictive, while GSIR and membrane integrity stains were not. In conclusion, OCR dose can predict CTO with high specificity and sensitivity and is a useful tool for evaluating islet preparations prior to clinical ITx. PMID:25131089

  17. Corrective Action Decision Document for Corrective Action Unit 340: Pesticide Release sites, Nevada Test Site, Nevada

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

    DOE /NV

    This Corrective Action Decision Document has been prepared for Corrective Action Unit 340, the NTS Pesticide Release Sites, in accordance with the Federal Facility Agreement and Consent Order of 1996 (FFACO, 1996). Corrective Action Unit 340 is located at the Nevada Test Site, Nevada, and is comprised of the following Corrective Action Sites: 23-21-01, Area 23 Quonset Hut 800 Pesticide Release Ditch; 23-18-03, Area 23 Skid Huts Pesticide Storage; and 15-18-02, Area 15 Quonset Hut 15-11 Pesticide Storage. The purpose of this Corrective Action Decision Document is to identify and provide a rationale for the selection of a recommended correctivemore » action alternative for each Corrective Action Site. The scope of this Corrective Action Decision Document consists of the following tasks: Develop corrective action objectives; Identify corrective action alternative screening criteria; Develop corrective action alternatives; Perform detailed and comparative evaluations of the corrective action alternatives in relation to the corrective action objectives and screening criteria; and Recommend and justify a preferred corrective action alternative for each Corrective Action Site.« less

  18. Release of Esterase Following Germination of Lettuce Seed (Lactuca sativa L.)

    PubMed Central

    Chandra, G. Ram; Toole, Vivian K.

    1977-01-01

    Light-insensitive lettuce seeds, Lactuca sativa L. cv. Great Lakes, release esterases for a period following radicle protrusion. Very little or no enzymes are released prior to 24 hours or after 48 hours of germination. As compared to intact seeds, half-seeds readily release esterases and the release is not affected by far red irradiation. Bulk of the released esterases are derived from the endosperm tissue and presumably exists in the intact seed as a component of the extraembryonic fluid. PMID:16659992

  19. GSH- and pH-responsive drug delivery system constructed by water-soluble pillar[5]arene and lysine derivative for controllable drug release.

    PubMed

    Wu, Xuan; Li, Yan; Lin, Chen; Hu, Xiao-Yu; Wang, Leyong

    2015-04-21

    Novel GSH- and pH-responsive supramolecular vesicles constructed by an amphiphilic inclusion complex formed from water-soluble pillar[5]arene and lysine derivative have been successfully developed, which can efficiently encapsulate anticancer drug MTZ and show rapid MTZ-release in a simulated acidic tumor environment with high GSH concentration, and exhibit potent antitumor activity.

  20. Optimization of a novel wax matrix system using aminoalkyl methacrylate copolymer E and ethylcellulose to suppress the bitter taste of acetaminophen.

    PubMed

    Shiino, Kai; Iwao, Yasunori; Miyagishima, Atsuo; Itai, Shigeru

    2010-08-16

    The purpose of the present study was to design and evaluate a novel wax matrix system containing various ratios of aminoalkyl methacrylate copolymer E (AMCE) and ethylcellulose (EC) as functional polymers in order to achieve the optimal acetaminophen (APAP) release rate for taste masking. A two factor, three level (3(2)) full factorial study design was used to optimize the ratios of AMCE and EC, and the release of APAP from the wax matrix was evaluated using a stationary disk in accordance with the paddle method. The disk was prepared by congealing glyceryl monostearate (GM), a wax with a low melting point, with various ratios of polymers and APAP. The criteria for release rate of APAP from the disk at pH 4.0 and pH 6.5 were calculated to be more than 0.5017 microg/(mlxmin) and less than 0.1414 microg/(mlxmin), respectively, under the assumption that the particle size of spherical matrix should be 100 microm. In multiple regression analysis, the release of APAP at pH 4.0 was found to increase markedly as the concentration of AMCE increased, whereas the release of APAP at pH 6.5 decreased as the EC concentration increased, even when a high level of AMCE was incorporated. Using principle component analysis, it was found that the viscosity of the matrix affects the pH-dependent release of APAP at pH 4.0 and pH 6.5. Furthermore, using multiple regression analysis, the optimum ratio of APAP:AMCE:EC:GM was found to be 30:7:10:53, and the release pattern of APAP from the optimum wax formulation nearly complied with the desired criteria. Therefore, the present study demonstrated that the incorporation of AMCE and EC into a wax matrix system enabled the appropriate release of APAP as a means of taste masking. Copyright (c) 2010 Elsevier B.V. All rights reserved.

  1. Protectiveness of water quality criteria for copper in western United States waters relative to predicted olfactory responses in juvenile Pacific salmon.

    PubMed

    DeForest, David K; Gensemer, Robert W; Van Genderen, Eric J; Gorsuch, Joseph W

    2011-07-01

    Copper (Cu) can impair olfaction in juvenile Pacific salmon (as well as other fishes), thus potentially inhibiting the ability of juveniles to avoid predators or to find food. Because Cu is commonly elevated in stormwater runoff in urban environments, storm events may result in elevated Cu concentrations in salmon-bearing streams. Accordingly, there is concern that existing Cu criteria, which were not derived using data for olfactory-related endpoints, may not be adequately protective of juvenile salmon. However, a modification of the US Environmental Protection Agency (USEPA) biotic ligand model (BLM) for deriving site-specific Cu criteria was recently proposed, which accounted for the sensitivity of olfactory endpoints. The modification was based on olfactory inhibition in juvenile coho salmon (Oncorhynchus kisutch) exposed to Cu in various combinations of pH, hardness, alkalinity, and dissolved organic carbon (DOC) concentrations. We used that olfactory-based BLM to derive 20% inhibition concentrations (IC20) values for Cu for 133 stream locations in the western United States. The olfactory BLM-based IC20 values were compared to the existing hardness-based Cu criteria and the USEPA's BLM-based Cu criteria for these representative natural waters of the western United States. Of the 133 sampling locations, mean hardness-dependent acute and chronic Cu criteria were below the mean olfactory-based BLM IC20 value in 122 (92%) and 129 (97%) of the waters, respectively (i.e., <20% olfactory impairment would have been predicted at the mean hardness-based Cu criteria concentrations). Waters characterized by a combination of high hardness and very low DOC were most likely to have hardness-based Cu criteria that were higher than the olfactory-based BLM IC20 values, because DOC strongly influences Cu bioavailability in the BLM. In all waters, the USEPA's current BLM-based criteria were below the mean olfactory-based BLM IC20 values, indicating that the USEPA's BLM-based criteria are protective of olfactory impairment in juvenile salmon. Copyright © 2011 SETAC.

  2. 40 CFR 228.6 - Specific criteria for site selection.

    Code of Federal Regulations, 2012 CFR

    2012-07-01

    ..., and proposed methods of release, including methods of packing the waste, if any; (5) Feasibility of... of special scientific importance and other legitimate uses of the ocean; (9) The existing water...

  3. 40 CFR 228.6 - Specific criteria for site selection.

    Code of Federal Regulations, 2013 CFR

    2013-07-01

    ..., and proposed methods of release, including methods of packing the waste, if any; (5) Feasibility of... of special scientific importance and other legitimate uses of the ocean; (9) The existing water...

  4. Evaluating Chemical Persistence in a Multimedia Environment: ACART Analysis

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

    Bennett, D.H.; McKone, T.E.; Kastenberg, W.E.

    1999-02-01

    For the thousands of chemicals continuously released into the environment, it is desirable to make prospective assessments of those likely to be persistent. Persistent chemicals are difficult to remove if adverse health or ecological effects are later discovered. A tiered approach using a classification scheme and a multimedia model for determining persistence is presented. Using specific criteria for persistence, a classification tree is developed to classify a chemical as ''persistent'' or ''non-persistent'' based on the chemical properties. In this approach, the classification is derived from the results of a standardized unit world multimedia model. Thus, the classifications are more robustmore » for multimedia pollutants than classifications using a single medium half-life. The method can be readily implemented and provides insight without requiring extensive and often unavailable data. This method can be used to classify chemicals when only a few properties are known and be used to direct further data collection. Case studies are presented to demonstrate the advantages of the approach.« less

  5. Active spice-derived components can inhibit inflammatory responses of adipose tissue in obesity by suppressing inflammatory actions of macrophages and release of monocyte chemoattractant protein-1 from adipocytes.

    PubMed

    Woo, Hae-Mi; Kang, Ji-Hye; Kawada, Teruo; Yoo, Hoon; Sung, Mi-Kyung; Yu, Rina

    2007-02-13

    Inflammation plays a key role in obesity-related pathologies such as cardiovascular disease, type II diabetes, and several types of cancer. Obesity-induced inflammation entails the enhancement of the recruitment of macrophages into adipose tissue and the release of various proinflammatory proteins from fat tissue. Therefore, the modulation of inflammatory responses in obesity may be useful for preventing or ameliorating obesity-related pathologies. Some spice-derived components, which are naturally occurring phytochemicals, elicit antiobesity and antiinflammatory properties. In this study, we investigated whether active spice-derived components can be applied to the suppression of obesity-induced inflammatory responses. Mesenteric adipose tissue was isolated from obese mice fed a high-fat diet and cultured to prepare an adipose tissue-conditioned medium. Raw 264.7 macrophages were treated with the adipose tissue-conditioned medium with or without active spice-derived components (i.e., diallyl disulfide, allyl isothiocyanate, piperine, zingerone and curcumin). Chemotaxis assay was performed to measure the degree of macrophage migration. Macrophage activation was estimated by measuring tumor necrosis factor-alpha (TNF-alpha), nitric oxide, and monocyte chemoattractant protein-1 (MCP-1) concentrations. The active spice-derived components markedly suppressed the migration of macrophages induced by the mesenteric adipose tissue-conditioned medium in a dose-dependent manner. Among the active spice-derived components studied, allyl isothiocyanate, zingerone, and curcumin significantly inhibited the cellular production of proinflammatory mediators such as TNF-alpha and nitric oxide, and significantly inhibited the release of MCP-1 from 3T3-L1 adipocytes. Our findings suggest that the spice-derived components can suppress obesity-induced inflammatory responses by suppressing adipose tissue macrophage accumulation or activation and inhibiting MCP-1 release from adipocytes. These spice-derived components may have a potential to improve chronic inflammatory conditions in obesity.

  6. Morphine 6 glucuronide stimulates nitric oxide release in mussel neural tissues: evidence for a morphine 6 glucuronide opiate receptor subtype.

    PubMed

    Mantione, K; Zhu, W; Rialas, C; Casares, F; Cadet, P; Franklin, A L; Tonnesen, J; Stefano, G B

    2002-03-01

    We have previously demonstrated that Mytilus edulis pedal ganglia contain opiate alkaloids, i.e., morphine and morphine 6 glucuronide (M6G), as well as mu opiate receptor subtype fragments exhibiting high sequence similarity to those found in mammals. Now we demonstrate that M6G stimulates pedal ganglia constitutive nitric oxide (NO) synthase (cNOS)-derived NO release at identical concentrations and to similar peak levels as morphine. However, the classic opiate antagonist, naloxone, only blocked the ability of morphine to stimulate cNOS-derived NO release and not that of M6G. CTOP, a mu-specific antagonist, blocked the ability of M6G to induce cNOS-derived NO release as well as that of morphine, suggesting that a novel mu opiate receptor was present and selective toward M6G. In examining a receptor displacement analysis, both opiate alkaloids displaced [3H]-dihydromorphine binding to the mu opiate receptor subtype. However, morphine exhibited a twofold higher affinity, again suggesting that a novel mu opiate receptor may be present.

  7. Microparticles release by adipocytes act as "find-me" signals to promote macrophage migration.

    PubMed

    Eguchi, Akiko; Mulya, Anny; Lazic, Milos; Radhakrishnan, Deepa; Berk, Michael P; Povero, Davide; Gornicka, Agnieszka; Feldstein, Ariel E

    2015-01-01

    Macrophage infiltration of adipose tissue during weight gain is a central event leading to the metabolic complications of obesity. However, what are the mechanisms attracting professional phagocytes to obese adipose tissue remains poorly understood. Here, we demonstrate that adipocyte-derived microparticles (MPs) are critical "find-me" signals for recruitment of monocytes and macrophages. Supernatants from stressed adipocytes stimulated the attraction of monocyte cells and primary macrophages. The activation of caspase 3 was required for release of these signals. Adipocytes exposed to saturated fatty acids showed marked release of MPs into the supernatant while common genetic mouse models of obesity demonstrate high levels of circulating adipocyte-derived MPs. The release of MPs was highly regulated and dependent on caspase 3 and Rho-associated kinase. Further analysis identified these MPs as a central chemoattractant in vitro and in vivo. In addition, intravenously transplanting circulating MPs from the ob/ob mice lead to activation of monocytes in circulation and adipose tissue of the wild type mice. These data identify adipocyte-derived MPs as novel "find me" signals that contributes to macrophage infiltration associated with obesity.

  8. Critical review of decision support tools for sustainability assessment of site remediation options.

    PubMed

    Huysegoms, Lies; Cappuyns, Valérie

    2017-07-01

    In Europe alone, there are more than 2,5 million potentially contaminated sites of which 14% are expected to require remediation. Contaminated soil and groundwater can cause damage to human health as well as to valuable ecosystems. Globally more attention has been paid to this problem of soil contamination in the past decades. For example, more than 58 000 sites have been remediated in Europe between 2006 and 2011. Together with this increase in remediation projects there has been a surge in the development of new remediation technologies and decision support tools to be able to match every site and its specific characteristics to the best possible remediation alternative. In the past years the development of decision support tools (DST) has evolved in a more sustainable direction. Several DSTs added the claim not only to denote effective or technologically and economically feasible remediation alternatives but also to point out the more or most sustainable remediation alternatives. These trends in the evaluation of site remediation options left users with a confusing clew of possibly applicable tools to assist them in decision making for contaminated site remediation. This review provides a structured overview on the extent decision support tools for contaminated site remediation, that claim to assist in choosing the most sustainable remediation alternative, actually include the different elements of sustainability proposed in our assessment framework. The review contains an in-depth analysis of thirteen tools specifically developed to assess the sustainability of site remediation alternatives. This analysis is based on six criteria derived from the definition of sustainable development of the Brundtland report. The six criteria were concretized by using the three pillars of sustainability, applied to site remediation according to the SuRF-UK framework, two criteria derived from Life Cycle Assessment and Cost-Benefit Analysis, and an 'User friendly' criterion. These elements come together in a framework, drafted for this study, containing six criteria covering the environmental, economic, social, time, uncertainty aspects and user friendliness of a sustainable site remediation. The main remarks uncovered by this review are the imbalance of used indicators still expressing a strong preference for the environmental aspect at the expense of the economic and social aspects of sustainability, the lack of consistency in the terminology used within the field and the failure in adapting released tools to recent legislation or scientific advancements. Copyright © 2017 Elsevier Ltd. All rights reserved.

  9. Pulse Jet Mixing Tests With Noncohesive Solids

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

    Meyer, Perry A.; Bamberger, Judith A.; Enderlin, Carl W.

    2009-05-11

    This report summarizes results from pulse jet mixing (PJM) tests with noncohesive solids in Newtonian liquid conducted during FY 2007 and 2008 to support the design of mixing systems for the Hanford Waste Treatment and Immobilization Plant (WTP). Tests were conducted at three geometric scales using noncohesive simulants. The test data were used to independently develop mixing models that can be used to predict full-scale WTP vessel performance and to rate current WTP mixing system designs against two specific performance requirements. One requirement is to ensure that all solids have been disturbed during the mixing action, which is important tomore » release gas from the solids. The second requirement is to maintain a suspended solids concentration below 20 weight percent at the pump inlet. The models predict the height to which solids will be lifted by the PJM action, and the minimum velocity needed to ensure all solids have been lifted from the floor. From the cloud height estimate we can calculate the concentration of solids at the pump inlet. The velocity needed to lift the solids is slightly more demanding than "disturbing" the solids, and is used as a surrogate for this metric. We applied the models to assess WTP mixing vessel performance with respect to the two perform¬ance requirements. Each mixing vessel was evaluated against these two criteria for two defined waste conditions. One of the wastes was defined by design limits and one was derived from Hanford waste characterization reports. The assessment predicts that three vessel types will satisfy the design criteria for all conditions evaluated. Seven vessel types will not satisfy the performance criteria used for any of the conditions evaluated. The remaining three vessel types provide varying assessments when the different particle characteristics are evaluated. The assessment predicts that three vessel types will satisfy the design criteria for all conditions evaluated. Seven vessel types will not satisfy the performance criteria used for any of the conditions evaluated. The remaining three vessel types provide varying assessments when the different particle characteristics are evaluated. The HLP-022 vessel was also evaluated using 12 m/s pulse jet velocity with 6-in. nozzles, and this design also did not satisfy the criteria for all of the conditions evaluated.« less

  10. Regulation of the nitric oxide oxidase activity of myeloperoxidase by pharmacological agents.

    PubMed

    Maiocchi, Sophie L; Morris, Jonathan C; Rees, Martin D; Thomas, Shane R

    2017-07-01

    The leukocyte-derived heme enzyme myeloperoxidase (MPO) is released extracellularly during inflammation and impairs nitric oxide (NO) bioavailability by directly oxidizing NO or producing NO-consuming substrate radicals. Here, structurally diverse pharmacological agents with activities as MPO substrates/inhibitors or antioxidants were screened for their effects on MPO NO oxidase activity in human plasma and physiological model systems containing endogenous MPO substrates/antioxidants (tyrosine, urate, ascorbate). Hydrazide-based irreversible/reversible MPO inhibitors (4-ABAH, isoniazid) or the sickle cell anaemia drug, hydroxyurea, all promoted MPO NO oxidase activity. This involved the capacity of NO to antagonize MPO inhibition by hydrazide-derived radicals and/or the ability of drug-derived radicals to stimulate MPO turnover thereby increasing NO consumption by MPO redox intermediates or NO-consuming radicals. In contrast, the mechanism-based irreversible MPO inhibitor 2-thioxanthine, potently inhibited MPO turnover and NO consumption. Although the phenolics acetaminophen and resveratrol initially increased MPO turnover and NO consumption, they limited the overall extent of NO loss by rapidly depleting H 2 O 2 and promoting the formation of ascorbyl radicals, which inefficiently consume NO. The vitamin E analogue trolox inhibited MPO NO oxidase activity in ascorbate-depleted fluids by scavenging NO-consuming tyrosyl and urate radicals. Tempol and related nitroxides decreased NO consumption in ascorbate-replete fluids by scavenging MPO-derived ascorbyl radicals. Indoles or apocynin yielded marginal effects. Kinetic analyses rationalized differences in drug activities and identified criteria for the improved inhibition of MPO NO oxidase activity. This study reveals that widely used agents have important implications for MPO NO oxidase activity under physiological conditions, highlighting new pharmacological strategies for preserving NO bioavailability during inflammation. Copyright © 2017 Elsevier Inc. All rights reserved.

  11. Validity criteria for Fermi's golden rule scattering rates applied to metallic nanowires.

    PubMed

    Moors, Kristof; Sorée, Bart; Magnus, Wim

    2016-09-14

    Fermi's golden rule underpins the investigation of mobile carriers propagating through various solids, being a standard tool to calculate their scattering rates. As such, it provides a perturbative estimate under the implicit assumption that the effect of the interaction Hamiltonian which causes the scattering events is sufficiently small. To check the validity of this assumption, we present a general framework to derive simple validity criteria in order to assess whether the scattering rates can be trusted for the system under consideration, given its statistical properties such as average size, electron density, impurity density et cetera. We derive concrete validity criteria for metallic nanowires with conduction electrons populating a single parabolic band subjected to different elastic scattering mechanisms: impurities, grain boundaries and surface roughness.

  12. RMP Guidance for Chemical Distributors - Chapter 3: Five-Year Accident History

    EPA Pesticide Factsheets

    A five year accident history must be completed for each covered process, and all accidental release events meeting specified criteria must be reported in the Risk Management Plan (RMP) for that process.

  13. Air Pollution.

    EPA Science Inventory

    Air quality is affected by many types of pollutants that are emitted from various sources, including stationary and mobile. These sources release both criteria and hazardous air pollutants, which cause health effects, ecological harm, and material damage. They are generally categ...

  14. A new criterion to evaluate water vapor interference in protein secondary structural analysis by FTIR spectroscopy.

    PubMed

    Zou, Ye; Ma, Gang

    2014-06-04

    Second derivative and Fourier self-deconvolution (FSD) are two commonly used techniques to resolve the overlapped component peaks from the often featureless amide I band in Fourier transform infrared (FTIR) curve-fitting approach for protein secondary structural analysis. Yet, the reliability of these two techniques is greatly affected by the omnipresent water vapor in the atmosphere. Several criteria are currently in use as quality controls to ensure the protein absorption spectrum is negligibly affected by water vapor interference. In this study, through a second derivative study of liquid water, we first argue that the previously established criteria cannot guarantee a reliable evaluation of water vapor interference due to a phenomenon that we refer to as sample's absorbance-dependent water vapor interference. Then, through a comparative study of protein and liquid water, we show that a protein absorption spectrum can still be significantly affected by water vapor interference even though it satisfies the established criteria. At last, we propose to use the comparison between the second derivative spectra of protein and liquid water as a new criterion to better evaluate water vapor interference for more reliable second derivative and FSD treatments on the protein amide I band.

  15. Analysis and the Derivation of Valid Objectives

    ERIC Educational Resources Information Center

    Tiemann, Philip W.

    1973-01-01

    Author states that "to the extent that behavioral objectives are derived from an analysis of relatively broad objectives, they can serve as valid criteria which enable our students to avoid trivia." (Author)

  16. Cyclodextrin modified hydrogels of PVP/PEG for sustained drug release.

    PubMed

    Nielsen, Anne Louise; Madsen, Flemming; Larsen, Kim Lambertsen

    2009-02-01

    Hydrogels are water swollen networks of polymers and especially hydrogels consisting of poly vinylpyrrolidone/poly ethyleneglycol-dimethacrylate (PVP/PEG-DMA) blends show promising wound care properties. Enhanced functionality of the hydrogels can be achieved by incorporating drugs and other substances that may assist wound healing into the gel matrix. Controlling the release of active compounds from the hydrogels may be possible by carefully modifying the polymer matrix. For this purpose, cyclodextrins (CD) were grafted to the polymer matrix in 4-5 w/w% in an attempt to retard the release of water-soluble drugs. Ibuprofenate (IBU) was chosen as model drug and loaded in IBU/CD ratios of 0.6, 1.2, and 2.5. Vinyl derivatives of alpha-, beta- and gamma-CD were produced, added to the prepolymer blend and cured by UV-light. During this curing process the CD derivatives were covalently incorporated into the hydrogel matrix. The modified hydrogels were loaded with ibuprofenate by swelling. The release of the model drug from CD modified hydrogels show that especially covalently bonded beta-cyclodextrin can change both the release rate and the release profile of ibuprofen.

  17. SUDOQU: a new dose model to derive criteria for surface contamination of non-food (consumer) goods, containers and conveyances.

    PubMed

    van Dillen, Teun

    2015-04-01

    The Fukushima nuclear accident (Japan, 11 March 2011) revealed the need for well-founded criteria for surface contamination and associated screening levels related to the import of non-food (consumer) goods, containers and conveyances. The only available European-harmonised criteria are those laid down in the IAEA transport regulations, but these criteria date back from the early 1960s and only apply to the safe transport of radioactive materials. The main problem is that a generic dose-assessment model for consumer products is missing. Therefore, RIVM (National Institute for Public Health and the Environment) developed a new methodology entitled SUDOQU (SUrface DOse QUantification) to calculate the annual effective dose for both consumers and non-radiological workers, addressing issues of removability of surface contamination. The methodology can be used to derive criteria and screening levels for surface contamination and could serve as a useful tool for policy-makers and radiation-protection specialists. © The Author 2014. Published by Oxford University Press. All rights reserved. For Permissions, please email: journals.permissions@oup.com.

  18. Caseinophosphopeptides released after tryptic hydrolysis versus simulated gastrointestinal digestion of a casein-derived by-product.

    PubMed

    Cruz-Huerta, E; García-Nebot, M J; Miralles, B; Recio, I; Amigo, L

    2015-02-01

    The production of caseinophosphopeptides from a casein-derived by-product generated during the manufacture of a functional ingredient based on antihypertensive peptides was attempted. The casein by-product was submitted to tryptic hydrolysis for 30, 60 and 120min and further precipitated with calcium chloride and ethanol at pH 4.0, 6.0 and 8.0. Identification and semi quantification of the derived products by tandem mass spectrometry revealed some qualitative and quantitative changes in the released caseinophosphopeptides over time at the different precipitation pHs. The by-product was also subjected to simulated gastrointestinal digestion. Comparison of the resulting peptides showed large sequence homology in the phosphopeptides released by tryptic hydrolysis and simulated gastrointestinal digestion. Some regions, specifically αS1-CN 43-59, αS1-CN 60-74, β-CN 1-25 and β-CN 30-50 showed resistance to both tryptic hydrolysis and simulated digestion. The results of the present study suggest that this casein-derived by-product can be used as a source of CPPs. Copyright © 2014 Elsevier Ltd. All rights reserved.

  19. Aquatic Life Criteria: The 1985 Guidelines and Beyond

    EPA Science Inventory

    The publication in 1985 of U.S. EPA’s “Guidelines for Deriving Numerical National Water Quality Criteria for the Protection of Aquatic Organisms and Their Uses” culminated several years of effort by personnel from the EPA’s Environmental Research Laborator...

  20. Fluor Daniel Hanford implementation plan for DOE Order 5480.28, Natural phenomena hazards mitigation

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

    Conrads, T.J.

    1997-09-12

    Natural phenomena hazards (NPH) are unexpected acts of nature that pose a threat or danger to workers, the public, or the environment. Earthquakes, extreme winds (hurricane and tornado), snow, flooding, volcanic ashfall, and lightning strikes are examples of NPH that could occur at the Hanford Site. U.S. Department of Energy (DOE) policy requires facilities to be designed, constructed, and operated in a manner that protects workers, the public, and the environment from hazards caused by natural phenomena. DOE Order 5480.28, Natural Phenomena Hazards Mitigation, includes rigorous new natural phenomena criteria for the design of new DOE facilities, as well asmore » for the evaluation and, if necessary, upgrade of existing DOE facilities. The Order was transmitted to Westinghouse Hanford Company in 1993 for compliance and is also identified in the Project Hanford Management Contract, Section J, Appendix C. Criteria and requirements of DOE Order 5480.28 are included in five standards, the last of which, DOE-STD-1023, was released in fiscal year 1996. Because the Order was released before all of its required standards were released, enforcement of the Order was waived pending release of the last standard and determination of an in-force date by DOE Richland Operations Office (DOE-RL). Agreement also was reached between the Management and Operations Contractor and DOE-RL that the Order would become enforceable for new structures, systems, and components (SSCS) 60 days following issue of a new order-based design criteria in HNF-PRO-97, Engineering Design and Evaluation. The order also requires that commitments addressing existing SSCs be included in an implementation plan that is to be issued 1 year following the release of the last standard. Subsequently, WHC-SP-1175, Westinghouse Hanford Company Implementation Plan for DOE Order 5480.28, Natural Phenomena Hazards Mitigation, Rev. 0, was issued in November 1996, and this document, HNF-SP-1175, Fluor Daniel Hanford Implementation Plan for DOE Order 5480.28, Natural Phenomena Hazards Mitigation, is Rev. 1 of that plan.« less

  1. Superoxide anion radical-triggered Ca2+ release from cardiac sarcoplasmic reticulum through ryanodine receptor Ca2+ channel.

    PubMed

    Kawakami, M; Okabe, E

    1998-03-01

    The ryanodine receptor Ca2+ channel (RyRC) constitutes the Ca2+-release pathway in sarcoplasmic reticulum (SR) of cardiac muscle. A direct mechanical and a Ca2+-triggered mechanism (Ca2+-induced Ca2+ release) have been proposed to explain the in situ activation of Ca2+ release in cardiac muscle. A variety of chemical oxidants have been shown to activate RyRC; however, the role of modification induced by oxygen-derived free radicals in pathological states of the muscle remains to be elucidated. It has been hypothesized that oxygen-derived free radicals initiate Ca2+-mediated functional changes in or damage to cardiac muscle by acting on the SR and promoting an increase in Ca2+ release. We confirmed that superoxide anion radical (O2-) generated from hypoxanthine-xanthine oxidase reaction decreases calmodulin content and increases 45Ca2+ efflux from the heavy fraction of canine cardiac SR vesicles; hypoxanthine-xanthine oxidase also decreases Ca2+ free within the intravesicular space of the SR with no effect on Ca2+-ATPase activity. Current fluctuations through single Ca2+-release channels have been monitored after incorporation into planar phospholipid bilayers. We demonstrate that activation of the channel by O2- is dependent of the presence of calmodulin and identified calmodulin as a functional mediator of O2--triggered Ca2+ release through the RyRC. For the first time, we show that O2- stimulates Ca2+ release from heavy SR vesicles and suggest the importance of accessory proteins such as calmodulin in modulating the effect of O2-. The decreased calmodulin content induced by oxygen-derived free radicals, especially O2-, is a likely mechanism of accumulation of cytosolic Ca2+ (due to increased Ca2+ release from SR) after reperfusion of the ischemic heart.

  2. Classical and alternative macrophages have impaired function during acute and chronic HIV-1 infection.

    PubMed

    Galvão-Lima, Leonardo J; Espíndola, Milena S; Soares, Luana S; Zambuzi, Fabiana A; Cacemiro, Maira; Fontanari, Caroline; Bollela, Valdes R; Frantz, Fabiani G

    Three decades after HIV recognition and its association with AIDS development, many advances have emerged - especially related to prevention and treatment. Undoubtedly, the development of Highly Active Antiretroviral Therapy (HAART) dramatically changed the future of the syndrome that we know today. In the present study, we evaluate the impact of Highly Active Antiretroviral Therapy on macrophage function and its relevance to HIV pathogenesis. PBMCs were isolated from blood samples and monocytes (CD14+ cells) were purified. Monocyte-Derived Macrophages (MDMs) were activated on classical (M GM-CSF+IFN-γ ) or alternative (M IL-4+IL13 ) patterns using human recombinant cytokines for six days. After this period, Monocyte-Derived Macrophages were stimulated with TLR2/Dectin-1 or TLR4 agonists and we evaluated the influence of HIV-1 infection and Highly Active Antiretroviral Therapy on the release of cytokines/chemokines by macrophages. The data were obtained using Monocyte-Derived Macrophages derived from HIV naïve or from patients on regular Highly Active Antiretroviral Therapy. Classically Monocyte-Derived Macrophages obtained from HIV-1 infected patients on Highly Active Antiretroviral Therapy released higher levels of IL-6 and IL-12 even without PAMPs stimuli when compared to control group. On the other hand, alternative Monocyte-Derived Macrophages derived from HIV-1 infected patients on Highly Active Antiretroviral Therapy released lower levels of IL-6, IL-10, TNF-α, IP-10 and RANTES after LPS stimuli when compared to control group. Furthermore, healthy individuals have a complex network of cytokines/chemokines released by Monocyte-Derived Macrophages after PAMP stimuli, which was deeply affected in MDMs obtained from naïve HIV-1 infected patients and only partially restored in MDMs derived from HIV-1 infected patients even on regular Highly Active Antiretroviral Therapy. Our therapy protocols were not effective in restoring the functional alterations induced by HIV, especially those found on macrophages. These findings indicate that we still need to develop new approaches and improve the current therapy protocols, focusing on the reestablishment of cellular functions and prevention/treatment of opportunistic infections. Copyright © 2016 Sociedade Brasileira de Infectologia. Published by Elsevier Editora Ltda. All rights reserved.

  3. Crimpy enables discrimination of pre and postsynaptic pools of a BMP at the Drosophila NMJ

    PubMed Central

    James, Rebecca E.; Hoover, Kendall M.; Bulgari, Dinara; McLaughlin, Colleen N.; Wilson, Christopher G.; Wharton, Kristi A.; Levitan, Edwin S.; Broihier, Heather T.

    2014-01-01

    Summary Distinct pools of the BMP Glass bottom boat (Gbb) control structure and function of the Drosophila neuromuscular junction. Specifically, motoneuron-derived Gbb regulates baseline neurotransmitter release, while muscle-derived Gbb regulates NMJ growth. Yet how cells differentiate between these ligand pools is not known. Here we present evidence that the neuronal Gbb-binding protein Crimpy (Cmpy) permits discrimination of pre and postsynaptic ligand by serving sequential functions in Gbb signaling. Cmpy first delivers Gbb to dense core vesicles (DCVs) for activity-dependent release from presynaptic terminals. In the absence of Cmpy, Gbb is no longer associated with DCVs and is not released by activity. Electrophysiological analyses demonstrate that Cmpy promotes Gbb's pro-neurotransmission function. Surprisingly, the Cmpy ectodomain is itself released upon DCV exocytosis, arguing that Cmpy serves a second function in BMP signaling. In addition to trafficking Gbb to DCVs, we propose that Gbb/Cmpy co-release from presynaptic terminals defines a neuronal pro-transmission signal. PMID:25453556

  4. REQUIREMENT VERIFICATION AND SYSTEMS ENGINEERING TECHNICAL REVIEW (SETR) ON A COMMERCIAL DERIVATIVE AIRCRAFT (CDA) PROGRAM

    DTIC Science & Technology

    2017-09-01

    the SETR entrance criteria of these events. Out of 30 evaluated SETR entrance criteria, 22 map to FAA elements. A case study of a military CDA...evaluated SETR entrance criteria, 22 map to FAA elements. A case study of a military CDA program, the Presidential Helicopter Replacement Program...3 C. SCOPE AND METHODOLOGY .................................................. 4 D. ORGANIZATION OF THESIS

  5. Color Transformations for the 2MASS Second Incremental Data Release

    NASA Astrophysics Data System (ADS)

    Carpenter, John M.

    2001-05-01

    Transformation equations are presented to convert colors and magnitudes measured in the AAO, ARNICA, CIT, DENIS, ESO, LCO (Persson standards), MSSSO, SAAO, and UKIRT photometric systems to the photometric system inherent in the 2MASS Second Incremental Data Release. The transformations have been derived by comparing 2MASS photometry with published magnitudes and colors for stars observed in these systems. Transformation equations have also been derived indirectly for the Bessell & Brett and Koornneef homogenized photometric systems.

  6. Eddy Seeding in the Labrador Sea: a Submerged Autonomous Launching Platform (SALP) Application

    NASA Astrophysics Data System (ADS)

    Furey, Heather H.; Femke de Jong, M.; Bower, Amy S.

    2013-04-01

    A simplified Submerged Autonomous Launch Platform (SALP) was used to release profiling floats into warm-core Irminger Rings (IRs) in order to investigate their vertical structure and evolution in the Labrador Sea from September 2007 - September 2009. IRs are thought to play an important role in restratification after convection in the Labrador Sea. The SALP is designed to release surface drifters or subsurface floats serially from a traditional ocean mooring, using real-time ocean measurements as criteria for launch. The original prototype instrument used properties measured at multiple depths, with information relayed to the SALP controller via acoustic modems. In our application, two SALP carousels were attached at 500 meters onto a heavily-instrumented deep water mooring, in the path of recently-shed IRs off the west Greenland shelf. A release algorithm was designed to use temperature and pressure measured at the SALP depth only to release one or two APEX profiling drifters each time an IR passed the mooring, using limited historical observations to set release thresholds. Mechanically and electronically, the SALP worked well: out of eleven releases, there was only one malfunction when a float was caught in the cage after the burn-wire had triggered. However, getting floats trapped in eddies met with limited success due to problems with the release algorithm and float ballasting. Out of seven floats launched from the platform using oceanographic criteria, four were released during warm water events that were not related to passing IRs. Also, after float release, it took on average about 2.6 days for the APEX to adjust from its initial ballast depth, about 600 meters, to its park point of 300 meters, leaving the float below the trapped core of water in the IRs. The other mooring instruments (at depths of 100 to 3000 m), revealed that 12 IRs passed by the mooring in the 2-year monitoring period. With this independent information, we were able to assess and improve the release algorithm, still based on ocean conditions measured only at one depth. We found that much better performance could have been achieved with an algorithm that detected IRs based on a temperature difference from a long-term running mean rather than a fixed temperature threshold. This highlights the challenge of designing an appropriate release strategy with limited a priori information on the amplitude and time scales of the background variability.

  7. Development of water quality criteria of ammonia for protecting aquatic life in freshwater using species sensitivity distribution method.

    PubMed

    Park, Tae-Jin; Lee, Jong-Hyeon; Lee, Myung-Sung; Park, Chang-Hee; Lee, Chang-Hoon; Moon, Seong-Dae; Chung, Jiwoong; Cui, Rongxue; An, Youn-Joo; Yeom, Dong-Hyuk; Lee, Soo-Hyung; Lee, Jae-Kwan; Zoh, Kyung-Duk

    2018-09-01

    Ammonia is deemed one of the most important pollutants in the freshwater environment because of its highly toxic nature and ubiquity in surface water. This study thus aims to derive the criteria for ammonia in freshwater to protect aquatic life because there are no water quality criteria for ammonia in Korea. Short-term lethal tests were conducted to perform the species sensitivity distribution (SSD) method. This method is widely used in ecological risk assessment to determine the chemical concentrations to protect aquatic species. Based on the species sensitivity distribution method using Korean indigenous aquatic biota, the hazardous concentration for 5% of biological species (HC 5 ) value calculated in this study was 44mg/L as total ammonia nitrogen (TAN). The value of the assessment factor was set at 2. Consequently, the criteria for ammonia were derived as 22mg/L at pH7 and 20°C. When the derived value was applied to the monitoring data nationwide, 0.51%, 0.09%, 0.18%, 0.20%, and 0.35% of the monitoring sites in Han River, Nakdong River, Geum River, Youngsan River, and lakes throughout the nation, respectively, exceeded this criteria. The Ministry of Environment in Korea has been considering introducing water quality standard of ammonia for protecting aquatic life. Therefore, our results can provide the basis for introducing the ammonia standard in Korea. Copyright © 2018 Elsevier B.V. All rights reserved.

  8. 48 CFR 2942.1503 - Procedures.

    Code of Federal Regulations, 2011 CFR

    2011-10-01

    ... at least annually for submission to the Past Performance Information Retrieval System (PPIRS), and... ADMINISTRATION AND AUDIT SERVICES Contractor Performance Information 2942.1503 Procedures. (a) In accordance with... criteria within their contracting activities. (d) Release of contractor performance evaluation information...

  9. 48 CFR 2942.1503 - Procedures.

    Code of Federal Regulations, 2014 CFR

    2014-10-01

    ... at least annually for submission to the Past Performance Information Retrieval System (PPIRS), and... ADMINISTRATION AND AUDIT SERVICES Contractor Performance Information 2942.1503 Procedures. (a) In accordance with... criteria within their contracting activities. (d) Release of contractor performance evaluation information...

  10. 48 CFR 2942.1503 - Procedures.

    Code of Federal Regulations, 2010 CFR

    2010-10-01

    ... at least annually for submission to the Past Performance Information Retrieval System (PPIRS), and... ADMINISTRATION AND AUDIT SERVICES Contractor Performance Information 2942.1503 Procedures. (a) In accordance with... criteria within their contracting activities. (d) Release of contractor performance evaluation information...

  11. 48 CFR 2942.1503 - Procedures.

    Code of Federal Regulations, 2013 CFR

    2013-10-01

    ... at least annually for submission to the Past Performance Information Retrieval System (PPIRS), and... ADMINISTRATION AND AUDIT SERVICES Contractor Performance Information 2942.1503 Procedures. (a) In accordance with... criteria within their contracting activities. (d) Release of contractor performance evaluation information...

  12. 48 CFR 2942.1503 - Procedures.

    Code of Federal Regulations, 2012 CFR

    2012-10-01

    ... at least annually for submission to the Past Performance Information Retrieval System (PPIRS), and... ADMINISTRATION AND AUDIT SERVICES Contractor Performance Information 2942.1503 Procedures. (a) In accordance with... criteria within their contracting activities. (d) Release of contractor performance evaluation information...

  13. Amphiphilic chitosan derivatives as carrier agents for rotenone

    NASA Astrophysics Data System (ADS)

    Kamari, Azlan; Aljafree, Nurul Farhana Ahmad

    2017-08-01

    In the present study, the feasibility of amphiphilic chitosan derivatives, namely oleoyl carboxymethyl chitosan (OCMCs), N,N-dimethylhexadecyl carboxymethyl chitosan (DCMCs) and deoxycholic acid carboxymethyl chitosan (DACMCs) as carrier agents for rotenone in water-insoluble pesticide formulations was investigated. Fourier Transform Infrared (FTIR) Spectrometer, CHN-O Elemental Analyser (CHN-O) and Transmission Electron Microscope (TEM) were used to characterise amphiphilic chitosan derivatives. The critical micelle concentration (CMC) of amphiphilic chitosan derivatives was determined using a Fluorescence Spectrometer. A High Performance Liquid Chromatography (HPLC) was used to determine the ability of OCMCs, DCMCs and DACMCs to load and release rotenone in an in vitro system. Based on TEM analysis, results have shown that amphiphilic chitosan derivatives formed self-assembly and exhibited spherical shape. The CMC values determined for OCMCs, DCMCs and DACMCs were 0.093, 0.098 and 0.468 mg/mL, respectively. The encapsulation efficiency (EE) values for the materials were more than 97.0%, meanwhile the loading capacity (LC) values were greater than 0.90%. OCMCs, DCMCs and DACMCs micelles exhibited an excellent ability to control the release of rotenone, of which 90.0% of rotenone was released within 40 to 52 h. In conclusion, OCMCs, DCMCs and DACMCs possess several key features to act as effective carrier agents for rotenone. Overall, amphiphilic chitosan derivatives produced in this study were successfully increased the solubility of rotenone by 49.0 times higher than free rotenone.

  14. USE OF MODELS TO SUPPORT WATER QUALTIY CRITERIA - A CASE STUDY

    EPA Science Inventory

    In the United States, current methods for deriving chemical criteria protective of aquatic life depend on acute and chronic toxicity test results involving several species. These results are analyzed statistically to identify chemical concentrations that protect the majority of ...

  15. Regulatory framework on bioequivalence criteria for locally acting gastrointestinal drugs: the case for oral modified release mesalamine formulations.

    PubMed

    Sferrazza, Gianluca; Siviero, Paolo D; Nicotera, Giuseppe; Turella, Paola; Serafino, Annalucia; Blandizzi, Corrado; Pierimarchi, Pasquale

    2017-09-01

    Bioequivalence testing for locally acting gastrointestinal drugs is a challenging issue for both regulatory authorities and pharmaceutical industries. The international regulatory framework has been characterized by the lack of specific bioequivalence tests that has generated a negative impact on the market competition and drug use in clinical practice. Areas covered: This review article provides an overview of the European Union and United States regulatory frameworks on bioequivalence criteria for locally acting gastrointestinal drugs, also discussing the most prominent scientific issues and advances that has been made in this field. A focus on oral modified release mesalamine formulations will be also provided, with practical examples of the regulatory pathways followed by pharmaceutical companies to determine bioequivalence. Expert commentary: The development of a scientific rationale to demonstrate bioequivalence in this field has been complex and often associated with uncertainties related to scientific and regulatory aspects. Only in recent years, thanks to advanced knowledge in this field, the criteria for bioequivalence assessment are undergoing substantial changes. This new scenario will likely result in a significant impact on pharmaceutical companies, promoting more competition through a clearer regulatory approach, conceived for streamlining the demonstration of therapeutic equivalence for locally acting gastrointestinal drugs.

  16. Development of the table of initial isolation distances and protective action distances for the 2004 emergency response guidebook.

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

    Brown, D. F.; Freeman, W. A.; Carhart, R. A.

    2005-09-23

    This report provides technical documentation for values in the Table of Initial Isolation and Protective Action Distances (PADs) in the 2004 Emergency Response Guidebook (ERG2004). The objective for choosing the PADs specified in the ERG2004 is to balance the need to adequately protect the public from exposure to potentially harmful substances against the risks and expenses that could result from overreacting to a spill. To quantify this balance, a statistical approach is adopted, whereby the best available information is used to conduct an accident scenario analysis and develop a set of up to 1,000,000 hypothetical incidents. The set accounts formore » differences in containers types, incident types, accident severity (i.e., amounts released), locations, times of day, times of year, and meteorological conditions. Each scenario is analyzed using detailed emission rate and atmospheric dispersion models to calculate the downwind chemical concentrations from which a 'safe distance' is determined. The safe distance is defined as the distance downwind from the source at which the chemical concentration falls below health protection criteria. The American Industrial Hygiene Association's Emergency Response Planning Guideline Level 2 (ERPG-2) or equivalent is the health criteria used. The statistical sample of safe distance values for all incidents considered in the analysis are separated into four categories: small spill/daytime release, small spill/nighttime release, large spill/daytime release, and large spill/nighttime release. The 90th-percentile safe distance values for each of these groups became the PADs that appear in the ERG2004.« less

  17. The role of criteria in design and management of space systems

    NASA Technical Reports Server (NTRS)

    Blair, J. C.; Ryan, R. S.

    1992-01-01

    Explicit requirements and standards arising in connection with space systems management serve as a framework for technical management and furnish legally binding control of development, verification, and operations. As a project develops, additional requirements are derived which are unique to the system in question; these are designated 'derived requirements'. The reliability and cost-effectiveness of a space system are best ensured where a balance has arisen between formal (legally binding) and informal. Attention is presently given to the development of criteria consistent with total quality management.

  18. The establishment of a bank of stored clinical bone marrow stromal cell products

    PubMed Central

    2012-01-01

    Background Bone marrow stromal cells (BMSCs) are being used to treat a variety of conditions. For many applications a supply of cryopreserved products that can be used for acute therapy is needed. The establishment of a bank of BMSC products from healthy third party donors is described. Methods The recruitment of healthy subjects willing to donate marrow for BMSC production and the Good Manufacturing Practices (GMP) used for assessing potential donors, collecting marrow, culturing BMSCs and BMSC cryopreservation are described. Results Seventeen subjects were enrolled in our marrow collection protocol for BMSC production. Six of the 17 subjects were found to be ineligible during the donor screening process and one became ill and their donation was cancelled. Approximately 12 ml of marrow was aspirated from one posterior iliac crest of 10 donors; one donor donated twice. The BMSCs were initially cultured in T-75 flasks and then expanded for three passages in multilayer cell factories. The final BMSC product was packaged into units of 100 × 106 viable cells, cryopreserved and stored in a vapor phase liquid nitrogen tank under continuous monitoring. BMSC products meeting all lot release criteria were obtained from 8 of the 11 marrow collections. The rate of growth of the primary cultures was similar for all products except those generated from the two oldest donors. One lot did not meet the criteria for final release; its CD34 antigen expression was greater than the cut off set at 5%. The mean number of BMSC units obtained from each donor was 17 and ranged from 3 to 40. Conclusions The production of large numbers of BMSCs from bone marrow aspirates of healthy donors is feasible, but is limited by the high number of donors that did not meet eligibility criteria and products that did not meet lot release criteria. PMID:22309358

  19. An Intuitionistic Multiplicative ORESTE Method for Patients’ Prioritization of Hospitalization

    PubMed Central

    Zhang, Cheng; Wu, Xingli; Wu, Di; Luo, Li; Herrera-Viedma, Enrique

    2018-01-01

    The tension brought about by sickbeds is a common and intractable issue in public hospitals in China due to the large population. Assigning the order of hospitalization of patients is difficult because of complex patient information such as disease type, emergency degree, and severity. It is critical to rank the patients taking full account of various factors. However, most of the evaluation criteria for hospitalization are qualitative, and the classical ranking method cannot derive the detailed relations between patients based on these criteria. Motivated by this, a comprehensive multiple criteria decision making method named the intuitionistic multiplicative ORESTE (organísation, rangement et Synthèse dedonnées relarionnelles, in French) was proposed to handle the problem. The subjective and objective weights of criteria were considered in the proposed method. To do so, first, considering the vagueness of human perceptions towards the alternatives, an intuitionistic multiplicative preference relation model is applied to represent the experts’ preferences over the pairwise alternatives with respect to the predetermined criteria. Then, a correlation coefficient-based weight determining method is developed to derive the objective weights of criteria. This method can overcome the biased results caused by highly-related criteria. Afterwards, we improved the general ranking method, ORESTE, by introducing a new score function which considers both the subjective and objective weights of criteria. An intuitionistic multiplicative ORESTE method was then developed and further highlighted by a case study concerning the patients’ prioritization. PMID:29673212

  20. Design Guidelines and Criteria for User/Operator Transactions with Battlefield Automated Systems. Volume IV. Provisional Guidelines and Criteria

    DTIC Science & Technology

    1981-02-01

    r’!3 JN 2 1982 Resarc Intitte orthe Behavioral and Social Sciences February 1981 Aagroiiied-jr Public release; distribution un’’m’teci. DISCLAIMER...ARMY RESEARCH INSTITUTE FOR THE BEHAVIORAL AND SOCIAL SCIENCES A Field Operating Agency under the Jurisdiction of the Deputy Chief of Staff for...of reports to: U.S. Army Research Institute for the Behavioral and Social Sciences, ATTN: PERI-TST, 5001 Eisenhower Avenue, Alexandria, Virginia 22333

  1. Effectiveness of Systems Engineering (SE) Tailored for the Science & Technology (S&T) Environment: Improvement of USAF Airdrop Accuracy

    DTIC Science & Technology

    2011-10-27

    public release; distribution is unlimited  Dr. Keith Bowman, AFRL, Precision Airdrop ( PAD ) Program Manager  Ms. Carol Ventresca, SynGenics Corporation...Presentation Outline  Entrance Criteria for PAD  Integrated Product Team (IPT)  S&T SE Process Steps  Initial Project S&T Development Strategy...Entrance Criteria for PAD  Integrated Product Team (IPT)  S&T SE Process Steps  Initial Project S&T Development Strategy  User Understanding of

  2. Validity criteria for Fermi’s golden rule scattering rates applied to metallic nanowires

    NASA Astrophysics Data System (ADS)

    Moors, Kristof; Sorée, Bart; Magnus, Wim

    2016-09-01

    Fermi’s golden rule underpins the investigation of mobile carriers propagating through various solids, being a standard tool to calculate their scattering rates. As such, it provides a perturbative estimate under the implicit assumption that the effect of the interaction Hamiltonian which causes the scattering events is sufficiently small. To check the validity of this assumption, we present a general framework to derive simple validity criteria in order to assess whether the scattering rates can be trusted for the system under consideration, given its statistical properties such as average size, electron density, impurity density et cetera. We derive concrete validity criteria for metallic nanowires with conduction electrons populating a single parabolic band subjected to different elastic scattering mechanisms: impurities, grain boundaries and surface roughness.

  3. A comparison of DSM-IV-TR and DSM-5 definitions for sexual dysfunctions: critiques and challenges.

    PubMed

    Sungur, Mehmet Z; Gündüz, Anil

    2014-02-01

    The diagnostic criteria of sexual dysfunctions (SDs) are paramount for the development of sexual medicine as reliable diagnoses are essential to guide treatment plans. Prior Diagnostic and Statistical Manual of Mental Disorders (DSM) classifications based definitions of SD mostly on expert opinions and included imprecise terms. The validity of diagnoses of SD has only recently been challenged, and efforts are made to make more operational definitions. This paper aims to compare and contrast the recently released Diagnostic and Statistical Manual of Mental Disorders-Fifth Edition (DSM-5) diagnostic criteria of SD with that of Diagnostic and Statistical Manual of Mental Disorders-Fourth Edition Text Revision (DSM-IV-TR) and explains the rationale for making changes in the new DSM-5. It also aims to address some issues to be considered further for the future. Online proposed American Psychiatric Association website DSM-5, the new released DSM-5, and DSM-IV-TR diagnostic criteria for SD were thoroughly inspected, and an extensive literature search was performed for comparative reasons. Changes in diagnostic criteria of DSM-5 were detected, and DSM-IV-TR and DSM-5 diagnostic criteria for SD were compared and contrasted. Diagnostic criteria were more operationalized, and explicit duration and frequency criteria were set up in DSM-5 for purposes of good clinical research. Classifications based on simple linear sexual response were abandoned, and diagnostic classifications were separately made for males and females. Desire and arousal disorders in women were merged. Drifting apart from linear sexual response cycle may be an advancement in establishing specific diagnostic criteria for different genders. However, it is still a question of debate whether there is enough evidence to lump sexual interest and arousal disorders in females. Making more precise definitions is important to differentiate disorders from other transient conditions. However, there is still room to improve our definitions and find a way to include gay and lesbian individuals. Further discussions and debates are expected to be continued in the future. © 2013 International Society for Sexual Medicine.

  4. Caprine Monocytes Release Extracellular Traps against Neospora caninum In Vitro

    PubMed Central

    Yang, Zhengtao; Wei, Zhengkai; Hermosilla, Carlos; Taubert, Anja; He, Xuexiu; Wang, Xiaocen; Gong, Pengtao; Li, Jianhua; Zhang, Xichen

    2018-01-01

    Neospora caninum is an obligate intracellular apicomplexan parasite that causes reproductive loss and severe economic losses in dairy and goat industry. In the present study, we aim to investigate the effects of N. caninum tachyzoites on the release of extracellular traps (ETs) in caprine monocytes and furthermore elucidated parts of its molecular mechanisms. N. caninum tachyzoite-induced monocytes-derived ETs formation was detected by scanning electron microscopy. H3 and myeloperoxidase (MPO) within monocyte-ETs structures were examined using laser scanning confocal microscopy analyses. The results showed that N. caninum tachyzoites were not only able to trigger ETs formation in caprine monocytes, but also that monocyte-released ETs were capable of entrapping viable tachyzoites. Histones and MPO were found to be decorating the DNA within the monocytes derived-ETs structures thus proving the classical components of ETs. Furthermore, inhibitors of NADPH oxidase-, MPO-, ERK 1/2-, or p38 MAPK-signaling pathway significantly decreased N. caninum tachyzoite-triggered caprine monocyte-derived ETosis. This is the first report of ETs release extruded from caprine monocytes after N. caninum exposure and thus showing that this early innate immune effector mechanism might be relevant during the acute phase of caprine neosporosis. PMID:29403487

  5. Effect of Quaternary Ammonium Carboxymethylchitosan on Release Rate In-vitro of Aspirin Sustained-release Matrix Tablets

    PubMed Central

    Meng, Lingbin; Teng, Zhongqiu; Zheng, Nannan; Meng, Weiwei; Dai, Rongji; Deng, Yulin

    2013-01-01

    The aim of this study was to develop a derivative of chitosan as pharmaceutical excipient used in sustained-release matrix tablets of poorly soluble drugs. A water-soluble quaternary ammonium carboxymethylchitosan was synthesized by a two-step reaction with carboxymethylchitosan (CMCTS), decylalkyl dimethyl ammonium and epichlorohydrin. The elemental analysis showed that the target product with 10.27% of the maximum grafting degree was obtained. To assess the preliminary safety of this biopolymer, cell toxicity assay was employed. In order to further investigate quaternary ammonium carboxymethylchitosan application as pharmaceutical excipient, aspirin was chosen as model drug. The effect of quaternary ammonium CMCTS on aspirin release rate from sustained-release matrix tablets was examined by in-vitro dissolution experiments. The results showed that this biopolymer had a great potential in increasing the dissolution of poorly soluble drug. With the addition of CMCTS-CEDA, the final cumulative release rate of drug rose up to 90%. After 12 h, at the grade of 10, 20 and 50 cps, the drug release rate increased from 58.1 to 90.7%, from 64.1 to 93.9%, from 69.3 to 96.1%, respectively. At the same time, aspirin release rate from sustainedrelease model was found to be related to the amount of quaternary ammonium CMCTS employed. With the increase of CMCTS-CEDA content, the accumulated release rate increased from 69.1% to 86.7%. The mechanism of aspirin release from sustained-release matrix tablets was also preliminary studied to be Fick diffusion. These data demonstrated that the chitosan derivative has positive effect on drug release from sustained-release matrix tablets. PMID:24250627

  6. Regulation of zinc homeostasis by inducible NO synthase-derived NO: nuclear metallothionein translocation and intranuclear Zn2+ release.

    PubMed

    Spahl, Daniela U; Berendji-Grün, Denise; Suschek, Christoph V; Kolb-Bachofen, Victoria; Kröncke, Klaus-D

    2003-11-25

    Zn2+ is critical for the functional and structural integrity of cells and contributes to a number of important processes including gene expression. It has been shown that NO exogenously applied via NO donors resulting in nitrosative stress leads to cytoplasmic Zn2+ release from the zinc storing protein metallothionein (MT) and probably other proteins that complex Zn2+ via cysteine thiols. We show here that, in cytokine-activated murine aortic endothelial cells, NO derived from the inducible NO synthase (iNOS) induces a transient nuclear release of Zn2+. This nuclear Zn2+ release depends on the presence of MT as shown by the lack of this effect in activated endothelial cells from MT-deficient mice and temporally correlates with nuclear MT translocation. Data also show that NO is an essential but not sufficient signal for MT-mediated Zn2+ trafficking from the cytoplasm into the nucleus. In addition, we found that, endogenously via iNOS, synthesized NO increases the constitutive mRNA expression of both MT-1 and MT-2 genes and that nitrosative stress exogenously applied via an NO donor increases constitutive MT mRNA expression via intracellular Zn2+ release. In conclusion, we here provide evidence for a signaling mechanism based on iNOS-derived NO through the regulation of intracellular Zn2+ trafficking and homeostasis.

  7. Regulation of zinc homeostasis by inducible NO synthase-derived NO: Nuclear metallothionein translocation and intranuclear Zn2+ release

    PubMed Central

    Spahl, Daniela U.; Berendji-Grün, Denise; Suschek, Christoph V.; Kolb-Bachofen, Victoria; Kröncke, Klaus-D.

    2003-01-01

    Zn2+ is critical for the functional and structural integrity of cells and contributes to a number of important processes including gene expression. It has been shown that NO exogenously applied via NO donors resulting in nitrosative stress leads to cytoplasmic Zn2+ release from the zinc storing protein metallothionein (MT) and probably other proteins that complex Zn2+ via cysteine thiols. We show here that, in cytokine-activated murine aortic endothelial cells, NO derived from the inducible NO synthase (iNOS) induces a transient nuclear release of Zn2+. This nuclear Zn2+ release depends on the presence of MT as shown by the lack of this effect in activated endothelial cells from MT-deficient mice and temporally correlates with nuclear MT translocation. Data also show that NO is an essential but not sufficient signal for MT-mediated Zn2+ trafficking from the cytoplasm into the nucleus. In addition, we found that, endogenously via iNOS, synthesized NO increases the constitutive mRNA expression of both MT-1 and MT-2 genes and that nitrosative stress exogenously applied via an NO donor increases constitutive MT mRNA expression via intracellular Zn2+ release. In conclusion, we here provide evidence for a signaling mechanism based on iNOS-derived NO through the regulation of intracellular Zn2+ trafficking and homeostasis. PMID:14617770

  8. Augmenting Species Diversity in Water Quality Criteria Derivation using Interspecies Correlation Models

    EPA Science Inventory

    The specific requirements for taxa diversity of the 1985 guidelines have limited the number of ambient water quality criteria (AWQC) developed for aquatic life protection. The EPA developed the Web-based Interspecies Correlation Estimation (Web-ICE) tool to allow extrapolation of...

  9. Decision Support Model for Introduction of Gamification Solution Using AHP

    PubMed Central

    2014-01-01

    Gamification means the use of various elements of game design in nongame contexts including workplace collaboration, marketing, education, military, and medical services. Gamification is effective for both improving workplace productivity and motivating employees. However, introduction of gamification is not easy because the planning and implementation processes of gamification are very complicated and it needs interdisciplinary knowledge such as information systems, organization behavior, and human psychology. Providing a systematic decision making method for gamification process is the purpose of this paper. This paper suggests the decision criteria for selection of gamification platform to support a systematic decision making process for managements. The criteria are derived from previous works on gamification, introduction of information systems, and analytic hierarchy process. The weights of decision criteria are calculated through a survey by the professionals on game, information systems, and business administration. The analytic hierarchy process is used to derive the weights. The decision criteria and weights provided in this paper could support the managements to make a systematic decision for selection of gamification platform. PMID:24892075

  10. Decision support model for introduction of gamification solution using AHP.

    PubMed

    Kim, Sangkyun

    2014-01-01

    Gamification means the use of various elements of game design in nongame contexts including workplace collaboration, marketing, education, military, and medical services. Gamification is effective for both improving workplace productivity and motivating employees. However, introduction of gamification is not easy because the planning and implementation processes of gamification are very complicated and it needs interdisciplinary knowledge such as information systems, organization behavior, and human psychology. Providing a systematic decision making method for gamification process is the purpose of this paper. This paper suggests the decision criteria for selection of gamification platform to support a systematic decision making process for managements. The criteria are derived from previous works on gamification, introduction of information systems, and analytic hierarchy process. The weights of decision criteria are calculated through a survey by the professionals on game, information systems, and business administration. The analytic hierarchy process is used to derive the weights. The decision criteria and weights provided in this paper could support the managements to make a systematic decision for selection of gamification platform.

  11. Gust alleviation - Criteria and control laws

    NASA Technical Reports Server (NTRS)

    Rynaski, E. G.

    1979-01-01

    The relationships between criteria specified for aircraft gust alleviation and the form of the control laws that result from the criteria are considered. Open-loop gust alleviation based on the linearized, small perturbation equations of aircraft motion is discussed, and an approximate solution of the open-loop control law is presented for the case in which the number of degrees of freedom of the aircraft exceeds the rank of the control effectiveness matrix. Excessive actuator lag is compensated for by taking into account actuator dynamics in the equations of motion, resulting in the specification of a general load network. Criteria for gust alleviation when output motions are gust alleviated and the closed-loop control law derived from them are examined and linear optimal control law is derived. Comparisons of the control laws reveal that the effectiveness of an open-loop control law is greatest at low aircraft frequencies but deteriorates as the natural frequency of the actuators is approached, while closed-loop methods are found to be more effective at higher frequencies.

  12. The glial cell line-derived neurotrophic factor (GDNF) does not acutely change acetylcholine release in developing and adult neuromuscular junction.

    PubMed

    Garcia, Neus; Santafé, Manel M; Tomàs, Marta; Lanuza, Maria A; Besalduch, Nuria; Priego, Merche; Tomàs, Josep

    2010-08-16

    We use immunocytochemistry to show that the trophic molecule glial cell line-derived neurotrophic factor (GDNF) and its receptor GDNF family receptor alpha-1 (GFRalpha-1) are present in both neonatal (P6) and adult (P45) rodent neuromuscular junctions (NMJ) colocalized with several synaptic markers. However, incubation with exogenous GDNF (10-200ng/ml, 1-3h), does not affect spontaneous ACh release. Moreover, GDNF does not change the size of the evoked ACh release from the weak and the strong axonal inputs on dually innervated postnatal endplates nor in the most developed singly-innervated synapses at P6 and P45. Our findings indicate that GDNF (unlike neurotrophins) does not acutely modulate transmitter release during the developmental process of synapse elimination nor as the NMJ matures. Copyright 2010 Elsevier Ireland Ltd. All rights reserved.

  13. Derivation of habitat-specific dissolved oxygen criteria for Chesapeake Bay and its tidal tributaries

    USGS Publications Warehouse

    Batiuk, Richard A.; Breitburg, Denise L.; Diaz, Robert J.; Cronin, Thomas M.; Secor, David H.; Thursby, Glen

    2009-01-01

    The Chesapeake 2000 Agreement committed its state and federal signatories to “define the water quality conditions necessary to protect aquatic living resources” in the Chesapeake Bay (USA) and its tidal tributaries. Hypoxia is one of the key water quality issues addressed as a result of the above Agreement. This paper summarizes the protection goals and specific criteria intended to achieve those goals for addressing hypoxia. The criteria take into account the variety of Bay habitats and the tendency towards low dissolved oxygen in some areas of the Bay. Stressful dissolved oxygen conditions were characterized for a diverse array of living resources of the Chesapeake Bay by different aquatic habitats: migratory fish spawning and nursery, shallow-water, open-water, deep-water, and deep-channel. The dissolved oxygen criteria derived for each of these habitats are intended to protect against adverse effects on survival, growth, reproduction and behavior. The criteria accommodate both spatial and temporal aspects of low oxygen events, and have been adopted into the Chesapeake Bay states – Maryland, Virginia, and Delaware – and the District of Columbia's water quality standards regulations. These criteria, now in the form of state regulatory standards, are driving an array of land-based and wastewater pollution reduction actions across the six-watershed.

  14. Disappointing performance of literature-derived selective screening criteria for asymptomatic Chlamydia trachomatis infection in an inner-city population.

    PubMed

    van Valkengoed, I G; Boeke, A J; Morré, S A; van den Brule, A J; Meijer, C J; Devillé, W; Bouter, L M

    2000-10-01

    In an inner-city population with a low prevalence of Chlamydia trachomatis infection, selective screening may be indicated to increase the efficiency of screening. To evaluate the performance of sets of selective screening criteria for asymptomatic Chlamydia trachomatis infection in an inner-city population. The criteria were derived from reports of studies carried out in various settings. A total of 5714 women age 15 to 40 years living in Amsterdam were invited for a screening based on home-obtained urine specimens. Criteria identified from the literature were applied to the screening population. A calculated area under the receiver-operator characteristic curve (AUC) of greater than 0.75 was considered a good measure of diagnostic accuracy. Of the four sets of criteria, selection based on the following determinants showed the highest diagnostic accuracy: younger than 25 years, being unmarried, number of partners during the previous 6 months, Surinam or Antillean origin (black), and vaginal douching (AUC, 0.67; 95% CI, 0.65-0.69). Selection based on age alone showed an AUC of 0.57 (95% CI, 0.55-0.69). The performance of selective screening criteria for asymptomatic C trachomatis infection in an inner-city population in Amsterdam was insufficient to recommend its implementation in practice.

  15. Shiga Toxin 2 and Lipopolysaccharide Induce Human Microvascular Endothelial Cells To Release Chemokines and Factors That Stimulate Platelet Function

    PubMed Central

    Guessous, Fadila; Marcinkiewicz, Marek; Polanowska-Grabowska, Renata; Kongkhum, Sudawadee; Heatherly, Daniel; Obrig, Tom; Gear, Adrian R. L.

    2005-01-01

    Shiga toxins (Stxs) produced by Shigella dysenteriae type 1 and enterohemorrhagic Escherichia coli are the most common cause of hemolytic-uremic syndrome (HUS). It is well established that vascular endothelial cells, mainly those located in the renal microvasculature, are targets for Stxs. The aim of the present research was to evaluate whether E. coli-derived Shiga toxin 2 (Stx2) incubated with human microvascular endothelial cells (HMEC-1) induces release of chemokines and other factors that might stimulate platelet function. HMEC-1 were exposed for 24 h in vitro to Stx2, lipopolysaccharide (LPS), or the Stx2-LPS combination, and chemokine production was assessed by immunoassay. More interleukin-8 was released than stromal cell-derived factor 1α (SDF-1α) or SDF-1β and RANTES. The Stx2-LPS combination potentiated chemokine release, but Stx2 alone caused more release of SDF-1α at 24 h than LPS or Stx2-LPS did. In the presence of low ADP levels, HMEC-1 supernatants activated platelet function assessed by classical aggregometry, single-particle counting, granule secretion, P-selectin exposure, and the formation of platelet-monocyte aggregates. Supernatants from HMEC-1 exposed only to Stx2 exhibited enhanced exposure of platelet P-selectin and platelet-THP-1 cell interactions. Blockade of platelet cyclooxygenase by indomethacin prevented functional activation. The chemokine RANTES enhanced platelet aggregation induced by SDF-1α, macrophage-derived chemokine, or thymus and activation-regulated chemokine in the presence of very low ADP levels. These data support the hypothesis that microvascular endothelial cells exposed to E. coli O157:H7-derived Stx2 and LPS release chemokines and other factors, which when combined with low levels of primary agonists, such as ADP, cause platelet activation and promote the renal thrombosis associated with HUS. PMID:16299328

  16. Extracellular MicroRNA Signature of Human Helper T Cell Subsets in Health and Autoimmunity.

    PubMed

    Torri, Anna; Carpi, Donatella; Bulgheroni, Elisabetta; Crosti, Maria-Cristina; Moro, Monica; Gruarin, Paola; Rossi, Riccardo L; Rossetti, Grazisa; Di Vizio, Dolores; Hoxha, Mirjam; Bollati, Valentina; Gagliani, Cristina; Tacchetti, Carlo; Paroni, Moira; Geginat, Jens; Corti, Laura; Venegoni, Luigia; Berti, Emilio; Pagani, Massimiliano; Matarese, Giuseppe; Abrignani, Sergio; de Candia, Paola

    2017-02-17

    Upon T cell receptor stimulation, CD4 + T helper (Th) lymphocytes release extracellular vesicles (EVs) containing microRNAs. However, no data are available on whether human CD4 + T cell subsets release EVs containing different pattern of microRNAs. The present work aimed at filling this gap by assessing the microRNA content in EVs released upon in vitro T cell receptor stimulation of Th1, Th17, and T regulatory (Treg) cells. Our results indicate that EVs released by Treg cells are significantly different compared with those released by the other subsets. In particular, miR-146a-5p, miR-150-5p, and miR-21-5p are enriched, whereas miR-106a-5p, miR-155-5p, and miR-19a-3p are depleted in Treg-derived EVs. The in vitro identified EV-associated microRNA signature was increased in serum of autoimmune patients with psoriasis and returned to healthy levels upon effective treatment with etanercept, a biological drug targeting the TNF pathway and suppressing inflammation. Moreover, Gene Set Enrichment Analysis showed an over-representation of genes relevant for T cell activation, such as CD40L, IRAK1, IRAK2, STAT1, and c-Myb in the list of validated targets of Treg-derived EV miRNAs. At functional level, Treg-derived (but not Th1/Th17-derived) EVs inhibited CD4 + T cell proliferation and suppressed two relevant targets of miR-146a-5p: STAT1 and IRAK2. In conclusion, our work identified the miRNAs specifically released by different human CD4 + T cell subsets and started to unveil the potential use of their quantity in human serum to mark the pathological elicitation of these cells in vivo and their biological effect in cell to cell communication during the adaptive immune response. © 2017 by The American Society for Biochemistry and Molecular Biology, Inc.

  17. Extracellular MicroRNA Signature of Human Helper T Cell Subsets in Health and Autoimmunity*

    PubMed Central

    Torri, Anna; Carpi, Donatella; Bulgheroni, Elisabetta; Crosti, Maria-Cristina; Moro, Monica; Gruarin, Paola; Rossi, Riccardo L.; Rossetti, Grazisa; Di Vizio, Dolores; Hoxha, Mirjam; Bollati, Valentina; Gagliani, Cristina; Tacchetti, Carlo; Paroni, Moira; Geginat, Jens; Corti, Laura; Venegoni, Luigia; Berti, Emilio; Pagani, Massimiliano; Matarese, Giuseppe; Abrignani, Sergio; de Candia, Paola

    2017-01-01

    Upon T cell receptor stimulation, CD4+ T helper (Th) lymphocytes release extracellular vesicles (EVs) containing microRNAs. However, no data are available on whether human CD4+ T cell subsets release EVs containing different pattern of microRNAs. The present work aimed at filling this gap by assessing the microRNA content in EVs released upon in vitro T cell receptor stimulation of Th1, Th17, and T regulatory (Treg) cells. Our results indicate that EVs released by Treg cells are significantly different compared with those released by the other subsets. In particular, miR-146a-5p, miR-150-5p, and miR-21-5p are enriched, whereas miR-106a-5p, miR-155-5p, and miR-19a-3p are depleted in Treg-derived EVs. The in vitro identified EV-associated microRNA signature was increased in serum of autoimmune patients with psoriasis and returned to healthy levels upon effective treatment with etanercept, a biological drug targeting the TNF pathway and suppressing inflammation. Moreover, Gene Set Enrichment Analysis showed an over-representation of genes relevant for T cell activation, such as CD40L, IRAK1, IRAK2, STAT1, and c-Myb in the list of validated targets of Treg-derived EV miRNAs. At functional level, Treg-derived (but not Th1/Th17-derived) EVs inhibited CD4+ T cell proliferation and suppressed two relevant targets of miR-146a-5p: STAT1 and IRAK2. In conclusion, our work identified the miRNAs specifically released by different human CD4+ T cell subsets and started to unveil the potential use of their quantity in human serum to mark the pathological elicitation of these cells in vivo and their biological effect in cell to cell communication during the adaptive immune response. PMID:28077577

  18. 28 CFR 33.30 - Program criteria.

    Code of Federal Regulations, 2012 CFR

    2012-07-01

    ... prosecutorial and defender services, juvenile delinquency agencies, and pretrial service or release agencies... reduction of narcotic addiction and juvenile delinquency. Section 901(a)(1) of the Act. ..., police efforts to prevent, control, or reduce crime or to apprehend criminals, including juveniles...

  19. 28 CFR 33.30 - Program criteria.

    Code of Federal Regulations, 2011 CFR

    2011-07-01

    ... prosecutorial and defender services, juvenile delinquency agencies, and pretrial service or release agencies... reduction of narcotic addiction and juvenile delinquency. Section 901(a)(1) of the Act. ..., police efforts to prevent, control, or reduce crime or to apprehend criminals, including juveniles...

  20. 28 CFR 33.30 - Program criteria.

    Code of Federal Regulations, 2013 CFR

    2013-07-01

    ... prosecutorial and defender services, juvenile delinquency agencies, and pretrial service or release agencies... reduction of narcotic addiction and juvenile delinquency. Section 901(a)(1) of the Act. ..., police efforts to prevent, control, or reduce crime or to apprehend criminals, including juveniles...

  1. RMP Guidance for Warehouses - Chapter 3: Five-Year Accident History

    EPA Pesticide Factsheets

    A five year accident history must be completed for each covered process, and all accidental releases meeting specified criteria must be reported in the Risk Management Plan (RMP). Must include details about each event and its impacts.

  2. 28 CFR 33.30 - Program criteria.

    Code of Federal Regulations, 2014 CFR

    2014-07-01

    ... prosecutorial and defender services, juvenile delinquency agencies, and pretrial service or release agencies... reduction of narcotic addiction and juvenile delinquency. Section 901(a)(1) of the Act. ..., police efforts to prevent, control, or reduce crime or to apprehend criminals, including juveniles...

  3. Chronic Obstructive Pulmonary Disease-Derived Circulating Cells Release IL-18 and IL-33 under Ultrafine Particulate Matter Exposure in a Caspase-1/8-Independent Manner

    PubMed Central

    De Falco, Gianluigi; Colarusso, Chiara; Terlizzi, Michela; Popolo, Ada; Pecoraro, Michela; Commodo, Mario; Minutolo, Patrizia; Sirignano, Mariano; D’Anna, Andrea; Aquino, Rita P.; Pinto, Aldo; Molino, Antonio; Sorrentino, Rosalinda

    2017-01-01

    Chronic obstructive pulmonary disease (COPD) is considered the fourth-leading causes of death worldwide; COPD is caused by inhalation of noxious indoor and outdoor particles, especially cigarette smoke that represents the first risk factor for this respiratory disorder. To mimic the effects of particulate matter on COPD, we isolated peripheral blood mononuclear cells (PBMCs) and treated them with combustion-generated ultrafine particles (UFPs) obtained from two different fuel mixtures, namely, pure ethylene and a mixture of ethylene and dimethylfuran (the latter mimicking the combustion of biofuels). UFPs were separated in two fractions: (1) sub-10 nm particles, named nano organic carbon (NOC) particles and (2) primarily soot particles of 20–40 nm and their agglomerates (200 nm). We found that both NOC and soot UFPs induced the release of IL-18 and IL-33 from unstable/exacerbated COPD-derived PBMCs. This effect was associated with higher levels of mitochondrial dysfunction and derived reactive oxygen species, which were higher in PBMCs from unstable COPD patients after combustion-generated UFP exposure. Moreover, lower mRNA expression of the repairing enzyme OGG1 was associated with the higher levels of 8-OH-dG compared with non-smoker and smokers. It was interesting that IL-18 and IL-33 release from PBMCs of unstable COPD patients was not NOD-like receptor 3/caspase-1 or caspase-8-dependent, but rather correlated to caspase-4 release. This effect was not evident in stable COPD-derived PBMCs. Our data suggest that combustion-generated UFPs induce the release of caspase-4-dependent inflammasome from PBMCs of COPD patients compared with healthy subjects, shedding new light into the biology of this key complex in COPD. PMID:29123531

  4. Medical privacy protection based on granular computing.

    PubMed

    Wang, Da-Wei; Liau, Churn-Jung; Hsu, Tsan-Sheng

    2004-10-01

    Based on granular computing methodology, we propose two criteria to quantitatively measure privacy invasion. The total cost criterion measures the effort needed for a data recipient to find private information. The average benefit criterion measures the benefit a data recipient obtains when he received the released data. These two criteria remedy the inadequacy of the deterministic privacy formulation proposed in Proceedings of Asia Pacific Medical Informatics Conference, 2000; Int J Med Inform 2003;71:17-23. Granular computing methodology provides a unified framework for these quantitative measurements and previous bin size and logical approaches. These two new criteria are implemented in a prototype system Cellsecu 2.0. Preliminary system performance evaluation is conducted and reviewed.

  5. Derivative based sensitivity analysis of gamma index

    PubMed Central

    Sarkar, Biplab; Pradhan, Anirudh; Ganesh, T.

    2015-01-01

    Originally developed as a tool for patient-specific quality assurance in advanced treatment delivery methods to compare between measured and calculated dose distributions, the gamma index (γ) concept was later extended to compare between any two dose distributions. It takes into effect both the dose difference (DD) and distance-to-agreement (DTA) measurements in the comparison. Its strength lies in its capability to give a quantitative value for the analysis, unlike other methods. For every point on the reference curve, if there is at least one point in the evaluated curve that satisfies the pass criteria (e.g., δDD = 1%, δDTA = 1 mm), the point is included in the quantitative score as “pass.” Gamma analysis does not account for the gradient of the evaluated curve - it looks at only the minimum gamma value, and if it is <1, then the point passes, no matter what the gradient of evaluated curve is. In this work, an attempt has been made to present a derivative-based method for the identification of dose gradient. A mathematically derived reference profile (RP) representing the penumbral region of 6 MV 10 cm × 10 cm field was generated from an error function. A general test profile (GTP) was created from this RP by introducing 1 mm distance error and 1% dose error at each point. This was considered as the first of the two evaluated curves. By its nature, this curve is a smooth curve and would satisfy the pass criteria for all points in it. The second evaluated profile was generated as a sawtooth test profile (STTP) which again would satisfy the pass criteria for every point on the RP. However, being a sawtooth curve, it is not a smooth one and would be obviously poor when compared with the smooth profile. Considering the smooth GTP as an acceptable profile when it passed the gamma pass criteria (1% DD and 1 mm DTA) against the RP, the first and second order derivatives of the DDs (δD’, δD”) between these two curves were derived and used as the boundary values for evaluating the STTP against the RP. Even though the STTP passed the simple gamma pass criteria, it was found failing at many locations when the derivatives were used as the boundary values. The proposed derivative-based method can identify a noisy curve and can prove to be a useful tool for improving the sensitivity of the gamma index. PMID:26865761

  6. Fan and pump noise control

    NASA Technical Reports Server (NTRS)

    Misoda, J.; Magliozzi, B.

    1973-01-01

    The development is described of improved, low noise level fan and pump concepts for the space shuttle. In addition, a set of noise design criteria for small fans and pumps was derived. The concepts and criteria were created by obtaining Apollo hardware test data to correlate and modify existing noise estimating procedures. A set of space shuttle selection criteria was used to determine preliminary fan and pump concepts. These concepts were tested and modified to obtain noise sources and characteristics which yield the design criteria and quiet, efficient space shuttle fan and pump concepts.

  7. A continuous optimization approach for inferring parameters in mathematical models of regulatory networks.

    PubMed

    Deng, Zhimin; Tian, Tianhai

    2014-07-29

    The advances of systems biology have raised a large number of sophisticated mathematical models for describing the dynamic property of complex biological systems. One of the major steps in developing mathematical models is to estimate unknown parameters of the model based on experimentally measured quantities. However, experimental conditions limit the amount of data that is available for mathematical modelling. The number of unknown parameters in mathematical models may be larger than the number of observation data. The imbalance between the number of experimental data and number of unknown parameters makes reverse-engineering problems particularly challenging. To address the issue of inadequate experimental data, we propose a continuous optimization approach for making reliable inference of model parameters. This approach first uses a spline interpolation to generate continuous functions of system dynamics as well as the first and second order derivatives of continuous functions. The expanded dataset is the basis to infer unknown model parameters using various continuous optimization criteria, including the error of simulation only, error of both simulation and the first derivative, or error of simulation as well as the first and second derivatives. We use three case studies to demonstrate the accuracy and reliability of the proposed new approach. Compared with the corresponding discrete criteria using experimental data at the measurement time points only, numerical results of the ERK kinase activation module show that the continuous absolute-error criteria using both function and high order derivatives generate estimates with better accuracy. This result is also supported by the second and third case studies for the G1/S transition network and the MAP kinase pathway, respectively. This suggests that the continuous absolute-error criteria lead to more accurate estimates than the corresponding discrete criteria. We also study the robustness property of these three models to examine the reliability of estimates. Simulation results show that the models with estimated parameters using continuous fitness functions have better robustness properties than those using the corresponding discrete fitness functions. The inference studies and robustness analysis suggest that the proposed continuous optimization criteria are effective and robust for estimating unknown parameters in mathematical models.

  8. Immunomodulatory role for membrane vesicles released by THP-1 macrophages and respiratory pathogens during macrophage infection.

    PubMed

    Volgers, Charlotte; Benedikter, Birke J; Grauls, Gert E; Savelkoul, Paul H M; Stassen, Frank R M

    2017-11-13

    During infection, inflammation is partially driven by the release of mediators which facilitate intercellular communication. Amongst these mediators are small membrane vesicles (MVs) that can be released by both host cells and Gram-negative and -positive bacteria. Bacterial membrane vesicles are known to exert immuno-modulatory and -stimulatory actions. Moreover, it has been proposed that host cell-derived vesicles, released during infection, also have immunostimulatory properties. In this study, we assessed the release and activity of host cell-derived and bacterial MVs during the first hours following infection of THP-1 macrophages with the common respiratory pathogens non-typeable Haemophilus influenzae, Moraxella catarrhalis, Streptococcus pneumoniae, and Pseudomonas aeruginosa. Using a combination of flow cytometry, tunable resistive pulse sensing (TRPS)-based analysis and electron microscopy, we demonstrated that the release of MVs occurs by both host cells and bacteria during infection. MVs released during infection and bacterial culture were found to induce a strong pro-inflammatory response by naive THP-1 macrophages. Yet, these MVs were also found to induce tolerance of host cells to secondary immunogenic stimuli and to enhance bacterial adherence and the number of intracellular bacteria. Bacterial MVs may play a dual role during infection, as they can both trigger and dampen immune responses thereby contributing to immune defence and bacterial survival.

  9. SENSITIVITY ANALYSIS OF THE APPLICATION OF CHEMICAL EXPOSURE CRITERIA FOR COMPARING SITES AND WATERSHEDS

    EPA Science Inventory

    A methodology was developed for deriving quantitative exposure criteria useful for comparing a site or watershed to a reference condition. The prototype method used indicators of exposures to oil contamination and combustion by-products, naphthalene and benzo(a)pyrene metabolites...

  10. Enzyme-triggered compound release using functionalized antimicrobial peptide derivatives† †Electronic supplementary information (ESI) available. See DOI: 10.1039/c6sc04435b Click here for additional data file.

    PubMed Central

    Kashibe, Masayoshi; Matsumoto, Kengo; Hori, Yuichiro

    2017-01-01

    Controlled release is one of the key technologies for medical innovation, and many stimulus-responsive nanocarriers have been developed to utilize this technology. Enzyme activity is one of the most useful stimuli, because many enzymes are specifically activated in diseased tissues. However, controlled release stimulated by enzyme activity has not been frequently reported. One of the reasons for this is the lack of versatility of carriers. Most of the reported stimulus-responsive systems involve a sophisticated design and a complicated process for the synthesis of stimulus-responsive nanocarrier components. The purpose of this study was to develop versatile controlled release systems triggered by various stimuli, including enzyme activity, without modifying the nanocarrier components. We developed two controlled release systems, both of which comprised a liposome as the nanocarrier and a membrane-damaging peptide, temporin L (TL), and its derivatives as the release-controllers. One system utilized branched peptides for proteases, and the other utilized phosphopeptides for phosphatases. In our systems, the target enzymes converted the non-membrane-damaging TL derivatives into membrane-damaging peptides and released the liposome inclusion. We demonstrated the use of our antimicrobial peptide-based controlled release systems for different enzymes and showed the promise of this technology as a novel theranostic tool. PMID:28451373

  11. Major Railroad Accidents Involving Hazardous Materials Release, Composite Summaries 1969-1978

    DOT National Transportation Integrated Search

    1980-07-31

    This report presents composite summaries describing 75 major railroad accidents in which hazardous materials were released. The selected accidents occurred during the years 1969-1978. The data contained in the individual summaries were derived from v...

  12. Bioavailability and stability of erythromycin delayed release tablets.

    PubMed

    Ogwal, S; Xide, T U

    2001-12-01

    Erythromycin is available as the free base, ethylsuccinate, estolate, stearate, gluceptate, and lactobionate derivatives. When given orally erythromycin and its derivatives except the estolate are inactivated to some extent by the gastric acid and poor absorption may result. To establish whether delayed release erythromycin tablets meet the bioequivalent requirement for the market. Sectrophotometric analysis was used to determine the dissolution percentage of the tablets in vitro. High performance liquid chromatography and IBM/XT microcomputer was used to determine the bioavailability and pharmacokinetic parameters in vivo. Dissolution percentage in thirty minutes reached 28.9% and in sixty minutes erythromycin was completely released. The parameters of the delayed release tablets were Tlag 2.3 hr, Tmax.4.5 hr, and Cmax 2.123 g/ml Ka 0.38048 hr(-1) T (1/2) 1.8 hr, V*C/F 49.721 AUC 12.9155. The relative bioavailability of erythromycin delayed release tablet to erythromycin capsules was 105.31% The content, appearance, and dissolution bioavailability of delayed release erythromycin tablets conforms to the United States pharmacopoeia standards. The tablets should be stored in a cool and dry place in airtight containers and the shelf life is temporarily assigned two years.

  13. Release of elements to natural water from sediments of Lake Roosevelt, Washington, USA

    USGS Publications Warehouse

    Paulson, Anthony J.; Cox, Stephen E.

    2007-01-01

    Reservoir sediments from Lake Roosevelt (WA, USA) that were contaminated with smelter waste discharged into the Columbia River (BC, Canada) were examined using three measures of elemental release reflecting varying degrees of physical mixing and time scales. Aqueous concentrations of Cd, Cu, Pb, and Zn in the interstitial water of reservoir sediments, in the gently stirred overlying waters of incubated sediment cores, and in supernatants of aggressively tumbled slurries of reservoir sediments generally were higher than the concentrations from a reference site. When compared to chronic water-quality criteria, all three measures of release suggest that slag-contaminated sediments near the U.S.-Canadian border are potentially toxic as a result of Cu release and Pb release in two of the three measures. All three measures of Cd release suggest potential toxicity for one site farther down the reservoir, probably contaminated as a result of transport and adsorption of Cd from smelter liquid waste. Releases of Zn and As did not appear to be potentially toxic. Carbonate geochemistry indirectly affects the potential toxicity by increasing water hardness.

  14. Quantitative determination of four nitrofuran metabolites in meat by isotope dilution liquid chromatography-electrospray ionisation-tandem mass spectrometry.

    PubMed

    Mottier, Pascal; Khong, Seu-Ping; Gremaud, Eric; Richoz, Janique; Delatour, Thierry; Goldmann, Till; Guy, Philippe A

    2005-03-04

    A confirmatory method based on isotope dilution liquid chromatography-tandem mass spectrometry (LC-MS/MS) has been developed for the low-level determination of residues of four nitrofuran veterinary drugs in meat, e.g., furazolidone, furaltadone, nitrofurantoin, and nitrofurazone. The procedure entails an acid-catalysed release of protein-bound metabolites, followed by their in situ conversion into the 2-nitrobenzaldehyde (NBA) imine-type derivatives. Liquid-liquid extraction and clean-up on a polymeric solid phase extraction cartridge are then performed before LC-MS/MS analysis by positive electrospray ionisation (ESI) applying multiple reaction monitoring of three transition reactions for each compound. Reliable quantitation is obtained by using one deuterated analogue per analyte (d4-NBA derivative) as internal standard (IS). Validation of the method in chicken meat was conducted following the European Union (EU) criteria for the analysis of veterinary drug residues in foods. The decision limits (CCalpha) were 0.11-0.21 microg/kg, and the detection capabilities (CCbeta) 0.19-0.36 microg/kg, thus below the minimum required performance limit (MRPL) set at 1 microg/kg by the EU. The method is robust and suitable for routine quality control operations, and more than 200 sample injections were performed without excessive pollution of the mass spectrometer or loss of LC column performance.

  15. Demonstrating compliance with protection objectives for non-human biota within post-closure safety cases for radioactive waste repositories.

    PubMed

    Jackson, D; Smith, K; Wood, M D

    2014-07-01

    Over recent years, a number of approaches have been developed that enable the calculation of dose rates to animals and plants following the release of radioactivity to the environment. These approaches can be used to assess the potential impacts of activities that may release radioactivity to the environment, such as the operation of waste repositories. A number of national and international studies have identified screening criteria to indicate those assessment results below which further consideration is not generally required. However no internationally agreed criteria are currently available and consistency in criteria between countries has not been achieved. Furthermore, since screening criteria are not intended to be applied as limits, it is clear that they cannot always form a sufficient basis for assessing the adequacy of protection afforded. Typically, exceeding a screening value leads to a regulatory requirement to undertake a further, more detailed assessment. It does not, per se, imply that there is inadequate protection of the organism types at the specific site under assessment. Therefore, there is a need to develop a more structured approach to dealing with situations in which current screening criteria are exceeded. As a contribution to the developing international discussions, and as an interim measure for application where assessments are required currently, a two-tier, three zone framework is proposed here, relevant to the long term assessment of potential impacts from the deep disposal of radioactive wastes. The purpose of the proposed framework is to promote a proportionate and risk-based approach to the level of effort required in undertaking and interpreting an assessment. Copyright © 2013. Published by Elsevier Ltd.

  16. Deriving Chesapeake Bay Water Quality Standards

    USGS Publications Warehouse

    Tango, Peter J.; Batiuk, Richard A.

    2013-01-01

    Achieving and maintaining the water quality conditions necessary to protect the aquatic living resources of the Chesapeake Bay and its tidal tributaries has required a foundation of quantifiable water quality criteria. Quantitative criteria serve as a critical basis for assessing the attainment of designated uses and measuring progress toward meeting water quality goals of the Chesapeake Bay Program partnership. In 1987, the Chesapeake Bay Program partnership committed to defining the water quality conditions necessary to protect aquatic living resources. Under section 303(c) of the Clean Water Act, States and authorized tribes have the primary responsibility for adopting water quality standards into law or regulation. The Chesapeake Bay Program partnership worked with U.S. Environmental Protection Agency to develop and publish a guidance framework of ambient water quality criteria with designated uses and assessment procedures for dissolved oxygen, water clarity, and chlorophyll a for Chesapeake Bay and its tidal tributaries in 2003. This article reviews the derivation of the water quality criteria, criteria assessment protocols, designated use boundaries, and their refinements published in six addendum documents since 2003 and successfully adopted into each jurisdiction's water quality standards used in developing the Chesapeake Bay Total Maximum Daily Load.

  17. Prevention of in-hospital falls: development of criteria for the conduct of a multi-site audit.

    PubMed

    Giles, Kristy; Stephenson, Matthew; McArthur, Alexa; Aromataris, Edoardo

    2015-06-01

    Patient falls are a significant issue for hospitals due to the high rates of morbidity and mortality associated with these events, as well as the financial costs for the healthcare system. To establish what constitutes best practice in terms of fall prevention in acute care facilities and use this to inform the development of best practice audit criteria. Criteria for clinical audit were developed from evidence derived from systematic reviews and guidelines. While these were drawn from the best available evidence, they were also developed in conjunction with clinicians undertaking a fall-prevention clinical audit and key stakeholders from the clinical settings to ensure their relevance and applicability to the acute care setting. Current literature recommends a comprehensive and multifactorial approach to fall prevention. Eight audit criteria were derived from the best available evidence including the domains of physical environment, hospital culture and care processes, use of technology and targeted interventions. Existing research evidence and consultation with stakeholders has allowed the development of applicable, evidence-based audit criteria for fall prevention in acute care settings. This model can promote engagement, impact clinical practice and lead to improved outcomes.

  18. Disintegration of highly soluble immediate release tablets: a surrogate for dissolution.

    PubMed

    Gupta, Abhay; Hunt, Robert L; Shah, Rakhi B; Sayeed, Vilayat A; Khan, Mansoor A

    2009-01-01

    The purpose of the work was to investigate correlation between disintegration and dissolution for immediate release tablets containing a high solubility drug and to identify formulations where disintegration test, instead of the dissolution test, may be used as the acceptance criteria based on International Conference on Harmonization Q6A guidelines. A statistical design of experiments was used to study the effect of filler, binder, disintegrating agent, and tablet hardness on the disintegration and dissolution of verapamil hydrochloride tablets. All formulation variables, i.e., filler, binder, and disintegrating agent, were found to influence tablet dissolution and disintegration, with the filler and disintegrating agent exerting the most significant influence. Slower dissolution was observed with increasing disintegration time when either the filler or the disintegrating agent was kept constant. However, no direct corelationship was observed between the disintegration and dissolution across all formulations due to the interactions between different formulation components. Although all tablets containing sodium carboxymethyl cellulose as the disintegrating agent, disintegrated in less than 3 min, half of them failed to meet the US Pharmacopeia 30 dissolution criteria for the verapamil hydrochloride tablets highlighting the dependence of dissolution process on the formulation components other than the disintegrating agent. The results identified only one formulation as suitable for using the disintegration test, instead of the dissolution test, as drug product acceptance criteria and highlight the need for systematic studies before using the disintegration test, instead of the dissolution test as the drug acceptance criteria.

  19. Marine cold seeps and their manifestations: geological control, biogeochemical criteria and environmental conditions

    NASA Astrophysics Data System (ADS)

    Suess, Erwin

    2014-10-01

    Characteristics of cold seeps at different geologic settings are the subject of this review primarily based on results of the Research Consortium SFB 574. Criteria are drawn from examples on the erosive convergent margin off Costa Rica, the accretionary margin off Chile supplemented by examples from the transform margin of the Golf of Cadiz and the convergent Hikurangi margin off New Zealand. Others are from well-studied passive margins of the Black Sea, the Golf of Mexico, the eastern Mediterranean Sea and the South China Sea. Seeps at all settings transport water and dissolved compounds to the ocean through the seafloor by different forcing mechanism and from different depths of the submerged geosphere (10s of meters to 10s of km). The compounds sustain oasis-type ecosystems by providing bioactive reductants sulfide, methane and hydrogen. Hereby, the interaction between fluid composition, flux rates and biota results in a diagnostic hydrocarbon-metazoan-microbe-carbonate association; currently, well over 100 active sites are known. The single most important reaction is microbially mediated anaerobic oxidation of methane with secondary reactions involving S-biogeochemistry and carbonate mineral precipitation. Seep fluids and their seafloor manifestations provide clues as to source depth, fluid-sediment/rock interaction during ascent, lifetime and cyclicity of seepage events but less so on the magnitude of return flow. At erosive margins, Cl-depleted and B-enriched fluids from clay dehydration provide criteria for source depth and temperature. The upward material flow generates mud volcanoes at the seafloor above the projected location of dehydration at depth. At accretionary margins, fluids are derived from more shallow depths by compaction of sediments as they ride on the incoming oceanic plate; they are emitted through thrust faults. At highly sedimented margins, organic-rich and evaporite-containing strata (when present) determine the final fluid composition, by emitting characteristically gas hydrate-derived methane, brine-associated non-methane hydrocarbons or leached elements and their isotopes (Li, δ7Li, B, Ba) from host sediments. Smectite-illite transformation and associated Cl-depletion from release of interlayer water is a pervasive process at these margins. Rare earth element pattern in conjunction with redox-sensitive metals retained in seep carbonates indicate whether or not they precipitated in contact with oxic bottom water or suboxic fluids; clear environmental characterization, though, currently remains inconclusive. More deeply sourced fluids as in transform margins may be characterized by their 87Sr/86Sr ratios from interaction with oceanic crustal rocks below. Quantification of flow and reliable estimates of total volatile output from fore-arcs remain a challenge to seep research, as does understanding the role of geologically derived methane in the global methane cycle.

  20. Conference on the Development of Fire-Resistant Aircraft Passenger Seats

    NASA Technical Reports Server (NTRS)

    Fewell, L. L.; Kourtides, D. A.; Rosser, R. W.; Parker, J. A.

    1976-01-01

    Papers are presented dealing with the development of aircraft seats with the minimum fire risk. Criteria examined include: flame spread, heat release, and smoke and/or toxic fumes. Materials and performance specifications of all seat material options are provided.

  1. 40 CFR 258.12 - Wetlands.

    Code of Federal Regulations, 2010 CFR

    2010-07-01

    ... Protection of Environment ENVIRONMENTAL PROTECTION AGENCY (CONTINUED) SOLID WASTES CRITERIA FOR MUNICIPAL SOLID WASTE LANDFILLS Location Restrictions § 258.12 Wetlands. (a) New MSWLF units and lateral...) Impacts on fish, wildlife, and other aquatic resources and their habitat from release of the solid waste...

  2. 40 CFR 258.12 - Wetlands.

    Code of Federal Regulations, 2011 CFR

    2011-07-01

    ... Protection of Environment ENVIRONMENTAL PROTECTION AGENCY (CONTINUED) SOLID WASTES CRITERIA FOR MUNICIPAL SOLID WASTE LANDFILLS Location Restrictions § 258.12 Wetlands. (a) New MSWLF units and lateral...) Impacts on fish, wildlife, and other aquatic resources and their habitat from release of the solid waste...

  3. Evaluation of micron size carbon fibers released from burning graphite composites

    NASA Technical Reports Server (NTRS)

    Sussholz, B.

    1980-01-01

    Quantitative estimates were developed of micron carbon fibers released during the burning of graphite composites. Evidence was found of fibrillated particles which were the predominant source of the micron fiber data obtained from large pool fire tests. The fibrillation phenomena were attributed to fiber oxidation effects caused by the fire environment. Analysis of propane burn test records indicated that wind sources can cause considerable carbon fiber oxidation. Criteria estimates were determined for the number of micron carbon fibers released during an aircraft accident. An extreme case analysis indicated that the upper limit of the micron carbon fiber concentration level was only about half the permissible asbestos ceiling concentration level.

  4. ESTIMATION OF EXPOSURE CRITERIA VALUES FOR BILIARY POLYCYCLIC AROMATIC HYDROCARBON METABOLITE CONCENTRATIONS IN WHITE SUCKERS (CATOSTOMUS COMMERSONI)

    EPA Science Inventory

    A methodology was developed for deriving quantitative exposure criteria useful for comparing a site or a watershed to a reference condition and for defining the occurrence of extreme exposures. The prototype method used indicators of exposures to oil contamination and combustion ...

  5. ESTIMATION OF EXPOSURE CRITERIA VALUES FOR BILIARY POLYCYCLIC AROMATIC HYDROCARBON METABOLITE CONCENTRATION IN WHITE SUCKERS (CATASTOMUS COMMERSONI)

    EPA Science Inventory

    A methodology was developed for deriving quantitative exposure criteria useful for comparing a site or a watershed to a reference condition and for defining the occurrence of extreme exposures. The prototype method used indicators of exposures to oil contamination and combustion ...

  6. Severity of Organized Item Theft in Computerized Adaptive Testing: A Simulation Study

    ERIC Educational Resources Information Center

    Yi, Qing; Zhang, Jinming; Chang, Hua-Hua

    2008-01-01

    Criteria had been proposed for assessing the severity of possible test security violations for computerized tests with high-stakes outcomes. However, these criteria resulted from theoretical derivations that assumed uniformly randomized item selection. This study investigated potential damage caused by organized item theft in computerized adaptive…

  7. Update on US EPA’s Revision to the 1985 Guidelines for Deriving Aquatic Life Criteria

    EPA Science Inventory

    National Water Quality Criteria for the Protection of Aquatic Organisms and Their Uses (Stephan et al. 1985), to reflect the current state-of-the-science for aquatic effects assessments. Following a 2015 public meeting soliciting early input from the scientific community, EPA dec...

  8. Evaluating Online CPD Using Educational Criteria Derived from the Experiential Learning Cycle.

    ERIC Educational Resources Information Center

    Friedman, Andrew; Watts, David; Croston, Judith; Durkin, Catherine

    2002-01-01

    Develops a set of educational evaluation criteria for online continuing professional development (CPD) courses using Kolb's experiential learning cycle theory. Evaluates five courses provided by online CPD Web sites, concludes that these online courses neglect parts of the learning cycle, and suggests improvements. (Author/LRW)

  9. VALIDATION OF AMBIENT WATER QUALITY CRITERIA (AWQC) BIOACCUMULATION METHODOLOGY USING FIELD DATA FROM GREEN BAY AND THE HUDSON RIVER

    EPA Science Inventory

    In 1998, EPA published its draft revision to the methodology for deriving ambient water quality criteria to protect human health. Four methods were proposed to determine lipid-normalized bioaccumulation factors based on freely-dissolved water concentrations (BAFs) for nonpolar or...

  10. Validity of Evidence-Derived Criteria for Reactive Attachment Disorder: Indiscriminately Social/Disinhibited and Emotionally Withdrawn/Inhibited Types

    ERIC Educational Resources Information Center

    Gleason, Mary Margaret; Fox, Nathan A.; Drury, Stacy; Smyke, Anna; Egger, Helen L.; Nelson, Charles A., III; Gregas, Matthew C.; Zeanah, Charles H.

    2011-01-01

    Objective: This study examined the validity of criteria for indiscriminately social/disinhibited and emotionally withdrawn/inhibited reactive attachment disorder (RAD). Method: As part of a longitudinal intervention trial of previously institutionalized children, caregiver interviews and direct observational measurements provided continuous and…

  11. Predicting red wolf release success in the southeastern United States

    USGS Publications Warehouse

    van Manen, Frank T.; Crawford, Barron A.; Clark, Joseph D.

    2000-01-01

    Although the red wolf (Canis rufus) was once found throughout the southeastern United States, indiscriminate killing and habitat destruction reduced its range to a small section of coastal Texas and Louisiana. Wolves trapped from 1973 to 1980 were taken to establish a captive breeding program that was used to repatriate 2 mainland and 3 island red wolf populations. We collected data from 320 red wolf releases in these areas and classified each as a success or failure based on survival and reproductive criteria, and whether recaptures were necessary to resolve conflicts with humans. We evaluated the relations between release success and conditions at the release sites, characteristics of released wolves, and release procedures. Although <44% of the variation in release success was explained, model performance based on jackknife tests indicated a 72-80% correct prediction rate for the 4 operational models we developed. The models indicated that success was associated with human influences on the landscape and the level of wolf habituation to humans prior to release. We applied the models to 31 prospective areas for wolf repatriation and calculated an index of release success for each area. Decision-makers can use these models to objectively rank prospective release areas and compare strengths and weaknesses of each.

  12. Reconstructing source terms from atmospheric concentration measurements: Optimality analysis of an inversion technique

    NASA Astrophysics Data System (ADS)

    Turbelin, Grégory; Singh, Sarvesh Kumar; Issartel, Jean-Pierre

    2014-12-01

    In the event of an accidental or intentional contaminant release in the atmosphere, it is imperative, for managing emergency response, to diagnose the release parameters of the source from measured data. Reconstruction of the source information exploiting measured data is called an inverse problem. To solve such a problem, several techniques are currently being developed. The first part of this paper provides a detailed description of one of them, known as the renormalization method. This technique, proposed by Issartel (2005), has been derived using an approach different from that of standard inversion methods and gives a linear solution to the continuous Source Term Estimation (STE) problem. In the second part of this paper, the discrete counterpart of this method is presented. By using matrix notation, common in data assimilation and suitable for numerical computing, it is shown that the discrete renormalized solution belongs to a family of well-known inverse solutions (minimum weighted norm solutions), which can be computed by using the concept of generalized inverse operator. It is shown that, when the weight matrix satisfies the renormalization condition, this operator satisfies the criteria used in geophysics to define good inverses. Notably, by means of the Model Resolution Matrix (MRM) formalism, we demonstrate that the renormalized solution fulfils optimal properties for the localization of single point sources. Throughout the article, the main concepts are illustrated with data from a wind tunnel experiment conducted at the Environmental Flow Research Centre at the University of Surrey, UK.

  13. Prevalence of Prescription Opioid Misuse/Abuse as Determined by International Classification of Diseases Codes: A Systematic Review.

    PubMed

    Roland, Carl L; Lake, Joanita; Oderda, Gary M

    2016-12-01

    We conducted a systematic review to evaluate worldwide human English published literature from 2009 to 2014 on prevalence of opioid misuse/abuse in retrospective databases where International Classification of Diseases (ICD) codes were used. Inclusion criteria for the studies were use of a retrospective database, measured abuse, dependence, and/or poisoning using ICD codes, stated prevalence or it could be derived, and documented time frame. A meta-analysis was not performed. A qualitative narrative synthesis was used, and 16 studies were included for data abstraction. ICD code use varies; 10 studies used ICD codes that encompassed all three terms: abuse, dependence, or poisoning. Eight studies limited determination of misuse/abuse to an opioid user population. Abuse prevalence among opioid users in commercial databases using all three terms of ICD codes varied depending on the opioid; 21 per 1000 persons (reformulated extended-release oxymorphone; 2011-2012) to 113 per 1000 persons (immediate-release opioids; 2010-2011). Abuse prevalence in general populations using all three ICD code terms ranged from 1.15 per 1000 persons (commercial; 6 months 2010) to 8.7 per 1000 persons (Medicaid; 2002-2003). Prevalence increased over time. When similar ICD codes are used, the highest prevalence is in US government-insured populations. Limiting population to continuous opioid users increases prevalence. Prevalence varies depending on ICD codes used, population, time frame, and years studied. Researchers using ICD codes to determine opioid abuse prevalence need to be aware of cautions and limitations.

  14. Influence of Litter Diversity on Dissolved Organic Matter Release and Soil Carbon Formation in a Mixed Beech Forest

    PubMed Central

    Scheibe, Andrea; Gleixner, Gerd

    2014-01-01

    We investigated the effect of leaf litter on below ground carbon export and soil carbon formation in order to understand how litter diversity affects carbon cycling in forest ecosystems. 13C labeled and unlabeled leaf litter of beech (Fagus sylvatica) and ash (Fraxinus excelsior), characterized by low and high decomposability, were used in a litter exchange experiment in the Hainich National Park (Thuringia, Germany). Litter was added in pure and mixed treatments with either beech or ash labeled with 13C. We collected soil water in 5 cm mineral soil depth below each treatment biweekly and determined dissolved organic carbon (DOC), δ13C values and anion contents. In addition, we measured carbon concentrations and δ13C values in the organic and mineral soil (collected in 1 cm increments) up to 5 cm soil depth at the end of the experiment. Litter-derived C contributes less than 1% to dissolved organic matter (DOM) collected in 5 cm mineral soil depth. Better decomposable ash litter released significantly more (0.50±0.17%) litter carbon than beech litter (0.17±0.07%). All soil layers held in total around 30% of litter-derived carbon, indicating the large retention potential of litter-derived C in the top soil. Interestingly, in mixed (ash and beech litter) treatments we did not find a higher contribution of better decomposable ash-derived carbon in DOM, O horizon or mineral soil. This suggest that the known selective decomposition of better decomposable litter by soil fauna has no or only minor effects on the release and formation of litter-derived DOM and soil organic matter. Overall our experiment showed that 1) litter-derived carbon is of low importance for dissolved organic carbon release and 2) litter of higher decomposability is faster decomposed, but litter diversity does not influence the carbon flow. PMID:25486628

  15. Influence of litter diversity on dissolved organic matter release and soil carbon formation in a mixed beech forest.

    PubMed

    Scheibe, Andrea; Gleixner, Gerd

    2014-01-01

    We investigated the effect of leaf litter on below ground carbon export and soil carbon formation in order to understand how litter diversity affects carbon cycling in forest ecosystems. 13C labeled and unlabeled leaf litter of beech (Fagus sylvatica) and ash (Fraxinus excelsior), characterized by low and high decomposability, were used in a litter exchange experiment in the Hainich National Park (Thuringia, Germany). Litter was added in pure and mixed treatments with either beech or ash labeled with 13C. We collected soil water in 5 cm mineral soil depth below each treatment biweekly and determined dissolved organic carbon (DOC), δ13C values and anion contents. In addition, we measured carbon concentrations and δ13C values in the organic and mineral soil (collected in 1 cm increments) up to 5 cm soil depth at the end of the experiment. Litter-derived C contributes less than 1% to dissolved organic matter (DOM) collected in 5 cm mineral soil depth. Better decomposable ash litter released significantly more (0.50±0.17%) litter carbon than beech litter (0.17±0.07%). All soil layers held in total around 30% of litter-derived carbon, indicating the large retention potential of litter-derived C in the top soil. Interestingly, in mixed (ash and beech litter) treatments we did not find a higher contribution of better decomposable ash-derived carbon in DOM, O horizon or mineral soil. This suggest that the known selective decomposition of better decomposable litter by soil fauna has no or only minor effects on the release and formation of litter-derived DOM and soil organic matter. Overall our experiment showed that 1) litter-derived carbon is of low importance for dissolved organic carbon release and 2) litter of higher decomposability is faster decomposed, but litter diversity does not influence the carbon flow.

  16. The Phenazine 2-Hydroxy-Phenazine-1-Carboxylic Acid Promotes Extracellular DNA Release and Has Broad Transcriptomic Consequences in Pseudomonas chlororaphis 30–84

    DOE PAGES

    Wang, Dongping; Yu, Jun Myoung; Dorosky, Robert J.; ...

    2016-01-26

    Enhanced production of 2-hydroxy-phenazine-1-carboxylic acid (2-OH-PCA) by the biological control strain Pseudomonas chlororaphis 30–84 derivative 30-84O* was shown previously to promote cell adhesion and alter the three-dimensional structure of surfaceattached biofilms compared to the wild type. The current study demonstrates that production of 2-OH-PCA promotes the release of extracellular DNA, which is correlated with the production of structured biofilm matrix. Moreover, the essential role of the extracellular DNA in maintaining the mass and structure of the 30–84 biofilm matrix is demonstrated. To better understand the role of different phenazines in biofilm matrix production and gene expression, transcriptomic analyses were conductedmore » comparing gene expression patterns of populations of wild type, 30-84O* and a derivative of 30–84 producing only PCA (30-84PCA) to a phenazine defective mutant (30-84ZN) when grown in static cultures. RNA-Seq analyses identified a group of 802 genes that were differentially expressed by the phenazine producing derivatives compared to 30-84ZN, including 240 genes shared by the two 2-OH-PCA producing derivatives, the wild type and 30-84O*. A gene cluster encoding a bacteriophage- derived pyocin and its lysis cassette was upregulated in 2-OH-PCA producing derivatives. A holin encoded in this gene cluster was found to contribute to the release of eDNA in 30–84 biofilm matrices, demonstrating that the influence of 2-OH-PCA on eDNA production is due in part to cell autolysis as a result of pyocin production and release. The results expand the current understanding of the functions different phenazines play in the survival of bacteria in biofilm-forming communities.« less

  17. The Phenazine 2-Hydroxy-Phenazine-1-Carboxylic Acid Promotes Extracellular DNA Release and Has Broad Transcriptomic Consequences in Pseudomonas chlororaphis 30–84

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

    Wang, Dongping; Yu, Jun Myoung; Dorosky, Robert J.

    Enhanced production of 2-hydroxy-phenazine-1-carboxylic acid (2-OH-PCA) by the biological control strain Pseudomonas chlororaphis 30–84 derivative 30-84O* was shown previously to promote cell adhesion and alter the three-dimensional structure of surfaceattached biofilms compared to the wild type. The current study demonstrates that production of 2-OH-PCA promotes the release of extracellular DNA, which is correlated with the production of structured biofilm matrix. Moreover, the essential role of the extracellular DNA in maintaining the mass and structure of the 30–84 biofilm matrix is demonstrated. To better understand the role of different phenazines in biofilm matrix production and gene expression, transcriptomic analyses were conductedmore » comparing gene expression patterns of populations of wild type, 30-84O* and a derivative of 30–84 producing only PCA (30-84PCA) to a phenazine defective mutant (30-84ZN) when grown in static cultures. RNA-Seq analyses identified a group of 802 genes that were differentially expressed by the phenazine producing derivatives compared to 30-84ZN, including 240 genes shared by the two 2-OH-PCA producing derivatives, the wild type and 30-84O*. A gene cluster encoding a bacteriophage- derived pyocin and its lysis cassette was upregulated in 2-OH-PCA producing derivatives. A holin encoded in this gene cluster was found to contribute to the release of eDNA in 30–84 biofilm matrices, demonstrating that the influence of 2-OH-PCA on eDNA production is due in part to cell autolysis as a result of pyocin production and release. The results expand the current understanding of the functions different phenazines play in the survival of bacteria in biofilm-forming communities.« less

  18. The Phenazine 2-Hydroxy-Phenazine-1-Carboxylic Acid Promotes Extracellular DNA Release and Has Broad Transcriptomic Consequences in Pseudomonas chlororaphis 30–84

    PubMed Central

    Wang, Dongping; Yu, Jun Myoung; Dorosky, Robert J.; Pierson, Leland S.; Pierson, Elizabeth A.

    2016-01-01

    Enhanced production of 2-hydroxy-phenazine-1-carboxylic acid (2-OH-PCA) by the biological control strain Pseudomonas chlororaphis 30–84 derivative 30-84O* was shown previously to promote cell adhesion and alter the three-dimensional structure of surface-attached biofilms compared to the wild type. The current study demonstrates that production of 2-OH-PCA promotes the release of extracellular DNA, which is correlated with the production of structured biofilm matrix. Moreover, the essential role of the extracellular DNA in maintaining the mass and structure of the 30–84 biofilm matrix is demonstrated. To better understand the role of different phenazines in biofilm matrix production and gene expression, transcriptomic analyses were conducted comparing gene expression patterns of populations of wild type, 30-84O* and a derivative of 30–84 producing only PCA (30-84PCA) to a phenazine defective mutant (30-84ZN) when grown in static cultures. RNA-Seq analyses identified a group of 802 genes that were differentially expressed by the phenazine producing derivatives compared to 30-84ZN, including 240 genes shared by the two 2-OH-PCA producing derivatives, the wild type and 30-84O*. A gene cluster encoding a bacteriophage-derived pyocin and its lysis cassette was upregulated in 2-OH-PCA producing derivatives. A holin encoded in this gene cluster was found to contribute to the release of eDNA in 30–84 biofilm matrices, demonstrating that the influence of 2-OH-PCA on eDNA production is due in part to cell autolysis as a result of pyocin production and release. The results expand the current understanding of the functions different phenazines play in the survival of bacteria in biofilm-forming communities. PMID:26812402

  19. Opioid tolerance and urine drug testing among initiates of extended-release or long-acting opioids in Food and Drug Administration's Sentinel System.

    PubMed

    Larochelle, Marc R; Cocoros, Noelle M; Popovic, Jennifer; Dee, Elizabeth C; Kornegay, Cynthia; Ju, Jing; Racoosin, Judith A

    A risk evaluation and mitigation strategy for extended-release and long-acting (ER/LA) opioid analgesics was approved by the Food and Drug Administration in 2012. Our objective was to assess frequency of opioid tolerance and urine drug testing for individuals initiating ER/LA opioid analgesics. Retrospective cohort study. Sentinel, a distributed database with electronic healthcare data on >190 million predominantly commercially insured members. Members under age 65 initiating ER/LA opioid analgesics between January 2009 and December 2013. We examined the proportion of opioid-tolerant-only ER/LA opioid analgesic initiates meeting tolerance criteria: receipt of ≥30 mg oxycodone equivalents per day in 7 days prior to the first opioid-tolerant-only dispensing. We separately examined the proportion of new users of extended-release oxycodone (ERO) and other ER/LA opioid analgesics with a claim for a urine drug test in the 30 days prior to, and separately for the 183 days after, dispensing. We identified 79,824 ERO, 7,343 extended-release hydromorphone, and 91,778 transdermal fentanyl opi-oid-tolerant-only episodes. Tolerance criteria were met in 64 percent of ERO, 64 percent of extended-release hydromorphone and 40 percent of transdermal fentanyl episodes. We identified 210,581 incident ERO and 311,660 other ER/LA opioid analgesic episodes. Use of urine drug testing for ERO compared with other ER/LA opioid analgesics was: 4 percent vs 14 percent respectively in the 30 days prior to initiation and 9 percent vs 23 percent respectively in the 183 days following initiation. These results suggest potential areas for improving appropriate ER/LA opioid analgesic prescribing practices.

  20. The pertinence of Sutton's law to exposure science: Lessons from unconventional shale gas drilling.

    PubMed

    Goldstein, Bernard D

    2018-01-04

    Sutton's Law urges the medical practitioner to utilize the test that goes directly to the problem. When applied to exposure science, Sutton's Law would argue that the major emphasis should be on techniques that directly measure exposure in or close to the human, animal or ecosystem receptors of concern. Exposure science largely and appropriately violates Sutton's Law by estimating exposure based on information on emissions or measurements obtained at a distance from the receptors of concern. I suggest four criteria to help determine whether Sutton's law should be violated for an innovative technology, and explore these criteria in relation to potential human exposure resulting from unconventional gas drilling (UGD): (1) The technological processes possibly leading to release of the chemical or physical agents of concern are reasonably understood; (2) the agents of concern are known; (3) the source and geographical location of the releases can be reasonably identified; and (4) there is information about the likely temporal pattern of the releases and resulting pollutant levels in relation to the temporal patterns of receptor susceptibility. For UGD, the complexity of the technology including many possible release points at different time periods; the existence of three variable mixtures of chemical and physical agents as well as possible unknown reactants; the demonstrated large variation in releases from site to site; and deficiencies in transparency and regulatory oversight, all suggest that studies of the potential health impact of UGD should follow Sutton's Law. This includes the use of techniques that more directly measure exposure close to or within the receptors of concern, such as biological markers or through community-based citizen science. Understanding the implications of Sutton's Law could help focus scientific and regulatory efforts on effective approaches to evaluate the potential health and ecosystem implications of new and evolving technologies.

  1. [Effect of slow-release aminophylline on pulmonary function in obstructive respiratory disease(author's transl)].

    PubMed

    Wiessmann, K J

    1975-09-05

    The effects on pulmonary function of a slow-release preparation of an oral broncholytic drug (containing 350 mg aminophylline, released over eight hours) was tested on 26 patients in a double-blind trial. There was a marked reduction of airway resistance and stimulation of breathing with decreased dynamic work of breathing. Distinctly improved alveolar function was demonstrated especially in a fall of arterial CO2 tension, but in some cases there was probably an increase in distribution abnormality. Central haemodynamic changes with a decreased in pulmonary artery pressure and changes in the other values lasted for more than ten hours on the first day of treatment, and were demonstrable on the fourth day even before the drug was taken that day. The criteria of an effective broncholytic slow-release drug with sustained effect were thus fulfilled.

  2. Components in Plasma-Derived Factor VIII, But Not in Recombinant Factor VIII Downregulate Anti-Inflammatory Surface Marker CD163 in Human Macrophages through Release of CXCL4 (Platelet Factor 4).

    PubMed

    Bertling, Anne; Brodde, Martin F; Visser, Mayken; Treffon, Janina; Fennen, Michelle; Fender, Anke C; Kelsch, Reinhard; Kehrel, Beate E

    2017-09-01

    Hemarthrosis, or bleeding into the joints, is a hallmark of hemophilia. Heme triggers oxidative stress, inflammation, and destruction of cartilage and bone. The haptoglobin-CD163-heme oxygenase-1 (HO-1) pathway circumvents heme toxicity through enzymatic degradation of heme and transcription of antioxidant genes. Plasma-derived factor concentrates contain many proteins that might impact on cellular pathways in joints, blood, and vessels. Activation of platelets from healthy volunteers was assessed by flow cytometry analysis of fibrinogen binding and CD62P expression. Platelet CXCL4 release was measured by ELISA. Human peripheral blood mononuclear cells were exposed to CXCL4 or platelet supernatants (untreated or pre-stimulated with factor VIII (FVIII) products) during their differentiation to macrophages and analyzed for CD163 expression. Some macrophage cultures were additionally incubated with autologous hemoglobin for 18 h for analysis of HO-1 expression. Platelet CXCL4 release was increased by all 8 tested plasma-derived FVIII products but not the 3 recombinant products. Macrophages exposed to supernatant from platelets treated with some plasma-derived FVIII products downregulated CD163 surface expression and failed to upregulate the athero- and joint protective enzyme HO-1 in response to hemoglobin. Plasma-derived FVIII products might promote bleeding-induced joint injury via generation of macrophages that are unable to counteract redox stress.

  3. Effectively Communicating Information about Dynamically Changing Arctic Sea Ice to the Public through the Global Fiducials Program

    NASA Astrophysics Data System (ADS)

    Molnia, B. F.; Friesen, B.; Wilson, E.; Noble, S.

    2015-12-01

    On July 15, 2009, the National Academy of Sciences (NAS) released a report, Scientific Value of Arctic Sea Ice Imagery Derived Products, advocating public release of Arctic images derived from classified data. In the NAS press release that announced the release, report lead Stephanie Pfirman states "To prepare for a possibly ice-free Arctic and its subsequent effects on the environment, economy, and national security, it is critical to have accurate projections of changes over the next several decades." In the same release NAS President Ralph Cicerone states "We hope that these images are the first of many that could help scientists learn how the changing climate could impact the environment and our society." The same day, Secretary of the Interior Ken Salazar announced that the requested images had been released and were available to the public on a US Geological Survey Global Fiducials Program (GFP) Library website (http://gfl.usgs.gov). The website was developed by the USGS to provide public access to the images and to support environmental analysis of global climate-related science. In the statement describing the release titled, Information Derived from Classified Materials Will Aid Understanding of Changing Climate, Secretary Salazar states "We need the best data from all places if we are to meet the challenges that rising carbon emissions are creating. This information will be invaluable to scientists, researchers, and the public as we tackle climate change." Initially about 700 Arctic sea ice images were released. Six years later, the number exceeds 1,500. The GFP continues to facilitate the acquisition of new Arctic sea ice imagery from US National Imagery Systems. This example demonstrates how information about dynamically changing Arctic sea ice continues to be effectively communicated to the public by the GFP. In addition to Arctic sea ice imagery, the GFP has publicly released imagery time series of more than 125 other environmentally important geographic locations. Recently, the GFP has developed a second website (http://gfp.usgs.gov) to provide more in-depth scientific descriptions of the time series to the public.

  4. 50 CFR 216.215 - Definitions, terms, and criteria

    Code of Federal Regulations, 2012 CFR

    2012-10-01

    ... design employed in order to determine the appropriate marine mammal mitigation/monitoring measures. (b... energy released during the detonation of an explosive-severance charge. (2) Predetonation survey (required for all scenarios) means any marine mammal monitoring survey (e.g., surface, aerial, or acoustic...

  5. 50 CFR 216.215 - Definitions, terms, and criteria

    Code of Federal Regulations, 2011 CFR

    2011-10-01

    ... design employed in order to determine the appropriate marine mammal mitigation/monitoring measures. (b... energy released during the detonation of an explosive-severance charge. (2) Predetonation survey (required for all scenarios) means any marine mammal monitoring survey (e.g., surface, aerial, or acoustic...

  6. 50 CFR 216.215 - Definitions, terms, and criteria

    Code of Federal Regulations, 2010 CFR

    2010-10-01

    ... design employed in order to determine the appropriate marine mammal mitigation/monitoring measures. (b... energy released during the detonation of an explosive-severance charge. (2) Predetonation survey (required for all scenarios) means any marine mammal monitoring survey (e.g., surface, aerial, or acoustic...

  7. Design criteria for payload workstation accommodations

    NASA Technical Reports Server (NTRS)

    Watters, H. H.; Stokes, J. W.

    1975-01-01

    Anticipated shuttle sortie payload man-system design criteria needs are investigated. Man-system interactions for the scientific disciplines are listed and the extent is assessed to which documented Skylab experience is expected to provide system design guidance for each of the identified interactions. Where the analysis revealed that the reduced Skylab data does not answer the anticipated needs candidate criteria, based on unreduced Skylab data, available prior research, original analysis, or related requirements derived from previous space programs, are provided.

  8. Recommended Water Quality Criteria for Octahydro-1,3,5,7-Tentranitro-1, 3,5,7-Tetrazocin (HMX).

    DTIC Science & Technology

    1989-03-27

    possible to derive water quality criteria for protection of aquatic life following USEPA guidelines. Based on the NOAEL of 50 mg/kg/day from the 13-week...special reference to those on human, mammalian, and aquatic health effects, and to generate water quality criteria for drinking water and for the...and discussed below. Aquatic Invertebrates Bentley et al. (1977) performed static acute toxicity tests on four species of freshwater invertebrates

  9. Estimating urban flood risk - uncertainty in design criteria

    NASA Astrophysics Data System (ADS)

    Newby, M.; Franks, S. W.; White, C. J.

    2015-06-01

    The design of urban stormwater infrastructure is generally performed assuming that climate is static. For engineering practitioners, stormwater infrastructure is designed using a peak flow method, such as the Rational Method as outlined in the Australian Rainfall and Runoff (AR&R) guidelines and estimates of design rainfall intensities. Changes to Australian rainfall intensity design criteria have been made through updated releases of the AR&R77, AR&R87 and the recent 2013 AR&R Intensity Frequency Distributions (IFDs). The primary focus of this study is to compare the three IFD sets from 51 locations Australia wide. Since the release of the AR&R77 IFDs, the duration and number of locations for rainfall data has increased and techniques for data analysis have changed. Updated terminology coinciding with the 2013 IFD release has also resulted in a practical change to the design rainfall. For example, infrastructure that is designed for a 1 : 5 year ARI correlates with an 18.13% AEP, however for practical purposes, hydraulic guidelines have been updated with the more intuitive 20% AEP. The evaluation of design rainfall variation across Australia has indicated that the changes are dependent upon location, recurrence interval and rainfall duration. The changes to design rainfall IFDs are due to the application of differing data analysis techniques, the length and number of data sets and the change in terminology from ARI to AEP. Such changes mean that developed infrastructure has been designed to a range of different design criteria indicating the likely inadequacy of earlier developments to the current estimates of flood risk. In many cases, the under-design of infrastructure is greater than the expected impact of increased rainfall intensity under climate change scenarios.

  10. Correlates of retention on extended-release naltrexone among persons living with HIV infection transitioning to the community from the criminal justice system.

    PubMed

    Springer, Sandra A; Brown, Shan-Estelle; Di Paola, Angela; Altice, Frederick L

    2015-12-01

    The acceptability of and retention on extended-release naltrexone (XR-NTX), an FDA-approved medication for the treatment of alcohol and opioid use disorders, among persons living with HIV disease (PLH) under criminal justice setting (CJS) supervision has not been evaluated to date. Two double-blind placebo-controlled randomized trials of XR-NTX for inmates with HIV disease transitioning to the community with (1) alcohol use disorders (AUDs) or (2) opioid use disorders, are underway. Reasons for not accepting XR-NTX and an evaluation of differences in demographic features between those who were retained on study drug and those who did not return for their second injection post-release are discussed. 70% of eligible persons consented to participate; almost 90% received their first injection; and almost 60% returned for their first injection after release. Variables found to be associated (p<0.10) with returning for the second injection included: not meeting criteria for hazardous drinking (p=0.035; OR 0.424 (CI 0.191-0.941)); being prescribed antiretroviral therapy (p=0.068; OR 2.170 (CI 0.943-4.992)); expressing experiencing serious depression 30 days prior to incarceration (p=0.068; OR 1.889 (CI 0.955-3.737)); not having a positive cocaine urine screen on the day of release (DOR) (p=0.011; OR 0.258 (CI 0.091-0.729)); and not meeting criteria for an AUD plus any substance use disorder (p=0.068; OR 0.521 (CI 0.259-1.048)). Only positive cocaine urine test on DOR was statistically significant after multivariate regression analyses (p=0.005; OR 0.207 (CI 0.068-0.623)). CJS based XR-NTX programs are highly acceptable among PLH, however retention on XR-NTX after release is negatively impacted by relapse to cocaine use. Published by Elsevier Ireland Ltd.

  11. Different design of enzyme-triggered CO-releasing molecules (ET-CORMs) reveals quantitative differences in biological activities in terms of toxicity and inflammation.

    PubMed

    Stamellou, E; Storz, D; Botov, S; Ntasis, E; Wedel, J; Sollazzo, S; Krämer, B K; van Son, W; Seelen, M; Schmalz, H G; Schmidt, A; Hafner, M; Yard, B A

    2014-01-01

    Acyloxydiene-Fe(CO)3 complexes can act as enzyme-triggered CO-releasing molecules (ET-CORMs). Their biological activity strongly depends on the mother compound from which they are derived, i.e. cyclohexenone or cyclohexanedione, and on the position of the ester functionality they harbour. The present study addresses if the latter characteristic affects CO release, if cytotoxicity of ET-CORMs is mediated through iron release or inhibition of cell respiration and to what extent cyclohexenone and cyclohexanedione derived ET-CORMs differ in their ability to counteract TNF-α mediated inflammation. Irrespective of the formulation (DMSO or cyclodextrin), toxicity in HUVEC was significantly higher for ET-CORMs bearing the ester functionality at the outer (rac-4), as compared to the inner (rac-1) position of the cyclohexenone moiety. This was paralleled by an increased CO release from the former ET-CORM. Toxicity was not mediated via iron as EC50 values for rac-4 were significantly lower than for FeCl2 or FeCl3 and were not influenced by iron chelation. ATP depletion preceded toxicity suggesting impaired cell respiration as putative cause for cell death. In long-term HUVEC cultures inhibition of VCAM-1 expression by rac-1 waned in time, while for the cyclohexanedione derived rac-8 inhibition seems to increase. NFκB was inhibited by both rac-1 and rac-8 independent of IκBα degradation. Both ET-CORMs activated Nrf-2 and consequently induced the expression of HO-1. This study further provides a rational framework for designing acyloxydiene-Fe(CO)3 complexes as ET-CORMs with differential CO release and biological activities. We also provide a better understanding of how these complexes affect cell-biology in mechanistic terms.

  12. Bioactive peptides derived from human milk proteins--mechanisms of action.

    PubMed

    Wada, Yasuaki; Lönnerdal, Bo

    2014-05-01

    Human milk contains a multitude of bioactive proteins with very diverse functions, which are beneficial for the rapidly growing neonate. The large variety of bioactivities is accomplished by the combination of bioactive proteins per se and gastrointestinal release of bioactive peptides derived from them. The bioactivities exerted by these peptides include enhancement of mineral absorption, immunomodulation, opioid, antihypertensive and antimicrobial activities. Notably, several of the activities are not attributed to the parental proteins, but exclusively to released bioactive peptides. This article reviews studies on bioactive peptides derived from major human milk proteins, such as caseins, α-lactalbumin and lactoferrin, during gastrointestinal digestion. Studies of bovine milk counterparts are also cited as a comparison. Copyright © 2014. Published by Elsevier Inc.

  13. Interaction between paliperidone extended release and TS-1(®), an oral anticancer drug containing a 5-fluorouracil derivative, in a schizophrenic patient.

    PubMed

    Yasui-Furukori, Norio; Hashimoto, Kojiro; Kubo, Kazutoshi; Tomita, Tetsu

    2013-01-01

    Until now there has been no information available on drug interaction between paliperidone and TS-1(®), an oral anticancer drug containing a 5-fluorouracil derivative. The patient in the case presented here was a 39-year-old man with a 15-year history of schizophrenia. The patient's usual treatment of 2 mg/day of risperidone was changed to 3 mg/day of paliperidone extended release. He experienced worsening psychotic symptoms after switching from risperidone to paliperidone while he was also receiving TS-1. Retrospective analyses showed plasma concentration of paliperidone was consistently lower during the treatment with TS-1 than without TS-1. This case suggests there is drug interaction between paliperidone extended-release tablets and TS-1.

  14. Photoaffinity-labeling and fluorescence-distribution studies of gonadotropin-releasing hormone receptors in ovarian granulosa cells.

    PubMed Central

    Hazum, E; Nimrod, A

    1982-01-01

    Photoaffinity labeling of rat ovarian granulosa cells and membrane preparations with a bioactive photoaffinity derivative of gonadotropin-releasing hormone resulted in identification of two specific components with apparent molecular weights of 60,000 and 54,000. Fluorescent visualization of gonadotropin-releasing hormone receptors in these cells, by using a bioactive rhodamine derivative of the hormone, indicated that the fluorescently labeled receptors were initially distributed uniformly on the cell surface and then formed patches that subsequently internalized (at 37 degrees C) into endocytic vesicles. These processes were dependent on specific binding sites for the rhodamine-labeled peptide on the granulosa cells. These studies may provide an experimental basis for understanding the molecular events involved in the action of the hormone in the ovary. Images PMID:6281784

  15. Using Algal Metrics and Biomass to Evaluate Multiple Ways of Defining Concentration-Based Nutrient Criteria in Streams and their Ecological Relevance

    EPA Science Inventory

    We examined the utility of nutrient criteria derived solely from total phosphorus (TP) concentrations in streams (regression models and percentile distributions) and evaluated their ecological relevance to diatom and algal biomass responses. We used a variety of statistics to cha...

  16. Deriving Criteria-supporting Benchmark Values from Empirical Response Relationships: Comparison of Statistical Techniques and Effect of Log-transforming the Nutrient Variable

    EPA Science Inventory

    In analyses supporting the development of numeric nutrient criteria, multiple statistical techniques can be used to extract critical values from stressor response relationships. However there is little guidance for choosing among techniques, and the extent to which log-transfor...

  17. USING REGIONAL EXPOSURE CRITERIA AND UPSTREAM REFERENCE DATA TO CHARACTERIZE SPATIAL AND TEMPORAL EXPOSURES TO CHEMICAL CONTAMINANTS

    EPA Science Inventory

    Analyses of biomarkers in fish were used to evaluate exposures among locations and across time. Two types of references were used for comparison, an upstream reference sample remote from known point sources and regional exposure criteria derived from a baseline of fish from refer...

  18. Moral Psychology and the Problem of Moral Criteria

    ERIC Educational Resources Information Center

    Welch, Patrick

    2011-01-01

    This article is intended as an initial investigation into the foundations of moral psychology. I primarily examine a recent work in moral education, Daniel Lapsley's and Darcia Narvaez"s "Character education", whose authors seem to assume at points that criteria for discerning moral actions and moral traits can be derived apart from ethics or…

  19. USING REGIONAL EXPOSURE CRITERIA AND UPSTREAM REFERENCE DATA TO CHARACTERIZE SPATIAL AND TEMPORAL EXPOSURES TO CHEMICAL CONTAMINANTS

    EPA Science Inventory

    Analyses of biomarkers in fish were used to evaluate exposures among locations and across time. Two types of references were used for comparison, an upstream reference sample remote from known point sources and regional exposure criteria derived from a basline of fish from refere...

  20. Poly(ethylene glycol)-containing hydrogels promote the release of primary granules from human blood-derived polymorphonuclear leukocytes

    PubMed Central

    Cohen, Hannah Caitlin; Lieberthal, Tyler Jacob; Kao, W. John

    2014-01-01

    Polymorphonuclear leukocytes (PMNs) are recruited to sites of injury and biomaterial implants. Once activated, PMNs can exocytose their granule subsets to recruit monocytes (MCs) and mediate MC/macrophage activation. We investigated the release of myeloperoxidase (MPO), a primary granule marker, and matrix metalloproteinase-9 (MMP-9), a tertiary granule marker, from human blood-derived PMNs cultured on poly(ethylene glycol) (PEG) hydrogels, polydimethylsiloxane (PDMS), tissue culture polystyrene (TCPS) and gelatin-PEG (GP) hydrogels, with and without the presence of the bacterial peptide formyl-Met-Leu-Phe. Supernatants from PMN cultures on PEG-containing hydrogels (i.e., PEG and GP hydrogels) had higher concentrations of MPO than those from PMN cultures on PDMS or TCPS at 2 hours. PMNs on all biomaterials released comparable levels of MMP-9 at 2 hours, indicating that PMNs cultured on PEG-containing hydrogels have different mechanisms of release for primary and tertiary granules. Src family kinases were involved in the release of MPO from PMNs cultured on PEG hydrogels, TCPS and GP hydrogels and in the release of MMP-9 from PMNs cultured on all four materials. The increased release of primary granules from PMNs on PEG-containing hydrogels did not significantly increase MC chemotaxis, indicating that additional co-effectors in the dynamic inflammatory milieu in vivo modulate PMN-mediated MC recruitment. PMID:24497370

  1. Sampling and Analysis Plan for Assessment of LANL-Derived Residual Radionuclides in Soils within Tract A-16-e for Land Conveyance

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

    Gillis, Jessica; Ruedig, Elizabeth

    2016-08-25

    Public Law 105-119 directs the U.S. Department of Energy (DOE) to convey or transfer parcels of land to the Incorporated County of Los Alamos or their designees and to the Department of Interior, Bureau of Indian Affairs, in trust for the Pueblo de San Ildefonso. Los Alamos National Security is tasked to support DOE in conveyance and/or transfer of identified land parcels no later than September 2022. Under DOE Order 458.1, Radiation Protection of the Public and the Environment (O458.1, 2013), and Los Alamos National Laboratory (LANL) implementing Policy 412 (P412, 2014a), real property with the potential to contain residualmore » radioactive material must meet the criteria for clearance and release to the public. This Sampling and Analysis Plan (SAP) investigates Tract A-16-e and proposes 50 project-specific soil samples for use in radiological clearance decisions consistent with LANL Procedure ENV-ES-TP-238 (2015a) and guidance in the Multi-Agency Radiation Survey and Site Investigation Manual (MARSSIM, 2000).« less

  2. Considering social and environmental concerns as reservoir operating objectives

    NASA Astrophysics Data System (ADS)

    Tilmant, A.; Georis, B.; Doulliez, P.

    2003-04-01

    Sustainability principles are now widely recognized as key criteria for water resource development schemes, such as hydroelectric and multipurpose reservoirs. Development decisions no longer rely solely on economic grounds, but also consider environmental and social concerns through the so-called environmental and social impact assessments. The objective of this paper is to show that environmental and social concerns can also be addressed in the management (operation) of existing or projected reservoir schemes. By either adequately exploiting the results of environmental and social impact assessments, or by carrying out survey of water users, experts and managers, efficient (Pareto optimal) reservoir operating rules can be derived using flexible mathematical programming techniques. By reformulating the problem as a multistage flexible constraint satisfaction problem, incommensurable and subjective operating objectives can contribute, along with classical economic objectives, to the determination of optimal release decisions. Employed in a simulation mode, the results can be used to assess the long-term impacts of various operating rules on the social well-being of affected populations as well as on the integrity of the environment. The methodology is illustrated with a reservoir reallocation problem in Chile.

  3. [Fundamentals of plasma chemistry and its application to drug engineering].

    PubMed

    Kuzuya, M

    1996-04-01

    In this review, our novel research works in both low temperature plasma chemistry and solid state plasma chemistry were described. As for low temperature plasma, the ESR study on plasma-induced radicals of several selected conventional polymers was shown including the detailed analyses of the radical structure and the mechanism by which the radicals were formed on typical degradable methacrylic polymers and cross-linkable polystyrene. One of the pharmaceutical applications of the plasma processing for drug delivery system (DDS) was also described, which includes the preparations of double-compressed tablet consisting of drugs as a core material and various types of polymers as a wall material followed by plasma-irradiation on such a tablet. As for solid state plasma, the detailed reaction mechanism of solid state mechanochemical polymerization was shown including the solid state single electron transfer and the special feature of the resulting polymers. The structural criteria for polymerizable monomer derived from the quantum chemical considerations were also established. Based on the above findings, we synthesized various polymeric prodrugs by mechanochemical polymerization and studied the nature of hydrolyses (drug release).

  4. The Profiles in Science Digital Library: Behind the Scenes.

    PubMed

    Gallagher, Marie E; Moffatt, Christie

    2012-01-01

    This demonstration shows the Profiles in Science ® digital library. Profiles in Science contains digitized selections from the personal manuscript collections of prominent biomedical researchers, medical practitioners, and those fostering science and health. The Profiles in Science Web site is the delivery mechanism for content derived from the digital library system. The system is designed according to our basic principles for digital library development [1]. The digital library includes the rules and software used for digitizing items, creating and editing database records and performing quality control as well as serving the digital content to the public. Among the types of data managed by the digital library are detailed item-level, collection-level and cross-collection metadata, digitized photographs, papers, audio clips, movies, born-digital electronic files, optical character recognized (OCR) text, and annotations (see Figure 1). The digital library also tracks the status of each item, including digitization quality, sensitivity of content, and copyright. Only items satisfying all required criteria are released to the public through the World Wide Web. External factors have influenced all aspects of the digital library's infrastructure.

  5. ACTION OF CHEMICALLY DIFFERENT PROSTAGLANDIN BLOCKERS ON THE ADRENAL HORMONES IN PIGEONS DURING STRESS.

    PubMed

    Sarkar, S; Ghosh, S; Sengupta, S; Dasadhikari, S; Ghosh, A

    1999-01-01

    The effect of prostaglandin (PG) inhibitors differing in their chemical nature, viz. Aspirin (acetylsalicylic acid), Mefenamic acid (fenamates), Diclofenac (phenylacetic acid derivative) and Piroxicam (oxicam derivative) on the adrenal hormones was studied in acutely stressed pigeons. None of these PG blockers exerted any significant effect on the catecholamine and corticosterone content of the control, i.e. unstressed pigeon adrenal gland excepting mefenamic acid which caused a release of epinephrine. Aspirin, diclofenac and piroxicam did not modulate the catecholamine or corticosterone secretion whereas mefenamic acid caused a released of both epinephrine and norepinephrine and increased the adrenal corticosterone content in the acutely stressed pigeons. These results were compared with those obtained from studies on the effects of other chemically different PG blockers, indomethacin (a methylated indole derivative) and ibuprofen (a propionic acid derivative). It is suggested that chemically and structurally different PG inhibitors show diverse action in the same species under similar stress conditions.

  6. Enhancement of wound closure by modifying dual release patterns of stromal-derived cell factor-1 and a macrophage recruitment agent from gelatin hydrogels.

    PubMed

    Kim, Yang-Hee; Tabata, Yasuhiko

    2017-11-01

    The objective of the present study is to evaluate the effects of the release patterns of stromal derived factor (SDF)-1 and sphingosine-1 phosphate agonist (SEW2871), used as MSC and macrophage recruitment agents, on the wound closure of diabetic mouse skin defects. To achieve different release patterns, hydrogels were prepared using two types of gelatin with isoelectric points (IEP) of 5 and 9, into which SDF-1 and SEW2871 were then incorporated in various combinations. When the hydrogels incorporating SDF-1 and SEW2871 were applied into wound defects of diabetic mice, the number of MSCs and macrophages recruited to the defects and the levels of pro- and anti- inflammatory cytokines were found to be dependent on the release profiles of SDF-1 and SEW2871. Of particular interest was the case of a rapid release of SDF-1 combined with a controlled release of SEW2871. This resulted in a higher number of M2 macrophages and gene expression levels of anti-inflammatory cytokines 3 days after implantation and faster wound closure than when pairing the controlled release of SDF-1 with a rapid release of SEW2871. Therefore, the present study demonstrates that different release patterns of SDF-1 and SEW2871 can enhance the in vivo recruitment of MSCs and macrophages, and can promote skin wound closure through the modulation of inflammation. Copyright © 2016 John Wiley & Sons, Ltd. Copyright © 2016 John Wiley & Sons, Ltd.

  7. Augmentation of the Ascending Component of the Peristaltic Reflex and Substance P Release by Glial Cell Line-Derived Neurotrophic Factor (GDNF)

    PubMed Central

    Grider, JR; Heuckeroth, RO; Kuemmerle, JF; Murthy, KS

    2010-01-01

    Glial cell line derived neurotrophic factor (GDNF) is present in adult gut although its role in the mature enteric nervous system is not well defined. The aim of the present study was to examine the role of GDNF as neuromodulator of the ascending phase of the peristaltic reflex. Colonic segments were prepared as flat sheets and placed in compartmented chambers so as to separate the sensory and motor limbs of the reflex. Ascending contraction was measured in the orad compartment and mucosal stroking stimuli (2-8 strokes) were applied in the caudad compartment. GDNF and substance P release were measured and the effects of GDNF and GDNF antibody on contraction and release were determined. Mice with reduced levels of GDNF (Gdnf+/-) and wild type littermates were also examined. GDNF was released in a stimulus-dependent manner into the orad motor but not caudad sensory compartment. Addition of GDNF to the orad motor but not caudad sensory compartment augmented ascending contraction and substance P release. Conversely, addition of GDNF antibody to the orad motor but not caudad sensory compartment reduced ascending contraction and substance P release. Similarly, the ascending contraction and substance P release into the orad motor compartment was reduced in Gdnf+/- mice as compared to wild type littermates. The results suggest that endogenous GDNF is released during the ascending contraction component of the peristaltic reflex where it acts as a neuromodulator to augment substance P release from motor neurons thereby augmenting contraction of circular muscle orad to the site of stimulation. PMID:20331804

  8. Augmentation of the ascending component of the peristaltic reflex and substance P release by glial cell line-derived neurotrophic factor.

    PubMed

    Grider, J R; Heuckeroth, R O; Kuemmerle, J F; Murthy, K S

    2010-07-01

    Glial cell line-derived neurotrophic factor (GDNF) is present in adult gut although its role in the mature enteric nervous system is not well defined. The aim of the present study was to examine the role of GDNF as neuromodulator of the ascending phase of the peristaltic reflex. Colonic segments were prepared as flat sheets and placed in compartmented chambers so as to separate the sensory and motor limbs of the reflex. Ascending contraction was measured in the orad compartment and mucosal stroking stimuli (two to eight strokes) were applied in the caudad compartment. GDNF and substance P (SP) release were measured and the effects of GDNF and GDNF antibody on contraction and release were determined. Mice with reduced levels of GDNF (Gdnf(+/-)) and wild type littermates were also examined. GDNF was released in a stimulus-dependent manner into the orad motor but not caudad sensory compartment. Addition of GDNF to the orad motor but not caudad sensory compartment augmented ascending contraction and SP release. Conversely, addition of GDNF antibody to the orad motor but not caudad sensory compartment reduced ascending contraction and SP release. Similarly, the ascending contraction and SP release into the orad motor compartment was reduced in Gdnf(+/-) mice as compared to wild type littermates. The results suggest that endogenous GDNF is released during the ascending contraction component of the peristaltic reflex where it acts as a neuromodulator to augment SP release from motor neurons thereby augmenting contraction of circular muscle orad to the site of stimulation.

  9. Crimpy enables discrimination of presynaptic and postsynaptic pools of a BMP at the Drosophila neuromuscular junction.

    PubMed

    James, Rebecca E; Hoover, Kendall M; Bulgari, Dinara; McLaughlin, Colleen N; Wilson, Christopher G; Wharton, Kristi A; Levitan, Edwin S; Broihier, Heather T

    2014-12-08

    Distinct pools of the bone morphogenetic protein (BMP) Glass bottom boat (Gbb) control structure and function of the Drosophila neuromuscular junction. Specifically, motoneuron-derived Gbb regulates baseline neurotransmitter release, whereas muscle-derived Gbb regulates neuromuscular junction growth. Yet how cells differentiate between these ligand pools is not known. Here we present evidence that the neuronal Gbb-binding protein Crimpy (Cmpy) permits discrimination of pre- and postsynaptic ligand by serving sequential functions in Gbb signaling. Cmpy first delivers Gbb to dense core vesicles (DCVs) for activity-dependent release from presynaptic terminals. In the absence of Cmpy, Gbb is no longer associated with DCVs and is not released by activity. Electrophysiological analyses demonstrate that Cmpy promotes Gbb's proneurotransmission function. Surprisingly, the Cmpy ectodomain is itself released upon DCV exocytosis, arguing that Cmpy serves a second function in BMP signaling. In addition to trafficking Gbb to DCVs, we propose that Gbb/Cmpy corelease from presynaptic terminals defines a neuronal protransmission signal. Copyright © 2014 Elsevier Inc. All rights reserved.

  10. Deduction of reservoir operating rules for application in global hydrological models

    NASA Astrophysics Data System (ADS)

    Coerver, Hubertus M.; Rutten, Martine M.; van de Giesen, Nick C.

    2018-01-01

    A big challenge in constructing global hydrological models is the inclusion of anthropogenic impacts on the water cycle, such as caused by dams. Dam operators make decisions based on experience and often uncertain information. In this study information generally available to dam operators, like inflow into the reservoir and storage levels, was used to derive fuzzy rules describing the way a reservoir is operated. Using an artificial neural network capable of mimicking fuzzy logic, called the ANFIS adaptive-network-based fuzzy inference system, fuzzy rules linking inflow and storage with reservoir release were determined for 11 reservoirs in central Asia, the US and Vietnam. By varying the input variables of the neural network, different configurations of fuzzy rules were created and tested. It was found that the release from relatively large reservoirs was significantly dependent on information concerning recent storage levels, while release from smaller reservoirs was more dependent on reservoir inflows. Subsequently, the derived rules were used to simulate reservoir release with an average Nash-Sutcliffe coefficient of 0.81.

  11. Morphology and vasoactive hormone profiles from endothelial cells derived from stem cells of different sources.

    PubMed

    Reed, Daniel M; Foldes, Gabor; Kirkby, Nicholas S; Ahmetaj-Shala, Blerina; Mataragka, Stefania; Mohamed, Nura A; Francis, Catherine; Gara, Edit; Harding, Sian E; Mitchell, Jane A

    2014-12-12

    Endothelial cells form a highly specialised lining of all blood vessels where they provide an anti-thrombotic surface on the luminal side and protect the underlying vascular smooth muscle on the abluminal side. Specialised functions of endothelial cells include their unique ability to release vasoactive hormones and to morphologically adapt to complex shear stress. Stem cell derived-endothelial cells have a growing number of applications and will be critical in any organ regeneration programme. Generally endothelial cells are identified in stem cell studies by well-recognised markers such as CD31. However, the ability of stem cell-derived endothelial cells to release vasoactive hormones and align with shear stress has not been studied extensively. With this in mind, we have compared directly the ability of endothelial cells derived from a range of stem cell sources, including embryonic stem cells (hESC-EC) and adult progenitors in blood (blood out growth endothelial cells, BOEC) with those cultured from mature vessels, to release the vasoconstrictor peptide endothelin (ET)-1, the cardioprotective hormone prostacyclin, and to respond morphologically to conditions of complex shear stress. All endothelial cell types, except hESC-EC, released high and comparable levels of ET-1 and prostacyclin. Under static culture conditions all endothelial cell types, except for hESC-EC, had the typical cobblestone morphology whilst hESC-EC had an elongated phenotype. When cells were grown under shear stress endothelial cells from vessels (human aorta) or BOEC elongated and aligned in the direction of shear. By contrast hESC-EC did not align in the direction of shear stress. These observations show key differences in endothelial cells derived from embryonic stem cells versus those from blood progenitor cells, and that BOEC are more similar than hESC-EC to endothelial cells from vessels. This may be advantageous in some settings particularly where an in vitro test bed is required. However, for other applications, because of low ET-1 release hESC-EC may prove to be protected from vascular inflammation. Copyright © 2014 Elsevier Inc. All rights reserved.

  12. The ability of retention, drug release and rheological properties of nanogel bioadhesives based on cellulose derivatives.

    PubMed

    Keshavarz, M; Kaffashi, B

    2014-12-01

    The rheological and drug release behavior of biopolymer nanocomposite gels based on the cellulose derivatives, formulated as the bioadhesive drug delivery platforms, were investigated. The bioadhesive gel is composed of the microcrystalline cellulose, sodium carboxymethyl cellulose and phosphate buffered saline (pH = 7.4 at 20 °C) as the dissolution and release medium. The reinforcing nanofillers such as MMT-clay, fumed porous silica and porous starch were used as additives in the nanogel bioadhesive. The constant steady state viscosities of this nanogels upon incorporation of various nanofillers into the systems is the sign of structural stability. Hence, this system is suitable for use in the controlled drug delivery systems in contact with the biological tissues. Based on the rheological measurements, the shear flow properties (i.e. zero shear viscosity and yield stress) were influenced by the concentration of polymers and nanoparticles. The results indicate that the nonlinear rheological data are fitted properly by the Giesekus model. Furthermore, the results showed that the nonlinear viscoelastic parameters (λ and α) are highly affected by the biogel and nanoparticles concentrations. Finally, the drug release was measured, and the results indicated that the biopolymer-clay nanocomposites have appropriate release pattern as the release is better controlled compared to the other nanogel formulations.

  13. Polymer-xerogel composites for controlled release wound dressings.

    PubMed

    Costache, Marius C; Qu, Haibo; Ducheyne, Paul; Devore, David I

    2010-08-01

    Many polymers and composites have been used to prepare active wound dressings. These materials have typically exhibited potentially toxic burst release of the drugs within the first few hours followed by a much slower, potentially ineffective drug release rate thereafter. Many of these materials also degraded to produce inflammatory and cytotoxic products. To overcome these limitations, composite active wound dressings were prepared here from two fully biodegradable and tissue compatible components, silicon oxide sol-gel (xerogel) microparticles that were embedded in tyrosine-poly(ethylene glycol)-derived poly(ether carbonate) copolymer matrices. Sustained, controlled release of drugs from these composites was demonstrated in vitro using bupivacaine and mepivacaine, two water-soluble local anesthetics commonly used in clinical applications. By systematically varying independent compositional parameters of the composites, including the hydrophilic:hydrophobic balance of the tyrosine-derived monomers and poly(ethylene glycol) in the copolymers and the porosity, weight ratio and drug content of the xerogels, drug release kinetics approaching zero-order were obtained. Composites with xerogel mass fractions up to 75% and drug payloads as high as 13% by weight in the final material were fabricated without compromising the physical integrity or the controlled release kinetics. The copolymer-xerogel composites thus provided a unique solution for the sustained delivery of therapeutic agents from tissue compatible wound dressings. 2010 Elsevier Ltd. All rights reserved.

  14. Histamine-releasing factor/translationally controlled tumor protein (HRF/TCTP)-induced histamine release is enhanced with SHIP-1 knockdown in cultured human mast cell and basophil models

    PubMed Central

    Langdon, Jacqueline M.; Schroeder, John T.; Vonakis, Becky M.; Bieneman, Anja P.; Chichester, Kristin; MacDonald, Susan M.

    2008-01-01

    Previously, we demonstrated a negative correlation between histamine release to histamine-releasing factor/translationally controlled tumor protein (HRF/TCTP) and protein levels of SHIP-1 in human basophils. The present study was conducted to investigate whether suppressing SHIP-1 using small interfering (si)RNA technology would alter the releasability of culture-derived mast cells and basophils, as determined by HRF/TCTP histamine release. Frozen CD34+ cells were obtained from the Fred Hutchinson Cancer Research Center (Seattle, WA, USA). Cells were grown in StemPro-34 medium containing cytokines: mast cells with IL-6 and stem cell factor (100 ng/ml each) for 6–8 weeks and basophils with IL-3 (6.7 ng/ml) for 2–3 weeks. siRNA transfections were performed during Week 6 for mast cells and Week 2 for basophils with siRNA for SHIP-1 or a negative control siRNA. Changes in SHIP-1 expression were determined by Western blot. The functional knockdown was measured by HRF/TCTP-induced histamine release. siRNA knockdown of SHIP-1 in mast cells ranged from 31% to 82%, mean 65 ± 12%, compared with control (n=4). Histamine release to HRF/TCTP was increased only slightly in two experiments. SHIP-1 knockdown in basophils ranged from 34% to 69%, mean 51.8 ± 7% (n=4). Histamine release to HRF/TCTP in these basophils was dependent on the amount of SHIP knockdown. Mast cells and basophils derived from CD34+ precursor cells represent suitable models for transfection studies. Reducing SHIP-1 protein in cultured mast cells and in cultured basophils increases releasability of the cells. PMID:18625911

  15. Phosphorus release from dairy manure, the manure-derived biochar, and their amended soil: effects of phosphorus nature and soil property.

    PubMed

    Liang, Yuan; Cao, Xinde; Zhao, Ling; Xu, Xiaoyun; Harris, Willie

    2014-07-01

    Land application of animal manure often risks excessive phosphorus (P) release into the surrounding water. The aim of this study was to convert the dairy manure into biochar, followed by their application into soil, and then to investigate P release from the manure and its derived biochar as well as from the manure- and biochar-amended soil. The results showed that P release was reduced when the manure was converted into biochar due to formation of less-soluble whitlockite [(Ca, Mg)(PO)]. The cumulative P released from biochar over 240 h was 0.26 g kg, a 76% reduction of that from the manure (1.07 g kg). The kinetic release of P from the manure was determined by the fast desorption process and was better fitted to Elovich equation, whereas P release from biochar was initially controlled by the diffusion process and then by slow but steady dissolution of (Ca,Mg)(PO), following the parabolic diffusion and linear models, respectively. When the manure or biochar was incorporated into the soil, P release in the CaCl and simulated acid rain water extraction from biochar-amended soil was consistently lower than that from the manure-amended soil during 210-d incubation. The lower P release in the biochar-amended soil was determined by stable P form (Ca, Mg)(PO) in the biochar itself, but less from the soil property effect. Results indicated that initial high P release from manure can be mitigated by converting the manure into biochar. Copyright © by the American Society of Agronomy, Crop Science Society of America, and Soil Science Society of America, Inc.

  16. Liver cell-derived microparticles activate hedgehog signaling and alter gene expression in hepatic endothelial cells.

    PubMed

    Witek, Rafal P; Yang, Liu; Liu, Renshui; Jung, Youngmi; Omenetti, Alessia; Syn, Wing-Kin; Choi, Steve S; Cheong, Yeiwon; Fearing, Caitlin M; Agboola, Kolade M; Chen, Wei; Diehl, Anna Mae

    2009-01-01

    Angiogenesis contributes to vascular remodeling during cirrhosis. In cirrhotic livers, cholangiocytes, and myofibroblastic hepatic stellate cells (MF-HSC) produce Hedgehog (Hh) ligands. During embryogenesis Hh ligands are released from ligand-producing cells in microparticles and activate Hh signaling in endothelial cells. We studied whether adult liver cell-derived microparticles contain Hh ligands that alter hepatic sinusoidal endothelial cells (SEC). MF-HSC and cholangiocytes were exposed to platelet-derived growth factor to induce Hh ligands; microparticles were isolated from medium, analyzed by transmission electron microscopy and immunoblots, and applied to Hh-reporter-containing cells. Microparticles were obtained from serum and bile of rats after bile duct ligation (BDL) or sham surgery and applied to normal primary liver SEC with or without cyclopamine, an Hh signaling inhibitor. Effects on SEC gene expression were evaluated by quantitative reverse-transcription polymerase chain reaction and immunoblotting. Hh target gene expression and SEC activation markers were compared in primary SEC and in liver sections from healthy and BDL rats. Platelet-derived growth factor-treated MF-HSC and cholangiocytes released exosome-enriched microparticles containing biologically-active Hh ligands. BDL increased release of Hh-containing exosome-enriched microparticles into plasma and bile. Transmission electron microscopy and immunoblots revealed similarities among microparticles from all sources; all microparticles induced similar Hh-dependent changes in SEC gene expression. SEC from healthy livers did not express Hh target genes or activation markers, but both were up-regulated in SEC after BDL. Hh-containing exosome-enriched microparticles released from liver cells alter hepatic SEC gene expression, suggesting a novel mechanism for cirrhotic vasculopathy.

  17. An evaluation of freshwater mussel toxicity data in the derivation of water quality guidance and standards for copper

    USGS Publications Warehouse

    March, F.A.; Dwyer, F.J.; Augspurger, T.; Ingersoll, C.G.; Wang, N.; Mebane, C.A.

    2007-01-01

    The state of Oklahoma has designated several areas as freshwater mussel sanctuaries in an attempt to provide freshwater mussel species a degree of protection and to facilitate their reproduction. We evaluated the protection afforded freshwater mussels by the U.S. Environmental Protection Agency (U.S. EPA) hardness-based 1996 ambient copper water quality criteria, the 2007 U.S. EPA water quality criteria based on the biotic ligand model and the 2005 state of Oklahoma copper water quality standards. Both the criterion maximum concentration and criterion continuous concentration were evaluated. Published acute and chronic copper toxicity data that met American Society for Testing and Materials guidance for test acceptability were obtained for exposures conducted with glochidia or juvenile freshwater mussels. We tabulated toxicity data for glochidia and juveniles to calculate 20 species mean acute values for freshwater mussels. Generally, freshwater mussel species mean acute values were similar to those of the more sensitive species included in the U.S. EPA water quality derivation database. When added to the database of genus mean acute values used in deriving 1996 copper water quality criteria, 14 freshwater mussel genus mean acute values included 10 of the lowest 15 genus mean acute values, with three mussel species having the lowest values. Chronic exposure and sublethal effects freshwater mussel data available for four species and acute to chronic ratios were used to evaluate the criterion continuous concentration. On the basis of the freshwater mussel toxicity data used in this assessment, the hardness-based 1996 U.S. EPA water quality criteria, the 2005 Oklahoma water quality standards, and the 2007 U.S. EPA water quality criteria based on the biotic ligand model might need to be revised to afford protection to freshwater mussels. ?? 2007 SETAC.

  18. Analytical validation of BRAF mutation testing from circulating free DNA using the amplification refractory mutation testing system.

    PubMed

    Aung, Kyaw L; Donald, Emma; Ellison, Gillian; Bujac, Sarah; Fletcher, Lynn; Cantarini, Mireille; Brady, Ged; Orr, Maria; Clack, Glen; Ranson, Malcolm; Dive, Caroline; Hughes, Andrew

    2014-05-01

    BRAF mutation testing from circulating free DNA (cfDNA) using the amplification refractory mutation testing system (ARMS) holds potential as a surrogate for tumor mutation testing. Robust assay validation is needed to establish the optimal clinical matrix for measurement and cfDNA-specific mutation calling criteria. Plasma- and serum-derived cfDNA samples from 221 advanced melanoma patients were analyzed for BRAF c.1799T>A (p.V600E) mutation using ARMS in two stages in a blinded fashion. cfDNA-specific mutation calling criteria were defined in stage 1 and validated in stage 2. cfDNA concentrations in serum and plasma, and the sensitivities and specificities of BRAF mutation detection in these two clinical matrices were compared. Sensitivity of BRAF c.1799T>A (p.V600E) mutation detection in cfDNA was increased by using mutation calling criteria optimized for cfDNA (these criteria were adjusted from those used for archival tumor biopsies) without compromising specificity. Sensitivity of BRAF mutation detection in serum was 44% (95% CI, 35% to 53%) and in plasma 52% (95% CI, 43% to 61%). Specificity was 96% (95% CI, 90% to 99%) in both matrices. Serum contains significantly higher total cfDNA than plasma, whereas the proportion of tumor-derived mutant DNA was significantly higher in plasma. Using mutation calling criteria optimized for cfDNA improves sensitivity of BRAF c.1799T>A (p.V600E) mutation detection. The proportion of tumor-derived cfDNA in plasma was significantly higher than in serum. Copyright © 2014 American Society for Investigative Pathology and the Association for Molecular Pathology. Published by Elsevier Inc. All rights reserved.

  19. A polymeric prodrug of 5-fluorouracil-1-acetic acid using a multi-hydroxyl polyethylene glycol derivative as the drug carrier.

    PubMed

    Li, Man; Liang, Zhen; Sun, Xun; Gong, Tao; Zhang, Zhirong

    2014-01-01

    Macromolecular prodrugs obtained by covalently conjugating small molecular drugs with polymeric carriers were proven to accomplish controlled and sustained release of the therapeutic agents in vitro and in vivo. Polyethylene glycol (PEG) has been extensively used due to its low toxicity, low immunogenicity and high biocompatibility. However, for linear PEG macromolecules, the number of available hydroxyl groups for drug coupling does not change with the length of polymeric chain, which limits the application of PEG for drug conjugation purposes. To increase the drug loading and prolong the retention time of 5-fluorouracil (5-Fu), a macromolecular prodrug of 5-Fu, 5-fluorouracil-1 acid-PAE derivative (5-FA-PAE) was synthesized and tested for the antitumor activity in vivo. PEG with a molecular weight of 38 kDa was selected to synthesize the multi-hydroxyl polyethylene glycol derivative (PAE) through an addition reaction. 5-fluorouracil-1 acetic acid (5-FA), a 5-Fu derivative was coupled with PEG derivatives via ester bond to form a macromolecular prodrug, 5-FA-PAE. The in vitro drug release, pharmacokinetics, in vivo distribution and antitumor effect of the prodrug were investigated, respectively. The PEG-based prodrug obtained in this study possessed an exceedingly high 5-FA loading efficiency of 10.58%, much higher than the maximum drug loading efficiency of unmodified PEG with the same molecular weight, which was 0.98% theoretically. Furthermore, 5-FA-PAE exhibited suitable sustained release in tumors. This study provides a new approach for the development of the delivery to tumors of anticancer agents with PEG derivatives.

  20. An index with improved diagnostic accuracy for the diagnosis of Crohn's disease derived from the Lennard-Jones criteria.

    PubMed

    Reinisch, S; Schweiger, K; Pablik, E; Collet-Fenetrier, B; Peyrin-Biroulet, L; Alfaro, I; Panés, J; Moayyedi, P; Reinisch, W

    2016-09-01

    The Lennard-Jones criteria are considered the gold standard for diagnosing Crohn's disease (CD) and include the items granuloma, macroscopic discontinuity, transmural inflammation, fibrosis, lymphoid aggregates and discontinuous inflammation on histology. The criteria have never been subjected to a formal validation process. To develop a validated and improved diagnostic index based on the items of Lennard-Jones criteria. Included were 328 adult patients with long-standing CD (median disease duration 10 years) from three centres and classified as 'established', 'probable' or 'non-CD' by Lennard-Jones criteria at time of diagnosis. Controls were patients with ulcerative colitis (n = 170). The performance of each of the six diagnostic items of Lennard-Jones criteria was modelled by logistic regression and a new index based on stepwise backward selection and cut-offs was developed. The diagnostic value of the new index was analysed by comparing sensitivity, specificity and accuracy vs. Lennard-Jones criteria. By Lennard-Jones criteria 49% (n = 162) of CD patients would have been diagnosed as 'non-CD' at time of diagnosis (sensitivity/specificity/accuracy, 'established' CD: 0.34/0.99/0.67; 'probable' CD: 0.51/0.95/0.73). A new index was derived from granuloma, fibrosis, transmural inflammation and macroscopic discontinuity, but excluded lymphoid aggregates and discontinuous inflammation on histology. Our index provided improved diagnostic accuracy for 'established' and 'probable' CD (sensitivity/specificity/accuracy, 'established' CD: 0.45/1/0.72; 'probable' CD: 0.8/0.85/0.82), including the subgroup isolated colonic CD ('probable' CD, new index: 0.73/0.85/0.79; Lennard-Jones criteria: 0.43/0.95/0.69). We developed an index based on items of Lennard-Jones criteria providing improved diagnostic accuracy for the differential diagnosis between CD and UC. © 2016 John Wiley & Sons Ltd.

  1. Design criteria for a self-actuated shutdown system to ensure limitation of core damage. [LMFBR

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

    Deane, N.A.; Atcheson, D.B.

    1981-09-01

    Safety-based functional requirements and design criteria for a self-actuated shutdown system (SASS) are derived in accordance with LOA-2 success criteria and reliability goals. The design basis transients have been defined and evaluated for the CDS Phase II design, which is a 2550 MWt mixed oxide heterogeneous core reactor. A partial set of reactor responses for selected transients is provided as a function of SASS characteristics such as reactivity worth, trip points, and insertion times.

  2. Carotid Consensus Panel duplex criteria can replace modified University of Washington criteria without affecting accuracy.

    PubMed

    Kim, Ann H; Augustin, Gener; Shevitz, Andrew; Kim, Hannah; Trivonovich, Michael R; Powell, Alexis R; Kumins, Norman; Tarr, Robert; Kashyap, Vikram S

    2018-04-01

    The decision to intervene for internal carotid stenosis often depends on the degree of stenosis seen on duplex ultrasound (US). The aim of this study is to compare the diagnostic accuracy of two criteria: modified University of Washington (UW) and 2003 Carotid Consensus Panel (CCP). All patients undergoing US in an accredited (IAC) vascular laboratory from January 2010 to June 2015 were reviewed ( n=18,772 US exams). Patients receiving a neck computed tomography angiography (CTA) within 6 months of the US were included in the study ( n=254). The degree of stenosis was determined by UW/CCP criteria and confirmed on CTA images using North American Symptomatic Carotid Endarterectomy Trial (NASCET)/European Carotid Surgery Trial (ECST) schema. Kappa analysis with 95% confidence intervals (CIs) were utilized to determine duplex-CTA agreement. A total of 417 carotid arteries from 221 patients were assessed in this study. The modified UW criteria accurately classified 266 (63.9%, kappa = 0.321, 95% CI 0.255 to 0.386) cases according to NASCET-derived measurements. The sensitivity, specificity, and accuracy at ≥ 60% stenosis were 65.7%, 81.3%, and 81.9%. The CCP criteria resulted in 296 (70.9%) accurate diagnoses (kappa = 0.359, 95% CI 0.280 to 0.437). At ≥ 70% stenosis, the sensitivity, specificity and accuracy were 38.8%, 91.6%, and 87.1% for NASCET. Comparison of the duplex results to ECST-derived CTA measurements revealed a similar trend (UW 53.1%, κ = 0.301 vs CCP 62.1%, κ = 0.315). The CCP criteria demonstrate a higher concordance rate with measurements taken from CTAs. The CCP criteria may be more sensitive in classifying clinically significant degrees of stenosis without a loss in diagnostic accuracy.

  3. Communicating ecological importance in a risk-based world: linking numeric nutrient criteria to waterbody expectations

    NASA Astrophysics Data System (ADS)

    Kaufman, G.; Crawford, T. N.

    2016-12-01

    To protect the integrity of US waters, the Clean Water Act calls for the development of water quality standards. One key component of standards is limits for pollutants, known as water quality criteria. A cornerstone of deriving water quality criteria is determining how nutrients and other chemicals affect the goals for a waterbody set by a state or tribe, known as designated uses. By establishing a quantifiable and predictable relationship between nutrients and nutrient sensitive organisms and processes, known as assessment endpoints, researchers can help policy makers to address the consequences of pollution in a risk-based, understandable way tied to the goals for a waterbody. Furthermore, public buy-in and effectiveness of criteria can be enhanced by using endpoints to show the connection between nutrient pollution and the uses of waters that are important to the public. This talk will communicate the work done by the US Environmental Protection Agency in cooperation with state, federal, and academic partners to explore the connections between biological and ecological responses and nutrient pollution to derive numeric nutrient criteria in estuarine and coastal waters. The presentation will examine the variety of endpoints that have been used in the work of various research efforts and assessment frameworks. Examples will also be given of numeric nutrient criteria development using assessment endpoints and some of the key decisions that were made during endpoint selection and criteria development will be discussed. Aspects of those decisions that will be presented include development of selection factors for endpoints, data considerations when selecting endpoints, and spatial and temporal representation of endpoints for criteria development. Promising endpoints and future research needs will also be highlighted.

  4. Communicating ecological importance in a risk-based world: linking numeric nutrient criteria to waterbody expectations

    NASA Astrophysics Data System (ADS)

    Kaufman, G.; Crawford, T. N.

    2016-02-01

    To protect the integrity of US waters, the Clean Water Act calls for the development of water quality standards. One key component of standards is limits for pollutants, known as water quality criteria. A cornerstone of deriving water quality criteria is determining how nutrients and other chemicals affect the goals for a waterbody set by a state or tribe, known as designated uses. By establishing a quantifiable and predictable relationship between nutrients and nutrient sensitive organisms and processes, known as assessment endpoints, researchers can help policy makers to address the consequences of pollution in a risk-based, understandable way tied to the goals for a waterbody. Furthermore, public buy-in and effectiveness of criteria can be enhanced by using endpoints to show the connection between nutrient pollution and the uses of waters that are important to the public. This talk will communicate the work done by the US Environmental Protection Agency in cooperation with state, federal, and academic partners to explore the connections between biological and ecological responses and nutrient pollution to derive numeric nutrient criteria in estuarine and coastal waters. The presentation will examine the variety of endpoints that have been used in the work of various research efforts and assessment frameworks. Examples will also be given of numeric nutrient criteria development using assessment endpoints and some of the key decisions that were made during endpoint selection and criteria development will be discussed. Aspects of those decisions that will be presented include development of selection factors for endpoints, data considerations when selecting endpoints, and spatial and temporal representation of endpoints for criteria development. Promising endpoints and future research needs will also be highlighted.

  5. Immune surveillance properties of human NK cell-derived exosomes.

    PubMed

    Lugini, Luana; Cecchetti, Serena; Huber, Veronica; Luciani, Francesca; Macchia, Gianfranco; Spadaro, Francesca; Paris, Luisa; Abalsamo, Laura; Colone, Marisa; Molinari, Agnese; Podo, Franca; Rivoltini, Licia; Ramoni, Carlo; Fais, Stefano

    2012-09-15

    Exosomes are nanovesicles released by normal and tumor cells, which are detectable in cell culture supernatant and human biological fluids, such as plasma. Functions of exosomes released by "normal" cells are not well understood. In fact, several studies have been carried out on exosomes derived from hematopoietic cells, but very little is known about NK cell exosomes, despite the importance of these cells in innate and adaptive immunity. In this paper, we report that resting and activated NK cells, freshly isolated from blood of healthy donors, release exosomes expressing typical protein markers of NK cells and containing killer proteins (i.e., Fas ligand and perforin molecules). These nanovesicles display cytotoxic activity against several tumor cell lines and activated, but not resting, immune cells. We also show that NK-derived exosomes undergo uptake by tumor target cells but not by resting PBMC. Exosomes purified from plasma of healthy donors express NK cell markers, including CD56+ and perforin, and exert cytotoxic activity against different human tumor target cells and activated immune cells as well. The results of this study propose an important role of NK cell-derived exosomes in immune surveillance and homeostasis. Moreover, this study supports the use of exosomes as an almost perfect example of biomimetic nanovesicles possibly useful in future therapeutic approaches against various diseases, including tumors.

  6. Basic design considerations for free-electron lasers driven by electron beams from RF accelerators

    NASA Astrophysics Data System (ADS)

    Gover, A.; Freund, H.; Granatstein, V. L.; McAdoo, J. H.; Tang, C.-M.

    A design procedure and design criteria are derived for free-electron lasers driven by electron beams from RF accelerators. The procedure and criteria permit an estimate of the oscillation-buildup time and the laser output power of various FEL schemes: with waveguide resonator or open resonator, with initial seed-radiation injection or with spontaneous-emission radiation source, with a linear wiggler or with a helical wiggler. Expressions are derived for computing the various FEL parameters, allowing for the design and optimization of the FEL operational characteristics under ideal conditions or with nonideal design parameters that may be limited by technological or practical constraints. The design procedure enables one to derive engineering curves and scaling laws for the FEL operating parameters. This can be done most conveniently with a computer program based on flowcharts given in the appendices.

  7. Preparation and In vitro Evaluation of Naproxen Suppositories

    PubMed Central

    Hargoli, S.; Farid, J.; Azarmi, S. H.; Ghanbarzadeh, S.; Zakeri-Milani, P.

    2013-01-01

    The aim of this work was to develop the best formulations for naproxen suppositories. The effects of different bases and surfactants on the physicochemical characteristics of the suppositories were determined by several tests such as weight variation, melting point, assay, hardness, and release rate. All formulations met the standard criteria for tested physicochemical parameters; weight variation (97-112%), content uniformity (97-105%), melting point (4.66-8.7 min) and hardness tests (>5400 g). Based on release rate studies, hydrophilic, and lipophilic bases without surfactants were not suitable bases for naproxen suppository. Amongst the formulations containing surfactants only Witepsol H15 with 0.5% w/w of Tween 80 and Witepsol W35 with 0.5% of cetylpyridinium chloride were suitable and released nearly complete drug during 30 and 60 min, respectively. This study demonstrates the effects of incorporation of known agents on the in vitro release characteristics of naproxen suppository. PMID:24019561

  8. Platelet lysate as a substitute for animal serum for the ex-vivo expansion of mesenchymal stem/stromal cells: present and future.

    PubMed

    Astori, Giuseppe; Amati, Eliana; Bambi, Franco; Bernardi, Martina; Chieregato, Katia; Schäfer, Richard; Sella, Sabrina; Rodeghiero, Francesco

    2016-07-13

    The use of fetal bovine serum (FBS) as a cell culture supplement is discouraged by regulatory authorities to limit the risk of zoonoses and xenogeneic immune reactions in the transplanted host. Additionally, FBS production came under scrutiny due to animal welfare concerns. Platelet derivatives have been proposed as FBS substitutes for the ex-vivo expansion of mesenchymal stem/stromal cells (MSCs) since platelet-derived growth factors can promote MSC ex-vivo expansion. Platelet-derived growth factors are present in platelet lysate (PL) obtained after repeated freezing-thawing cycles of the platelet-rich plasma or by applying physiological stimuli such as thrombin or CaCl2.PL-expanded MSCs have been used already in the clinic, taking advantage of their faster proliferation compared with FBS-expanded preparations. Should PL be applied to other biopharmaceutical products, its demand is likely to increase dramatically. The use of fresh platelet units for the production of PL raises concerns due to limited availability of platelet donors. Expired units might represent an alternative, but further data are needed to define safety, including pathogen reduction, and functionality of the obtained PL. In addition, relevant questions concerning the definition of PL release criteria, including concentration ranges of specific growth factors in PL batches for various clinical indications, also need to be addressed. We are still far from a common definition of PL and standardized PL manufacture due to our limited knowledge of the mechanisms that mediate PL-promoting cell growth. Here, we concisely discuss aspects of PL as MSC culture supplement as a preliminary step towards an agreed definition of the required characteristics of PL for the requirements of manufacturers and users.

  9. Implications of expanding indications for drug treatment to prevent fracture in older men in United States: cross sectional and longitudinal analysis of prospective cohort study.

    PubMed

    Ensrud, Kristine E; Taylor, Brent C; Peters, Katherine W; Gourlay, Margaret L; Donaldson, Meghan G; Leslie, William D; Blackwell, Terri L; Fink, Howard A; Orwoll, Eric S; Schousboe, John

    2014-07-03

    To quantify incremental effects of applying different criteria to identify men who are candidates for drug treatment to prevent fracture and to examine the extent to which fracture probabilities vary across distinct categories of men defined by these criteria. Cross sectional and longitudinal analysis of a prospective cohort study. Multicenter Osteoporotic Fractures in Men (MrOS) study in the United States. 5880 untreated community dwelling men aged 65 years or over classified into four distinct groups: osteoporosis by World Health Organization criteria alone; osteoporosis by National Osteoporosis Foundation (NOF) but not WHO criteria; no osteoporosis but at high fracture risk (at or above NOF derived FRAX intervention thresholds recommended for US); and no osteoporosis and at low fracture risk (below NOF derived FRAX intervention thresholds recommended for US). Proportion of men identified for drug treatment; predicted 10 year probabilities of hip and major osteoporotic fracture calculated using FRAX algorithm with femoral neck bone mineral density; observed 10 year probabilities for confirmed incident hip and major osteoporotic (hip, clinical vertebral, wrist, or humerus) fracture events calculated using cumulative incidence estimation, accounting for competing risk of mortality. 130 (2.2%) men were identified as having osteoporosis by using the WHO definition, and an additional 422 were identified by applying the NOF definition (total osteoporosis prevalence 9.4%). Application of NOF derived FRAX intervention thresholds led to 936 (15.9%) additional men without osteoporosis being identified as at high fracture risk, raising the total prevalence of men potentially eligible for drug treatment to 25.3%. Observed 10 year hip fracture probabilities were 20.6% for men with osteoporosis by WHO criteria alone, 6.8% for men with osteoporosis by NOF (but not WHO) criteria, 6.4% for men without osteoporosis but classified as at high fracture risk, and 1.5% for men without osteoporosis and classified as at low fracture risk. A similar pattern was noted in observed fracture probabilities for major osteoporotic fracture. Among men with osteoporosis by WHO criteria, observed fracture probabilities were greater than FRAX predicted probabilities (20.6% v 9.5% for hip fracture and 30.0% v 17.4% for major osteoporotic fracture). Choice of definition of osteoporosis and use of NOF derived FRAX intervention thresholds have major effects on the proportion of older men identified as warranting drug treatment to prevent fracture. Among men identified with osteoporosis by WHO criteria, who comprised 2% of the study population, actual observed fracture probabilities during 10 years of follow-up were highest and exceeded FRAX predicted fracture probabilities. On the basis of findings from randomized trials in women, these men are most likely to benefit from treatment. Expanding indications for treatment beyond this small group has uncertain value owing to lower observed fracture probabilities and uncertain benefits of treatment among men not selected on the basis of WHO criteria. © Ensrud et al 2014.

  10. A systematic study of the release of bisphenol A by orthodontic materials and its biological effects.

    PubMed

    Halimi, Abdelali; Benyahia, Hicham; Bahije, Loubna; Adli, Hanane; Azeroual, Mohamed-Faouzi; Zaoui, Fatima

    2016-12-01

    Bisphenol A (BPA) is a synthetic chemical substance used as a starting ingredient in the manufacturing process of a number or orthodontic materials. It is a well-known endocrine disruptor with low estrogenic properties. The aim of this investigation is to present a systematic review regarding the issue of bisphenol A release by orthodontic materials and its impact in orthodontics. A systematic analysis was performed by electronic search (between 1936 and 2015) on several data bases. The search was limited by using several specific key-words in two languages, English and French. Two investigators selected the responses, which met the selection criteria. Of the 376 studies found, only 21 met our selection criteria: 11 of these dealt with the release of bisphenol by orthodontic materials and 10 in vitro studies described the effects of BPA leaching from orthodontic materials on human and murine cells. The rate of BPA release was well below the daily tolerable intake (DTI) (50mg/kg/day in 2006, then 50μg/kg/day in 2015) according to the European Food Safety Authority (EFSA). Theoretical exposure to BPA was 11,000 times lower than recommendations. However, other studies have shown the presence of BPA and of monomers released in large quantities at very low doses. The effects of observed BPA varied significantly (toxic and carcinogenic potential) while some studies found no effects at all. The relatively small number of studies dealing with the release of Bisphenol A by orthodontic materials, apart from orthodontic materials and their significant biological effects, has led to the absence of standard protocols and has hindered precise determination of released BPA. Moreover, the lack of coherence between the various methodological approaches and variations in the experimental protocols have resulted in a low level of proof regarding the impact of BPA by orthodontic materials. Through this study, the authors encourage clinicians to observe the following recommendations designed to reduce the amount of BPA released by materials used in orthodontics: keep the tip of the light-curing lamp as close as possible to the composite and perform indirect rather than direct light-curing; Pumice-polish the composite after bonding so as to reduce the potential amount of BPA released; reduce exposure by brushing or rinsing with a mouthwash during the first hour after bonding; follow a standardized, reproducible and expert-validated research protocol aimed at better understanding of BPA release. Copyright © 2016 CEO. Published by Elsevier Masson SAS. All rights reserved.

  11. VizieR Online Data Catalog: L and T dwarfs from UKIDSS LAS (Marocco+, 2015)

    NASA Astrophysics Data System (ADS)

    Marocco, F.; Jones, H. R. A.; Day-Jones, A. C.; Pinfield, D. J.; Lucas, P. W.; Burningham, B.; Zhang, Z. H.; Smart, R. L.; Gomes, J. I.; Smith, L.

    2015-11-01

    The objects presented here have been selected from the UKIDSS LAS 7th Data Release. The details of the selection criteria can be found in Day-Jones et al. (2013, Cat. J/MNRAS/430/1171, hereafter ADJ13). (5 data files).

  12. 45 CFR 671.7 - General issuance criteria.

    Code of Federal Regulations, 2010 CFR

    2010-10-01

    ... making this decision, the Director will carefully consider any comments or suggestions received from... wastes may be issued only if, based on relevant available information, the Director determines that such use or release will not pose a substantial hazard to health or the environment, taking into account...

  13. A combined chitosan/nano-size hydroxyapatite system for the controlled release of icariin.

    PubMed

    Fan, Junjun; Bi, Long; Wu, Tao; Cao, Liangguo; Wang, Dexin; Nan, Kaihui; Chen, Jingdi; Jin, Dan; Jiang, Shan; Pei, Guoxian

    2012-02-01

    Icariin, a plant-derived flavonol glycoside, has been proved as an osteoinductive agent for bone regeneration. For this reason, we developed an icariin-loaded chitosan/nano-sized hydroxyapatite (IC-CS/HA) system which controls the release kinetics of icariin to enhance bone repairing. First, by Fourier transform infrared spectroscopy, we found that icariin was stable in the system developed without undergoing any chemical changes. On the other hand, X-ray diffraction, scanning electron microscopy and mechanical test revealed that the introduction of icariin did not remarkably change the phase, morphology, porosity and mechanical strength of the CS/HA composite. Then the hydrolytic degradation and drug release kinetics in vitro were investigated by incubation in phosphate buffered saline solution. The results indicated that the icariin was released in a temporally controlled manner and the release kinetics could be governed by degradation of both chitosan and hydroxyapatite matrix. Finally the in vitro bioactivity assay revealed that the loaded icariin was biologically active as evidenced by stimulation of bone marrow derived stroma cell alkaline phosphatase activity and formation of mineralized nodules. This successful IC-CS/HA system offers a new delivery method of osteoinductive agents and a useful scaffold design for bone regeneration.

  14. Impact of Decision Criteria on Federal Aviation Administration Certification of Military Commercial Derivative Aircraft

    DTIC Science & Technology

    2012-03-01

    Capt Low was a member of the Sigma Iota Epsilon professional management fraternity. He has performed as an on-equipment and off-equipment...FAA Certification, Military Commercial Derivative Aircraft, Multi-Attribute Decision Making 16. SECURITY CLASSIFICATION OF: 17. LIMITATION OF

  15. Comparison of Species Sensitivity Distributions Derived from Interspecies Correlation Models to Distributions used to Derive Water Quality Criteria

    EPA Science Inventory

    Species sensitivity distributions (SSD) require a large number of measured toxicity values to define a chemical’s toxicity to multiple species. This investigation comprehensively evaluated the accuracy of SSDs generated from toxicity values predicted from interspecies correlation...

  16. Equivalence of Gyn GEC-ESTRO guidelines for image guided cervical brachytherapy with EUD-based dose prescription

    PubMed Central

    2013-01-01

    Background To establish a generalized equivalent uniform dose (gEUD) -based prescription method for Image Guided Brachytherapy (IGBT) that reproduces the Gyn GEC-ESTRO WG (GGE) prescription for cervix carcinoma patients on CT images with limited soft tissue resolution. Methods The equivalence of two IGBT planning approaches was investigated in 20 patients who received external beam radiotherapy (EBT) and 5 concomitant high dose rate IGBT treatments. The GGE planning strategy based on dose to the most exposed 2 cm3 (D2cc) was used to derive criteria for the gEUD-based planning of the bladder and rectum. The safety of gEUD constraints in terms of GGE criteria was tested by maximizing dose to the gEUD constraints for individual fractions. Results The gEUD constraints of 3.55 Gy for the rectum and 5.19 Gy for the bladder were derived. Rectum and bladder gEUD-maximized plans resulted in D2cc averages very similar to the initial GGE criteria. Average D2ccs and EUDs from the full treatment course were comparable for the two techniques within both sets of normal tissue constraints. The same was found for the tumor doses. Conclusions The derived gEUD criteria for normal organs result in GGE-equivalent IGBT treatment plans. The gEUD-based planning considers the entire dose distribution of organs in contrast to a single dose-volume-histogram point. PMID:24225184

  17. Correlation of in Vitro Cytokine Responses with the Chemical Composition of Soil-Derived Particulate Matter

    PubMed Central

    Veranth, John M.; Moss, Tyler A.; Chow, Judith C.; Labban, Raed; Nichols, William K.; Walton, John C.; Watson, John G.; Yost, Garold S.

    2006-01-01

    We treated human lung epithelial cells, type BEAS-2B, with 10–80 μg/cm2 of dust from soils and road surfaces in the western United States that contained particulate matter (PM) < 2.5 μm aerodynamic diameter. Cell viability and cytokine secretion responses were measured at 24 hr. Each dust sample is a complex mixture containing particles from different minerals mixed with biogenic and anthropogenic materials. We determined the particle chemical composition using methods based on the U.S. Environmental Protection Agency Speciation Trends Network (STN) and the National Park Service Interagency Monitoring of Protected Visual Environments (IMPROVE) network. The functionally defined carbon fractions reported by the ambient monitoring networks have not been widely used for toxicology studies. The soil-derived PM2.5 from different sites showed a wide range of potency for inducing the release of the proinflammatory cytokines interleukin-6 (IL-6) and IL-8 in vitro. Univariate regression and multivariate redundancy analysis were used to test for correlation of viability and cytokine release with the concentrations of 40 elements, 7 ions, and 8 carbon fractions. The particles showed positive correlation between IL-6 release and the elemental and pyrolyzable carbon fractions, and the strongest correlation involving crustal elements was between IL-6 release and the aluminum:silicon ratio. The observed correlations between low-volatility organic components of soil- and road-derived dusts and the cytokine release by BEAS-2B cells are relevant for investigation of mechanisms linking specific air pollution particle types with the initiating events leading to airway inflammation in sensitive populations. PMID:16507455

  18. Severity of Organized Item Theft in Computerized Adaptive Testing: An Empirical Study. Research Report. ETS RR-06-22

    ERIC Educational Resources Information Center

    Yi, Qing; Zhang, Jinming; Chang, Hua-Hua

    2006-01-01

    Chang and Zhang (2002, 2003) proposed several baseline criteria for assessing the severity of possible test security violations for computerized tests with high-stakes outcomes. However, these criteria were obtained from theoretical derivations that assumed uniformly randomized item selection. The current study investigated potential damage caused…

  19. FURTHER REFINEMENTS AND TESTING OF APEX3.0: EPA'S POPULATION EXPOSURE MODEL FOR CRITERIA AND AIR TOXIC INHALATION

    EPA Science Inventory

    The Air Pollutants Exposure Model (APEX(3.0)) is a PC-based model that was derived from the probabilistic NAAQS Exposure Model for carbon monoxide (pNEM/CO). APEX will be one of the tools used to estimate human population exposure for criteria and air toxic pollutants as part ...

  20. Recommended Interim Criteria for Three Environmental Polluting Compounds of Rocky Mountain Arsenal

    DTIC Science & Technology

    1984-10-01

    derivation ox criteria will have to be assessed. All the criLeria recommended herein are also subject to change when any new scientific data on the...weight, it follows that dhuman/ danimal - (WE/WA)/ and dhuman/WH = (W 1/3 Sanimal/WA where WH = average body weight for a human adult, 70 kg WA - average

  1. Components in Plasma-Derived Factor VIII, But Not in Recombinant Factor VIII Downregulate Anti-Inflammatory Surface Marker CD163 in Human Macrophages through Release of CXCL4 (Platelet Factor 4)

    PubMed Central

    Bertling, Anne; Brodde, Martin F.; Visser, Mayken; Treffon, Janina; Fennen, Michelle; Fender, Anke C.; Kelsch, Reinhard; Kehrel, Beate E.

    2017-01-01

    Background Hemarthrosis, or bleeding into the joints, is a hallmark of hemophilia. Heme triggers oxidative stress, inflammation, and destruction of cartilage and bone. The haptoglobin-CD163-heme oxygenase-1 (HO-1) pathway circumvents heme toxicity through enzymatic degradation of heme and transcription of antioxidant genes. Plasma-derived factor concentrates contain many proteins that might impact on cellular pathways in joints, blood, and vessels. Methods Activation of platelets from healthy volunteers was assessed by flow cytometry analysis of fibrinogen binding and CD62P expression. Platelet CXCL4 release was measured by ELISA. Human peripheral blood mononuclear cells were exposed to CXCL4 or platelet supernatants (untreated or pre-stimulated with factor VIII (FVIII) products) during their differentiation to macrophages and analyzed for CD163 expression. Some macrophage cultures were additionally incubated with autologous hemoglobin for 18 h for analysis of HO-1 expression. Results Platelet CXCL4 release was increased by all 8 tested plasma-derived FVIII products but not the 3 recombinant products. Macrophages exposed to supernatant from platelets treated with some plasma-derived FVIII products downregulated CD163 surface expression and failed to upregulate the athero- and joint protective enzyme HO-1 in response to hemoglobin. Conclusion Plasma-derived FVIII products might promote bleeding-induced joint injury via generation of macrophages that are unable to counteract redox stress. PMID:29070980

  2. Fractal Model of Fission Product Release in Nuclear Fuel

    NASA Astrophysics Data System (ADS)

    Stankunas, Gediminas

    2012-09-01

    A model of fission gas migration in nuclear fuel pellet is proposed. Diffusion process of fission gas in granular structure of nuclear fuel with presence of inter-granular bubbles in the fuel matrix is simulated by fractional diffusion model. The Grunwald-Letnikov derivative parameter characterizes the influence of porous fuel matrix on the diffusion process of fission gas. A finite-difference method for solving fractional diffusion equations is considered. Numerical solution of diffusion equation shows correlation of fission gas release and Grunwald-Letnikov derivative parameter. Calculated profile of fission gas concentration distribution is similar to that obtained in the experimental studies. Diffusion of fission gas is modeled for real RBMK-1500 fuel operation conditions. A functional dependence of Grunwald-Letnikov derivative parameter with fuel burn-up is established.

  3. Host-guest chemistry of cyclodextrin carbamates and cellulose derivatives in aqueous solution.

    PubMed

    Guo, Xin; Jia, Xiangxiang; Du, Jiaojiao; Xiao, Longqiang; Li, Feifei; Liao, Liqiong; Liu, Lijian

    2013-10-15

    Supramolecular polymer micelles were prepared on basis of the inclusion complexation between cyclodextrin carbamates and cellulose derivatives in aqueous media. Cyclodextrin carbamates were synthesized by microwave-assisted method from cyclodextrin and urea. The urea modified cyclodextrin shows the higher yield than the physical mixture of urea/cyclodextrin in the micellization with cellulose derivatives. The supramolecular structure of the core-shell micelles was demonstrated by (1)H NMR spectra, TEM images, and fluorescence spectra. The drug release behavior of the supramolecular polymer micelles was evaluated using prednisone acetate as a model drug. The drug loaded micelles showed steady and long time drug release behavior. With these properties, the supramolecular polymer micelles are attractive as drug carriers for pharmaceutical applications. Copyright © 2013 Elsevier Ltd. All rights reserved.

  4. Registration of 'Dan' winter hulless barley

    USDA-ARS?s Scientific Manuscript database

    Dan’ (Reg. No. CV- , PI 659066) six-rowed winter hulless barley (Hordeum vulgare L.) was developed and released by the Virginia Agricultural Experiment Station in March 2009. Dan was derived from the cross VA96-41-17 / SC872143. It was released for production in the eastern United States, as a poten...

  5. DSCOVR EPIC L2 VESDR V1 Product Announcement

    Atmospheric Science Data Center

    2018-06-13

    ... Boston University announce the public release of Vegetation Earth System Data Record (VESDR) derived from the Earth Polychromatic Imaging ... derived products.   We also provide two ancillary science data products, namely, 10 km Land Cover Type and Distribution of ...

  6. Implementation of the analytical hierarchy process with VBA in ArcGIS

    NASA Astrophysics Data System (ADS)

    Marinoni, Oswald

    2004-07-01

    Decisions on landuse have become progressively more difficult in the last decades. The main reasons for this development lie in the increasing population combined with an increasing demand for new land and resources and in the growing consciousness for sustainable land and resource use. The steady reduction of valuable land leads to an increase of conflicts in land use decision-making processes since more interests are being affected and therefore more stakeholders with different land use interests and different valuation criteria are being involved in the decision-making process. In the course of such a decision process all identified criteria are weighted according to their relative importance. But assigning weights to the relevant criteria quickly becomes a difficult task when a greater number of criteria are being considered, especially with regard to land use decisions where decision makers expect some kind of mapped result it is therefore useful to use procedures that not only help to derive criteria weights but also accelerate the visualisation and mapping of land use assessment results. Both aspects can easily be facilitated in a GIS. This paper focuses the development of an ArcGIS VBA macro which enables the user to derive criteria weights with the analytical hierarchy process and which allows a mapping of the land use assessment results by a weighted summation of GIS raster data sets. A dynamic link library for the calculation of the eigenvalues and eigenvectors of a square matrix is provided.

  7. Subsumption principles underlying medical concept systems and their formal reconstruction.

    PubMed Central

    Bernauer, J.

    1994-01-01

    Conventional medical concept systems represent generic concept relations by hierarchical coding principles. Often, these coding principles constrain the concept system and reduce the potential for automatical derivation of subsumption. Formal reconstruction of medical concept systems is an approach that bases on the conceptual representation of meanings and that allows for the application of formal criteria for subsumption. Those criteria must reflect intuitive principles of subordination which are underlying conventional medical concept systems. Particularly these are: The subordinate concept results (1) from adding a specializing criterion to the superordinate concept, (2) from refining the primary category, or a criterion of the superordinate concept, by a concept that is less general, (3) from adding a partitive criterion to a criterion of the superordinate, (4) from refining a criterion by a concept that is less comprehensive, and finally (5) from coordinating the superordinate concept, or one of its criteria. This paper introduces a formalism called BERNWARD that aims at the formal reconstruction of medical concept systems according to these intuitive principles. The automatical derivation of hierarchical relations is primarily supported by explicit generic and explicit partititive hierarchies of concepts, secondly, by two formal criteria that base on the structure of concept descriptions and explicit hierarchical relations between their elements, namely: formal subsumption and part-sensitive subsumption. Formal subsumption takes only generic relations into account, part-sensitive subsumption additionally regards partive relations between criteria. This approach seems to be flexible enough to cope with unforeseeable effects of partitive criteria on subsumption. PMID:7949907

  8. Arachidonic acid and prostaglandin endoperoxide metabolism in isolated rabbit and coronary microvessels and isolated and cultivated coronary microvessel endothelial cells.

    PubMed Central

    Gerritsen, M E; Cheli, C D

    1983-01-01

    Isolated microvessels and isolated and cultured microvessel endothelial cells were prepared from rabbit cardiac muscle. Pathways of arachidonic acid metabolism were determined by measurement of exogenous substrate utilization [( 1-14C]arachidonic acid incorporation and release from intact tissue and cells; [1-14C]prostaglandin H2 (PGH2) metabolism by broken cell preparations) and by quantification of endogenous products (immunoreactive 6-keto-prostaglandin F1 alpha (PGF1 alpha) and prostaglandin E (PGE) release) by selective radioimmunoassay. Rabbit coronary microvessels and derived microvascular endothelial cells (RCME cells) synthesized two major products of the cyclooxygenase pathway: 6-keto-PGF1 alpha (hydrolytic product of prostaglandin I2) and PGE2. A reduced glutathione requiring PGH-E isomerase was demonstrated in coronary microvessels and RCME cells, but not in rabbit circumflex coronary artery or aorta. In addition, a minor amount of a compound exhibiting similar characteristics to 6-keto-PGE1 was found to be produced by microvessels and RCME cells. Measurement of endogenously released prostaglandins indicated that under basal and stimulated conditions, PGE release exceeded that of 6-keto-PGF1 alpha. Microvessels and microvessel endothelial cells derived from cardiac muscle of rabbit exhibit pathways of arachidonate metabolism that are different from those of many large blood vessels and derived endothelial cells. Images PMID:6415116

  9. Strain energy release rate analysis of the end-notched flexure specimen using the finite-element method

    NASA Technical Reports Server (NTRS)

    Salpekar, S. A.; Raju, I. S.; O'Brien, T. K.

    1988-01-01

    Two-dimensional finite-element analysis of the end-notched flexure specimen was performed using 8-node isoparametric, parabolic elements to evaluate compliance and mode II strain energy release rates, G sub II. The G sub II values were computed using two different techniques: the virtual crack-closure technique (VCCT) and the rate of change of compliance with crack length (compliance derivative method). The analysis was performed for various crack-length-to-semi-span (a/L) ratios ranging from 0.2 to 0.9. Three material systems representing a wide range of material properties were analyzed. The compliance and strain energy release rates of the specimen calculated with the present finite-element analysis agree very well with beam theory equations including transverse shear. The G sub II values calculated using the compliance derivative method compared extremely well with those calculated using the VCCT. The G sub II values obtained by the compliance derivative method using the top or bottom beam deflections agreed closely with each other. The strain energy release rates from a plane-stress analysis were higher than the plane-strain values by only a small percentage, indicating that either assumption may be used in the analysis. The G sub II values for one material system calculated from the finte-element analysis agreed with one solution in the literature and disagreed with the other solution in the literature.

  10. Strain-energy-release rate analysis of the end-notched flexure specimen using the finite-element method

    NASA Technical Reports Server (NTRS)

    Salpekar, S. A.; Raju, I. S.; Obrien, T. K.

    1987-01-01

    Two-dimensional finite-element analysis of the end-notched flexure specimen was performed using 8-node isoparametric, parabolic elements to evaluate compliance and mode II strain energy release rates, G sub II. The G sub II values were computed using two different techniques: the virtural crack-closure technique (VCCT) and the rate of change of compliance with crack length (compliance derivative method). The analysis was performed for various crack-length-to-semi-span (a/L) ratios ranging from 0.2 to 0.9. Three material systems representing a wide range of material properties were analyzed. The compliance and strain energy release rates of the specimen calculated with the present finite-element analysis agree very well with beam theory equations including transverse shear. The G sub II values calculated using the compliance derivative method compared extremely well with those calculated using the VCCT. The G sub II values obtained by the compliance derivative method using the top or bottom beam deflections agreed closely with each other. The strain energy release rates from a plane-stress analysis were higher than the plane-strain values by only a small percentage, indicating that either assumption may be used in the analysis. The G sub II values for one material system calculated from the finite-element analysis agreed with one solution in the literature and disagreed with the other solution in the literature.

  11. A Selection of Nitric Oxide-Releasing Materials Incorporating S-Nitrosothiols

    NASA Astrophysics Data System (ADS)

    Lutzke, Alec

    Nitric oxide (NO) is a diatomic radical that occurs as a crucial component of mammalian biochemistry. As a signaling molecule, NO participates in the regulation of vascular tone and maintains the natural antithrombotic function of the healthy endothelium. Furthermore, NO is produced by phagocytes as part of the immune response, and exhibits both antimicrobial and wound-healing effects. In combination, these beneficial properties have led to the use of exogenous NO as a multifunctional therapeutic agent. However, the comparatively short half-life of NO under physiological conditions often renders systemic administration infeasible. This limitation is addressed by the use of NO-releasing polymeric materials, which permit the localized delivery of NO directly at the intended site of action. Such polymers have been utilized in the development of antithrombotic or antibacterial materials for biointerfacial applications, including tissue engineering and the fabrication of medical devices. NO release from polymers has most frequently been achieved through the incorporation of functional groups that are susceptible to NO-forming chemical decomposition in response to appropriate environmental stimuli. While numerous synthetic sources of NO are known, the S-nitrosothiol (RSNO) functional group occurs naturally in the form of S-nitrosocysteine residues in both proteins and small molecule species such as S-nitrosoglutathione. RSNOs are synthesized directly from thiol precursors, and their NO-forming decay has generally been established to produce the corresponding disulfide as a relatively benign organic byproduct. For these reasons, RSNOs have been conscripted as practical NO donors within a physiological environment. This dissertation describes the synthesis and characterization of RSNO-based NO-releasing polymers derived from the polysaccharides chitin and chitosan, as well as the development of amino acid ester-based NO-releasing biodegradable poly(organophosphazenes) (POPs). The broad use of chitin and chitosan in the development of materials for tissue engineering and wound treatment results in a significant overlap with the therapeutic properties of NO. NO-releasing derivatives of chitin and chitosan were prepared through partial substitution of the carbohydrate hydroxyl groups with the symmetrical dithiols 1,2-ethanedithiol, 1,3-propanedithiol, and 1,6-hexanedithiol, followed by S-nitrosation. Similarly, thiol-bearing polyphosphazenes were synthesized and used to produce NO-releasing variants. Polyphosphazenes are a unique polymer class possessing an inorganic backbone composed of alternating phosphorus and nitrogen atoms, and hydrolytically-sensitive POP derivatives with organic substituents have been prepared with distinctive physical and chemical properties. Although POPs have been evaluated as biomaterials, their potential as NO release platforms has not been previous explored. This work describes the development of NO-releasing biodegradable POPs derived from both the ethyl ester of L-cysteine and the 3-mercapto-3-methylbutyl ester of glycine. The NO release properties of all polymers were evaluated at physiological temperature and pH, and the results suggested potential suitability in future biomaterials applications.

  12. Role of external and internal calcium on heterocarrier-mediated transmitter release.

    PubMed

    Fassio, A; Bonanno, G; Fontana, G; Usai, C; Marchi, M; Raiteri, M

    1996-04-01

    Release-regulating heterocarriers exist on brain nerve endings. We have investigated in this study the mechanisms involved in the neurotransmitter release evoked by GABA heterocarrier activation. GABA increased the basal release of [3H]acetylcholine and [3H]noradrenaline from rat hippocampal synaptosomes and of [3H]dopamine from striatal synaptosomes. These GABA effects, insensitive to GABA receptor antagonists, were prevented by inhibiting GABA uptake but not by blocking noradrenaline, choline, or dopamine transport. Lack of extracellular Ca2+ or addition of tetrodotoxin selectively abolished the GABA-evoked release of [3H]noradrenaline, leaving unaffected that of [3H]acetylcholine or [3H]dopamine. 1,2-Bis(2-aminophenoxyl)-ethane-N,N,N',N'-tetraacetic acid acetoxymethyl ester (BAPTA-AM) or vesamicol attenuated the release of [3H]acetylcholine elicited by GABA. Reserpine, but not BAPTA-AM, prevented the effect of GABA on [3H] dopamine release. Autoreceptor activation inhibited the GABA-evoked release of [3H]noradrenaline but not that of [3H]acetylcholine or [3H]dopamine. It is concluded that (a) the release of [3H]noradrenaline consequent to activation of GABA heterocarriers sited on noradrenergic terminals meets the criteria of a conventional exocytotic process, (b) the extracellular [Ca2+]-independent releases of [3H]acetylcholine and [3H]dopamine appear to occur from vesicles possibly through involvement of intraterminal Ca2+, and (c) autoreceptor activation only affects heterocarrier-mediated vesicular release linked to entry of extracellular Ca2+.

  13. 75 FR 37445 - Agency Forms Undergoing Paperwork Reduction Act Review

    Federal Register 2010, 2011, 2012, 2013, 2014

    2010-06-29

    ... released from jail/prison and meet screening criteria. The interviews will identify their attitudes towards... identify variables for a survey that will examine attitudes towards HIV testing, socio-cultural norms, and... DEPARTMENT OF HEALTH AND HUMAN SERVICES Centers for Disease Control and Prevention [30Day-10-09CJ...

  14. 40 CFR 262.104 - What are the minimum performance criteria?

    Code of Federal Regulations, 2010 CFR

    2010-07-01

    ... XL Project-Laboratory Environmental Management Standard § 262.104 What are the minimum performance... container management. (f) The management of laboratory waste must not result in the release of hazardous... waste management program approved under 40 CFR part 271) if it is determined in the laboratory by the...

  15. 40 CFR 260.34 - Standards and criteria for non-waste determinations.

    Code of Federal Regulations, 2010 CFR

    2010-07-01

    ... reasonable time frame and ensure that the hazardous secondary material will not be abandoned (for example... statistical or from a health and environmental risk perspective than would otherwise be released by the... hazardous secondary material in a reasonable time frame and ensure that the hazardous secondary material...

  16. AIR QUALITY CRITERIA FOR PARTICULATE MATTER DOCUMENT

    EPA Science Inventory

    A Planning Document was produced by NCEA/RTP and reviewed by the Clean Air Scientific Advisory Committee (CASAC) (62 FR 55201, October 23, 1997). In FY99, a workshop draft of the PM AQCD was completed, a peer input workshop held, and an External Review Draft released for public ...

  17. 10 CFR Appendix B to Part 50 - Quality Assurance Criteria for Nuclear Power Plants and Fuel Reprocessing Plants

    Code of Federal Regulations, 2012 CFR

    2012-01-01

    ... executing. III. Design Control Measures shall be established to assure that applicable regulatory... control of design interfaces and for coordination among participating design organizations. These measures..., approval, release, distribution, and revision of documents involving design interfaces. The design control...

  18. 10 CFR Appendix B to Part 50 - Quality Assurance Criteria for Nuclear Power Plants and Fuel Reprocessing Plants

    Code of Federal Regulations, 2013 CFR

    2013-01-01

    ... executing. III. Design Control Measures shall be established to assure that applicable regulatory... control of design interfaces and for coordination among participating design organizations. These measures..., approval, release, distribution, and revision of documents involving design interfaces. The design control...

  19. 32 CFR 310.23 - Disclosures to commercial enterprises.

    Code of Federal Regulations, 2010 CFR

    2010-07-01

    ... 32 National Defense 2 2010-07-01 2010-07-01 false Disclosures to commercial enterprises. 310.23... Third Parties § 310.23 Disclosures to commercial enterprises. (a) General policy. (1) Make releases of personal information to commercial enterprises under the criteria established by 32 CFR part 286. (2) The...

  20. Exploring the Perception of Asperger's Disorder

    ERIC Educational Resources Information Center

    Kite, Donna M.; Tyson, Graham A.; Gullifer, Judith M.

    2011-01-01

    With current preparation for the release of the fifth edition of the "Diagnostic and Statistical Manual of Mental Disorders" (DSM-5) in 2013, many changes have been proposed for the diagnostic criteria, including changes to the pervasive development disorder category--of which Asperger's disorder is a part. Using focus group discussions…

  1. [Correspondence between advances of dental composites and adhesives and clinical guidelines for direct restorations].

    PubMed

    Wang, X Y; Yue, L

    2018-06-09

    The longevity of direct adhesive restoration is related to the restorative materials, the patient and the professional. On one hand, dental composites/adhesives have been modified and developed to fulfill the criteria for clinical application. On the other hand, the clinical guidelines for adhesive restorations have been released and updated accordingly, which would prolong the longevity of restorations. In this commentary, the removal of carious tissues, interface preparation for bonding and application of adhesives are emphasized. The administrative measures for registration and clinical evaluation criteria for adhesive restorative material are also introduced.

  2. Treatment of three patients with systemic mastocytosis with interferon alpha-2b.

    PubMed

    Worobec, A S; Kirshenbaum, A S; Schwartz, L B; Metcalfe, D D

    1996-08-01

    It has been reported that the administration of interferon alpha-2b is of potential benefit in the treatment of mastocytosis based on a single patient study (NEJM, Feb 27, 1992, 326(9):619-623). Following this report, we administered interferon alpha-2b at a dose of 4 to 5 million units per square meter of body surface area for at least 12 months to one patient with mastocytosis with an associated hematologic disorder (patient 1), one patient with aggressive systemic mastocytosis (patient 2), and one patient with indolent mastocytosis (patient 3). Patients were monitored with the following clinical and laboratory parameters: serial bone marrow biopsies and aspirates, patient log of histamine release attacks, medication dependency, plasma tryptase levels, serum lactate dehydrogenase (LDH) levels, white blood cell counts and differentials, extent of urticaria pigmentosa lesions, bony involvement, and extent of gastrointestinal involvement and hepatomegaly. We also examined the ability of interferon alpha-2b to inhibit recombinant human stem cell factor (rhSCF)-dependent mast cell proliferation from CD34+ bone marrow-derived cells. All patients demonstrated continued progression of disease in one or more clinical criteria at one year of therapy. Similarly, interferon alpha-2b did not inhibit the culture of mast cells from CD34+ bone marrow-derived cells in the presence of SCF. Thus, in our study of three patients with systemic mastocytosis, treatment with interferon alpha-2b was found to be ineffective in controlling progression of disease.

  3. 3,4-Methylenedioxyamphetamine (MDA) analogues exhibit differential effects on synaptosomal release of 3H-dopamine and 3H-5-hydroxytryptamine

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

    McKenna, D.J.; Guan, X.M.; Shulgin, A.T.

    1991-03-01

    The effect of various analogues of the neurotoxic amphetamine derivative, MDA (3,4-methylenedioxyamphetamine) on carrier-mediated, calcium-independent release of 3H-5-HT and 3H-DA from rat brain synaptosomes was investigated. Both enantiomers of the neurotoxic analogues MDA and MDMA (3,4-methylenedioxymethamphetamine) induce synaptosomal release of 3H-5-HT and 3H-DA in vitro. The release of 3H-5-HT induced by MDMA is partially blocked by 10(-6) M fluoxetine. The (+) enantiomers of both MDA and MDMA are more potent than the (-) enantiomers as releasers of both 3H-5-HT and 3H-DA. Eleven analogues, differing from MDA with respect to the nature and number of ring and/or side chain substituents, alsomore » show some activity in the release experiments, and are more potent as releasers of 3H-5-HT than of 3H-DA. The amphetamine derivatives {plus minus}fenfluramine, {plus minus}norfenfluramine, {plus minus}MDE, {plus minus}PCA, and d-methamphetamine are all potent releasers of 3H-5-HT and show varying degrees of activity as 3H-DA releasers. The hallucinogen DOM does not cause significant release of either 3H-monoamine. Possible long-term serotonergic neurotoxicity was assessed by quantifying the density of 5-HT uptake sites in rats treated with multiple doses of selected analogues using 3H-paroxetine to label 5-HT uptake sites. In the neurotoxicity study of the compounds investigated, only (+)MDA caused a significant loss of 5-HT uptake sites in comparison to saline-treated controls. These results are discussed in terms of the apparent structure-activity properties affecting 3H-monoamine release and their possible relevance to neurotoxicity in this series of MDA congeners.« less

  4. Vascular smooth muscle cell calcification is mediated by regulated exosome secretion.

    PubMed

    Kapustin, Alexander N; Chatrou, Martijn L L; Drozdov, Ignat; Zheng, Ying; Davidson, Sean M; Soong, Daniel; Furmanik, Malgorzata; Sanchis, Pilar; De Rosales, Rafael Torres Martin; Alvarez-Hernandez, Daniel; Shroff, Rukshana; Yin, Xiaoke; Muller, Karin; Skepper, Jeremy N; Mayr, Manuel; Reutelingsperger, Chris P; Chester, Adrian; Bertazzo, Sergio; Schurgers, Leon J; Shanahan, Catherine M

    2015-04-10

    Matrix vesicles (MVs), secreted by vascular smooth muscle cells (VSMCs), form the first nidus for mineralization and fetuin-A, a potent circulating inhibitor of calcification, is specifically loaded into MVs. However, the processes of fetuin-A intracellular trafficking and MV biogenesis are poorly understood. The objective of this study is to investigate the regulation, and role, of MV biogenesis in VSMC calcification. Alexa488-labeled fetuin-A was internalized by human VSMCs, trafficked via the endosomal system, and exocytosed from multivesicular bodies via exosome release. VSMC-derived exosomes were enriched with the tetraspanins CD9, CD63, and CD81, and their release was regulated by sphingomyelin phosphodiesterase 3. Comparative proteomics showed that VSMC-derived exosomes were compositionally similar to exosomes from other cell sources but also shared components with osteoblast-derived MVs including calcium-binding and extracellular matrix proteins. Elevated extracellular calcium was found to induce sphingomyelin phosphodiesterase 3 expression and the secretion of calcifying exosomes from VSMCs in vitro, and chemical inhibition of sphingomyelin phosphodiesterase 3 prevented VSMC calcification. In vivo, multivesicular bodies containing exosomes were observed in vessels from chronic kidney disease patients on dialysis, and CD63 was found to colocalize with calcification. Importantly, factors such as tumor necrosis factor-α and platelet derived growth factor-BB were also found to increase exosome production, leading to increased calcification of VSMCs in response to calcifying conditions. This study identifies MVs as exosomes and shows that factors that can increase exosome release can promote vascular calcification in response to environmental calcium stress. Modulation of the exosome release pathway may be as a novel therapeutic target for prevention. © 2015 American Heart Association, Inc.

  5. A Polymeric Prodrug of 5-Fluorouracil-1-Acetic Acid Using a Multi-Hydroxyl Polyethylene Glycol Derivative as the Drug Carrier

    PubMed Central

    Sun, Xun; Gong, Tao; Zhang, Zhirong

    2014-01-01

    Purpose Macromolecular prodrugs obtained by covalently conjugating small molecular drugs with polymeric carriers were proven to accomplish controlled and sustained release of the therapeutic agents in vitro and in vivo. Polyethylene glycol (PEG) has been extensively used due to its low toxicity, low immunogenicity and high biocompatibility. However, for linear PEG macromolecules, the number of available hydroxyl groups for drug coupling does not change with the length of polymeric chain, which limits the application of PEG for drug conjugation purposes. To increase the drug loading and prolong the retention time of 5-fluorouracil (5-Fu), a macromolecular prodrug of 5-Fu, 5-fluorouracil-1 acid-PAE derivative (5-FA-PAE) was synthesized and tested for the antitumor activity in vivo. Methods PEG with a molecular weight of 38 kDa was selected to synthesize the multi-hydroxyl polyethylene glycol derivative (PAE) through an addition reaction. 5-fluorouracil-1 acetic acid (5-FA), a 5-Fu derivative was coupled with PEG derivatives via ester bond to form a macromolecular prodrug, 5-FA-PAE. The in vitro drug release, pharmacokinetics, in vivo distribution and antitumor effect of the prodrug were investigated, respectively. Results The PEG-based prodrug obtained in this study possessed an exceedingly high 5-FA loading efficiency of 10.58%, much higher than the maximum drug loading efficiency of unmodified PEG with the same molecular weight, which was 0.98% theoretically. Furthermore, 5-FA-PAE exhibited suitable sustained release in tumors. Conclusion This study provides a new approach for the development of the delivery to tumors of anticancer agents with PEG derivatives. PMID:25389968

  6. Potential of Phytase-Mediated Iron Release from Cereal-Based Foods: A Quantitative View

    PubMed Central

    Nielsen, Anne V. F.; Tetens, Inge; Meyer, Anne S.

    2013-01-01

    The major part of iron present in plant foods such as cereals is largely unavailable for direct absorption in humans due to complexation with the negatively charged phosphate groups of phytate (myo-inositol (1,2,3,4,5,6)-hexakisphosphate). Human biology has not evolved an efficient mechanism to naturally release iron from iron phytate complexes. This narrative review will evaluate the quantitative significance of phytase-catalysed iron release from cereal foods. In vivo studies have shown how addition of microbially derived phytases to cereal-based foods has produced increased iron absorption via enzyme-catalysed dephosphorylation of phytate, indicating the potential of this strategy for preventing and treating iron deficiency anaemia. Despite the immense promise of this strategy and the prevalence of iron deficiency worldwide, the number of human studies elucidating the significance of phytase-mediated improvements in iron absorption and ultimately in iron status in particularly vulnerable groups is still low. A more detailed understanding of (1) the uptake mechanism for iron released from partially dephosphorylated phytate chelates, (2) the affinity of microbially derived phytases towards insoluble iron phytate complexes, and (3) the extent of phytate dephosphorylation required for iron release from inositol phosphates is warranted. Phytase-mediated iron release can improve iron absorption from plant foods. There is a need for development of innovative strategies to obtain better effects. PMID:23917170

  7. Insulin secretion from isolated rat islets induced by the novel hypoglycemic agent A-4166, a derivative of D-phenylalanine.

    PubMed

    Tsukuda, K; Sakurada, M; Niki, I; Oka, Y; Kikuchi, M

    1998-01-01

    A derivative of D-phenylalanine, A-4166, reportedly evokes a more rapid and short-lived hypoglycemic action in vivo than any of the currently available sulfonylureas. This novel oral hypoglycemic agent is structurally different from sulfonylureas. Therefore, studies were designed to elucidate the mechanisms by which A-4166 stimulates insulin secretion. Insulin release from incubated or perifused rat islets was dose-dependently stimulated by 10 to 200 mumol/l A-4166, in the presence of 2.8 mmol/l glucose. Both A-4166 and tolbutamide evoke a prompt rise in insulin secretion followed by a sustained gradually decreasing release from perfused islets in the presence of low glucose, although A-4166 appeared to be more sensitive than tolbutamide to subthreshold glucose concentration. Diazoxide abolished the initial release and blunted sustained release. Removing calcium from the perifusate abolished insulin release within 15 minutes. A-4166 inhibited [3H]-glibenclamide binding to HIT cell membranes and 86Rb efflux from ATP-depleted or diazoxide-treated cells. These results suggest that the insulin release induced by A-4166 is relevant to this agent occupying the tolbutamide binding sites. Therefore, one possible mechanism accounting for the more rapid and short-lived hypoglycemic action of A-4166 in vivo, as compared with tolbutamide, may involve the reported differences in the bioavailability of A-4166.

  8. Molt patterns, age, and sex criteria for selected highland Costa Rican resident landbirds

    Treesearch

    Jared D. Wolfe; Richard B. Chandler; David I. King

    2009-01-01

    Demographic studies within temperate latitudes often use molt and plumage-based criteria to differentiate age and sex classes (Bayne & Hobson 2002, Brown et al. 2002, Jones et al. 2004). Despite their critical nature (Pyle et al. 2004, DuVal 2005, Doucet et al. 2007), molt and plumage data derived from resident tropical species remain scarce (Dickey & van...

  9. Controlled Release Strategies for Bone, Cartilage, and Osteochondral Engineering—Part I: Recapitulation of Native Tissue Healing and Variables for the Design of Delivery Systems

    PubMed Central

    Santo, Vítor E.; Mano, João F.; Reis, Rui L.

    2013-01-01

    The potential of growth factors to stimulate tissue healing through the enhancement of cell proliferation, migration, and differentiation is undeniable. However, critical parameters on the design of adequate carriers, such as uncontrolled spatiotemporal presence of bioactive factors, inadequate release profiles, and supraphysiological dosages of growth factors, have impaired the translation of these systems onto clinical practice. This review describes the healing cascades for bone, cartilage, and osteochondral interface, highlighting the role of specific growth factors for triggering the reactions leading to tissue regeneration. Critical criteria on the design of carriers for controlled release of bioactive factors are also reported, focusing on the need to provide a spatiotemporal control over the delivery and presentation of these molecules. PMID:23268651

  10. Deriving Freshwater Quality Criteria for Iron, Lead, Nickel, and Zinc for Protection of Aquatic Life in Malaysia

    PubMed Central

    Shuhaimi-Othman, M.; Nadzifah, Y.; Nur-Amalina, R.; Umirah, N. S.

    2012-01-01

    Freshwater quality criteria for iron (Fe), lead (Pb), nickel (Ni), and zinc (Zn) were developed with particular reference to aquatic biota in Malaysia, and based on USEPA's guidelines. Acute toxicity tests were performed on eight different freshwater domestic species in Malaysia which were Macrobrachium lanchesteri (prawn), two fish: Poecilia reticulata and Rasbora sumatrana, Melanoides tuberculata (snail), Stenocypris major (ostracod), Chironomus javanus (midge larvae), Nais elinguis (annelid), and Duttaphrynus melanostictus (tadpole) to determine 96 h LC50 values for Fe, Pb, Ni, and Zn. The final acute value (FAV) for Fe, Pb, Ni, and Zn were 74.5, 17.0, 165, and 304.9 μg L−1, respectively. Using an estimated acute-to-chronic ratio (ACR) of 8.3, the value for final chronic value (FCV) was derived. Based on FAV and FCV, a criterion maximum concentration (CMC) and a criterion continuous concentration (CCC) for Fe, Pb, Ni, and Zn that are 37.2, 8.5, 82.5, and 152.4 μg L−1 and 9.0, 2.0, 19.9, and 36.7 μg L−1, respectively, were derived. The results of this study provide useful data for deriving national or local water quality criteria for Fe, Pb, Ni, and Zn based on aquatic biota in Malaysia. Based on LC50 values, this study indicated that N. elinguis, M. lanchesteri, N. elinguis, and R. sumatrana were the most sensitive to Fe, Pb, Ni, and Zn, respectively. PMID:22919358

  11. Demonstrating Encapsulation and Release: A New Take on Alginate Complexation and the Nylon Rope Trick

    ERIC Educational Resources Information Center

    Friedli, Andrienne C.; Schlager, Inge R.; Wright, Stephen W.

    2005-01-01

    Three variations on a classroom demonstration of the encapsulation of droplets and evidence for release of the interior solution are described. The first two demonstrations mimic biocompatible applications of encapsulation. Reversible formation of capsules from aqueous solutions of sodium alginate, a negatively charged polysaccharide derived from…

  12. Release of ‘UI Platinum’ hard white spring wheat

    USDA-ARS?s Scientific Manuscript database

    ‘UI Platinum’ (Reg. No. CV------, PI 672533) hard white spring wheat (Triticum aestivum L.) was developed by the Idaho Agricultural Experiment Station and released in 2014. UI Platinum was derived from the cross ‘Blanca Grande’ x ‘Jerome’ and tested under experimental numbers A01178S, IDO694, and I...

  13. Impact of different environmental stimuli on the release of 1-MCP from boron-MCP complexes

    USDA-ARS?s Scientific Manuscript database

    In our previous report, boron derivatives of methylene cyclopropane complexes (B-MCP) were developed to stabilize the gaseous 1-MCP (1-methylcyclopropene), a commercial plant growth regulator, for eventual release in open crop fields when under humid conditions or in contact with water. To meet the ...

  14. Design, synthesis and biological evaluation of novel hydrogen sulfide releasing capsaicin derivatives.

    PubMed

    Gao, Mingxiang; Li, Jinyu; Nie, Cunbin; Song, Beibei; Yan, Lin; Qian, Hai

    2018-05-15

    Capsaicin (CAP), the prototypical TRPV1 agonist, is the major active component in chili peppers with health-promoting benefits. However, its use is limited by the low bioavailability and irritating quality. In this study, for improving the activity of CAP and alleviating its irritating effects, a series of H 2 S-releasing CAPs were designed and synthesized by combining capsaicin and dihydro capsaicin with various hydrogen sulfide donors. The resulting compounds were evaluated their TRPV1 agonist activity, analgesic activity, anticancer activities, H 2 S-releasing ability, and gastric mucosa irritation. Biological evaluation indicated that the most active compound B 9 , containing 5-(4-hydroxyphenyl)-3H-1,2-dithiole-3-thione moiety as H 2 S donor, had better analgesic activity and displayed more potent cytotoxic effects on the test cell lines than the lead compound CAP. Furthermore, the preferred compound, B 9 reduced rat gastric mucosa irritation caused by CAP. Notably, the improved properties of this derivative are associated with its H 2 S-releasing capability. Copyright © 2018 Elsevier Ltd. All rights reserved.

  15. Amino Acid Derivatives as Palmitoylethanolamide Prodrugs: Synthesis, In Vitro Metabolism and In Vivo Plasma Profile in Rats

    PubMed Central

    Vacondio, Federica; Bassi, Michele; Silva, Claudia; Castelli, Riccardo; Carmi, Caterina; Scalvini, Laura; Lodola, Alessio; Vivo, Valentina; Flammini, Lisa; Barocelli, Elisabetta; Mor, Marco; Rivara, Silvia

    2015-01-01

    Palmitoylethanolamide (PEA) has antinflammatory and antinociceptive properties widely exploited in veterinary and human medicine, despite its poor pharmacokinetics. Looking for prodrugs that could progressively release PEA to maintain effective plasma concentrations, we prepared carbonates, esters and carbamates at the hydroxyl group of PEA. Chemical stability (pH 7.4) and stability in rat plasma and liver homogenate were evaluated by in vitro assays. Carbonates and carbamates resulted too labile and too resistant in plasma, respectively. Ester derivatives, prepared by conjugating PEA with various amino acids, allowed to modulate the kinetics of PEA release in plasma and stability in liver homogenate. L-Val-PEA, with suitable PEA release in plasma, and D-Val-PEA, with high resistance to hepatic degradation, were orally administered to rats and plasma levels of prodrugs and PEA were measured at different time points. Both prodrugs showed significant release of PEA, but provided lower plasma concentrations than those obtained with equimolar doses of PEA. Amino-acid esters of PEA are a promising class to develop prodrugs, even if they need further chemical optimization. PMID:26053855

  16. Studies on `allergoids' prepared from naturally occurring allergens

    PubMed Central

    Marsh, D. G.; Lichtenstein, L. M.; Campbell, D. H.

    1970-01-01

    The highly purified major allergenic component of rye grass pollen (Group I) was used to investigate the possibility of destroying selectively the allergenic properties of an antigen, while largely retaining its original immunizing capacities. The allergen was treated under mild conditions with formalin alone or formalin plus a reactive low molecular weight additive. Certain derivatives (allergoids) showed well over 99 per cent reduction in allergenicity, determined by the histamine released from allergic human leucocytes in vitro, but were still able to combine with rabbit antibody against native antigen. Furthermore, the allergoids stimulated production (in guinea-pigs) of appreciable amounts of antibody able to inhibit native allergen-mediated human allergic histamine release in vitro and to cross-react with native antigen by PCA tests in normal guinea-pigs. Residual allergenicity and cross-immunogenicity (by the inhibition assay) of the different formalinized derivatives varied appreciably according to the additive used in formalinization, but the cross-reactivities of the different preparations in quantitative precipitin analysis against rabbit anti-native antigen serum were similar. The residual allergenicities of individual derivatives varied by up to 1000-fold in different cell preparations, suggesting a heterogeneity of allergenic determinants. Allergoid derivatives showed no hapten-like activity in that they were unable to inhibit allergen-mediated histamine release from leucocytes. The theoretical and practical application of allergoids is discussed, including their potential usefulness in improving the immunotheraphy of atopic humans. ImagesFIG. 2 PMID:4192674

  17. Differential MMP-9 activity in CD34⁺progenitor cell-derived foam cells from diabetic and normoglycemic patients.

    PubMed

    Schmohl, J U; Daub, K; von Ungern-Sternberg, S N I; Lindemann, S; Schönberger, T; Geisler, T; Gawaz, M; Seizer, P

    2015-05-01

    Upon coincubation with platelet aggregates, CD34(+) progenitor cells have the potential to differentiate into foam cells. There is evidence that progenitor cells from diabetic and nondiabetic patients have different properties, which may affect the patients' prognosis. In this study we investigated an in vitro model of foam cell formation based on patient-derived CD34(+) progenitor cells. We analyzed the growth characteristics as well as the M-CSF-release and matrix metalloproteinase (MMP) synthesis from CD34(+) progenitor cell-derived foam cells originating from diabetic and nondiabetic patients. Bone marrow samples were obtained from 38 patients who were elected for thoracic surgery. CD34(+) progenitor cells from diabetic and nondiabetic patients were isolated and incubated with platelets from healthy volunteers. Foam cell formation was confirmed by immunostaining (CD68) and quantified by light microscopy. Whereas the absolute number of foam cells was not affected, the negative slope in the growth curve was seen significantly later in the diabetic group. In supernatants derived from"diabetic" CD34(+) progenitor cells, MMP-9 was significantly enhanced, whereas MMP-2 activity or M-CSF-release was not affected significantly. In a coculture model of CD34(+) progenitor cells with platelets, we show for the first time that"diabetic" CD34(+) progenitor cells exhibit functional differences in their differentiation to foam cells concerning growth characteristics and release of MMP-9.

  18. Mechanisms and functions of extracellular vesicle release in vivo-What we can learn from flies and worms.

    PubMed

    Beer, Katharina B; Wehman, Ann Marie

    2017-03-04

    Cells from bacteria to man release extracellular vesicles (EVs) that contain signaling molecules like proteins, lipids, and nucleic acids. The content, formation, and signaling roles of these conserved vesicles are diverse, but the physiological relevance of EV signaling in vivo is still debated. Studies in classical genetic model organisms like C. elegans and Drosophila have begun to reveal the developmental and behavioral roles for EVs. In this review, we discuss the emerging evidence for the in vivo signaling roles of EVs. Significant effort has also been made to understand the mechanisms behind the formation and release of EVs, specifically of exosomes derived from exocytosis of multivesicular bodies and of microvesicles derived from plasma membrane budding called ectocytosis. In this review, we detail the impact of flies and worms on understanding the proteins and lipids involved in EV biogenesis and highlight the open questions in the field.

  19. AND logic-like pH- and light-dual controlled drug delivery by surface modified mesoporous silica nanoparticles.

    PubMed

    Zhao, Junwei; He, Zhaoshuai; Li, Biao; Cheng, Tanyu; Liu, Guohua

    2017-04-01

    Recently, the controlled drug delivery system has become a potential platform for biomedical application. Herein, we developed a pH and light-dual controlled cargo release system exhibiting AND logic based on MCM-41 mesoporous silica nanoparticles, which was surface modified using β-cyclodextrin (β-CD) with imine bond and azobenzene derivative. The complex of β-CD and azobenzene derivative effectively blocked the cargo delivery in pH=7.0 phosphate buffered saline (PBS) solution without 365nm UV light irradiation. The cargo was fully released when both factors of acidic environment (pH=5.0 PBS) and 365nm UV light irradiation were satisfied, meanwhile only very little cargo was delivered if one factor was satisfied. The result also demonstrates that the opening/closing of the gate and the release of the cargo in small portions can be controlled. Copyright © 2016 Elsevier B.V. All rights reserved.

  20. Approaches for derivation of environmental quality criteria for substances applied in risk assessment of discharges from offshore drilling operations.

    PubMed

    Altin, Dag; Frost, Tone Karin; Nilssen, Ingunn

    2008-04-01

    In order to achieve the offshore petroleum industries "zero harm" goal to the environment, the environmental impact factor for drilling discharges was developed as a tool to identify and quantify the environmental risks associated with disposal of drilling discharges to the marine environment. As an initial step in this work the main categories of substances associated with drilling discharges and assumed to contribute to toxic or nontoxic stress were identified and evaluated for inclusion in the risk assessment. The selection were based on the known toxicological properties of the substances, or the total amount discharged together with their potential for accumulation in the water column or sediments to levels that could be expected to cause toxic or nontoxic stress to the biota. Based on these criteria 3 categories of chemicals were identified for risk assessment the water column and sediments: Natural organic substances, metals, and drilling fluid chemicals. Several approaches for deriving the environmentally safe threshold concentrations as predicted no effect concentrations were evaluated in the process. For the water column consensus were reached for using the species sensitivity distribution approach for metals and the assessment factor approach for natural organic substances and added drilling chemicals. For the sediments the equilibrium partitioning approach was selected for all three categories of chemicals. The theoretically derived sediment quality criteria were compared to field-derived threshold effect values based on statistical approaches applied on sediment monitoring data from the Norwegian Continental Shelf. The basis for derivation of predicted no effect concentration values for drilling discharges should be consistent with the principles of environmental risk assessment as described in the Technical Guidance Document on Risk Assessment issued by the European Union.

  1. Evaluating methods to establish habitat suitability criteria: A case study in the upper Delaware River Basin, USA

    USGS Publications Warehouse

    Galbraith, Heather S.; Blakeslee, Carrie J.; Cole, Jeffrey C.; Talbert, Colin; Maloney, Kelly O.

    2016-01-01

    Defining habitat suitability criteria (HSC) of aquatic biota can be a key component to environmental flow science. HSC can be developed through numerous methods; however, few studies have evaluated the consistency of HSC developed by different methodologies. We directly compared HSC for depth and velocity developed by the Delphi method (expert opinion) and by two primary literature meta-analyses (literature-derived range and interquartile range) to assess whether these independent methods produce analogous criteria for multiple species (rainbow trout, brown trout, American shad, and shallow fast guild) and life stages. We further evaluated how these two independently developed HSC affect calculations of habitat availability under three alternative reservoir management scenarios in the upper Delaware River at a mesohabitat (main channel, stream margins, and flood plain), reach, and basin scale. In general, literature-derived HSC fell within the range of the Delphi HSC, with highest congruence for velocity habitat. Habitat area predicted using the Delphi HSC fell between the habitat area predicted using two literature-derived HSC, both at the basin and the site scale. Predicted habitat increased in shallow regions (stream margins and flood plain) using literature-derived HSC while Delphi-derived HSC predicted increased channel habitat. HSC generally favoured the same reservoir management scenario; however, no favoured reservoir management scenario was the most common outcome when applying the literature range HSC. The differences found in this study lend insight into how different methodologies can shape HSC and their consequences for predicted habitat and water management decisions. Published 2016. This article is a U.S. Government work and is in the public domain in the USA.

  2. Drug Release Studies from Caesalpinia pulcherrima Seed Polysaccharide.

    PubMed

    Jeevanandham, Somasundaram; Dhachinamoorthi, Duraiswamy; Bannoth Chandra Sekhar, Kothapalli

    2011-01-01

    This study examines the controlled release behavior of both water-soluble (acetaminophen, caffeine, theophylline and salicylic acid) and water insoluble (indomethacin) drugs derived from Caesalpinia pulcherrima seed Gum isolated from Caesalpinia pulcherrima kernel powder. It further investigates the effect of incorporating diluents such as microcrystalline cellulose and lactose on caffeine release. In addition the effect the gum's (polysaccharide) partial cross-linking had on release of acetaminophen was examined. Applying the exponential equation, the soluble drugs mechanism of release was found to be anomalous. The insoluble drugs showed a near case II or zero order release mechanism. The rate of release in descending order was caffeine, acetaminophen, theophylline, salicylic acid and indomethacin. An increase in the release kinetics of the drug was observed on blending with diluents. However, the rate of release varied with the type and amount of blend within the matrix. The mechanism of release due to effect of diluents was found to be anomalous. The rate of drug release decreased upon partial cross-linking and the mechanism of release was found to be of super case II.

  3. Criteria for genuine N -partite continuous-variable entanglement and Einstein-Podolsky-Rosen steering

    NASA Astrophysics Data System (ADS)

    Teh, R. Y.; Reid, M. D.

    2014-12-01

    Following previous work, we distinguish between genuine N -partite entanglement and full N -partite inseparability. Accordingly, we derive criteria to detect genuine multipartite entanglement using continuous-variable (position and momentum) measurements. Our criteria are similar but different to those based on the van Loock-Furusawa inequalities, which detect full N -partite inseparability. We explain how the criteria can be used to detect the genuine N -partite entanglement of continuous variable states generated from squeezed and vacuum state inputs, including the continuous-variable Greenberger-Horne-Zeilinger state, with explicit predictions for up to N =9 . This makes our work accessible to experiment. For N =3 , we also present criteria for tripartite Einstein-Podolsky-Rosen (EPR) steering. These criteria provide a means to demonstrate a genuine three-party EPR paradox, in which any single party is steerable by the remaining two parties.

  4. The release of nickel and other trace elements from electric kettles and coffee machines.

    PubMed

    Berg, T; Petersen, A; Pedersen, G A; Petersen, J; Madsen, C

    2000-03-01

    The release of nickel, chromium and lead from electric kettles to water under conditions simulating regular household use was investigated. Ten out of 26 kettles sold on the Danish market released more than 50 micrograms/l nickel to water, whereas neither lead nor chromium was released in any significant amount. Fifty micrograms/l of nickel in water was chosen as the threshold of action, because concentrations below this value were considered unlikely to provide outbreaks of eczema for those consumers suffering from contact allergy to nickel, who are also sensitive to the content of nickel in the diet. This first part of the study was followed up by a dialogue between the kettle producers and the Danish authorities, leading to a change of construction or design for those kettles that did not comply with the criteria. As a follow-up study another ten kettles were studied to check whether compliance was improved. Two of these ten kettles still released more than 50 micrograms/l nickel to water under the test conditions. These two kettles, however, were subsequently withdrawn from the market. Coffee machines tested similarly did not release aluminium, lead, chromium or nickel in quantities of any significance.

  5. All-Cause and External Mortality in Released Prisoners: Systematic Review and Meta-Analysis

    PubMed Central

    Zlodre, Jakov

    2012-01-01

    Objectives. We systematically reviewed studies of mortality following release from prison and examined possible demographic and methodological factors associated with variation in mortality rates. Methods. We searched 5 computer-based literature indexes to conduct a systematic review of studies that reported all-cause, drug-related, suicide, and homicide deaths of released prisoners. We extracted and meta-analyzed crude death rates and standardized mortality ratios by age, gender, and race/ethnicity, where reported. Results. Eighteen cohorts met review criteria reporting 26 163 deaths with substantial heterogeneity in rates. The all-cause crude death rates ranged from 720 to 2054 per 100 000 person-years. Male all-cause standardized mortality ratios ranged from 1.0 to 9.4 and female standardized mortality ratios from 2.6 to 41.3. There were higher standardized mortality ratios in White, female, and younger prisoners. Conclusions. Released prisoners are at increased risk for death following release from prison, particularly in the early period. Aftercare planning for released prisoners could potentially have a large public health impact, and further work is needed to determine whether certain groups should be targeted as part of strategies to reduce mortality. PMID:23078476

  6. Matrix metalloproteinase 9 (MMP-9) mediated release of MMP-9 resistant stromal cell-derived factor 1α (SDF-1α) from surface modified polymer films.

    PubMed

    Steinhagen, Max; Hoffmeister, Peter-Georg; Nordsieck, Karoline; Hötzel, Rudi; Baumann, Lars; Hacker, Michael C; Schulz-Siegmund, Michaela; Beck-Sickinger, Annette G

    2014-04-23

    Preparation of smart materials by coatings of established surfaces with biomolecules will lead to the next generation of functionalized biomaterials. Rejection of implants is still a major problem in medical applications but masking the implant material with protein coatings is a promising approach. These layers not only disguise the material but also equip it with a certain biological function. The anti-inflammatory chemokine stromal cell-derived factor 1α (SDF-1α) is well suited to take over this function, because it efficiently attracts stem cells and promotes their differentiation and proliferation. At least the initial stem cell homing requires the formation of a concentration gradient. Thus, a reliable and robust release mechanism of SDF-1α from the material is essential. Several proteases, most notably matrix metalloproteinases, are upregulated during inflammation, which, in principle, can be exploited for a tightly controlled release of SDF-1α. Herein, we present the covalent immobilization of M-[S4V]-SDF-1α on novel biodegradable polymer films, which consist of heterobifunctional poly(ethylene glycol) and oligolactide-based functionalized macromers. A peptidic linker with a trimeric matrix metalloproteinase 9 (MMP-9) cleavage site (MCS) was used as connection and the linkage between the three components was achieved by combination of expressed protein ligation and Cu(I) catalyzed azide/alkyne cycloaddition. The MCS was used for MMP-9 mediated release of M-[S4V]-SDF-1α from the biomaterial and the released SDF-1α derivative was biologically active and induced strong cell migration, which demonstrates the great potential of this system.

  7. Creation of bony microenvironment with CaP and cell-derived ECM to enhance human bone-marrow MSC behavior and delivery of BMP-2

    PubMed Central

    Kang, Yunqing; Kim, Sungwoo; Khademhosseini, Ali; Yang, Yunzhi

    2011-01-01

    Extracellular matrix (ECM) comprises a rich meshwork of proteins and proteoglycans, which not only contains biological cues for cell behavior, but is also a reservoir for binding growth factors and controlling their release. Here we aimed to create a suitable bony microenvironment with cell-derived ECM and biodegradable β-tricalcium phosphate (β-TCP). More specifically, we investigated whether the ECM produced by bone marrow-derived mesenchymal stem cells (hBMSC) on a β-TCP scaffold can bind bone morphogenetic protein-2 (BMP-2) and control its release in a sustained manner, and further examined the effect of ECM and the BMP-2 released from ECM on cell behaviors. The ECM was obtained through culturing the hBMSC on a β-TCP porous scaffold and performing decellularization and sterilization. SEM, XPS, FTIR, and immunofluorescent staining results indicated the presence of ECM on the β-TCP and the amount of ECM increased with the incubation time. BMP-2 was loaded onto the β-TCP with and without ECM by immersing the scaffolds in the BMP-2 solution. The loading and release kinetics of the BMP-2 on the β-TCP/ECM were significantly slower than those on the β-TCP. The β-TCP/ECM exhibited a sustained release profile of the BMP-2, which was also affected by the amount of ECM. This is probably because the β-TCP/ECM has different binding mechanisms with BMP-2. The β-TCP/ECM promoted cell proliferation. Furthermore, the BMP-2-loaded β-TCP/ECM stimulated reorganization of the actin cytoskeleton, increased expression of alkaline phosphatase and calcium deposition by the cells compared to those without BMP-2 loading and the β-TCP with BMP-2 loading. PMID:21632105

  8. Impulsive stabilization and impulsive synchronization of discrete-time delayed neural networks.

    PubMed

    Chen, Wu-Hua; Lu, Xiaomei; Zheng, Wei Xing

    2015-04-01

    This paper investigates the problems of impulsive stabilization and impulsive synchronization of discrete-time delayed neural networks (DDNNs). Two types of DDNNs with stabilizing impulses are studied. By introducing the time-varying Lyapunov functional to capture the dynamical characteristics of discrete-time impulsive delayed neural networks (DIDNNs) and by using a convex combination technique, new exponential stability criteria are derived in terms of linear matrix inequalities. The stability criteria for DIDNNs are independent of the size of time delay but rely on the lengths of impulsive intervals. With the newly obtained stability results, sufficient conditions on the existence of linear-state feedback impulsive controllers are derived. Moreover, a novel impulsive synchronization scheme for two identical DDNNs is proposed. The novel impulsive synchronization scheme allows synchronizing two identical DDNNs with unknown delays. Simulation results are given to validate the effectiveness of the proposed criteria of impulsive stabilization and impulsive synchronization of DDNNs. Finally, an application of the obtained impulsive synchronization result for two identical chaotic DDNNs to a secure communication scheme is presented.

  9. Derivation and application of the energy dissipation factor in the design of fishways

    USGS Publications Warehouse

    Towler, Brett; Mulligan, Kevin; Haro, Alexander J.

    2015-01-01

    Reducing turbulence and associated air entrainment is generally considered advantageous in the engineering design of fish passage facilities. The well-known energy dissipation factor, or EDF, correlates with observations of the phenomena. However, inconsistencies in EDF forms exist and the bases for volumetric energy dissipation rate criteria are often misunderstood. A comprehensive survey of EDF criteria is presented. Clarity in the application of the EDF and resolutions to these inconsistencies are provided through formal derivations; it is demonstrated that kinetic energy represents only 1/3 of the total energy input for the special case of a broad-crested weir. Specific errors in published design manuals are identified and resolved. New, fundamentally sound, design equations for culvert outlet pools and standard Denil Fishway resting pools are developed. The findings underscore the utility of EDF equations, demonstrate the transferability of volumetric energy dissipation rates, and provide a foundation for future refinement of component-, species-, and life-stage-specific EDF criteria.

  10. DRAFT METHODOLOGY FOR DERIVATION OF WATER ...

    EPA Pesticide Factsheets

    Development and body functions of many organisms are directed by the endocrine system. Endocrine Disrupting Chemicals (EDCs), are those exogenous (and endogenous) compounds that may interfere with this regulatory function because they may either mimic or suppress the action of the body’s natural hormones. Because these chemicals are increasingly present in the environment as a result of human activities and they only require tiny amounts to disrupt endocrine functions, EDCs may have major impacts on ecology and particularly aquatic life as evidenced by the abundance of field observations verified by both laboratory and controlled in situ experiments. The Clean Water Act § 304(a)(1) authorizes the Administrator to develop and publish criteria for water quality that are protective of aquatic life. Traditionally, ambient water quality criteria for the protection of aquatic life have been derived using the 1985 Guidelines (Guidelines for Deriving Numerical National Water Quality Criteria for the Protection of Aquatic Life and Their Uses). These guidelines have comprehensive data requirements for toxicity tests using a variety of aquatic taxa, thus ensuring protection of the existing aquatic assemblage, and helping to ensure a goal of protecting and restoring “ecological integrity”. Some “Pharmaceuticals and Personal Care Products” (PPCPs), particularly those exhibiting endocrine disrupting activity, have two unique features, which distinguish them from

  11. A Framework to Evaluate the Impact of Armourstones on the Chemical Quality of Surface Water.

    PubMed

    Duester, Lars; Wahrendorf, Dierk-Steffen; Brinkmann, Corinna; Fabricius, Anne-Lena; Meermann, Björn; Pelzer, Juergen; Ecker, Dennis; Renner, Monika; Schmid, Harald; Ternes, Thomas A; Heininger, Peter

    2017-01-01

    Today, basic requirements for construction works include the protection of human health and of the environment. In the tension area between economic demands, circular flow economy and environmental safety, a link between the results from standardized leaching tests and the respective environmental quality standards must be created. To derive maximum release limits of metals and metalloids for armourstones in hydraulic engineering, this link is accomplished via a simple model approach. By treating natural materials and industrial by-products the same way, the article delivers an overview on the recent regulative situation in Europe as well as describes and discusses an innovative approach to derive maximum release limits for monolithic construction products in hydraulic engineering on a conceptual level. On a practical level, a list of test parameters is derived by connecting an extensive dataset (seven armourstone materials with five repetitions and 31 elements tested with the worldwide applied dynamic surface leaching test) with surface water quality standards and predicted no effect concentrations. Finally, the leaching tests results are compared with the envisaged maximum release limits, offering a direct comparison between natural materials and industrial by-products.

  12. Dynamic release and clearance of circulating microparticles during cardiac stress.

    PubMed

    Augustine, Daniel; Ayers, Lisa V; Lima, Eduardo; Newton, Laura; Lewandowski, Adam J; Davis, Esther F; Ferry, Berne; Leeson, Paul

    2014-01-03

    Microparticles are cell-derived membrane vesicles, relevant to a range of biological responses and known to be elevated in cardiovascular disease. To investigate microparticle release during cardiac stress and how this response differs in those with vascular disease. We measured a comprehensive panel of circulating cell-derived microparticles by a standardized flow cytometric protocol in 119 patients referred for stress echocardiography. Procoagulant, platelet, erythrocyte, and endothelial but not leukocyte, granulocyte, or monocyte-derived microparticles were elevated immediately after a standardized dobutamine stress echocardiogram and decreased after 1 hour. Twenty-five patients developed stress-induced wall motion abnormalities suggestive of myocardial ischemia. They had similar baseline microparticle levels to those who did not develop ischemia, but, interestingly, their microparticle levels did not change during stress. Furthermore, no stress-induced increase was observed in those without inducible ischemia but with a history of vascular disease. Fourteen patients subsequently underwent coronary angiography. A microparticle rise during stress echocardiography had occurred only in those with normal coronary arteries. Procoagulant, platelet, erythrocyte, and endothelial microparticles are released during cardiac stress and then clear from the circulation during the next hour. This stress-induced rise seems to be a normal physiological response that is diminished in those with vascular disease.

  13. Effects of Mastery Criterion on the Emergence of Derived Equivalence Relations

    ERIC Educational Resources Information Center

    Fienup, Daniel M.; Brodsky, Julia

    2017-01-01

    In this study, we manipulated mastery criterion form (rolling or block) and stringency (across 6 or 12 trials) and measured the emergence of derived relations. College students learned neuroanatomy equivalence classes and experienced one of two rolling mastery criteria (6 or 12 consecutive correct responses) or a block mastery criterion (12 trials…

  14. A Field-Based Aquatic Life Benchmark for Conductivity in Central Appalachian Streams (2010) (External Review Draft)

    EPA Science Inventory

    This report adapts the standard U.S. EPA methodology for deriving ambient water quality criteria. Rather than use toxicity test results, the adaptation uses field data to determine the loss of 5% of genera from streams. The method is applied to derive effect benchmarks for disso...

  15. Mass spectral analysis of C3 and C4 aliphatic amino acid derivatives.

    NASA Technical Reports Server (NTRS)

    Lawless, J. G.; Chadha, M. S.

    1971-01-01

    Diagnostic criteria are obtained for the distinction of alpha, beta, gamma, and N-methyl isomers of the C3 and C4 aliphatic amino acids, using mass spectral analysis of the derivatives of these acids. The use of deuterium labeling has helped in the understanding of certain fragmentation pathways.

  16. Limited contribution of permafrost carbon to methane release from thawing peatlands

    NASA Astrophysics Data System (ADS)

    Cooper, Mark D. A.; Estop-Aragonés, Cristian; Fisher, James P.; Thierry, Aaron; Garnett, Mark H.; Charman, Dan J.; Murton, Julian B.; Phoenix, Gareth K.; Treharne, Rachael; Kokelj, Steve V.; Wolfe, Stephen A.; Lewkowicz, Antoni G.; Williams, Mathew; Hartley, Iain P.

    2017-07-01

    Models predict that thaw of permafrost soils at northern high latitudes will release tens of billions of tonnes of carbon (C) to the atmosphere by 2100 (refs ,,). The effect on the Earth’s climate depends strongly on the proportion of this C that is released as the more powerful greenhouse gas methane (CH4), rather than carbon dioxide (CO2) (refs ,); even if CH4 emissions represent just 2% of the C release, they would contribute approximately one-quarter of the climate forcing. In northern peatlands, thaw of ice-rich permafrost causes surface subsidence (thermokarst) and water-logging, exposing substantial stores (tens of kilograms of C per square meter, ref. ) of previously frozen organic matter to anaerobic conditions, and generating ideal conditions for permafrost-derived CH4 release. Here we show that, contrary to expectations, although substantial CH4 fluxes (>20 g CH4 m-2 yr-1) were recorded from thawing peatlands in northern Canada, only a small amount was derived from previously frozen C (<2 g CH4 m-2 yr-1). Instead, fluxes were driven by anaerobic decomposition of recent C inputs. We conclude that thaw-induced changes in surface wetness and wetland area, rather than the anaerobic decomposition of previously frozen C, may determine the effect of permafrost thaw on CH4 emissions from northern peatlands.

  17. Endothelium-derived relaxing factor produced and released from artery and vein is nitric oxide

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

    Ignarro, L.J.; Buga, G.M.; Wood, K.S.

    1987-12-01

    The objective of this study was to determine whether nitric oxide (NO) is responsible for the vascular smooth muscle relaxation elicited by endothelium-derived relaxing factor (EDRF). EDRF is an unstable humoral substance released from artery and vein that mediates the action of endothelium-dependent vasodilators. NO is and unstable endothelium-independent vasodilator that is released from vasodilator drugs such as nitroprusside and glyceryl trinitrate. The authors have repeatedly observed that the actions of NO on vascular smooth muscle closely resemble those of EDRF. In the present study the vascular effects of EDRF released from perfused bovine intrapulmonary artery and vein were comparedmore » with the effects of NO delivered by superfusion over endothelium-denuded arterial and venous strips arranged in a cascade. EDRF was indistinguishable from NO in that both were labile inactivated by pyrogallol or superoxide anion, stabilized by superoxide dismutase, and inhibited by oxyhemoglobin or potassium. Both EDRF and NO produced comparable increases in cyclic GMP accumulation in artery and vein, and this cyclic GMP accumulation was inhibited by pyrogallol, oxyhemoglobin, potassium, and methylene blue. EDRF was identified chemically as NO, or a labile nitroso species, by two procedures. Thus, EDRF released from artery and vein possesses identical and biological and chemical properties as NO.« less

  18. Characterization of protein release from photocrosslinkable hyaluronic acid-polyethylene glycol hydrogel tissue engineering scaffolds.

    PubMed

    Leach, Jennie B; Schmidt, Christine E

    2005-01-01

    The goal of this work was to utilize the naturally derived bioactive polymer hyaluronic acid (HA) to create a combination tissue engineering scaffold and protein delivery device. HA is a non-immunogenic, non-adhesive glycosaminoglycan that plays significant roles in several cellular processes, including angiogenesis and the regulation of inflammation. In previous work, we created photopolymerizable glycidyl methacrylate-hyaluronic acid (GMHA) hydrogels that had controlled degradation rates, were cytocompatible, and were able to be modified with peptide moieties. In the present studies, we characterized the release of a model protein, bovine serum albumin (BSA), from GMHA and GMHA-polyethylene glycol (PEG) hydrogels. Although BSA could be released rapidly (> 60% within 6 h) from 1% GMHA hydrogels, we found that increasing either the GMHA or the PEG concentrations could lengthen the duration of protein delivery. Preliminary size exclusion chromatography studies indicated that the released BSA was almost entirely in its native monomeric form. Lastly, protein release was extended to several weeks by suspending BSA-poly(lactic-co-glycolic acid) microspheres within the hydrogel bulk. These initial studies indicate that the naturally derived biopolymer HA can be employed to design novel photopolymerizable composites that are suitable for delivering stable proteins from scaffolding in tissue engineering applications.

  19. Bio-based Interpenetrating Network Polymer Composites from Locust Sawdust as Coating Material for Environmentally Friendly Controlled-Release Urea Fertilizers.

    PubMed

    Zhang, Shugang; Yang, Yuechao; Gao, Bin; Wan, Yongshan; Li, Yuncong C; Zhao, Chenhao

    2016-07-20

    A novel polymer-coated nitrogen (N) fertilizer was developed using bio-based polyurethane (PU) derived from liquefied locust sawdust as the coating material. The bio-based PU was successfully coated on the surface of the urea fertilizer prills to form polymer-coated urea (PCU) fertilizer for controlled N release. Epoxy resin (EP) was also used to further modify the bio-based PU to synthesize the interpenetrating network (IPN), enhancing the slow-release properties of the PCU. The N release characteristics of the EP-modified PCU (EMPCU) in water were determine at 25 °C and compared to that of PCU and EP-coated urea (ECU). The results showed that the EP modification reduced the N release rate and increased the longevity of the fertilizer coated with bio-based PU. A corn growth study was conducted to further evaluate the filed application of the EMPCU. In comparison to commercial PCU and conventional urea fertilizer, EMPCU was more effective and increased the yield and total dry matter accumulation of the corn. Findings from this work indicated that bio-based PU derived from sawdust can be used as coating materials for PCU, particularly after EP modification. The resulting EMPCU was more environmentally friendly and cost-effective than conventional urea fertilizers coated by EP.

  20. Experimental criteria for steering and the Einstein-Podolsky-Rosen paradox

    NASA Astrophysics Data System (ADS)

    Cavalcanti, E. G.; Jones, S. J.; Wiseman, H. M.; Reid, M. D.

    2009-09-01

    We formally link the concept of steering (a concept created by Schrödinger but only recently formalized by Wiseman, Jones, and Doherty [Phys. Rev. Lett. 98, 140402 (2007)]) and the criteria for demonstrations of Einstein-Podolsky-Rosen (EPR) paradox introduced by Reid [Phys. Rev. A 40, 913 (1989)]. We develop a general theory of experimental EPR-steering criteria, derive a number of criteria applicable to discrete as well as continuous-variable observables, and study their efficacy in detecting that form of nonlocality in some classes of quantum states. We show that previous versions of EPR-type criteria can be rederived within this formalism, thus unifying these efforts from a modern quantum-information perspective and clarifying their conceptual and formal origin. The theory follows in close analogy with criteria for other forms of quantum nonlocality (Bell nonlocality and entanglement), and because it is a hybrid of those two, it may lead to insights into the relationship between the different forms of nonlocality and the criteria that are able to detect them.

  1. An application of almost marginal conditional stochastic dominance (AMCSD) on forming efficient portfolios

    NASA Astrophysics Data System (ADS)

    Slamet, Isnandar; Mardiana Putri Carissa, Siska; Pratiwi, Hasih

    2017-10-01

    Investors always seek an efficient portfolio which is a portfolio that has a maximum return on specific risk or minimal risk on specific return. Almost marginal conditional stochastic dominance (AMCSD) criteria can be used to form the efficient portfolio. The aim of this research is to apply the AMCSD criteria to form an efficient portfolio of bank shares listed in the LQ-45. This criteria is used when there are areas that do not meet the criteria of marginal conditional stochastic dominance (MCSD). On the other words, this criteria can be derived from quotient of areas that violate the MCSD criteria with the area that violate and not violate the MCSD criteria. Based on the data bank stocks listed on LQ-45, it can be stated that there are 38 efficient portfolios of 420 portfolios where each portfolio comprises of 4 stocks and 315 efficient portfolios of 1710 portfolios with each of portfolio has 3 stocks.

  2. Particles from wood smoke and traffic induce differential pro-inflammatory response patterns in co-cultures

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

    Kocbach, Anette; Herseth, Jan Inge; Lag, Marit

    2008-10-15

    The inflammatory potential of particles from wood smoke and traffic has not been well elucidated. In this study, a contact co-culture of monocytes and pneumocytes was exposed to 10-40 {mu}g/cm{sup 2} of particles from wood smoke and traffic for 12, 40 and 64 h to determine their influence on pro-inflammatory cytokine release (TNF-{alpha}, IL-1, IL-6, IL-8) and viability. To investigate the role of organic constituents in cytokine release the response to particles, their organic extracts and the washed particles were compared. Antagonists were used to investigate source-dependent differences in intercellular signalling (TNF-{alpha}, IL-1). The cytotoxicity was low after exposure tomore » particles from both sources. However, wood smoke, and to a lesser degree traffic-derived particles, induced a reduction in cell number, which was associated with the organic fraction. The release of pro-inflammatory cytokines was similar for both sources after 12 h, but traffic induced a greater release than wood smoke particles with increasing exposure time. The organic fraction accounted for the majority of the cytokine release induced by wood smoke, whereas the washed traffic particles induced a stronger response than the corresponding organic extract. TNF-{alpha} and IL-1 antagonists reduced the release of IL-8 induced by particles from both sources. In contrast, the IL-6 release was only reduced by the IL-1 antagonist during exposure to traffic-derived particles. In summary, particles from wood smoke and traffic induced differential pro-inflammatory response patterns with respect to cytokine release and cell number. Moreover, the influence of the organic particle fraction and intercellular signalling on the pro-inflammatory response seemed to be source-dependent.« less

  3. Evaluating the combined effects of source zone mass release rates and aquifer heterogeneity on solute discharge uncertainty

    NASA Astrophysics Data System (ADS)

    de Barros, Felipe P. J.

    2018-07-01

    Quantifying the uncertainty in solute mass discharge at an environmentally sensitive location is key to assess the risks due to groundwater contamination. Solute mass fluxes are strongly affected by the spatial variability of hydrogeological properties as well as release conditions at the source zone. This paper provides a methodological framework to investigate the interaction between the ubiquitous heterogeneity of the hydraulic conductivity and the mass release rate at the source zone on the uncertainty of mass discharge. Through the use of perturbation theory, we derive analytical and semi-analytical expressions for the statistics of the solute mass discharge at a control plane in a three-dimensional aquifer while accounting for the solute mass release rates at the source. The derived solutions are limited to aquifers displaying low-to-mild heterogeneity. Results illustrate the significance of the source zone mass release rate in controlling the mass discharge uncertainty. The relative importance of the mass release rate on the mean solute discharge depends on the distance between the source and the control plane. On the other hand, we find that the solute release rate at the source zone has a strong impact on the variance of the mass discharge. Within a risk context, we also compute the peak mean discharge as a function of the parameters governing the spatial heterogeneity of the hydraulic conductivity field and mass release rates at the source zone. The proposed physically-based framework is application-oriented, computationally efficient and capable of propagating uncertainty from different parameters onto risk metrics. Furthermore, it can be used for preliminary screening purposes to guide site managers to perform system-level sensitivity analysis and better allocate resources.

  4. A Biopharmaceutical Industry Perspective on the Control of Visible Particles in Biotechnology-Derived Injectable Drug Products.

    PubMed

    Mathonet, Serge; Mahler, Hanns-Christian; Esswein, Stefan T; Mazaheri, Maryam; Cash, Patricia W; Wuchner, Klaus; Kallmeyer, Georg; Das, Tapan K; Finkler, Christof; Lennard, Andrew

    2016-01-01

    Regulatory monographs in Europe and the United States require drug products for parenteral administration to be "practically free" or "essentially free" of visible particles, respectively. Both terms have been used interchangeably and acknowledge the probabilistic nature of visual particle inspection. The probability of seeing a particle in a drug product container varies according to the size and nature of the particles as well as container and inspection conditions. Therefore, the term "without visible particles" can be highly misleading in the context of what is practically achievable. This may lead to differences in understanding between industry practitioners and regulatory agencies. Is this term intended to mean "zero particles", or is there any intention to distinguish between particle type such as "zero extraneous visible particles" or "zero proteinaceous particles"? Furthermore, how can "zero" particles as a criterion for release testing be reconciled with "practically free from particles" as stated in the definition and a low, justified level of proteinaceous particles after production?The purpose of this position paper is to review best practices in the industry in terms of visual inspection process and associated operator training, quality control sampling, testing, and setting acceptance criteria corresponding to "practically free of visible particles" and providing considerations when visible proteinaceous particles are deemed unavoidable. It also provides a brief overview of visible particle characterization and gives perspectives on patient safety. This position paper applies to biotechnology-derived drug products including monoclonal antibodies in late-phase development to licensed products. In the 2011 monoclonal antibody monograph revision, European Pharmacopoeia experts acknowledged that protein products may also contain proteinaceous particles at release or that protein particles may form during storage. Indeed, industry experience has demonstrated that therapeutic proteins such as monoclonal antibodies can exhibit a propensity for self-association leading to the formation of aggregates that range in size from nanometres (oligomers) to microns (subvisible and visible particles). As a result, the requirement for drug product appearance for monoclonal antibodies was changed from "without visible particles" to "without visible particles unless otherwise authorised or justified". In our view, "practically free from particles" should be considered a suitable acceptance criterion for injectable biotechnology and small-molecule products, as long as appropriately defined. Furthermore, we argue that visual inspection is a suitable quality control release test and that "practically free from particles" is a suitable specification when adequately described. © PDA, Inc. 2016.

  5. Interpretation of standard leaching test BS EN 12457-2: is your sample hazardous or inert?

    PubMed

    Zandi, Mohammad; Russell, Nigel V; Edyvean, Robert G J; Hand, Russell J; Ward, Philip

    2007-12-01

    A slag sample from a lead refiner has been obtained and given to two analytical laboratories to determine the release of trace elements from the sample according to BS EN 12457-2. Samples analysed by one laboratory passed waste acceptance criteria, leading it to be classified as an inert material; samples of the same material analysed by the other laboratory failed waste acceptance criteria and were classified as hazardous. It was found that the sample preparation procedure is the critical step in the leaching analysis and that the effects of particle size on leachability should be taken into account when using this standard. The purpose of this paper is to open a debate on designing a better defined standard leaching test and making current waste acceptance criteria more flexible.

  6. 40 CFR 63.95 - Additional approval criteria for accidental release prevention programs.

    Code of Federal Regulations, 2011 CFR

    2011-07-01

    ... basis. (3) Procedures for reviewing risk management plans and providing technical assistance to... chapter; and (ii) A requirement that any source subject to the State's part 68 program submit a Risk Management Plan (RMP) that reports at least the same information in the same format as required under part 68...

  7. 10 CFR 850.31 - Release criteria.

    Code of Federal Regulations, 2010 CFR

    2010-01-01

    ... lowest contamination level practicable, but not to exceed the levels established in paragraphs (b) and (c... contamination level of equipment or item surfaces does not exceed the higher of 0.2 µg/100 cm 2 or the... the equipment or item and its future use and the nature of the beryllium contamination. (c) Before...

  8. 28 CFR 2.62 - Rewarding assistance in the prosecution of other offenders; criteria and guidelines.

    Code of Federal Regulations, 2010 CFR

    2010-07-01

    ... an offender other than the prisoner. Other significant assistance (e.g., providing information... in sufficient detail to permit a full evaluation. However, no promises, express or implied, as to a... release of the prisoner must not threaten the public safety. (4) The assistance must not have been...

  9. Rewarding Faculty Scholarship at Two-Year Colleges: Incentive for Change or Perceived Threat?

    ERIC Educational Resources Information Center

    Padovan, Patricia; Whittington, Dale

    1998-01-01

    Explores the definition and relevance of faculty scholarship in the community college. Examines positive and negative attitudes toward various scholarship criteria in the faculty-reward (promotion, tenure, salary increase, and release time) systems, and discusses concerns about scholarship as an additional facet of faculty evaluation. (25…

  10. VALIDATION OF EPA METHOD 1682: SALMONELLA IN BIOSOLIDS BY MODIFIED, SEMISOLID RAPPAPORT-VASSILIADIS (MSRV) MEDIUM

    EPA Science Inventory

    Treated biosolids may be applied to land as a crop nutrient and soil conditioner. However, land application of biosolids may pose the risk of releasing pathogens into the environment if disinfection and use criteria established by EPA at 40 CFR part 503 are not met. Among these c...

  11. 40 CFR 63.95 - Additional approval criteria for accidental release prevention programs.

    Code of Federal Regulations, 2010 CFR

    2010-07-01

    ... basis. (3) Procedures for reviewing risk management plans and providing technical assistance to... chapter; and (ii) A requirement that any source subject to the State's part 68 program submit a Risk Management Plan (RMP) that reports at least the same information in the same format as required under part 68...

  12. Teaching Literature in an Age of Text Complexity

    ERIC Educational Resources Information Center

    Alsup, Janet

    2013-01-01

    The recently released Common Core State Standards increase classroom emphasis on informational texts in high school and recommend a three-part measurement for text complexity when selecting texts for classroom use. In this commentary I argue that fictional narratives can not only meet these stated criteria for complex texts and result in critical…

  13. Biowaiver monographs for immediate release solid oral dosage forms: efavirenz.

    PubMed

    Cristofoletti, Rodrigo; Nair, Anita; Abrahamsson, Bertil; Groot, D W; Kopp, Sabine; Langguth, Peter; Polli, James E; Shah, Vinod P; Dressman, Jennifer B

    2013-02-01

    Literature data pertaining to the decision to allow a waiver of in vivo bioequivalence testing for the approval of immediate-release (IR) solid oral dosage forms containing efavirenz as the only active pharmaceutical ingredient (API) are reviewed. Because of lack of conclusive data about efavirenz's permeability and its failure to comply with the "high solubility" criteria according to the Biopharmaceutics Classification System (BCS), the API can be classified as BCS Class II/IV. In line with the solubility characteristics, the innovator product does not meet the dissolution criteria for a "rapidly dissolving product." Furthermore, product variations containing commonly used excipients or in the manufacturing process have been reported to impact the rate and extent of efavirenz absorption. Despite its wide therapeutic index, subtherapeutic levels of efavirenz can lead to treatment failure and also facilitate the emergence of efavirenz-resistant mutants. For all these reasons, a biowaiver for IR solid oral dosage forms containing efavirenz as the sole API is not scientifically justified for reformulated or multisource drug products. Copyright © 2012 Wiley Periodicals, Inc.

  14. In situ release rates of Cu and Zn from commercial antifouling paints at different salinities.

    PubMed

    Lagerström, Maria; Lindgren, J Fredrik; Holmqvist, Albin; Dahlström, Mia; Ytreberg, Erik

    2018-02-01

    Antifouling paints are environmentally risk assessed based on their biocidal release rates to the water phase. In situ release rates of copper (Cu) and zinc (Zn) were derived for five commercial paints in two recreational marinas with different salinities (5 and 14 PSU) using an X-Ray Fluorescence spectrometer (XRF). Salinity was found to significantly affect the Cu release, with twice the amount of Cu released at the higher salinity, while its influence on the Zn release was paint-specific. Site-specific release rates for water bodies with salinity gradients, e.g. the Baltic Sea, are therefore necessary for more realistic risk assessments of antifouling paints. Furthermore, the in situ release rates were up to 8 times higher than those generated using standardized laboratory or calculation methods. The environmental risk assessment repeated with the field release rates concludes that it is questionable whether the studied products should be allowed on the Swedish market. Copyright © 2017 The Authors. Published by Elsevier Ltd.. All rights reserved.

  15. Lyophilized insulin nanoparticles prepared from quaternized N-aryl derivatives of chitosan as a new strategy for oral delivery of insulin: in vitro, ex vivo and in vivo characterizations.

    PubMed

    Mahjub, Reza; Radmehr, Moojan; Dorkoosh, Farid Abedin; Ostad, Seyed Naser; Rafiee-Tehrani, Morteza

    2014-12-01

    The purpose of this research was the development, in vitro, ex vivo and in vivo characterization of lyophilized insulin nanoparticles prepared from quaternized N-aryl derivatives of chitosan. Insulin nanoparticles were prepared from methylated N-(4-N,N-dimethylaminobenzyl), methylated N-(4 pyridinyl) and methylated N-(benzyl). Insulin nanoparticles containing non-modified chitosan and also trimethyl chiotsan (TMC) were also prepared as control. The effects of the freeze-drying process on physico-chemical properties of nanoparticles were investigated. The release of insulin from the nanoparticles was studied in vitro. The mechanism of the release of insulin from different types of nanoparticles was determined using curve fitting. The secondary structure of the insulin released from the nanoparticles was analyzed using circular dichroism and the cell cytotoxicity of nanoparticles on a Caco-2 cell line was determined. Ex vivo studies were performed on excised rat jejunum using Frantz diffusion cells. In vivo studies were performed on diabetic male Wistar rats and blood glucose level and insulin serum concentration were determined. Optimized nanoparticles with proper physico-chemical properties were obtained. The lyophilization process was found to cause a decrease in zeta potential and an increase in PdI as well as and a decrease in entrapment efficiency (EE%) and loading efficiency (LE%) but conservation in size of nanoparticles. Atomic force microscopy (AFM) images showed non-aggregated, stable and spherical to sub-spherical nanoparticles. The in vitro release study revealed higher release rates for lyophilized compared to non-lyophilized nanoparticles. Cytotoxicity studies on Caco-2 cells revealed no significant cytotoxicity for prepared nanoparticles after 3-h post-incubation but did show the concentration-dependent cytotoxicity after 24 h. The percentage of cumulative insulin determined from ex vivo studies was significantly higher in nanoparticles prepared from quaternized aromatic derivatives of chitosan. In vivo data showed significantly higher insulin intestinal absorption in nanoparticles prepared from methylated N-(4-N, N-dimethylaminobenzyl) chitosan nanoparticles compared to trimethyl chitosan. These data obtained demonstrated that as the result of optimized physico-chemical properties, drug release rate, cytotoxicity profile, ex vivo permeation enhancement and increased in vivo absorption, nanoparticles prepared from N-aryl derivatives of chitosan can be considered as valuable method for the oral delivery of insulin.

  16. Role of In Vitro Release Methods in Liposomal Formulation Development: Challenges and Regulatory Perspective.

    PubMed

    Solomon, Deepak; Gupta, Nilesh; Mulla, Nihal S; Shukla, Snehal; Guerrero, Yadir A; Gupta, Vivek

    2017-11-01

    In the past few years, measurement of drug release from pharmaceutical dosage forms has been a focus of extensive research because the release profile obtained in vitro can give an indication of the drug's performance in vivo. Currently, there are no compendial in vitro release methods designed for liposomes owing to a range of experimental challenges, which has created a major hurdle for both development and regulatory acceptance of liposome-based drug products. In this paper, we review the current techniques that are most often used to assess in vitro drug release from liposomal products; these include the membrane diffusion techniques (dialysis, reverse dialysis, fractional dialysis, and microdialysis), the sample-and-separate approach, the in situ method, the continuous flow, and the modified United States Pharmacopeia methods (USP I and USP IV). We discuss the principles behind each of the methods and the criteria that assist in choosing the most appropriate method for studying drug release from a liposomal formulation. Also, we have included information concerning the current regulatory requirements for liposomal drug products in the United States and in Europe. In light of increasing costs of preclinical and clinical trials, applying a reliable in vitro release method could serve as a proxy to expensive in vivo bioavailability studies. Graphical Abstract Appropriate in-vitro drug release test from liposomal products is important to predict the in-vivo performance.

  17. Drug delivery systems with modified release for systemic and biophase bioavailability.

    PubMed

    Leucuta, Sorin E

    2012-11-01

    This review describes the most important new generations of pharmaceutical systems: medicines with extended release, controlled release pharmaceutical systems, pharmaceutical systems for the targeted delivery of drug substances. The latest advances and approaches for delivering small molecular weight drugs and other biologically active agents such as proteins and nucleic acids require novel delivery technologies, the success of a drug being many times dependent on the delivery method. All these dosage forms are qualitatively superior to medicines with immediate release, in that they ensure optimal drug concentrations depending on specific demands of different disease particularities of the body. Drug delivery of these pharmaceutical formulations has the benefit of improving product efficacy and safety, as well as patient convenience and compliance. This paper describes the biopharmaceutical, pharmacokinetic, pharmacologic and technological principles in the design of drug delivery systems with modified release as well as the formulation criteria of prolonged and controlled release drug delivery systems. The paper presents pharmaceutical prolonged and controlled release dosage forms intended for different routes of administration: oral, ocular, transdermal, parenteral, pulmonary, mucoadhesive, but also orally fast dissolving tablets, gastroretentive drug delivery systems, colon-specific drug delivery systems, pulsatile drug delivery systems and carrier or ligand mediated transport for site specific or receptor drug targeting. Specific technologies are given on the dosage forms with modified release as well as examples of marketed products, and current research in these areas.

  18. Methadone dose at the time of release from prison significantly influences retention in treatment: implications from a pilot study of HIV-infected prisoners transitioning to the community in Malaysia.

    PubMed

    Wickersham, Jeffrey A; Zahari, Muhammad Muhsin; Azar, Marwan M; Kamarulzaman, Adeeba; Altice, Frederick L

    2013-09-01

    To evaluate the impact of methadone dose on post-release retention in treatment among HIV-infected prisoners initiating methadone maintenance treatment (MMT) within prison. Thirty HIV-infected prisoners meeting DSM-IV pre-incarceration criteria for opioid dependence were enrolled in a prison-based, pre-release MMT program in Klang Valley, Malaysia; 3 died before release from prison leaving 27 evaluable participants. Beginning 4 months before release, standardized methadone initiation and dose escalation procedures began with 5mg daily for the first week and 5mg/daily increases weekly until 80 mg/day or craving was satisfied. Participants were followed for 12 months post-release at a MMT clinic within 25 kilometers of the prison. Kaplan-Meier survival analysis was used to evaluate the impact of methadone dose on post-release retention in treatment. Methadone dose ≥80 mg/day at the time of release was significantly associated with retention in treatment. After 12 months of release, only 21.4% of participants on <80 mg were retained at 12 months compared to 61.5% of those on ≥80 mg (Log Rank χ(2)=(1,26) 7.6, p<0.01). Higher doses of MMT at time of release are associated with greater retention on MMT after release to the community. Important attention should be given to monitoring and optimizing MMT doses to address cravings and side effects prior to community re-entry from prisons. Copyright © 2013 Elsevier Ireland Ltd. All rights reserved.

  19. Methadone Dose at the Time of Release from Prison Significantly Influences Retention in Treatment: Implications From a Pilot Study of HIV-Infected Prisoners Transitioning to the Community in Malaysia

    PubMed Central

    Wickersham, Jeffrey A.; Muhsin Zahari, Muhammad; Azar, Marwan M.; Kamarulzaman, Adeeba; Altice, Frederick L.

    2013-01-01

    Objective To evaluate the impact of methadone dose on post-release retention in treatment among HIV-infected prisoners initiating methadone maintenance treatment (MMT) within prison. Methods Thirty HIV-infected prisoners meeting DSM-IV pre-incarceration criteria for opioid dependence were enrolled in a prison-based, pre-release MMT program in Klang Valley, Malaysia; 3 died before release from prison leaving 27 evaluable participants. Beginning 4 months before release, standardized methadone initiation and dose escalation procedures began with 5mg daily for the first week and 5mg/daily increases weekly until 80 mg/day or craving was satisfied. Participants were followed for 12 months post-release at a MMT clinic within 25 kilometers of the prison. Kaplan-Meier survival analysis was used to evaluate the impact of methadone dose on post-release retention in treatment. Findings Methadone dose ≥80 mg/day at the time of release was significantly associated with retention in treatment. After 12 months of release, only 21.4% of participants on <80mg were retained at 12 months compared to 61.5% of those on ≥80mg (Log Rank χ2=(1,26) 7.6, p <0.01). Conclusions Higher doses of MMT at time of release are associated with greater retention on MMT after release to the community. Important attention should be given to monitoring and optimizing MMT doses to address cravings and side effects prior to community re-entry from prisons. PMID:23414931

  20. [Correlation of clinical and radiologic results of complete subtalar release in congenital clubfoot].

    PubMed

    Kalenderer, Onder; Ağuş, Haluk; Ak, Mümtaz; Ozlük, Serkan

    2003-01-01

    We evaluated the mid-term results in patients who underwent complete subtalar release with the use of the Cincinnati incision for congenital clubfoot. Complete subtalar release was performed in 30 feet of 23 patients (16 boys, 7 girls; 7 bilateral cases). The mean age at surgery was 17.5 months (range 2 to 84 months). Clinically, cosmetic appearance, adduction of the forefoot, the range of motion of the ankle joint, and muscle strength were evaluated. Radiologic evaluations included talocalcaneal angles on antero-posterior and lateral views, talocalcaneal index, talar-first metatarsal angles, calcaneal-fifth metatarsal angles, and Bohler angles. Talar and navicular bone lengths were compared with the other side in unilateral patients. The results were evaluated according to the Simons' criteria. The mean follow-up was 9 years and 8 months (range 7 years to 14 years). The mean range of motion of the ankle joint was measured as 47 degrees (range 10 degrees to 60 degrees ). The parents of three patients were not satisfied with the clinical results. Clinically, six patients had metatarsus adductus. Radiologically, flattening of the talar head (7 patients) and the talar dome (2 patients) were detected in unilateral patients. Navicular dorsal subluxation was found in seven feet. Compared to the normal side, the mean navicular shortening was 2.6 mm (range 0 to 4 mm), the mean talar shortening was 4.8 mm (range 2 to 11 mm). According to the Simons' criteria, the results were satisfactory in 27 feet (90%) and unsatisfactory in three feet (10%). Our results suggest that complete subtalar release for the treatment of clubfoot enables correction of all components of the deformity at a single session, and that its clinical results are more favorable than radiologic results, without requiring a close cooperation of the parents.

  1. Bypass system modification at Bonneville Dam on the Columbia River improved the survival of juvenile salmon

    USGS Publications Warehouse

    Ferguson, J.W.; Sandford, B.P.; Reagan, R.E.; Gilbreath, L.G.; Meyer, E.B.; Ledgerwood, R.D.; Adams, N.S.

    2007-01-01

    From 1987 to 1992, we evaluated a fish bypass system at Bonneville Dam Powerhouse 2 on the Columbia River. The survival of subyearling Chinook salmon Oncorhynchus tshawytscha released into the system ranged from 0.774 to 0.911 and was significantly lower than the survival of test fish released into turbines and the area immediately below the powerhouse where bypass system flow reentered the river. Yearling and subyearling Chinook salmon and yearling coho salmon O. kisutch released into the bypass system were injured or descaled. Also, levels of blood plasma cortisol and lactate were significantly higher in yearling and subyearling Chinook salmon that passed through the bypass system than in fish released directly into a net located over the bypass exit. This original system was then extensively modified using updated design criteria, and the site where juvenile fish reentered the river was relocated 2.8 km further downstream to reduce predation on bypassed fish by northern pikeminnow Ptychocheilus oregonensis. Based on studies conducted from 1999 to 2001, the new bypass system resulted in high fish survival, virtually no injuries to fish, fish passage times that were generally similar to water travel times, and mild stress responses from which fish recovered quickly. The mean estimated survival of subyearling Chinook salmon passing through the new bypass system was 0.946 in 2001, which was an usually low-flow year. Survival, physical condition, passage timing, and blood physiological indicators of stress were all useful metrics for assessing the performance of both bypass systems and are discussed. The engineering and hydraulic criteria used to design the new bypass system that resulted in improved fish passage conditions are described.

  2. Breeding seasons, molt patterns, and gender and age criteria for selected northeastern Costa Rican resident landbirds

    Treesearch

    Jared D. Wolfe; Peter Pyle; C. John Ralph

    2009-01-01

    Detailed accounts of molt and breeding cycles remain elusive for the majority of resident tropical bird species. We used data derived from a museum review and 12 years of banding data to infer breeding seasonality, molt patterns, and age and gender criteria for 27 common landbird species in northeastern Costa Rica. Prealternate molts appear to be rare, only occurring...

  3. Slopeland utilizable limitation classification using landslide inventory

    NASA Astrophysics Data System (ADS)

    Tsai, Shu Fen; Lin, Chao Yuan

    2016-04-01

    In 1976, "Slopeland Conservation and Utilization Act" was promulgated as well as the criteria for slopeland utilization limitation classification (SULC) i.e., average slope, effective soil depth, degree of soil erosion, and parent rock became standardized. Due to the development areas on slope land steadily increased and the extreme rainfall events occurred frequently, the areas affected by landslides also increased year by year. According to the act, the land which damaged by disaster must be categorized to the conservation land and required rehabilitation. Nevertheless, the large-scale disaster on slope land and the limitation of SWCB officers are the constraint of field investigation. Therefore, how to establish the ongoing inspective procedure of post-disaster SULC using remote sensing was essential. A-Li-Shan, Ai-Liao, and Tai-Ma-Li Watershed were selected to be case studies in this project. The spatial data from big data i.e., Digital Elevation Model (DEM), soil map, and satellite images integrated with Geographic Information Systems (GIS) were applied to post-disaster SULC. The collapse and deposition area which delineated by vegetation recovery rate was established landslide inventory of cadastral unit combined with watershed unit. The results were verified with field survey and the accuracy was 97%. The landslide inventory could be an effective reference for sediment disaster investigation and a practical evidence for judgement to expropriation. Finally, the results showed that the ongoing inspective procedure of post-disaster SULC was practicable. From the four criteria, the average slope was the major factor. It was found that the non-uniform slopes, especially derived from cadastral units, often produce significant slope difference and lead to errors of average slope evaluation. Therefore, the Grid-based DEM slope derivation has been recommended as the standard method to calculate the average slope. Others criteria were previously required to classify the farm land tax. However, as a result of environmental change and advancements in farm machinery, it seems that those criteria were further inappropriate criteria for agricultural land. In conclusion, soil and water conservation works, which were enhanced to disaster prevention under climate change, should reconsider the SULC criteria. The average slope from DEM derivation and the sediment disaster from landslide inventory were suggested and adequate for SULC.

  4. Genetic Determinants of Volatile-Thiol Release by Saccharomyces cerevisiae during Wine Fermentation

    PubMed Central

    Howell, Kate S.; Klein, Mathias; Swiegers, Jan H.; Hayasaka, Yoji; Elsey, Gordon M.; Fleet, Graham H.; Høj, Peter B.; Pretorius, Isak S.; de Barros Lopes, Miguel A.

    2005-01-01

    Volatile thiols, particularly 4-mercapto-4-methylpentan-2-one (4MMP), make an important contribution to the aroma of wine. During wine fermentation, Saccharomyces cerevisiae mediates the cleavage of a nonvolatile cysteinylated precursor in grape juice (Cys-4MMP) to release the volatile thiol 4MMP. Carbon-sulfur lyases are anticipated to be involved in this reaction. To establish the mechanism of 4MMP release and to develop strains that modulate its release, the effect of deleting genes encoding putative yeast carbon-sulfur lyases on the cleavage of Cys-4MMP was tested. The results led to the identification of four genes that influence the release of the volatile thiol 4MMP in a laboratory strain, indicating that the mechanism of release involves multiple genes. Deletion of the same genes from a homozygous derivative of the commercial wine yeast VL3 confirmed the importance of these genes in affecting 4MMP release. A strain deleted in a putative carbon-sulfur lyase gene, YAL012W, produced a second sulfur compound at significantly higher concentrations than those produced by the wild-type strain. Using mass spectrometry, this compound was identified as 2-methyltetrathiophen-3-one (MTHT), which was previously shown to contribute to wine aroma but was of unknown biosynthetic origin. The formation of MTHT in YAL012W deletion strains indicates a yeast biosynthetic origin of MTHT. The results demonstrate that the mechanism of synthesis of yeast-derived wine aroma components, even those present in small concentrations, can be investigated using genetic screens. PMID:16151133

  5. Polycross populations of the native grass Festuca roemeri as pre-varietal germplasm: their derivation, release, increase, and use

    Treesearch

    Dale C. Darris; Barbara L. Wilson; Rob Fiegener; Matthew E. Horning

    2008-01-01

    Results of a recent common-garden study provide evidence needed to delineate appropriate seed transfer zones for the native grass Festuca roemeri (Pavlick) E. B. Alexeev (Poaceae). That information has been used to develop pre-variety germplasm releases to provide ecologically and genetically appropriate seeds for habitat restoration, erosion...

  6. Exposure assessment of veterinary medicines in aquatic systems

    USGS Publications Warehouse

    Metcalfe, Chris; Boxall, Alistair; Fenner, Kathrin; Kolpin, Dana W.; Silberhorn, Eric; Staveley, Jane

    2008-01-01

    The release of veterinary medicines into the aquatic environment may occur through direct or indirect pathways. An example of direct release is the use of medicines in aquaculture (Armstrong et al. 2005; Davies et al. 1998), where chemicals used to treat fish are added directly to water. Indirect releases, in which medicines make their way to water through transport from other matrices, include the application of animal manure to land or direct excretion of residues onto pasture land, from which the therapeutic chemicals may be transported into the aquatic environment (Jørgensen and Halling-Sørensen 2000; Boxall et al. 2003, 2004). Veterinary medicines used to treat companion animals may also be transported into the aquatic environment through disposal of unused medicines, veterinary waste, or animal carcasses (Daughton and Ternes 1999, Boxall et al. 2004). The potential for a veterinary medicine to be released to the aquatic environment will be determined by several different criteria, including the method of treatment, agriculture or aquaculture practices, environmental conditions, and the properties of the veterinary medicine.

  7. Biosafety assessment protocols for new organisms in New Zealand: Can they apply internationally to emerging technologies?

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

    Barratt, B.I.P.; Moeed, A.; Malone, L.A.

    2006-05-15

    An analysis of established biosafety protocols for release into the environment of exotic plants and biological control agents for weeds and arthropod pests has been carried out to determine whether such protocols can be applied to relatively new and emerging technologies intended for the primary production industries, such as transgenic plants. Example case studies are described to indicate the scope of issues considered by regulators who make decisions on new organism releases. No transgenic plants have been released to date in New Zealand, but two field test approvals are described as examples. An analysis of the biosafety protocols has shownmore » that, while many of the risk criteria considered for decision-making by regulators are similar for all new organisms, a case-by-case examination of risks and potential impacts is required in order to fully assess risk. The value of post-release monitoring and validation of decisions made by regulators is emphasised.« less

  8. Reuse and recycle--considering the soil below constructions.

    PubMed

    Suer, Pascal; Wik, Ola; Erlandsson, Martin

    2014-07-01

    The European Construction Products Regulation provides a life cycle based framework for the environmental assessment of construction products. Harmonised European standards for the assessment of the release of dangerous substances and for declaration of environmental performance are in progress. Risk based limit values for the protection of soil and groundwater below construction works will still bet set nationally. In this paper we review the possibilities to expand the ongoing harmonisation to include risk assessment and life cycle assessment (LCA). Based on reviews of national European limit value models (LMVs) for assessment of release to soil and groundwater, two areas for harmonisation emerge: 1- The toxicological criteria. Toxicological endpoints to protect human health and environment are similar, and data from the same toxicological data sets are used to establish acceptance criteria. 2- The emission part of LMVs. We extracted six generic construction works for granular materials. These encompass the most common choices and span the different release scenarios applied. Harmonised emission models would also facilitate LCA and environmental product declaration (EPD). The immission or transport part of the LVMs is less promising for harmonisation. Locating the acceptance criteria point of compliance close to the construction works is advantageous from many aspects and would facilitate harmonisation of assessments. We have identified two different strategies to include recycling in the assessments: 1- Tiered procedure where assessment and declaration of performance are made for the intended primary use of the product only and renewed assessments are made whenever the construction works are demolished and the product is recovered. 2- Scenario based procedure where future recycling scenarios, into new products and construction works, are forecasted. In this case the initial assessment and declaration of environmental performance of a construction product is performed both for the intended primary use of the product and for the recycling scenarios. Copyright © 2014 Elsevier B.V. All rights reserved.

  9. Metabolically-Derived Human Ventilation Rates: A Revised Approach Based Upon Oxygen Consumption Rates (External Review Draft)

    EPA Science Inventory

    EPA has released a draft report entitled, Metabolically-Derived Human Ventilation Rates: A Revised Approach Based Upon Oxygen Consumption Rates, for independent external peer review and public comment. NCEA published the Exposure Factors Handbook in 1997. This comprehens...

  10. Yield stability in genotypes derived through basic breeding

    USDA-ARS?s Scientific Manuscript database

    The sugarcane variety ‘LCP 85-384’ was derived through basic (introgression) breeding, and after its release in 1995, the variety quickly gained acreage in the state of Louisiana. The primary reason for the popularity of the variety was the plant vigor and increase in the number of ratoon harvests ...

  11. A nanomaterial release model for waste shredding using a Bayesian belief network

    NASA Astrophysics Data System (ADS)

    Shandilya, Neeraj; Ligthart, Tom; van Voorde, Imelda; Stahlmecke, Burkhard; Clavaguera, Simon; Philippot, Cecile; Ding, Yaobo; Goede, Henk

    2018-02-01

    The shredding of waste of electrical and electronic equipment (WEEE) and other products, incorporated with nanomaterials, can lead to a substantial release of nanomaterials. Considering the uncertainty, complexity, and scarcity of experimental data on release, we present the development of a Bayesian belief network (BBN) model. This baseline model aims to give a first prediction of the release of nanomaterials (excluding nanofibers) during their mechanical shredding. With a focus on the description of the model development methodology, we characterize nanomaterial release in terms of number, size, mass, and composition of released particles. Through a sensitivity analysis of the model, we find the material-specific parameters like affinity of nanomaterials to the matrix of the composite and their state of dispersion inside the matrix to reduce the nanomaterial release up to 50%. The shredder-specific parameters like number of shafts in a shredder and input and output size of the material for shredding could minimize it up to 98%. The comparison with two experimental test cases shows promising outcome on the prediction capacity of the model. As additional experimental data on nanomaterial release becomes available, the model is able to further adapt and update risk forecasts. When adapting the model with additional expert beliefs, experts should be selected using criteria, e.g., substantial contribution to nanomaterial and/or particulate matter release-related scientific literature, the capacity and willingness to contribute to further development of the BBN model, and openness to accepting deviating opinions. [Figure not available: see fulltext.

  12. Human amniotic epithelial cells inhibit CD4+ T cell activation in acute kidney injury patients by influencing the miR-101-c-Rel-IL-2 pathway.

    PubMed

    Liu, Junfeng; Hua, Rong; Gong, Zhangbin; Shang, Bin; Huang, Yongyi; Guo, Lihe; Liu, Te; Xue, Jun

    2017-01-01

    In the pathogenesis of acute kidney injury (AKI), the release of multiple interleukins can lead to increased kidney damage. Human amniotic epithelial cells (HuAECs) can inhibit immune cell activation in vivo and in vitro. We hypothesized that HuAECs could weaken patient-derived peripheral blood CD4+ T-cell activation and decreasing the ability of these cells to express and release IL-2. -Cell proliferation assay revealed that under the same culture conditions, activated AKI patient-derived CD4+ T cells had a significantly reduced proliferation rate when were co-cultured with HuAECs. And the level of IL-2 released was also significantly reduced. Western blot and qRT-PCR assays showed that the expression of c-Rel in the CD4+ T cells was also significantly reduced. However, the expression level of endogenous miR-101 in the CD4+ T cells co-cultured with HuAECs was significantly increased. Luciferase reporter assay results suggested that miR-101 could bind to a specific site in the c-Rel 3' UTR and induce the post-transcriptional silencing of c-Rel. Subsequently, we over-expressed miR-101 in AKI patient-derived CD4+ T cells. The qRT-PCR and western blot assay results revealed that the expression of endogenous c-Rel was significantly reduced, while the ELISA results indicated that the level of IL-2 released was also significantly decreased. Finally, ChIP-PCR assay results showed that the miR-101-overexpressing CD4+ T-cell group and the HuAEC co-culture CD4+ T-cell group exhibited significantly decreased binding capacities between the 'c-Rel-NFκB' complex and the IL-2 gene promoter, and the transcriptional activity of IL-2 was also significantly decreased. Therefore, we confirmed that HuAECs can stimulate miR-101 expression in AKI patient-derived peripheral blood CD4+ T cells, thus inhibiting the expression of the miR-101 target gene c-Rel and leading to a reduction in IL-2 expression and release. Copyright © 2016 Elsevier Ltd. All rights reserved.

  13. Pathways of acetylcholine synthesis, transport and release as targets for treatment of adult-onset cognitive dysfunction.

    PubMed

    Amenta, F; Tayebati, S K

    2008-01-01

    Acetylcholine (ACh) is a neurotransmitter widely diffused in central, peripheral, autonomic and enteric nervous system. This paper has reviewed the main mechanisms of ACh synthesis, storage, and release. Presynaptic choline transport supports ACh production and release, and cholinergic terminals express a unique transporter critical for neurotransmitter release. Neurons cannot synthesize choline, which is ultimately derived from the diet and is delivered through the blood stream. ACh released from cholinergic synapses is hydrolyzed by acetylcholinesterase into choline and acetyl coenzyme A and almost 50% of choline derived from ACh hydrolysis is recovered by a high-affinity choline transporter. Parallel with the development of cholinergic hypothesis of geriatric memory dysfunction, cholinergic precursor loading strategy was tried for treating cognitive impairment occurring in Alzheimer's disease. Controlled clinical studies denied clinical usefulness of choline and lecithin (phosphatidylcholine), whereas for other phospholipids involved in choline biosynthetic pathways such as cytidine 5'-diphosphocholine (CDP-choline) or alpha-glyceryl-phosphorylcholine (choline alphoscerate) a modest improvement of cognitive dysfunction in adult-onset dementia disorders is documented. These inconsistencies have probably a metabolic explanation. Free choline administration increases brain choline availability but it does not increase ACh synthesis/or release. Cholinergic precursors to serve for ACh biosynthesis should be incorporate and stored into phospholipids in brain. It is probable that appropriate ACh precursors and other correlated molecules (natural or synthesized) could represent a tool for developing therapeutic strategies by revisiting and updating treatments/supplementations coming out from this therapeutic stalemate.

  14. Pros and cons of conjoint analysis of discrete choice experiments to define classification and response criteria in rheumatology.

    PubMed

    Taylor, William J

    2016-03-01

    Conjoint analysis of choice or preference data has been used in marketing for over 40 years but has appeared in healthcare settings much more recently. It may be a useful technique for applications within the rheumatology field. Conjoint analysis in rheumatology contexts has mainly used the approaches implemented in 1000Minds Ltd, Dunedin, New Zealand, Sawtooth Software, Orem UT, USA. Examples include classification criteria, composite response criteria, service prioritization tools and utilities assessment. Limitations imposed by very many attributes can be managed using new techniques. Conjoint analysis studies of classification and response criteria suggest that the assumption of equal weighting of attributes cannot be met, which challenges traditional approaches to composite criteria construction. Weights elicited through choice experiments with experts can derive more accurate classification criteria, than unweighted criteria. Studies that find significant variation in attribute weights for composite response criteria for gout make construction of such criteria problematic. Better understanding of various multiattribute phenomena is likely to increase with increased use of conjoint analysis, especially when the attributes concern individual perceptions or opinions. In addition to classification criteria, some applications for conjoint analysis that are emerging in rheumatology include prioritization tools, remission criteria, and utilities for life areas.

  15. Analysis of proposed criteria for human response to vibration

    NASA Technical Reports Server (NTRS)

    Janeway, R. N.

    1975-01-01

    The development of criteria for human vibration response is reviewed, including the evolution of the ISO standard 2631. The document is analyzed to show why its application to vehicle ride evaluation is strongly opposed. Alternative vertical horizontal limits for comfort are recommended in the ground vehicle ride frequency range above 1 Hz. These values are derived by correlating the absorbed power findings of Pradko and Lee with other established criteria. Special emphasis is placed on working limits in the frequency range of 1 to 10 Hz since this is the most significant area in ground vehicle ride evaluation.

  16. Study of Adaptive Mathematical Models for Deriving Automated Pilot Performance Measurement Techniques. Volume I. Model Development.

    ERIC Educational Resources Information Center

    Connelly, Edward A.; And Others

    A new approach to deriving human performance measures and criteria for use in automatically evaluating trainee performance is documented in this report. The ultimate application of the research is to provide methods for automatically measuring pilot performance in a flight simulator or from recorded in-flight data. An efficient method of…

  17. Study of Adaptive Mathematical Models for Deriving Automated Pilot Performance Measurement Techniques. Volume II. Appendices. Final Report.

    ERIC Educational Resources Information Center

    Connelly, E. M.; And Others

    A new approach to deriving human performance measures and criteria for use in automatically evaluating trainee performance is described. Ultimately, this approach will allow automatic measurement of pilot performance in a flight simulator or from recorded in-flight data. An efficient method of representing performance data within a computer is…

  18. A New Newton-Like Iterative Method for Roots of Analytic Functions

    ERIC Educational Resources Information Center

    Otolorin, Olayiwola

    2005-01-01

    A new Newton-like iterative formula for the solution of non-linear equations is proposed. To derive the formula, the convergence criteria of the one-parameter iteration formula, and also the quasilinearization in the derivation of Newton's formula are reviewed. The result is a new formula which eliminates the limitations of other methods. There is…

  19. Deriving Oral Assessment Scales across Different Tests and Rater Groups.

    ERIC Educational Resources Information Center

    Chalhoub-Deville, Micheline

    1995-01-01

    The purpose of this study was to derive the criteria/dimensions underlying learners' second-language oral ability scores across three tests: an oral interview, a narration, and a read-aloud. A stimulus tape of 18 speech samples was presented to 3 native speaker rater groups for evaluation. Results indicate that researchers might need to reconsider…

  20. Tracking of Drug Release and Material Fate for Naturally Derived Omega-3 Fatty Acid Biomaterials.

    PubMed

    Faucher, Keith M; Artzi, Natalie; Beck, Moshe; Beckerman, Rita; Moodie, Geoff; Albergo, Theresa; Conroy, Suzanne; Dale, Alicia; Corbeil, Scott; Martakos, Paul; Edelman, Elazer R

    2016-03-01

    In vitro and in vivo studies were conducted on omega-3 fatty acid-derived biomaterials to determine their utility as an implantable material for adhesion prevention following soft tissue hernia repair and as a means to allow for the local delivery of antimicrobial or antibiofilm agents. Naturally derived biomaterials offer several advantages over synthetic materials in the field of medical device development. These advantages include enhanced biocompatibility, elimination of risks posed by the presence of toxic catalysts and chemical crosslinking agents, and derivation from renewable resources. Omega-3 fatty acids are readily available from fish and plant sources and can be used to create implantable biomaterials either as a stand-alone device or as a device coating that can be utilized in local drug delivery applications. In-depth characterization of material erosion degradation over time using non-destructive imaging and chemical characterization techniques provided mechanistic insight into material structure: function relationship. This in turn guided rational tailoring of the material based on varying fatty acid composition to control material residence time and hence drug release. These studies demonstrate the utility of omega-3 fatty acid derived biomaterials as an absorbable material for soft tissue hernia repair and drug delivery applications.

  1. Toxicity reference values for protecting aquatic birds in China from the effects of polychlorinated biphenyls.

    PubMed

    Su, Hailei; Wu, Fengchang; Zhang, Ruiqing; Zhao, Xiaoli; Mu, Yunsong; Feng, Chenglian; Giesy, John P

    2014-01-01

    PCBs are typical of persistent, bioaccumulative and toxic compounds (PBTs) that are widely distributed in the environment and can biomagnify through aquatic food webs, because of their stability and lipophilic properties. Fish-eating birds are top predators in the aquatic food chain and may suffer adverse effects from exposure to PCB concentrations. In this review, we address the toxicity of PCBs to birds and have derived tissue residue guidelines (TRGs) and toxic reference values (TRVs) for PCBs for protecting birds in China. In deriving these protective indices, we utilized available data and three approaches, to wit: species sensitivity distribution (SSD), critical study approach (CSA) and toxicity percentile rank method (TPRM). The TRGs and TRVs arrived at by using these methods were 42.3, I 0. 7, 4.3 pg TEQs/g diet wm and 16.7, 15.5, and 5.5 pg TEQs/g tissue wm for the CSA SSD and TPRM approaches, respectively. These criteria values were analyzed and compared with those derived by others. The following TRG and TRY, derived by SSD, were recommended as avian criteria for protecting avian species in China: 10.7 pg TEQs/g diet wm and 15.5 pg TEQs/g tissue wm, respectively. The hazard of PCBs to birds was assessed by comparing the TRVs and TRGs derived in this study with actual PCB concentrations detected in birds or fish. The criteria values derived in this study can be used to evaluate the risk of PCBs to birds in China, and to provide indices that are more reasonable for protecting Chinese avian species. However, several sources of uncertainty exists when deriving TRGs and TRVs for the PCBs in birds, such as lack of adequate toxicity data for birds and need to use uncertainty factors. Clearly, relevant work on PCBs and birds in China are needed in the future. For example, PCB toxicity data for resident avian species in China are needed. In addition, studies are needed on the actual PCB levels in birds and fish in China. Such information is needed to serve as a more firm foundation for future risk assessments.

  2. Biological control of invasive plant species: a reassessment for the Anthropocene.

    PubMed

    Seastedt, Timothy R

    2015-01-01

    The science of finding, testing and releasing herbivores and pathogens to control invasive plant species has achieved a level of maturity and success that argues for continued and expanded use of this program. The practice, however, remains unpopular with some conservationists, invasion biologists, and stakeholders. The ecological and economic benefits of controlling densities of problematic plant species using biological control agents can be quantified, but the risks and net benefits of biological control programs are often derived from social or cultural rather than scientific criteria. Management of invasive plants is a 'wicked problem', and local outcomes to wicked problems have both positive and negative consequences differentially affecting various groups of stakeholders. The program has inherent uncertainties; inserting species into communities that are experiencing directional or even transformational changes can produce multiple outcomes due to context-specific factors that are further confounded by environmental change drivers. Despite these uncertainties, biological control could play a larger role in mitigation and adaptation strategies used to maintain biological diversity as well as contribute to human well-being by protecting food and fiber resources. © 2014 The Author New Phytologist © 2014 New Phytologist Trust.

  3. Formulation, in vitro evaluation and study of variables on tri-layered gastro-retentive delivery system of diltiazem HCl.

    PubMed

    Raut Desai, Shilpa; Rohera, Bhagwan D

    2014-03-01

    Tri-layered floating tablets using only one grade of polyethylene oxide (PEO) would enable easy manufacturing, reproducibility and controlled release for highly soluble drugs. To evaluate the potential of PEO as a sole polymer for the controlled release and to study the effect of formulation variables on release and gastric retention of highly soluble Diltiazem hydrochloride (DTZ). Tablets were compressed with middle layer consisting of drug and polymer while outer layers consisted of polymer with sodium bicarbonate. Design of formulation to obtain 12 h, zero-order release and rapid floatation was done by varying the grades, quantity of PEO and sodium bicarbonate. Dissolution data were fitted in drug release models and swelling/erosion studies were undertaken to verify the drug release mechanism. Effect of formulation variables and tablet surface morphology using scanning electron microscopy were studied. The optimized formula passed the criteria of USP dissolution test I and exhibited floating lag-time of 3-4 min. Drug release was faster from low molecular weight (MW) PEO as compared to high MW. With an increase in the amount of sodium bicarbonate, faster buoyancy was achieved due to the increased CO2 gas formation. Drug release followed zero-order and gave a good fit to the Korsmeyer-Peppas model, which suggested that drug release was due to diffusion through polymer swelling. Zero-order, controlled release profile with the desired buoyancy can be achieved by using optimum formula quantities of sodium bicarbonate and polymer. The tri-layered system shows promising delivery of DTZ, and possibly other water-soluble drugs.

  4. pH-sensitive inulin-based nanomicelles for intestinal site-specific and controlled release of celecoxib.

    PubMed

    Mandracchia, Delia; Trapani, Adriana; Perteghella, Sara; Sorrenti, Milena; Catenacci, Laura; Torre, Maria Luisa; Trapani, Giuseppe; Tripodo, Giuseppe

    2018-02-01

    Aiming at a site-specific drug release in the lower intestinal tract, this paper deals with the synthesis and physicochemical/biological characterization of pH-sensitive nanomicelles from an inulin (INU) amphiphilic derivative. To allow an intestinal site specific release of the payload, INU-Vitamin E (INVITE) bioconjugates were functionalized with succinic anhydride to provide the system with pH-sensitive groups preventing a premature release of the payload into the stomach. The obtained INVITESA micelles resulted nanosized, with a low critical aggregation concentration and the release studies showed a marked pH-dependent release. The drug loading stabilized the micelles against the acidic hydrolysis. From transport studies on Caco-2 cells, resulted that INVITESA nanomicelles cross the cellular monolayer but are actively re-transported in the secretory (basolateral-apical) direction when loaded in apical side. It suggests that the entrapped drug could not be absorbed before the release from the micelles, enabling so a local release of the active. Copyright © 2017 Elsevier Ltd. All rights reserved.

  5. Active bio-based food-packaging: Diffusion and release of active substances through and from cellulose nanofiber coating toward food-packaging design.

    PubMed

    Lavoine, Nathalie; Guillard, Valérie; Desloges, Isabelle; Gontard, Nathalie; Bras, Julien

    2016-09-20

    Cellulose nanofibers (CNFs) were recently investigated for the elaboration of new functional food-packaging materials. Their nanoporous network was especially of interest for controlling the release of active species. Qualitative release studies were conducted, but quantification of the diffusion phenomenon observed when the active species are released from and through CNF coating has not yet been studied. Therefore, this work aims to model CNF-coated paper substrates as controlled release system for food-packaging using release data obtained for two model molecules, namely caffeine and chlorhexidine digluconate. The applied mathematical model - derived from Fickian diffusion - was validated for caffeine only. When the active species chemically interacts with the release device, another model is required as a non-predominantly diffusion-controlled release was observed. From caffeine modeling data, a theoretical active food-packaging material was designed. The use of CNFs as barrier coating was proved to be the ideal material configuration that best meets specifications. Copyright © 2016. Published by Elsevier Ltd.

  6. Discordance between age- and size-based criteria of child passenger restraint appropriateness.

    PubMed

    Smiley, Mary L; Bingham, C Raymond; Jacobson, Peter D; Macy, Michelle L

    2018-04-03

    In this study, we sought to accomplish the following objectives: to (1) calculate the percentage of children considered appropriately restrained across 8 criteria of increasing restrictiveness; (2) examine agreement between age- and size-based appropriateness criteria; (3) assess for changes in the percentage of children considered appropriately restrained by the 8 criteria between 2011 (shortly after updates to U.S. guidelines) and 2015. Data from 2 cross-sectional surveys of 928 parents of children younger than 12 years old (n = 591 in 2011, n = 337 in 2015) were analyzed in 2017. Child age, weight, and height were measured at an emergency department visit and used to determine whether the parent-reported child passenger restraint was considered appropriate according to 8 criteria. Age-based criteria were derived from Michigan law and U.S. Weight, height, and size-based criteria were derived from typical restraints available in the United States in 2007 and 2011. The percentage appropriate restraint use was calculated for each criterion. The kappa statistic was used to measure agreement between criteria. Change in appropriateness from 2011 to 2015 was assessed with chi-square statistics. Percentage appropriate restraint use varied from a low of 19% for higher weight limits in 2011 to a high of 91% for Michigan law in 2015. Agreement between criteria was slight to moderate. The lowest kappa was for Michigan law and higher weight limits in 2011 (κ = 0.06) and highest for U.S. guidelines and lower weight limits in 2011 (κ = 0.60). Percentage appropriate restraint use was higher in 2015 than 2011 for the following criteria: U.S. guidelines (74 vs. 58%, P < .001), lower weight (57 vs. 47%, P = .005), higher weight (25 vs. 19%, P = .03), greater height (39 vs. 26%, P < .001), and greater size (42 vs. 30%, P = .001). The percentage of children considered to be using an appropriate restraint varied substantially across criteria. Aligning the definition of appropriate restraint use with current U.S. guidelines would increase consistency in reporting results from studies of child passenger safety in the United States. Potential explanations for the increased percentage of children considered appropriately restrained between 2011 and 2015 include adoption of the updated U.S. guidelines and the use of child passenger restraints with higher weight and height limits.

  7. Radial SI latches vibration test data review

    NASA Technical Reports Server (NTRS)

    Harrison, P. M.; Smith, J. L.

    1984-01-01

    Dynamic testing of the Space Telescope Scientific Instrument Radial Latches was performed as specified by the designated test criteria. No structural failures were observed during the test. The alignment stability of the instrument simulator was within required tolerances after testing. Particulates were discovered around the latch bases, after testing, due to wearing at the B and C latch interface surfaces. This report covers criteria derivation, testing, and test results.

  8. A meta-analysis of an implicit measure of personality functioning: the Mutuality of Autonomy Scale.

    PubMed

    Graceffo, Robert A; Mihura, Joni L; Meyer, Gregory J

    2014-01-01

    The Mutuality of Autonomy scale (MA) is a Rorschach variable designed to capture the degree to which individuals mentally represent self and other as mutually autonomous versus pathologically destructive (Urist, 1977). Discussions of the MA's validity found in articles and chapters usually claim good support, which we evaluated by a systematic review and meta-analysis of its construct validity. Overall, in a random effects analysis across 24 samples (N = 1,801) and 91 effect sizes, the MA scale was found to maintain a relationship of r =.20, 95% CI [.16,.25], with relevant validity criteria. We hypothesized that MA summary scores that aggregate more MA response-level data would maintain the strongest relationship with relevant validity criteria. Results supported this hypothesis (aggregated scoring method: r =.24, k = 57, S = 24; nonaggregated scoring methods: r =.15, k = 34, S = 10; p =.039, 2-tailed). Across 7 exploratory moderator analyses, only 1 (criterion method) produced significant results. Criteria derived from the Thematic Apperception Test produced smaller effects than clinician ratings, diagnostic differentiation, and self-attributed characteristics; criteria derived from observer reports produced smaller effects than clinician ratings and self-attributed characteristics. Implications of the study's findings are discussed in terms of both research and clinical work.

  9. Altered soluble epoxide hydrolase-derived oxylipins in patients with seasonal major depression: An exploratory study.

    PubMed

    Hennebelle, Marie; Otoki, Yurika; Yang, Jun; Hammock, Bruce D; Levitt, Anthony J; Taha, Ameer Y; Swardfager, Walter

    2017-06-01

    Many cytochrome p450-derived lipids promote resolution of inflammation, in contrast to their soluble epoxide hydrolase(sEH)-derived oxylipin breakdown products. Here we compare plasma oxylipins and precursor fatty acids between seasons in participants with major depressive disorder with seasonal pattern (MDD-s). Euthymic participants with a history of MDD-s recruited in summer-fall were followed-up in winter. At both visits, a structured clinical interview (DSM-5 criteria) and the Beck Depression Inventory II (BDI-II) were administered. Unesterified and total oxylipin pools were assayed by liquid chromatography tandem mass-spectrometry (LC-MS/MS). Precursor fatty acids were measured by gas chromatography. In nine unmedicated participants euthymic at baseline who met depression criteria in winter, BDI-II scores increased from 4.9±4.4 to 19.9±7.7. Four sEH-derived oxylipins increased in winter compared to summer-fall with moderate to large effect sizes. An auto-oxidation product (unesterified epoxyketooctadecadienoic acid) and lipoxygenase-derived 13-hydroxyoctadecadienoic acid also increased in winter. The cytochrome p450-derived 20-COOH-leukotriene B4 (unesterified) and total 14(15)-epoxyeicosatetraenoic acid, and the sEH-derived 14,15-dihydroxyeicostrienoic acid (unesterified), decreased in winter. We conclude that winter depression was associated with changes in cytochrome p450- and sEH-derived oxylipins, suggesting that seasonal shifts in omega-6 and omega-3 fatty acid metabolism mediated by sEH may underlie inflammatory states in symptomatic MDD-s. Copyright © 2017 Elsevier Ireland Ltd. All rights reserved.

  10. 10 CFR Appendix A to Part 40 - Criteria Relating to the Operation of Uranium Mills and the Disposition of Tailings or Wastes...

    Code of Federal Regulations, 2010 CFR

    2010-01-01

    ... to be relied upon for seepage control, tests must be conducted with representative tailings solutions... itself. (6) The design requirements in this criterion for longevity and control of radon releases apply... licensee shall control, minimize, or eliminate post-closure escape of nonradiological hazardous...

  11. 76 FR 77877 - Self-Regulatory Organizations; NASDAQ OMX PHLX LLC; Notice of Withdrawal of Proposed Rule Change...

    Federal Register 2010, 2011, 2012, 2013, 2014

    2011-12-14

    ... SECURITIES AND EXCHANGE COMMISSION [Release No. 34-65917; File No. SR-Phlx-2011-143] Self... Commentary .01 to Rule 1009 Regarding Criteria for Listing an Option on an Underlying Covered Security December 8, 2011. On October 24, 2011, NASDAQ OMX PHLX LLC (``Phlx'') filed with the Securities and...

  12. 75 FR 67361 - Release of Final Document Related to the Review of the National Ambient Air Quality Standards for...

    Federal Register 2010, 2011, 2012, 2013, 2014

    2010-11-02

    ... Administrator identifies and lists certain pollutants which ``cause or contribute to air pollution which may reasonably be anticipated to endanger public health or welfare.'' The EPA then issues air quality criteria... establishes primary (health-based) and secondary (welfare-based) national ambient air quality standards (NAAQS...

  13. Validation of an In Vitro Bioaccessability Test Method for the Estimation of the Bioavailability of Arsenic from Soil and Sediment

    DTIC Science & Technology

    2012-12-01

    evaluate predictive performance following methods described in Malinowski et al. (1997). Acceptance criteria and control limits will be based on...69: 69–78. Malinowski , H., P. Marroum, V.R. Uppoor, et al. 1997. Draft guidance for industry extended release solid oral dosage forms. In: Young D

  14. ‘Carolina Broadleaf’ mustard green (Brassica juncea L.) resistant to the bacterial leaf blight pathogen Pseudomonas cannabina pv. alisalensis

    USDA-ARS?s Scientific Manuscript database

    A leafy-green mustard (Brassica juncea L.) cultivar designated ‘Carolina Broadleaf’ has been released by the Agricultural Research Service of the U.S. Dept. of Agriculture in 2015. This released cultivar is a narrow-based population of leafy-green mustard derived from a U.S. plant introduction (PI)...

  15. Registration of N6002 soybean germplasm with enhanced yield derived from Japanese cultivars Fukuyutaka and Nakasennari and elevated seed protein content

    USDA-ARS?s Scientific Manuscript database

    This release is part of a continuing effort to broaden the genetic base of applied North American soybean [Glycine max L. (Merr.)] breeding programs. N6002 was cooperatively developed and released by the USDA-ARS and the North Carolina Agricultural Research Service in September 2014 as a convention...

  16. Spatial Release from Masking in Adults with Bilateral Cochlear Implants: Effects of Distracter Azimuth and Microphone Location

    ERIC Educational Resources Information Center

    Davis, Timothy J.; Gifford, René H.

    2018-01-01

    Purpose: The primary purpose of this study was to derive spatial release from masking (SRM) performance-azimuth functions for bilateral cochlear implant (CI) users to provide a thorough description of SRM as a function of target/distracter spatial configuration. The secondary purpose of this study was to investigate the effect of the microphone…

  17. Tumor and Endothelial Cell-Derived Microvesicles Carry Distinct CEACAMs and Influence T-Cell Behavior

    PubMed Central

    Muturi, Harrison T.; Dreesen, Janine D.; Nilewski, Elena; Jastrow, Holger; Giebel, Bernd; Ergun, Suleyman; Singer, Bernhard B.

    2013-01-01

    Normal and malignant cells release a variety of different vesicles into their extracellular environment. The most prominent vesicles are the microvesicles (MVs, 100-1 000 nm in diameter), which are shed of the plasma membrane, and the exosomes (70-120 nm in diameter), derivates of the endosomal system. MVs have been associated with intercellular communication processes and transport numerous proteins, lipids and RNAs. As essential component of immune-escape mechanisms tumor-derived MVs suppress immune responses. Additionally, tumor-derived MVs have been found to promote metastasis, tumor-stroma interactions and angiogenesis. Since members of the carcinoembryonic antigen related cell adhesion molecule (CEACAM)-family have been associated with similar processes, we studied the distribution and function of CEACAMs in MV fractions of different human epithelial tumor cells and of human and murine endothelial cells. Here we demonstrate that in association to their cell surface phenotype, MVs released from different human epithelial tumor cells contain CEACAM1, CEACAM5 and CEACAM6, while human and murine endothelial cells were positive for CEACAM1 only. Furthermore, MVs derived from CEACAM1 transfected CHO cells carried CEACAM1. In terms of their secretion kinetics, we show that MVs are permanently released in low doses, which are extensively increased upon cellular starvation stress. Although CEACAM1 did not transmit signals into MVs it served as ligand for CEACAM expressing cell types. We gained evidence that CEACAM1-positive MVs significantly increase the CD3 and CD3/CD28-induced T-cell proliferation. All together, our data demonstrate that MV-bound forms of CEACAMs play important roles in intercellular communication processes, which can modulate immune response, tumor progression, metastasis and angiogenesis. PMID:24040308

  18. Exosome release of ADAM15 and the functional implications of human macrophage-derived ADAM15 exosomes.

    PubMed

    Lee, Hee Doo; Koo, Bon-Hun; Kim, Yeon Hyang; Jeon, Ok-Hee; Kim, Doo-Sik

    2012-07-01

    A disintegrin and metalloproteinase 15 (ADAM15), the only ADAM protein containing an Arg-Gly-Asp (RGD) motif in its disintegrin-like domain, is a widely expressed membrane protein that is involved in tumor progression and suppression. However, the underlying mechanism of ADAM15-mediated tumor suppression is not clearly understood. This study demonstrates that ADAM15 is released as an exosomal component, and ADAM15 exosomes exert tumor suppressive activities. We found that exosomal ADAM15 release is stimulated by phorbol 12-myristate 13-acetate, a typical protein kinase C activator, in various tumor cell types, and this results in a corresponding decrease in plasma membrane-associated ADAM15. Exosomes rich in ADAM15 display enhanced binding affinity for integrin αvβ3 in an RGD-dependent manner and suppress vitronectin- and fibronectin-induced cell adhesion, growth, and migration, as well as in vivo tumor growth. Exosomal ADAM15 is released from human macrophages, and macrophage-derived ADAM15 exosomes have tumor inhibitory effects. This work suggests a primary role of ADAM15 for exosome-mediated tumor suppression, as well as functional significance of exosomal ADAM protein in antitumor immunity.

  19. Delivery of Brain-Derived Neurotrophic Factor by 3D Biocompatible Polymeric Scaffolds for Neural Tissue Engineering and Neuronal Regeneration.

    PubMed

    Limongi, T; Rocchi, A; Cesca, F; Tan, H; Miele, E; Giugni, A; Orlando, M; Perrone Donnorso, M; Perozziello, G; Benfenati, Fabio; Di Fabrizio, Enzo

    2018-03-29

    Biopolymers are increasingly employed for neuroscience applications as scaffolds to drive and promote neural regrowth, thanks to their ability to mediate the upload and subsequent release of active molecules and drugs. Synthetic degradable polymers are characterized by different responses ranging from tunable distension or shrinkage to total dissolution, depending on the function they are designed for. In this paper we present a biocompatible microfabricated poly-ε-caprolactone (PCL) scaffold for primary neuron growth and maturation that has been optimized for the in vitro controlled release of brain-derived neurotrophic factor (BDNF). We demonstrate that the designed morphology confers to these devices an enhanced drug delivery capability with respect to monolithic unstructured supports. After incubation with BDNF, micropillared PCL devices progressively release the neurotrophin over 21 days in vitro. Moreover, the bioactivity of released BDNF is confirmed using primary neuronal cultures, where it mediates a consistent activation of BDNF signaling cascades, increased synaptic density, and neuronal survival. These results provide the proof-of-principle on the fabrication process of micropatterned PCL devices, which represent a promising therapeutic option to enhance neuronal regeneration after lesion and for neural tissue engineering and prosthetics.

  20. Monitoring multiple myeloma by idiotype-specific peptide binders of tumor-derived exosomes.

    PubMed

    Iaccino, Enrico; Mimmi, Selena; Dattilo, Vincenzo; Marino, Fabiola; Candeloro, Patrizio; Di Loria, Antonio; Marimpietri, Danilo; Pisano, Antonio; Albano, Francesco; Vecchio, Eleonora; Ceglia, Simona; Golino, Gaetanina; Lupia, Antonio; Fiume, Giuseppe; Quinto, Ileana; Scala, Giuseppe

    2017-10-13

    Tumor-derived exosomes (TDEs) play a pivotal role in tumor establishment and progression, and are emerging biomarkers for tumor diagnosis in personalized medicine. To date, there is a lack of efficient technology platforms for exosome isolation and characterization. Multiple myeloma (MM) is an incurable B-cell malignancy due to the rapid development of drug-resistance. MM-released exosomes express the immunoglobulin B-cell receptor (Ig-BCR) of the tumor B-cells, which can be targeted by Idiotype-binding peptides (Id-peptides). In this study, we analyzed the production of MM-released exosomes in the murine 5T33MM multiple myeloma model as biomarkers of tumor growth. To this end, we selected Id-peptides by screening a phage display library using as bait the Ig-BCR expressed by 5T33MM cells. By FACS, the FITC-conjugated Id-peptides detected the MM-released exosomes in the serum of 5T33MM-engrafted mice, levels of which are correlated with tumor progression at an earlier time point compared to serum paraprotein. These results indicate that Id-peptide-based recognition of MM-released exosomes may represent a very sensitive diagnostic approach for clinical evaluation of disease progression.

  1. Derivation of freshwater quality criteria for zinc using interspecies correlation estimation models to protect aquatic life in China.

    PubMed

    Feng, C L; Wu, F C; Dyer, S D; Chang, H; Zhao, X L

    2013-01-01

    Species sensitivity distributions (SSDs) are usually used in the development of water quality criteria and require a large number of toxicity values to define a hazard level to protect the majority of species. However, some toxicity data for certain chemicals are limited, especially for endangered and threatened species. Thus, it is important to predict the unknown species toxicity data using available toxicity data. To address this need, interspecies correlation estimation (ICE) models were developed by US EPA to predict acute toxicity of chemicals to diverse species based on a more limited data set of surrogate species toxicity data. Use of SSDs generated from ICE models allows for the prediction of protective water quality criteria, such as the HC5 (hazard concentration, 5th percentile). In the present study, we tested this concept using toxicity data collected for zinc. ICE-based-SSDs were generated using three surrogate species (common carp (Cyprinus carpio), rainbow trout (Oncorhynchus mykiss), and Daphnia magna) and compared with the measured-based SSD and corresponding HC5. The results showed that no significant differences were observed between the ICE- and the measured-based SSDs and HC5s. Furthermore, the examination of species placements within the SSDs indicated that the most sensitive species to zinc were invertebrates, especially crustaceans. Given the similarity of SSD and HC5s for zinc, the use of ICE to derive potential water quality criteria for diverse chemicals in China is proposed. Further, a combination of measured and ICE-derived data will prove useful for assessing water quality and chemical risks in the near future. Copyright © 2012 Elsevier Ltd. All rights reserved.

  2. Development of extended-release solid dispersion granules of tacrolimus: evaluation of release mechanism and human oral bioavailability.

    PubMed

    Tsunashima, Daisuke; Yamashita, Kazunari; Ogawara, Ken-Ichi; Sako, Kazuhiro; Hakomori, Tadashi; Higaki, Kazutaka

    2017-12-01

    We aimed to prepare a once-daily modified-release oral formulation of tacrolimus by utilizing an extended-release granules (ERG). Extended-release granules were prepared using ethylcellulose (EC), hydroxypropylmethylcellulose (HPMC) and lactose via a solvent evaporation method with ethanol. Physicochemical and biopharmaceutical studies were performed to determine the formulation with optimum release profile of tacrolimus from ERG. Tacrolimus existed in an amorphous state in ERG. Tacrolimus release from ERG was attenuated by EC and facilitated by lactose, suggesting that drug release kinetics could adequately be regulated by these components. Those release profiles were consistent with Higuchi's equation, suggesting a diffusion-type release mechanism. Smooth surface of ERG changed to the structure with pores after the release test, likely derived from the dissolution of HPMC and lactose. But ERG structure formed by EC was still maintained after the release test, leading to the longer maintenance of diffusion-type release. Two ERG formulations selected by blood concentration simulation successfully provided long-term retention of tacrolimus in blood in a human absorption study. We successfully developed the formulation exhibiting a significant reduction in C max , the longer mean residence time and AUC close to that of an immediate-release tacrolimus formulation, being preferred from the viewpoint of safe and effective immunosuppressant pharmacotherapy. © 2017 Royal Pharmaceutical Society.

  3. Technical Assessment of Internal Surface Smoothness and Particle Transmission to the American National Standard ANSI/HPS N13.1-2011

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

    Fritz, Brad G.; Barnett, J. M.

    2015-11-01

    Clause 6.4.4 in the American National Standards Institute / Health Physics Society (ANSI/HPS) N13.1 standard, Sampling and Monitoring Releases of Airborne Radioactive Substances From the Stacks and Ducts of Nuclear Facilities, addresses the internal smoothness of sample transport lines present between the nozzle and the analyzer (or collector). This paper evaluates the appropriateness of this clause by comparing roughness length of various materials against the required relative roughness, and by conducting computational fluid dynamic modeling. The results indicate that the inclusion of numerical criteria for the relative roughness of pipe by the ANSI Standard N13.1 (Section 6.4.4) is not appropriate.more » Recommended alternatives would be elimination of the numerical criteria, or modification of the standard to include a variable criteria for relative roughness.« less

  4. Rapid release of protoplasts from Eremothecium ashbyii in comparison with Trichoderma reesei and Penicillium chrysogenum using novozyme and funcelase.

    PubMed

    Lakshmi, B R; Chandra, T S

    1993-08-01

    Protoplast release in Eremothecium ashbyii, Trichoderma reesei, and Penicillium chrysogenum was achieved using commercially available enzymes, Novozyme 234 and Funcelase. A rapid release of protoplasts was observed in E. ashbyii, yielding nearly 4.0 x 10(7) protoplasts ml-1 in 10-35 min. The regeneration frequency of protoplasts from T. reesei, P. chrysogenum, and E. ashbyii using Funcelase was 51.77, 28.32, and 7.64%, respectively, and was higher in comparison with Novozyme-derived protoplasts.

  5. Large-scale manufacturing of GMP-compliant anti-EGFR targeted nanocarriers: production of doxorubicin-loaded anti-EGFR-immunoliposomes for a first-in-man clinical trial.

    PubMed

    Wicki, Andreas; Ritschard, Reto; Loesch, Uli; Deuster, Stefanie; Rochlitz, Christoph; Mamot, Christoph

    2015-04-30

    We describe the large-scale, GMP-compliant production process of doxorubicin-loaded and anti-EGFR-coated immunoliposomes (anti-EGFR-ILs-dox) used in a first-in-man, dose escalation clinical trial. 10 batches of this nanoparticle have been produced in clean room facilities. Stability data from the pre-GMP and the GMP batch indicate that the anti-EGFR-ILs-dox nanoparticle was stable for at least 18 months after release. Release criteria included visual inspection, sterility testing, as well as measurements of pH (pH 5.0-7.0), doxorubicin HCl concentration (0.45-0.55 mg/ml), endotoxin concentration (<1.21 IU/ml), leakage (<10%), particle size (Z-average of Caelyx ± 20 nm), and particle uptake (uptake absolute: >0.50 ng doxorubicin/μg protein; uptake relatively to PLD: >5 fold). All batches fulfilled the defined release criteria, indicating a high reproducibility as well as batch-to-batch uniformity of the main physico-chemical features of the nanoparticles in the setting of the large-scale GMP process. In the clinical trial, 29 patients were treated with this nanoparticle between 2007 and 2010. Pharmacokinetic data of anti-EGFR-ILs-dox collected during the clinical study revealed stability of the nanocarrier in vivo. Thus, reliable and GMP-compliant production of anti-EGFR-targeted nanoparticles for clinical application is feasible. Copyright © 2015 Elsevier B.V. All rights reserved.

  6. 76 FR 61438 - Self-Regulatory Organizations; International Securities Exchange, LLC; Notice of Proposed Rule...

    Federal Register 2010, 2011, 2012, 2013, 2014

    2011-10-04

    ... clarify that 2102(e) applies to trading halts in new derivative securities, so as to not be confused with... derivative securities products when a temporary interruption occurs in the calculation or wide dissemination... SECURITIES AND EXCHANGE COMMISSION [Release No. 34-65425; File No. SR-ISE-2011-61] Self-Regulatory...

  7. 78 FR 40788 - Self-Regulatory Organizations; Chicago Stock Exchange, Inc.; Notice of Filing and Immediate...

    Federal Register 2010, 2011, 2012, 2013, 2014

    2013-07-08

    ... eliminate references in Sections E.1 and E.8 to ``Derivative Securities Products'' (``DSPs'') and ``Non-Derivative Securities Products'' (``Non-DSPs'') and to eliminate references in Section E.1 to ``Regular... SECURITIES AND EXCHANGE COMMISSION [Release No. 34-69903; File No. SR-CHX-2013-12] Self-Regulatory...

  8. 78 FR 78424 - Self-Regulatory Organizations; Chicago Stock Exchange, Inc.; Notice of Filing and Immediate...

    Federal Register 2010, 2011, 2012, 2013, 2014

    2013-12-26

    ... Tapes, eliminated the distinction between Derivative Securities Products and Non-Derivative Securities... SECURITIES AND EXCHANGE COMMISSION [Release No. 34-71137; File No. SR-CHX-2013-22] Self-Regulatory...) \\1\\ of the Securities Exchange Act of 1934 (``Act'') \\2\\ and Rule 19b-4 thereunder,\\3\\ notice is...

  9. 77 FR 71020 - Self-Regulatory Organizations; NYSE Arca, Inc.; Notice of Filing and Immediate Effectiveness of...

    Federal Register 2010, 2011, 2012, 2013, 2014

    2012-11-28

    ... Products with that of derivative securities products, like ETFs, that are listed on the Exchange. In this regard, the Exchange believes that derivative securities products and Structured Products share certain... SECURITIES AND EXCHANGE COMMISSION [Release No. 34-68280; File No. SR-NYSEArca-2012-127] Self...

  10. Biomarker-indicated extent of oxidation of plant-derived organic carbon (OC) in relation to geomorphology in an arsenic contaminated Holocene aquifer, Cambodia.

    PubMed

    Magnone, Daniel; Richards, Laura A; Polya, David A; Bryant, Charlotte; Jones, Merren; van Dongen, Bart E

    2017-10-12

    The poisoning of rural populations in South and Southeast Asia due to high groundwater arsenic concentrations is one of the world's largest ongoing natural disasters. It is important to consider environmental processes related to the release of geogenic arsenic, including geomorphological and organic geochemical processes. Arsenic is released from sediments when iron-oxide minerals, onto which arsenic is adsorbed or incorporated, react with organic carbon (OC) and the OC is oxidised. In this study we build a new geomorphological framework for Kandal Province, a highly studied arsenic affected region of Cambodia, and tie this into wider regional environmental change throughout the Holocene. Analyses shows that the concentration of OC in the sediments is strongly inversely correlated to grainsize. Furthermore, the type of OC is also related to grain size with the clay containing mostly (immature) plant derived OC and sand containing mostly thermally mature derived OC. Finally, analyses indicate that within the plant derived OC relative oxidation is strongly grouped by stratigraphy with the older bound OC more oxidised than younger OC.

  11. Design, synthesis, and in vitro evaluation of new amphiphilic cyclodextrin-based nanoparticles for the incorporation and controlled release of acyclovir.

    PubMed

    Perret, Florent; Duffour, Marine; Chevalier, Yves; Parrot-Lopez, Hélène

    2013-01-01

    Acyclovir possesses low solubility in water and in lipid bilayers, so that its dosage forms do not allow suitable drug levels at target sites following oral, local, or parenteral administration. In order to improve this lack of solubility, new cyclodextrin-based amphiphilic derivatives have been designed to form nanoparticles, allowing the efficient encapsulation of this hydrophobic antiviral agent. The present work first describes the synthesis and characterization of five new O-2,O-3 permethylated O-6 alkylthio- and perfluoroalkyl-propanethio-amphiphilic β-cyclodextrins. These derivatives have been obtained with good overall yields. The capacity of these molecules to form nanoparticles in water and to encapsulate acyclovir has then been studied. The nanoparticles prepared from the new β-cyclodextrin derivatives have been characterized by dynamic light scattering and have an average size of 120nm for the fluorinated derivatives and 220nm for the hydrogenated analogs. They all allowed high loading and sustained release of acyclovir. Copyright © 2012 Elsevier B.V. All rights reserved.

  12. The UKIRT Hemisphere Survey: definition and J-band data release

    NASA Astrophysics Data System (ADS)

    Dye, S.; Lawrence, A.; Read, M. A.; Fan, X.; Kerr, T.; Varricatt, W.; Furnell, K. E.; Edge, A. C.; Irwin, M.; Hambly, N.; Lucas, P.; Almaini, O.; Chambers, K.; Green, R.; Hewett, P.; Liu, M. C.; McGreer, I.; Best, W.; Zhang, Z.; Sutorius, E.; Froebrich, D.; Magnier, E.; Hasinger, G.; Lederer, S. M.; Bold, M.; Tedds, J. A.

    2018-02-01

    This paper defines the UK Infra-Red Telescope (UKIRT) Hemisphere Survey (UHS) and release of the remaining ∼12 700 deg2 of J-band survey data products. The UHS will provide continuous J- and K-band coverage in the Northern hemisphere from a declination of 0° to 60° by combining the existing Large Area Survey, Galactic Plane Survey and Galactic Clusters Survey conducted under the UKIRT Infra-red Deep Sky Survey (UKIDSS) programme with this new additional area not covered by UKIDSS. The released data include J-band imaging and source catalogues over the new area, which, together with UKIDSS, completes the J-band UHS coverage over the full ∼17 900 deg2 area. 98 per cent of the data in this release have passed quality control criteria. The remaining 2 per cent have been scheduled for re-observation. The median 5σ point source sensitivity of the released data is 19.6 mag (Vega). The median full width at half-maximum of the point spread function across the data set is 0.75 arcsec. In this paper, we outline the survey management, data acquisition, processing and calibration, quality control and archiving as well as summarizing the characteristics of the released data products. The data are initially available to a limited consortium with a world-wide release scheduled for 2018 August.

  13. Glucose-Responsive Supramolecular Vesicles Based on Water-Soluble Pillar[5]arene and Pyridylboronic Acid Derivatives for Controlled Insulin Delivery.

    PubMed

    Gao, Lei; Wang, Tingting; Jia, Keke; Wu, Xuan; Yao, Chenhao; Shao, Wei; Zhang, Dongmei; Hu, Xiao-Yu; Wang, Leyong

    2017-05-11

    The stimuli-responsive behavior of supramolecular nanocarriers is crucial for their potential applications as smart drug delivery systems. We hereby constructed a glucose-responsive supramolecular drug delivery system based on the host-guest interaction between a water-soluble pillar[5]arene (WP5) and a pyridylboronic acid derivative (G) for insulin delivery and controlled release under physiological conditions. The approach represents the ideal treatment of diabetes mellitus. The drug loading and in vitro drug release experiments demonstrated that large molecular weight insulin could be encapsulated into the vesicles with high loading efficiency, which, to our knowledge, is the first example of small-size supramolecular vesicles with excellent encapsulation capacity of a large protein molecule. Moreover, FITC-labeled insulin was used to evaluate the release behavior of insulin, and it was demonstrated that high glucose concentration could facilitate the quick release of insulin, suggesting a smart drug delivery system for potential application in controlled insulin release only under hyperglycemic conditions. Finally, we demonstrated that these supramolecular nanocarriers have good cytocompatibility, which is essential for their further biomedical applications. The present study provides a novel strategy for the construction of glucose-responsive smart supramolecular drug delivery systems, which has potential applications for the treatment of diabetes mellitus. © 2017 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim.

  14. Histamine H4-Receptors Inhibit Mast Cell Renin Release in Ischemia/Reperfusion via Protein Kinase Cε-Dependent Aldehyde Dehydrogenase Type-2 Activation

    PubMed Central

    Aldi, Silvia; Takano, Ken-ichi; Tomita, Kengo; Koda, Kenichiro; Chan, Noel Y.-K.; Marino, Alice; Salazar-Rodriguez, Mariselis; Thurmond, Robin L.

    2014-01-01

    Renin released by ischemia/reperfusion (I/R) from cardiac mast cells (MCs) activates a local renin-angiotensin system (RAS) causing arrhythmic dysfunction. Ischemic preconditioning (IPC) inhibits MC renin release and consequent activation of this local RAS. We postulated that MC histamine H4-receptors (H4Rs), being Gαi/o-coupled, might activate a protein kinase C isotype–ε (PKCε)–aldehyde dehydrogenase type-2 (ALDH2) cascade, ultimately eliminating MC-degranulating and renin-releasing effects of aldehydes formed in I/R and associated arrhythmias. We tested this hypothesis in ex vivo hearts, human mastocytoma cells, and bone marrow–derived MCs from wild-type and H4R knockout mice. We found that activation of MC H4Rs mimics the cardioprotective anti-RAS effects of IPC and that protection depends on the sequential activation of PKCε and ALDH2 in MCs, reducing aldehyde-induced MC degranulation and renin release and alleviating reperfusion arrhythmias. These cardioprotective effects are mimicked by selective H4R agonists and disappear when H4Rs are pharmacologically blocked or genetically deleted. Our results uncover a novel cardioprotective pathway in I/R, whereby activation of H4Rs on the MC membrane, possibly by MC-derived histamine, leads sequentially to PKCε and ALDH2 activation, reduction of toxic aldehyde-induced MC renin release, prevention of RAS activation, reduction of norepinephrine release, and ultimately to alleviation of reperfusion arrhythmias. This newly discovered protective pathway suggests that MC H4Rs may represent a new pharmacologic and therapeutic target for the direct alleviation of RAS-induced cardiac dysfunctions, including ischemic heart disease and congestive heart failure. PMID:24696042

  15. Use of loading rates to establish dioxin criteria for land application of sludge

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

    Thiel, D.A.; Martin, S.G.; Goodman, B.B.

    1995-08-01

    A methodology derived from empirical field and laboratory data on wildlife toxicology, chemical concentrations, and loading rates is developed for defining criteria for protecting wildlife exposed to landspread materials containing 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) and TCDD-like compounds. The method controls mass loading, giving it clear advantages over soil-concentration-based criteria in situations where material is spread in a relatively thin layer on the surface and not incorporated into the soil. It also controls dioxin toxic equivalents in the target organism rather than in the landspread material. It achieves a high level of protection for bird embryos by applying a safety factor to amore » no-observed-adverse-effect level (NOAEL) derived from egg toxicity data and combining this adjusted NOAEL with bioaccumulation data from the most efficient avian accumulator of TCDD on a landspread site. Assuming that bird embryos are among the most sensitive organisms to TCDD in the terrestrial environment, dioxin restrictions adequate to safeguard eggs will protect other wildlife inhabiting landspread sites. Using this methodology, the Wisconsin Department of Natural Resources has derived the following wildlife dioxin criterion for surface spreading (i.e., no incorporation) a paper industry sludge: The sum of the mass of TCDD plus 0.0013 times the mass of 2,3,7,8-tetrachlorodibenzofuran (TCDF) shall not exceed 1.3 mg per hectare.« less

  16. Expressions for the Total Yaw Angle

    DTIC Science & Technology

    2016-09-01

    1. Introduction 1 2. Mathematical Notation 1 3. Total Yaw Expression Derivations 2 3.1 First Derivation 2 3.2 Second Derivation 4 3.3 Other...4 iv Approved for public release; distribution is unlimited. 1. Introduction The total yaw angle, γt , of a ballistic projectile is... elevation angles from spherical coordinates.∗ We again place point A at the end point of V. Now imagine a plane parallel to the y-z plane that includes

  17. Ceramide-1-phosphate regulates migration of multipotent stromal cells (MSCs) and endothelial progenitor cells (EPCs) – implications for tissue regeneration

    PubMed Central

    Kim, ChiHwa; Schneider, Gabriela; Abdel-Latif, Ahmed; Mierzejewska, Kasia; Sunkara, Manjula; Borkowska, Sylwia; Ratajczak, Janina; Morris, Andrew J.; Kucia, Magda; Ratajczak, Mariusz Z.

    2012-01-01

    Ceramide-1-phosphate (C1P) is a bioactive lipid that, in contrast to ceramide, is an anti-apoptotic molecule released from cells that are damaged and “leaky”. As reported recently, C1P promotes migration of hematopoietic cells. In the current paper, we tested the hypothesis that C1P released upon tissue damage may play an underappreciated role in chemoattraction of various types of stem cells and endothelial cells involved in tissue/organ regeneration. We show for a first time that C1P is upregulated in damaged tissues and chemoattracts BM-derived multipotent stroma cells (MSCs), endothelial progenitor cells (EPCs), and very small embryonic-like stem cells (VSELs). Furthermore, compared to other bioactive lipids, C1P more potently chemoattracted human umbilical vein endothelial cells (HUVECs) and stimulated tube formation by these cells. C1P also promoted in vivo vascularization of Matrigel implants and stimulated secretion of stromal derived factor-1 (SDF-1) from BM-derived fibroblasts. Thus, our data demonstrate, for the first time, that C1P is a potent bioactive lipid released from damaged cells that potentially plays an important and novel role in recruitment of stem/progenitor cells to damaged organs and may promote their vascularization. PMID:23193025

  18. Fertilizer-derived uranium and sulfur in rangeland soil and runoff: A case study in central Florida

    USGS Publications Warehouse

    Zielinski, R.A.; Orem, W.H.; Simmons, K.R.; Bohlen, P.J.

    2006-01-01

    Fertilizer applications to rangeland and pastures in central Florida have potential impact on the nutrient-sensitive ecosystems of Lake Okeechobee and the Northern Everglades. To investigate the effects of fertilizer applications, three soil profiles from variably managed and improved rangeland, and four samples of surface runoff from both fertilized and unfertilized pasture were collected. In addition to determining nutrient concentrations, isotopic analyses of uranium (U) and sulfur (S) were performed to provide isotopic evidence for U derived from historically applied phosphate (P)-bearing fertilizer ( 234 U 238U activity ratio =1.0 ?? 0.05), and Sderived from recently applied ammonium sulfate fertilizer(??34 S=3.5permil).The distribution and mobility of fertilizer-derived U in these samples is considered to be analogous to that of fertilizer-derived phosphate.Variations of U concentrations and 234 U/238 U activity ratios in soils indicate contribution of fertilizer-derived U in the upper portions of the fertilized soil (15-}34 percent of total U). The U isotope data for runoff from the fertilized field also are consistent with some contribution from fertilizer-derived U. Parallel investigations of S showed no consistent chemical or isotopic evidence for significant fertilizer-derived sulfate in rangeland soil or runoff. Relatively abundant and isotopically variable S present in the local environment hinders detection of fertilizer-derived sulfate. The results indicate a continuing slow-release of fertilizer-derived U and, by inference, P, to the P-sensitive ecosystem, and a relatively rapid release of sulfate of possible natural origin. ?? Springer 2006.

  19. Host cell recruitment patterns by bone morphogenetic protein-2 releasing hyaluronic acid hydrogels in a mouse subcutaneous environment.

    PubMed

    Todeschi, Maria R; El Backly, Rania M; Varghese, Oommen P; Hilborn, Jöns; Cancedda, Ranieri; Mastrogiacomo, Maddalena

    2017-07-01

    This study aimed to identify host cell recruitment patterns in a mouse model in response to rhBMP-2 releasing hyaluronic acid hydrogels and influence of added nano-hydroxyapatite particles on rhBMP-2 release and pattern of bone formation. Implanted gels were retrieved after implantation and cells were enzymatically dissociated for flow cytometric analysis. Percentages of macrophages, progenitor endothelial cells and putative mesenchymal stem cells were measured. Implants were evaluated for BMP-2 release by ELISA and by histology to monitor tissue formation. Hyaluronic acid+BMP-2 gels influenced the inflammatory response in the bone healing microenvironment. Host-derived putative mesenchymal stem cells were major contributors. Addition of hydroxyapatite nanoparticles modified the release pattern of rhBMP-2, resulting in enhanced bone formation.

  20. Release of superoxide and change in morphology by neutrophils in response to phorbol esters: antagonism by inhibitors of calcium-binding proteins

    PubMed Central

    1985-01-01

    The ability of phorbol derivatives to function as stimulating agents for superoxide (O2-) release by guinea pig neutrophils has been evaluated and compared to the known ability of each compound to activate protein kinase C. Those that activate the kinase also stimulate O2- release, while those that are inactive with respect to the kinase have no effect on O2- release. The same correlation was observed with respect to the ability of phorbol esters to induce morphological changes in neutrophils, i.e., vesiculation and reduction in granule content. Certain phenothiazines and naphthalene sulfonamides that are known antagonists of calcium-binding proteins blocked both phorbol ester-induced O2- release and morphological changes in these cells. PMID:2993312

  1. Gc protein-derived macrophage activating factor (GcMAF): isoelectric focusing pattern and tumoricidal activity.

    PubMed

    Mohamad, Saharuddin Bin; Nagasawa, Hideko; Sasaki, Hideyuki; Uto, Yoshihiro; Nakagawa, Yoshinori; Kawashima, Ken; Hori, Hitoshi

    2003-01-01

    Gc protein is the precursor for Gc protein-derived macrophage activating factor (GcMAF), with three phenotypes: Gc1f, Gc1s and Gc2, based on its electrophoretic mobility. The difference in electrophoretic mobility is because of the difference in its posttranslational sugar moiety composition. We compared the difference between Gc protein and GcMAF electrophoretic mobility using the isoelectric focusing (IEF) method. The tumoricidal activity of GcMAF-treated macrophage was evaluated after coculture with L-929 cell. The tumoricidal mechanism was investigated using TNF bioassay and nitric oxide (NO) release. The difference in Gc protein and GcMAF electrophoretic mobility was detected. The tumoricidal activity of GcMAF-treated macrophage was detected, but no release of TNF and NO was detected. The difference of isoelectric focusing mobility in Gc protein and GcMAF would be useful to develop a GcMAF detection method. GcMAF increased macrophage tumoricidal activity but TNF and NO release were not involved in the mechanism.

  2. Neutrophil-derived resistin release induced by Aggregatibacter actinomycetemcomitans.

    PubMed

    Furugen, Reiko; Hayashida, Hideaki; Yoshii, Yumiko; Saito, Toshiyuki

    2011-08-01

    Resistin is an adipokine that induces insulin resistance in mice. In humans, resistin is not produced in adipocytes, but in various leukocytes instead, and it acts as a proinflammatory molecule. The present investigation demonstrated high levels of resistin in culture supernatants of neutrophils that are stimulated by a highly leukotoxic strain of Aggregatibacter actinomycetemcomitans. In contrast, the level of resistin was remarkably low when neutrophils were exposed to two other strains that produce minimal levels of leukotoxin and a further isogenic mutant strain incapable of producing leukotoxin. Pretreatment of neutrophils with a monoclonal antibody to CD18, β chain of lymphocyte function-associated molecule 1 (LFA-1), or an Src family tyrosine kinase inhibitor before incubation with the highly leukotoxic strain inhibited the release of resistin. These results show that A. actinomycetemcomitans-expressed leukotoxin induces extracellular release of human neutrophil-derived resistin by interacting with LFA-1 on the surface of neutrophils and, consequently, activating Src family tyrosine kinases. 2011 Federation of European Microbiological Societies. Published by Blackwell Publishing Ltd. All rights reserved.

  3. New biodegradable dextran-based hydrogels for protein delivery: Synthesis and characterization.

    PubMed

    Pacelli, Settimio; Paolicelli, Patrizia; Casadei, Maria Antonietta

    2015-08-01

    A new derivative of dextran grafted with polyethylene glycol methacrylate through a carbonate bond (DEX-PEG-MA) has been synthesized and characterized. The photo-crosslinking reaction of DEX-PEG-MA allowed the obtainment of biodegradable networks tested for their mechanical and release properties. The new hydrogels were compared with those made of dextran methacrylate (DEX-MA), often employed as drug delivery systems of small molecules. The inclusion of PEG as a spacer created additional interactions among the polymeric chains improving the extreme fragility and lack of hardness typical of gels made of DEX-MA. Moreover, the different behavior in terms of swelling and degradability of the networks was able to affect the release of a model macromolecule over time, making DEX-PEG-MA matrices suitable candidates for the delivery of high molecular weight peptides. Interestingly, the combination of the two dextran derivatives showed intermediate ability to modulate the release of high molecular weight macromolecules. Copyright © 2015 Elsevier Ltd. All rights reserved.

  4. Gastrointestinal defense mechanisms.

    PubMed

    Said, Hyder; Kaunitz, Jonathan D

    2016-11-01

    To summarize and illuminate the recent findings regarding gastroduodenal mucosal defense mechanisms and the specific biomolecules involved in regulating this process, such as glucagon-like peptides (GLPs). There has been a growing interest in luminal nutrient chemosensing and its physiological effects throughout the digestive system. From the ingestion of food in the oral cavity to the processing and absorption of nutrients in the intestines, nutrient chemosensing receptors signal the production and release of numerous bioactive peptides from enteroendocrine cells, such as the proglucagon-derived peptides. There has been a major emphasis on two proglucagon-derived peptides, namely GLP-1 and GLP-2, due to their apparent beneficial effect on gut structure, function, and on metabolic processes. As an incretin, GLP-1 not only enhances the effect and release of insulin on pancreatic βcells but also has been implicated in having trophic effects on the intestinal epithelium. In addition, GLP-2, the other major proglucagon-derived peptide, has potent intestinotrophic effects, such as increasing the rate of mucosal stem cell proliferation, mucosal blood flow, and fluid absorption, as well as augmenting the rate of duodenal bicarbonate secretion to improve gastric mucosal health and longevity. Understanding the mechanisms underlying nutrient chemosensing and how it relates to GLP release can further elucidate how the gut functions in response to cellular changes and disturbances. Furthermore, a more in-depth comprehension of GLP release and its tissue-specific effects will help improve the utility of GLP-1 and GLP-2 receptor agonists in clinical settings. This, in turn, should help patients suffering from intestinal failure, malabsorption, and mucosal injury.

  5. Liver Cell-Derived Microparticles Activate Hedgehog Signaling and Alter Gene Expression in Hepatic Endothelial Cells

    PubMed Central

    Witek, Rafal P.; Yang, Liu; Liu, Renshui; Jung, Youngmi; Omenetti, Alessia; Syn, Wing-Kin; Choi, Steve S.; Cheong, Yeiwon; Fearing, Caitlin M.; Agboola, Kolade M.; Chen, Wei; Diehl, Anna Mae

    2013-01-01

    Background & Aims Angiogenesis contributes to vascular remodeling during cirrhosis. In cirrhotic livers, cholangiocytes and myofibroblastic hepatic stellate cells (MF-HSC) produce Hedgehog (Hh) ligands. During embryogenesis Hh ligands are released from ligand-producing cells in microparticles and activate Hh signaling in endothelial cells. We studied whether adult liver cell-derived microparticles contain Hh ligands that alter hepatic sinusoidal endothelial cells (SEC). Methods MF-HSCs and cholangiocytes were exposed to platelet-derived growth factor (PDGF) to induce Hh ligands; microparticles were isolated from medium, analyzed by transmission electron microscopy (TEM) and immunoblots, and applied to Hh-reporter containing cells. Microparticles were also obtained from serum and bile of rats after bile duct ligation (BDL) or sham surgery and applied to normal primary liver SEC with or without cyclopamine, a Hh signaling inhibitor. Effects on SEC gene expression were evaluated by QRT-PCR and immunoblotting. Finally, Hh target gene expression and SEC activation markers were compared in primary SEC and in liver sections from healthy and BDL rats. Results PDGF-treated MF-HSC and cholangiocytes released exosome-enriched microparticles containing biologically active Hh ligands. BDL also increased release of Hh-containing exosome-enriched microparticles into plasma and bile. TEM and immunoblots revealed similarities among microparticles from all sources; all microparticles induced similar Hh-dependent changes in SEC gene expression. SEC from healthy livers did not express Hh target genes or activation markers, but both were up-regulated in SEC after BDL. Conclusions Hh-containing exosome-enriched microparticles released from liver cells alter hepatic SEC gene expression, suggesting a novel mechanism for cirrhotic vasculopathy. PMID:19013163

  6. The principle of homologous groups in regulatory affairs of allergen products--a proposal.

    PubMed

    Lorenz, A R; Lüttkopf, D; May, S; Scheurer, S; Vieths, S

    2009-01-01

    Among other legal regulations, the Note for Guidance on Allergen Products CPMP/BWP/243/96 released by the European Medicines Agency provides regulatory instructions regarding the quality of allergen extracts for diagnostic or therapeutic purposes. The current revision of this guideline intends to transform the so-called 'principle of taxonomic families' to the 'principle of homologous groups'. According to this concept, the data of one allergen extract demonstrating stability, efficacy and safety can, to a limited extent, be extrapolated to other allergen extracts belonging to the same homologous groups. The present work proposes the formation of homologous groups for pollen species and animal-derived materials on the basis of similar biochemical composition and homology/cross-reactivity of allergens or allergen sources. Some tree pollen species could be assigned to three different homologous groups, some weed pollen species to one homologous group and numerous grass pollen species to one homologous group on condition that data rely on single defined representative species. A homologous group for mites is limited to the Dermatophagoides species and the grouping of vertebrate-derived materials such as dander could be possible under restrictions. The criteria for the formation of the proposed homologous groups are illustrated in detail to provide an opportunity for extending existing homologous groups by further species in case of new insights in allergens and cross-reactivity of allergen sources. In this way, the concept of homologous groups could serve as a dynamic tool in the regulation of allergen products. (c) 2008 S. Karger AG, Basel.

  7. Design enhancement tools in MSC/NASTRAN

    NASA Technical Reports Server (NTRS)

    Wallerstein, D. V.

    1984-01-01

    Design sensitivity is the calculation of derivatives of constraint functions with respect to design variables. While a knowledge of these derivatives is useful in its own right, the derivatives are required in many efficient optimization methods. Constraint derivatives are also required in some reanalysis methods. It is shown where the sensitivity coefficients fit into the scheme of a basic organization of an optimization procedure. The analyzer is to be taken as MSC/NASTRAN. The terminator program monitors the termination criteria and ends the optimization procedure when the criteria are satisfied. This program can reside in several plances: in the optimizer itself, in a user written code, or as part of the MSC/EOS (Engineering Operating System) MSC/EOS currently under development. Since several excellent optimization codes exist and since they require such very specialized technical knowledge, the optimizer under the new MSC/EOS is considered to be selected and supplied by the user to meet his specific needs and preferences. The one exception to this is a fully stressed design (FSD) based on simple scaling. The gradients are currently supplied by various design sensitivity options now existing in MSC/NASTRAN's design sensitivity analysis (DSA).

  8. Hyperglycemic clamp and oral glucose tolerance test for 3-year prediction of clinical onset in persistently autoantibody-positive offspring and siblings of type 1 diabetic patients.

    PubMed

    Balti, Eric V; Vandemeulebroucke, Evy; Weets, Ilse; Van De Velde, Ursule; Van Dalem, Annelien; Demeester, Simke; Verhaeghen, Katrijn; Gillard, Pieter; De Block, Christophe; Ruige, Johannes; Keymeulen, Bart; Pipeleers, Daniel G; Decochez, Katelijn; Gorus, Frans K

    2015-02-01

    In preparation of future prevention trials, we aimed to identify predictors of 3-year diabetes onset among oral glucose tolerance test (OGTT)- and hyperglycemic clamp-derived metabolic markers in persistently islet autoantibody positive (autoAb(+)) offspring and siblings of patients with type 1 diabetes (T1D). The design is a registry-based study. Functional tests were performed in a hospital setting. Persistently autoAb(+) first-degree relatives of patients with T1D (n = 81; age 5-39 years). We assessed 3-year predictive ability of OGTT- and clamp-derived markers using receiver operating characteristics (ROC) and Cox regression analysis. Area under the curve of clamp-derived first-phase C-peptide release (AUC(5-10 min); min 5-10) was determined in all relatives and second-phase release (AUC(120-150 min); min 120-150) in those aged 12-39 years (n = 62). Overall, the predictive ability of AUC(5-10 min) was better than that of peak C-peptide, the best predictor among OGTT-derived parameters (ROC-AUC [95%CI]: 0.89 [0.80-0.98] vs 0.81 [0.70-0.93]). Fasting blood glucose (FBG) and AUC(5-10 min) provided the best combination of markers for prediction of diabetes within 3 years; (ROC-AUC [95%CI]: 0.92 [0.84-1.00]). In multivariate Cox regression analysis, AUC(5-10 min)) (P = .001) was the strongest independent predictor and interacted significantly with all tested OGTT-derived parameters. AUC(5-10 min) below percentile 10 of controls was associated with 50-70% progression to T1D regardless of age. Similar results were obtained for AUC(120-150 min). Clamp-derived first-phase C-peptide release can be used as an efficient and simple screening strategy in persistently autoAb(+) offspring and siblings of T1D patients to predict impending diabetes.

  9. Intracellular sphingosine releases calcium from lysosomes.

    PubMed

    Höglinger, Doris; Haberkant, Per; Aguilera-Romero, Auxiliadora; Riezman, Howard; Porter, Forbes D; Platt, Frances M; Galione, Antony; Schultz, Carsten

    2015-11-27

    To elucidate new functions of sphingosine (Sph), we demonstrate that the spontaneous elevation of intracellular Sph levels via caged Sph leads to a significant and transient calcium release from acidic stores that is independent of sphingosine 1-phosphate, extracellular and ER calcium levels. This photo-induced Sph-driven calcium release requires the two-pore channel 1 (TPC1) residing on endosomes and lysosomes. Further, uncaging of Sph leads to the translocation of the autophagy-relevant transcription factor EB (TFEB) to the nucleus specifically after lysosomal calcium release. We confirm that Sph accumulates in late endosomes and lysosomes of cells derived from Niemann-Pick disease type C (NPC) patients and demonstrate a greatly reduced calcium release upon Sph uncaging. We conclude that sphingosine is a positive regulator of calcium release from acidic stores and that understanding the interplay between Sph homeostasis, calcium signaling and autophagy will be crucial in developing new therapies for lipid storage disorders such as NPC.

  10. Pest persistence and eradication conditions in a deterministic model for sterile insect release.

    PubMed

    Gordillo, Luis F

    2015-01-01

    The release of sterile insects is an environment friendly pest control method used in integrated pest management programmes. Difference or differential equations based on Knipling's model often provide satisfactory qualitative descriptions of pest populations subject to sterile release at relatively high densities with large mating encounter rates, but fail otherwise. In this paper, I derive and explore numerically deterministic population models that include sterile release together with scarce mating encounters in the particular case of species with long lifespan and multiple matings. The differential equations account separately the effects of mating failure due to sterile male release and the frequency of mating encounters. When insects spatial spread is incorporated through diffusion terms, computations reveal the possibility of steady pest persistence in finite size patches. In the presence of density dependence regulation, it is observed that sterile release might contribute to induce sudden suppression of the pest population.

  11. Advances in mechanistic understanding of release rate control mechanisms of extended-release hydrophilic matrix tablets.

    PubMed

    Timmins, Peter; Desai, Divyakant; Chen, Wei; Wray, Patrick; Brown, Jonathan; Hanley, Sarah

    2016-08-01

    Approaches to characterizing and developing understanding around the mechanisms that control the release of drugs from hydrophilic matrix tablets are reviewed. While historical context is provided and direct physical characterization methods are described, recent advances including the role of percolation thresholds, the application on magnetic resonance and other spectroscopic imaging techniques are considered. The influence of polymer and dosage form characteristics are reviewed. The utility of mathematical modeling is described. Finally, how all the information derived from applying the developed mechanistic understanding from all of these tools can be brought together to develop a robust and reliable hydrophilic matrix extended-release tablet formulation is proposed.

  12. Modifying the release of leuprolide from spray dried OED microparticles.

    PubMed

    Alcock, R; Blair, J A; O'Mahony, D J; Raoof, A; Quirk, A V

    2002-08-21

    A range of oligosaccharide ester derivatives (OEDs) have been designed as drug delivery matrices for controlled release. The synthetic hormone analogue, leuprolide, was encapsulated within these matrices using hydrophobic ion pairing and solvent spray drying. The particles produced modified the release of leuprolide in vitro (dissolution in phosphate buffered saline) and in vivo (subcutaneous and pulmonary delivery in the rat). Release rate was dependent on drug loading and could be manipulated by choice of OED and by combining different OEDs in different ratios. Leuprolide encapsulated in the OEDs retained biological activity as evidenced by elevation in plasma luteinising hormone levels following subcutaneous injection of leuprolide recovered from OED particles in vitro prior to in vivo administration.

  13. Psychometric analysis of the new ADHD DSM-V derived symptoms.

    PubMed

    Ghanizadeh, Ahmad

    2012-03-20

    Following the agreements on the reformulating and revising of ADHD diagnostic criteria, recently, the proposed revision for ADHD added 4 new symptoms to the hyperactivity and Impulsivity aspect in DSM-V. This study investigates the psychometric properties of the proposed ADHD diagnostic criteria. ADHD diagnosis was made according to DSM-IV. The parents completed the screening test of ADHD checklist of Child Symptom Inventory-4 and the 4 items describing the new proposed symptoms in DSM-V. The confirmatory factor analysis of the ADHD DSM-V derived items supports the loading of two factors including inattentiveness and hyperactivity/impulsivity. There is a sufficient reliability for the items. However, confirmatory factor analysis showed that the three-factor model is better fitted than the two-factor one. Moreover, the results of the exploratory analysis raised some concerns about the factor loading of the four new items. The current results support the two-factor model of the DSM-V ADHD diagnostic criteria including inattentiveness and hyperactivity/impulsivity. However, the four new items can be considered as a third factor.

  14. Near-Earth object hazardous impact: A Multi-Criteria Decision Making approach.

    PubMed

    Sánchez-Lozano, J M; Fernández-Martínez, M

    2016-11-16

    The impact of a near-Earth object (NEO) may release large amounts of energy and cause serious damage. Several NEO hazard studies conducted over the past few years provide forecasts, impact probabilities and assessment ratings, such as the Torino and Palermo scales. These high-risk NEO assessments involve several criteria, including impact energy, mass, and absolute magnitude. The main objective of this paper is to provide the first Multi-Criteria Decision Making (MCDM) approach to classify hazardous NEOs. Our approach applies a combination of two methods from a widely utilized decision making theory. Specifically, the Analytic Hierarchy Process (AHP) methodology is employed to determine the criteria weights, which influence the decision making, and the Technique for Order Performance by Similarity to Ideal Solution (TOPSIS) is used to obtain a ranking of alternatives (potentially hazardous NEOs). In addition, NEO datasets provided by the NASA Near-Earth Object Program are utilized. This approach allows the classification of NEOs by descending order of their TOPSIS ratio, a single quantity that contains all of the relevant information for each object.

  15. Healthcare-associated infection surveillance and bedside alerts.

    PubMed

    Adlassnig, Klaus-Peter; Berger, Angelika; Koller, Walter; Blacky, Alexander; Mandl, Harald; Unterasinger, Lukas; Rappelsberger, Andrea

    2014-01-01

    Expectations and requirements concerning the identification and surveillance of healthcare-associated infections (HAIs) are increasing, calling for differentiated automated approaches. In an attempt to bridge the "definition swamp" of these infections and serve the needs of different users, we improved the monitoring of nosocomial infections (MONI) software to create better surveillance reports according to consented national and international definitions, as well as produce infection overviews on complex clinical matters including alerts for the clinician's ward and bedside work. MONI contains and processes surveillance definitions for intensive-care-unit-acquired infections from the European Centre for Disease Prevention and Control, Sweden, as well as the Centers for Disease Control and Prevention, USA. The latest release of MONI also includes KISS criteria of the German National Reference Center for Surveillance of Nosocomial Infections. In addition to these "classic" surveillance criteria, clinical alert criteria--which are similar but not identical to the surveillance criteria--were established together with intensivists. This is an important step to support both infection control and clinical personnel; and--last but not least--to foster co-evolution of the two groups of definitions: surveillance and alerts.

  16. Lack of muco-cutaneous signs of toxic shock syndrome when T cells are absent: S.aureus shock in immunodeficient adults with multiple myeloma

    PubMed Central

    KAMEL, N S; BANKS, M C; DOSIK, A; URSEA, D; YARILINA, A A; POSNETT, D N

    2002-01-01

    Staphylococcal toxic shock syndrome (TSS) is an acute life threatening disease. The diagnosis can be made clinically based on diagnostic criteria. The clinical manifestations are caused in large part by the release of high levels of T-cell-derived cytokines as a result of potent toxins, also called superantigens (SAg), produced by Staphylococcus aureus, but it is not clear which clinical symptoms/signs are strictly T-cell dependent. Here, we report on three adults with multiple myeloma (MM) presenting with S. aureus sepsis/shock, and two patients with typical TSS. The MM patients had compromised humoral immunity because of depression of normal immunoglobulin (Ig) levels at the expense of the M protein. In addition, their T cells were absent due to high dose chemotherapy initiated for bone marrow transplantation. The MM cases lacked mucosal hyperemia, erythroderma and desquamation, but were otherwise indistinguishable from the TSS cases. All patients grew S. aureus and in each case, SAg genes were detected by PCR. In several cases, the plasma contained biological SAg activity resulting in Vβ specific proliferation of indicator T cells in vitro. The same specific activity was observed with the supernatant fluids of S. aureus broth cultures from the respective bacterial isolates. This confirms the presence of bio-active toxins in the plasma but did not lead to full blown TSS when T cells were lacking. Thus, S.aureus sepsis/shock can be clinically distinguished from typical TSS, and we suggest that muco-cutaneous manifestations of TSS are the most telling signs of massive T-cell-dependent cytokine release. PMID:12033193

  17. In pursuit of goodness in bioethics: analysis of an exemplary article.

    PubMed

    Hofmann, Bjørn; Magelssen, Morten

    2018-06-15

    What is good bioethics? Addressing this question is key for reinforcing and developing the field. In particular, a discussion of potential quality criteria can heighten awareness and contribute to the quality of bioethics publications. Accordingly, the objective of this article is threefold: first, we want to identify a set of criteria for quality in bioethics. Second, we want to illustrate the added value of a novel method: in-depth analysis of a single article with the aim of deriving quality criteria. The third and ultimate goal is to stimulate a broad and vivid debate on goodness in bioethics. An initial literature search reveals a range of diverse quality criteria. In order to expand on the realm of such quality criteria, we perform an in-depth analysis of an article that is acclaimed for being exemplary. The analysis results in eleven specific quality criteria for good bioethics in three categories: argumentative, empirical, and dialectic. Although we do not claim that the identified criteria are universal or absolute, we argue that they are fruitful for fueling a continuous constitutive debate on what is "good bioethics." Identifying, debating, refining, and applying such criteria is an important part of defining and improving bioethics.

  18. Development of an environmental impact model for the steel industry in Libya

    NASA Astrophysics Data System (ADS)

    Zaghinin, Mansur Salem

    The global demand for steel is rising due to the infrastructural development of emergent economies in countries such as India, China, Thailand and Libya. Consequently, global steel production has increased dramatically and is expected to grow further in the future. Processing iron and steel is associated with a number of sustainable development challenges, including various economic, environmental and social issues. The increasing prominence of environmental issues in international and national political discourse, including the developing countries, means that stakeholders demand that manufacturers minimise the negative impacts of their operations.The steel industry must be able to measure and assess its environmental impacts and demonstrate continuous improvements. This requires an environmental management strategy to manage and minimise impacts on the environment. This study focuses on developing an environmental impacts model in steel industry to investigate the most important environmental parameters and their importance in order to mitigate environmental impacts.Based on the literature review and the elements that are considered as waste (derived from the waste survey in Libyan iron and steel industry), the potential environmental impacts of the steel industry are identified as criteria and sub-criteria. Then, a model is built using the Analytical Hierarchy Process (AHP) software based on the identified criteria and sub-criteria.The model also illustrates the overall goal which is creating environmental impacts model for steel industry, in addition, criteria and sub-criteria are listed to clarify the situation and make the analysis clearer and understandable. Pair wise comparisons are used to derive accurate ratio scale priorities.The results are analysed and presented as prioritised list of environmental impacts. Moreover, a series of sensitivity analyses are conducted to investigate the impact of changing the priority of the criteria on the alternatives' ranking. The validation of the proposed model is carried out to assess its validity and to see this model from the perspectives of the professionals from steel industry.

  19. 2017 European League Against Rheumatism/American College of Rheumatology classification criteria for adult and juvenile idiopathic inflammatory myopathies and their major subgroups.

    PubMed

    Lundberg, Ingrid E; Tjärnlund, Anna; Bottai, Matteo; Werth, Victoria P; Pilkington, Clarissa; Visser, Marianne de; Alfredsson, Lars; Amato, Anthony A; Barohn, Richard J; Liang, Matthew H; Singh, Jasvinder A; Aggarwal, Rohit; Arnardottir, Snjolaug; Chinoy, Hector; Cooper, Robert G; Dankó, Katalin; Dimachkie, Mazen M; Feldman, Brian M; Torre, Ignacio Garcia-De La; Gordon, Patrick; Hayashi, Taichi; Katz, James D; Kohsaka, Hitoshi; Lachenbruch, Peter A; Lang, Bianca A; Li, Yuhui; Oddis, Chester V; Olesinska, Marzena; Reed, Ann M; Rutkowska-Sak, Lidia; Sanner, Helga; Selva-O'Callaghan, Albert; Song, Yeong-Wook; Vencovsky, Jiri; Ytterberg, Steven R; Miller, Frederick W; Rider, Lisa G

    2017-12-01

    To develop and validate new classification criteria for adult and juvenile idiopathic inflammatory myopathies (IIM) and their major subgroups. Candidate variables were assembled from published criteria and expert opinion using consensus methodology. Data were collected from 47 rheumatology, dermatology, neurology and paediatric clinics worldwide. Several statistical methods were used to derive the classification criteria. Based on data from 976 IIM patients (74% adults; 26% children) and 624 non-IIM patients with mimicking conditions (82% adults; 18% children), new criteria were derived. Each item is assigned a weighted score. The total score corresponds to a probability of having IIM. Subclassification is performed using a classification tree. A probability cut-off of 55%, corresponding to a score of 5.5 (6.7 with muscle biopsy) 'probable IIM', had best sensitivity/specificity (87%/82% without biopsies, 93%/88% with biopsies) and is recommended as a minimum to classify a patient as having IIM. A probability of ≥90%, corresponding to a score of ≥7.5 (≥8.7 with muscle biopsy), corresponds to 'definite IIM'. A probability of <50%, corresponding to a score of <5.3 (<6.5 with muscle biopsy), rules out IIM, leaving a probability of ≥50 to <55% as 'possible IIM'. The European League Against Rheumatism/American College of Rheumatology (EULAR/ACR) classification criteria for IIM have been endorsed by international rheumatology, dermatology, neurology and paediatric groups. They employ easily accessible and operationally defined elements, and have been partially validated. They allow classification of 'definite', 'probable' and 'possible' IIM, in addition to the major subgroups of IIM, including juvenile IIM. They generally perform better than existing criteria. © Article author(s) (or their employer(s) unless otherwise stated in the text of the article) 2017. All rights reserved. No commercial use is permitted unless otherwise expressly granted.

  20. The in vitro release of cytokines and growth factors from fibrin membranes produced through horizontal centrifugation.

    PubMed

    Lourenço, Emanuelle Stellet; Mourão, Carlos Fernando de Almeida Barros; Leite, Paulo Emílio Corrêa; Granjeiro, José Mauro; Calasans-Maia, Mônica Diuana; Alves, Gutemberg Gomes

    2018-05-01

    Platelet-rich fibrin membranes are biomaterials widely used for therapeutic purposes, and canonically produced through the processing of peripheral blood with fixed-angle rotor centrifuges. In this work, we evaluate the in vitro stability and release of cytokines and growth factors when these biomaterials are produced with a horizontal swing-out clinical centrifuge. Membranes produced from the blood of 14 donors were morphologically evaluated by scanning electron microscopy and fluorescence microscopy, and their stability was assessed by photographic recording after incubation in culture medium for up to 28 days. The release of 27 cytokines and growth factors was monitored for three weeks through a multiparametric immunoassay. The fibrin membranes presented complex three-dimensional structure with a high density of nucleated cells. A large release of growth factors [platelet derived growth factor, fibroblastic growth factor (bFGF), and vascular endothelial growth factor] was detected in the first 24 h, followed by time-dependent decay, maintaining significant concentrations after three weeks. Both anti-inflammatory and pro-inflammatory cytokines presented different release peaks, maintaining high rates of elution for up to 21 days. Chemokines of relevance in tissue repair [RANTES, granulocyte colony-stimulating factor (G-CSF)] were also produced in large quantities throughout the experimental period. The present results demonstrate that blood-derived fibrin membranes with high structural stability and cell content can be generated by horizontal centrifugation, being able of a prolonged production/release of growth factors and pro- and anti-inflammatory cytokines. © 2018 Wiley Periodicals, Inc. J Biomed Mater Res Part A: 106A: 1373-1380, 2018. © 2018 Wiley Periodicals, Inc.

  1. The Effect of the Local Delivery of Platelet-derived Growth Factor from Reactive Two-Component Polyurethane Scaffolds on the Healing in Rat Skin Excisional Wounds

    PubMed Central

    Li, Bing; Davidson, Jeffrey M.; Guelcher, Scott A.

    2009-01-01

    A key tenet of tissue engineering is the principle that the scaffold can perform the dual roles of biomechanical and biochemical support through presentation of the appropriate mediators to surrounding tissue. While growth factors have been incorporated into scaffolds to achieve sustained release, there are a limited number of studies investigating release of biologically active molecules from reactive two-component polymers, which have potential application as injectable delivery systems. In this study, we report the sustained release of platelet-derived growth factor (PDGF) from a reactive two-component polyurethane. The release of PDGF was bi-phasic, characterized by an initial burst followed by a period of sustained release for up to 21 days. Despite the potential for amine and hydroxyl groups in the protein to react with the isocyanate groups in the reactive polyurethane, the in vitro bioactivity of the released PDGF was largely preserved when added as a lyophilized powder. PUR/PDGF scaffolds implanted in rat skin excisional wounds accelerated wound healing relative to the blank PUR control, resulting in almost complete healing with reepithelization at day 14. The presence of PDGF attracted both fibroblasts and mononuclear cells, significantly accelerating degradation of the polymer and enhancing formation of new granulation tissue as early as day 3. The ability of reactive two-component PUR scaffolds to promote new tissue formation in vivo through local delivery of PDGF may present compelling opportunities for the development of novel injectable therapeutics. PMID:19328544

  2. Long-term balance in heavy metal adsorption and release in biochar derived from sewage sludge

    NASA Astrophysics Data System (ADS)

    Sohi, Saran; Cleat, Robert; Graham, Margaret; Cross, Andrew

    2014-05-01

    In Europe, sewage sludge has major potential as a resource for producing biochar. Biochar from sludge could offer a means for the controlled recycling of phosphorus to soil, with the additional benefit of carbon stabilisation. Biochar made from contaminated feedstock could, however, also leach heavy metals into soil. Counter to release of metals, biochar from fresh plant biomass has a documented affinity and adsorption capacity. The longer term balance of release and adsorption of metals in sludge-derived biochar has not been established. Our work compared the adsorption and release of both indigenous metals and metals adsorbed to sludge derived biochar. The hypotheses were threefold: (1) the capacity to adsorb metals is lower than the potential to release them, (2) the affinity for indigenous metals is higher than for metals in solution, 3) oxidative ageing of biochar leads to partial release of adsorbed metals. Sludge biochar was produced in a horizontal, externally heated kiln at a feed rate of approx. 0.5 kg/hr. Dry sludge was converted in a 20 min. transit time with peak kiln temperature of 550°C. Elemental analysis using ICP OES (after a published preparation step) showed Zn, Pb and Cu to be the most abundant heavy metals in the biochar. The same elements were assessed in sequential water and Mehlich III extracts. Adsorption of the metals from pure and mixed Zn, Pb and Pb solutions were undertaken before and after the other extractions. All the treatments were applied to the same biochar after oxidative ageing, in which biochar C was also found to be very stable. Extractability of all three metals from fresh biochar was low (less than 5 %), but for two of the metals it was lower after ageing. For one of the metals, ageing increased extractability. For the same metal, adsorption was lower when undertaken with a mixed rather than pure solution. Capacity for adsorption of one of the other metals was higher after biochar ageing; the general capacity for metal adsorption was similar to indigenous content. The affinity of biochar for adsorbed metals was higher after ageing than it had been for fresh biochar. The findings provide a quite positive picture in terms of the potential for safe use of sludge-derived biochar in agriculture, over the long- as well as near-term. Integrating further work on metals and its integration with work biochar phosphorus and C stability could lead to strategies that successfully address multiple goals and are also economically feasible.

  3. Modulation of active pharmaceutical material release from a novel 'tablet in capsule system' containing an effervescent blend.

    PubMed

    Gohel, Mukesh C; Sumitra G, Manhapra

    2002-02-19

    The objective of the present study was to obtain programmed drug delivery from hard gelatin capsules containing a hydrophilic plug (HPMC or guar gum). The significance of factors such as type of plug (powder or tablet), plug thickness and the formulation of fill material on the release pattern of diltiazem HCl, a model drug, was investigated. The body portion of the hard gelatin capsules was cross-linked by the combined effect of formaldehyde and heat treatment. A linear relationship was observed between weight of HPMC K15M and log % drug released at 4 h from the capsules containing the plug in powder form. In order to accelerate the drug release after a lag time of 4 h, addition of an effervescent blend, NaHCO(3) and citric acid, in the capsules was found to be essential. The plugs of HPMC in tablet form, with or without a water soluble adjuvant (NaCl or lactose) were used for obtaining immediate drug release after the lag time. Sodium chloride did not cause significant influence on drug release whereas lactose favourably affected the drug release. The capsules containing HPMC K15M tablet plug (200 mg) and 35 mg effervescent blend in body portion of the capsule met the selection criteria of less than 10% drug release in 4 h and immediate drug release thereafter. It is further shown that the drug release was also dependant on the type of swellable hydrophilic agent (HPMC or guar gum) and molecular weight of HPMC (K15M or 20 cPs). The results reveal that programmed drug delivery can be obtained from hard gelatin capsules by systemic formulation approach.

  4. Extracellular Vesicles from Bone Marrow‐Derived Mesenchymal Stem Cells Improve Survival from Lethal Hepatic Failure in Mice

    PubMed Central

    Haga, Hiroaki; Yan, Irene K.; Takahashi, Kenji; Matsuda, Akiko

    2017-01-01

    Abstract Stem cell‐based therapies have potential for treatment of liver injury by contributing to regenerative responses, through functional tissue replacement or paracrine effects. The release of extracellular vesicles (EV) from cells has been implicated in intercellular communication, and may contribute to beneficial paracrine effects of stem cell‐based therapies. Therapeutic effects of bone‐marrow derived mesenchymal stem cells (MSC) and vesicles released by these cells were examined in a lethal murine model of hepatic failure induced by d‐galactosamine/tumor necrosis factor‐α (TNF‐α). Systemically administered EV derived from MSC accumulated within the injured liver following systemic administration, reduced hepatic injury, and modulated cytokine expression. Moreover, survival was dramatically increased by EV derived from either murine or human MSC. Similar results were observed with the use of cryopreserved mMSC‐EV after 3 months. Y‐RNA‐1 was identified as a highly enriched noncoding RNA within hMSC‐EV compared to cells of origin. Moreover, siRNA mediated knockdown of Y‐RNA‐1 reduced the protective effects of MSC‐EV on TNF‐α/ActD‐mediated hepatocyte apoptosis in vitro. These data support a critical role for MSC‐derived EV in mediating reparative responses following hepatic injury, and provide compelling evidence to support the therapeutic use of MSC‐derived EV in fulminant hepatic failure. Stem Cells Translational Medicine 2017;6:1262–1272 PMID:28213967

  5. M7 germplasm release: A tetraploid clone derived from Solanum infundibuliforme for use in expanding the germplasm base for french fry processing

    USDA-ARS?s Scientific Manuscript database

    A new source of russet germplasm has been identified as a parent for processing and fresh market breeding programs. It was derived via bilateral sexual polyploidization following a cross between a diploid cultivated potato and the diploid wild species Solanum infundibuliforme. This clone, designated...

  6. 78 FR 29187 - Self-Regulatory Organizations; The NASDAQ Stock Market LLC; Notice of Filing and Immediate...

    Federal Register 2010, 2011, 2012, 2013, 2014

    2013-05-17

    ... disseminated as required (Rule 4120(a)(9)); a halt in a Derivative Securities Product (as defined in Rule 4120... trading halt in a Derivative Security Product traded pursuant to unlisted trading privileges for which a... SECURITIES AND EXCHANGE COMMISSION [Release No. 34-69563; File No. SR-NASDAQ-2013-073] Self...

  7. 78 FR 11258 - Self-Regulatory Organizations; Chicago Stock Exchange, Inc.; Notice of Filing and Immediate...

    Federal Register 2010, 2011, 2012, 2013, 2014

    2013-02-15

    ....0022/share in all Derivative Securities Products priced $1.00/share or more executed in the Regular....0022/share in all Derivative Securities Products priced $1.00/share or more executed in the Regular... SECURITIES AND EXCHANGE COMMISSION [Release No. 34-68894; File No. SR-CHX-2013-06] Self-Regulatory...

  8. Redefining Autism Spectrum Disorder Using DSM-5: The Implications of the Proposed DSM-5 Criteria for Autism Spectrum Disorders

    ERIC Educational Resources Information Center

    Young, Robyn L.; Rodi, Melissa L.

    2014-01-01

    A number of changes were made to pervasive developmental disorders (PDDs) in the recently released diagnostic and statistical manual of mental disorders (APA, "Diagnostic and statistical manual of mental disorders," American Psychiatric Publishing, Arlington, VA, 2013). Of the 210 participants in the present study who met DSM-IV-TR…

  9. 10 CFR Appendix A to Part 40 - Criteria Relating to the Operation of Uranium Mills and the Disposition of Tailings or Wastes...

    Code of Federal Regulations, 2012 CFR

    2012-01-01

    ... itself. (6) The design requirements in this criterion for longevity and control of radon releases apply... radiological and nonradiological hazards associated with the sites, which is equivalent to, to the extent... “reasonably achievable” as equivalent terms. Decisions involved these terms will take into account the state...

  10. Assessing the Sustainability of Agricultural and Urban Forests in the United States

    Treesearch

    Guy Robertson; Andy Mason

    2016-01-01

    The Forest Service, an agency of the U.S. Department of Agriculture (USDA), published the National Report on Sustainable Forests-2010 (USDA Forest Service 2011) (hereafter, National Report) several years ago and will be releasing a subsequent version of the report in 2017. Based on the Montreal Process Criteria and Indicators for Forest Sustainability, the National...

  11. 10 CFR Appendix A to Part 40 - Criteria Relating to the Operation of Uranium Mills and the Disposition of Tailings or Wastes...

    Code of Federal Regulations, 2013 CFR

    2013-01-01

    ... relatively thin, in-situ clay soils are to be relied upon for seepage control, tests must be conducted with... itself. (6) The design requirements in this criterion for longevity and control of radon releases apply... licensee shall control, minimize, or eliminate post-closure escape of nonradiological hazardous...

  12. Technical bases and guidance for the use of composite soil sampling for demonstrating compliance with radiological release criteria

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

    Vitkus, Timothy J.

    2012-04-24

    This guidance provides information on methodologies and the technical bases that licensees should consider for incorporating composite sampling strategies into final status survey (FSS) plans. In addition, this guidance also includes appropriate uses of composite sampling for generating the data for other decommissioning site investigations such as characterization or other preliminary site investigations.

  13. Decision Modeling for Socio-Cultural Data

    DTIC Science & Technology

    2011-02-01

    REFERENCES [1] Malczewski, J. (1999) GIS and Multicriteria Decision Analysis . John Wiley and Sons, New York. [2] Ehrgott, M., and Gandibleux, X. (Eds...up, nonexclusive, irrevocable worldwide license to use , modify, reproduce, release, perform, display, or disclose the work by or on behalf of the...criteria decision analysis (MCDA), into a geospatial environment to support decision making for campaign management. Our development approach supports

  14. Gaia DR2 documentation Chapter 1: Introduction

    NASA Astrophysics Data System (ADS)

    de Bruijne, J. H. J.; Abreu, A.; Brown, A. G. A.; Castañeda, J.; Cheek, N.; Crowley, C.; De Angeli, F.; Drimmel, R.; Fabricius, C.; Fleitas, J.; Gracia-Abril, G.; Guerra, R.; Hutton, A.; Messineo, R.; Mora, A.; Nienartowicz, K.; Panem, C.; Siddiqui, H.

    2018-04-01

    This chapter of the Gaia DR2 documentation describes the Gaia mission, the Gaia spacecraft, and the organisation of the Gaia Data Processing and Analysis Consortium (DPAC), which is responsible for the processing and analysis of the Gaia data. Furthermore, various properties of the data release are summarised, including statistical properties, object statistics, completeness, selection and filtering criteria, and limitations of the data.

  15. 40 CFR Appendix A to Subpart Ddddd... - Methodology and Criteria for Demonstrating Eligibility for the Health-Based Compliance Alternatives

    Code of Federal Regulations, 2012 CFR

    2012-07-01

    ... rate, type of control devices, process parameters (e.g., maximum heat input), and non-process... control systems (if applicable) and explain why the conditions are worst-case. (c) Number of test runs... located at the outlet of the control device and prior to any releases to the atmosphere. (e) Collection of...

  16. 40 CFR Appendix A to Subpart Ddddd... - Methodology and Criteria for Demonstrating Eligibility for the Health-Based Compliance Alternatives

    Code of Federal Regulations, 2011 CFR

    2011-07-01

    ... rate, type of control devices, process parameters (e.g., maximum heat input), and non-process... control systems (if applicable) and explain why the conditions are worst-case. (c) Number of test runs... located at the outlet of the control device and prior to any releases to the atmosphere. (e) Collection of...

  17. 40 CFR Appendix A to Subpart Ddddd... - Methodology and Criteria for Demonstrating Eligibility for the Health-Based Compliance Alternatives

    Code of Federal Regulations, 2010 CFR

    2010-07-01

    ... rate, type of control devices, process parameters (e.g., maximum heat input), and non-process... control systems (if applicable) and explain why the conditions are worst-case. (c) Number of test runs... located at the outlet of the control device and prior to any releases to the atmosphere. (e) Collection of...

  18. Sill intrusion driven fluid flow and vent formation in volcanic basins: Modeling rates of volatile release and paleoclimate effects

    NASA Astrophysics Data System (ADS)

    Iyer, Karthik; Schmid, Daniel

    2016-04-01

    Evidence of mass extinction events in conjunction with climate change occur throughout the geological record and may be accompanied by pronounced negative carbon isotope excursions. The processes that trigger such globally destructive changes are still under considerable debate. These include mechanisms such as poisoning from trace metals released during large volcanic eruptions (Vogt, 1972), CO2 released from lava degassing during the formation of Large Igneous Provinces (LIPs) (Courtillot and Renne, 2003) and CH4 release during the destabilization of sub-seafloor methane (Dickens et al., 1995), to name a few. Thermogenic methane derived from contact metamorphism associated with magma emplacement and cooling in sedimentary basins has been recently gaining considerable attention as a potential mechanism that may have triggered global climate events in the past (e.g. Svensen and Jamtveit, 2010). The discovery of hydrothermal vent complexes that are spatially associated with such basins also supports the discharge of greenhouse gases into the atmosphere (e.g. Jamtveit et al., 2004; Planke et al., 2005; Svensen et al., 2006). A previous study that investigated this process using a fluid flow model (Iyer et al., 2013) suggested that although hydrothermal plume formation resulting from sill emplacement may indeed release large quantities of methane at the surface, the rate at which this methane is released into the atmosphere is too slow to trigger, by itself, some of the negative δ13C excursions observed in the fossil record over short time scales observed in the fossil record. Here, we reinvestigate the rates of gas release during sill emplacement in a case study from the Harstad Basin off-shore Norway with a special emphasis on vent formation. The presented study is based on a seismic line that crosses multiple sill structures emplaced around 55 Ma within the Lower Cretaceous sediments. A single well-defined vent complex is interpreted above the termination of the main sill in the region. We use a 2D, hybrid FEM/FVM model that solves for fully compressible fluid flow to quantify the thermogenic release and transport of methane and to evaluate flow patterns within these systems. Additionally, vent formation in the model is implemented by simple fracture criteria that modify the permeability structure when the fluid pressure exceeds a threshold determined by the lithostatic pressure. The model with fracture formation is able to reproduce a single vent complex at the observed location above the main sill tip. This is very different from hydrothermal plume formation elsewhere in the region and occurs over short time scales (hundreds of years) and results in fluid focusing in that region. The rate of degassing and the resulting negative δ13C excursion from the vent model is then compared to models where only hydrothermal plume formation results in gas transportation. Lastly, variations in the amount of gas liberated in the system are investigated based on kerogen type and other mineral reactions such as limestone decarbonation and halite breakdown in the affected source rock.

  19. On the effectiveness of recession analysis methods for capturing the characteristic storage-discharge relation: An intercomparison study

    NASA Astrophysics Data System (ADS)

    Chen, X.; Kumar, M.; Basso, S.; Marani, M.

    2017-12-01

    Storage-discharge (S-Q) relations are widely used to derive watershed properties and predict streamflow responses. These relations are often obtained using different recession analysis methods, which vary in recession period identification criteria and Q vs. -dQ/dt fitting scheme. Although previous studies have indicated that different recession analysis methods can result in significantly different S-Q relations and subsequently derived hydrological variables, this observation has often been overlooked and S-Q relations have been used in as is form. This study evaluated the effectiveness of four recession analysis methods in obtaining the characteristic S-Q relation and reconstructing the streamflow. Results indicate that while some methods generally performed better than others, none of them consistently outperformed the others. Even the best-performing method could not yield accurate reconstructed streamflow time series and its PDFs in some watersheds, implying that either derived S-Q relations might not be reliable or S-Q relations cannot be used for hydrological simulations. Notably, accuracy of the methods is influenced by the extent of scatter in the ln(-dQ/dt) vs. ln(Q) plot. In addition, the derived S-Q relation was very sensitive to the criteria used for identifying recession periods. This result raises a warning sign against indiscriminate application of recession analysis methods and derived S-Q relations for watershed characterizations or hydrologic simulations. Thorough evaluation of representativeness of the derived S-Q relation should be performed before it is used for hydrologic analysis.

  20. Hematoma-inspired alginate/platelet releasate/CaPO4 composite: initiation of the inflammatory-mediated response associated with fracture repair in vitro and ex vivo injection delivery.

    PubMed

    McCanless, Jonathan D; Jennings, Lisa K; Bumgardner, Joel D; Cole, Judith A; Haggard, Warren O

    2012-08-01

    A clinical need continues for consistent bone remodeling within problematic sites such as those of fracture nonunion, avascular necrosis, or irregular bone formations. In attempt to address such needs, a biomaterial system is proposed to induce early inflammatory responses after implantation and to provide later osteoconductive scaffolding for bone regeneration. Biomaterial-induced inflammation would parallel the early stage of hematoma-induced fracture repair and allow scaffold-promoted remodeling of osseous tissue to a healthy state. Initiation of the wound healing cascade by two human concentrated platelet releasate-containing alginate/β-tricalcium phosphate biocomposites has been studied in vitro using the TIB-71™ RAW264.7 mouse monocyte cell line. Inflammatory responses inherent to the base material were found and could be modulated through incorporation of platelet releasate. Differences in hydrogel wt% (2 vs. 8 %) and/or calcium phosphate granule vol.% (20 vs. 10 %) allowed for tuning the response associated with platelet releasate-associated growth factor elution. Tunability from completely suppressing the inflammatory response to augmenting the response was observed through varied elution profiles of both releasate-derived bioagents and impurities inherent to alginate. A 2.5-fold upregulation of inducible-nitric oxide synthase gene expression followed by a tenfold increase in nitrite media levels was induced by inclusion of releasate within the 8 wt%/10 vol.% formulation and was comparable to an endotoxin positive control. Whereas, near complete elimination of inflammation was seen when releasate was included within the 2 wt%/20 vol.% formulation. These in vitro results suggested tunable interactions between the multiple platelet releasate-derived bioagents and the biocomposites for enhancing hematoma-like fracture repair. Additionally, minimally invasive delivery for in situ curing of the implant system via injection was demonstrated in rat tail vertebrae using microcomputed tomography.

  1. Quantitative analysis of serotonin secreted by human embryonic stem cells-derived serotonergic neurons via pH-mediated online stacking-CE-ESI-MRM.

    PubMed

    Zhong, Xuefei; Hao, Ling; Lu, Jianfeng; Ye, Hui; Zhang, Su-Chun; Li, Lingjun

    2016-04-01

    A CE-ESI-MRM-based assay was developed for targeted analysis of serotonin released by human embryonic stem cells-derived serotonergic neurons in a chemically defined environment. A discontinuous electrolyte system was optimized for pH-mediated online stacking of serotonin. Combining with a liquid-liquid extraction procedure, LOD of serotonin in the Krebs'-Ringer's solution by CE-ESI-MS/MS on a 3D ion trap MS was0.15 ng/mL. The quantitative results confirmed the serotonergic identity of the in vitro developed neurons and the capacity of these neurons to release serotonin in response to stimulus. © 2016 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

  2. Functional significance of brain glycogen in sustaining glutamatergic neurotransmission.

    PubMed

    Sickmann, Helle M; Walls, Anne B; Schousboe, Arne; Bouman, Stephan D; Waagepetersen, Helle S

    2009-05-01

    The involvement of brain glycogen in sustaining neuronal activity has previously been demonstrated. However, to what extent energy derived from glycogen is consumed by astrocytes themselves or is transferred to the neurons in the form of lactate for oxidative metabolism to proceed is at present unclear. The significance of glycogen in fueling glutamate uptake into astrocytes was specifically addressed in cultured astrocytes. Moreover, the objective was to elucidate whether glycogen derived energy is important for maintaining glutamatergic neurotransmission, induced by repetitive exposure to NMDA in co-cultures of cerebellar neurons and astrocytes. In the astrocytes it was shown that uptake of the glutamate analogue D-[3H]aspartate was impaired when glycogen degradation was inhibited irrespective of the presence of glucose, signifying that energy derived from glycogen degradation is important for the astrocytic compartment. By inhibiting glycogen degradation in co-cultures it was evident that glycogen provides energy to sustain glutamatergic neurotransmission, i.e. release and uptake of glutamate. The relocation of glycogen derived lactate to the neuronal compartment was investigated by employing d-lactate, a competitive substrate for the monocarboxylate transporters. Neurotransmitter release was affected by the presence of d-lactate indicating that glycogen derived energy is important not only in the astrocytic but also in the neuronal compartment.

  3. CD73-derived adenosine and tenascin-C control cytokine production by epicardium-derived cells formed after myocardial infarction.

    PubMed

    Hesse, Julia; Leberling, Stella; Boden, Elisabeth; Friebe, Daniela; Schmidt, Timo; Ding, Zhaoping; Dieterich, Peter; Deussen, Andreas; Roderigo, Claudia; Rose, Christine R; Floss, Doreen M; Scheller, Jürgen; Schrader, Jürgen

    2017-07-01

    Epicardium-derived cells (EPDCs) play a fundamental role in embryonic cardiac development and are reactivated in the adult heart in response to myocardial infarction (MI). In this study, EPDCs from post-MI rat hearts highly expressed the ectoenzyme CD73 and secreted the profibrotic matricellular protein tenascin-C (TNC). CD73 on EPDCs extensively generated adenosine from both extracellular ATP and NAD. This in turn stimulated the release of additional nucleotides from a Brefeldin A-sensitive intracellular pool via adenosine-A 2B R signaling, forming a positive-feedback loop. A 2B R activation, in addition, strongly promoted the release of major regulatory cytokines, such as IL-6, IL-11, and VEGF. TNC was found to stimulate EPDC migration and, together with ATP-P2X 7 R signaling, to activate inflammasomes in EPDCs via TLR4. Our results demonstrate that EPDCs are an important source of various proinflammatory factors in the post-MI heart controlled by purinergic and TNC signaling.-Hesse, J., Leberling, S., Boden, E., Friebe, D., Schmidt, T., Ding, Z., Dieterich, P., Deussen, A., Roderigo, C., Rose, C. R., Floss, D. M., Scheller, J., Schrader, J. CD73-derived adenosine and tenascin-C control cytokine production by epicardium-derived cells formed after myocardial infarction. © FASEB.

  4. Paper-based microfluidics with an erodible polymeric bridge giving controlled release and timed flow shutoff.

    PubMed

    Jahanshahi-Anbuhi, Sana; Henry, Aleah; Leung, Vincent; Sicard, Clémence; Pennings, Kevin; Pelton, Robert; Brennan, John D; Filipe, Carlos D M

    2014-01-07

    Water soluble pullulan films were formatted into paper-based microfluidic devices, serving as a controlled time shutoff valve. The utility of the valve was demonstrated by a one-step, fully automatic implementation of a complex pesticide assay requiring timed, sequential exposure of an immobilized enzyme layer to separate liquid streams. Pullulan film dissolution and the capillary wicking of aqueous solutions through the device were measured and modeled providing valve design criteria. The films dissolve mainly by surface erosion, meaning the film thickness mainly controls the shutoff time. This method can also provide time-dependent sequential release of reagents without compromising the simplicity and low cost of paper-based devices.

  5. RCRA/UST, superfund, and EPCRA hotline training module. Introduction to: RCRA subtitle I. Underground storage tanks (40 cfr part 280). Updated as of July 1996

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

    NONE

    1996-07-01

    This module explains the Underground Storage Tank Regulatory Program established in 1988, that includes technical requirements to prevent, protect, and clean up releases from Underground Storage Tanks (USTs), as well as financial responsibility requirements to guarantee that UST owners and operators have enough money set aside to clean up releases and compensate third parties. Describes the Universe of USTs and the technical and financial requirements that apply to them. Defines underground storage tank and provides criteria for determining which USTs are subject to regulation. Discusses deadlines for upgrading tanks and the closure and corrective action requirements.

  6. The diabetic frozen shoulder: arthroscopic release.

    PubMed

    Ogilvie-Harris, D J; Myerthall, S

    1997-02-01

    Seventeen patients who were diabetics developed frozen shoulders which failed to respond to conservative management. They had persistent pain, stiffness, and limited function. An arthroscopic release was performed by progressively releasing the anterior structures from superior to inferior. Starting from the interval area we progressed to the anterior superior glenohumeral ligament, the intra-articular portion of the subscapularis, the anterior capsule, and the inferior capsule. Postoperatively physiotherapy was carried out daily to maintain the range of movement. At a follow up of 1 to 5 years the patients were assessed using the American Shoulder Society scheme. In addition the patients were assessed preoperatively and postoperatively on four criteria; pain, external rotation, abduction, and function. We found that the patients were statistically significantly improved in all four categories. Thirteen of the 17 patients had no pain, full range of motion compared with the opposite side, and full function. There was one poor result with no improvement. The remaining three patients had improved but still had residual abnormalities. We consider arthroscopic release to be an effective treatment for the resistant diabetic frozen shoulder.

  7. Preparations for the IGS realization of ITRF2014

    NASA Astrophysics Data System (ADS)

    Rebischung, Paul; Schmid, Ralf

    2016-04-01

    The International GNSS Service (IGS) currently prepares its own realization, called IGS14, of the latest release of the International Terrestrial Reference Frame (ITRF2014). This preparation involves: - a selection of the most suitable reference frame (RF) stations from the complete set of GNSS stations in ITRF2014; - the design of a well-distributed core network of RF stations for the purpose of aligning global GNSS solutions; - a re-evaluation of the GPS and GLONASS satellite antenna phase center offsets (PCOs), based on the SINEX files provided by the IGS Analysis Centers (ACs) in the frame of the second IGS reprocessing campaign repro2. This presentation will first cover the criteria used for the selection of the IGS14 and IGS14 core RF stations as well as preliminary station selection results. We will then use the preliminary IGS14 RF to re-align the daily IGS combined repro2 SINEX solutions and study the impact of the RF change on GNSS-derived geodetic parameter time series. In a second part, we will focus on the re-evaluation of the GNSS satellite antenna PCOs. A re-evaluation of at least their radial (z) components is indeed required, despite the negligible scale difference between ITRF2008 and ITRF2014, because of modeling changes recently introduced within the IGS which affect the scale of GNSS terrestrial frames (Earth radiation pressure, antenna thrust). Moreover, the 13 GPS and GLONASS satellites launched since September 2012 are currently assigned preliminary block-specific mean PCO values which need to be updated. From the daily AC repro2 SINEX files, we will therefore derive time series of satellite z-PCO estimates and analyze the resulting time series. Since several ACs provided all three components of the satellite PCOs in their SINEX files, we will additionally derive similar x- and y-PCO time series and discuss the relevance of their potential re-evaluation.

  8. White Dwarfs in Wide Binaries and the Age of the Galaxy

    NASA Astrophysics Data System (ADS)

    Smith, John Allyn

    A comprehensive study of common proper binary systems suspected of containing white dwarf stars is being conducted by Oswalt and collaborators (Oswalt et al. 1988). These systems usually contain a white dwarf and a main sequence star. In the present study, we use the white dwarf luminosity function to determine the age of the local Galactic disk as well as the local space density of white dwarfs. We obtained BVRI photometry of approximately 475 systems (of 512) which were found to contain about 325 white dwarfs. Of these white dwarfs, 152 met the selection criteria for our study and were used in the final analysis. Using this largest sample of cool white dwarfs in binary systems observed to date, we have determined an age for the Galactic disk of 9.7-0.8+0.9 Gyr which yields a lower limit age for the Universe of about 11.7 Gyr. Recent globular cluster studies agree to within ±1σ for the Galaxy age derived from our Disk age. The latest cosmologically derived age for the Universe, modified for the recently released Hipparcos data, is now in accordance with our age estimates for the Universe, for H o (69 km s-1 Mpc-1) and an inflationary cosmology. Further, our age is in accord with the ages derived for the Galaxy from nucleocomsochronology and meteoritic sample analyses. As a part of this work, we have determined the white dwarf space density to be 4.5 ± 1.0 10-3 pc-3, in accord with the results previously reported by Liebert, Dahn & Monet (1987). This space density corresponds to a white dwarf birthrate of 4.65 × 10-13 yr-1 pc-3. This research also details a unique approach to calculating and correcting for the incompleteness of a proper motion and magnitude selected stellar sample.

  9. Derivation of gender and age-specific reference intervals from fully normal Japanese individuals and the implications for health screening.

    PubMed

    Yamakado, Minoru; Ichihara, Kiyoshi; Matsumoto, Yoshiyuki; Ishikawa, Yoshiki; Kato, Kiminori; Komatsubara, Yusuke; Takaya, Norihide; Tomita, Shohken; Kawano, Reo; Takada, Keisuke; Watanabe, Kiyoaki

    2015-07-20

    With nationwide standardization of laboratory tests among institutions for health screening in Japan, common reference intervals (RIs) were derived from records of 1,500,000 health check attendees. Targets were 20 basic laboratory tests including body mass index (BMI) and systolic and diastolic blood pressures (SBP, DBP). Individuals fulfilling the following strict criteria were chosen: SBP<130, DBP<85mmHg, BMI<25kg/m(2), non-smoking, ethanol consumption<20g/day and under no mediation with no remarkable current/past illnesses. The latent abnormal values exclusion (LAVE) method was applied to ensure fully normal results. RIs were derived by parametric method using modified Box-Cox power transformation. Among all attendees, 23% fulfilled the criteria. Application of the LAVE method further reduced the dataset by 40%-50%. Age-related charts of test results differed greatly between genders in almost all tests. Comparison of derived RIs with clinical decision limits (CDLs) revealed that the upper limits of RIs differed from CDLs according to gender and age. Implementation of gender and age-specific RIs derived from individuals with fully normal health attributes will (1) enable appropriate interpretation of test results in health screening and (2) promote judicious application of CDLs for therapeutic intervention, taking into account gender, age and other health attributes. Copyright © 2015 Elsevier B.V. All rights reserved.

  10. Challenges and opportunities in establishing scientific and regulatory standards for determining therapeutic equivalence of modified-release products: Workshop summary report.

    PubMed

    Chen, Mei-Ling; Shah, Vinod P; Ganes, Derek; Midha, Kamal K; Caro, James; Nambiar, Prabu; Rocci, Mario L; Thombre, Avinash G; Abrahamsson, Bertil; Conner, Dale; Davit, Barbara; Fackler, Paul; Farrell, Colm; Gupta, Suneel; Katz, Russell; Mehta, Mehul; Preskorn, Sheldon H; Sanderink, Gerard; Stavchansky, Salomon; Temple, Robert; Wang, Yaning; Winkle, Helen; Yu, Lawrence

    2010-09-01

    Modified-release (MR) products are complex dosage forms designed to release drug in a controlled manner to achieve the desired efficacy and safety profiles. Inappropriate control of drug release from such products may result in reduced efficacy or increased toxicity. This paper is a summary report of the American Association of Pharmaceutical Scientists, International Pharmaceutical Federation, and Product Quality Research Institute workshop titled "Challenges and Opportunities in Establishing Scientific and Regulatory Standards for Assuring Therapeutic Equivalence of Modified Release Products", held October 1-2, 2009, in Baltimore, Maryland. The workshop provided an opportunity for pharmaceutical scientists from academia, industry, and regulatory agencies to discuss current regulatory expectations and industry practices for evaluating the pharmaceutical equivalence and bioequivalence of oral MR products. In the case of conventional monophasic MR formulations, the current regulatory approaches and criteria for bioequivalence evaluation were considered adequate for the assessment of therapeutic equivalence and inter-changeability of drug products. Additional measures may occasionally be needed to determine the bioequivalence of multiphasic MR products. The metric of partial AUC proposed by the US Food and Drug Administration received broad support as an additional measure for evaluating bioequivalence of multiphasic MR products designed to have a rapid onset of drug action followed by sustained response. The cutoff for partial AUCs may be based on the pharmacokinetic/pharmacodynamic or pharmacokinetic/ response characteristics of the products under examination. If the new metric is highly variable, the bioequivalence limits may be set based on the known within-subject variability for the reference product. The current regulatory approaches and criteria for bioequivalence evaluation were considered adequate for the assessment of therapeutic equivalence and interchangeability of conventional monophasic MR products. Additional measures may occasionally be needed to establish the bioequivalence of multiphasic MR products, and development of such measures is an important objective. The metric of partial AUC was proposed for products designed to have a rapid drug action followed by sustained response. Copyright © 2010 Excerpta Medica Inc. All rights reserved.

  11. Technical Report Series on Global Modeling and Data Assimilation. Volume 40; Soil Moisture Active Passive (SMAP) Project Assessment Report for the Beta-Release L4_SM Data Product

    NASA Technical Reports Server (NTRS)

    Koster, Randal D.; Reichle, Rolf H.; De Lannoy, Gabrielle J. M.; Liu, Qing; Colliander, Andreas; Conaty, Austin; Jackson, Thomas; Kimball, John

    2015-01-01

    During the post-launch SMAP calibration and validation (Cal/Val) phase there are two objectives for each science data product team: 1) calibrate, verify, and improve the performance of the science algorithm, and 2) validate the accuracy of the science data product as specified in the science requirements and according to the Cal/Val schedule. This report provides an assessment of the SMAP Level 4 Surface and Root Zone Soil Moisture Passive (L4_SM) product specifically for the product's public beta release scheduled for 30 October 2015. The primary objective of the beta release is to allow users to familiarize themselves with the data product before the validated product becomes available. The beta release also allows users to conduct their own assessment of the data and to provide feedback to the L4_SM science data product team. The assessment of the L4_SM data product includes comparisons of SMAP L4_SM soil moisture estimates with in situ soil moisture observations from core validation sites and sparse networks. The assessment further includes a global evaluation of the internal diagnostics from the ensemble-based data assimilation system that is used to generate the L4_SM product. This evaluation focuses on the statistics of the observation-minus-forecast (O-F) residuals and the analysis increments. Together, the core validation site comparisons and the statistics of the assimilation diagnostics are considered primary validation methodologies for the L4_SM product. Comparisons against in situ measurements from regional-scale sparse networks are considered a secondary validation methodology because such in situ measurements are subject to upscaling errors from the point-scale to the grid cell scale of the data product. Based on the limited set of core validation sites, the assessment presented here meets the criteria established by the Committee on Earth Observing Satellites for Stage 1 validation and supports the beta release of the data. The validation against sparse network measurements and the evaluation of the assimilation diagnostics address Stage 2 validation criteria by expanding the assessment to regional and global scales.

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

    Saboia, A.; Toscano, F.; Walborn, S. P.

    We derive a family of entanglement criteria for continuous-variable systems based on the Renyi entropy of complementary distributions. We show that these entanglement witnesses can be more sensitive than those based on second-order moments, as well as previous tests involving the Shannon entropy [Phys. Rev. Lett. 103, 160505 (2009)]. We extend our results to include the case of discrete sampling. We provide several numerical results which show that our criteria can be used to identify entanglement in a number of experimentally relevant quantum states.

  13. Male and Female Cervical Spine Biomechanics and Anatomy: Implication for Scaling Injury Criteria.

    PubMed

    Yoganandan, Narayan; Bass, Cameron R; Voo, Liming; Pintar, Frank A

    2017-05-01

    There is an increased need to develop female-specific injury criteria and anthropomorphic test devices (dummies) for military and automotive environments, especially as women take occupational roles traditionally reserved for men. Although some exhaustive reviews on the biomechanics and injuries of the human spine have appeared in clinical and bioengineering literatures, focus has been largely ignored on the difference between male and female cervical spine responses and characteristics. Current neck injury criteria for automotive dummies for assessing crashworthiness and occupant safety are obtained from animal and human cadaver experiments, computational modeling, and human volunteer studies. They are also used in the military. Since the average human female spines are smaller than average male spines, metrics specific to the female population may be derived using simple geometric scaling, based on the assumption that male and female spines are geometrically scalable. However, as described in this technical brief, studies have shown that the biomechanical responses between males and females do not obey strict geometric similitude. Anatomical differences in terms of the structural component geometry are also different between the two cervical spines. Postural, physiological, and motion responses under automotive scenarios are also different. This technical brief, focused on such nonuniform differences, underscores the need to conduct female spine-specific evaluations/experiments to derive injury criteria for this important group of the population.

  14. Correction to "What is a fractional derivative?" by Ortigueira and Machado [Journal of Computational Physics, Volume 293, 15 July 2015, Pages 4-13. Special issue on Fractional PDEs

    NASA Astrophysics Data System (ADS)

    Katugampola, Udita N.

    2016-09-01

    There is a debate among contemporary mathematicians about what it really means by a fractional derivative. The question arose as a consequence of introducing a 'new' definition of a fractional derivative in [1]. In a reply, Ortigueira and Machado [2] came up with several very important criteria to determine whether a given derivative is a fractional derivative. According to their criterion, the new fractional derivative, called conformable fractional derivative, introduced by Khalil et al. [1] turns out not to be a fractional derivative, but rather a controlled or conformable derivative. In proving the claim the authors in [2] use an example [2, p. 6]. It turns out that the explanation given there needs some corrections and it is the sole purpose of this note.

  15. Venturing in coral larval chimerism: a compact functional domain with fostered genotypic diversity

    NASA Astrophysics Data System (ADS)

    Rinkevich, Baruch; Shaish, Lee; Douek, Jacob; Ben-Shlomo, Rachel

    2016-01-01

    The globally distributed coral species Pocillopora damicornis is known to release either sexual or asexual derived planula-larvae in various reef locations. Using microsatellite loci as markers, we documented the release of asexually derived chimeric larvae (CL), originating from mosaicked maternal colonies that were also chimeras, at Thai and Philippines reefs. The CL, each presenting different combinations of maternal genotypic constituents, create genetically-complex sets of asexual propagules. This novel mode of inheritance in corals challenges classical postulations of sexual/asexual reproduction traits, as asexual derived CL represent an alliance between genotypes that significantly sways the recruits’ absolute fitness. This type of inherited chimerism, while enhancing intra-entity genetic heterogeneity, is an evolutionary tactic used to increase genetic-heterogeneity, primarily in new areas colonized by a limited number of larvae. Chimerism may also facilitate combat global change impacts by exhibiting adjustable genomic combinations of within-chimera traits that could withstand alterable environmental pressures, helping Pocillopora become a successful cosmopolitan species.

  16. Effects of titanium dioxide nanoparticles derived from consumer products on the marine diatom Thalassiosira pseudonana.

    PubMed

    Galletti, Andrea; Seo, Seokju; Joo, Sung Hee; Su, Chunming; Blackwelder, Pat

    2016-10-01

    Increased manufacture of TiO 2 nanoproducts has caused concern about the potential toxicity of these products to the environment and in public health. Identification and confirmation of the presence of TiO 2 nanoparticles derived from consumer products as opposed to industrial TiO 2 NPs warrant examination in exploring the significance of their release and resultant impacts on the environment. To this end, we examined the significance of the release of these particles and their toxic effect on the marine diatom algae Thalassiosira pseudonana. Our results indicate that nano-TiO 2 sunscreen and toothpaste exhibit more toxicity in comparison to industrial TiO 2 and inhibited the growth of the marine diatom T. pseudonana. This inhibition was proportional to the exposure time and concentrations of nano-TiO 2 . Our findings indicate a significant effect, and therefore, further research is warranted in evaluation and assessment of the toxicity of modified nano-TiO 2 derived from consumer products and their physicochemical properties.

  17. Effects of titanium dioxide nanoparticles derived from ...

    EPA Pesticide Factsheets

    Increased manufacture of TiO2 nano-products has caused concern about the potential toxicity of these products to the environment and in public health. Identification and confirmation of the presence of TiO2 nanoparticles derived from consumer products as opposed to industrial TiO2 NPs warrants examination in exploring the significance of their release and resultant impacts on the environment. To this end we examined the significance of the release of these particles and their toxic effect on the marine diatom algae Thalassiosira pseudonana. Our results indicate that nano-TiO2 sunscreen and toothpaste exhibit more toxicity in comparison to industrial TiO2, and inhibited the growth of the marine diatom Thalassiosira pseudonana. This inhibition was proportional to the exposure time and concentrations of nano-TiO2. Our findings indicate a significant effect, and therefore further research is warranted in evaluation and assessment of the toxicity of modified nano-TiO2 derived from consumer products and their physicochemical properties. Submit to journal Environmental Science and Pollution Research.

  18. Say NO to ET.

    PubMed

    Vanhoutte, P M

    2000-07-03

    The endothelial cells release both relaxing [nitric oxide (NO), endothelium-derived hyperpolarizing factor (EDHF), prostacyclin] and contracting factors [endoperoxides, thromboxane A(2), superoxide anions, endothelin-1 (ET)]. The production of ET is inhibited by NO. The latter also strongly opposes the direct effects of the former on vascular smooth muscle. With aging and vascular disease, the production of enothelial NO declines, and thus ET can be released, act and contribute to the symptoms.

  19. A curcumin activated carboxymethyl cellulose-montmorillonite clay nanocomposite having enhanced curcumin release in aqueous media.

    PubMed

    Madusanka, Nadeesh; de Silva, K M Nalin; Amaratunga, Gehan

    2015-12-10

    A novel curcumin activated carboxymethylcellulose-montmorillonite nanocomposite is reported. A superabsorbent biopolymer; carboxymethyl cellulose (CMC) was used as an emulsifier for curcumin which is a turmeric derived water insoluble polyphenolic compound with antibacterial/anti-cancer properties. Montmorillonite (MMT) nanoclay was incorporated in the formulation as a matrix material which also plays a role in release kinetics. It was observed that water solubility of curcumin in the nanocomposite has significantly increased (60% release within 2h and 30 min in distilled water at pH 5.4) compared to pure curcumin. The prepared curcumin activated carboxymethylcellulose-montmorillonite nanocomposite is suitable as a curcumin carrier having enhanced release and structural properties. Copyright © 2015 Elsevier Ltd. All rights reserved.

  20. ECP Milestone Report WBS 2.3.4.13 ECP/VTK-m FY18Q1 [MS-18/01-03] Multiblock / Gradients / Release STDA05-5.

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

    Moreland, Kenneth D.; Pugmire, David; Geveci, Berk

    The FY18Q1 milestone of the ECP/VTK-m project includes the implementation of a multiblock data set, the completion of a gradients filtering operation, and the release of version 1.1 of the VTK-m software. With the completion of this milestone, the new multiblock data set allows us to iteratively schedule algorithms on composite data structures such as assemblies or hierarchies like AMR. The new gradient algorithms approximate derivatives of fields in 3D structures with finite differences. Finally, the release of VTK-m version 1.1 tags a stable release of the software that can more easily be incorporated into external projects.

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