Speech-induced striatal dopamine release is left lateralized and coupled to functional striatal circuits in healthy humans: A combined PET, fMRI and DTI study

PubMed Central

Simonyan, Kristina; Herscovitch, Peter; Horwitz, Barry

2013-01-01

Considerable progress has been recently made in understanding the brain mechanisms underlying speech and language control. However, the neurochemical underpinnings of normal speech production remain largely unknown. We investigated the extent of striatal endogenous dopamine release and its influences on the organization of functional striatal speech networks during production of meaningful English sentences using a combination of positron emission tomography (PET) with the dopamine D2/D3 receptor radioligand [11C]raclopride and functional MRI (fMRI). In addition, we used diffusion tensor tractography (DTI) to examine the extent of dopaminergic modulatory influences on striatal structural network organization. We found that, during sentence production, endogenous dopamine was released in the ventromedial portion of the dorsal striatum, in its both associative and sensorimotor functional divisions. In the associative striatum, speech-induced dopamine release established a significant relationship with neural activity and influenced the left-hemispheric lateralization of striatal functional networks. In contrast, there were no significant effects of endogenous dopamine release on the lateralization of striatal structural networks. Our data provide the first evidence for endogenous dopamine release in the dorsal striatum during normal speaking and point to the possible mechanisms behind the modulatory influences of dopamine on the organization of functional brain circuits controlling normal human speech. PMID:23277111

Inflammatory role and prognostic value of platelet chemokines in acute coronary syndrome.

PubMed

Blanchet, X; Cesarek, K; Brandt, J; Herwald, H; Teupser, D; Küchenhoff, H; Karshovska, E; Mause, S F; Siess, W; Wasmuth, H; Soehnlein, O; Koenen, R R; Weber, C; von Hundelshausen, P

2014-12-01

Activated platelets and neutrophils exacerbate atherosclerosis. Platelets release the chemokines CXCL4, CXCL4L1 and CCL5, whereas myeloperoxidase (MPO) and azurocidin are neutrophil-derived. We investigated whether plasma levels of these platelet and neutrophil mediators are affected by the acute coronary syndrome (ACS), its medical treatment, concomitant clinical or laboratory parameters, and predictive for the progression of coronary artery disease (CAD). In an observational study, the association of various factors with plasma concentrations of platelet chemokines and neutrophil mediators in 204 patients, either upon admission with ACS and 6 hours later or without ACS or CAD, was determined by multiple linear regression. Mediator release was further analysed after activation of blood with ACS-associated triggers such as plaque material. CXCL4, CXCL4L1, CCL5, MPO and azurocidin levels were elevated in ACS. CXCL4 and CCL5 but not CXCL4L1 or MPO were associated with platelet counts and CRP. CXCL4 (in association with heparin treatment) and MPO declined over 6 hours during ACS. Elevated CCL5 was associated with a progression of CAD. Incubating blood with plaque material, PAR1 and PAR4 activation induced a marked release of CXCL4 and CCL5, whereas CXCL4L1 and MPO were hardly or not altered. Platelet chemokines and neutrophil products are concomitantly elevated in ACS and differentially modulated by heparin treatment. CCL5 levels during ACS predict a progression of preexisting CAD. Platelet-derived products appear to dominate the inflammatory response during ACS, adding to the emerging evidence that ACS per se may promote vascular inflammation.

Controlled drug delivery systems: past forward and future back.

PubMed

Park, Kinam

2014-09-28

Controlled drug delivery technology has progressed over the last six decades. This progression began in 1952 with the introduction of the first sustained release formulation. The 1st generation of drug delivery (1950-1980) focused on developing oral and transdermal sustained release systems and establishing controlled drug release mechanisms. The 2nd generation (1980-2010) was dedicated to the development of zero-order release systems, self-regulated drug delivery systems, long-term depot formulations, and nanotechnology-based delivery systems. The latter part of the 2nd generation was largely focused on studying nanoparticle formulations. The Journal of Controlled Release (JCR) has played a pivotal role in the 2nd generation of drug delivery technologies, and it will continue playing a leading role in the next generation. The best path towards a productive 3rd generation of drug delivery technology requires an honest, open dialog without any preconceived ideas of the past. The drug delivery field needs to take a bold approach to designing future drug delivery formulations primarily based on today's necessities, to produce the necessary innovations. The JCR provides a forum for sharing the new ideas that will shape the 3rd generation of drug delivery technology. Copyright © 2014 Elsevier B.V. All rights reserved.

Force and number of myosin motors during muscle shortening and the coupling with the release of the ATP hydrolysis products

PubMed Central

Caremani, Marco; Melli, Luca; Dolfi, Mario; Lombardi, Vincenzo; Linari, Marco

2015-01-01

The chemo-mechanical cycle of the myosin II–actin reaction in situ has been investigated in Ca2+-activated skinned fibres from rabbit psoas, by determining the number and strain (s) of myosin motors interacting during steady shortening at different velocities (V) and the effect of raising inorganic phosphate (Pi) concentration. It was found that in control conditions (no added Pi), shortening at V ≤ 350 nm s–1 per half-sarcomere, corresponding to force (T) greater than half the isometric force (T0), decreases the number of myosin motors in proportion to the reduction of T, so that s remains practically constant and similar to the T0 value independent of V. At higher V the number of motors decreases less than in proportion to T, so that s progressively decreases. Raising Pi concentration by 10 mm, which reduces T0 and the number of motors by 40–50%, does not influence the dependence on V of number and strain. A model simulation of the myosin–actin reaction in which the structural transitions responsible for the myosin working stroke and the release of the hydrolysis products are orthogonal explains the results assuming that Pi and then ADP are released with rates that increase as the motor progresses through the working stroke. The rate of ADP release from the conformation at the end of the working stroke is also strain-sensitive, further increasing by one order of magnitude within a few nanometres of negative strain. These results provide the molecular explanation of the relation between the rate of energy liberation and the load during muscle contraction. Key points Muscle contraction is due to cyclical ATP-driven working strokes in the myosin motors while attached to the actin filament. Each working stroke is accompanied by the release of the hydrolysis products, orthophosphate and ADP. The rate of myosin–actin interactions increases with the increase in shortening velocity. We used fast half-sarcomere mechanics on skinned muscle fibres to determine the relation between shortening velocity and the number and strain of myosin motors and the effect of orthophosphate concentration. A model simulation of the myosin–actin reaction explains the results assuming that orthophosphate and then ADP are released with rates that increase as the motor progresses through the working stroke. The ADP release rate further increases by one order of magnitude with the rise of negative strain in the final motor conformation. These results provide the molecular explanation of the relation between the rate of energy liberation and shortening velocity during muscle contraction. PMID:26041599

Pan-STARRS Data Release 2

NASA Astrophysics Data System (ADS)

Flewelling, Heather

2018-01-01

On December 19, 2016, Pan-STARRS released the stacked images, mean attributes catalogs, and static sky catalogs for the 3pi survey, in 5 filters (g,r,i,z,y), covering 3/4 of the sky, everything north of -30 in declination. This set of data is called Data Release 1 (DR1), and it is available to all at http://panstarrs.stsci.edu. It contains more than 10 billion objects, 3 billion of those objects have stack photometry. We give an update on the progress of the forthcoming Data Release (DR2) database, which will provide time domain catalogs and single exposures for the 3pi survey. This includes 3pi data taken between 2010 and 2014, covering approximately 60 epochs per patch of sky, and includes measurements detected in the single exposures as well as forced photometry measurements (photometry measured on single exposures using the positions from sources detected in the stacks). We also provide informations on futures releases (DR3 and beyond), which will contain the rest of the 3pi database (specifically, the data products related to difference imaging), as well as the data products for the Medium Deep (MD) survey.

Progress in understanding fission-product behaviour in coated uranium-dioxide fuel particles

NASA Astrophysics Data System (ADS)

Barrachin, M.; Dubourg, R.; Kissane, M. P.; Ozrin, V.

2009-03-01

Supported by results of calculations performed with two analytical tools (MFPR, which takes account of physical and chemical mechanisms in calculating the chemical forms and physical locations of fission products in UO2, and MEPHISTA, a thermodynamic database), this paper presents an investigation of some important aspects of the fuel microstructure and chemical evolutions of irradiated TRISO particles. The following main conclusions can be identified with respect to irradiated TRISO fuel: first, the relatively low oxygen potential within the fuel particles with respect to PWR fuel leads to chemical speciation that is not typical of PWR fuels, e.g., the relatively volatile behaviour of barium; secondly, the safety-critical fission-product caesium is released from the urania kernel but the buffer and pyrolytic-carbon coatings could form an important chemical barrier to further migration (i.e., formation of carbides). Finally, significant releases of fission gases from the urania kernel are expected even in nominal conditions.

Detecting cell lysis using viscosity monitoring in E. coli fermentation to prevent product loss.

PubMed

Newton, Joseph M; Schofield, Desmond; Vlahopoulou, Joanna; Zhou, Yuhong

2016-07-08

Monitoring the physical or chemical properties of cell broths to infer cell status is often challenging due to the complex nature of the broth. Key factors indicative of cell status include cell density, cell viability, product leakage, and DNA release to the fermentation broth. The rapid and accurate prediction of cell status for hosts with intracellular protein products can minimise product loss due to leakage at the onset of cell lysis in fermentation. This article reports the rheological examination of an industrially relevant E. coli fermentation producing antibody fragments (Fab'). Viscosity monitoring showed an increase in viscosity during the exponential phase in relation to the cell density increase, a relatively flat profile in the stationary phase, followed by a rapid increase which correlated well with product loss, DNA release and loss of cell viability. This phenomenon was observed over several fermentations that a 25% increase in broth viscosity (using induction-point viscosity as a reference) indicated 10% product loss. Our results suggest that viscosity can accurately detect cell lysis and product leakage in postinduction cell cultures, and can identify cell lysis earlier than several other common fermentation monitoring techniques. This work demonstrates the utility of rapidly monitoring the physical properties of fermentation broths, and that viscosity monitoring has the potential to be a tool for process development to determine the optimal harvest time and minimise product loss. © 2016 The Authors. Biotechnology Progress published by Wiley Periodicals, Inc. on behalf of American Institute of Chemical Engineers, 32:1069-1076, 2016. © 2016 The Authors. Biotechnology Progress published by Wiley Periodicals, Inc. on behalf of American Institute of Chemical Engineers.

Controlled Release from Recombinant Polymers

PubMed Central

Price, Robert; Poursaid, Azadeh; Ghandehari, Hamidreza

2014-01-01

Recombinant polymers provide a high degree of molecular definition for correlating structure with function in controlled release. The wide array of amino acids available as building blocks for these materials lend many advantages including biorecognition, biodegradability, potential biocompatibility, and control over mechanical properties among other attributes. Genetic engineering and DNA manipulation techniques enable the optimization of structure for precise control over spatial and temporal release. Unlike the majority of chemical synthetic strategies used, recombinant DNA technology has allowed for the production of monodisperse polymers with specifically defined sequences. Several classes of recombinant polymers have been used for controlled drug delivery. These include, but are not limited to, elastin-like, silk-like, and silk-elastinlike proteins, as well as emerging cationic polymers for gene delivery. In this article, progress and prospects of recombinant polymers used in controlled release will be reviewed. PMID:24956486

Effect of Nisin's Controlled Release on Microbial Growth as Modeled for Micrococcus luteus.

PubMed

Balasubramanian, Aishwarya; Lee, Dong Sun; Chikindas, Michael L; Yam, Kit L

2011-06-01

The need for safe food products has motivated food scientists and industry to find novel technologies for antimicrobial delivery for improving food safety and quality. Controlled release packaging is a novel technology that uses the package to deliver antimicrobials in a controlled manner and sustain antimicrobial stress on the targeted microorganism over the required shelf life. This work studied the effect of controlled release of nisin to inhibit growth of Micrococcus luteus (a model microorganism) using a computerized syringe pump system to mimic the release of nisin from packaging films which was characterized by an initially fast rate and a slower rate as time progressed. The results show that controlled release of nisin was strikingly more effective than instantly added ("formulated") nisin. While instant addition experiments achieved microbial inhibition only at the beginning, controlled release experiments achieved complete microbial inhibition for a longer time, even when as little as 15% of the amount of nisin was used as compared to instant addition.

The impact of mast cells on cardiovascular diseases.

PubMed

Kritikou, Eva; Kuiper, Johan; Kovanen, Petri T; Bot, Ilze

2016-05-05

Mast cells comprise an innate immune cell population, which accumulates in tissues proximal to the outside environment and, upon activation, augments the progression of immunological reactions through the release and diffusion of either pre-formed or newly generated mediators. The released products of mast cells include histamine, proteases, as well as a variety of cytokines, chemokines and growth factors, which act on the surrounding microenvironment thereby shaping the immune responses triggered in various diseased states. Mast cells have also been detected in the arterial wall and are implicated in the onset and progression of numerous cardiovascular diseases. Notably, modulation of distinct mast cell actions using genetic and pharmacological approaches highlights the crucial role of this cell type in cardiovascular syndromes. The acquired evidence renders mast cells and their mediators as potential prognostic markers and therapeutic targets in a broad spectrum of pathophysiological conditions related to cardiovascular diseases. Copyright © 2015 Elsevier B.V. All rights reserved.

SAGA: A project to automate the management of software production systems

NASA Technical Reports Server (NTRS)

Campbell, R. H.

1983-01-01

The current work in progress for the SAGA project are described. The highlights of this research are: a parser independent SAGA editor, design for the screen editing facilities of the editor, delivery to NASA of release 1 of Olorin, the SAGA parser generator, personal workstation environment research, release 1 of the SAGA symbol table manager, delta generation in SAGA, requirements for a proof management system, documentation for and testing of the cyber pascal make prototype, a prototype cyber-based slicing facility, a June 1984 demonstration plan, SAGA utility programs, summary of UNIX software engineering support, and theorem prover review.

The Fourth National Climate Assessment: Progress and Next Steps

NASA Astrophysics Data System (ADS)

Reidmiller, D.; Lewis, K.; Reeves, K.

2017-12-01

The Global Change Research Act of 1990 mandates the production of a quadrennial National Climate Assessment (NCA) that integrates, evaluates, and interprets global change science. The NCA analyzes observed and projected trends in global change and evaluates related impacts across a range of sectors and regions in the United States. The fourth assessment, NCA4, is currently under development by nearly 300 Federal and non-Federal experts and is expected to be available for public comment in Fall 2017 and released in late 2018. NCA4 is a key component of the US Global Change Research Program's Sustained Assessment process, which aims to advance the science of global change and provide authoritative, relevant information for decision makers. This talk will highlight the progress of NCA4, including an overview of the current draft of the assessment and advances since the third NCA, released in 2014. It will highlight the Climate Science Special Report, an essential component of NCA4, as well as provide insight into the public engagement process-including opportunities to participate-and identify scientific inputs and tools critical to its development, such as the 2nd State of the Carbon Cycle Report and USGCRP's new scenario products website.

Mesoporous silica formulation strategies for drug dissolution enhancement: a review.

PubMed

McCarthy, Carol A; Ahern, Robert J; Dontireddy, Rakesh; Ryan, Katie B; Crean, Abina M

2016-01-01

Silica materials, in particular mesoporous silicas, have demonstrated excellent properties to enhance the oral bioavailability of poorly water-soluble drugs. Current research in this area is focused on investigating the kinetic profile of drug release from these carriers and manufacturing approaches to scale-up production for commercial manufacture. This review provides an overview of different methods utilized to load drugs onto mesoporous silica carriers. The influence of silica properties and silica pore architecture on drug loading and release are discussed. The kinetics of drug release from mesoporous silica systems is examined and the manufacturability and stability of these formulations are reviewed. Finally, the future prospects of mesoporous silica drug delivery systems are considered. Substantial progress has been made in the characterization and development of mesoporous drug delivery systems for drug dissolution enhancement. However, more research is required to fully understand the drug release kinetic profile from mesoporous silica materials. Incomplete drug release from the carrier and the possibility of drug re-adsorption onto the silica surface need to be investigated. Issues to be addressed include the manufacturability and regulation status of formulation approaches employing mesoporous silica to enhance drug dissolution. While more research is needed to support the move of this technology from the bench to a commercial medicinal product, it is a realistic prospect for the near future.

Conceptual model for quantifying pre-smolt production from flow-dependent physical habitat and water temperature

USGS Publications Warehouse

Williamson, S. C.; Bartholow, J. M.; Stalnaker, C. B.

1993-01-01

A conceptual model has been developed to test river regulation concepts by linking physical habitat and water temperature with salmonid population and production in cold water streams. Work is in progress to examine numerous questions as part of flow evaluation and habitat restoration programmes in the Trinity River of California and elsewhere. For instance, how much change in pre-smolt chinook salmon (Oncorhynchus tshawytscha) production in the Trinity River would result from a different annual instream allocation (i.e. up or down from 271 × 106 m3released in the late 1980s) and how much change in pre-smolt production would result from a different release pattern (i.e. different from the 8.5 m3 s−1 year-round release). The conceptual model is being used to: design, integrate and improve young-of-year population data collection efforts; test hypotheses that physical habitat significantly influences movement, growth and mortality of salmonid fishes; and analyse the relative severity of limiting factors during each life stage. The conceptual model, in conjunction with previously developed tools in the Instream Flow Incremental Methodology, should provide the means to more effectively manage a fishery resource below a regulated reservoir and to provide positive feedback to planning of annual reservoir operations.

Effects of N-acetyl-L-cysteine on the membrane vesicle release and growth of respiratory pathogens.

PubMed

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

2017-05-01

Bacterial infections contribute to the disease progression of chronic obstructive pulmonary disease by stimulating mucus production in the airways. This increased mucus production and other symptoms are often alleviated when patients are treated with mucolytics such as N-acetyl-L-cysteine (NAC). Moreover, NAC has been suggested to inhibit bacterial growth. Bacteria can release membrane vesicles (MVs) in response to stress, and recent studies report a role for these proinflammatory MVs in the pathogenesis of airways disease. Yet, until now it is not clear whether NAC also affects the release of these MVs. This study set out to determine whether NAC, at concentrations reached during high-dose nebulization, affects bacterial growth and MV release of the respiratory pathogens non-typeable Haemophilus influenzae (NTHi), Moraxella catarrhalis (Mrc), Streptococcus pneumoniae (Spn) and Pseudomonas aeruginosa (Psa). We observed that NAC exerted a strong bacteriostatic effect, but also induced the release of proinflammatory MVs by NTHi, Mrc and Psa, but not by Spn. Interestingly, NAC also markedly blunted the release of TNF-α by naive macrophages in response to MVs. This suggests that the application of NAC by nebulization at a high dosage may be beneficial for patients with airway conditions associated with bacterial infections. © FEMS 2017. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.

Intracellular and extracellular adenosine triphosphate in regulation of insulin secretion from pancreatic β cells (β).

PubMed

Wang, Chunjiong; Geng, Bin; Cui, Qinghua; Guan, Youfei; Yang, Jichun

2014-03-01

Adenosine triphosphate (ATP) synthesis and release in mitochondria play critical roles in regulating insulin secretion in pancreatic β cells. Mitochondrial dysfunction is mainly characterized by a decrease in ATP production, which is a central event in the progression of pancreatic β cell dysfunction and diabetes. ATP has been demonstrated to regulate insulin secretion via several pathways: (i) Intracellular ATP directly closes ATP-sensitive potassium channel to open L-type calcium channel, leading to an increase in free cytosolic calcium levels and exocytosis of insulin granules; (ii) A decrease in ATP production is always associated with an increase in production of reactive oxygen species, which exerts deleterious effects on pancreatic β cell survival and insulin secretion; and (iii) ATP can be co-secreted with insulin from pancreatic β cells, and the released ATP functions as an autocrine signal to modulate insulin secretory process via P2 receptors on the cell membrane. In this review, the recent findings regarding the role and mechanism of ATP synthesis and release in regulation of insulin secretion from pancreatic β cells will be summarized and discussed. © 2013 Ruijin Hospital, Shanghai Jiaotong University School of Medicine and Wiley Publishing Asia Pty Ltd.

Light-Water-Reactor safety research program. Quarterly progress report, January--March 1977

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

None

The report summarizes the Argonne National Laboratory work performed during January, February, and March 1977 on water-reactor-safety problems. The following research and development areas are covered: (1) loss-of-coolant accident research: heat transfer and fluid dynamics; (2) transient fuel response and fission-product release program; (3) mechanical properties of zircaloy containing oxygen; and (4) steam-explosion studies.

First Nations, Metis and Inuit Education Policy Framework: Progress Report, 2008

ERIC Educational Resources Information Center

Alberta Education, 2008

2008-01-01

This progress report describes the work currently underway toward improving the success of First Nations, Metis and Inuit (FNMI) students in Alberta. It provides an update on the progress made since the release of the Framework in 2002 and the 2004 Progress Report up to December 31, 2007. Since the release of the Framework, a new Ministry of…

The Productive Ward: releasing Time to Care(™)--what we can learn from the literature for implementation.

PubMed

White, Mark; Wells, John Sg; Butterworth, Tony

2014-10-01

This paper reviews the Productive Ward: Releasing Time to Care™ literature, identifying and discussing the key characteristics that may contribute to successful implementation. It is 5 years since the official UK launch of the Productive Ward, and the Republic of Ireland commenced a phased, national implementation programme in 2011. Thus it is timely to reflect on the implementation lessons learned to date and described in the literature. Using taxonomic mapping, this paper evaluates the current state of the literature that pertains to Productive Ward implementation experience; success factors; reports, and assessments. Seven common contextual characteristics were identified: robust and engaging communication; enabling and empowering roles; appropriate training; project planning and management; leadership; corporate/management engagement and support; and financial and human resource commitment. The key characteristics identified have a direct impact on the implementation of the Productive Ward. The interplay between these key characteristics and how this interplay influences successful implementation of the Productive Ward warrants further research. Acknowledging and embracing the seven characteristics during implementation will positively improve the progress and success of the initiatives implementation. © 2013 John Wiley & Sons Ltd.

Pharmacological hypothesis: Nitric oxide-induced inhibition of ADAM-17 activity as well as vesicle release can in turn prevent the production of soluble endothelin-converting enzyme.

PubMed

Kuruppu, Sanjaya; Rajapakse, Niwanthi W; Parkington, Helena C; Smith, Ian

2017-10-01

Endothelin-1 (ET-1) and nitric oxide (NO) are two highly potent vasoactive molecules with opposing effects on the vasculature. Endothelin-converting enzyme (ECE) and nitric oxide synthase (NOS) catalyse the production of ET-1 and NO, respectively. It is well established that these molecules play a crucial role in the initiation and progression of cardiovascular diseases and have therefore become targets of therapy. Many studies have examined the mechanism(s) by which NO regulates ET-1 production. Expression and localization of ECE-1 is a key factor that determines the rate of ET-1 production. ECE-1 can either be membrane bound or be released from the cell surface to produce a soluble form. NO has been shown to reduce the expression of both membrane-bound and soluble ECE-1. Several studies have examined the mechanism(s) behind NO-mediated inhibition of ECE expression on the cell membrane. However, the precise mechanism(s) behind NO-mediated inhibition of soluble ECE production are unknown. We hypothesize that both exogenous and endogenous NO, inhibits the production of soluble ECE-1 by preventing its release via extracellular vesicles (e.g., exosomes), and/or by inhibiting the activity of A Disintegrin and Metalloprotease-17 (ADAM17). If this hypothesis is proven correct in future studies, these pathways represent targets for the therapeutic manipulation of soluble ECE-1 production. © 2017 The Authors. Pharmacology Research & Perspectives published by John Wiley & Sons Ltd, British Pharmacological Society and American Society for Pharmacology and Experimental Therapeutics.

Project SQUID. Quarterly Progress Report

DTIC Science & Technology

1948-10-01

cata- lysts imbedded in the liner walls, and endothermic diffusion processes. Summary The paper entitled Heat Transfer in Laminar Boundary Layer...in mixture strength must be effected up to that required for maximum heat release to prevent blow -off of the annu- lus flame. It is possible to...these films. An X-ray diffraction investigation of the effect of polishing agent on the character of oxidation product has been started. Samples

Silicosis and coal workers' pneumoconiosis.

PubMed Central

Castranova, V; Vallyathan, V

2000-01-01

Exposure to coal mine dust and/or crystalline silica results in pneumoconiosis with initiation and progression of pulmonary fibrosis. This review presents characteristics of simple and complicated coal workers' pneumoconiosis (CWP) as well as pathologic indices of acute and chronic silicosis by summarizing results of in vitro, animal, and human investigations. These results support four basic mechanisms in the etiology of CWP and silicosis: a) direct cytotoxicity of coal dust or silica, resulting in lung cell damage, release of lipases and proteases, and eventual lung scarring; b) activation of oxidant production by pulmonary phagocytes, which overwhelms the antioxidant defenses and leads to lipid peroxidation, protein nitrosation, cell injury, and lung scarring; c) activation of mediator release from alveolar macrophages and epithelial cells, which leads to recruitment of polymorphonuclear leukocytes and macrophages, resulting in the production of proinflammatory cytokines and reactive species and in further lung injury and scarring; d) secretion of growth factors from alveolar macrophages and epithelial cells, stimulating fibroblast proliferation and eventual scarring. Results of in vitro and animal studies provide a basis for proposing these mechanisms for the initiation and progression of pneumoconiosis. Data obtained from exposed workers lend support to these mechanisms. Images Figure 1 Figure 2 Figure 3 Figure 4 Figure 5 Figure 6 PMID:10931786

Stimulation of interleukin-6 production of periodontal ligament cells by Porphyromonas endodontalis lipopolysaccharide.

PubMed

Ogura, N; Shibata, Y; Kamino, Y; Matsuda, U; Hayakawa, M; Oikawa, T; Takiguchi, H; Izumi, H; Abiko, Y

1994-12-01

Interleukin-6 (IL-6), which is a multifunctional cytokine, has important roles in acute and chronic inflammation and may also be implicated in bone resorption. We examined the IL-6 production in periodontal ligament (PDL) cells which were treated with lipopolysaccharide (LPS) from several oral inflammatory pathogens. The LPS from Porphyromonas endodontalis, which was isolated from infected root canals and radicular cyst fluids, was more potent than the LPS from any other periodontal organisms examined. P. endodontalis LPS stimulated IL-6 release from PDL cells in a time- and dose-dependent manner. Northern blot hybridization analysis revealed that the IL-6 mRNA level in PDL cells was increased by P. endodontalis LPS. These results suggest that stimulation of the IL-6 release of PDL cells by P. endodontalis LPS may have a role in the progression of inflammation and alveolar bone resorption in periodontal and periapical diseases.

Large scale preparation of high mannose and paucimannose N-glycans from soybean proteins by oxidative release of natural glycans (ORNG).

PubMed

Zhu, Yuyang; Yan, Maomao; Lasanajak, Yi; Smith, David F; Song, Xuezheng

2018-07-15

Despite the important advances in chemical and chemoenzymatic synthesis of glycans, access to large quantities of complex natural glycans remains a major impediment to progress in Glycoscience. Here we report a large-scale preparation of N-glycans from a kilogram of commercial soy proteins using oxidative release of natural glycans (ORNG). The high mannose and paucimannose N-glycans were labeled with a fluorescent tag and purified by size exclusion and multidimensional preparative HPLC. Side products are identified and potential mechanisms for the oxidative release of natural N-glycans from glycoproteins are proposed. This study demonstrates the potential for using the ORNG approach as a complementary route to synthetic approaches for the preparation of multi-milligram quantities of biomedically relevant complex glycans. Copyright © 2018 Elsevier Ltd. All rights reserved.

Postproduction Handling and Administration of Protein Pharmaceuticals and Potential Instability Issues.

PubMed

Nejadnik, M Reza; Randolph, Theodore W; Volkin, David B; Schöneich, Christian; Carpenter, John F; Crommelin, Daan J A; Jiskoot, Wim

2018-04-14

The safety and efficacy of protein pharmaceuticals depend not only on biological activity but also on purity levels. Impurities may be process related because of limitations in manufacturing or product related because of protein degradation occurring throughout the life history of a product. Although the pharmaceutical biotechnology industry has made great progress in improving bulk and drug product manufacturing as well as company-controlled storage and transportation conditions to minimize the level of degradation, there is less control over the many factors that may subsequently affect product quality after the protein pharmaceuticals are released and shipped by the manufacturer. Routine handling or unintentional mishandling of therapeutic protein products may cause protein degradation that remains unnoticed but can potentially compromise the clinical safety and efficacy of the product. In this commentary, we address some potential risks associated with (mis)handling of protein pharmaceuticals after release by the manufacturer. We summarize the environmental stress factors that have been shown to cause protein degradation and that may be encountered during typical handling procedures of protein pharmaceuticals in a hospital setting or during self-administration by patients. Moreover, we provide recommendations for improvements in product handling to help ensure the quality of protein pharmaceuticals during use. Copyright © 2018 American Pharmacists Association®. Published by Elsevier Inc. All rights reserved.

Carcinoembryonic antigen promotes colorectal cancer progression by targeting adherens junction complexes

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

Bajenova, Olga, E-mail: o.bazhenova@spbu.ru; Department of Genetics and Biotechnology, St. Petersburg State University, St. Petersburg 199034; Department of Surgery and Biomedical Sciences, Creighton University, Omaha, NE 68178

2014-06-10

Oncomarkers play important roles in the detection and management of human malignancies. Carcinoembryonic antigen (CEA, CEACAM5) and epithelial cadherin (E-cadherin) are considered as independent tumor markers in monitoring metastatic colorectal cancer. They are both expressed by cancer cells and can be detected in the blood serum. We investigated the effect of CEA production by MIP101 colorectal carcinoma cell lines on E-cadherin adherens junction (AJ) protein complexes. No direct interaction between E-cadherin and CEA was detected; however, the functional relationships between E-cadherin and its AJ partners: α-, β- and p120 catenins were impaired. We discovered a novel interaction between CEA andmore » beta-catenin protein in the CEA producing cells. It is shown in the current study that CEA overexpression alters the splicing of p120 catenin and triggers the release of soluble E-cadherin. The influence of CEA production by colorectal cancer cells on the function of E-cadherin junction complexes may explain the link between the elevated levels of CEA and the increase in soluble E-cadherin during the progression of colorectal cancer. - Highlights: • Elevated level of CEA increases the release of soluble E-cadherin during the progression of colorectal cancer. • CEA over-expression alters the binding preferences between E-cadherin and its partners: α-, β- and p120 catenins in adherens junction complexes. • CEA produced by colorectal cancer cells interacts with beta-catenin protein. • CEA over-expression triggers the increase in nuclear beta-catenin. • CEA over-expression alters the splicing of p120 catenin protein.« less

Progress and challenges to the global waste management system.

PubMed

Singh, Jagdeep; Laurenti, Rafael; Sinha, Rajib; Frostell, Björn

2014-09-01

Rapid economic growth, urbanization and increasing population have caused (materially intensive) resource consumption to increase, and consequently the release of large amounts of waste to the environment. From a global perspective, current waste and resource management lacks a holistic approach covering the whole chain of product design, raw material extraction, production, consumption, recycling and waste management. In this article, progress and different sustainability challenges facing the global waste management system are presented and discussed. The study leads to the conclusion that the current, rather isolated efforts, in different systems for waste management, waste reduction and resource management are indeed not sufficient in a long term sustainability perspective. In the future, to manage resources and wastes sustainably, waste management requires a more systems-oriented approach that addresses the root causes for the problems. A specific issue to address is the development of improved feedback information (statistics) on how waste generation is linked to consumption. © The Author(s) 2014.

Soluble microbial products (SMPs) release in activated sludge systems: a review

PubMed Central

2012-01-01

This review discusses the characterization, production and implications of soluble microbial products (SMPs) in biological wastewater treatment. The precise definition of SMPs is open to talk about, but is currently regarded as “the pool of organic compounds that are released into solution from substrate metabolism and biomass decay”'. Some of the SMPs have been identified as humic acids, polysaccharides, proteins, amino acids, antibiotics, extracellular enzymes and structural components of cells and products of energy metabolism. They adversely affect the kinetic activity, flocculating and settling properties of sludge. This review outlines some important findings with regard to biodegradability and treatability of SMPs and also the effect of process parameters on their production. As SMPs are produced during biological treatment process, their trace amounts normally remain in the effluent that defines the highest COD removal efficiency. Their presence in effluent represents a high potential risk of toxic by-product formation during chlorine disinfection. Studies have indicated that among all wastewater post-treatment processes, the adsorption by granular activated carbon combined with biologically induced degradation is the most effective method for removal of SMPs. However, it may be concludes that the knowledge regarding SMPs is still under progress and more work is required to fully understand their contribution to the treatment process. PMID:23369231

Soluble microbial products (SMPs) release in activated sludge systems: a review.

PubMed

Azami, Hamed; Sarrafzadeh, Mohammad Hossein; Mehrnia, Mohammad Reza

2012-12-18

This review discusses the characterization, production and implications of soluble microbial products (SMPs) in biological wastewater treatment. The precise definition of SMPs is open to talk about, but is currently regarded as "the pool of organic compounds that are released into solution from substrate metabolism and biomass decay"'. Some of the SMPs have been identified as humic acids, polysaccharides, proteins, amino acids, antibiotics, extracellular enzymes and structural components of cells and products of energy metabolism. They adversely affect the kinetic activity, flocculating and settling properties of sludge. This review outlines some important findings with regard to biodegradability and treatability of SMPs and also the effect of process parameters on their production. As SMPs are produced during biological treatment process, their trace amounts normally remain in the effluent that defines the highest COD removal efficiency. Their presence in effluent represents a high potential risk of toxic by-product formation during chlorine disinfection. Studies have indicated that among all wastewater post-treatment processes, the adsorption by granular activated carbon combined with biologically induced degradation is the most effective method for removal of SMPs. However, it may be concludes that the knowledge regarding SMPs is still under progress and more work is required to fully understand their contribution to the treatment process.

Poly(NIPAm-AMPS) nanoparticles for targeted delivery of anti-inflammatory cell penetrating peptides

NASA Astrophysics Data System (ADS)

Bartlett, Rush Lloyd, II

Inflammatory diseases such as osteoarthritis and rheumatoid arthritis cause $127.8 billion in US healthcare expenditures each year and are the cause of disability for 27% of disabled persons in the United States. Current treatment options rarely halt disease progression and often result in significant unwanted and debilitating side effects. Our laboratory has previously developed a family of cell penetrating peptides (CPPs) which inhibit the activity of mitogen activated protein kinase activate protein kinase 2 (MK2). MK2 mediates the inflammatory response by activating Tristetraprline (TTP). Once activated, TTP rapidly stabilizes AU rich regions of pro-inflammatory cytokine mRNA which allows translation of pro-inflammatory cytokines to occur. Blocking MK2 with our labs CPPs yields a decrease in inflammatory activity but CPPs by are highly non specific and prone to rapid enzymatic degradation in vivo.. In order to increase the potency of MK2 inhibiting CPPs we have developed a novel nanoparticle drug carrier composed of poly(N-isopropylacrylamide-co-2-acrylamido-2-methyl-1-propanesulfonic acid). This drug carrier has been shown to have preliminary efficacy in vitro and ex vivo for suppressing pro-inflammatory cytokine production when releasing CPPs. This thesis will present progress made on three aims: Specific Aim 1) Create and validate a NIPAm based drug delivery system that mimics the binding and release previously observed between cell penetrating peptides and glycosaminoglycans. Specific Aim 2) Engineer degradability into poly(NIPAm-AMPS) nanoparticles to enable more drug to be released and qualify that system in vitro. Specific Aim 3) Validate poly(NIPAm-AMPS) nanoparticles for targeted drug delivery in an ex vivo inflammatory model. Overall we have developed a novel anionic nanoparticle system that is biocompatible and efficient at loading and releasing cell penetrating peptides to inflamed tissue. Once loaded with a CPP the nanoparticle drug complex is capable of targeting diseased tissue and preventing the production of pro-inflammatory cytokines in both in vitro and ex vivo models.

Accident Source Terms for Pressurized Water Reactors with High-Burnup Cores Calculated using MELCOR 1.8.5.

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

Gauntt, Randall O.; Goldmann, Andrew; Kalinich, Donald A.

2016-12-01

In this study, risk-significant pressurized-water reactor severe accident sequences are examined using MELCOR 1.8.5 to explore the range of fission product releases to the reactor containment building. Advances in the understanding of fission product release and transport behavior and severe accident progression are used to render best estimate analyses of selected accident sequences. Particular emphasis is placed on estimating the effects of high fuel burnup in contrast with low burnup on fission product releases to the containment. Supporting this emphasis, recent data available on fission product release from high-burnup (HBU) fuel from the French VERCOR project are used in thismore » study. The results of these analyses are treated as samples from a population of accident sequences in order to employ approximate order statistics characterization of the results. These trends and tendencies are then compared to the NUREG-1465 alternative source term prescription used today for regulatory applications. In general, greater differences are observed between the state-of-the-art calculations for either HBU or low-burnup (LBU) fuel and the NUREG-1465 containment release fractions than exist between HBU and LBU release fractions. Current analyses suggest that retention of fission products within the vessel and the reactor coolant system (RCS) are greater than contemplated in the NUREG-1465 prescription, and that, overall, release fractions to the containment are therefore lower across the board in the present analyses than suggested in NUREG-1465. The decreased volatility of Cs 2 MoO 4 compared to CsI or CsOH increases the predicted RCS retention of cesium, and as a result, cesium and iodine do not follow identical behaviors with respect to distribution among vessel, RCS, and containment. With respect to the regulatory alternative source term, greater differences are observed between the NUREG-1465 prescription and both HBU and LBU predictions than exist between HBU and LBU analyses. Additionally, current analyses suggest that the NUREG-1465 release fractions are conservative by about a factor of 2 in terms of release fractions and that release durations for in-vessel and late in-vessel release periods are in fact longer than the NUREG-1465 durations. It is currently planned that a subsequent report will further characterize these results using more refined statistical methods, permitting a more precise reformulation of the NUREG-1465 alternative source term for both LBU and HBU fuels, with the most important finding being that the NUREG-1465 formula appears to embody significant conservatism compared to current best-estimate analyses. ACKNOWLEDGEMENTS This work was supported by the United States Nuclear Regulatory Commission, Office of Nuclear Regulatory Research. The authors would like to thank Dr. Ian Gauld and Dr. Germina Ilas, of Oak Ridge National Laboratory, for their contributions to this work. In addition to development of core fission product inventory and decay heat information for use in MELCOR models, their insights related to fuel management practices and resulting effects on spatial distribution of fission products in the core was instrumental in completion of our work.« less

Development of orally disintegrating tablets comprising controlled-release multiparticulate beads

PubMed Central

2012-01-01

Melperone is an atypical antipsychotic agent that has shown a wide spectrum of neuroleptic properties, particularly effective in the treatment of senile dementia and Parkinson’s-associated psychosis, and is marketed in Europe as an immediate-release (IR) tablet and syrup. An orally disintegrating tablet (ODT) dosage form would be advantageous for patients who experience difficulty in swallowing large tablets or capsules or those who experience dysphagia. Controlled-release (CR) capsule and ODT formulations containing melperone HCl were developed with target in vitro release profiles suitable for a once-daily dosing regimen. Both dosage forms allow for the convenient production of dose-proportional multiple strengths. Two ODT formulations exhibiting fast and medium release profiles and one medium release profile capsule formulation (each 50 mg) were tested in vivo using IR syrup as the reference. The two medium release formulations were shown to be bioequivalent to each other and are suitable for once-daily dosing. Based on the analytical and organoleptic test results, as well as the blend uniformity and in-process compression data at various compression forces using coated beads produced at one-tenth (1/10) commercial scale, both formulations in the form of CR capsules and CR ODTs have shown suitability for progression into further clinical development. PMID:22356215

Tobacco and e-cigarette products initiate Kupffer cell inflammatory responses.

PubMed

Rubenstein, David A; Hom, Sarah; Ghebrehiwet, Berhane; Yin, Wei

2015-10-01

Kupffer cells are liver resident macrophages that are responsible for screening and clearing blood of pathogens and foreign particles. It has recently been shown that Kupffer cells interact with platelets, through an adhesion based mechanism, to aid in pathogen clearance and then these platelets re-enter the general systemic circulation. Thus, a mechanism has been identified that relates liver inflammation to possible changes in the systemic circulation. However, the role that Kupffer cells play in cardiovascular disease initiation/progression has not been elucidated. Thus, our objective was to determine whether or not Kupffer cells are responsive to a classical cardiovascular risk factor and if these changes can be transmitted into the general systemic circulation. If Kupffer cells initiate inflammatory responses after exposure to classical cardiovascular risk factors, then this provides a potential alternative/synergistic pathway for cardiovascular disease initiation. We aimed to elucidate the prevalence of this potential pathway. We hypothesized that Kupffer cells would initiate a robust inflammatory response after exposure to tobacco cigarette or e-cigarette products and that the inflammatory response would have the potential to antagonize other salient cells for cardiovascular disease progression. To test this, Kupffer cells were incubated with tobacco smoke extracts, e-cigarette vapor extracts or pure nicotine. Complement deposition onto Kupffer cells, Kupffer cell complement receptor expression, oxidative stress production, cytokine release and viability and density were assessed after the exposure. We observed a robust inflammatory response, oxidative stress production and cytokine release after Kupffer cells were exposed to tobacco or e-cigarette extracts. We also observed a marginal decrease in cell viability coupled with a significant decrease in cell density. In general, this was not a function of the extract formulation (e.g. tobacco vs. e-cigarette products or the formulation of the cigarette product). These results indicate that Kupffer cells are responsive to classical cardiovascular risk factors and that an inflammatory response is initiated that may pass into the general systemic circulation. Copyright © 2015 Elsevier Ltd. All rights reserved.

Controlled release for crop and wood protection: Recent progress toward sustainable and safe nanostructured biocidal systems.

PubMed

Mattos, Bruno D; Tardy, Blaise L; Magalhães, Washington L E; Rojas, Orlando J

2017-09-28

We review biocide delivery systems (BDS), which are designed to deter or control harmful organisms that damage agricultural crops, forests and forest products. This is a timely topic, given the growing socio-economical concerns that have motivated major developments in sustainable BDS. Associated designs aim at improving or replacing traditional systems, which often consist of biocides with extreme behavior as far as their solubility in water. This includes those that compromise or pollute soil and water (highly soluble or volatile biocides) or those that present low bioavailability (poorly soluble biocides). Major breakthroughs are sought to mitigate or eliminate consequential environmental and health impacts in agriculture and silviculture. Here, we consider the most important BDS vehicles or carriers, their synthesis, the environmental impact of their constituents and interactions with the active components together with the factors that affect their rates of release such as environmental factors and interaction of BDS with the crops or forest products. We put in perspective the state-of-the-art nanostructured carriers for controlled release, which need to address many of the challenges that exist in the application of BDS. Copyright © 2017 Elsevier B.V. All rights reserved.

Caffeic acid, a phenol found in white wine, modulates endothelial nitric oxide production and protects from oxidative stress-associated endothelial cell injury.

PubMed

Migliori, Massimiliano; Cantaluppi, Vincenzo; Mannari, Claudio; Bertelli, Alberto A E; Medica, Davide; Quercia, Alessandro Domenico; Navarro, Victor; Scatena, Alessia; Giovannini, Luca; Biancone, Luigi; Panichi, Vincenzo

2015-01-01

Several studies demonstrated that endothelium dependent vasodilatation is impaired in cardiovascular and chronic kidney diseases because of oxidant stress-induced nitric oxide availability reduction. The Mediterranean diet, which is characterized by food containing phenols, was correlated with a reduced incidence of cardiovascular diseases and delayed progression toward end stage chronic renal failure. Previous studies demonstrated that both red and white wine exert cardioprotective effects. In particular, wine contains Caffeic acid (CAF), an active component with known antioxidant activities. The aim of the present study was to investigate the protective effect of low doses of CAF on oxidative stress-induced endothelial injury. CAF increased basal as well as acetylcholine-induced NO release by a mechanism independent from eNOS expression and phosphorylation. In addition, low doses of CAF (100 nM and 1 μM) increased proliferation and angiogenesis and inhibited leukocyte adhesion and endothelial cell apoptosis induced by hypoxia or by the uremic toxins ADMA, p-cresyl sulfate and indoxyl sulfate. The biological effects exerted by CAF on endothelial cells may be at least in part ascribed to modulation of NO release and by decreased ROS production. In an experimental model of kidney ischemia-reperfusion injury in mice, CAF significantly decreased tubular cell apoptosis, intraluminal cast deposition and leukocyte infiltration. The results of the present study suggest that CAF, at very low dosages similar to those observed after moderate white wine consumption, may exert a protective effect on endothelial cell function by modulating NO release independently from eNOS expression and phosphorylation. CAF-induced NO modulation may limit cardiovascular and kidney disease progression associated with oxidative stress-mediated endothelial injury.

Summary of Research, Academic Departments, 1982-1983.

DTIC Science & Technology

1983-10-01

Office to pursue fur- - and the production of towing tank models is de - ther proof of concept tests and seek improvements ,’ scribed. The design...followed b" Haskind. Rci,,ncr. * as "Cable Fire Studies: Progress Report in Evaluation of Timman, van de Vooren and Greidanus. and Release Rate Apparatus...diameter of the in the capture chamber have been compared with a system is increased, the draft of the device is de - limited amount of experimental data

Laquinimod dampens hyperactive cytokine production in Huntington's disease patient myeloid cells.

PubMed

Dobson, Lucianne; Träger, Ulrike; Farmer, Ruth; Hayardeny, Liat; Loupe, Pippa; Hayden, Michael R; Tabrizi, Sarah J

2016-06-01

Huntington's disease (HD) is a neurodegenerative condition characterized by pathology in the brain and peripheral tissues. Hyperactivity of the innate immune system, due in part to NFκB pathway dysregulation, is an early and active component of HD. Evidence suggests targeting immune disruption may slow disease progression. Laquinimod is an orally active immunomodulator that down-regulates proinflammatory cytokine production in peripheral blood mononuclear cells, and in the brain down-regulates astrocytic and microglial activation by modulating NFκB signalling. Laquinimod had beneficial effects on inflammation, brain atrophy and disease progression in multiple sclerosis (MS) in two phase III clinical trials. This study investigated the effects of laquinimod on hyperactive proinflammatory cytokine release and NFκB signalling in HD patient myeloid cell cultures. Monocytes from manifest (manHD) and pre-manifest (preHD) HD gene carriers and healthy volunteers (HV) were treated with laquinimod and stimulated with lipopolysaccharide. After 24 h pre-treatment with 5 μM laquinimod, manHD monocytes released lower levels of IL-1β, IL-5, IL-8, IL-10, IL-13 and TNFα in response to stimulation. PreHD monocytes released lower levels of IL-8, IL-10 and IL-13, with no reduction observed in HV monocytes. The effects of laquinimod on dysfunctional NFκB signalling in HD was assessed by inhibitor of kappa B (IκB) degradation kinetics, nuclear translocation of NFκB and interactions between IκB kinase (IKK) and HTT, in HD myeloid cells. No differences were observed between laquinimod-treated and untreated conditions. These results provide evidence that laquinimod dampens hyper-reactive cytokine release from manHD and preHD monocytes, with a much reduced effect on HV monocytes. Evidence suggests targeting CNS and peripheral immune disruption may slow Huntington's disease (HD) neurodegenerative processes. The effects of laquinimod, an orally active immunomodulator, on hyperactive cytokine release and dysfunctional NFκB signalling in stimulated myeloid cell cultures from pre-manifest and manifest HD gene carriers and healthy volunteers were investigated. Laquinimod dampened cytokine release but did not impact NFκB signalling. Read the Editorial Highlight for this article on page 670. © 2016 The Authors. Journal of Neurochemistry published by John Wiley & Sons Ltd on behalf of International Society for Neurochemistry.

Soluble adhesion molecules in human cancers: sources and fates.

PubMed

van Kilsdonk, Jeroen W J; van Kempen, Léon C L T; van Muijen, Goos N P; Ruiter, Dirk J; Swart, Guido W M

2010-06-01

Adhesion molecules endow tumor cells with the necessary cell-cell contacts and cell-matrix interactions. As such, adhesion molecules are involved in cell signalling, proliferation and tumor growth. Rearrangements in the adhesion repertoire allow tumor cells to migrate, invade and form metastases. Besides these membrane-bound adhesion molecules several soluble adhesion molecules are detected in the supernatant of tumor cell lines and patient body fluids. Truncated soluble adhesion molecules can be generated by several conventional mechanisms, including alternative splicing of mRNA transcripts, chromosomal translocation, and extracellular proteolytic ectodomain shedding. Secretion of vesicles (ectosomes and exosomes) is an alternative mechanism mediating the release of full-length adhesion molecules. Soluble adhesion molecules function as modulators of cell adhesion, induce proteolytic activity and facilitate cell signalling. Additionally, adhesion molecules present on secreted vesicles might be involved in the vesicle-target cell interaction. Based on currently available data, released soluble adhesion molecules contribute to cancer progression and therefore should not be regarded as unrelated and non-functional side products of tumor progression. 2010 Elsevier GmbH. All rights reserved.

EPA releases progress report on hydraulic fracturing study

NASA Astrophysics Data System (ADS)

Showstack, Randy

2013-01-01

The U.S. Environmental Protection Agency (EPA) provided a 21 December progress report on its ongoing national study about the potential impacts of hydraulic fracturing on drinking water resources. The agency said that a draft of the congressionally requested study will be released in 2014 for public and peer review and that its progress report does not draw conclusions about the potential impacts of hydraulic fracturing, often referred to as fracking.

Recent progress in [11 C]carbon dioxide ([11 C]CO2 ) and [11 C]carbon monoxide ([11 C]CO) chemistry.

PubMed

Taddei, Carlotta; Gee, Antony D

2018-03-01

[ 11 C]Carbon dioxide ([ 11 C]CO 2 ) and [ 11 C]carbon monoxide ([ 11 C]CO) are 2 attractive precursors for labelling the carbonyl position (C═O) in a vast range of functionalised molecules (eg, ureas, amides, and carboxylic acids). The development of radiosynthetic methods to produce functionalised 11 C-labelled compounds is required to enhance the radiotracers available for positron emission tomography, molecular, and medical imaging applications. Following a brief summary of secondary 11 C-precursor production and uses, the review focuses on recent progress with direct 11 C-carboxylation routes with [ 11 C]CO 2 and 11 C-carbonylation with [ 11 C]CO. Novel approaches to generate [ 11 C]CO using CO-releasing molecules (CO-RMs), such as silacarboxylic acids and disilanes, applied to radiochemistry are described and compared with standard [ 11 C]CO production methods. These innovative [ 11 C]CO synthesis strategies represent efficient and reliable [ 11 C]CO production processes, enabling the widespread use of [ 11 C]CO chemistry within the wider radiochemistry community. Copyright © 2017 John Wiley & Sons, Ltd.

Nutritional quality of new food products released into the Australian retail food market in 2015 - is the food industry part of the solution?

PubMed

Spiteri, Sheree A; Olstad, Dana Lee; Woods, Julie L

2018-02-07

Food manufacturers have made public statements and voluntary commitments, such as the Healthier Australia Commitment (HAC), to improve the nutritional quality of foods. However, limited information about the nutritional quality or healthfulness of new products makes it difficult to determine if manufacturers are doing this. The purpose of this study was to assess the healthfulness of new food products released into the Australian retail market in 2015, and whether those companies who were HAC members released healthier food options compared to non-HAC members. This cross-sectional study assessed the healthfulness of all new retail food products launched in Australia in 2015 as indexed in Mintel's Global New Products Database. Healthfulness was assessed using three classification schemes: Healthy Choices Framework Victoria, Australian Dietary Guidelines and NOVA Food Classification System. Descriptive statistics and chi-squared tests described and compared the number and proportions of new foods falling within each of the food classification schemes' categories for companies that were and were not HAC members. In 2015, 4143 new food products were launched into the Australian market. The majority of new products were classified in each schemes' least healthy category (i.e. red, discretionary and ultra-processed). Fruits and vegetables represented just 3% of new products. HAC members launched a significantly greater proportion of foods classified as red (59% vs 51% for members and non-members, respectively) discretionary (79% vs 61%), and ultra-processed (94% vs 81%), and significantly fewer were classified as green (8% vs 15%), core foods (18% vs 36%) and minimally processed (0% vs 6%) (all p < 0.001). This study found that the majority of new products released into the Australian retail food market in 2015 were classified in each of three schemes' least healthy categories. A greater proportion of new products launched by companies that publicly committed to improve the nutritional quality of their products were unhealthy, and a lower proportion were healthy, compared with new products launched by companies that did not so commit. Greater monitoring of industry progress in improving the healthfulness of the food supply may be warranted, with public accountability if the necessary changes are not seen.

ARM Climate Research Facility Quarterly Value-Added Product Report

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

Sivaraman, C.

The purpose of this report is to provide a concise status update for Value-Added Products (VAPs) implemented by the Atmospheric Radiation Measurement (ARM) Climate Research Facility. The report is divided into the following sections: (1) new VAPs for which development has begun; (2) progress on existing VAPs; (3) future VAPs that have been recently approved; (4) other work that leads to a VAP; (5) top requested VAPs from the ARM Data Archive; and (6) a summary of VAP and data releases to production and evaluation. New information is highlighted in blue text. New information about processed data by the developermore » is highlighted in red text. The upcoming milestones and dates are highlighted in green.« less

Stimulation of interleukin-1 beta production of human dental pulp cells by Porphyromonas endodontalis lipopolysaccharide.

PubMed

Hosoya, S; Matsushima, K

1997-01-01

IL-1 beta is synthesized as an inactive precursor, which is subsequently processed by IL-1 beta converting enzyme (ICE) and found extracellularly as a mature biologically active polypeptide. Also, IL-1 beta has been detected in necrotic and inflamed dental pulp. We examined the IL-1 beta production in human dental pulp (HDP) cells treated with lipopolysaccharide (LPS) from Porphyromonas endodontalis (P. e.) isolated from root canals and radicular cyst fluids. We demonstrated that P. e. LPS stimulated IL-1 beta release from HDP cells in a time- and dose-dependent manner. However, ICE activity was not increased by P. e. LPS. Northern blot hybridization analysis revealed that the IL-1 beta mRNA level in HDP cells was increased by P. e. LPS. These results suggest that stimulation of IL-1 beta release from HDP cells by P. e. LPS may have an important role in the progression of inflammation in pulpal and periapical disease.

Osthole Mitigates Progressive IgA Nephropathy by Inhibiting Reactive Oxygen Species Generation and NF-κB/NLRP3 Pathway

PubMed Central

Hua, Kuo-Feng; Yang, Shun-Min; Kao, Tzu-Yang; Chang, Jia-Ming; Chen, Hui-Ling; Tsai, Yung-Jen; Chen, Ann; Yang, Sung-Sen; Chao, Louis Kuoping; Ka, Shuk-Man

2013-01-01

Renal reactive oxygen species (ROS) and mononuclear leukocyte infiltration are involved in the progressive stage (exacerbation) of IgA nephropathy (IgAN), which is characterized by glomerular proliferation and renal inflammation. The identification of the mechanism responsible for this critical stage of IgAN and the development of a therapeutic strategy remain a challenge. Osthole is a pure compound isolated from Cnidiummonnieri (L.) Cusson seeds, which are used as a traditional Chinese medicine, and is anti-inflammatory, anti-apoptotic, and anti-fibrotic both in vitro and in vivo. Recently, we showed that osthole acts as an anti-inflammatory agent by reducing nuclear factor-kappa B (NF-κB) activation in and ROS release by activated macrophages. In this study, we examined whether osthole could prevent the progression of IgAN using a progressive IgAN (Prg-IgAN) model in mice. Our results showed that osthole administration resulted in prevention of albuminuria, improved renal function, and blocking of renal progressive lesions, including glomerular proliferation, glomerular sclerosis, and periglomerular mononuclear leukocyte infiltration. These findings were associated with (1) reduced renal superoxide anion levels and increased Nrf2 nuclear translocation, (2) inhibited renal activation of NF-κB and the NLRP3 inflammasome, (3) decreased renal MCP-1 expression and mononuclear leukocyte infiltration, (4) inhibited ROS production and NLRP3 inflammasome activation in cultured, activated macrophages, and (5) inhibited ROS production and MCP-1 protein levels in cultured, activated mesangial cells. The results suggest that osthole exerts its reno-protective effects on the progression of IgAN by inhibiting ROS production and activation of NF-κB and the NLRP3 inflammasome in the kidney. Our data also confirm that ROS generation and activation of NF-κB and the NLRP3 inflammasome are crucial mechanistic events involved in the progression of the renal disorder. PMID:24204969

Is Liver Enzyme Release Really Associated with Cell Necrosis Induced by Oxidant Stress?

PubMed

Contreras-Zentella, Martha Lucinda; Hernández-Muñoz, Rolando

2016-01-01

Hepatic diseases are a major concern worldwide. Increased specific plasma enzyme activities are considered diagnostic features for liver diseases, since enzymes are released into the blood compartment following the deterioration of the organ. Release of liver mitochondrial enzymes is considered strong evidence for hepatic necrosis, which is associated with an increased production of ROS, often leading to greater hepatic lipid peroxidation. Lipotoxic mediators and intracellular signals activated Kupffer cells, which provides evidence strongly suggesting the participation of oxidant stress in acute liver damage, inducing the progression of liver injury to chronic liver damage. Elevated transaminase activities are considered as an index marker of hepatotoxicity, linked to oxidant stress. However, a drastic increase of serum activities of liver enzyme markers ought not necessarily to reflect liver cell death. In fact, increased serum levels of cytoplasmic enzymes have readily been observed after partial hepatectomy (PH) in the regenerating liver of rats. In this regard, we are now showing that in vitro modifications of the oxidant status affect differentially the release of liver enzymes, indicating that this release is a strictly controlled event and not directly related to the onset of oxidant stress of the liver.

Migration of epoxidised soybean oil from PVC gaskets of commercial lids: simulation of migration under various conditions and screening of food products from Czech markets.

PubMed

Hanušová, Kristýna; Vrbík, Karel; Rajchl, Aleš; Dobiáš, Jaroslav; Sosnovcová, Jitka

2015-01-01

Previous studies have shown that a large number of polyvinylchloride (PVC) lid gaskets exceed the existing migration limits for epoxidised soybean oil (ESBO) and correct prediction of ESBO release into food therefore appears to be a difficult issue. ESBO migration from PVC gaskets of metal closures into food simulants and food products from the Czech market is evaluated during a survey in 2009 and subsequently one in 2012 to assess progress in lid manufacturing and official testing conditions. ESBO migration from lids into various food simulants was studied at various temperatures (25, 40 and 60°C) during storage times up to 12 months. ESBO released into food simulants or food products was transmethylated, derivatised and analysed by GC-MS. The levels of ESBO migration in foodstuffs in 2012 exceeded the specific migration limit (SML) in fewer products in comparison with the previous survey. However, most of the products were analysed at a time far from the expiry date and exceedance of the SML at the end of the product shelf life is not therefore excluded. More severe test conditions (60°C for 10 days) for specific migration given by the current European Union legislation (Regulation (EU) No. 10/2011) still seem to be insufficient for the simulation of ESBO migration during long-term storage.

Report on Progress Toward Security and Stability in Afghanistan and United States Plan for Sustaining the Afghanistan National Security Forces

DTIC Science & Technology

2011-04-01

Ug99 stem rust resistant wheat breeder seed to MAIL, which will be released to farmers for commercial planting in fall 2011. Poppy yields decreased...level continues to improve the Afghan Government’s overall agricultural sector. Wheat is a key staple in Afghanistan, accounting for over one-half of...tight global supply could affect the country’s food security. Afghanistan’s wheat production routinely does not meet demand and is subject to sizable

Attosecond Optics and Technology: Progress to Date and Future Prospects [Invited

DTIC Science & Technology

2016-06-01

1s electron in the hydrogen atom experiences is 5.14 × 109 V∕cm. In such a strong external field, an electron can be freed from an atom via tunneling ...been replaced by laser diodes , which leads to user-friendly products that deliver either single-longitudinal mode beams for pumping laser oscillators...steps. First, an electron is released by tunneling through the potential barrier formed by the atomic Coulomb field and the driving laser field. Then

HMGB1 promotes ductular reaction and tumorigenesis in autophagy-deficient livers.

PubMed

Khambu, Bilon; Huda, Nazmul; Chen, Xiaoyun; Antoine, Daniel J; Li, Yong; Dai, Guoli; Köhler, Ulrike A; Zong, Wei-Xing; Waguri, Satoshi; Werner, Sabine; Oury, Tim D; Dong, Zheng; Yin, Xiao-Ming

2018-06-01

Autophagy is important for liver homeostasis, and the deficiency leads to injury, inflammation, ductular reaction (DR), fibrosis, and tumorigenesis. It is not clear how these events are mechanistically linked to autophagy deficiency. Here, we reveal the role of high-mobility group box 1 (HMGB1) in two of these processes. First, HMGB1 was required for DR, which represents the expansion of hepatic progenitor cells (HPCs) implicated in liver repair and regeneration. DR caused by hepatotoxic diets (3,5-diethoxycarbonyl-1,4-dihydrocollidine [DDC] or choline-deficient, ethionine-supplemented [CDE]) also depended on HMGB1, indicating that HMGB1 may be generally required for DR in various injury scenarios. Second, HMGB1 promoted tumor progression in autophagy-deficient livers. Receptor for advanced glycation end product (RAGE), a receptor for HMGB1, was required in the same two processes and could mediate the proliferative effects of HMBG1 in isolated HPCs. HMGB1 was released from autophagy-deficient hepatocytes independently of cellular injury but depended on NRF2 and the inflammasome, which was activated by NRF2. Pharmacological or genetic activation of NRF2 alone, without disabling autophagy or causing injury, was sufficient to cause inflammasome-dependent HMGB1 release. In conclusion, HMGB1 release is a critical mechanism in hepatic pathogenesis under autophagy-deficient conditions and leads to HPC expansion as well as tumor progression.

Aldehydic load and aldehyde dehydrogenase 2 profile during the progression of post-myocardial infarction cardiomyopathy: benefits of Alda-1

PubMed Central

Gomes, Katia M.S.; Bechara, Luiz R.G.; Lima, Vanessa M.; Ribeiro, Márcio A.C.; Campos, Juliane C.; Dourado, Paulo M.; Kowaltowski, Alicia J.; Mochly-Rosen, Daria; Ferreira, Julio C.B.

2015-01-01

Background/Objectives We previously demonstrated that reducing cardiac aldehydic load by aldehyde dehydrogenase 2 (ALDH2), a mitochondrial enzyme responsible for metabolizing the major lipid peroxidation product, protects against acute ischemia/reperfusion injury and chronic heart failure. However, time-dependent changes in ALDH2 profile, aldehydic load and mitochondrial bioenergetics during progression of post-myocardial infarction (post-MI) cardiomyopathy is unknown and should be established to determine the optimal time window for drug treatment. Methods Here we characterized cardiac ALDH2 activity and expression, lipid peroxidation, 4-hydroxy-2-nonenal (4-HNE) adduct formation, glutathione pool and mitochondrial energy metabolism and H2O2 release during the 4 weeks after permanent left anterior descending (LAD) coronary artery occlusion in rats. Results We observed a sustained disruption of cardiac mitochondrial function during the progression of post-MI cardiomyopathy, characterized by >50% reduced mitochondrial respiratory control ratios and up to 2 fold increase in H2O2 release. Mitochondrial dysfunction was accompanied by accumulation of cardiac and circulating lipid peroxides and 4-HNE protein adducts and down-regulation of electron transport chain complexes I and V. Moreover, increased aldehydic load was associated with a 90% reduction in cardiac ALDH2 activity and increased glutathione pool. Further supporting an ALDH2 mechanism, sustained Alda-1 treatment (starting 24hrs after permanent LAD occlusion surgery) prevented aldehydic overload, mitochondrial dysfunction and improved ventricular function in post-MI cardiomyopathy rats. Conclusion Taken together, our findings demonstrate a disrupted mitochondrial metabolism along with an insufficient cardiac ALDH2-mediated aldehyde clearance during the progression of ventricular dysfunction, suggesting a potential therapeutic value of ALDH2 activators during the progression of post-myocardial infarction cardiomyopathy. PMID:25464432

Industry progress to market a healthful diet to American children and adolescents.

PubMed

Kraak, Vivica I; Story, Mary; Wartella, Ellen A; Ginter, Jaya

2011-09-01

The IOM released an expert committee report in 2005 that assessed the nature, extent, and influence of food and beverage marketing practices on the diets and health of American children and adolescents. The report concluded that prevailing marketing practices did not support a healthful diet and offered recommendations for diverse stakeholders to promote a healthful diet. The investigators evaluated progress made by food, beverage, and restaurant companies; trade associations; entertainment companies; and the media to achieve the IOM report recommendations over 5 years. A literature review was conducted of electronic databases and relevant government, industry, and media websites between December 1, 2005, and January 31, 2011. Evidence selection was guided by the IOM LEAD principles (i.e., locate, evaluate, and assemble evidence to inform decisions) and five qualitative-research criteria, and it was validated by data and investigator triangulation. The investigators selected and categorized 117 data sources into two evidence tables used to evaluate industry progress (i.e., no, limited, moderate, and extensive). Food and beverage companies made moderate progress; however, limited progress was made by other industry subsectors. Industry stakeholders used integrated marketing communications (IMC) to promote primarily unhealthy products, which threaten children's and adolescents' health and miss opportunities to promote a healthy eating environment. Diverse industry stakeholders have several untapped opportunities to advance progress by promoting IMC to support a healthful diet; substantially strengthening self-regulatory programs; supporting truthful and non-misleading product labeling and health claims; engaging in partnerships; and funding independent evaluations of collective efforts. Copyright © 2011 American Journal of Preventive Medicine. Published by Elsevier Inc. All rights reserved.

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.

Environmental Sustainability Analysis and Nutritional Strategies of Animal Production in China.

PubMed

Tan, Bie; Yin, Yulong

2017-02-08

Animal production in China has achieved considerable progress and contributes to 46% of the total agriculture output value of the country. However, this fast expansion of animal production has led to environmental pollution. In this article, we review the status of soil, water, and air pollution associated with animal production in China and analyze the main sources of the pollutants. The government has promulgated regulations and standards, and effective models and technologies have been developed to control pollution during the last 10 years. Because nutrition and feed strategies represent the most effective method of controlling environmental pollution at the source, this review focuses on nutritional technologies, including accurate feed formulation, rational use of additives, and proper processing of feeds. The advances of modern biotechnology and big data systems also provide more modern approaches to decreasing wastage release. These nutritional strategies are expected to promote sustainable development of animal production.

IL-18 associated with lung lymphoid aggregates drives IFNγ production in severe COPD.

PubMed

Briend, Emmanuel; Ferguson, G John; Mori, Michiko; Damera, Gautam; Stephenson, Katherine; Karp, Natasha A; Sethi, Sanjay; Ward, Christine K; Sleeman, Matthew A; Erjefält, Jonas S; Finch, Donna K

2017-08-22

Increased interferon gamma (IFNγ) release occurs in Chronic Obstructive Pulmonary Disease (COPD) lungs. IFNγ supports optimal viral clearance, but if dysregulated could increase lung tissue destruction. The present study investigates which mediators most closely correlate with IFNγ in sputum in stable and exacerbating disease, and seeks to shed light on the spatial requirements for innate production of IFNγ, as reported in mouse lymph nodes, to observe whether such microenvironmental cellular organisation is relevant to IFNγ production in COPD lung. We show tertiary follicle formation in severe disease alters the dominant mechanistic drivers of IFNγ production, because cells producing interleukin-18, a key regulator of IFNγ, are highly associated with such structures. Interleukin-1 family cytokines correlated with IFNγ in COPD sputum. We observed that the primary source of IL-18 in COPD lungs was myeloid cells within lymphoid aggregates and IL-18 was increased in severe disease. IL-18 released from infected epithelium or from activated myeloid cells, was more dominant in driving IFNγ when IL-18-producing and responder cells were in close proximity. Unlike tight regulation to control infection spread in lymphoid organs, this local interface between IL-18-expressing and responder cell is increasingly supported in lung as disease progresses, increasing its potential to increase tissue damage via IFNγ.

A silicone elastomer vaginal ring for HIV prevention containing two microbicides with different mechanisms of action.

PubMed

Fetherston, Susan M; Boyd, Peter; McCoy, Clare F; McBride, Marcella C; Edwards, Karen-Leigh; Ampofo, Stephen; Malcolm, R Karl

2013-02-14

Vaginal rings are currently being developed for the long-term (at least 30 days) continuous delivery of microbicides against human immunodeficiency virus (HIV). Research to date has mostly focused on devices containing a single antiretroviral compound, exemplified by the 25mg dapivirine ring currently being evaluated in a Phase III clinical study. However, there is a strong clinical rationale for combining antiretrovirals with different mechanisms of action in a bid to increase breadth of protection and limit the emergence of resistant strains. Here we report the development of a combination antiretroviral silicone elastomer matrix-type vaginal ring for simultaneous controlled release of dapivirine, a non-nucleoside reverse transcriptase inhibitor, and maraviroc, a CCR5-targeted HIV-1 entry inhibitor. Vaginal rings loaded with 25mg dapivirine and various quantities of maraviroc (50-400mg) were manufactured and in vitro release assessed. The 25mg dapivirine and 100mg maraviroc formulation was selected for further study. A 24-month pharmaceutical stability evaluation was conducted, indicating good product stability in terms of in vitro release, content assay, mechanical properties and related substances. This combination ring product has now progressed to Phase I clinical testing. Copyright © 2012 Elsevier B.V. All rights reserved.

Changes in peat chemistry associated with permafrost thaw increase greenhouse gas production

PubMed Central

Hodgkins, Suzanne B.; Tfaily, Malak M.; McCalley, Carmody K.; Logan, Tyler A.; Crill, Patrick M.; Saleska, Scott R.; Rich, Virginia I.; Chanton, Jeffrey P.

2014-01-01

Carbon release due to permafrost thaw represents a potentially major positive climate change feedback. The magnitude of carbon loss and the proportion lost as methane (CH4) vs. carbon dioxide (CO2) depend on factors including temperature, mobilization of previously frozen carbon, hydrology, and changes in organic matter chemistry associated with environmental responses to thaw. While the first three of these effects are relatively well understood, the effect of organic matter chemistry remains largely unstudied. To address this gap, we examined the biogeochemistry of peat and dissolved organic matter (DOM) along a ∼40-y permafrost thaw progression from recently- to fully thawed sites in Stordalen Mire (68.35°N, 19.05°E), a thawing peat plateau in northern Sweden. Thaw-induced subsidence and the resulting inundation along this progression led to succession in vegetation types accompanied by an evolution in organic matter chemistry. Peat C/N ratios decreased whereas humification rates increased, and DOM shifted toward lower molecular weight compounds with lower aromaticity, lower organic oxygen content, and more abundant microbially produced compounds. Corresponding changes in decomposition along this gradient included increasing CH4 and CO2 production potentials, higher relative CH4/CO2 ratios, and a shift in CH4 production pathway from CO2 reduction to acetate cleavage. These results imply that subsidence and thermokarst-associated increases in organic matter lability cause shifts in biogeochemical processes toward faster decomposition with an increasing proportion of carbon released as CH4. This impact of permafrost thaw on organic matter chemistry could intensify the predicted climate feedbacks of increasing temperatures, permafrost carbon mobilization, and hydrologic changes. PMID:24711402

Releasing Effect of Individual Potential: Formation of Productive Collective and Children's Self-Transcendence in a Chinese School.

PubMed

Wu, Aruna; Li, Xiao-Wen; Zhang, Qian

2017-09-01

We describe the intricate relations between social demand structures and their role in facilitation of individual development of children and teachers in a Chinese classroom. The relationship of an individual to the immediate social group is further qualified by the inclusion in a collective which enables the participants to transform their individual self-structures through taking on social roles in everyday collective activities, which release further potential for their individual development. We describe that releasing effect in the case of an intervention program in a Chinese school for the children of rural migrants re-settled in a city, demonstrating gradually how the inter-individual competitive orientation promoted by autocratic teaching style becomes transformed into collective good oriented joint actions towards excellence in educational endeavors (Jiti). The productive nature of the Jiti makes an ecology with multiple nested and open systems, in which every group and student is producer and consumer of each other, and personal self-transcendence is actualized in the process. The releasing effect is demonstrated through observing the co-emergence of new forms of progressive conduct and new problems, presented in pupils' positive participation in activities. The description of the intervention in a Chinese school provides us with insight on how concrete social inclusion frameworks with the underpinning Chinese philosophy of "acting up to trends" can prevent the emergence of direct animosities and lead to new integration of self and society.

Crosstalk between the heart and peripheral organs in heart failure

PubMed Central

Jahng, James Won Suk; Song, Erfei; Sweeney, Gary

2016-01-01

Mediators from peripheral tissues can influence the development and progression of heart failure (HF). For example, in obesity, an altered profile of adipokines secreted from adipose tissue increases the incidence of myocardial infarction (MI). Less appreciated is that heart remodeling releases cardiokines, which can strongly impact various peripheral tissues. Inflammation, and, in particular, activation of the nucleotide-binding oligomerization domain-like receptors with pyrin domain (NLRP3) inflammasome are likely to have a central role in cardiac remodeling and mediating crosstalk with other organs. Activation of the NLRP3 inflammasome in response to cardiac injury induces the production and secretion of the inflammatory cytokines interleukin (IL)-1β and IL-18. In addition to having local effects in the myocardium, these pro-inflammatory cytokines are released into circulation and cause remodeling in the spleen, kidney, skeletal muscle and adipose tissue. The collective effects of various cardiokines on peripheral organs depend on the degree and duration of myocardial injury, with systematic inflammation and peripheral tissue damage observed as HF progresses. In this article, we review mechanisms regulating myocardial inflammation in HF and the role of factors secreted by the heart in communication with peripheral tissues. PMID:26964833

The low molecular weight fraction of human serum albumin upregulates production of 15d-PGJ2 in Peripheral Blood Mononuclear Cells.

PubMed

Thomas, Gregory W; Rael, Leonard T; Hausburg, Melissa; Frederick, Elizabeth D; Mains, Charles W; Slone, Denetta; Carrick, Matthew M; Bar-Or, David

2016-05-13

Activation of the innate immune system involves a series of events designed to counteract the initial insult followed by the clearance of debris and promotion of healing. Aberrant regulation can lead to systemic inflammatory response syndrome, multiple organ failure, and chronic inflammation. A better understanding of the innate immune response may help manage complications while allowing for proper immune progression. In this study, the ability of several classes of anti-inflammatory drugs to affect LPS-induced cytokine and prostaglandin release from peripheral blood mononuclear cells (PBMC) was evaluated. PBMC were cultured in the presence of dexamethasone (DEX), ibuprofen (IBU), and the low molecular weight fraction of 5% albumin (LMWF5A) followed by stimulation with LPS. After 24 h, TNFα, PGE2, and 15d-PGJ2 release was determined by ELISA. Distinct immunomodulation patterns emerged following LPS stimulation of PBMC in the presence of said compounds. DEX, a steroid with strong immunosuppressive properties, reduced TNFα, PGE2, and 15d-PGJ2 release. IBU caused significant reduction in prostaglandin release while TNFα release was unchanged. An emerging biologic with known anti-inflammatory properties, LMWF5A, significantly reduced TNFα release while enhancing PGE2 and 15d-PGJ2 release. Incubating LMWF5A together with IBU negated this observed increased prostaglandin release without affecting the suppression of TNFα release. Additionally, LMWF5A caused an increase in COX-2 transcription and translation. LMWF5A exhibited a unique immune modulation pattern in PBMC, disparate from steroid or NSAID administration. This enhancement of prostaglandin release (specifically 15d-PGJ2), in conjunction with a decrease in TNFα release, suggests a switch that favors resolution and decreased inflammation. Copyright © 2016 Elsevier Inc. All rights reserved.

The HST Frontier Fields: High-Level Science Data Products for the First 4 Completed Clusters, and for the Last 2 Clusters Currently in Progress

NASA Astrophysics Data System (ADS)

Koekemoer, Anton M.; Mack, Jennifer; Lotz, Jennifer M.; Anderson, Jay; Avila, Roberto J.; Barker, Elizabeth A.; Borncamp, David; Gunning, Heather C.; Hilbert, Bryan; Khandrika, Harish G.; Lucas, Ray A.; Ogaz, Sara; Porterfield, Blair; Sunnquist, Ben; Grogin, Norman A.; Robberto, Massimo; Sembach, Kenneth; Flanagan, Kathryn; Mountain, Matt; HST Frontier Fields Team

2016-06-01

The Hubble Space Telescope Frontier Fields program (PI: J. Lotz) is a large Director's Discretionary program of 840 orbits, to obtain ultra-deep observations of six strong lensing clusters of galaxies, together with parallel deep blank fields, making use of the strong lensing amplification by these clusters of distant background galaxies to detect the faintest galaxies currently observable in the high-redshift universe. The first four of these clusters are now complete, namely Abell 2744, MACS J0416.1-2403, MACS J0717.5+3745 and MACS J1149.5+2223, with each of these having been observed over two epochs, to a total depth of 140 orbits on the main cluster and an associated parallel field, using ACS (F435W, F606W, F814W) and WFC3/IR (F105W, F125W, F140W, F160W). The remaining two clusters, Abell 370 and Abell S1063, are currently in progress, with the first epoch for each having been completed. Full sets of high-level science products have been generated for all these clusters by the team at STScI, including cumulative-depth v0.5 data releases during each epoch, as well as full-depth version 1.0 releases after the completion of each epoch. These products include all the full-depth distortion-corrected mosaics and associated products for each cluster, which are science-ready to facilitate the construction of lensing models as well as enabling a wide range of other science projects. Many improvements beyond default calibration for ACS and WFC3/IR are implemented in these data products, including corrections for persistence, time-variable sky, and low-level dark current residuals, as well as improvements in astrometric alignment to achieve milliarcsecond-level accuracy. The full set of resulting high-level science products are publicly delivered to the community via the Mikulski Archive for Space Telescopes (MAST) to enable the widest scientific use of these data, as well as ensuring a public legacy dataset of the highest possible quality that is of lasting value to the entire community.

Quantification of Energy Release in Composite Structures

NASA Technical Reports Server (NTRS)

Minnetyan, Levon

2003-01-01

Energy release rate is usually suggested as a quantifier for assessing structural damage tolerance. Computational prediction of energy release rate is based on composite mechanics with micro-stress level damage assessment, finite element structural analysis and damage progression tracking modules. This report examines several issues associated with energy release rates in composite structures as follows: Chapter I demonstrates computational simulation of an adhesively bonded composite joint and validates the computed energy release rates by comparison with acoustic emission signals in the overall sense. Chapter II investigates the effect of crack plane orientation with respect to fiber direction on the energy release rates. Chapter III quantifies the effects of contiguous constraint plies on the residual stiffness of a 90 ply subjected to transverse tensile fractures. Chapter IV compares ICAN and ICAN/JAVA solutions of composites. Chapter V examines the effects of composite structural geometry and boundary conditions on damage progression characteristics.

Quantification of Energy Release in Composite Structures

NASA Technical Reports Server (NTRS)

Minnetyan, Levon; Chamis, Christos C. (Technical Monitor)

2003-01-01

Energy release rate is usually suggested as a quantifier for assessing structural damage tolerance. Computational prediction of energy release rate is based on composite mechanics with micro-stress level damage assessment, finite element structural analysis and damage progression tracking modules. This report examines several issues associated with energy release rates in composite structures as follows: Chapter I demonstrates computational simulation of an adhesively bonded composite joint and validates the computed energy release rates by comparison with acoustic emission signals in the overall sense. Chapter II investigates the effect of crack plane orientation with respect to fiber direction on the energy release rates. Chapter III quantifies the effects of contiguous constraint plies on the residual stiffness of a 90 deg ply subjected to transverse tensile fractures. Chapter IV compares ICAN and ICAN/JAVA solutions of composites. Chapter V examines the effects of composite structural geometry and boundary conditions on damage progression characteristics.

Silk-elastin-like protein biomaterials for the controlled delivery of therapeutics.

PubMed

Huang, Wenwen; Rollett, Alexandra; Kaplan, David L

2015-05-01

Genetically engineered biomaterials are useful for controlled delivery owing to their rational design, tunable structure-function, biocompatibility, degradability and target specificity. Silk-elastin-like proteins (SELPs), a family of genetically engineered recombinant protein polymers, possess these properties. Additionally, given the benefits of combining semi-crystalline silk-blocks and elastomeric elastin-blocks, SELPs possess multi-stimuli-responsive properties and tunability, thereby becoming promising candidates for targeted cancer therapeutics delivery and controlled gene release. An overview of SELP biomaterials for drug delivery and gene release is provided. Biosynthetic strategies used for SELP production, fundamental physicochemical properties and self-assembly mechanisms are discussed. The review focuses on sequence-structure-function relationships, stimuli-responsive features and current and potential drug delivery applications. The tunable material properties allow SELPs to be pursued as promising biomaterials for nanocarriers and injectable drug release systems. Current applications of SELPs have focused on thermally-triggered biomaterial formats for the delivery of therapeutics, based on local hyperthermia in tumors or infections. Other prominent controlled release applications of SELPs as injectable hydrogels for gene release have also been pursued. Further biomedical applications that utilize other stimuli to trigger the reversible material responses of SELPs for targeted delivery, including pH, ionic strength, redox, enzymatic stimuli and electric field, are in progress. Exploiting these additional stimuli-responsive features will provide a broader range of functional biomaterials for controlled therapeutics release and tissue regeneration.

[Induction and regulation of cellulase expression in filamentous fungi: a review].

PubMed

Zhang, Fei; Bai, Fengwu; Zhao, Xinqing

2016-11-25

Production of bioenergy and bio-based chemicals by using fermentable sugars released from low-cost renewable lignocellulosic biomass has received great attention. Efficient cellulolytic enzymes are crucial for lignocellulose bioconversion, but high cellulase production cost is limiting the bioconversion efficiency of cellulosic biomass and industrial applications of lignocellulose biorefinery. Studies on induction and regulation of cellulase in filamentous fungi will help to further develop superior fungal strains for efficient cellulase production and reduce cellulase production cost. With the advances in high-throughput sequencing and gene manipulation technology using fungal strains, an in-depth understanding of cellulase induction and regulation mechanisms of enzyme expression has been achieved. We reviewed recent progresses in the induction and regulation of cellulase expression in several model filamentous fungi, emphasizing sugar transporters, transcription factors and chromatin remodeling. Future prospects in application of artificial zinc finger proteins for cellulase induction and regulation in filamentous fungi were discussed.

Detecting cell lysis using viscosity monitoring in E. coli fermentation to prevent product loss

PubMed Central

Newton, Joseph M.; Schofield, Desmond; Vlahopoulou, Joanna

2016-01-01

Monitoring the physical or chemical properties of cell broths to infer cell status is often challenging due to the complex nature of the broth. Key factors indicative of cell status include cell density, cell viability, product leakage, and DNA release to the fermentation broth. The rapid and accurate prediction of cell status for hosts with intracellular protein products can minimise product loss due to leakage at the onset of cell lysis in fermentation. This article reports the rheological examination of an industrially relevant E. coli fermentation producing antibody fragments (Fab'). Viscosity monitoring showed an increase in viscosity during the exponential phase in relation to the cell density increase, a relatively flat profile in the stationary phase, followed by a rapid increase which correlated well with product loss, DNA release and loss of cell viability. This phenomenon was observed over several fermentations that a 25% increase in broth viscosity (using induction‐point viscosity as a reference) indicated 10% product loss. Our results suggest that viscosity can accurately detect cell lysis and product leakage in postinduction cell cultures, and can identify cell lysis earlier than several other common fermentation monitoring techniques. This work demonstrates the utility of rapidly monitoring the physical properties of fermentation broths, and that viscosity monitoring has the potential to be a tool for process development to determine the optimal harvest time and minimise product loss. © 2016 The Authors. Biotechnology Progress published by Wiley Periodicals, Inc. on behalf of American Institute of Chemical Engineers, 32:1069–1076, 2016 PMID:27111912

Purification and cultivation of human pituitary growth hormone secreting cells

NASA Technical Reports Server (NTRS)

Hymer, W. C.

1979-01-01

Efforts were directed towards maintenance of actively secreting human pituitary growth hormone cells (somatotrophs) in vitro. The production of human growth hormone (hGH) by this means would be of benefit for the treatment of certain human hypopituitary diseases such as dwarfism. One of the primary approaches was the testing of agents which may logically be expected to increase hGH release. The progress towards this goal is summarized. Results from preliminary experiments dealing with electrophoresis of pituitary cell for the purpose of somatotroph separation are described.

Feasibility study of an Integrated Program for Aerospace-vehicle Design (IPAD) system. Volume 6: Implementation schedule, development costs, operational costs, benefit assessment, impact on company organization, spin-off assessment, phase 1, tasks 3 to 8

NASA Technical Reports Server (NTRS)

Garrocq, C. A.; Hurley, M. J.; Dublin, M.

1973-01-01

A baseline implementation plan, including alternative implementation approaches for critical software elements and variants to the plan, was developed. The basic philosophy was aimed at: (1) a progressive release of capability for three major computing systems, (2) an end product that was a working tool, (3) giving participation to industry, government agencies, and universities, and (4) emphasizing the development of critical elements of the IPAD framework software. The results of these tasks indicate an IPAD first release capability 45 months after go-ahead, a five year total implementation schedule, and a total developmental cost of 2027 man-months and 1074 computer hours. Several areas of operational cost increases were identified mainly due to the impact of additional equipment needed and additional computer overhead. The benefits of an IPAD system were related mainly to potential savings in engineering man-hours, reduction of design-cycle calendar time, and indirect upgrading of product quality and performance.

3D-Printing: an emerging and a revolutionary technology in pharmaceuticals.

PubMed

Singhvi, Gautam; Patil, Shalini; Girdhar, Vishal; Chellappan, Dinesh K; Gupta, Gaurav; Dua, Kamal

2018-06-01

One of the novel and progressive technology employed in pharmaceutical manufacturing, design of medical device and tissue engineering is threedimensional (3D) printing. 3D printing technologies provide great advantages in 3D scaffolds fabrication over traditional methods in the control of pore size, porosity, and interconnectivity. Various techniques of 3Dprinting include powder bed fusion, fused deposition modeling, binder deposition, inkjet printing, photopolymerization and many others which are still evolving. 3Dprinting technique been employed in developing immediate release products, various systems to deliver multiple release modalities etc. 3D printing has opened the door for new generation of customized drug delivery with builtin flexibility for safer and effective therapy. Our minireview provides a quick snapshot on an overview of 3D printing, various techniques employed, applications and its advancements in pharmaceutical sciences.

Smart Coating for Corrosion Indication and Prevention: Recent Progress

NASA Technical Reports Server (NTRS)

Li, Wenyan; Hintze, Paul; Calle, Luz M.; Buhrow, Jerry; Curran, Jerry; Muehlberg, A. J.; Gelling, V. J.; Webster, D. C.; Croll, S. G.; Contu, F.;

Research Finds Link Between Statin Use and Progressive Muscle Disease

MedlinePlus

... Syndrome Press Release | October 29, 2015 NIAMS launches new Spanish-language website Press Release | September 10, 2015 In uveitis, bacteria in gut may instruct immune cells to attack the eye Press Release | August 18, 2015 High-resolution 3D ...

One-step fabrication of multifunctional micromotors

NASA Astrophysics Data System (ADS)

Gao, Wenlong; Liu, Mei; Liu, Limei; Zhang, Hui; Dong, Bin; Li, Christopher Y.

2015-08-01

Although artificial micromotors have undergone tremendous progress in recent years, their fabrication normally requires complex steps or expensive equipment. In this paper, we report a facile one-step method based on an emulsion solvent evaporation process to fabricate multifunctional micromotors. By simultaneously incorporating various components into an oil-in-water droplet, upon emulsification and solidification, a sphere-shaped, asymmetric, and multifunctional micromotor is formed. Some of the attractive functions of this model micromotor include autonomous movement in high ionic strength solution, remote control, enzymatic disassembly and sustained release. This one-step, versatile fabrication method can be easily scaled up and therefore may have great potential in mass production of multifunctional micromotors for a wide range of practical applications.Although artificial micromotors have undergone tremendous progress in recent years, their fabrication normally requires complex steps or expensive equipment. In this paper, we report a facile one-step method based on an emulsion solvent evaporation process to fabricate multifunctional micromotors. By simultaneously incorporating various components into an oil-in-water droplet, upon emulsification and solidification, a sphere-shaped, asymmetric, and multifunctional micromotor is formed. Some of the attractive functions of this model micromotor include autonomous movement in high ionic strength solution, remote control, enzymatic disassembly and sustained release. This one-step, versatile fabrication method can be easily scaled up and therefore may have great potential in mass production of multifunctional micromotors for a wide range of practical applications. Electronic supplementary information (ESI) available: Videos S1-S4 and Fig. S1-S3. See DOI: 10.1039/c5nr03574k

Total RNA Sequencing Analysis of DCIS Progressing to Invasive Breast Cancer

DTIC Science & Technology

2017-09-01

Public Release; Distribution Unlimited The views , opinions and/or findings contained in this report are those of the author(s) and should not be...STATEMENT Approved for Public Release; Distribution Unlimited 13. SUPPLEMENTARY NOTES 14. ABSTRACT: This project is designed to complement a multi ...fact progress to invasive disease (IBC), and complements our multi -institutional, NIH-funded study of genetic and epigenetic alterations of pre

Key issues in life cycle assessment of ethanol production from lignocellulosic biomass: Challenges and perspectives.

PubMed

Singh, Anoop; Pant, Deepak; Korres, Nicholas E; Nizami, Abdul-Sattar; Prasad, Shiv; Murphy, Jerry D

2010-07-01

Progressive depletion of conventional fossil fuels with increasing energy consumption and greenhouse gas (GHG) emissions have led to a move towards renewable and sustainable energy sources. Lignocellulosic biomass is available in massive quantities and provides enormous potential for bioethanol production. However, to ascertain optimal biofuel strategies, it is necessary to take into account environmental impacts from cradle to grave. Life cycle assessment (LCA) techniques allow detailed analysis of material and energy fluxes on regional and global scales. This includes indirect inputs to the production process and associated wastes and emissions, and the downstream fate of products in the future. At the same time if not used properly, LCA can lead to incorrect and inappropriate actions on the part of industry and/or policy makers. This paper aims to list key issues for quantifying the use of resources and releases to the environment associated with the entire life cycle of lignocellulosic bioethanol production. Copyright 2009 Elsevier Ltd. All rights reserved.

Syngas formation in methane flames and carbon monoxide release during quenching

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

Weinberg, Felix; Carleton, Fred; Houdmont, Raphael

Following a recent investigation into chemi-ionization and chemiluminescence during gradual aeration of small, laminar methane flames, we proposed that partial oxidation products, or syngas constituents, formed in the pre-flame zone well below the luminous region, were responsible for the observed effects. We therefore map temperature, CO, and H{sub 2} for geometries and conditions relevant to burners in domestic boiler systems, to assess the potential hazard of CO release into the ambient atmosphere, should any partial quenching occur. CO concentrations peaks of 5.5 volume % are recorded in the core surrounding the axis. Appreciable CO concentrations are also found in themore » absence of added air. Experiments on various burner port geometries and temperatures suggest that this is not due to air entrainment at the flame base but to diffusion from zones closer to the flame. Next, quenching surfaces such as grids, perforated plates and flame trap matrices of different metals are progressively lowered into the flame. To avoid flow line distortion, suction aspirates the quenched products. The highest emission rate occurs with the quenching plane some 4 mm above the burner; further lowering of the quenching surface causes flame extinction. The maximum CO release is close to converting 10% of the CH{sub 4} feed, with some variation with quenching material. Expressing this potential release in terms of, e.g. boiler power, predicts a potentially serious hazard. Results of numerical simulations adequately parallel the experimental sampling profiles and provide insights into local concentrations, as well as the spatially resolved CO flux, which is calculated for a parabolic inlet flow profile. Integration across the stream implies, on the basis of the simulation, a possible tripling of the experimental CO release, were quenching simply to release the local gas composition into the atmosphere. Comparison with experiment suggests some chemical interaction with the quenching surface. (author)« less

Reintroduction of Lake Sturgeon (Acipenser fulvescens) into the St. Regis River, NY: Post-release assessment of habitat use and growth

USGS Publications Warehouse

Dittman, Dawn E.; Chalupnicki, Marc A.; Johnson, James H.; Snyder, James

2015-01-01

One of the depleted endemic fish species of the Great Lakes, Acipenser fulvescens (Lake Sturgeon), has been the target of extensive conservation efforts. One strategy is reintroduction into historically productive waters. The St. Regis River, NY, represents one such adaptive-management effort, with shared management between New York and the St. Regis Mohawk Tribe. Between 1998 and 2004, a total of 4977 young-of-year Lake Sturgeon were released. Adaptive management requires intermediate progress metrics. During 2004 and 2005, we measured growth, habitat use, and survivorship metrics of the released fish. We captured a total of 95 individuals of all stocked ages. Year-class minimal-survival rates ranged from 0.19–2.1%. The size-at-age and length/biomass relationships were comparable to those reported for juveniles in other Great Lakes waters. These intermediate assessment metrics can provide feedback to resource managers who make restoration-program decisions on a much shorter time-scale than the time-frame in which the ultimate goal of a self-sustaining population can be attained.

Oxalate, inflammasome, and progression of kidney disease

PubMed Central

Ermer, Theresa; Eckardt, Kai-Uwe; Aronson, Peter S.; Knauf, Felix

2016-01-01

Purpose of review Oxalate is an end product of metabolism excreted via the kidney. Excess urinary oxalate, whether from primary or enteric hyperoxaluria, can lead to oxalate deposition in the kidney. Oxalate crystals are associated with renal inflammation, fibrosis and progressive renal failure. It has long been known that as glomerular filtration rate (GFR) becomes reduced in chronic kidney disease (CKD), there is striking elevation of plasma oxalate. Taken together, these findings raise the possibility that elevation of plasma oxalate in CKD may promote renal inflammation and more rapid progression of CKD independent of primary etiology. Recent findings The inflammasome has recently been identified to play a critical role in oxalate-induced renal inflammation. Oxalate crystals have been shown to activate the nucleotide-binding domain, leucine-rich repeat inflammasome 3 (also known as NALP3, NLRP3 or cryopyrin), resulting in release of Interleukin-1β and macrophage infiltration. Deletion of inflammasome proteins in mice protects from oxalate-induced renal inflammation and progressive renal failure. Summary The findings reviewed in this article expand our understanding of the relevance of elevated plasma oxalate levels leading to inflammasome activation. We propose that inhibiting oxalate-induced inflammasome activation, or lowering plasma oxalate, may prevent or mitigate progressive renal damage in CKD, and warrants clinical trials. PMID:27191349

Nonesterified fatty acid accumulation and release during heart muscle-cell (myocyte) injury: modulation by extracellular "acceptor".

PubMed

Janero, D R; Burghardt, C

1989-07-01

Long-chain nonesterified fatty acid (NEFA) accumulation in the heart muscle cell (myocyte) and NEFA release to the extracellular milieu are considered contributors to the pathogenesis of myocardial injury in a number of cardiovascular disease states. Reported here is a study of the factors which influence and control the interactions among NEFA formation, intracellular NEFA accumulation, and NEFA release to the extracellular compartment by the irreversibly injured myocyte. Under conditions of metabolic inhibition, neonatal rat myocytes in primary monolayer culture became virtually depleted of ATP within 8 h. The metabolically inhibited myocytes evidenced membrane phospholipid degradation and a resultant net accumulation of NEFA produced thereby in the extracellular medium. However, under conditions of nutrient deprivation, the injured myocytes retained the NEFA produced from phospholipid catabolism intracellularly and did not release it to the culture medium, although the extent of myocyte ATP depletion was the same as it had been from metabolic inhibition. Serum could elicit, in a concentration-dependent fashion, the quantitative release of NEFA from metabolically inhibited myocytes to the culture medium but did not influence the net production of NEFA by the injured cells. Similarly, NEFA release from nutrient-deprived myocytes incubated in serum-free, substrate-free medium or in physiological buffer could be induced by supplementing the medium or buffer with bovine serum albumin (BSA), and the extent of NEFA release, but not NEFA formation, was dependent upon the extracellular BSA concentration. No manipulations to media other than changing their serum content or supplementing them with BSA were found to influence the disposition of NEFA produced during phospholipid catabolism in the irreversibly injured, ATP-depleted myocyte. Therefore, although progressive metabolic compromise in the myocyte was correlated with increasing, net NEFA formation, the distribution of the NEFA between the intracellular and the extracellular compartments was not determined by the magnitude of ATP loss or by the nature or duration of at least two injury stimuli, metabolic inhibition and nutrient deprivation. Rather, the net release of NEFA from the ATP-depleted myocyte to the culture medium and the consequent reduction of intracellular myocyte NEFA overload were critically and causally dependent upon the presence and concentration of extracellular NEFA "acceptor". The influence of acceptor on the mobilization of NEFA from the injured myocyte has implications regarding the use of NEFA release as an index of myocyte pathology and could serve to modify the progression and extent of myocardial injury in vivo.

Inhibitory effect of double atmospheric pressure argon cold plasma on spores and mycotoxin production of Aspergillus niger contaminating date palm fruits.

PubMed

Ouf, Salama A; Basher, Abdulrahman H; Mohamed, Abdel-Aleam H

2015-12-01

Aspergillus niger has been reported as a potentially dangerous pathogen of date-palm fruits in Saudi Arabia due to the production of fumonisin B2 (FB2 ) and ochratoxin A (OTA). In a trial to disinfect this product, a double atmospheric pressure argon cold plasma (DAPACP) jet system was set up and evaluated against spore germination and mycotoxin production of the pathogen. The plasma jets were characterised photographically, electrically and spectroscopically. DAPACP jet length increases with the increase of argon flow rate, with optimum rate at 3.5 L min(-1) . The viability of A. niger spores, inoculated onto sterilised date palm fruit discs, progressively decreases with extension of the exposure time of DAPACP due to the more quantitative amount of OH and O radicals interacting with the examined samples. There was a progressive reduction of the amount of FB2 and OTA detected in date palm discs on extension of the exposure time of the plasma-treated inoculums at flow rate of 3.5 L min(-1) . FB2 was not detected in the discs inoculated with 6-min plasma-treated A. niger, while OTA was completely absent when the fungus was treated for 7.5 min. DAPACP showed promising results in dry fruit decontamination and in inhibition of mycotoxin release by A. niger contaminating the fruits. The progress in the commercial application of cold plasma needs further investigation concerning the ideal width of the plasma output to enable it to cover wider surfaces of the sample and consequently inducing greater plasma performance. © 2014 Society of Chemical Industry.

Protective Role of BST2 Polymorphisms in Mother-to-Child Transmission of HIV-1 and Adult AIDS Progression.

PubMed

Kamada, Anselmo J; Bianco, Anna M; Zupin, Luisa; Girardelli, Martina; Matte, Maria C C; Medeiros, Rúbia Marília de; Almeida, Sabrina Esteves de Matos; Rocha, Marineide M; Segat, Ludovica; Chies, José A B; Kuhn, Louise; Crovella, Sergio

2016-07-01

Bone marrow stromal cell antigen-2 (BST-2)/Tetherin is a restriction factor that prevents Human immunodeficiency virus type 1 (HIV-1) release from infected cells and mediates pro-inflammatory cytokine production. This study investigated the risk conferred by single nucleotide polymorphisms (rs919266, rs9192677, and rs9576) at BST-2 coding gene (BST2) in HIV-1 mother-to-child transmission and in disease progression. Initially, 101 HIV-1+ pregnant women and 331 neonates exposed to HIV-1 from Zambia were enrolled. Additional BST2 single nucleotide polymorphism analyses were performed in 2 cohorts with acquired immunodeficiency syndrome (AIDS) progression: an adult Brazilian cohort (37 rapid, 30 chronic and 21 long-term non-progressors) and an Italian pediatric cohort (21 rapid and 67 slow progressors). The rs9576A allele was nominally associated with protection during breastfeeding (P = 0.019) and individuals carrying rs919266 GA showed slower progression to AIDS (P = 0.033). Despite the influence of rs919266 and rs9576 on BST2 expression being still undetermined, a preventive role by BST2 polymorphisms was found during HIV-1 infection.

Environmental release of living modified organisms: current approaches and case studies.

PubMed

Thomas, E; Nickson, Ph D

2005-01-01

Agricultural biotechnology is being rapidly adopted as evidenced by the acreage of genetically modified (GM) crops planted and tonnes of product (grain and fiber) harvested. Concurrent with this technological progress, is a growing concern that the worlds biological diversity is coming under increasing threat from human activities. As such, ecological risk assessment approaches are being developed for GM crop plants as international agreements regulating the transboundary movements of these products are being implemented. This paper reviews the ecological risk assessment approach that has been used to date to approve GM crops to date. The process has been case-by-case, using a comparative, science-based approach balancing the potential risks and benefits of the new technology versus those present with the currently accepted practices. The approach used to evaluate and approve these products is consistent with the conditions and requirements outlined in the Cartagena Protocol.

Antioxidants Modulate the Antiproliferative Effects of Nitric Oxide on Vascular Smooth Muscle Cells and Adventitial Fibroblasts by Regulating Oxidative Stress

PubMed Central

Gregory, Elaine K.; Vavra, Ashley K.; Moreira, Edward S.; Havelka, George E.; Jiang, Qun; Lee, Vanessa R.; Van Lith, Robert; Ameer, Guillermo A.; Kibbe, Melina R.

2011-01-01

Background S-nitrosothiols (SNO) release nitric oxide (NO) through interaction with ascorbic acid (AA). However, little is known about their combined effect in the vasculature. The aim of this study is to investigate the effect of AA on SNO-mediated NO release, proliferation, cell cycle progression, cell death and oxidative stress in vascular cells. Methods VSMC and adventitial fibroblasts (AF) harvested from the aortae of Sprague Dawley rats were treated with AA, ± S-nitrosoglutathione (GSNO), or ± diethylenetriamine NONOate (DETA/NO). NO release, proliferation, cell cycle progression, cell death, and oxidative stress were determined by the Greiss reaction, [3H]-thymidine incorporation, flow cytometry, trypan blue exclusion, and DCF staining, respectively. Results AA increased NO release from GSNO 3-fold (p<0.001). GSNO and DETA/NO significantly decreased proliferation, but AA abrogated this effect (p<0.05). Mirroring the proliferation data, changes in cell cycle progression induced by GSNO and DETA/NO were reversed by addition of AA. GSNO- and DETA/NO-mediated increases in oxidative stress were significantly decreased by addition of AA (p<0.001). Conclusion Despite causing increased NO release from GSNO, AA reduced the antiproliferative and cell cycle effects of GSNO and DETA/NO through modulation of oxidative stress. PMID:21944289

Investigation of Molecular Mechanism of JC virus Viroporin Activity.

PubMed

Suzuki, Tadaki

2015-01-01

Viroporins are small and hydrophobic viral proteins that form pores on host cell membranes, and their expression can increase the permeability of cellular membranes and the production of progeny virus particles. JC virus (JCV) is the causative agent of progressive multifocal leukoenchephalopathy (PML). We demonstrate that JCV Agno, which is the small and hydrophobic protein, andincreases the plasma membrane permeability and virion release, acts as a viroporin. We also demonstrate that an interaction of Agno with a host cellular protein regulates the viroporin activity of Agno. These findings indicate a new paradigm in virus-host interactions regulating viroporin activity and viral replication.

OrganoRelease - A framework for modeling the release of organic chemicals from the use and post-use of consumer products.

PubMed

Tao, Mengya; Li, Dingsheng; Song, Runsheng; Suh, Sangwon; Keller, Arturo A

2018-03-01

Chemicals in consumer products have become the focus of recent regulatory developments including California's Safer Consumer Products Act. However, quantifying the amount of chemicals released during the use and post-use phases of consumer products is challenging, limiting the ability to understand their impacts. Here we present a comprehensive framework, OrganoRelease, for estimating the release of organic chemicals from the use and post-use of consumer products given limited information. First, a novel Chemical Functional Use Classifier estimates functional uses based on chemical structure. Second, the quantity of chemicals entering different product streams is estimated based on market share data of the chemical functional uses. Third, chemical releases are estimated based on either chemical product categories or functional uses by using the Specific Environmental Release Categories and EU Technological Guidance Documents. OrganoRelease connects 19 unique functional uses and 14 product categories across 4 data sources and provides multiple pathways for chemical release estimation. Available user information can be incorporated in the framework at various stages. The Chemical Functional Use Classifier achieved an average accuracy above 84% for nine functional uses, which enables the OrganoRelease to provide release estimates for the chemical, mostly using only the molecular structure. The results can be can be used as input for methods estimating environmental fate and exposure. Copyright © 2017 Elsevier Ltd. All rights reserved.

Oenothera paradoxa defatted seeds extract and its bioactive component penta-O-galloyl-β-D-glucose decreased production of reactive oxygen species and inhibited release of leukotriene B4, interleukin-8, elastase, and myeloperoxidase in human neutrophils.

PubMed

Kiss, Anna K; Filipek, Agnieszka; Czerwińska, Monika; Naruszewicz, Marek

2010-09-22

In this study, we analyzed ex vivo the effect of an aqueous extract of Oenothera paradoxa defatted seeds on the formation of neutrophil-derived oxidants. For defining active compounds, we also tested lypophilic extract constituents such as gallic acid, (+)-catechin, ellagic acid, and penta-O-galloyl-β-D-glucose and a hydrophilic fraction containing polymeric procyanidins. The anti-inflammatory potential of the extract and compounds was tested by determining the release from activated neutrophils of elastase, myeloperoxidase, interleukin-8 (IL-8), and leukotriene B4 (LTB4), which are considered relevant for the pathogenesis of cardiovascular diseases. The extract of O. paradoxa defatted seeds displays potent antioxidant effects against both 4β-phorbol-12β-myristate-α13-acetate- and formyl-met-leu-phenylalanine-induced reactive oxygen species production in neutrophils with IC50 values around 0.2 μg/mL. All types of polyphenolics present in the extract contributed to the extract antioxidant activity. According to their IC50 values, penta-O-galloyl-β-D-glucose was the more potent constituent of the extract. In cell-free assays, we demonstrated that this effect is partially due to the scavenging of O2- and H2O2 oxygen species. The extract and especially penta-O-galloyl-β-D-glucose significantly inhibit elastase, myeloperoxidase IL-8, and LTB4 release with an IC50 for penta-O-galloyl-β-D-glucose of 17±1, 15±1, 6.5±2.5, and around 20 μM, respectively. The inhibition of penta-O-galloyl-β-D-glucose on reactive oxygen species and especially on O2- production, myeloperoxidase, and chemoattractant release may reduce the interaction of polymorphonuclear leukocyte with the vascular endothelium and by that potentially diminish the risk of progression of atherosclerosis development.

Overview of the Integrated Programs for Aerospace Vehicle Design (IPAD) project

NASA Technical Reports Server (NTRS)

Venneri, S. L.

1983-01-01

To respond to national needs for improved productivity in engineering design and manufacturing, a NASA supported joint industry/government project is underway denoted Integrated Programs for Aerospace Vehicle Design (IPAD). The objective is to improve engineering productivity through better use of computer technology. It focuses on development of data base management technology and associated software for integrated company wide management of engineering and manufacturing information. Results to date on the IPAD project include an in depth documentation of a representative design process for a large engineering project, the definition and design of computer aided design software needed to support that process, and the release of prototype software to manage engineering information. This paper provides an overview of the IPAD project and summarizes progress to date and future plans.

Biotechnological approaches for field applications of chitooligosaccharides (COS) to induce innate immunity in plants.

PubMed

Das, Subha Narayan; Madhuprakash, Jogi; Sarma, P V S R N; Purushotham, Pallinti; Suma, Katta; Manjeet, Kaur; Rambabu, Samudrala; Gueddari, Nour Eddine El; Moerschbacher, Bruno M; Podile, Appa Rao

2015-03-01

Plants have evolved mechanisms to recognize a wide range of pathogen-derived molecules and to express induced resistance against pathogen attack. Exploitation of induced resistance, by application of novel bioactive elicitors, is an attractive alternative for crop protection. Chitooligosaccharide (COS) elicitors, released during plant fungal interactions, induce plant defenses upon recognition. Detailed analyses of structure/function relationships of bioactive chitosans as well as recent progress towards understanding the mechanism of COS sensing in plants through the identification and characterization of their cognate receptors have generated fresh impetus for approaches that would induce innate immunity in plants. These progresses combined with the application of chitin/chitosan/COS in disease management are reviewed here. In considering the field application of COS, however, efficient and large-scale production of desired COS is a challenging task. The available methods, including chemical or enzymatic hydrolysis and chemical or biotechnological synthesis to produce COS, are also reviewed.

Fukushima Daiichi unit 1 uncertainty analysis--Preliminary selection of uncertain parameters and analysis methodology

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

Cardoni, Jeffrey N.; Kalinich, Donald A.

2014-02-01

Sandia National Laboratories (SNL) plans to conduct uncertainty analyses (UA) on the Fukushima Daiichi unit (1F1) plant with the MELCOR code. The model to be used was developed for a previous accident reconstruction investigation jointly sponsored by the US Department of Energy (DOE) and Nuclear Regulatory Commission (NRC). However, that study only examined a handful of various model inputs and boundary conditions, and the predictions yielded only fair agreement with plant data and current release estimates. The goal of this uncertainty study is to perform a focused evaluation of uncertainty in core melt progression behavior and its effect on keymore » figures-of-merit (e.g., hydrogen production, vessel lower head failure, etc.). In preparation for the SNL Fukushima UA work, a scoping study has been completed to identify important core melt progression parameters for the uncertainty analysis. The study also lays out a preliminary UA methodology.« less

Regulation of nucleolus assembly by non-coding RNA polymerase II transcripts

PubMed Central

Caudron-Herger, Maïwen; Pankert, Teresa; Rippe, Karsten

2016-01-01

ABSTRACT The nucleolus is a nuclear subcompartment for tightly regulated rRNA production and ribosome subunit biogenesis. It also acts as a cellular stress sensor and can release enriched factors in response to cellular stimuli. Accordingly, the content and structure of the nucleolus change dynamically, which is particularly evident during cell cycle progression: the nucleolus completely disassembles during mitosis and reassembles in interphase. Although the mechanisms that drive nucleolar (re)organization have been the subject of a number of studies, they are only partly understood. Recently, we identified Alu element-containing RNA polymerase II transcripts (aluRNAs) as important for nucleolar structure and rRNA synthesis. Integrating these findings with studies on the liquid droplet-like nature of the nucleolus leads us to propose a model on how RNA polymerase II transcripts could regulate the assembly of the nucleolus in response to external stimuli and during cell cycle progression. PMID:27416361

Regulation of nucleolus assembly by non-coding RNA polymerase II transcripts.

PubMed

Caudron-Herger, Maïwen; Pankert, Teresa; Rippe, Karsten

2016-05-03

The nucleolus is a nuclear subcompartment for tightly regulated rRNA production and ribosome subunit biogenesis. It also acts as a cellular stress sensor and can release enriched factors in response to cellular stimuli. Accordingly, the content and structure of the nucleolus change dynamically, which is particularly evident during cell cycle progression: the nucleolus completely disassembles during mitosis and reassembles in interphase. Although the mechanisms that drive nucleolar (re)organization have been the subject of a number of studies, they are only partly understood. Recently, we identified Alu element-containing RNA polymerase II transcripts (aluRNAs) as important for nucleolar structure and rRNA synthesis. Integrating these findings with studies on the liquid droplet-like nature of the nucleolus leads us to propose a model on how RNA polymerase II transcripts could regulate the assembly of the nucleolus in response to external stimuli and during cell cycle progression.

Exosomes Function in Tumor Immune Microenvironment.

PubMed

Huang, Yin; Liu, Keli; Li, Qing; Yao, Yikun; Wang, Ying

2018-01-01

Immune cells and mesenchymal stem/stromal cells are the major cellular components in tumor microenvironment that actively migrate to tumor sites by sensing "signals" released from tumor cells. Together with other stromal cells, they form the soil for malignant cell progression. In the crosstalk between tumor cells and its surrounded microenvironment, exosomes exert multiple functions in shaping tumor immune responses. In tumor cells, their exosomes can lead to pro-tumor immune responses, whereas in immune cells, their derived exosomes can operate on tumor cells and regulate their ability to growth, metastasis, even reaction to chemotherapy. Employing exosomes as vehicles for the delivery products to initiate anti-tumor immune responses has striking therapeutic effects on tumor progression. Thus, exosomes are potential therapeutic targets in tumor-related clinical conditions. Here we discuss the role of exosomes in regulating tumor immune microenvironment and future indications for the clinical application of exosomes.

Correlating Transcription Initiation and Conformational Changes by a Single-Subunit RNA Polymerase with Near Base-Pair Resolution.

PubMed

Koh, Hye Ran; Roy, Rahul; Sorokina, Maria; Tang, Guo-Qing; Nandakumar, Divya; Patel, Smita S; Ha, Taekjip

2018-05-17

We provide a comprehensive analysis of transcription in real time by T7 RNA Polymerase (RNAP) using single-molecule fluorescence resonance energy transfer by monitoring the entire life history of transcription initiation, including stepwise RNA synthesis with near base-pair resolution, abortive cycling, and transition into elongation. Kinetically branching pathways were observed for abortive initiation with an RNAP either recycling on the same promoter or exchanging with another RNAP from solution. We detected fast and slow populations of RNAP in their transition into elongation, consistent with the efficient and delayed promoter release, respectively, observed in ensemble studies. Real-time monitoring of abortive cycling using three-probe analysis showed that the initiation events are stochastically branched into productive and failed transcription. The abortive products are generated primarily from initiation events that fail to progress to elongation, and a majority of the productive events transit to elongation without making abortive products. Copyright © 2018 Elsevier Inc. All rights reserved.

[Therapeutically active dressings--biomaterials in a study of collagen glycation].

PubMed

Pielesz, Anna; Paluch, Jadwiga

2012-01-01

Active dressings (biomaterials, hydrogels) are cross-linked three-dimensional macromolecular networks. One of the most important properties of active dressings, is their ability for controlled uptake, release and retention of molecules. The formation of advanced glycation end products AGEs progressively increases with normal aging. However, AGE products are formed at accelerated rates in age and stress-related diseases (burns, in wound healing) and also in vitro. The aim will be also to develop a series of gels showing ability of controlled uptake, release and retention of molecules. The hydrogels can be used as biologically and therapeutically (antibacterial and anticancer) active biomaterials. The following materials and reagents were used in the examination: dried plants: Equisetum arvense L., Pulmonaria officinalis L., Agropyron repens. Non-defatted films were extracted from the dried plants. The suspension was stirred and extracted. Temperature was controlled using a water bath. The filtrate was vacuum condensed. The gelling precipitate was poured onto Petri plates and dried. The swelling ratio and the percent loading were calculated. The released amount of CaCl2 at different time intervals was determined by measuring the conductivity. The extent of glycation in collagen was measured. Novel types of swelling hydrogels have been prepared from dried plants and alginic acid. The active dressings showed swelling in aqueous medium, swelling characteristics were dependent on the chemical composition of hydrogel. The hydrogels were also loaded with CaCl2 and their potential for release was judged by measuring conductivity. The activity of hydrogels--active dressings on collagen incubated with glucose showed an decrease in glycation. So, hydrogels--active dressings, a known antiglycating agent which have therapeutic role in wound healing.

Hood River Production Program Monitoring and Evaluation (M&E) - Confederated Tribes of Warm Springs : Annual Report For Fiscal Year, October 2007 – September 2008.

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

Gerstenberger, Ryan

2009-07-27

This progress report describes work performed by the Confederated Tribes of Warm Springs (CTWSRO) portion of the Hood River Production Program Monitoring and Evaluation Project (HRPP) during the 2008 fiscal year. A total of 64,736 hatchery winter steelhead, 12,108 hatchery summer steelhead, and 68,426 hatchery spring Chinook salmon smolts were acclimated and released in the Hood River basin during the spring. The HRPP exceeded program goals for a release of and 50,000 winter steelhead but fell short of the steelhead release goals of 30,000 summer steelhead and 75,000 spring Chinook in 2008. Passive Integrated Transponders (PIT) tags were implanted inmore » 6,652 hatchery winter steelhead, and 1,196 hatchery summer steelhead, to compare migratory attributes and survival rates of hatchery fish released into the Hood River. Water temperatures were recorded at six locations within the Hood River subbasin to monitor for compliance with Oregon Department of Environmental Quality water quality standards. A preseason spring Chinook salmon adult run forecast was generated, which predicted an abundant return adequate to meet escapement goal and brood stock needs. As a result the tribal and sport fisheries were opened. A tribal creel was conducted from May 22 to July 18 during which an estimated 172 spring Chinook were harvested. One hundred sixteen Spring Chinook salmon redds were observed and 72 carcasses were inspected on 19.4 miles of spawning grounds throughout the Hood River Basin during 2008. Annual salvage operations were completed in two irrigation canals resulting in the liberation of 1,641 fish back to the Hood River.« less

The path from mitochondrial ROS to aging runs through the mitochondrial permeability transition pore.

PubMed

Rottenberg, Hagai; Hoek, Jan B

2017-10-01

Excessive production of mitochondrial reactive oxygen species (mROS) is strongly associated with mitochondrial and cellular oxidative damage, aging, and degenerative diseases. However, mROS also induces pathways of protection of mitochondria that slow aging, inhibit cell death, and increase lifespan. Recent studies show that the activation of the mitochondrial permeability transition pore (mPTP), which is triggered by mROS and mitochondrial calcium overloading, is enhanced in aged animals and humans and in aging-related degenerative diseases. mPTP opening initiates further production and release of mROS that damage both mitochondrial and nuclear DNA, proteins, and phospholipids, and also releases matrix NAD that is hydrolyzed in the intermembrane space, thus contributing to the depletion of cellular NAD that accelerates aging. Oxidative damage to calcium transporters leads to calcium overload and more frequent opening of mPTP. Because aging enhances the opening of the mPTP and mPTP opening accelerates aging, we suggest that mPTP opening drives the progression of aging. Activation of the mPTP is regulated, directly and indirectly, not only by the mitochondrial protection pathways that are induced by mROS, but also by pro-apoptotic signals that are induced by DNA damage. We suggest that the integration of these contrasting signals by the mPTP largely determines the rate of cell aging and the initiation of cell death, and thus animal lifespan. The suggestion that the control of mPTP activation is critical for the progression of aging can explain the conflicting and confusing evidence regarding the beneficial and deleterious effects of mROS on health and lifespan. © 2017 The Authors. Aging Cell published by the Anatomical Society and John Wiley & Sons Ltd.

The role of maternal age and context-dependent maternal effects in the offspring provisioning of a long-lived marine teleost

PubMed Central

Smith, Wade D.; Spencer, Paul D.; Evans, Allison N.; Heppell, Scott A.; Heppell, Selina S.

2018-01-01

Despite evidence of maternal age effects in a number of teleost species, there have been challenges to the assertion that maternal age intrinsically influences offspring quality. From an evolutionary perspective, maternal age effects result in young females paradoxically investing in less fit offspring despite a greater potential fitness benefit that might be gained by allocating this energy to individual somatic growth. Although a narrow range of conditions could lead to a maternal fitness benefit via the production of lower quality offspring, evolutionary theorists suggest these conditions are seldom met and that the reported maternal age effects are more likely products of the environmental context. Our goal was to determine if maternal effects operated on offspring provisioning in a long-lived rockfish (genus Sebastes), and to evaluate any such effects as an intrinsic function of maternal age or a context-dependent effect of the offspring release environment. We found that offspring provisioning is a function of both maternal age and the timing of offspring release; older females exhibit increased provisioning over younger females throughout the spawning season despite a decrease in provisioning across all maternal ages as the season progresses. These findings suggest a role for both maternal age effects and a potential context-dependent maternal effect in population productivity, carrying important implications when modelling population persistence and resilience. PMID:29410808

Review on Molecular Mechanisms of Antifouling Compounds: An Update since 2012.

PubMed

Chen, Lianguo; Qian, Pei-Yuan

2017-08-28

Better understanding of the mechanisms of antifouling compounds is recognized to be of high value in establishing sensitive biomarkers, allowing the targeted optimization of antifouling compounds and guaranteeing environmental safety. Despite vigorous efforts to find new antifouling compounds, information about the mechanisms of antifouling is still scarce. This review summarizes the progress into understanding the molecular mechanisms underlying antifouling activity since 2012. Non-toxic mechanisms aimed at specific targets, including inhibitors of transmembrane transport, quorum sensing inhibitors, neurotransmission blockers, adhesive production/release inhibitors and enzyme/protein inhibitors, are put forward for natural antifouling products or shelf-stable chemicals. Several molecular targets show good potential for use as biomarkers in future mechanistic screening, such as acetylcholine esterase for neurotransmission, phenoloxidase/tyrosinase for the formation of adhesive plaques, N -acyl homoserine lactone for quorum sensing and intracellular Ca 2+ levels as second messenger. The studies on overall responses to challenges by antifoulants can be categorized as general targets, including protein expression/metabolic activity regulators, oxidative stress inducers, neurotransmission blockers, surface modifiers, biofilm inhibitors, adhesive production/release inhibitors and toxic killing. Given the current situation and the knowledge gaps regarding the development of alternative antifoulants, a basic workflow is proposed that covers the indispensable steps, including preliminary mechanism- or bioassay-guided screening, evaluation of environmental risks, field antifouling performance, clarification of antifouling mechanisms and the establishment of sensitive biomarkers, which are combined to construct a positive feedback loop.

Short communication: Effect of on-farm feeding practices on rumen protected lysine products.

PubMed

Ji, P; Tucker, H A; Clark, R E; Miura, M; Ballard, C S

2016-02-01

Two independent studies were conducted to determine whether mechanical mixing of total mixed ration (TMR) or TMR dry matter alters Lys release from 6 rumen-protected Lys (RPL) products (A, B, C, D, E, and F). In the first study, routine mixing procedures were simulated to determine if inclusion of RPL products in TMR altered in situ release of Lys. Following mixing, Dacron bags containing RPL products were ruminally incubated for 0, 6, 12, or 24 h to determine Lys release. The second study occurred independently of the first, in which Lys release from RPL products was evaluated when incorporated into a TMR that differed in dry matter (DM) content. Bags containing TMR and RPL product mixture were stored at room temperature for 0, 6, 18, and 24 h to simulate RPL product exposure to TMR when mixed and delivered once per day. Concentration of free Lys in both studies was determined using ultra-performance liquid chromatography. Following mechanical mixing, ruminal Lys release was significantly greater for C and tended to increase for F. Mechanical mixing did not alter ruminal Lys release from other RPL products evaluated. Hours of ruminal incubation significantly altered Lys release for all products evaluated, and a significant interaction of mechanical mixing and hours of ruminal incubation was observed for A and C. Exposure to lower TMR DM (40.5 versus 51.8%) significantly increased Lys release from B but did not alter Lys release from the other RPL products evaluated. Moreover, time of exposure to TMR significantly increased Lys release from all RPL products evaluated, and a significant interaction of TMR DM and time of exposure to TMR was observed for B and E. These data suggest mechanical mixing and variation in TMR DM may compromise the rumen protection of RPL products; therefore, on-farm feeding practices may alter efficacy of RPL products in dairy rations. Copyright © 2016 American Dairy Science Association. Published by Elsevier Inc. All rights reserved.

Antioxidants modulate the antiproliferative effects of nitric oxide on vascular smooth muscle cells and adventitial fibroblasts by regulating oxidative stress.

PubMed

Gregory, Elaine K; Vavra, Ashley K; Moreira, Edward S; Havelka, George E; Jiang, Qun; Lee, Vanessa R; Van Lith, Robert; Ameer, Guillermo A; Kibbe, Melina R

2011-11-01

S-nitrosothiols (SNO) release nitric oxide (NO) through interaction with ascorbic acid (AA). However, little is known about their combined effect in the vasculature. The aim of this study was to investigate the effect of AA on SNO-mediated NO release, proliferation, cell cycle progression, cell death, and oxidative stress in vascular cells. Vascular smooth muscle cells and adventitial fibroblasts harvested from the aortae of Sprague-Dawley rats were treated with AA, ± S-nitrosoglutathione (GSNO), or ± diethylenetriamine NONOate (DETA/NO). NO release, proliferation, cell cycle progression, cell death, and oxidative stress were determined by the Griess reaction, [(3)H]-thymidine incorporation, flow cytometry, trypan blue exclusion, and 5-(and-6)chloromethyl-2',7'dichlorodihydrofluorescein staining, respectively. AA increased NO release from GSNO 3-fold (P < .001). GSNO and DETA/NO significantly decreased proliferation, but AA abrogated this effect (P < .05). Mirroring the proliferation data, changes in cell cycle progression induced by GSNO and DETA/NO were reversed by the addition of AA. GSNO- and DETA/NO-mediated increases in oxidative stress were significantly decreased by the addition of AA (P < .001). Despite causing increased NO release from GSNO, AA reduced the antiproliferative and cell cycle effects of GSNO and DETA/NO through the modulation of oxidative stress. Copyright © 2011 Elsevier Inc. All rights reserved.

Encapsulation of anticancer drug copper bis(8-hydroxyquinoline) in hydroxyapatite for pH-sensitive targeted delivery and slow release.

PubMed

Weerasuriya, D R K; Wijesinghe, W P S L; Rajapakse, R M G

2017-02-01

There is a conspicuous progress in increasing anticancer drug delivery through the utilization of nanoparticles (NPs) as drug delivery agents. Hydroxyapatite (HA) gives improved clinical effectiveness of drugs by reducing systemic toxicity and broadening the spectrum of drug delivery since it is biocompatible and it can be targeted towards tumor cells. Herein, investigation of the potential of enhancing controlled drug release of the template model drug, copper bis-(8-hydroxyquinoline), by encapsulating it in hollow hydroxyapatite nano-carriers, is presented. Hydroxyapatite nanoparticles are synthesized by following four different routes to optimize its efficacy of drug loading. Copper bis-(8-hydroxyquinoline) is encapsulated by Method (a) which was effected by stirring the model drug and porous HA NPs in colloidal solution and Method (b) which was done during synthesis of hydroxyapatite nanoparticles in a solution of the model drug. In synthesizing nanoporous HA NPs, calcium carbonate is used as a template to create voids in HA. In each method, Ca/P ratio was ensured to be kept at 1.67:1. Appealing results are reported for the encapsulated product which was prepared by Method (a2). Method (a) was done at three different molar ratios of PO 4 3- :CO 3 2- and best result was obtained for that utilized 2.003:1 molar ratio (Method (a2).). It produced 98.67% of encapsulation efficiency and 2.9522mg/g of drug loading capacity. Release kinetics was studied at a range of pH values; the lower the pH of the medium the higher is the drug release. For instance, when considering the product which exhibited high encapsulation efficiency and high drug loading capacity, at pH3.5 during the first 8h it elicited about 13% of release, at pH5.0 about 8% release while at pH6.0 it was just 2.5%. During the 24-hour span, pH3.5 exhibited about 23.8%, at pH5.0 approximately 9% with an increasing trend of release and at pH6.0 showed a value just above 2.5%. As such, acidity of the cancerous cells can be made use to increase the drug slow-release kinetics at the vicinity of the cancer cells. Copyright © 2016 Elsevier B.V. All rights reserved.

Quetiapine for hypnogogic musical release hallucinations.

PubMed

David, R R; Fernandez, H H

2000-01-01

Musical release hallucinations are complex auditory phenomena, affecting mostly the deaf geriatric population, in which individuals hear vocal or instrumental music. Progressive hearing loss from otosclerosis disrupts the usual external sensory stimuli necessary to inhibit the emergence of memory traces within the brain, thereby "releasing" previously recorded perceptions. Responses to conventional antipsychotic agents have been variable and extrapyramidal and other side effects have limited their use. We report the first case of hypnogogic release hallucinations successfully treated with the atypical antipsychotic quetiapine. The patient is an 88-year-old woman with progressive deafness who complained of hearing the piano, drums, or a full orchestra every time she was about to fall asleep. She accused her neighbor of hosting loud parties. Physical, neurologic, and psychiatric examination and work-up were unremarkable. She was treated with low-dose quetiapine affording near total resolution of hallucinations without adverse effects.

Health Effects of Cut Gas Lines and Other Petroleum Product Release Incidents - Seven States, 2010-2012.

PubMed

Anderson, Ayana R

2015-06-12

Large mass casualty gas explosions and catastrophic oil spills are widely reported and receive considerable regulatory attention. Smaller, less catastrophic petroleum product releases are less likely to receive publicity, although study of these incidents might help focus and prioritize prevention efforts. To describe the causes and health impacts of petroleum product release incidents (including gas explosions and oil spills), the Agency for Toxic Substances and Disease Registry (ATSDR) analyzed 2010-2012 data from the National Toxic Substance Incidents Program (NTSIP). A total of 1,369 petroleum product release incidents were reported from seven states, resulting in 512 injuries and 36 deaths. Approximately one fourth of the incidents were associated with utilities, and approximately one fifth were associated with private vehicles or residences. Approximately 10% of petroleum product releases resulted from inadvertent damage to utility lines. Understanding the characteristics of acute petroleum product releases can aid the public and utility workers in the development of preventive strategies and reduce the morbidity and mortality associated with such releases.

Chitosan nanoparticle based delivery systems for sustainable agriculture.

PubMed

Kashyap, Prem Lal; Xiang, Xu; Heiden, Patricia

2015-01-01

Development of technologies that improve food productivity without any adverse impact on the ecosystem is the need of hour. In this context, development of controlled delivery systems for slow and sustained release of agrochemicals or genetic materials is crucial. Chitosan has emerged as a valuable carrier for controlled delivery of agrochemicals and genetic materials because of its proven biocompatibility, biodegradability, non-toxicity, and adsorption abilities. The major advantages of encapsulating agrochemicals and genetic material in a chitosan matrix include its ability to function as a protective reservoir for the active ingredients, protecting the ingredients from the surrounding environment while they are in the chitosan domain, and then controlling their release, allowing them to serve as efficient gene delivery systems for plant transformation or controlled release of pesticides. Despite the great progress in the use of chitosan in the area of medical and pharmaceutical sciences, there is still a wide knowledge gap regarding the potential application of chitosan for encapsulation of active ingredients in agriculture. Hence, the present article describes the current status of chitosan nanoparticle-based delivery systems in agriculture, and to highlight challenges that need to be overcome. Copyright © 2015 Elsevier B.V. All rights reserved.

Dietary toxins, endoplasmic reticulum (ER) stress and diabetes.

PubMed

Hettiarachchi, Kalindi D; Zimmet, Paul Z; Myers, Mark A

2008-05-01

The incidence of Type 1 diabetes has been increasing at a rate too rapid to be due to changes in genetic risk. Instead changes in environmental factors are the likely culprit. The endoplasmic reticulum (ER) plays an important role in the production of newly synthesized proteins and interference with these processes leads to ER stress. The insulin-producing beta cells are particularly prone to ER stress as a result of their heavy engagement in insulin production. Increasing evidence suggests ER stress is central to initiation and progression of Type 1 diabetes. An early environmental exposure, such as toxins and viral infections, can impart a significant physiological load on beta cells to initiate abnormal processing of proinsulin, ER stress and insulin secretory defects. Release of altered proinsulin from the beta cells early in life may trigger autoimmunity in those with genetic susceptibility leading to cytokine-induced nitric oxide production and so exacerbating ER stress in beta cells, ultimately leading to apoptosis of beta cells and diabetes. Here we suggest that ER stress is an inherent cause of beta cell dysfunction and environmental factors, in particular dietary toxins derived from Streptomyces in infected root vegetables, can impart additional stress that aggravates beta cell death and progression to diabetes. Furthermore, we propose that the increasing incidence of Type 1 diabetes may be accounted for by increased dietary exposure to ER-stress-inducing Streptomyces toxins.

Hyperphagia in male melanocortin 4 receptor deficient mice promotes growth independently of growth hormone.

PubMed

Tan, H Y; Steyn, F J; Huang, L; Cowley, M; Veldhuis, J D; Chen, C

2016-12-15

Loss of function of the melanocortin 4 receptor (MC4R) results in hyperphagia, obesity and increased growth. Despite knowing that MC4Rs control food intake, we are yet to understand why defects in the function of the MC4R receptor contribute to rapid linear growth. We show that hyperphagia following germline loss of MC4R in male mice promotes growth while suppressing the growth hormone-insulin-like growth factor-1 (GH-IGF-1) axis. We propose that hyperinsulinaemia promotes growth while suppressing the GH-IGF-1 axis. It is argued that physiological responses essential to maintain energy flux override conventional mechanisms of pubertal growth to promote the storage of excess energy while ensuring growth. Defects in melanocortin-4-receptor (MC4R) signalling result in hyperphagia, obesity and increased growth. Clinical observations suggest that loss of MC4R function may enhance growth hormone (GH)-mediated growth, although this remains untested. Using male mice with germline loss of the MC4R, we assessed pulsatile GH release and insulin-like growth factor-1 (IGF-1) production and/or release relative to pubertal growth. We demonstrate early-onset suppression of GH release in rapidly growing MC4R deficient (MC4RKO) mice, confirming that increased linear growth in MC4RKO mice does not occur in response to enhanced activation of the GH-IGF-1 axis. The progressive suppression of GH release in MC4RKO mice occurred alongside increased adiposity and the progressive worsening of hyperphagia-associated hyperinsulinaemia. We next prevented hyperphagia in MC4RKO mice through restricting calorie intake in these mice to match that of wild-type (WT) littermates. Pair feeding of MC4RKO mice did not prevent increased adiposity, but attenuated hyperinsulinaemia, recovered GH release, and normalized linear growth rate to that seen in pair-fed WT littermate controls. We conclude that the suppression of GH release in MC4RKO mice occurs independently of increased adipose mass, and is a consequence of hyperphagia-associated hyperinsulinaemia. It is proposed that physiological responses essential to maintain energy flux (hyperinsulinaemia and the suppression of GH release) override conventional mechanisms of pubertal growth to promote the storage of excess energy while ensuring growth. Implications of these findings are likely to extend beyond individuals with defects in MC4R signalling, encompassing physiological changes central to mechanisms of growth and energy homeostasis universal to hyperphagia-associated childhood-onset obesity. © 2016 The Authors. The Journal of Physiology © 2016 The Physiological Society.

Hyperphagia in male melanocortin 4 receptor deficient mice promotes growth independently of growth hormone

PubMed Central

Tan, H. Y.; Huang, L.; Cowley, M.; Veldhuis, J. D.; Chen, C.

2016-01-01

Key points Loss of function of the melanocortin 4 receptor (MC4R) results in hyperphagia, obesity and increased growth.Despite knowing that MC4Rs control food intake, we are yet to understand why defects in the function of the MC4R receptor contribute to rapid linear growth.We show that hyperphagia following germline loss of MC4R in male mice promotes growth while suppressing the growth hormone–insulin‐like growth factor‐1 (GH–IGF‐1) axis.We propose that hyperinsulinaemia promotes growth while suppressing the GH–IGF‐1 axis.It is argued that physiological responses essential to maintain energy flux override conventional mechanisms of pubertal growth to promote the storage of excess energy while ensuring growth. Abstract Defects in melanocortin‐4‐receptor (MC4R) signalling result in hyperphagia, obesity and increased growth. Clinical observations suggest that loss of MC4R function may enhance growth hormone (GH)‐mediated growth, although this remains untested. Using male mice with germline loss of the MC4R, we assessed pulsatile GH release and insulin‐like growth factor‐1 (IGF‐1) production and/or release relative to pubertal growth. We demonstrate early‐onset suppression of GH release in rapidly growing MC4R deficient (MC4RKO) mice, confirming that increased linear growth in MC4RKO mice does not occur in response to enhanced activation of the GH–IGF‐1 axis. The progressive suppression of GH release in MC4RKO mice occurred alongside increased adiposity and the progressive worsening of hyperphagia‐associated hyperinsulinaemia. We next prevented hyperphagia in MC4RKO mice through restricting calorie intake in these mice to match that of wild‐type (WT) littermates. Pair feeding of MC4RKO mice did not prevent increased adiposity, but attenuated hyperinsulinaemia, recovered GH release, and normalized linear growth rate to that seen in pair‐fed WT littermate controls. We conclude that the suppression of GH release in MC4RKO mice occurs independently of increased adipose mass, and is a consequence of hyperphagia‐associated hyperinsulinaemia. It is proposed that physiological responses essential to maintain energy flux (hyperinsulinaemia and the suppression of GH release) override conventional mechanisms of pubertal growth to promote the storage of excess energy while ensuring growth. Implications of these findings are likely to extend beyond individuals with defects in MC4R signalling, encompassing physiological changes central to mechanisms of growth and energy homeostasis universal to hyperphagia‐associated childhood‐onset obesity. PMID:27558671

Preparation of Simulated LBL Defects for Round Robin Experiment

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

Gerczak, Tyler J.; Baldwin, Charles A.; Hunn, John D.

2016-01-01

A critical characteristic of the TRISO fuel design is its ability to retain fission products. During reactor operation, the TRISO layers act as barriers to release of fission products not stabilized in the kernel. Each component of the TRISO particle and compact construction plays a unique role in retaining select fission products, and layer performance is often interrelated. The IPyC, SiC, and OPyC layers are barriers to the release of fission product gases such as Kr and Xe. The SiC layer provides the primary barrier to release of metallic fission products not retained in the kernel, as transport across themore » SiC layer is rate limiting due to the greater permeability of the IPyC and OPyC layers to many metallic fission products. These attributes allow intact TRISO coatings to successfully retain most fission products released from the kernel, with the majority of released fission products during operation being due to defective, damaged, or failed coatings. This dominant release of fission products from compromised particles contributes to the overall source term in reactor; causing safety and maintenance concerns and limiting the lifetime of the fuel. Under these considerations, an understanding of the nature and frequency of compromised particles is an important part of predicting the expected fission product release and ensuring safe and efficient operation.« less

[Testing of medicinal products produced from pooled plasma].

PubMed

Unkelbach, U; Hunfeld, A; Breitner-Ruddock, S

2014-10-01

Medicinal products produced from human plasma fall under the administrative batch release procedure of the competent authority. In Germany, this has been carried out since 1995 by the Paul Ehrlich Institute (PEI), the responsible state control agency for blood products. Medicinal products released for the European and national market are tested for quality, efficacy and safety. Experimental testing of the final product and the starting materials, the plasma pools, as well as control of the production documentation guarantee a constantly high product safety. In the 28,000 batches tested since the beginning of the state controlled batch release testing of these blood products at the PEI, there has been no transmission of infectious viruses (HIV, HBV and HCV) to any patient. The batch release has made a contribution to the improvement of product quality. This procedure is still an important tool to ensure safety of blood products. The PEI is integrated in the batch release network of the European Directorate for the Quality of Medicines & Health Care (EDQM) in Strasbourg. Regulations and guidelines for official control authority batch release (OCABR) ensure harmonized procedures for mutual recognition of batch release on the European level. The EU certificates and German national certificates are requested and accepted in over 70 countries worldwide. Experimental testing in the EU and the requisite certificates have developed into a seal of quality for the world market.

Application of Nuclear Techniques to Improve the Mass Production and Management of Fruit Fly Parasitoids

PubMed Central

Cancino, Jorge; Ruíz, Lía; Viscarret, Mariana; Sivinski, John; Hendrichs, Jorge

2012-01-01

The use of irradiated hosts in mass rearing tephritid parasitoids represents an important technical advance in fruit fly augmentative biological control. Irradiation assures that fly emergence is avoided in non-parasitized hosts, while at the same time it has no appreciable effect on parasitoid quality, i.e., fecundity, longevity and flight capability. Parasitoids of fruit fly eggs, larvae and pupae have all been shown to successfully develop in irradiated hosts, allowing a broad range of species to be shipped and released without post-rearing delays waiting for fly emergence and costly procedures to separate flies and wasps. This facilitates the early, more effective and less damaging shipment of natural enemies within hosts and across quarantined borders. In addition, the survival and dispersal of released parasitoids can be monitored by placing irradiated sentinel-hosts in the field. The optimal radiation dosages for host-sterility and parasitoid-fitness differ among species, and considerable progress has been made in integrating radiation into a variety of rearing procedures. PMID:26466729

Potential release scenarios for carbon nanotubes used in composites.

PubMed

Nowack, Bernd; David, Raymond M; Fissan, Heinz; Morris, Howard; Shatkin, Jo Anne; Stintz, Michael; Zepp, Richard; Brouwer, Derk

2013-09-01

The expected widespread use of carbon nanotube (CNT)-composites in consumer products calls for an assessment of the possible release and exposure to workers, consumers and the environment. Release of CNTs may occur at all steps in the life cycle of products, but to date only limited information is available about release of CNTs from actual products and articles. As a starting point for exposure assessment, exploring sources and pathways of release helps to identify relevant applications and situations where the environment and especially humans may encounter releases of CNTs. It is the aim of this review to identify various potential release scenarios for CNTs used in polymers and identify the greatest likelihood of release at the various stages throughout the life-cycle of the product. The available information on release of CNTs from products and articles is reviewed in a first part. In a second part nine relevant release scenarios are described in detail: injection molding, manufacturing, sports equipment, electronics, windmill blades, fuel system components, tires, textiles, incineration, and landfills. Release from products can potentially occur by two pathways; (a) where free CNTs are released directly, or more frequently (b) where the initial release is a particle with CNTs embedded in the matrix, potentially followed by the subsequent release of CNTs from the matrix. The potential for release during manufacturing exists for all scenarios, however, this is also the situation when exposure can be best controlled. For most of the other life cycle stages and their corresponding release scenarios, potential release of CNTs can be considered to be low, but it cannot be excluded totally. Direct release to the environment is also considered to be very low for most scenarios except for the use of CNTs in tires where significant abrasion during use and release into the environment would occur. Also the possible future use of CNTs in textiles could result in consumer exposure. A possibility for significant release also exists during recycling operations when the polymers containing CNTs are handled together with other polymers and mainly occupational users would be exposed. It can be concluded that in general, significant release of CNTs from products and articles is unlikely except in manufacturing and subsequent processing, tires, recycling, and potentially in textiles. However except for high energy machining processes, most likely the resulting exposure for these scenarios will be low and to a non-pristine form of CNTs. Actual exposure studies, which quantify the amount of material released should be conducted to provide further evidence for this conclusion. Copyright © 2013 The Authors. Published by Elsevier Ltd.. All rights reserved.

Children's Services Report Card, 1996: Measuring Minnesota's Progress for Children. Summary Report.

ERIC Educational Resources Information Center

Fong, Richard

This report was developed by Minnesota Planning to help counties measure their progress toward meeting the Minnesota Milestones goals for social and educational services for children. The report card is composed of 21 indicators of children's well-being. Since the 1994 report card was released, Minnesota has made progress in eight areas (1) abused…

Effects of artemisinin sustained-release granules on mixed alga growth and microcystins production and release.

PubMed

Ni, Lixiao; Li, Danye; Hu, Shuzhen; Wang, Peifang; Li, Shiyin; Li, Yiping; Li, Yong; Acharya, Kumud

2015-12-01

To safely and effectively apply artemisinin sustained-release granules to control and prevent algal water-blooms, the effects of artemisinin and its sustained-release granules on freshwater alga (Scenedesmus obliquus (S. obliquus) and Microcystis aeruginosa (M. aeruginosa)), as well as the production and release of microcystins (MCs) were studied. The results showed that artemisinin sustained-release granules inhibited the growth of M. aeruginosa (above 95% IR) and S. obliquus (about 90% IR), with M. aeruginosa more sensitive. The artemisinin sustained-release granules had a longer inhibition effect on growth of pure algae and algal coexistence than direct artemisinin dosing. The artemisinin sustained-release granules could decrease the production and release of algal toxins due to the continued stress of artemisinin released from artemisinin sustained-release granules. There was no increase in the total amount of MC-LR in the algal cell culture medium.

Natural product-based nanomedicine: recent advances and issues

PubMed Central

Watkins, Rebekah; Wu, Ling; Zhang, Chenming; Davis, Richey M; Xu, Bin

2015-01-01

Natural products have been used in medicine for many years. Many top-selling pharmaceuticals are natural compounds or their derivatives. These plant- or microorganism-derived compounds have shown potential as therapeutic agents against cancer, microbial infection, inflammation, and other disease conditions. However, their success in clinical trials has been less impressive, partly due to the compounds’ low bioavailability. The incorporation of nanoparticles into a delivery system for natural products would be a major advance in the efforts to increase their therapeutic effects. Recently, advances have been made showing that nanoparticles can significantly increase the bioavailability of natural products both in vitro and in vivo. Nanotechnology has demonstrated its capability to manipulate particles in order to target specific areas of the body and control the release of drugs. Although there are many benefits to applying nanotechnology for better delivery of natural products, it is not without issues. Drug targeting remains a challenge and potential nanoparticle toxicity needs to be further investigated, especially if these systems are to be used to treat chronic human diseases. This review aims to summarize recent progress in several key areas relevant to natural products in nanoparticle delivery systems for biomedical applications. PMID:26451111

Magnetic-confinement fusion

NASA Astrophysics Data System (ADS)

Ongena, J.; Koch, R.; Wolf, R.; Zohm, H.

2016-05-01

Our modern society requires environmentally friendly solutions for energy production. Energy can be released not only from the fission of heavy nuclei but also from the fusion of light nuclei. Nuclear fusion is an important option for a clean and safe solution for our long-term energy needs. The extremely high temperatures required for the fusion reaction are routinely realized in several magnetic-fusion machines. Since the early 1990s, up to 16 MW of fusion power has been released in pulses of a few seconds, corresponding to a power multiplication close to break-even. Our understanding of the very complex behaviour of a magnetized plasma at temperatures between 150 and 200 million °C surrounded by cold walls has also advanced substantially. This steady progress has resulted in the construction of ITER, a fusion device with a planned fusion power output of 500 MW in pulses of 400 s. ITER should provide answers to remaining important questions on the integration of physics and technology, through a full-size demonstration of a tenfold power multiplication, and on nuclear safety aspects. Here we review the basic physics underlying magnetic fusion: past achievements, present efforts and the prospects for future production of electrical energy. We also discuss questions related to the safety, waste management and decommissioning of a future fusion power plant.

Emerging Players at the Intersection of Chondrocyte Loss of Maturational Arrest, Oxidative Stress, Senescence and Low-Grade Inflammation in Osteoarthritis.

PubMed

Minguzzi, Manuela; Cetrullo, Silvia; D'Adamo, Stefania; Silvestri, Ylenia; Flamigni, Flavio; Borzì, Rosa Maria

2018-01-01

The prevalence of Osteoarthritis (OA) is increasing because of the progressive aging and unhealthy lifestyle. These risk factors trigger OA by removing constraints that keep the tightly regulated low turnover of the extracellular matrix (ECM) of articular cartilage, the correct chondrocyte phenotype, and the functionality of major homeostatic mechanisms, such as mitophagy, that allows for the clearance of dysfunctional mitochondria, preventing increased production of reactive oxygen species, oxidative stress, and senescence. After OA onset, the presence of ECM degradation products is perceived as a "danger" signal by the chondrocytes and the synovial macrophages that release alarmins with autocrine/paracrine effects on the same cells. Alarmins trigger innate immunity in the joint, with important systemic crosstalks that explain the beneficial effects of dietary interventions and improved lifestyle. Alarmins also boost low-grade inflammation: the release of inflammatory molecules and chemokines sustained by continuous triggering of NF- κ B within an altered cellular setting that allows its higher transcriptional activity. Chemokines exert pleiotropic functions in OA, including the recruitment of inflammatory cells and the induction of ECM remodeling. Some chemokines have been successfully targeted to attenuate structural damage or pain in OA animal models. This represents a promising strategy for the future management of human OA.

MELCOR computer code manuals

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

Summers, R.M.; Cole, R.K. Jr.; Smith, R.C.

1995-03-01

MELCOR is a fully integrated, engineering-level computer code that models the progression of severe accidents in light water reactor nuclear power plants. MELCOR is being developed at Sandia National Laboratories for the U.S. Nuclear Regulatory Commission as a second-generation plant risk assessment tool and the successor to the Source Term Code Package. A broad spectrum of severe accident phenomena in both boiling and pressurized water reactors is treated in MELCOR in a unified framework. These include: thermal-hydraulic response in the reactor coolant system, reactor cavity, containment, and confinement buildings; core heatup, degradation, and relocation; core-concrete attack; hydrogen production, transport, andmore » combustion; fission product release and transport; and the impact of engineered safety features on thermal-hydraulic and radionuclide behavior. Current uses of MELCOR include estimation of severe accident source terms and their sensitivities and uncertainties in a variety of applications. This publication of the MELCOR computer code manuals corresponds to MELCOR 1.8.3, released to users in August, 1994. Volume 1 contains a primer that describes MELCOR`s phenomenological scope, organization (by package), and documentation. The remainder of Volume 1 contains the MELCOR Users Guides, which provide the input instructions and guidelines for each package. Volume 2 contains the MELCOR Reference Manuals, which describe the phenomenological models that have been implemented in each package.« less

Assessment of antimicrobial effects of food contact materials containing silver on growth of Salmonella Typhimurium.

PubMed

Williams, Katherine; Valencia, Luis; Gokulan, Kuppan; Trbojevich, Raul; Khare, Sangeeta

2017-02-01

Food contact materials containing antibacterial properties are progressively appearing in the market. Items intended to provide antimicrobial effects such as increased shelf life and food safety are incorporating silver materials during the manufacture of such products. This study examined the total silver content, release capacity, and antibacterial activity of three different silver-containing food contact materials: plastic food storage containers, a plastic cutting board, and food wrapping paper. Silver content and release were determined by Inductively Coupled Plasma Mass Spectrometry, and the results showed that, although the amount of silver in each product was similar, migration varied considerably with kind of material and simulant choice. Antimicrobial effect was tested by measuring the growth of Salmonella Typhimurium during or after exposure to the different food contact materials. The results showed that the food storage containers and wrapping paper delayed the growth of S. Typhimurium under certain conditions, but that these effects were short-lived. The strain of S. Typhimurium used in this study was found to be negative for the presence of tested silver resistance genes. The results of this study suggest that a thorough investigation should be required to show/claim the efficacy of silver-containing food contact materials for food safety purposes. Published by Elsevier Ltd.

[Practice of botulism].

PubMed

Ikeguchi, Kunihiko

2011-07-01

Botulism is a rare but potentially life-threatening motor and autonomic paralytic syndrome caused by the action of neurotoxins released by Clostridium botulinum. The modern syndromes of botulism have 6 forms: 4 naturally occurring syndromes and 2 human-induced syndromes. Food-borne botulism is caused by ingestion of foods contaminated with botulinum toxin. Wound botulism is caused by C. botulinum infection of a wound and in situ toxin production. Infant botulism and adult intestinal botulism are caused by intestinal colonization and in situ toxin production. Air-borne botulism results from aerosolization of botulinum toxin, whereas iatrogenic botulism occurs due to injection of a large dose of the toxin. Another human-induced form may occur when the aerosolized toxin is released as an act of bioterrorism. All forms of botulism produce a similar syndrome: symmetrical cranial motor nerve palsies followed by descending, symmetrical motor weakness, which may progress to respiratory failure requiring intubation and respiratory support. The clinical diagnosis can be confirmed by electrophysiological studies. Laboratory diagnosis includes serum analysis of toxin by bioassay in mice. Analysis of stool, vomitus, and suspected food items may reveal the toxin. In wound botulism, isolation of C. botulinum from the wound site is diagnostic. The mainstays of therapy are meticulous intensive care including respiratory support, when necessary, and timely administration of the antitoxin.

Climate conditions, workplace heat and occupational health in South-East Asia in the context of climate change.

PubMed

Kjellstrom, Tord; Lemke, Bruno; Otto, Matthias

2017-09-01

Occupational health is particularly affected by high heat exposures in workplaces, which will be an increasing problem as climate change progresses. People working in jobs of moderate or heavy work intensity in hot environments are at particular risk, owing to exposure to high environmental heat and internal heat production. This heat needs to be released to protect health, and such release is difficult or impossible at high temperatures and high air humidity. A range of clinical health effects can occur, and the heat-related physical exhaustion leads to a reduction of work capacity and labour productivity, which may cause substantial economic losses. Current trends in countries of the World Health Organization South-East Asia Region are towards higher ambient heat levels during large parts of each year, and modelling indicates continuing trends, which will particularly affect low-income individuals and communities. Prevention activities need to address the climate policies of each country, and to apply currently available heat-reducing technologies in workplaces whenever possible. Work activities can be adjusted to reduce exposure to daily heat peaks or seasonal heat concerns. Application of basic occupational health principles, such as supply of drinking water, enforcement of rest periods and training of workers and supervisors, is essential.

Can quaternary ammonium methacrylates inhibit matrix MMPs and cathepsins?

PubMed Central

Tezvergil-Mutluay, Arzu; Agee, Kelli A.; Mazzoni, Annalisa; Carvalho, Ricardo M.; Carrilho, Marcela; Tersariol, Ivarne L.; Nascimento, Fabio D.; Imazato, Satoshi; Tjäderhane, Leo; Breschi, Lorenzo; Tay, Franklin R; Pashley, David H.

2014-01-01

Objective Dentin matrices release ICTP and CTX fragments during collagen degradation. ICTP fragments are known to be produced by MMPs. CTX fragments are thought to come from cathepsin K activity. The purpose of this study was to determine if quaternary methacrylates (QAMs) can inhibit matrix MMPs and cathepsins. Methods Dentin beams were demineralizated, and dried to constant weight. Beams were incubated with rh-cathepsin B, K, L or S for 24 h at pH 7.4 to identify which cathepsins release CTX at neutral pH. Beams were dipped in ATA, an antimicrobial QAM to determine if it can inhibit dentin matrix proteases. Other beams were dipped in another QAM (MDPB) to determine if it produced similar inhibition of dentin proteases. Results Only beams incubated with cathepsin K lost more dry mass than the controls and released CTX. Dentin beams dipped in ATA and incubated for 1 week at pH 7.4, showed a concentration-dependent reduction in weight-loss. There was no change in ICTP release from control values, meaning that ATA did not inhibit MMPs. Media concentrations of CTX fell significantly at 15 wt% ATA indicating that ATA inhibits capthesins. Beams dipped in increasing concentrations of MDPB lost progressively less mass, showing that MDPB is a protease-inhibitor. ICTP released from controls or beams exposed to low concentrations were the same, while 5 or 10% MDPB significantly lowered ICTP production. CTX levels were strongly inhibited by 2.5–10% MDPB, indicating that MDPB is a potent inhibitor of both MMPs and cathepsin K. Significance CTX seems to be released from dentin matrix only by cathepsin K. MMPs and cathepsin K and B may all contribute to matrix degradation. PMID:25467953

Programmable release of multiple protein drugs from aptamer-functionalized hydrogels via nucleic acid hybridization.

PubMed

Battig, Mark R; Soontornworajit, Boonchoy; Wang, Yong

2012-08-01

Polymeric delivery systems have been extensively studied to achieve localized and controlled release of protein drugs. However, it is still challenging to control the release of multiple protein drugs in distinct stages according to the progress of disease or treatment. This study successfully demonstrates that multiple protein drugs can be released from aptamer-functionalized hydrogels with adjustable release rates at predetermined time points using complementary sequences (CSs) as biomolecular triggers. Because both aptamer-protein interactions and aptamer-CS hybridization are sequence-specific, aptamer-functionalized hydrogels constitute a promising polymeric delivery system for the programmable release of multiple protein drugs to treat complex human diseases.

The International Xenotransplantation Association consensus statement on conditions for undertaking clinical trials of porcine islet products in type 1 diabetes--chapter 3: Pig islet product manufacturing and release testing.

PubMed

Korbutt, Gregory S

2009-01-01

This chapter provides recommendations on pig islet product manufacturing and release testing to scientific and corporate programs interested in future clinical studies using xenogeneic porcine pancreatic islet cell products for the treatment of type 1 diabetes.To facilitate control of manufacturing as well as reproducibility and consistency of product lots, the manufacturing process, and the manufacturing facility must be in compliance with current Good Manufacturing Practices regulations. Data must be provided to demonstrate that islet products can be consistently prepared that would meet basic lot release requirements. To facilitate product safety: (i) materials used in the manufacturing process, including the pig pancreas, must be free of adventitious agents; (ii) islets must be manufactured using aseptic processing; and (iii) final product must undergo tests for sterility, mycoplasma (if cultured) and endotoxin. Safety specifications for pig islet product release include a negative Gram stain and an endotoxin content of <5.0 EU/kg recipient body weight. Product post-release assessments must include sterility cultures on the final product. Because results for sterility are available only retrospectively, a plan of action must be in place for patient notification and treatment in case the sterility culture results are positive for contamination. Product characterization information must address important aspects of lot release testing such as identity/purity (cell composition), quantity [islet equivalents (IE), cell number] and potency (insulin secretory capacity, oxygen consumption rate corrected for DNA or transplant bioassay in immunoincompetent diabetic mice). This information is also critical to demonstrate manufacturing control and product consistency across multiple islet preparations (lots). Providing islet products containing an islet mass sufficient to restore euglycemia in trial participants (>or=10 000 IE/kg) requires pooling of islets from multiple donor pancreata (two to four from adult donors and seven to 10 from neonatal donors). Demonstration of product consistency across products from individual pancreata would warrant release testing to be performed on a sample of the pooled product. As product development and clinical trials advance, the increasingly more detailed specifications of potency assays on adult porcine islet products are expected to be predictive of post-transplant glycemic control. The immaturity of fetal and neonatal porcine islet tissue precludes the use of in vitro insulin secretion as a potency test as part of lot release testing; another measure of potency appropriate to fetal and neonatal cells will need to be developed for product release testing and evaluation of aliquots of these products in mouse transplant bioassays should be performed to provide meaningful post-release information.

48 CFR 752.7035 - Public notices.

Code of Federal Regulations, 2011 CFR

2011-10-01

... notices. The following clause is for use when the cognizant technical office determines that the contract... to time, to announce progress and accomplishments. Press releases or other public notices should... cognizant technical officer and to USAID's Legislative and Public Affairs (LPA) as far in advance of release...

Suppression of soil nitrification by plants.

PubMed

Subbarao, Guntur Venkata; Yoshihashi, Tadashi; Worthington, Margaret; Nakahara, Kazuhiko; Ando, Yasuo; Sahrawat, Kanwar Lal; Rao, Idupulapati Madhusudhana; Lata, Jean-Christophe; Kishii, Masahiro; Braun, Hans-Joachim

2015-04-01

Nitrification, the biological oxidation of ammonium to nitrate, weakens the soil's ability to retain N and facilitates N-losses from production agriculture through nitrate-leaching and denitrification. This process has a profound influence on what form of mineral-N is absorbed, used by plants, and retained in the soil, or lost to the environment, which in turn affects N-cycling, N-use efficiency (NUE) and ecosystem health and services. As reactive-N is often the most limiting in natural ecosystems, plants have acquired a range of mechanisms that suppress soil-nitrifier activity to limit N-losses via N-leaching and denitrification. Plants' ability to produce and release nitrification inhibitors from roots and suppress soil-nitrifier activity is termed 'biological nitrification inhibition' (BNI). With recent developments in methodology for in-situ measurement of nitrification inhibition, it is now possible to characterize BNI function in plants. This review assesses the current status of our understanding of the production and release of biological nitrification inhibitors (BNIs) and their potential in improving NUE in agriculture. A suite of genetic, soil and environmental factors regulate BNI activity in plants. BNI-function can be genetically exploited to improve the BNI-capacity of major food- and feed-crops to develop next-generation production systems with reduced nitrification and N2O emission rates to benefit both agriculture and the environment. The feasibility of such an approach is discussed based on the progresses made. Copyright © 2015 Elsevier Ireland Ltd. All rights reserved.

Review on Molecular Mechanisms of Antifouling Compounds: An Update since 2012

PubMed Central

Chen, Lianguo; Qian, Pei-Yuan

2017-01-01

Better understanding of the mechanisms of antifouling compounds is recognized to be of high value in establishing sensitive biomarkers, allowing the targeted optimization of antifouling compounds and guaranteeing environmental safety. Despite vigorous efforts to find new antifouling compounds, information about the mechanisms of antifouling is still scarce. This review summarizes the progress into understanding the molecular mechanisms underlying antifouling activity since 2012. Non-toxic mechanisms aimed at specific targets, including inhibitors of transmembrane transport, quorum sensing inhibitors, neurotransmission blockers, adhesive production/release inhibitors and enzyme/protein inhibitors, are put forward for natural antifouling products or shelf-stable chemicals. Several molecular targets show good potential for use as biomarkers in future mechanistic screening, such as acetylcholine esterase for neurotransmission, phenoloxidase/tyrosinase for the formation of adhesive plaques, N-acyl homoserine lactone for quorum sensing and intracellular Ca2+ levels as second messenger. The studies on overall responses to challenges by antifoulants can be categorized as general targets, including protein expression/metabolic activity regulators, oxidative stress inducers, neurotransmission blockers, surface modifiers, biofilm inhibitors, adhesive production/release inhibitors and toxic killing. Given the current situation and the knowledge gaps regarding the development of alternative antifoulants, a basic workflow is proposed that covers the indispensable steps, including preliminary mechanism- or bioassay-guided screening, evaluation of environmental risks, field antifouling performance, clarification of antifouling mechanisms and the establishment of sensitive biomarkers, which are combined to construct a positive feedback loop. PMID:28846624

Functionalized nanocompartments (Synthosomes): limitations and prospective applications in industrial biotechnology.

PubMed

Onaca, Ozana; Nallani, Madhavan; Ihle, Saskia; Schenk, Alexander; Schwaneberg, Ulrich

2006-01-01

Synthosomes are mechanically stable vesicles with a block copolymer membrane and an engineered transmembrane protein acting as selective gate. The polymer vesicles are nanometer-sized (50-1000 nm) and functionalized by loading them with enzymes for bioconversions or encapsulating charged macromolecules for selective compound recovery/release. The Synthosome system might become a novel technology platform for biocatalysis and selective product recovery. Progress in Synthosome research comprises employed block copolymers, transmembrane channel engineering, and functionalizations, which are discussed here in detail. The challenges in transmembrane protein engineering, as well as cost-effective production, in block copolymer design and the state of the art in Synthosome characterization comprising quantification of encapsulated protein, translocation efficiency, number of transmembrane channels per vesicle, and enzyme kinetics are also presented and discussed. An assessment of the Synthosome technology platform for prospective applications in industrial (white) biotechnology concludes this review.

Regulation of exosome release from mammary epithelial and breast cancer cells - a new regulatory pathway.

PubMed

Riches, Andrew; Campbell, Elaine; Borger, Eva; Powis, Simon

2014-03-01

Exosomes are small 50-100nm sized extracellular vesicles released from normal and tumour cells and are a source of a new intercellular communication pathway. Tumour exosomes promote tumour growth and progression. What regulates the release and homoeostatic levels of exosomes, in cancer, in body fluids remains undefined. We utilised a human mammary epithelial cell line (HMEC B42) and a breast cancer cell line derived from it (B42 clone 16) to investigate exosome production and regulation. Exosome numbers were quantified using a Nanosight LM10 and measured in culture supernatants in the absence and presence of exosomes in the medium. Concentrated suspensions of exosomes from the normal mammary epithelial cells, the breast cancer cells and bladder cancer cells were used. The interaction of exosomes with tumour cells was also investigated using fluorescently labelled exosomes. Exosome release from normal human mammary epithelial cells and breast cancer cells is regulated by the presence of exosomes, derived from their own cells, in the extracellular environment of the cells. Exosomes from normal mammary epithelial cells also inhibit exosome secretion by breast cancer cells, which occurs in a tissue specific manner. Labelled exosomes from mammary epithelial cells are internalised into the tumour cells implicating a dynamic equilibrium and suggesting a mechanism for feedback control. These data suggest a previously unknown novel feedback regulatory mechanism for controlling exosome release, which may highlight a new therapeutic approach to controlling the deleterious effects of tumour exosomes. This regulatory mechanism is likely to be generic to other tumours. Copyright © 2014 Elsevier Ltd. All rights reserved.

Retro-Nasal Aroma Release Is Correlated with Variations in the In-Mouth Air Cavity Volume after Empty Deglutition

PubMed Central

Mishellany-Dutour, Anne; Woda, Alain; Labouré, Hélène; Bourdiol, Pierre; Lachaze, Pauline; Guichard, Elisabeth; Feron, Gilles

2012-01-01

We hypothesized that interindividual differences in motor activities during chewing and/or swallowing were determining factors for the transfer of volatile aroma from the in-mouth air cavity (IMAC) toward the olfactory mucosa. In our first experiment, we looked for changes in IMAC volume after saliva deglutition in 12 healthy subjects. The mean IMAC volume was measured after empty deglutition using an acoustic pharyngometer device. Based on the time course of the IMAC volume after swallowing, we discerned two groups of subjects. The first group displayed a small, constant IMAC volume (2.26 mL ±0.62) that corresponded to a high tongue position. The second group displayed a progressive increase in IMAC (from 6.82 mL ±2.37 to 22.82 mL ±3.04) that corresponded to a progressive lowering of the tongue to its resting position. In our second experiment, we investigated the relationship between IMAC volume changes after deglutition and the level of aroma release at the nostril. For this purpose, the release of menthone was measured at the nostril level in 25 subjects who consumed similar amounts of a mint tablet. The subjects were separated into two groups corresponding to two levels of menthone release: high (H) and low (L). The mean volume of IMAC was measured during and after empty deglutition. Group H displayed a small, constant amplitude of IMAC volume change after deglutition, while Group L displayed a progressive increase in IMAC. It is likely that Group H continuously released the aroma through the veloglossal isthmus as the mint was consumed, while Group L trapped the aroma in the oral cavity and then released it into the nasal cavity upon swallowing. These results show that the in vivo aroma release profile in humans depends closely on the different motor patterns at work during empty deglutition. PMID:22815986

Structure of a low-population intermediate state in the release of an enzyme product.

PubMed

De Simone, Alfonso; Aprile, Francesco A; Dhulesia, Anne; Dobson, Christopher M; Vendruscolo, Michele

2015-01-09

Enzymes can increase the rate of biomolecular reactions by several orders of magnitude. Although the steps of substrate capture and product release are essential in the enzymatic process, complete atomic-level descriptions of these steps are difficult to obtain because of the transient nature of the intermediate conformations, which makes them largely inaccessible to standard structure determination methods. We describe here the determination of the structure of a low-population intermediate in the product release process by human lysozyme through a combination of NMR spectroscopy and molecular dynamics simulations. We validate this structure by rationally designing two mutations, the first engineered to destabilise the intermediate and the second to stabilise it, thus slowing down or speeding up, respectively, product release. These results illustrate how product release by an enzyme can be facilitated by the presence of a metastable intermediate with transient weak interactions between the enzyme and product.

A multifunctional multimaterial system for on-demand protein release.

PubMed

Tuncaboylu, Deniz Ceylan; Friess, Fabian; Wischke, Christian; Lendlein, Andreas

2018-06-15

In order to provide best control of the regeneration process for each individual patient, the release of protein drugs administered during surgery may need to be timely adapted and/or delayed according to the progress of healing/regeneration. This study aims to establish a multifunctional implant system for a local on-demand release, which is applicable for various types of proteins. It was hypothesized that a tubular multimaterial container kit, which hosts the protein of interest as a solution or gel formulation, would enable on-demand release if equipped with the capacity of diameter reduction upon external stimulation. Using devices from poly(ɛ-caprolactone) networks, it could be demonstrated that a shape-memory effect activated by heat or NIR light enabled on-demand tube shrinkage. The decrease of diameter of these shape-memory tubes (SMT) allowed expelling the payload as demonstrated for several proteins including SDF-1α, a therapeutically relevant chemotactic protein, to achieve e.g. continuous release with a triggered add-on dosing (open tube) or an on-demand onset of bolus or sustained release (sealed tube). Considering the clinical relevance of protein factors in (stem) cell attraction to lesions and the progress in monitoring biomarkers in body fluids, such on-demand release systems may be further explored e.g. in heart, nerve, or bone regeneration in the future. Copyright © 2018. Published by Elsevier B.V.

Pharmacokinetics of colon-specific pH and time-dependent flurbiprofen tablets.

PubMed

Vemula, Sateesh Kumar; Veerareddy, Prabhakar Reddy; Devadasu, Venkat Ratnam

2015-09-01

Present research deals with the development of compression-coated flurbiprofen colon-targeted tablets to retard the drug release in the upper gastro intestinal system, but progressively release the drug in the colon. Flurbiprofen core tablets were prepared by direct compression method and were compression coated using sodium alginate and Eudragit S100. The formulation is optimized based on the in vitro drug release study and further evaluated by X-ray imaging and pharmacokinetic studies in healthy humans for colonic delivery. The optimized formulation showed negligible drug release (4.33 ± 0.06 %) in the initial lag period followed by progressive release (100.78 ± 0.64 %) for 24 h. The X-ray imaging in human volunteers showed that the tablets reached the colon without disintegrating in the upper gastrointestinal tract. The C max of colon-targeted tablets was 12,374.67 ng/ml at T max 10 h, where as in case of immediate release tablets the C max was 15,677.52 ng/ml at T max 3 h, that signifies the ability of compression-coated tablets to target the colon. Development of compression-coated tablets using combination of time-dependent and pH-sensitive approaches was suitable to target the flurbiprofen to colon.

De novo Fatty Acid Biosynthesis Contributes Significantly to Establishment of a Bioenergetically Favorable Environment for Vaccinia Virus Infection

PubMed Central

Greseth, Matthew D.; Traktman, Paula

2014-01-01

The poxvirus life cycle, although physically autonomous from the host nucleus, is nevertheless dependent upon cellular functions. A requirement for de novo fatty acid biosynthesis was implied by our previous demonstration that cerulenin, a fatty acid synthase inhibitor, impaired vaccinia virus production. Here we show that additional inhibitors of this pathway, TOFA and C75, reduce viral yield significantly, with partial rescue provided by exogenous palmitate, the pathway's end-product. Palmitate's major role during infection is not for phospholipid synthesis or protein palmitoylation. Instead, the mitochondrial import and β-oxidation of palmitate are essential, as shown by the impact of etomoxir and trimetazidine, which target these two processes respectively. Moreover, the impact of these inhibitors is exacerbated in the absence of exogenous glucose, which is otherwise dispensable for infection. In contrast to glucose, glutamine is essential for productive viral infection, providing intermediates that sustain the TCA cycle (anaplerosis). Cumulatively, these data suggest that productive infection requires the mitochondrial β-oxidation of palmitate which drives the TCA cycle and energy production. Additionally, infection causes a significant rise in the cellular oxygen consumption rate (ATP synthesis) that is ablated by etomoxir. The biochemical progression of the vaccinia life cycle is not impaired in the presence of TOFA, C75, or etomoxir, although the levels of viral DNA and proteins synthesized are somewhat diminished. However, by reversibly arresting infections at the onset of morphogenesis, and then monitoring virus production after release of the block, we determined that virion assembly is highly sensitive to TOFA and C75. Electron microscopic analysis of cells released into C75 revealed fragmented aggregates of viroplasm which failed to be enclosed by developing virion membranes. Taken together, these data indicate that vaccinia infection, and in particular virion assembly, relies on the synthesis and mitochondrial import of fatty acids, where their β-oxidation drives robust ATP production. PMID:24651651

De novo fatty acid biosynthesis contributes significantly to establishment of a bioenergetically favorable environment for vaccinia virus infection.

PubMed

Greseth, Matthew D; Traktman, Paula

2014-03-01

The poxvirus life cycle, although physically autonomous from the host nucleus, is nevertheless dependent upon cellular functions. A requirement for de novo fatty acid biosynthesis was implied by our previous demonstration that cerulenin, a fatty acid synthase inhibitor, impaired vaccinia virus production. Here we show that additional inhibitors of this pathway, TOFA and C75, reduce viral yield significantly, with partial rescue provided by exogenous palmitate, the pathway's end-product. Palmitate's major role during infection is not for phospholipid synthesis or protein palmitoylation. Instead, the mitochondrial import and β-oxidation of palmitate are essential, as shown by the impact of etomoxir and trimetazidine, which target these two processes respectively. Moreover, the impact of these inhibitors is exacerbated in the absence of exogenous glucose, which is otherwise dispensable for infection. In contrast to glucose, glutamine is essential for productive viral infection, providing intermediates that sustain the TCA cycle (anaplerosis). Cumulatively, these data suggest that productive infection requires the mitochondrial β-oxidation of palmitate which drives the TCA cycle and energy production. Additionally, infection causes a significant rise in the cellular oxygen consumption rate (ATP synthesis) that is ablated by etomoxir. The biochemical progression of the vaccinia life cycle is not impaired in the presence of TOFA, C75, or etomoxir, although the levels of viral DNA and proteins synthesized are somewhat diminished. However, by reversibly arresting infections at the onset of morphogenesis, and then monitoring virus production after release of the block, we determined that virion assembly is highly sensitive to TOFA and C75. Electron microscopic analysis of cells released into C75 revealed fragmented aggregates of viroplasm which failed to be enclosed by developing virion membranes. Taken together, these data indicate that vaccinia infection, and in particular virion assembly, relies on the synthesis and mitochondrial import of fatty acids, where their β-oxidation drives robust ATP production.

Acrylamide formation in different foods and potential strategies for reduction.

PubMed

Stadler, Richard H

2005-01-01

This paper summarizes the progress made to date on acrylamide research pertaining to analytical methods, mechanisms of formation, and mitigation research in the major food categories. Initial difficulties with the establishment of reliable analytical methods have today in most cases been overcome, but challenges still remain in terms of the needs to develop simple and rapid test methods. Several researchers have identified that the main pathway of formation of acrylamide in foods is linked to the Maillard reaction and in particular the amino acid asparagine. Decarboxylation of the resulting Schiff base is a key step, and the reaction product may either furnish acrylamide directly or via 3-aminopropionamide. An alternative proposal is that the corresponding decarboxylated Amadori compound may release acrylamide by a beta-elimination reaction. Many experimental trials have been conducted in different foods, and a number of possible measures identified to relatively lower the amounts of acrylamide in food. The validity of laboratory trials must, however, be assessed under actual food processing conditions. Some progress in relatively lowering acrylamide in certain food categories has been achieved, but can at this stage be considered marginal. However, any options that are chosen to reduce acrylamide must be technologically feasible and also not negatively impact the quality and safety of the final product.

Toxic AGE (TAGE) Theory for the Pathophysiology of the Onset/Progression of NAFLD and ALD

PubMed Central

Takeuchi, Masayoshi; Takino, Jun-ichi; Sakasai-Sakai, Akiko; Takata, Takanobu; Tsutsumi, Mikihiro

2017-01-01

Non-alcoholic fatty liver disease (NAFLD) and alcoholic liver disease (ALD) are among the most common causes of chronic liver diseases in the westernized world. NAFLD and ALD are frequently accompanied by extrahepatic complications, including hepatocellular carcinoma and cardiovascular diseases, which have a negative impact on patient survival. The chronic ingestion of an excessive daily diet containing sugar/high-fructose corn syrup increases the level of the fructose/glucose metabolite, glyceraldehyde (GA), while the chronic consumption of an excessive number of alcoholic beverages increases the level of the alcohol metabolite, acetaldehyde (AA) in the liver. GA and AA are known to react non-enzymatically with the ε- or α-amino groups of proteins, thereby generating advanced glycation end-products (AGEs, GA-AGEs, and AA-AGEs, respectively) in vivo. The interaction between GA-AGEs and the receptor for AGEs (RAGE) alters intracellular signaling, gene expression, and the release of pro-inflammatory molecules and also elicits the production of reactive oxygen species by human hepatocytes and hepatic stellate cells, all of which may contribute to the pathological changes associated with chronic liver diseases. We herein discuss the pathophysiological roles of GA-AGEs and AA-AGEs (toxic AGEs, TAGE) and a related novel theory for preventing the onset/progression of NAFLD and ALD. PMID:28632197

MARMOT update for oxide fuel modeling

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

Zhang, Yongfeng; Schwen, Daniel; Chakraborty, Pritam

This report summarizes the lower-length-scale research and development progresses in FY16 at Idaho National Laboratory in developing mechanistic materials models for oxide fuels, in parallel to the development of the MARMOT code which will be summarized in a separate report. This effort is a critical component of the microstructure based fuel performance modeling approach, supported by the Fuels Product Line in the Nuclear Energy Advanced Modeling and Simulation (NEAMS) program. The progresses can be classified into three categories: 1) development of materials models to be used in engineering scale fuel performance modeling regarding the effect of lattice defects on thermal conductivity, 2) development of modeling capabilities for mesoscale fuel behaviors including stage-3 gas release, grain growth, high burn-up structure, fracture and creep, and 3) improved understanding in material science by calculating the anisotropic grain boundary energies in UOmore » $$_2$$ and obtaining thermodynamic data for solid fission products. Many of these topics are still under active development. They are updated in the report with proper amount of details. For some topics, separate reports are generated in parallel and so stated in the text. The accomplishments have led to better understanding of fuel behaviors and enhance capability of the MOOSE-BISON-MARMOT toolkit.« less

One-step fabrication of multifunctional micromotors.

PubMed

Gao, Wenlong; Liu, Mei; Liu, Limei; Zhang, Hui; Dong, Bin; Li, Christopher Y

2015-09-07

Although artificial micromotors have undergone tremendous progress in recent years, their fabrication normally requires complex steps or expensive equipment. In this paper, we report a facile one-step method based on an emulsion solvent evaporation process to fabricate multifunctional micromotors. By simultaneously incorporating various components into an oil-in-water droplet, upon emulsification and solidification, a sphere-shaped, asymmetric, and multifunctional micromotor is formed. Some of the attractive functions of this model micromotor include autonomous movement in high ionic strength solution, remote control, enzymatic disassembly and sustained release. This one-step, versatile fabrication method can be easily scaled up and therefore may have great potential in mass production of multifunctional micromotors for a wide range of practical applications.

Plasma levels of endothelial and B-cell-derived microparticles are restored by fingolimod treatment in multiple sclerosis patients.

PubMed

Zinger, Anna; Latham, Sharissa L; Combes, Valery; Byrne, Scott; Barnett, Michael H; Hawke, Simon; Grau, Georges E

2016-12-01

No molecular marker can monitor disease progression and treatment efficacy in multiple sclerosis (MS). Circulating microparticles represent a potential snapshot of disease activity at the blood brain barrier. To profile plasma microparticles by flow cytometry in MS and determine how fingolimod could impact endothelial microparticles production. In non-treated MS patients compared to healthy and fingolimod-treated patients, endothelial microparticles were higher, while B-cell-microparticle numbers were lower. Fingolimod dramatically reduced tumour necrosis factor (TNF)-induced endothelial microparticle release in vitro. Fingolimod restored dysregulated endothelial and B-cell-microparticle numbers, which could serve as a biomarker in MS. © The Author(s), 2016.

Dynamic Model for the Stocks and Release Flows of Engineered Nanomaterials.

PubMed

Song, Runsheng; Qin, Yuwei; Suh, Sangwon; Keller, Arturo A

2017-11-07

Most existing life-cycle release models for engineered nanomaterials (ENM) are static, ignoring the dynamics of stock and flows of ENMs. Our model, nanoRelease, estimates the annual releases of ENMs from manufacturing, use, and disposal of a product explicitly taking stock and flow dynamics into account. Given the variabilities in key parameters (e.g., service life of products and annual release rate during use) nanoRelease is designed as a stochastic model. We apply nanoRelease to three ENMs (TiO 2 , SiO 2 and FeO x ) used in paints and coatings through seven product applications, including construction and building, household and furniture, and automotive for the period from 2000 to 2020 using production volume and market projection information. We also consider model uncertainties using Monte Carlo simulation. Compared with 2016, the total annual releases of ENMs in 2020 will increase by 34-40%, and the stock will increase by 28-34%. The fraction of the end-of-life release among total release flows will increase from 11% in 2002 to 43% in 2020. As compared to static models, our dynamic model predicts about an order of magnitude lower values for the amount of ENM released from this sector in the near-term while stock continues to build up in the system.

Formaldehyde in cosmetics in patch tested dermatitis patients with and without contact allergy to formaldehyde.

PubMed

Hauksson, Inese; Pontén, Ann; Isaksson, Marléne; Hamada, Haneen; Engfeldt, Malin; Bruze, Magnus

2016-03-01

Formaldehyde is a well-known contact sensitizer. Formaldehyde releasers are widely used preservatives in cosmetics. To survey the release of formaldehyde in cosmetics brought by patients investigated because of suspected allergic contact dermatitis, to compare it with information given by the manufacturers on the packages, and to investigate whether formaldehyde-allergic patients are potentially exposed to more cosmetics releasing formaldehyde than dermatitis patients without contact allergy to formaldehyde. Cosmetics from 10 formaldehyde-allergic and 30 non-allergic patients (controls) matched for age and sex were investigated with the chromotropic acid spot test, which is a semiquantitative method measuring the release of formaldehyde. Formaldehyde was found in 58 of 245 (23.7%) products. Twenty-six of 126 (20.6%) leave-on products released formaldehyde, and 17 of 26 (65.4%) of these were not declared to contain formaldehyde or formaldehyde releasers. Among the rinse-off products, there were 32 of 119 (26.8%) formaldehyde-releasing products, and nine of 32 (28.0%) of these were not labelled as containing formaldehyde or formaldehyde releasers. Five of 10 formaldehyde-allergic patients brought leave-on products with ≥ 40 ppm formaldehyde, as compared with 4 of 30 in the control group (p = 0.029). Cosmetic products used by formaldehyde-allergic patients that are not declared to contain formaldehyde or formaldehyde-releasing preservatives should be analysed. © 2015 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

Experiments on the high-temperature behaviour of neutron-irradiated uranium dioxide and fission products, volume 8, number 1

NASA Astrophysics Data System (ADS)

Tanke, R. H. J.

The release rate of fission products from overheated UO2, the chemical form of these fission products, and the transport mechanism inside the nuclear fuel are determined. UO spheres of approximately 1 mm diameter, irradiated in a high-flux reactor were used for the experiments. The chemical forms of the particles released from the spheres during evaporation were determined by mass spectrometry and the release rate of the mission products was determined by gamma spectrometry. A gamma topographer was developed to determine the change with temperature in the three dimensional distribution of radioactive fission products in the spheres. No clear relationship between the stoichiometry of the spheres and uranium consumption were shown. A diffusion model was used to determine the activation energy for the diffusion of fission products. It is concluded that the microstructure of the nuclear fuel greatly affects the number of free oxygen atoms, the release rate and the chemical form of the fission products. The evaporation of the UO2 matrix is the main mechanism for the release of all fission products at temperatures above 2300 K. Barium can be as volatile as iodine. Niobium and lanthenum can be volatile. Molecular combinations of the fission products, iodine, cesium and tellurium, are highly unlikely to be present inside the fuel. Barium and nobium may form compounds with oxygen and are then released as simple oxides. Fission products are released from overheated UO2 or as oxides. A new model is proposed for describing the behavior of oxygen in irradiated nuclear fuel.

RIVER DELL CENTER FOR THE PROMOTION OF THE HUMANITIES. PROGRESS REPORT ON PRINTED INFORMATION, CONFERENCES AND VISITATIONS TO NOVEMBER 30, 1966. (TITLE SUPPLIED).

ERIC Educational Resources Information Center

River Dell Regional Schools, Oradell, NJ.

THIS REPORT CITES THE PROGRESS AND ACCOMPLISHMENTS OF THE RIVER DELL CENTER. INFORMATION IS PRESENTED OF (1) PRINTED RELEASES, (2) CONTACTS MADE, (3) ON INSERVICE COURSE OFFERED, (4) DISSEMINATION OF COURSE INFORMATION, (5) VISITATIONS, AND (6) IN-PROGRESS ACTIVITIES. TWO REGIONAL SCHOOL NEWSLETTERS ALONG WITH CORRESPONDENCE LETTERS TO THE NEW…

DNA Methylation as an Epigenetic Factor in the Development and Progression of Polycythemia Vera

DTIC Science & Technology

2007-11-01

in the Development and Progression of Polycythemia Vera PRINCIPAL INVESTIGATOR: Jean-Pierre Issa, M.D. CONTRACTING...NUMBER DNA Methylation as an Epigenetic Factor in the Development and Progression of Polycythemia Vera 5b. GRANT NUMBER W81XWH-05-1-0535 5c...AVAILABILITY STATEMENT Approved for Public Release; Distribution Unlimited 13. SUPPLEMENTARY NOTES 14. ABSTRACT Polycythemia vera (PV

Release of engineered nanomaterials from personal care products throughout their life cycle

NASA Astrophysics Data System (ADS)

Keller, Arturo A.; Vosti, William; Wang, Hongtao; Lazareva, Anastasiya

2014-07-01

The impetus for this study was to provide release estimates that can serve to improve predictions of engineered nanomaterial (ENM) exposure for risk assessment. We determined the likely release of ENMs from personal care products (PCPs) through a consumer survey on use and disposal habits, and research on the types and quantities of ENMs in PCPs. Our estimates show that in the US zinc oxide (ZnO), with 1,800-2,100 mt yr-1, and titanium dioxide (TiO2), with 870-1,000 mt yr-1, represent 94 % of ENMs released into the environment or landfills from the use of PCPs. Around 36-43 % of ENMs from PCPs were estimated to end up in landfills, 24-36 % released to soils, 0.7-0.8 % to air, and 28-32 % to water bodies. ENMs in sunscreen represent around 81-82 % of total release, from ZnO and TiO2 as UV blockers, followed by facial moisturizer (7.5 %), foundation (5.7 %), and hair coloring products (3.1 %). Daily care products such as body wash, shampoo, and conditioner had by far the highest per capita and total use, but contributed little to the ENM release estimates as these products generally contain little or no ENMs. However, if ENMs are incorporated into these daily care products, this may substantially increase ENM release.

Current trend in drug delivery considerations for subcutaneous insulin depots to treat diabetes.

PubMed

P V, Jayakrishnapillai; Nair, Shantikumar V; Kamalasanan, Kaladhar

2017-05-01

Diabetes mellitus (DM) is a metabolic disorder due to irregularities in glucose metabolism, as a result of insulin disregulation. Chronic DM (Type 1) is treated by daily insulin injections by subcutaneous route. Daily injections cause serious patient non-compliance and medication non-adherence. Insulin Depots (ID) are parenteral formulations designed to release the insulin over a specified period of time, to control the plasma blood glucose level for intended duration. Physiologically, pancreas produces and secretes insulin in basal and pulsatile mode into the blood. Delivery systems mimicking basal release profiles are known as open-loop systems and current marketed products are open-loop systems. Future trend in open-loop systems is to reduce the number of injections per week by enhancing duration of action, by modifying the depot properties. The next generation technologies are closed-loop systems that mimic the pulsatile mode of delivery by pancreas. In closed-loop systems insulin will be released in response to plasma glucose. This review focuses on future trend in open-loop systems; by understanding (a) the secretion of insulin from pancreas, (b) the insulin regulation normal and in DM, (c) insulin depots and (d) the recent progress in open-loop depot technology particularly with respect to nanosystems. Copyright © 2017 Elsevier B.V. All rights reserved.

Biogenic organic emissions, air quality and climate

NASA Astrophysics Data System (ADS)

Guenther, A. B.

2015-12-01

Living organisms produce copious amounts of a diverse array of metabolites including many volatile organic compounds that are released into the atmosphere. These compounds participate in numerous chemical reactions that influence the atmospheric abundance of important air pollutants and short-lived climate forcers including organic aerosol, ozone and methane. The production and release of these organics are strongly influenced by environmental conditions including air pollution, temperature, solar radiation, and water availability and they are highly sensitive to stress and extreme events. As a result, releases of biogenic organics to the atmosphere have an impact on, and are sensitive to, air quality and climate leading to potential feedback couplings. Their role in linking air quality and climate is conceptually clear but an accurate quantitative representation is needed for predictive models. Progress towards this goal will be presented including numerical model development and assessments of the predictive capability of the Model of Emission of Gases and Aerosols from Nature (MEGAN). Recent studies of processes controlling the magnitude and variations in biogenic organic emissions will be described and observations of their impact on atmospheric composition will be shown. Recent advances and priorities for future research will be discussed including laboratory process studies, long-term measurements, multi-scale regional studies, global satellite observations, and the development of a next generation model for simulating land-atmosphere chemical exchange.

Progress Made in Lunar In-Situ Resource Utilization Under NASA's Exploration Technology and Development Program

NASA Technical Reports Server (NTRS)

Sanders, Gerald B.; Larson, William E.

2012-01-01

Incorporation of In-Situ Resource Utilization (ISRU) and the production of mission critical consumables for 9 propulsion, power, and life support into mission architectures can greatly reduce the mass, cost, and risk of missions 10 leading to a sustainable and affordable approach to human exploration beyond Earth. ISRU and its products can 11 also greatly affect how other exploration systems are developed, including determining which technologies are 12 important or enabling. While the concept of lunar ISRU has existed for over 40 years, the technologies and systems 13 had not progressed much past simple laboratory proof-of-concept tests. With the release of the Vision for Space 14 Exploration in 2004 with the goal of harnessing the Moon.s resources, NASA initiated the ISRU Project in the 15 Exploration Technology Development Program (ETDP) to develop the technologies and systems needed to meet 16 this goal. In the five years of work in the ISRU Project, significant advancements and accomplishments occurred in 17 several important areas of lunar ISRU. Also, two analog field tests held in Hawaii in 2008 and 2010 demonstrated 18 all the steps in ISRU capabilities required along with the integration of ISRU products and hardware with 19 propulsion, power, and cryogenic storage systems. This paper will review the scope of the ISRU Project in the 20 ETDP, ISRU incorporation and development strategies utilized by the ISRU Project, and ISRU development and 21 test accomplishments over the five years of funded project activity.

The Release of Nanosilver from Consumer Products Used in the Home

PubMed Central

Benn, Troy; Cavanagh, Bridget; Hristovski, Kiril; Posner, Jonathan D.; Westerhoff, Paul

2016-01-01

Nanosilver has become one of the most widely used nanomaterials in consumer products because of its antimicrobial properties. Public concern over the potential adverse effects of nanosilver's environmental release has prompted discussion of federal regulation. In this paper, we assess several classes of consumer products for their silver content and potential to release nanosilver into water, air, or soil. Silver was quantified in a shirt, a medical mask and cloth, toothpaste, shampoo, detergent, a towel, a toy teddy bear, and two humidifiers. Silver concentrations ranged from 1.4 to 270,000 μg Ag g product−1. Products were washed in 500 mL of tap water to assess the potential release of silver into aqueous environmental matrices (wastewater, surface water, saliva, etc.). Silver was released in quantities up to 45 μg Ag g product−1, and size fractions were both larger and smaller than 100 nm. Scanning electron microscopy confirmed the presence of nanoparticle silver in most products as well as in the wash water samples. Four products were subjected to a toxicity characterization leaching procedure to assess the release of silver in a landfill. The medical cloth released an amount of silver comparable to the toxicity characterization limit. This paper presents methodologies that can be used to quantify and characterize silver and other nanomaterials in consumer products. The quantities of silver in consumer products can in turn be used to estimate real-world human and environmental exposure levels. PMID:21284285

Elevated serum progastrin-releasing peptide (31-98) in metastatic and androgen-independent prostate cancer patients.

PubMed

Yashi, Masahiro; Muraishi, Osamu; Kobayashi, Yutaka; Tokue, Akihiko; Nanjo, Hiroshi

2002-05-01

Increases in neuroendocrine phenotype and secretory products are closely correlated with tumor progression and androgen independence in prostate cancer. In this study, we explored this correlation using serum progastrin-releasing peptide (ProGRP), a carboxy-terminal region common to three subtypes of precursors for gastrin-releasing peptide (GRP), which is released from the neuroendocrine phenotype to act as a growth factor. In 60 patients with benign prostatic hyperplasia (BPH) and 200 with prostate cancer, serum ProGRP levels were determined with an enzyme-linked immunosorbent assay (ELISA) kit and evaluated in relation to clinical stage, hormonal treatment, and prostate-specific antigen (PSA) values. Fourteen randomly selected patients were entered in the follow-up study. Additionally, expression of ProGRP as determined by immunohistochemical analysis was compared to that of chromogranin-A (CgA) in tissue samples from several subjects. We found a positive correlation between PSA and ProGRP in patients with untreated prostate cancer; no correlation was found in the treated groups. The increases in the ProGRP value and in the percentage of patients with higher than normal values were significant (P < 0.0001), especially in the androgen-independent group (P < 0.0001). A longitudinal study showed that, in a subset of patients, the ProGRP values tended to increase transiently when the cancer became androgen independent, but remained unchanged or decreased at the androgen-dependent stage. Positive staining for ProGRP occurred in a different distribution in neuroendocrine tissues than that of staining for CgA. The clinical results demonstrated the existence of a regulatory mechanism for GRP, which to date had only been observed in cell lines. These findings suggest that GRP is a growth factor potentially upregulated by androgen but that does not rely principally on androgen modulation. The large overlap in levels of ProGRP among the groups limits the use of this value as a monitoring tool. Measurement of ProGRP, however, does have potential as an independent parameter to evaluate androgen-independent progression and to facilitate a new therapeutic strategy that may compensate for current limitations of diagnosis based on PSA alone. Copyright 2002 Wiley-Liss, Inc.

Genetic progress in oat associated with fungicide use in Rio Grande do Sul, Brazil.

PubMed

Follmann, D N; Cargnelutti Filho, A; Lúcio, A D; de Souza, V Q; Caraffa, M; Wartha, C A

2016-12-19

The State of Rio Grande do Sul (RS) is the largest producer of oat in Brazil with the aid of consolidated breeding programs, which are constantly releasing new cultivars. The main objectives of this study were to: 1) evaluate the annual genetic progress in grain yield and hectoliter weight of the oat cultivars in RS, with and without fungicide use on aerial parts of plants; and 2) evaluate the efficiency of oat breeding programs in introducing disease-resistant genes in the released cultivars through network yield trials conducted with and without fungicide use on aerial plant parts. The data on grain yield and hectoliter weight were obtained from 89 competition field trials of oat cultivars carried out from 2007 to 2014 in nine municipalities of RS. Of the total 89 trials, 44 were carried out with fungicide application on aerial plant parts and 45 were carried out without fungicide application. The annual genetic progress in oat cultivars was studied using the methodology proposed by Vencovsky (1988). The annual genetic progress in oat grain yield was 1.02% with fungicide use and 4.02% without fungicide use during the eight-year study period in RS. The annual genetic progress with respect to the hectoliter weight was 0.08% for trials with fungicide use and 0.71% for trials without fungicide use. Performing network yield trials with and without fungicide use on the aerial plants parts is a feasible method to evaluate the efficiency of oat breeding programs in introducing disease-resistant genes in the released cultivars.

Advances in Japanese pear breeding in Japan

PubMed Central

Saito, Toshihiro

2016-01-01

The Japanese pear (Pyrus pyrifolia Nakai) is one of the most widely grown fruit trees in Japan, and it has been used throughout Japan’s history. The commercial production of pears increased rapidly with the successive discoveries of the chance seedling cultivars ‘Chojuro’ and ‘Nijisseiki’ around 1890, and the development of new cultivars has continued since 1915. The late-maturing, leading cultivars ‘Niitaka’ and ‘Shinko’ were released during the initial breeding stage. Furthermore, systematic breeding by the Horticultural Research Station (currently, NARO Institute of Fruit Tree Science, National Agriculture and Food Research Organization (NIFTS)) began in 1935, which mainly aimed to improve fruit quality by focusing on flesh texture and black spot disease resistance. To date, 22 cultivars have been released, including ‘Kosui’, ‘Hosui’, and ‘Akizuki’, which are current leading cultivars from the breeding program. Four induced mutant cultivars induced by gamma irradiation, which exhibit some resistance to black spot disease, were released from the Institute of Radiation Breeding. Among these cultivars, ‘Gold Nijisseiki’ has become a leading cultivar. Moreover, ‘Nansui’ from the Nagano prefectural institute breeding program was released, and it has also become a leading cultivar. Current breeding objectives at NIFTS mainly combine superior fruit quality with traits related to labor and cost reduction, multiple disease resistance, or self-compatibility. Regarding future breeding, marker-assisted selection for each trait, QTL analyses, genome-wide association studies, and genomic selection analyses are currently in progress. PMID:27069390

Concerted vs. Sequential. Two Activation Patterns of Vast Arrays of Intracellular Ca2+ Channels in Muscle

PubMed Central

Zhou, Jinsong; Brum, Gustavo; González, Adom; Launikonis, Bradley S.; Stern, Michael D.; Ríos, Eduardo

2005-01-01

To signal cell responses, Ca2+ is released from storage through intracellular Ca2+ channels. Unlike most plasmalemmal channels, these are clustered in quasi-crystalline arrays, which should endow them with unique properties. Two distinct patterns of local activation of Ca2+ release were revealed in images of Ca2+ sparks in permeabilized cells of amphibian muscle. In the presence of sulfate, an anion that enters the SR and precipitates Ca2+, sparks became wider than in the conventional, glutamate-based solution. Some of these were “protoplatykurtic” (had a flat top from early on), suggesting an extensive array of channels that activate simultaneously. Under these conditions the rate of production of signal mass was roughly constant during the rise time of the spark and could be as high as 5 μm3 ms−1, consistent with a release current >50 pA since the beginning of the event. This pattern, called “concerted activation,” was observed also in rat muscle fibers. When sulfate was combined with a reduced cytosolic [Ca2+] (50 nM) these sparks coexisted (and interfered) with a sequential progression of channel opening, probably mediated by Ca2+-induced Ca2+ release (CICR). Sequential propagation, observed only in frogs, may require parajunctional channels, of RyR isoform β, which are absent in the rat. Concerted opening instead appears to be a property of RyR α in the amphibian and the homologous isoform 1 in the mammal. PMID:16186560

19 CFR 12.9 - Release for final delivery to consignee.

Code of Federal Regulations, 2010 CFR

2010-04-01

...; DEPARTMENT OF THE TREASURY SPECIAL CLASSES OF MERCHANDISE Meat and Meat-Food Products § 12.9 Release for final delivery to consignee. No meat, meat-food products, or animal casings shall be released for final...

19 CFR 12.9 - Release for final delivery to consignee.

Code of Federal Regulations, 2011 CFR

2011-04-01

...; DEPARTMENT OF THE TREASURY SPECIAL CLASSES OF MERCHANDISE Meat and Meat-Food Products § 12.9 Release for final delivery to consignee. No meat, meat-food products, or animal casings shall be released for final...

AGEs, RAGEs and s-RAGE; friend or foe for cancer.

PubMed

Ahmad, Saheem; Khan, Hamda; Siddiqui, Zeba; Khan, Mohd Yasir; Rehman, Shahnawaz; Shahab, Uzma; Godovikova, Tatyana; Silnikov, Vladimir; Moinuddin

2018-04-01

Impaired awareness of glycation biology in cancer initiation and progression is one of the fundamental reasons for its meticulous investigation of the molecules involved in signalling pathway. Glycation of biological macromolecules results in the progression of advanced glycation end-products (AGEs) that proliferates the process of carcinogenesis by activation of transcription factors and release of cytokines. The receptor for advanced glycation end-products (RAGEs) with the binding of its different ligands like; AGEs, HMGB1 and S100 activate the signalling arrays. The activation of downstream signalling pathway ultimately leads to the pathophysiological conditions of diabetes, ageing, neurological disorders and cancers as well as a result of the activation of transcription factors which is discussed in the main body text of this review. However, there might be a likelihood of the positive effect of the HMGB1 and S100 proteins in cancer. Still, some untouched mechanisms might be responsible for the establishment of the function of AGE-RAGE or AGE-sRAGE axis activation that leads to the friend-foe association with the cancers. The levels of RAGE and s-RAGE may be a useful biomarker of ligand-RAGE pathway activation and cancer. Thus, the possibility of providing a potential complement to carcinogenesis is very high which might be an interesting target for therapeutic interventions. This article is an insightful assessment on AGE, RAGE and s-RAGE for its possible role in cancer onset and progression. The novel therapeutic targets for cancer prevention or inhibition are also explained in brief in relation to AGE and RAGE. Copyright © 2017 Elsevier Ltd. All rights reserved.

Development of clinical recommendations for progressive return to activity after military mild traumatic brain injury: guidance for rehabilitation providers.

PubMed

McCulloch, Karen L; Goldman, Sarah; Lowe, Lynn; Radomski, Mary Vining; Reynolds, John; Shapiro, Rita; West, Therese A

2015-01-01

Previously published mild traumatic brain injury (mTBI) management guidelines provide very general recommendations to return individuals with mTBI to activity. This lack of specific guidance creates variation in military rehabilitation. The Office of the Army Surgeon General in collaboration with the Defense and Veterans Brain Injury Center, a component center of the Defense Centers of Excellence for Psychological Health and Traumatic Brain Injury, convened an expert working group to review the existing literature and propose clinical recommendations that standardize rehabilitation activity progression following mTBI. A Progressive Activity Working Group consisted of 11 Department of Defense representatives across all service branches, 7 Defense Centers of Excellence for Psychological Health and Traumatic Brain Injury representatives, and 8 academic/research/civilian experts with experience assessing and treating individuals with mTBI for return to activity. An expert working group meeting included the Progressive Activity Working Group and 15 additional subject matter experts. In February 2012, the Progressive Activity Working Group was established to determine the need and purpose of the rehabilitation recommendations. Following literature review, a table was created on the basis of the progression from the Zurich consensus statement on concussion in sport. Issues were identified for discussion with a meeting of the larger expert group during a July 2012 conference. Following development of rehabilitation guidance, the Defense Centers of Excellence for Psychological Health and Traumatic Brain Injury coordinated a similar process for military primary care providers. End products for rehabilitation and primary care providers include specific recommendations for return to activity after concussion. A 6-stage progression specifies activities in physical, cognitive, and balance/vestibular domains and allows for resumption of activity for those with low-level or preinjury symptom complaints. The clinical recommendations for progressive return to activity represent an important effort to standardize activity progression across functional domains and offer providers duty-specific activities to incorporate into intervention. Recommendations were released in January 2014.

Physiologically Based Absorption Modeling to Design Extended-Release Clinical Products for an Ester Prodrug.

PubMed

Ding, Xuan; Day, Jeffrey S; Sperry, David C

2016-11-01

Absorption modeling has demonstrated its great value in modern drug product development due to its utility in understanding and predicting in vivo performance. In this case, we integrated physiologically based modeling in the development processes to effectively design extended-release (ER) clinical products for an ester prodrug LY545694. By simulating the trial results of immediate-release products, we delineated complex pharmacokinetics due to prodrug conversion and established an absorption model to describe the clinical observations. This model suggested the prodrug has optimal biopharmaceutical properties to warrant developing an ER product. Subsequently, we incorporated release profiles of prototype ER tablets into the absorption model to simulate the in vivo performance of these products observed in an exploratory trial. The models suggested that the absorption of these ER tablets was lower than the IR products because the extended release from the formulations prevented the drug from taking advantage of the optimal absorption window. Using these models, we formed a strategy to optimize the ER product to minimize the impact of the absorption window limitation. Accurate prediction of the performance of these optimized products by modeling was confirmed in a third clinical trial.

Mechanism of Mg2+-Accompanied Product Release in Sugar Nucleotidyltransferases.

PubMed

Vithani, Neha; Ankush Jagtap, Pravin Kumar; Verma, Sunil Kumar; Tripathi, Ravi; Awasthi, Shalini; Nair, Nisanth N; Prakash, Balaji

2018-03-06

The nucleotidyl transfer reaction, catalyzed by sugar nucleotidyltransferases (SNTs), is assisted by two active site Mg 2+ ions. While studying this reaction using X-ray crystallography, we captured snapshots of the pyrophosphate (product) as it exits along a pocket. Surprisingly, one of the active site Mg 2+ ions remains coordinated to the exiting pyrophosphate. This hints at the participation of Mg 2+ in the process of product release, besides its role in catalyzing nucleotidyl transfer. These observations are further supported by enhanced sampling molecular dynamics simulations. Free energy computations suggest that the product release is likely to be rate limiting in SNTs, and the origin of the high free energy barrier for product release could be traced back to the "slow" conformational change of an Arg residue at the exit end of the pocket. These results establish a dual role for Mg 2+ , and propose a general mechanism of product release during the nucleotidyl transfer by SNTs. Copyright © 2018 Elsevier Ltd. All rights reserved.

Hyperforin is a modulator of inducible nitric oxide synthase and phagocytosis in microglia and macrophages.

PubMed

Kraus, Birgit; Wolff, Horst; Elstner, Erich F; Heilmann, Jörg

2010-06-01

Upon activation, microglia, the immunocompetent cells in the brain, get highly phagocytic and release pro-inflammatory mediators like nitric oxide (NO). Excessive NO production is pivotal in neurodegenerative disorders, and there is evidence that abnormalities in NO production and inflammatory responses may at least support a range of neuropsychiatric disorders, including depression. Although extracts of St. John's wort (Hypericum perforatum L.) have been used for centuries in traditional medicine, notably for the treatment of depression, there is still considerable lack in scientific knowledge about the impact on microglia. We used N11 and BV2 mouse microglia, as well as RAW 264.7 macrophages to investigate the effects of St. John's wort extract and constituents thereof on NO production Moreover, flow cytometry and fluorescence microscopy were employed to analyze the influence on phagocytosis, transcription factor activation states, and cell motility. We found that extracts of St. John's wort efficiently suppress lipopolysaccharide-induced NO release and identified hyperforin as the responsible compound, being effective at concentrations between 0.25 and 0.75 microM. The reduced NO production was mediated by diminished inducible nitric oxide synthase expression on the mRNA and protein level. In addition, at similar concentrations, hyperforin reduced zymosan phygocytosis to 20-40% and putatively acted by downregulating the CD206 macrophage mannose receptor and modulation of cell motility. We found that the observed effects correlate with a suppression of the activated state of Nf-kappaB and phospho-CREB, while c-JUN, STAT1, and HIF-1alpha activity and cyclooxygenase-2 expression remained unaffected by hyperforin. These results reveal that hyperforin influences pro-inflammatory and immunological responses of microglia that are involved in the progression of neuropathologic disorders.

Progress on Fabrication of Planar Diffusion Couples with Representative TRISO PyC/SiC Microstructure

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

Hunn, John D.; Jolly, Brian C.; Gerczak, Tyler J.

Release of fission products from tristructural-isotropic (TRISO) coated particle fuel limits the fuel’s operational lifetime and creates potential safety and maintenance concerns. A need for diffusion analysis in representative TRISO layers exists to provide fuel performance models with high fidelity data to improve fuel performance and efficiency. An effort has been initiated to better understand fission product transport in, and release from, quality TRISO fuel by investigating diffusion couples with representative pyrocarbon (PyC) and silicon carbide (SiC). Here planar PyC/SiC diffusion couples are being developed with representative PyC/SiC layers using a fluidized bed chemical vapor deposition (FBCVD) system identical tomore » those used to produce laboratory-scale TRISO fuel for the Advanced Gas Reactor Fuel Qualification and Development Program’s (AGR) first fuel irradiation. The diffusivity of silver, the silver and palladium system, europium, and strontium in the PyC/SiC will be studied at elevated temperatures and under high temperature neutron irradiation. The study also includes a comparative study of PyC/SiC diffusion couples with varying TRISO layer properties to understand the influence of SiC microstructure (grain size) and the PyC/SiC interface on fission product transport. The first step in accomplishing these goals is the development of the planar diffusion couples. The diffusion couple construction consists of multiple steps which includes fabrication of the primary PyC/SiC structures with targeted layer properties, introduction of fission product species and seal coating to create an isolated system. Coating development has shown planar PyC/SiC diffusion couples with similar properties to AGR TRISO fuel can be produced. A summary of the coating development process, characterization methods, and status are presented.« less

Nanostructural control of methane release in kerogen and its implications to wellbore production decline

NASA Astrophysics Data System (ADS)

Ho, Tuan Anh; Criscenti, Louise J.; Wang, Yifeng

2016-06-01

Despite massive success of shale gas production in the US in the last few decades there are still major concerns with the steep decline in wellbore production and the large uncertainty in a long-term projection of decline curves. A reliable projection must rely on a mechanistic understanding of methane release in shale matrix-a limiting step in shale gas extraction. Using molecular simulations, we here show that methane release in nanoporous kerogen matrix is characterized by fast release of pressurized free gas (accounting for ~30-47% recovery) followed by slow release of adsorbed gas as the gas pressure decreases. The first stage is driven by the gas pressure gradient while the second stage is controlled by gas desorption and diffusion. We further show that diffusion of all methane in nanoporous kerogen behaves differently from the bulk phase, with much smaller diffusion coefficients. The MD simulations also indicate that a significant fraction (3-35%) of methane deposited in kerogen can potentially become trapped in isolated nanopores and thus not recoverable. Our results shed a new light on mechanistic understanding gas release and production decline in unconventional reservoirs. The long-term production decline appears controlled by the second stage of gas release.

A Nitrogen Inventory of Major Water Regions Across the USA as a Benchmark for Future Progress in Mitigating Nitrogen Pollution

NASA Astrophysics Data System (ADS)

Boyer, E. W.; Galloway, J. N.; Alexander, R. B.

2012-12-01

We present a contemporary inventory of reactive nitrogen (Nr) inputs and, air, and surface waters throughout major water regions in the United States. Inputs of Nr to the nation and the world have been increasing, largely due to human activities associated with food production and energy consumption via the combustion of fossil fuels and biofuels. Despite the obvious essential benefits of a plentiful supply of food and energy, the adverse consequences associated with the accumulation of Nr in the environment are large. Most of the Nr created by anthropogenic activities is released to the environment, often with unintended negative consequences. The greater the inputs of Nr to the landscape, the greater the potential for negative effects, caused by greenhouse gas production, ground level ozone, acid deposition, and Nr overload that can contribute to climate change, degradation of soils and vegetation, acidification of surface waters, coastal eutrophication, hypoxia and habitat loss. Here, we present a consistent accounting method for quantifying Nr sources and transport that was used in our inventory, and discuss associated data needs for tallying Nr inputs at regional scales. The inventory is a necessary tool for exploring the role of Nr contributed to the environment from various sources (e.g., from fertilizers, manure, biological fixation, human waste, atmospheric deposition) and from various industrial sectors (e.g., from agriculture, transportation, electricity generation). Agriculture and use of fertilizers to produce food, feed, and fiber (including bioenergy and biological nitrogen fixation) and combustion of fossil fuels are the largest sources of Nr released into the environment in the USA. Our inventory can be used as a benchmark of the current Nr situation against which future progress can be assessed in varying regions of the country, amidst changing Nr inputs and implementation of policy and management strategies to mitigate Nr pollution.

A contemporary national nitrogen inventory as a benchmark for future progress in mitigating nitrogen pollution in the USA

NASA Astrophysics Data System (ADS)

Boyer, E. W.; Galloway, J. N.; Theis, T.; Alexander, R. B.

2011-12-01

We present a contemporary inventory of reactive nitrogen (Nr) inputs to land, air, and water in the United States. Inputs of Nr to the nation and the world have been increasing, largely due to human activities associated with food production and energy consumption via the combustion of fossil fuels and biofuels. Despite the obvious essential benefits of a plentiful supply of food and energy, the adverse consequences associated with the accumulation of Nr in the environment are large. Most of the Nr created by anthropogenic activities is released to the environment, often with unintended negative consequences. The greater the inputs of Nr to the landscape, the greater the potential for negative effects, caused by greenhouse gas production, ground level ozone, acid deposition, and Nr overload that can contribute to climate change, degradation of soils and vegetation, acidification of surface waters, coastal eutrophication, hypoxia and habitat loss. Here, we present a consistent accounting method for quantifying Nr sources and transport that was used in our inventory, and discuss associated data needs for tallying Nr inputs at regional scales. The inventory is a necessary tool for exploring the role of Nr contributed to the environment from various sources (e.g., from fertilizers, manure, biological fixation, human waste, atmospheric deposition) and from various industrial sectors (e.g., from agriculture, transportation, electricity generation). Agriculture and use of fertilizers to produce food, feed, and fiber (including bioenergy and biological nitrogen fixation) and combustion of fossil fuels are the largest sources of Nr released into the environment in the USA. Our inventory is currently being used by the U.S. Environmental Protection Agency as a benchmark of the current Nr situation against which future progress can be assessed -- amidst changing Nr inputs and implementation of policy and management strategies to mitigate Nr pollution.

Life Cycle Assessment and Release Studies for 15 Nanosilver-Enabled Consumer Products: Investigating Hotspots and Patterns of Contribution.

PubMed

Pourzahedi, Leila; Vance, Marina; Eckelman, Matthew J

2017-06-20

Increasing use of silver nanoparticles (AgNPs) in consumer products as antimicrobial agents has prompted extensive research toward the evaluation of their potential release to the environment and subsequent ecotoxicity to aquatic organisms. It has also been shown that AgNPs can pose significant burdens to the environment from life cycle emissions associated with their production, but these impacts must be considered in the context of actual products that contain nanosilver. Here, a cradle-to-gate life cycle assessment for the production of 15 different AgNP-enabled consumer products was performed, coupled with release studies of those same products, thus providing a consistent analytical platform for investigation of potential nanosilver impacts across a range of product types and concentrations. Environmental burdens were assessed over multiple impact categories defined by the United States Environmental Protection Agency's Tool for the Reduction and Assessment of Chemical and Other Environmental Impacts (TRACI 2.1) method. Depending on the product composition and silver loading, the contribution of AgNP synthesis to the overall impacts was seen to vary over a wide range from 1% to 99%. Release studies found that solid polymeric samples lost more silver during wash compared to fibrous materials. Estimates of direct ecotoxicity impacts of AgNP releases from those products with the highest leaching rates resulted in lower impact levels compared to cradle-to-gate ecotoxicity from production for those products. Considering both cradle-to-gate production impacts and nanoparticle release studies, in conjunction with estimates of life cycle environmental and health benefits of nanoparticle incorporation, can inform sustainable nanoenabled product design.

Background and Recent Progress in Anomalous Transport Simulation

DTIC Science & Technology

2017-07-19

NUMBER (Include area code) 19 July 2017 Briefing Charts 14 June 2017 - 19 July 2017 Background and Recent Progress in Anomalous Transport Simulation ...and Recent Progress in Anomalous Transport Simulation 19 Jul 2017 Justin Koo AFRL/RQRS Edwards AFB, CA 2DISTRIBUTION A: Approved for public release...Baalrud, S.D. and Chabert, P., “Theory for the anomalous electron transport in Hall effect thrusters. I. Insights from particle-in-cell simulations

Source term estimates of radioxenon released from the BaTek medical isotope production facility using external measured air concentrations.

PubMed

Eslinger, Paul W; Cameron, Ian M; Dumais, Johannes Robert; Imardjoko, Yudi; Marsoem, Pujadi; McIntyre, Justin I; Miley, Harry S; Stoehlker, Ulrich; Widodo, Susilo; Woods, Vincent T

2015-10-01

BATAN Teknologi (BaTek) operates an isotope production facility in Serpong, Indonesia that supplies (99m)Tc for use in medical procedures. Atmospheric releases of (133)Xe in the production process at BaTek are known to influence the measurements taken at the closest stations of the radionuclide network of the International Monitoring System (IMS). The purpose of the IMS is to detect evidence of nuclear explosions, including atmospheric releases of radionuclides. The major xenon isotopes released from BaTek are also produced in a nuclear explosion, but the isotopic ratios are different. Knowledge of the magnitude of releases from the isotope production facility helps inform analysts trying to decide if a specific measurement result could have originated from a nuclear explosion. A stack monitor deployed at BaTek in 2013 measured releases to the atmosphere for several isotopes. The facility operates on a weekly cycle, and the stack data for June 15-21, 2013 show a release of 1.84 × 10(13) Bq of (133)Xe. Concentrations of (133)Xe in the air are available at the same time from a xenon sampler located 14 km from BaTek. An optimization process using atmospheric transport modeling and the sampler air concentrations produced a release estimate of 1.88 × 10(13) Bq. The same optimization process yielded a release estimate of 1.70 × 10(13) Bq for a different week in 2012. The stack release value and the two optimized estimates are all within 10% of each other. Unpublished production data and the release estimate from June 2013 yield a rough annual release estimate of 8 × 10(14) Bq of (133)Xe in 2014. These multiple lines of evidence cross-validate the stack release estimates and the release estimates based on atmospheric samplers. Copyright © 2015 Elsevier Ltd. All rights reserved.

Straight A's: Public Education Policy and Progress. Volume 4, Number 17

ERIC Educational Resources Information Center

Amos, Jason, Ed.

2004-01-01

"Straight A's: Public Education Policy and Progress" is a biweekly newsletter that focuses on education news and events both in Washington, DC and around the country. The following articles are included in this issue: (1) "Profiles in Leadership": Alliance Releases a Collection of Essays from America's Foremost Education…

Inflammatory Mechanisms and Oxidative Stress as Key Factors Responsible for Progression of Neurodegeneration: Role of Brain Innate Immune System.

PubMed

Leszek, Jerzy; Barreto, George E; Gąsiorowski, Kazimierz; Koutsouraki, Euphrosyni; Ávila-Rodrigues, Marco; Aliev, Gjumrakch

2016-01-01

Chronic inflammation is characterized by longstanding microglial activation followed by sustained release of inflammatory mediators, which aid in enhanced nitrosative and oxidative stress. The sustained release of inflammatory mediators propels the inflammatory cycle by increased microglial activation, promoting their proliferation and thus stimulating enhanced release of inflammatory factors. Elevated levels of several cytokines and chronic neuroinflammation have been associated with many neurodegenerative disorders of central nervous system like age-related macular degeneration, Alzheimer disease, multiple sclerosis, Parkinson's disease, Huntington' disease, and tauopathies. This review highlights the basic mechanisms of neuroinflammation, the characteristics of neurodegenerative diseases, and the main immunologic responses in CNS neurodegenerative disorders. A comprehensive outline for the crucial role of microglia in neuroinflammation and neurodegeneration and the role of Toll-like receptor signalling in coexistence of inflammatory mechanisms and oxidative stress as major factors responsible for progression of neurodegeneration have also been presented.

Estimates of Radioxenon Released from Southern Hemisphere Medical isotope Production Facilities Using Measured Air Concentrations and Atmospheric Transport Modeling

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

Eslinger, Paul W.; Friese, Judah I.; Lowrey, Justin D.

2014-09-01

Abstract The International Monitoring System (IMS) of the Comprehensive-Nuclear-Test-Ban-Treaty monitors the atmosphere for radioactive xenon leaking from underground nuclear explosions. Emissions from medical isotope production represent a challenging background signal when determining whether measured radioxenon in the atmosphere is associated with a nuclear explosion prohibited by the treaty. The Australian Nuclear Science and Technology Organisation (ANSTO) operates a reactor and medical isotope production facility in Lucas Heights, Australia. This study uses two years of release data from the ANSTO medical isotope production facility and Xe-133 data from three IMS sampling locations to estimate the annual releases of Xe-133 from medicalmore » isotope production facilities in Argentina, South Africa, and Indonesia. Atmospheric dilution factors derived from a global atmospheric transport model were used in an optimization scheme to estimate annual release values by facility. The annual releases of about 6.8×1014 Bq from the ANSTO medical isotope production facility are in good agreement with the sampled concentrations at these three IMS sampling locations. Annual release estimates for the facility in South Africa vary from 1.2×1016 to 2.5×1016 Bq and estimates for the facility in Indonesia vary from 6.1×1013 to 3.6×1014 Bq. Although some releases from the facility in Argentina may reach these IMS sampling locations, the solution to the objective function is insensitive to the magnitude of those releases.« less

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.

Dual-Functionalization Device for Therapy through Dopamine Release and Monitoring.

PubMed

Fabregat, Georgina; Giménez, Alessia; Díaz, Angélica; Puiggalí, Jordi; Alemán, Carlos

2018-05-01

A dual-functional device is fabricated to release progressively dopamine (DA) from a biohydrogel under real-time monitoring via electrochemical detection. For this purpose, a poly-γ-glutamic acid biohydrogel is assembled with a poly(3,4-ethylenedioxythiophene) (PEDOT) layer, previously deposited onto a screen printed electrode. The biohydrogel is formulated to achieve dimensional stability and maximum DA-loading capacity. Conditions for DA-loading are influenced by the oxidation of the neurotransmitter in acid environments and the poor resistance of PEDOT to the lyophilization. The performance of the device is proved in a medium with the physiological pH of blood and the cerebrospinal fluid. The progressive release of DA is successfully monitored by the device, the limit of detection and sensitivity of the integrated sensor being 450 × 10 -9 m and 8 × 10 -5 mA µm -1 , respectively. The effect of electrochemical stimulation in the kinetics of the DA release is also investigated applying potential ramps in cyclic phase to alter the biohydrogel morphology. © 2018 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

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

Pirhonen, P.

Life-cycle assessment is usually based on regular discharges that occur at a more or less constant rate. Nevertheless, the more factors that are taken into account in the LCA the better picture it gives on the environmental aspects of a product. In this study an approach to incorporate accidental releases into a products` life-cycle assessment was developed. In this approach accidental releases are divided into two categories. The first category consists of those unplanned releases which occur with a predicted level and frequency. Due to the high frequency and small release size at a time, these accidental releases can bemore » compared to continuous emissions. Their global impacts are studied in this approach. Accidental releases of the second category are sudden, unplanned releases caused by exceptional situations, e.g. technical failure, action error or disturbances in process conditions. These releases have a singular character and local impacts are typical of them. As far as the accidental releases of the second category are concerned, the approach introduced in this study results in a risk value for every stage of a life-cycle, the sum of which is a risk value for the whole life-cycle. Risk value is based on occurrence frequencies of incidents and potential environmental damage caused by releases. Risk value illustrates the level of potential damage caused by accidental releases related to the system under study and is meant to be used for comparison of these levels of two different products. It can also be used to compare the risk levels of different stages of the life-cycle. An approach was illustrated using petrol as an example product. The whole life-cycle of petrol from crude oil production to the consumption of petrol was studied.« less

Scaffold-mediated BMP-2 minicircle DNA delivery accelerated bone repair in a mouse critical-size calvarial defect model.

PubMed

Keeney, Michael; Chung, Michael T; Zielins, Elizabeth R; Paik, Kevin J; McArdle, Adrian; Morrison, Shane D; Ransom, Ryan C; Barbhaiya, Namrata; Atashroo, David; Jacobson, Gunilla; Zare, Richard N; Longaker, Michael T; Wan, Derrick C; Yang, Fan

2016-08-01

Scaffold-mediated gene delivery holds great promise for tissue regeneration. However, previous attempts to induce bone regeneration using scaffold-mediated non-viral gene delivery rarely resulted in satisfactory healing. We report a novel platform with sustained release of minicircle DNA (MC) from PLGA scaffolds to accelerate bone repair. MC was encapsulated inside PLGA scaffolds using supercritical CO2 , which showed prolonged release of MC. Skull-derived osteoblasts transfected with BMP-2 MC in vitro result in higher osteocalcin gene expression and mineralized bone formation. When implanted in a critical-size mouse calvarial defect, scaffolds containing luciferase MC lead to robust in situ protein production up to at least 60 days. Scaffold-mediated BMP-2 MC delivery leads to substantially accelerated bone repair as early as two weeks, which continues to progress over 12 weeks. This platform represents an efficient, long-term nonviral gene delivery system, and may be applicable for enhancing repair of a broad range of tissues types. © 2016 Wiley Periodicals, Inc. J Biomed Mater Res Part A: 104A: 2099-2107, 2016. © 2016 Wiley Periodicals, Inc.

IGF-1 Receptor Differentially Regulates Spontaneous and Evoked Transmission via Mitochondria at Hippocampal Synapses

PubMed Central

Gazit, Neta; Vertkin, Irena; Shapira, Ilana; Helm, Martin; Slomowitz, Edden; Sheiba, Maayan; Mor, Yael; Rizzoli, Silvio; Slutsky, Inna

2016-01-01

Summary The insulin-like growth factor-1 receptor (IGF-1R) signaling is a key regulator of lifespan, growth, and development. While reduced IGF-1R signaling delays aging and Alzheimer’s disease progression, whether and how it regulates information processing at central synapses remains elusive. Here, we show that presynaptic IGF-1Rs are basally active, regulating synaptic vesicle release and short-term plasticity in excitatory hippocampal neurons. Acute IGF-1R blockade or transient knockdown suppresses spike-evoked synaptic transmission and presynaptic cytosolic Ca2+ transients, while promoting spontaneous transmission and resting Ca2+ level. This dual effect on transmitter release is mediated by mitochondria that attenuate Ca2+ buffering in the absence of spikes and decrease ATP production during spiking activity. We conclude that the mitochondria, activated by IGF-1R signaling, constitute a critical regulator of information processing in hippocampal neurons by maintaining evoked-to-spontaneous transmission ratio, while constraining synaptic facilitation at high frequencies. Excessive IGF-1R tone may contribute to hippocampal hyperactivity associated with Alzheimer’s disease. Video Abstract PMID:26804996

Aerobic Exercise Modulates the Free Fatty Acids and Inflammatory Response During Obesity and Cancer Cachexia.

PubMed

Teixeira, Alexandre Abilio de Souza; Lira, Fábio Santos; Pimentel, Gustavo D; Oliveira de Souza, Camila; Batatinha, Helena; Biondo, Luana A; Yamashita, Alex S; Junior, Edson A Lima; Neto, José Cesar Rosa

2016-01-01

White adipose tissue (WAT) is no longer considered a tissue whose main function is the storage of TAG. Since the discovery of leptin in 1994, several studies have elucidated the important role of WAT as an endocrine organ, the source of the adipokines. The low-grade inflammation observed in obese and cancer cachexia patients is explained, at least partially, by the exacerbated release of proinflammatory adipokines. Despite of the recent progress in the characterization of the various adipokines and lipokines produced by WAT, little is known about the mechanisms regulating the secretion of these molecules in different physiological and pathological circumstances. Chronic exercise is a nonpharmacological therapy employed in several chronic diseases and shows an anti-inflammatory effect through the regulation of the cytokine network. In this review, we address the potential mechanisms by which the aerobic physical exercise modulate the production and release of inflammatory adipokines, as well as the inflammation-lipolysis axis in WAT, with special focus in the therapeutic role of exercise in obesity-associated insulin resistance and cancer cachexia.

Release of cellular tension signals self-restorative ventral lamellipodia to heal barrier micro-wounds

PubMed Central

Martinelli, Roberta; Kamei, Masataka; Sage, Peter T.; Massol, Ramiro; Varghese, Laya; Sciuto, Tracey; Toporsian, Mourad; Dvorak, Ann M.; Kirchhausen, Tomas; Springer, Timothy A.

2013-01-01

Basic mechanisms by which cellular barriers sense and respond to integrity disruptions remain poorly understood. Despite its tenuous structure and constitutive exposure to disruptive strains, the vascular endothelium exhibits robust barrier function. We show that in response to micrometer-scale disruptions induced by transmigrating leukocytes, endothelial cells generate unique ventral lamellipodia that propagate via integrins toward and across these “micro-wounds” to close them. This novel actin remodeling activity progressively healed multiple micro-wounds in succession and changed direction during this process. Mechanical probe-induced micro-wounding of both endothelia and epithelia suggests that ventral lamellipodia formed as a response to force imbalance and specifically loss of isometric tension. Ventral lamellipodia were enriched in the Rac1 effectors cortactin, IQGAP, and p47Phox and exhibited localized production of hydrogen peroxide. Together with Apr2/3, these were functionally required for effective micro-wound healing. We propose that barrier disruptions are detected as local release of isometric tension/force unloading, which is directly coupled to reactive oxygen species–dependent self-restorative actin remodeling dynamics. PMID:23629967

Model Based Definition

NASA Technical Reports Server (NTRS)

Rowe, Sidney E.

2010-01-01

In September 2007, the Engineering Directorate at the Marshall Space Flight Center (MSFC) created the Design System Focus Team (DSFT). MSFC was responsible for the in-house design and development of the Ares 1 Upper Stage and the Engineering Directorate was preparing to deploy a new electronic Configuration Management and Data Management System with the Design Data Management System (DDMS) based upon a Commercial Off The Shelf (COTS) Product Data Management (PDM) System. The DSFT was to establish standardized CAD practices and a new data life cycle for design data. Of special interest here, the design teams were to implement Model Based Definition (MBD) in support of the Upper Stage manufacturing contract. It is noted that this MBD does use partially dimensioned drawings for auxiliary information to the model. The design data lifecycle implemented several new release states to be used prior to formal release that allowed the models to move through a flow of progressive maturity. The DSFT identified some 17 Lessons Learned as outcomes of the standards development, pathfinder deployments and initial application to the Upper Stage design completion. Some of the high value examples are reviewed.

Dissolution of Intact, Divided and Crushed Circadin Tablets: Prolonged vs. Immediate Release of Melatonin.

PubMed

Chua, Hui Ming; Hauet Richer, Nathalie; Swedrowska, Magda; Ingham, Stephen; Tomlin, Stephen; Forbes, Ben

2016-01-07

Circadin 2 mg prolonged-release tablet is the only licensed melatonin product available in the UK. Circadin is indicated for patients with primary insomnia aged 55 and over, but is more widely used "off-label" to treat sleep disorders especially in the paediatric population. Children and older people often have difficulty swallowing tablets and dividing the tablet is sometimes required to ease administration. The aim of this study was to measure the release profile of melatonin from Circadin tablets when divided or crushed, and compare this with release from intact tablets. Dissolution testing was also performed for unlicensed melatonin products for comparison. Dissolution tests were performed using the pharmacopoeial paddle apparatus, with melatonin release analyzed by high performance liquid chromatography. Melatonin content, hardness, friability, and disintegration of the products were also evaluated. The prolonged release of melatonin from Circadin tablets was unlike that of any other product tested. When divided into halves, Circadin preserved most of the prolonged-release characteristic (f2 = 58), whereas quarter-cut and crushed tablet had a more immediate melatonin release profile. Circadin is significantly less expensive and should be preferred to unlicensed medicines which are not pharmaceutically equivalent and offer less quality assurance.

MELCOR computer code manuals: Primer and user`s guides, Version 1.8.3 September 1994. Volume 1

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

Summers, R.M.; Cole, R.K. Jr.; Smith, R.C.

1995-03-01

MELCOR is a fully integrated, engineering-level computer code that models the progression of severe accidents in light water reactor nuclear power plants. MELCOR is being developed at Sandia National Laboratories for the US Nuclear Regulatory Commission as a second-generation plant risk assessment tool and the successor to the Source Term Code Package. A broad spectrum of severe accident phenomena in both boiling and pressurized water reactors is treated in MELCOR in a unified framework. These include: thermal-hydraulic response in the reactor coolant system, reactor cavity, containment, and confinement buildings; core heatup, degradation, and relocation; core-concrete attack; hydrogen production, transport, andmore » combustion; fission product release and transport; and the impact of engineered safety features on thermal-hydraulic and radionuclide behavior. Current uses of MELCOR include estimation of severe accident source terms and their sensitivities and uncertainties in a variety of applications. This publication of the MELCOR computer code manuals corresponds to MELCOR 1.8.3, released to users in August, 1994. Volume 1 contains a primer that describes MELCOR`s phenomenological scope, organization (by package), and documentation. The remainder of Volume 1 contains the MELCOR Users` Guides, which provide the input instructions and guidelines for each package. Volume 2 contains the MELCOR Reference Manuals, which describe the phenomenological models that have been implemented in each package.« less

Correlation of recent fission product release data

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

Kress, T.S.; Lorenz, R.A.; Nakamura, T.

For the calculation of source terms associated with severe accidents, it is necessary to model the release of fission products from fuel as it heats and melts. Perhaps the most definitive model for fission product release is that of the FASTGRASS computer code developed at Argonne National Laboratory. There is persuasive evidence that these processes, as well as additional chemical and gas phase mass transport processes, are important in the release of fission products from fuel. Nevertheless, it has been found convenient to have simplified fission product release correlations that may not be as definitive as models like FASTGRASS butmore » which attempt in some simple way to capture the essence of the mechanisms. One of the most widely used such correlation is called CORSOR-M which is the present fission product/aerosol release model used in the NRC Source Term Code Package. CORSOR has been criticized as having too much uncertainty in the calculated releases and as not accurately reproducing some experimental data. It is currently believed that these discrepancies between CORSOR and the more recent data have resulted because of the better time resolution of the more recent data compared to the data base that went into the CORSOR correlation. This document discusses a simple correlational model for use in connection with NUREG risk uncertainty exercises. 8 refs., 4 figs., 1 tab.« less

YUCCA Mountain Project - Argonne National Laboratory, Annual Progress Report, FY 1997 for activity WP 1221 unsaturated drip condition testing of spent fuel and unsaturated dissolution tests of glass.

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

Bates, J. K.; Buck, E. C.; Emery, J. W.

1998-09-18

This document reports on the work done by the Nuclear Waste Management Section of the Chemical Technology Division of Argonne National Laboratory in the period of October 1996 through September 1997. Studies have been performed to evaluate the behavior of nuclear waste glass and spent fuel samples under the unsaturated conditions (low-volume water contact) that are likely to exist in the Yucca Mountain environment being considered as a potential site for a high-level waste repository. Tests with actinide-doped waste glasses, in progress for over 11 years, indicate that the transuranic element release is dominated by colloids that continuously form andmore » span from the glass surface. The nature of the colloids that form in the glass and spent fuel testing programs is being investigated by dynamic light scattering to determine the size distribution, by autoradiography to determine the chemistry, and by zeta potential to measure the electrical properties of the colloids. Tests with UO{sub 2} have been ongoing for 12 years. They show that the oxidation of UO{sub 2} occurs rapidly, and the resulting paragenetic sequence of secondary phases forming on the sample surface is similar to that observed for uranium found in natural oxidizing environments. The reaction of spent fuel samples in conditions similar to those used with UO{sub 2} have been in progress for over six years, and the results suggest that spent fuel forms many of the same alteration products as UO{sub 2}. With spent fuel, the bulk of the reaction occurs via a through-grain reaction process, although grain boundary attack is sufficient to have reacted all of the grain boundary regions in the samples. New test methods are under development to evaluate the behavior of spent fuel samples with intact cladding: the rate at which alteration and radionuclide release occurs when water penetrates fuel sections and whether the reaction causes the cladding to split. Alteration phases have been formed on fine grains of UO{sub 2} in contact with small volumes of water within a several month period when the radiolysis product H{sub 2}O{sub 2} is added to the groundwater solution. The test setup has been mocked up for operation with spent fuel in the hot-cell.« less

Mechanism and Kinetics of Inducible Nitric Oxide Synthase Auto-S-Nitrosation and Inactivation†

PubMed Central

Smith, Brian C.; Fernhoff, Nathaniel B.; Marletta, Michael A.

2012-01-01

Nitric oxide (NO), the product of the nitric oxide synthase (NOS) reaction, was previously shown to result in S-nitrosation of the NOS Zn2+-tetrathiolate and inactivation of the enzyme. To probe the potential physiological significance of NOS S-nitrosation, the inactivation timescale of the inducible NOS isoform (iNOS) was determined and found to directly correlate with an increase in iNOS S-nitrosation. A kinetic model of NOS inactivation in which arginine is treated as a suicide substrate was developed. In this model, NO synthesized at the heme cofactor is partitioned between release into solution (NO release pathway) and NOS S-nitrosation followed by NOS inactivation (inactivation pathway). Experimentally determined progress curves of NO formation were fit to the model. The NO release pathway was perturbed through addition of the NO traps oxymyoglobin (MbO2) and β2 H-NOX, which yielded partition ratios between NO release and inactivation of ~100 at 4 μM MbO2 and ~22,000 at saturating trap concentrations. The results suggest that a portion of the NO synthesized at the heme cofactor reacts with the Zn2+-tetrathiolate without being released into solution. Perturbation of the inactivation pathway through addition of the reducing agents GSH or TCEP resulted in a concentration-dependent decrease in iNOS S-nitrosation that directly correlated with protection from iNOS inactivation. iNOS inactivation was most responsive to physiological concentrations of GSH with an apparent Km value of 13 mM. NOS turnover that leads to NOS S-nitrosation might be a mechanism to control NOS activity, and NOS S-nitrosation could play a role in the physiological generation of nitrosothiols. PMID:22242685

Ghrelin and cancer progression.

PubMed

Lin, Tsung-Chieh; Hsiao, Michael

2017-08-01

Ghrelin is a small peptide with 28 amino acids, and has been characterized as the ligand of the growth hormone secretagogue receptor (GHSR). In addition to its original function in stimulating pituitary growth hormone release, ghrelin is multifunctional and plays a role in the regulation of energy balance, gastric acid release, appetite, insulin secretion, gastric motility and the turnover of gastric and intestinal mucosa. The discovery of ghrelin and GHSR expression beyond normal tissues suggests its role other than physiological function. Emerging evidences have revealed ghrelin's function in regulating several processes related to cancer progression, especially in metastasis and proliferation. We further show the relative GHRL and GHSR expression in pan-cancers from The Cancer Genome Atlas (TCGA), suggesting the potential pathological role of the axis in cancers. This review focuses on ghrelin's biological function in cancer progression, and reveals its clinical significance especially the impact on cancer patient outcome. Copyright © 2017 The Authors. Published by Elsevier B.V. All rights reserved.

Fission product release from fuel under LWR accident conditions

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

Osborne, M.F.; Lorenz, R.A.; Norwood, K.S.

Three tests have provided additional data on fission product release under LWR accident conditions in a temperature range (1400 to 2000/sup 0/C). In the release rate data are compared with curves from a recent NRC-sponsored review of available fission product release data. Although the iodine release in test HI-3 was inexplicably low, the other data points for Kr, I, and Cs fall reasonably close to the corresponding curve, thereby tending to verify the NRC review. The limited data for antimony and silver release fall below the curves. Results of spark source mass spectrometric analyses were in agreement with the gammamore » spectrometric results. Nonradioactive fission products such as Rb and Br appeared to behave like their chemical analogs Cs and I. Results suggest that Te, Ag, Sn, and Sb are released from the fuel in elemental form. Analysis of the cesium and iodine profiles in the thermal gradient tube indicates that iodine was deposited as CsT along with some other less volatile cesium compound. The cesium profiles and chemical reactivity indicate the presence of more than one cesium species.« less

Accuracy of the paracetamol-aminotransferase multiplication product to predict hepatotoxicity in modified-release paracetamol overdose.

PubMed

Wong, Anselm; Sivilotti, Marco L A; Graudins, Andis

2017-06-01

The paracetamol-aminotransferase multiplication product (APAP × ALT) is a risk predictor of hepatotoxicity that is somewhat independent of time and type of ingestion. However, its accuracy following ingestion of modified-release formulations is not known, as the product has been derived and validated after immediate-release paracetamol overdoses. The aim of this retrospective cohort study was to evaluate the accuracy of the multiplication product to predict hepatotoxicity in a cohort of patients with modified-release paracetamol overdose. We assessed all patients with modified-release paracetamol overdose presenting to our hospital network from October 2009 to July 2016. Ingestion of a modified-release formulation was identified by patient self-report or retrieval of the original container. Hepatotoxicity was defined as peak alanine aminotransferase ≥1000 IU/L, and acute liver injury (ALI) as a doubling of baseline ALT to more than 50 IU/L. Of 1989 paracetamol overdose presentations, we identified 73 modified-release paracetamol exposures treated with acetylcysteine. Five patients developed hepatotoxicity, including one who received acetylcysteine within eight hours of an acute ingestion. No patient with an initial multiplication product <10,000 mg/L × IU/L developed hepatotoxicity (sensitivity 100% [95%CI 48%, 100%], specificity 97% [90%, 100%]). Specificity fell to 54% (95%CI: 34, 59%) at a product cut-off point <1500 mg/L × IU/L. When calculated within eight hours of ingestion, mild elevations of the multiplication product fell quickly on repeat testing in patients without ALI or hepatotoxicity. In modified-release paracetamol overdose treated with acetylcysteine, the paracetamol-aminotransferase multiplication product demonstrated similar accuracy and temporal profile to previous reports involving mostly immediate-release formulations. Above a cut-point of 10,000 mg/L × IU/L, it was very strongly associated with the development of acute liver injury and hepatotoxicity, especially when calculated more than eight hours post-ingestion. When below 1500 mg/L × IU/L the likelihood of developing hepatotoxicity was very low. Persistently high serial multiplication product calculations were associated with the greatest risk of hepatotoxicity.

Pharmaceutical Product Lead Optimization for Better In vivo Bioequivalence Performance: A case study of Diclofenac Sodium Extended Release Matrix Tablets.

PubMed

Shahiwala, Aliasgar; Zarar, Aisha

2018-01-01

In order to prove the validity of a new formulation, a considerable amount of effort is required to study bioequivalence, which not only increases the burden of carrying out a number of bioequivalence studies but also eventually increases the cost of the optimization process. The aim of the present study was to develop sustained release matrix tablets containing diclofenac sodium using natural polymers and to demonstrate step by step process of product development till the prediction of in vivo marketed product equivalence of the developed product. Different batches of tablets were prepared by direct compression. In vitro drug release studies were performed as per USP. The drug release data were assessed using model-dependent, modelindependent and convolution approaches. Drug release profiles showed that extended release action were in the following order: Gum Tragacanth > Sodium Alginate > Gum Acacia. Amongst the different batches prepared, only F1 and F8 passed the USP criteria of drug release. Developed formulas were found to fit Higuchi kinetics model with Fickian (case I) diffusion-mediated release mechanism. Model- independent kinetics confirmed that total of four batches were passed depending on the similarity factors based on the comparison with the marketed Diclofenac. The results of in vivo predictive convolution model indicated that predicted AUC, Cmax and Tmax values for batch F8 were similar to that of marketed product. This study provides simple yet effective outline of pharmaceutical product development process that will minimize the formulation development trials and maximize the product success in bioequivalence studies. Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.org.

Toward Higher QA: From Parametric Release of Sterile Parenteral Products to PAT for Other Pharmaceutical Dosage Forms.

PubMed

Hock, Sia Chong; Constance, Neo Xue Rui; Wah, Chan Lai

2012-01-01

Pharmaceutical products are generally subjected to end-product batch testing as a means of quality control. Due to the inherent limitations of conventional batch testing, this is not the most ideal approach for determining the pharmaceutical quality of the finished dosage form. In the case of terminally sterilized parenteral products, the limitations of conventional batch testing have been successfully addressed with the application of parametric release (the release of a product based on control of process parameters instead of batch sterility testing at the end of the manufacturing process). Consequently, there has been an increasing interest in applying parametric release to other pharmaceutical dosage forms, beyond terminally sterilized parenteral products. For parametric release to be possible, manufacturers must be capable of designing quality into the product, monitoring the manufacturing processes, and controlling the quality of intermediates and finished products in real-time. Process analytical technology (PAT) has been thought to be capable of contributing to these prerequisites. It is believed that the appropriate use of PAT tools can eventually lead to the possibility of real-time release of other pharmaceutical dosage forms, by-passing the need for end-product batch testing. Hence, this literature review attempts to present the basic principles of PAT, introduce the various PAT tools that are currently available, present their recent applications to pharmaceutical processing, and explain the potential benefits that PAT can bring to conventional ways of processing and quality assurance of pharmaceutical products. Last but not least, current regulations governing the use of PAT and the manufacturing challenges associated with PAT implementation are also discussed. Pharmaceutical products are generally subjected to end-product batch testing as a means of quality control. Due to the inherent limitations of conventional batch testing, this is not the most ideal approach. In the case of terminally sterilized parenteral products, these limitations have been successfully addressed with the application of parametric release (the release of a product based on control of process parameters instead of batch sterility testing at the end of the manufacturing process). Consequently, there has been an increasing interest in applying parametric release to other pharmaceutical dosage forms. With the advancement of process analytical technology (PAT), it is possible to monitor the manufacturing processes closely. This will eventually enable quality control of the intermediates and finished products, and thus their release in real-time. Hence, this literature review attempts to present the basic principles of PAT, introduce the various PAT tools that are currently available, present their recent applications to pharmaceutical processing, and explain the potential benefits that PAT can bring to conventional ways of processing and quality assurance of pharmaceutical products. It will also discuss the current regulations governing the use of PAT and the manufacturing challenges associated with the implementation of PAT.

No surgery required: the future of feline sterilization: An overview of the Michelson Prize & Grants in Reproductive Biology.

PubMed

Johnston, Shirley; Rhodes, Linda

2015-09-01

For many years, researchers have been studying reproduction of cats and dogs, including approaches to non-surgical sterilization, but scant funding has been available for this work. Recognizing the need to fund research and to attract researchers from the biomedical community to apply their expertise to this area, the Michelson Prize & Grants (MPG) in Reproductive Biology program was founded. Since 2009, it has funded 34 research projects in seven countries toward discovery of a safe single-administration lifetime non-surgical sterilant in male and female cats and dogs. The goal of the MPG program is the reduction or elimination of the approximately 2.7 million deaths of healthy shelter cats and dogs in the US every year. The successful product is expected to be a single-dose injectable product approved by the US Food and Drug Administration as a veterinary prescription item. The most optimistic prediction is that such a product will reach the hands of practicing veterinarians within the next decade. Active research is in progress using approaches such as immunocontraception with a single-administration vaccine against gonadotropin releasing hormone (GnRH). Long-term therapy with GnRH agonists such as deslorelin administered in controlled-release devices is also being studied. Other scientists are targeting cells in the brain or gonads with cytotoxins, such as are used in cancer chemotherapy. Gene therapy expressing proteins that suppress reproduction and gene silencing of peptides essential to reproduction are further avenues of research. Findings are available at www.michelsonprizeandgrants.org/michelson-grants/research-findings. © The Author(s) 2015.

Atmospheric plume progression as a function of time and distance from the release point for radioactive isotopes

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

Eslinger, Paul W.; Bowyer, Ted W.; Cameron, Ian M.

2015-10-01

The International Monitoring System contains up to 80 stations around the world that have aerosol and xenon monitoring systems designed to detect releases of radioactive materials to the atmosphere from nuclear tests. A rule of thumb description of plume concentration and duration versus time and distance from the release point is useful when designing and deploying new sample collection systems. This paper uses plume development from atmospheric transport modeling to provide a power-law rule describing atmospheric dilution factors as a function of distance from the release point.

Inflammatory peroxidases promote breast cancer progression in mice via regulation of the tumour microenvironment.

PubMed

Panagopoulos, Vasilios; Leach, Damien A; Zinonos, Irene; Ponomarev, Vladimir; Licari, Giovanni; Liapis, Vasilios; Ingman, Wendy V; Anderson, Peter; DeNichilo, Mark O; Evdokiou, Andreas

2017-04-01

Myeloperoxidase (MPO) and eosinophil peroxidase (EPO) are heme-containing enzymes, well known for their antimicrobial activity, are released in high quantities by infiltrating immune cells in breast cancer. However, the functional importance of their presence within the tumour microenvironment is unclear. We have recently described a new role for peroxidases as key regulators of fibroblast and endothelial cell functionality. In the present study, we investigate for the first time, the ability of peroxidases to promote breast cancer development and progression. Using the 4T1 syngeneic murine orthotopic breast cancer model, we examined whether increased levels of peroxidases in developing mammary tumours influences primary tumour growth and metastasis. We showed that MPO and EPO stimulation increased mammary tumour growth and enhanced lung metastases, effects that were associated with reduced tumour necrosis, increased collagen deposition and neo-vascularisation within the primary tumour. In vitro, peroxidase treatment, robustly stimulated human mammary fibroblast migration and collagen type I and type VI secretion. Mechanistically, peroxidases induced the transcription of pro-tumorigenic and metastatic MMP1, MMP3 and COX-2 genes. Taken together, these findings identify peroxidases as key contributors to cancer progression by augmenting pro-tumorigenic collagen production and angiogenesis. Importantly, this identifies inflammatory peroxidases as therapeutic targets in breast cancer therapy.

Inventory of Engineered Nanoparticle-Containing Consumer Products Available in the Singapore Retail Market and Likelihood of Release into the Aquatic Environment.

PubMed

Zhang, Yuanyuan; Leu, Yu-Rui; Aitken, Robert J; Riediker, Michael

2015-07-24

Consumer products containing engineered nanoparticles (ENP) are already entering the marketplace. This leads, inter alia, to questions about the potential for release of ENP into the environment from commercial products. We have inventoried the prevalence of ENP-containing consumer products in the Singapore market by carrying out onsite assessments of products sold in all major chains of retail and cosmetic stores. We have assessed their usage patterns and estimated release factors and emission quantities to obtain a better understanding of the quantities of ENP that are released into which compartments of the aquatic environment in Singapore. Products investigated were assessed for their likelihood to contain ENP based on the declaration of ENP by producers, feature descriptions, and the information on particle size from the literature. Among the 1,432 products investigated, 138 were "confirmed" and 293 were "likely" to contain ENP. Product categories included sunscreens, cosmetics, health and fitness, automotive, food, home and garden, clothing and footwear, and eyeglass/lens coatings. Among the 27 different types of nanomaterials identified, SiO2 was predominant, followed by TiO2 and ZnO, Carbon Black, Ag, and Au. The amounts of ENP released into the aquatic system, which was estimated on the basis of typical product use, ENP concentration in the product, daily use quantity, release factor, and market share, were in the range of several hundred tons per year. As these quantities are likely to increase, it will be important to further study the fate of ENP that reach the aquatic environment in Singapore.

Inventory of Engineered Nanoparticle-Containing Consumer Products Available in the Singapore Retail Market and Likelihood of Release into the Aquatic Environment

PubMed Central

Zhang, Yuanyuan; Leu, Yu-Rui; Aitken, Robert J.; Riediker, Michael

2015-01-01

Consumer products containing engineered nanoparticles (ENP) are already entering the marketplace. This leads, inter alia, to questions about the potential for release of ENP into the environment from commercial products. We have inventoried the prevalence of ENP-containing consumer products in the Singapore market by carrying out onsite assessments of products sold in all major chains of retail and cosmetic stores. We have assessed their usage patterns and estimated release factors and emission quantities to obtain a better understanding of the quantities of ENP that are released into which compartments of the aquatic environment in Singapore. Products investigated were assessed for their likelihood to contain ENP based on the declaration of ENP by producers, feature descriptions, and the information on particle size from the literature. Among the 1,432 products investigated, 138 were “confirmed” and 293 were “likely” to contain ENP. Product categories included sunscreens, cosmetics, health and fitness, automotive, food, home and garden, clothing and footwear, and eyeglass/lens coatings. Among the 27 different types of nanomaterials identified, SiO2 was predominant, followed by TiO2 and ZnO, Carbon Black, Ag, and Au. The amounts of ENP released into the aquatic system, which was estimated on the basis of typical product use, ENP concentration in the product, daily use quantity, release factor, and market share, were in the range of several hundred tons per year. As these quantities are likely to increase, it will be important to further study the fate of ENP that reach the aquatic environment in Singapore. PMID:26213957

Total RNA Sequencing Analysis of DCIS Progressing to Invasive Breast Cancer

DTIC Science & Technology

2016-09-01

AWARD NUMBER: W81XWH-14-1-0080 TITLE: Total RNA Sequencing Analysis of DCIS Progressing to Invasive Breast Cancer. PRINCIPAL INVESTIGATOR...PREPARED FOR: U.S. Army Medical Research and Materiel Command Fort Detrick, Maryland 21702-5012 DISTRIBUTION STATEMENT: Approved for Public Release...SUBTITLE Total RNA Sequencing Analysis of DCIS Progressing to Invasive Breast Cancer. 5a. CONTRACT NUMBER 5b. GRANT NUMBER W81XWH-14-1-0080 GRANT11489

HIV-1 Infection Induces Interleukin-1β Production via TLR8 Protein-dependent and NLRP3 Inflammasome Mechanisms in Human Monocytes*

PubMed Central

Guo, Haitao; Gao, Jianmei; Taxman, Debra J.; Ting, Jenny P. Y.; Su, Lishan

2014-01-01

The induction of inflammatory cytokines such as IL-1β is associated with the progression of human immunodeficiency virus, type 1 (HIV-1) disease or AIDS. Unlike most inflammatory cytokines that are regulated by NF-κB at the transcriptional level, production of mature IL-1β also depends on inflammasome activation. The mechanism by which HIV-1 induces pro-IL-1β expression and activates inflammasomes to cleave pro-IL-1β into its bioactive form is not clearly defined. We report here that HIV-1 infection in human monocytes efficiently induced IL-1β expression and inflammasome activation. Toll-like receptor 8 (TLR8) was required for inducing pro-IL-1β expression, whereas the NLRP3 inflammasome was required for IL-1β maturation and release. Furthermore, the lysosomal protease cathepsin B and HIV-1 induced production of reactive oxygen species were critical for HIV-induced inflammasome activation and IL-1β production. HIV-1 entry, reverse transcription, and integration were all required for both pro-IL-1β expression and inflammasome activation. Finally, we show that HIV-1-derived RNA was sufficient to induce both pro-IL-1β expression and inflammasome activation. We conclude that HIV-1 infection induced the expression of pro-IL-1β via TLR8-mediated mechanisms and activated caspase-1 through the NLRP3 inflammasome to cleave pro-IL-1β into bioactive IL-1β. These findings help to elucidate mechanisms of HIV-1 disease progression and identify novel targets for treating HIV-1 induced inflammation and immune activation. PMID:24939850

Nanostructural control of methane release in kerogen and its implications to wellbore production decline

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

Ho, Tuan Anh; Criscenti, Louise J.; Wang, Yifeng

In spite of the massive success of shale gas production in the US in the last few decades there are still major concerns with the steep decline in wellbore production and the large uncertainty in a long-term projection of decline curves. A reliable projection must rely on a mechanistic understanding of methane release in shale matrix–a limiting step in shale gas extraction. Here we show that methane release in nanoporous kerogen matrix is characterized by fast release of pressurized free gas (accounting for ~30–47% recovery) followed by slow release of adsorbed gas as the gas pressure decreases, and we usemore » molecular simulations to demonstrate it. The first stage is driven by the gas pressure gradient while the second stage is controlled by gas desorption and diffusion. We further show that diffusion of all methane in nanoporous kerogen behaves differently from the bulk phase, with much smaller diffusion coefficients. The MD simulations also indicate that a significant fraction (3–35%) of methane deposited in kerogen can potentially become trapped in isolated nanopores and thus not recoverable. Finally, our results shed a new light on mechanistic understanding gas release and production decline in unconventional reservoirs. The long-term production decline appears controlled by the second stage of gas release.« less

Nanostructural control of methane release in kerogen and its implications to wellbore production decline

PubMed Central

Ho, Tuan Anh; Criscenti, Louise J.; Wang, Yifeng

2016-01-01

Despite massive success of shale gas production in the US in the last few decades there are still major concerns with the steep decline in wellbore production and the large uncertainty in a long-term projection of decline curves. A reliable projection must rely on a mechanistic understanding of methane release in shale matrix–a limiting step in shale gas extraction. Using molecular simulations, we here show that methane release in nanoporous kerogen matrix is characterized by fast release of pressurized free gas (accounting for ~30–47% recovery) followed by slow release of adsorbed gas as the gas pressure decreases. The first stage is driven by the gas pressure gradient while the second stage is controlled by gas desorption and diffusion. We further show that diffusion of all methane in nanoporous kerogen behaves differently from the bulk phase, with much smaller diffusion coefficients. The MD simulations also indicate that a significant fraction (3–35%) of methane deposited in kerogen can potentially become trapped in isolated nanopores and thus not recoverable. Our results shed a new light on mechanistic understanding gas release and production decline in unconventional reservoirs. The long-term production decline appears controlled by the second stage of gas release. PMID:27306967

Nanostructural control of methane release in kerogen and its implications to wellbore production decline

DOE PAGES

Ho, Tuan Anh; Criscenti, Louise J.; Wang, Yifeng

2016-06-16

In spite of the massive success of shale gas production in the US in the last few decades there are still major concerns with the steep decline in wellbore production and the large uncertainty in a long-term projection of decline curves. A reliable projection must rely on a mechanistic understanding of methane release in shale matrix–a limiting step in shale gas extraction. Here we show that methane release in nanoporous kerogen matrix is characterized by fast release of pressurized free gas (accounting for ~30–47% recovery) followed by slow release of adsorbed gas as the gas pressure decreases, and we usemore » molecular simulations to demonstrate it. The first stage is driven by the gas pressure gradient while the second stage is controlled by gas desorption and diffusion. We further show that diffusion of all methane in nanoporous kerogen behaves differently from the bulk phase, with much smaller diffusion coefficients. The MD simulations also indicate that a significant fraction (3–35%) of methane deposited in kerogen can potentially become trapped in isolated nanopores and thus not recoverable. Finally, our results shed a new light on mechanistic understanding gas release and production decline in unconventional reservoirs. The long-term production decline appears controlled by the second stage of gas release.« less

Helminths in the gastrointestinal tract as modulators of immunity and pathology

PubMed Central

Varyani, Fumi; Fleming, John O.

2017-01-01

Helminth parasites are highly prevalent in many low- and middle-income countries, in which inflammatory bowel disease and other immunopathologies are less frequent than in the developed world. Many of the most common helminths establish themselves in the gastrointestinal tract and can exert counter-inflammatory influences on the host immune system. For these reasons, interest has arisen as to how parasites may ameliorate intestinal inflammation and whether these organisms, or products they release, could offer future therapies for immune disorders. In this review, we discuss interactions between helminth parasites and the mucosal immune system, as well as the progress being made toward identifying mechanisms and molecular mediators through which it may be possible to attenuate pathology in the intestinal tract. PMID:28302598

Publications of the Jet Propulsion Laboratory, 1981

NASA Technical Reports Server (NTRS)

1982-01-01

Over 500 externally distributed technical reports released during 1981 that resulted from scientific and engineering work performed, or managed by Jet Propulsion Laboratory are listed by primary author. Of the total number of entries, 311 are from the bimonthly Deep Space Network Progress Report, and its successor, the Telecommunications and Data Acquisition Progress Report.

Canadian Environmental Concerns: Winnipeg, Manitoba. Progress Report. Project Canada West.

ERIC Educational Resources Information Center

Western Curriculum Project on Canada Studies, Edmonton (Alberta).

Part I of this progress report places emphasis on curriculum development from the standpoint of the teacher-developer. The role is defined and factors such as teacher selection, release time, administrative cooperation, work schedules, assigned work space, and benefits to the school division and to the teacher are discussed. Recommendations deal…

ACHP | The Protection of Indian Sacred Sites

Science.gov Websites

signatories issued an action plan for implementation of the MOU and in March 2014, issued a progress report , Action Plan, Progress Report, and other information may be accessed by clicking the links below: 2016 Action Plan ACHP News Announcement Department of the Interior Press Release DOI/Forest Service Updates

Straight A's: Public Education Policy and Progress. Volume 10, Number 3

ERIC Educational Resources Information Center

Alliance for Excellent Education, 2010

2010-01-01

"Straight A's: Public Education Policy and Progress" is a biweekly newsletter that focuses on education news and events both in Washington, DC and around the country. The following articles are included in this issue: (1) Obama Releases FY 2011 Budget: Obama's 7.5 Percent Increase for Education Programs Signals Commitment to Reauthorize…

Patterns of Reasoning about Ecological Systemic Reasoning for Early Elementary Students

ERIC Educational Resources Information Center

Hokayem, H.

2016-01-01

Systems and system models are recognized as a crosscutting concept in the newly released framework for K-12 science education (NRC [National Research Council], 2012). In previous work, I developed a learning progression for systemic reasoning in ecology at the elementary level. The learning progression captured five levels of students' reasoning…

Data summary report for fission product release test VI-5

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

Osborne, M.F.; Lorenz, R.A.; Travis, J.R.

Test VI-5, the fifth in a series of high-temperature fission product release tests in a vertical test apparatus, was conducted in a flowing mixture of hydrogen and helium. The test specimen was a 15.2-cm-long section of a fuel rod from the BR3 reactor in Belgium which had been irradiated to a burnup of {approximately}42 MWd/kg. Using a hot cell-mounted test apparatus, the fuel rod was heated in an induction furnace under simulated LWR accident conditions to two test temperatures, 2000 K for 20 min and then 2700 K for an additional 20 min. The released fission products were collected inmore » three sequentially operated collection trains on components designed to measure fission product transport characteristics and facilitate sampling and analysis. The results from this test were compared with those obtained in previous tests in this series and with the CORSOR-M and ORNL diffusion release models for fission product release. 21 refs., 19 figs., 12 tabs.« less

31 CFR 593.412 - Release of any round log or timber product originating in Liberia from a bonded warehouse or...

Code of Federal Regulations, 2012 CFR

2012-07-01

... 31 Money and Finance:Treasury 3 2012-07-01 2012-07-01 false Release of any round log or timber... Interpretations § 593.412 Release of any round log or timber product originating in Liberia from a bonded... from a bonded warehouse or foreign trade zone of any round log or timber product originating in Liberia...

31 CFR 593.412 - Release of any round log or timber product originating in Liberia from a bonded warehouse or...

Code of Federal Regulations, 2013 CFR

2013-07-01

... 31 Money and Finance:Treasury 3 2013-07-01 2013-07-01 false Release of any round log or timber... Interpretations § 593.412 Release of any round log or timber product originating in Liberia from a bonded... from a bonded warehouse or foreign trade zone of any round log or timber product originating in Liberia...

Imputing at-work productivity loss using results of a randomized controlled trial comparing tapentadol extended release and oxycodone controlled release for osteoarthritis pain.

PubMed

Lerner, Debra; Chang, Hong; Rogers, William H; Benson, Carmela; Chow, Wing; Kim, Myoung S; Biondi, David

2012-08-01

: To determine the impact of tapentadol extended release (ER) versus placebo or oxycodone controlled release (CR) on the work productivity of adults with chronic moderate to severe knee osteoarthritis pain. : Using clinical trial data on pain outcomes, a validated methodology imputed treatment group differences in at-work productivity and associated differences in productivity costs (assuming a $100,000 annual salary per participant). : Imputed improvements in at-work productivity were significantly greater for tapentadol ER compared with either placebo (mean, 1.96% vs 1.51%; P = 0.001) or oxycodone CR (mean, 1.96% vs 1.40%; P < 0.001). Mean net savings per participant were $450 (P < 0.01) for tapentadol ER versus placebo and $560 (P = 0.001) for tapentadol ER versus oxycodone CR. : Effective osteoarthritis pain treatment also may help employees to function better at work and reduce their employers' productivity costs.

Undeclared Formaldehyde Levels in Patient Consumer Products: Formaldehyde Test Kit Utility.

PubMed

Ham, Jason E; Siegel, Paul; Maibach, Howard

2018-05-03

Formaldehyde allergic contact dermatitis (ACD) may be due to products with free formaldehyde or formaldehyde-releasing agents, however, assessment of formaldehyde levels in such products is infrequently conducted. The present study quantifies total releasable formaldehyde from "in-use" products associated with formaldehyde ACD and tests the utility of commercially available formaldehyde spot test kits. Personal care products from 2 patients with ACD to formaldehyde were initially screened at the clinic for formaldehyde using a formaldehyde spot test kit. Formaldehyde positive products were sent to the laboratory for confirmation by gas chromatography-mass spectrometry. In addition, 4 formaldehyde spot test kits were evaluated for potential utility in a clinical setting. Nine of the 10 formaldehyde spot test kit positive products obtained from formaldehyde allergic patients had formaldehyde with total releasable formaldehyde levels ranging from 5.4 to 269.4 µg/g. Of these, only 2 shampoos tested listed a formaldehyde-releasing agent in the ingredients or product literature. Subsequently, commercially available formaldehyde spot test kits were evaluated in the laboratory for ability to identify formaldehyde in personal care products. Chemical based formaldehyde spot test were more reliable than the enzymatic based test in identifying product releasable formaldehyde content. It is concluded that product labeled ingredient lists and available information are often inadequate to confirm the potential for formaldehyde exposure and chemical based spot test kits may have utility for identification of potential formaldehyde exposure from personal care products.

Antibodies to elastin peptides in sera of Belgian Draught horses with chronic progressive lymphoedema.

PubMed

van Brantegem, L; de Cock, H E V; Affolter, V K; Duchateau, L; Hoogewijs, M K; Govaere, J; Ferraro, G L; Ducatelle, R

2007-09-01

Chronic progressive lymphoedema (CPL) is a recently recognised disease of the lymphatic system characterised by lesions in the skin of the lower legs in several draught horse breeds, including the Belgian Draught hourse. Clinical signs slowly progress and result in severe disfigurement of the limbs. Ideally, supportive treatment should be started early in the disease process. However early diagnosis and monitoring progression of CPL is still a challenge. Elastin changes, characterised by morphological alterations as well as increased desmosine levels, in the skin of the distal limbs of horses affected with CPL are probably associated with a marked release of elastin degradation products, which elicit production of circulating anti-elastin antibodies (AEAbs) in the serum. An enzyme-linked immunosorbent assay (ELISA) for detection of serum AEAbs may document elastin breakdown. An ELISA technique was used to evaluate levels of AEAbs in sera of 97 affected Belgian Draught horses that were clinically healthy except for possible skin lesions, associated with CPL in their distal limbs. The horses were divided into 5 groups according to the severity of these skin lesions: normal horses (Group 1, n = 36), horses with mild lesions (Group 2, n = 43), horses with moderate lesions (Group 3, n = 8), horses with severe lesions (Group 4, n = 10) and, as a control, healthy Warmblood horses, unaffected by the disease (Group 5, n = 83). Horses with clinical signs of CPL had significantly higher AEAb levels compared to clinically normal Belgian Draught horses and to healthy Warmblood horses. These levels correlated with severity of lesions. CPL in draught horses is associated with an increase of serum AEAbs. Evaluation of serum levels of AEAbs by ELISA might be a useful diagnostic aid for CPL. Pathological degradation of elastic fibres, resulting in deficient support of the distal lymphatics, is proposed as a contributing factor for CPL in Belgian Draught horses.

The impact of shape memory test on degradation profile of a bioresorbable polymer.

PubMed

Musioł, Marta; Jurczyk, Sebastian; Kwiecień, Michał; Smola-Dmochowska, Anna; Domański, Marian; Janeczek, Henryk; Włodarczyk, Jakub; Klim, Magdalena; Rydz, Joanna; Kawalec, Michał; Sobota, Michał

2018-05-01

The semicrystalline poly(L-lactide) (PLLA) belongs to the materials with shape memory effect (SME) and as a bioresorbable and biocompatible polymer it have found many applications in medical and pharmaceutical field. Assessment of the SME impact on the polymer degradation profile plays crucial role in applications such as drug release systems or in regenerative medicine. Herein, the results of in vitro degradation studies of PLLA samples after SME full test cycle are presented. The samples were loaded and deformed in two manners: progressive and non-progressive. The performed experiments illustrate also influence of the material mechanical damages, caused e.g. during incorrect implantation of PLLA product, on hydrolytic degradation profile. Apparently, degradation profiles are significantly different for the material which was not subjected to the deformation and the deformed ones. The materials after deformation of 50% (in SME cycle) was characterized by non-reversible morphology changes. The effect was observed in deformed samples during the SME test which were carried out ten times. Copyright © 2018 Elsevier Ltd. All rights reserved.

Biomarkers in adult posthemorrhagic hydrocephalus.

PubMed

Hua, Cong; Zhao, Gang

2017-08-01

Posthemorrhagic hydrocephalus is a severe complication following intracranial hemorrhage. Posthemorrhagic hydrocephalus is often associated with high morbidity and mortality and serves as an important clinical predictor of adverse outcomes after intracranial hemorrhage. Currently, no effective medical intervention exists to improve functional outcomes in posthemorrhagic hydrocephalus patients because little is still known about the mechanisms of posthemorrhagic hydrocephalus pathogenesis. Because a better understanding of the posthemorrhagic hydrocephalus pathogenesis would facilitate development of clinical treatments, this is an active research area. The purpose of this review is to describe recent progress in elucidation of molecular mechanisms that cause posthemorrhagic hydrocephalus. What we are certain of is that the entry of blood into the ventricular system and subarachnoid space results in release of lytic blood products which cause a series of physiological and pathological changes in the brain. Blood components that can be linked to pathology would serve as disease biomarkers. From studies of posthemorrhagic hydrocephalus, such biomarkers are known to mutually synergize to initiate and promote posthemorrhagic hydrocephalus progression. These findings suggest that modulation of biomarker expression or function may benefit posthemorrhagic hydrocephalus patients.

Defining the Structural Basis for Allosteric Product Release from E. coli Dihydrofolate Reductase Using NMR Relaxation Dispersion.

PubMed

Oyen, David; Fenwick, R Bryn; Aoto, Phillip C; Stanfield, Robyn L; Wilson, Ian A; Dyson, H Jane; Wright, Peter E

2017-08-16

The rate-determining step in the catalytic cycle of E. coli dihydrofolate reductase is tetrahydrofolate (THF) product release, which can occur via an allosteric or an intrinsic pathway. The allosteric pathway, which becomes accessible when the reduced cofactor NADPH is bound, involves transient sampling of a higher energy conformational state, greatly increasing the product dissociation rate as compared to the intrinsic pathway that obtains when NADPH is absent. Although the kinetics of this process are known, the enzyme structure and the THF product conformation in the transiently formed excited state remain elusive. Here, we use side-chain proton NMR relaxation dispersion measurements, X-ray crystallography, and structure-based chemical shift predictions to explore the structural basis of allosteric product release. In the excited state of the E:THF:NADPH product release complex, the reduced nicotinamide ring of the cofactor transiently enters the active site where it displaces the pterin ring of the THF product. The p-aminobenzoyl-l-glutamate tail of THF remains weakly bound in a widened binding cleft. Thus, through transient entry of the nicotinamide ring into the active site, the NADPH cofactor remodels the enzyme structure and the conformation of the THF to form a weakly populated excited state that is poised for rapid product release.

21 CFR 172.880 - Petrolatum.

Code of Federal Regulations, 2010 CFR

2010-04-01

... bakery products; as release agent and lubricant With white mineral oil, not to exceed 0.15 percent of bakery product. In confectionery; as release agent and as sealing and polishing agent Not to exceed 0.2 percent of confectionery. In dehydrated fruits and vegetables; as release agent Not to exceed 0.02 percent...

Potential release scenarios for carbon nanotubes used in composites

EPA Science Inventory

The expected widespread use of carbon nanotube (CNT)-composites in consumer products calls for an assessment of the possible release and exposure to workers, consumers and the environment. Release of CNTs may occur at all steps in the life cycle of products, but to date only limi...

Novel slow release nanocomposite nitrogen fertilizers: the impact of polymers on nanocomposite properties and function

USDA-ARS?s Scientific Manuscript database

Efficient use of fertilizers, especially nitrogen, is essential and strategic to agricultural production. Among the technologies that can contribute to efficient use of fertilizers are slow or controlled release products. This paper describes the impact on structure, urea release rate and function i...

Sustained release of diltiazem HCl tableted after co-spray drying and physical mixing with PVAc and PVP.

PubMed

Al-Zoubi, Nizar; Al-Obaidi, Ghada; Tashtoush, Bassam; Malamataris, Stavros

2016-01-01

In this work, aqueous diltiazem HCl and polyvinyl-pyrrolidone (PVP) solutions were mixed with Kollicoat SR 30D and spray dried to microparticles of different drug:excipient ratio and PVP content. Co-spray dried products and physical mixtures of drug, Kollidon SR and PVP were tableted. Spray drying process, co-spray dried products and compressibility/compactability of co-spray dried and physical mixtures, as well as drug release and water uptake of matrix-tablets was evaluated. Simple power equation fitted drug release and water uptake (R(2) > 0.909 and 0.938, respectively) and correlations between them were examined. Co-spray dried products with PVP content lower than in physical mixtures result in slower release, while at equal PVP content (19 and 29% w/w of excipient) in similar release (f2 > 50). Increase of PVP content increases release rate and co-spray drying might be an alternative, when physical mixing is inadequate. Co-spray dried products show better compressibility/compatibility but higher stickiness to the die-wall compared to physical mixtures. SEM observations and comparison of release and swelling showed that distribution of tableted component affects only the swelling, while PVP content for both co-spray dried and physical mixes is major reason for release alterations and an aid for drug release control.

ALKALINITY, PH, AND COPPER CORROSION BY-PRODUCT RELEASE

EPA Science Inventory

Contrary to expectations, higher bicarbonate concentrations exacerbate copper corrosion rates and by-product release. In fact, as illustrated by monitoring experiences of large utilities and by laboratory data, the concentration of copper corrosion by-products in drinking water i...

Smart drug release systems based on stimuli-responsive polymers.

PubMed

Qing, Guangyan; Li, Minmin; Deng, Lijing; Lv, Ziyu; Ding, Peng; Sun, Taolei

2013-07-01

Stimuli-responsive polymers could respond to external stimuli, such as temperature, pH, photo-irradiation, electric field, biomolecules in solution, etc., which further induce reversible transformations in the structures and conformations of polymers, providing an excellent platform for controllable drug release, while the accuracy of drug delivery could obtain obvious improvement in this system. In this review, recent progresses in the drug release systems based on stimuli-responsive polymers are summarized, in which drugs can be released in an intelligent mode with high accuracy and efficiency, while potential damages to normal cells and tissues can also be effectively prevented owing to the unique characteristics of materials. Moreover, we introduce some smart nanoparticles-polymers conjugates and drug release devices, which are especially suitable for the long-term sustained drug release.

Preparation and properties of a double-coated slow-release and water-retention urea fertilizer.

PubMed

Liang, Rui; Liu, Mingzhu

2006-02-22

A double-coated, slow-release, and water-retention urea fertilizer (DSWU) was prepared by cross-linked poly(acrylic acid)-containing urea (PAAU) (the outer coating), polystyrene (PS) (the inner coating), and urea granule (the core). Elemental analysis results showed that the nitrogen content of the product was 33.6 wt %. The outer coating (PAAU) regulated the nitrogen release rate and protected the inner coating from damage. The slow-release property of the product was investigated in water and in soil. The possible mechanism of nitrogen release was proposed. The influences of PS coating percentage, temperature, water absorbency, and pH on the release of nitrogen were also investigated. It was found that PS coating percentage, temperature, and water absorbency had a significant influence on the release of nitrogen. However, the pH had no effect. The water-retention property of the product was also investigated. The results showed that the product not only had a good slow-release property but also excellent water-retention capacity, which could effectively improve the utilization of fertilizer and water resources. The results of the present work indicated that the DSWU would find good application in agriculture and horticulture, especially in drought-prone areas where the availability of water is insufficient.

Biogas Opportunities Roadmap Progress Report

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

None, None

In support of the Obama Administration's Climate Action Plan, the U.S. Department of Energy, the U.S. Environmental Protection Agency, and U.S. Department of Agriculture jointly released the Biogas Opportunities Roadmap Progress Report, updating the federal government's progress to reduce methane emissions through biogas systems since the Biogas Opportunities Roadmap was completed by the three agencies in July 2014. The report highlights actions taken, outlines challenges and opportunities, and identifies next steps to the growth of a robust biogas industry.

Interpretation and modelling of fission product Ba and Mo releases from fuel

NASA Astrophysics Data System (ADS)

Brillant, G.

2010-02-01

The release mechanisms of two fission products (namely barium and molybdenum) in severe accident conditions are studied using the VERCORS experimental observations. Barium is observed to be mostly released under reducing conditions while molybdenum release is most observed under oxidizing conditions. As well, the volatility of some precipitates in fuel is evaluated by thermodynamic equilibrium calculations. The polymeric species (MoO 3) n are calculated to largely contribute to molybdenum partial pressure and barium volatility is greatly enhanced if the gas atmosphere is reducing. Analytical models of fission product release from fuel are proposed for barium and molybdenum. Finally, these models have been integrated in the ASTEC/ELSA code and validation calculations have been performed on several experimental tests.

Subgroup A : nuclear model codes report to the Sixteenth Meeting of the WPEC

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

Talou, P.; Chadwick, M. B.; Dietrich, F. S.

2004-01-01

The Subgroup A activities focus on the development of nuclear reaction models and codes, used in evaluation work for nuclear reactions from the unresolved energy region up to the pion threshold production limit, and for target nuclides from the low teens and heavier. Much of the efforts are devoted by each participant to the continuing development of their own Institution codes. Progresses in this arena are reported in detail for each code in the present document. EMPIRE-II is of public access. The release of the TALYS code has been announced for the ND2004 Conference in Santa Fe, NM, October 2004.more » McGNASH is still under development and is not expected to be released in the very near future. In addition, Subgroup A members have demonstrated a growing interest in working on common modeling and codes capabilities, which would significantly reduce the amount of duplicate work, help manage efficiently the growing lines of existing codes, and render codes inter-comparison much easier. A recent and important activity of the Subgroup A has therefore been to develop the framework and the first bricks of the ModLib library, which is constituted of mostly independent pieces of codes written in Fortran 90 (and above) to be used in existing and future nuclear reaction codes. Significant progresses in the development of ModLib have been made during the past year. Several physics modules have been added to the library, and a few more have been planned in detail for the coming year.« less

Source Term Estimates of Radioxenon Released from the BaTek Medical Isotope Production Facility Using External Measured Air Concentrations

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

Eslinger, Paul W.; Cameron, Ian M.; Dumais, Johannes R.

2015-10-01

Abstract Batan Teknologi (BaTek) operates an isotope production facility in Serpong, Indonesia that supplies 99mTc for use in medical procedures. Atmospheric releases of Xe-133 in the production process at BaTek are known to influence the measurements taken at the closest stations of the International Monitoring System (IMS). The purpose of the IMS is to detect evidence of nuclear explosions, including atmospheric releases of radionuclides. The xenon isotopes released from BaTek are the same as those produced in a nuclear explosion, but the isotopic ratios are different. Knowledge of the magnitude of releases from the isotope production facility helps inform analystsmore » trying to decide whether a specific measurement result came from a nuclear explosion. A stack monitor deployed at BaTek in 2013 measured releases to the atmosphere for several isotopes. The facility operates on a weekly cycle, and the stack data for June 15-21, 2013 show a release of 1.84E13 Bq of Xe-133. Concentrations of Xe-133 in the air are available at the same time from a xenon sampler located 14 km from BaTek. An optimization process using atmospheric transport modeling and the sampler air concentrations produced a release estimate of 1.88E13 Bq. The same optimization process yielded a release estimate of 1.70E13 Bq for a different week in 2012. The stack release value and the two optimized estimates are all within 10 percent of each other. Weekly release estimates of 1.8E13 Bq and a 40 percent facility operation rate yields a rough annual release estimate of 3.7E13 Bq of Xe-133. This value is consistent with previously published estimates of annual releases for this facility, which are based on measurements at three IMS stations. These multiple lines of evidence cross-validate the stack release estimates and the release estimates from atmospheric samplers.« less

Constructing early warning information release system in towns enterprise clean production

NASA Astrophysics Data System (ADS)

Yuwen, Huixin; He, Xueqiu; Qian, Xinming; Yuan, Mengqi

2017-08-01

China’s industry boom has not only brought unprecedented prosperity, but also caused the gradual depletion of various resources and the worsening of the natural environment. Experts admit that China is facing serious environmental problem, but they believe that they can seek a new path to overcome it through joint efforts. Early warning information release and clean production are the important concepts in addressing the imminent crisis. Early warning information release system can monitor and forecast the risk that affects the clean production. The author drawn the experiences and lessons from developed countries, combined with China’s reality, put forward countermeasures and suggestions about constructing early warning information release system in process of Chinese town-scaled enterprises clean production.

Carbon monoxide-releasing molecule-3 suppresses Prevotella intermedia lipopolysaccharide-induced production of nitric oxide and interleukin-1β in murine macrophages.

PubMed

Choi, Eun-Young; Choe, So-Hui; Hyeon, Jin-Yi; Choi, Jeom-Il; Choi, In Soon; Kim, Sung-Jo

2015-10-05

This study was performed to analyze the effect of carbon monoxide (CO)-releasing molecule-3 (CORM-3) in alleviating the production of proinflammatory mediators in macrophages treated with lipopolysaccharide (LPS) from Prevotella intermedia, a pathogen associated with periodontal disease, and its possible mechanisms of action. LPS was isolated using the hot phenol-water method. Culture supernatants were assayed for nitric oxide (NO) and interleukin-1β (IL-1β). Gene expression was quantified by real-time PCR, and protein expression by immunoblotting. DNA-binding activities of NF-κB subunits were determined using an ELISA-based kit. CORM-3 suppressed the production of inducible NO synthase (iNOS)-derived NO and IL-1β at both gene transcription and translation levels in P. intermedia LPS-activated RAW264.7 cells. CORM-3 enhanced heme oxygenase-1 (HO-1) expression in cells stimulated with P. intermedia LPS, and inhibition of HO-1 activity by SnPP notably reversed the suppressive effect of CORM-3 on LPS-induced production of NO. LPS-induced phosphorylation of p38 and JNK was not affected by CORM-3. CORM-3 did not influence P. intermedia LPS-induced degradation of IκB-α. Instead, nuclear translocation of NF-κB p65 and p50 subunits was blocked by CORM-3 in LPS-treated cells. In addition, CORM-3 reduced LPS-induced p65 and p50 binding to DNA. Besides, CORM-3 significantly suppressed P. intermedia LPS-induced phosphorylation of STAT1. Overall, this study indicates that CORM-3 suppresses the production of NO and IL-1β in P. intermedia LPS-activated murine macrophages via HO-1 induction and inhibition of NF-κB and STAT1 pathways. The modulation of host inflammatory response by CORM-3 would be an attractive therapeutic approach to attenuate the progression of periodontal disease. Copyright © 2015 Elsevier B.V. All rights reserved.

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.

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

Loyalka, Sudarshan

High and Very High Temperatures Gas Reactors (HTGRs/VHTRs) have five barriers to fission product (FP) release: the TRISO fuel coating, the fuel elements, the core graphite, the primary coolant system, and the reactor building. This project focused on measurements and computations of FP diffusion in graphite, FP adsorption on graphite and FP interactions with dust particles of arbitrary shape. Diffusion Coefficients of Cs and Iodine in two nuclear graphite were obtained by the release method and use of Inductively Coupled Plasma-Mass Spectroscopy (ICP-MS) and Instrumented Neutron Activation Analysis (INAA). A new mathematical model for fission gas release from nuclear fuelmore » was also developed. Several techniques were explored to measure adsorption isotherms, notably a Knudsen Effusion Mass Spectrometer (KEMS) and Instrumented Neutron Activation Analysis (INAA). Some of these measurements are still in progress. The results will be reported in a supplemental report later. Studies of FP interactions with dust and shape factors for both chain-like particles and agglomerates over a wide size range were obtained through solutions of the diffusion and transport equations. The Green's Function Method for diffusion and Monte Carlo technique for transport were used, and it was found that the shape factors are sensitive to the particle arrangements, and that diffusion and transport of FPs can be hindered. Several journal articles relating to the above work have been published, and more are in submission and preparation.« less

Responses of human neutrophils to nicotine and/or Porphyromonas gingivalis.

PubMed

Al-Shibani, Nouf K; Labban, Nawaf Y; Kowolik, Michael J; Ruby, John D; Windsor, L Jack

2011-10-01

Tobacco smoking is considered a major modifiable risk factor for periodontal disease. Nicotine is the addictive ingredient in tobacco and has been shown to affect multiple cellular processes. Neutrophils are the first line of host defense and are critical cells in the maintenance of periodontal health through their role in the control of bacteria, but they can also contribute to the progression of periodontal disease by the production and release of reactive oxygen species (ROS). Virulence factors from periodontal pathogens, such as Porphyromonas gingivalis (Pg), stimulate the respiratory burst of neutrophils. The objective of this study is to explore the oxidative activity of neutrophils when stimulated with Pg, nicotine, or both. Neutrophils were separated from buffy coats by the double dextran gradient method. The generation of ROS by neutrophils was determined using luminol-dependent chemiluminescence assays. The reaction was followed for 90 minutes, and the neutrophil activation was recorded as the total integrated energy output. The Pg and Pg plus nicotine groups had a significantly higher active and peak chemiluminescence than the nicotine group (all with P <0.0001). The Pg and Pg with nicotine groups were not significantly different (P = 0.90). In the presence of Pg, the nicotine did not further enhance the ROS release by the neutrophils, suggesting that the bacteria induced the maximum ROS release in this model system.

Regulation of Tumor Progression by Programmed Necrosis

PubMed Central

Jeon, Hyun Min; Jeong, Eui Kyong; Lee, Yig Ji; Kim, Cho Hee; Park, Hye Gyeong

2018-01-01

Rapidly growing malignant tumors frequently encounter hypoxia and nutrient (e.g., glucose) deprivation, which occurs because of insufficient blood supply. This results in necrotic cell death in the core region of solid tumors. Necrotic cells release their cellular cytoplasmic contents into the extracellular space, such as high mobility group box 1 (HMGB1), which is a nonhistone nuclear protein, but acts as a proinflammatory and tumor-promoting cytokine when released by necrotic cells. These released molecules recruit immune and inflammatory cells, which exert tumor-promoting activity by inducing angiogenesis, proliferation, and invasion. Development of a necrotic core in cancer patients is also associated with poor prognosis. Conventionally, necrosis has been thought of as an unregulated process, unlike programmed cell death processes like apoptosis and autophagy. Recently, necrosis has been recognized as a programmed cell death, encompassing processes such as oncosis, necroptosis, and others. Metabolic stress-induced necrosis and its regulatory mechanisms have been poorly investigated until recently. Snail and Dlx-2, EMT-inducing transcription factors, are responsible for metabolic stress-induced necrosis in tumors. Snail and Dlx-2 contribute to tumor progression by promoting necrosis and inducing EMT and oncogenic metabolism. Oncogenic metabolism has been shown to play a role(s) in initiating necrosis. Here, we discuss the molecular mechanisms underlying metabolic stress-induced programmed necrosis that promote tumor progression and aggressiveness. PMID:29636841

Streptococcus pneumoniae triggers progression of pulmonary fibrosis through pneumolysin.

PubMed

Knippenberg, Sarah; Ueberberg, Bianca; Maus, Regina; Bohling, Jennifer; Ding, Nadine; Tort Tarres, Meritxell; Hoymann, Heinz-Gerd; Jonigk, Danny; Izykowski, Nicole; Paton, James C; Ogunniyi, Abiodun D; Lindig, Sandro; Bauer, Michael; Welte, Tobias; Seeger, Werner; Guenther, Andreas; Sisson, Thomas H; Gauldie, Jack; Kolb, Martin; Maus, Ulrich A

2015-07-01

Respiratory tract infections are common in patients suffering from pulmonary fibrosis. The interplay between bacterial infection and fibrosis is characterised poorly. To assess the effect of Gram-positive bacterial infection on fibrosis exacerbation in mice. Fibrosis progression in response to Streptococcus pneumoniae was examined in two different mouse models of pulmonary fibrosis. We demonstrate that wild-type mice exposed to adenoviral vector delivery of active transforming growth factor-β1 (TGFß1) or diphteria toxin (DT) treatment of transgenic mice expressing the DT receptor (DTR) under control of the surfactant protein C (SPC) promoter (SPC-DTR) to induce pulmonary fibrosis developed progressive fibrosis following infection with Spn, without exhibiting impaired lung protective immunity against Spn. Antibiotic treatment abolished infection-induced fibrosis progression. The cytotoxin pneumolysin (Ply) of Spn caused this phenomenon in a TLR4-independent manner, as Spn lacking Ply (SpnΔply) failed to trigger progressive fibrogenesis, whereas purified recombinant Ply did. Progressive fibrogenesis was also observed in AdTGFβ1-exposed Ply-challenged TLR4 KO mice. Increased apoptotic cell death of alveolar epithelial cells along with an attenuated intrapulmonary release of antifibrogenic prostaglandin E2 was found to underlie progressive fibrogenesis in Ply-challenged AdTGFβ1-exposed mice. Importantly, vaccination of mice with the non-cytotoxic Ply derivative B (PdB) substantially attenuated Ply-induced progression of lung fibrosis in AdTGFβ1-exposed mice. Our data unravel a novel mechanism by which infection with Spn through Ply release induces progression of established lung fibrosis, which can be attenuated by protein-based vaccination of mice. Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to http://group.bmj.com/group/rights-licensing/permissions.

A Nonpolar Blueberry Fraction Blunts NADPH Oxidase Activation in Neuronal Cells Exposed to Tumor Necrosis Factor-α

PubMed Central

Gustafson, Sally J.; Dunlap, Kriya L.; McGill, Colin M.; Kuhn, Thomas B.

2012-01-01

Inflammation and oxidative stress are key to the progressive neuronal degeneration common to chronic pathologies, traumatic injuries, and aging processes in the CNS. The proinflammatory cytokine tumor necrosis factor-alpha (TNF-α) orchestrates cellular stress by stimulating the production and release of neurotoxic mediators including reactive oxygen species (ROS). NADPH oxidases (NOX), ubiquitously expressed in all cells, have recently emerged as pivotal ROS sources in aging and disease. We demonstrated the presence of potent NOX inhibitors in wild Alaska bog blueberries partitioning discretely into a nonpolar fraction with minimal antioxidant capacity and largely devoid of polyphenols. Incubation of SH-SY5Y human neuroblastoma cells with nonpolar blueberry fractions obstructed the coalescing of lipid rafts into large domains disrupting NOX assembly therein and abolishing ROS production characteristic for TNF-α exposure. These findings illuminate nutrition-derived lipid raft modulation as a novel therapeutic approach to blunt inflammatory and oxidative stress in the aging or diseased CNS. PMID:22530077

Straight A's: Public Education Policy and Progress. Volume 11, Number 19

ERIC Educational Resources Information Center

Amos, Jason, Ed.

2011-01-01

"Straight A's: Public Education Policy and Progress" is a biweekly newsletter that focuses on education news and events both in Washington, DC and around the country. The following articles are included in this issue: (1) U.S. Senators Harkin and Enzi Release Draft Language to Revise NCLB: Senate Committee to Consider Draft Containing…

On the mechanism of tachyphylaxis to tyramine in the isolated rat heart

PubMed Central

Axelrod, J.; Gordon, Edna; Hertting, G.; Kopin, I. J.; Potter, L. T.

1962-01-01

Tyramine was shown to release [3H]-catecholamines from an isolated rat heart previously perfused with [3H]-noradrenaline. With successive injections of tyramine the amount of [3H]-catecholamine released fell progressively and there was a parallel decrease in the increment of amplitude and rate of contraction of the heart. Reserpinized hearts were shown to take up less [3H]-noradrenaline than normal hearts. Release of radioactivity and loss of responsiveness to tyramine occurred more rapidly in the reserpinized heart. In the same preparation the uptake of [14C]-tyramine exceeded the quantity of the noradrenaline released. ImagesFig. 4 PMID:13863453

U.S. Sanctions on Burma

DTIC Science & Technology

2010-07-16

3)(a)(3)—progress on human rights, release of all political prisoners, freedom of speech and the press, freedom of association, peaceful...release of all political prisoners, freedom of speech and the press, freedom of association, peaceful exercise of religion, democratic governance, not...political prisoners, allowing freedom of speech , the press, and association, permitting the peaceful exercise of religion, and concluding an agreement

Get Up to Speed on the Latest Product Releases in the Education Market

ERIC Educational Resources Information Center

Technology & Learning, 2007

2007-01-01

This article provides brief descriptions of the latest product releases in the education market. These products include hardware, software, and resources. The following products are presented in this article, but not limited to: (1) Radius Audio Learning System(www.learningresources.com); (2) The Indigo Learning System from LearningSoft, LLC…

Greenhouse production of Impatiens wallerana using a controlled-release fertiliser produces quality finished plants with enhanced garden performance

USDA-ARS?s Scientific Manuscript database

Nutrient management during production can greatly influence post-production quality of plants. The objective of this research was to evaluate the effect of controlled release fertilizer (CRF) applied at the time of plug planting on the garden performance (post-production) of impatiens (Impatiens wal...

27 CFR 41.85 - Release from customs custody of imported tobacco products or cigarette papers or tubes.

Code of Federal Regulations, 2014 CFR

2014-04-01

... custody of imported tobacco products or cigarette papers or tubes. 41.85 Section 41.85 Alcohol, Tobacco...) TOBACCO IMPORTATION OF TOBACCO PRODUCTS, CIGARETTE PAPERS AND TUBES, AND PROCESSED TOBACCO Tobacco Products and Cigarette Papers and Tubes, Imported Into or Returned to the United States Release from...

19 CFR 12.8 - Inspection; bond; release.

Code of Federal Regulations, 2010 CFR

2010-04-01

... TREASURY SPECIAL CLASSES OF MERCHANDISE Meat and Meat-Food Products § 12.8 Inspection; bond; release. (a) All imported meat, meat-food products horse meat and horse meat-food products offered for entry into... section 306, Tariff Act of 1930. The term “meat and meat-food products,” for the purpose of this section...

Evaluation of rate of swelling and erosion of verapamil (VRP) sustained-release matrix tablets.

PubMed

Khamanga, Sandile M; Walker, Roderick B

2006-01-01

Tablets manufactured in-house were compared to a marketed sustained-release product of verapamil to investigate the rate of hydration, erosion, and drug-release mechanism by measuring the wet and subsequent dry weights of the products. Swelling and erosion rates depended on the polymer and granulating fluid used, which ultimately pointed to their permeability characteristics. Erosion rate of the marketed product was highest, which suggests that the gel layer that formed around these tablets was weak as opposed to the robust and resistant layers of test products. Anomalous and near zero-order transport mechanisms were dominant in tests and commercial product, respectively.

19 CFR 142.42 - Application for Line Release processing.

Code of Federal Regulations, 2010 CFR

2010-04-01

... 19 Customs Duties 2 2010-04-01 2010-04-01 false Application for Line Release processing. 142.42... processing. In order to obtain approval for processing import transactions through Line Release, a broker or... level for particular product or range of HTSUS numbers at sub-heading levels for multiple products for...

27 CFR 41.86 - Procedure for release.

Code of Federal Regulations, 2012 CFR

2012-04-01

..., DEPARTMENT OF THE TREASURY (CONTINUED) TOBACCO IMPORTATION OF TOBACCO PRODUCTS, CIGARETTE PAPERS AND TUBES, AND PROCESSED TOBACCO Tobacco Products and Cigarette Papers and Tubes, Imported Into or Returned to the United States Release from Customs Custody of Tobacco Products and Cigarette Papers and Tubes...

Products Released from Enzymically Active Cell Wall Stimulate Ethylene Production and Ripening in Preclimacteric Tomato (Lycopersicon esculentum Mill.) Fruit 1

PubMed Central

Brecht, Jeffrey K.; Huber, Donald J.

1988-01-01

Enzymically active cell wall from ripe tomato (Lycopersicon esculentum Mill.) fruit pericarp release uronic acids through the action of wall-bound polygalacturonase. The potential involvement of products of wall hydrolysis in the induction of ethylene synthesis during tomato ripening was investigated by vacuum infiltrating preclimacteric (green) fruit with solutions containing pectin fragments enzymically released from cell wall from ripe fruit. Ripening initiation was accelerated in pectin-infiltrated fruit compared to control (buffer-infiltrated) fruit as measured by initiation of climacteric CO2 and ethylene production and appearance of red color. The response to infiltration was maximum at a concentration of 25 micrograms pectin per fruit; higher concentrations (up to 125 micrograms per fruit) had no additional effect. When products released from isolated cell wall from ripe pericarp were separated on Bio-Gel P-2 and specific size classes infiltrated into preclimacteric fruit, ripening-promotive activity was found only in the larger (degree of polymerization >8) fragments. Products released from pectin derived from preclimacteric pericarp upon treatment with polygalacturonase from ripe pericarp did not stimulate ripening when infiltrated into preclimacteric fruit. PMID:16666417

Cathelicidin production and release by mammary epithelial cells during infectious mastitis.

PubMed

Cubeddu, Tiziana; Cacciotto, Carla; Pisanu, Salvatore; Tedde, Vittorio; Alberti, Alberto; Pittau, Marco; Dore, Simone; Cannas, Agnese; Uzzau, Sergio; Rocca, Stefano; Addis, Maria Filippa

2017-07-01

Cathelicidins are well-characterized antimicrobial peptides (AMPs) that are present in significant amounts in mastitic milk. Neutrophils are believed to be the main producers of these AMPs, while the role of mammary epithelial cells (MECs) in their production and release is still unclear. In this work, cathelicidin production patterns were investigated in mammary tissues of ewes infected by Staphylococcus aureus, Streptococcus uberis, or Mycoplasma agalactiae, with a combined approach including immunohistochemistry, immune-colocalization, and fluorescent in situ hybridization. Our results confirm that MECs produce and release cathelicidins in response to different mastitis pathogens. As opposed to neutrophils, however, MECs do not seem to store the preformed protein precursor in their cytoplasm, but appear to synthesize and release it only upon exposure to the microorganisms. Cathelicidin production by MECs appears to occur before leukocyte influx in the milk, suggesting a role for these cells in the initial response of the mammary epithelium to microbial infection. Once in the milk, infiltrating neutrophils release massive amounts of cathelicidin by degranulation and production of neutrophil extracellular traps, acting as the main contributor for cathelicidin abundance in mastitic milk. Taken together, our results support the active contribution of MECs to cathelicidin production and release, and reinforce the value of cathelicidins as sensitive and pathogen-independent mastitis markers. Copyright © 2017 Elsevier B.V. All rights reserved.

LARC-1: a Los Alamos release calculation program for fission product transport in HTGRs during the LOFC accident

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

Carruthers, L.M.; Lee, C.E.

1976-10-01

The theoretical and numerical data base development of the LARC-1 code is described. Four analytical models of fission product release from an HTGR core during the loss of forced circulation accident are developed. Effects of diffusion, adsorption and evaporation of the metallics and precursors are neglected in this first LARC model. Comparison of the analytic models indicates that the constant release-renormalized model is adequate to describe the processes involved. The numerical data base for release constants, temperature modeling, fission product release rates, coated fuel particle failure fraction and aged coated fuel particle failure fractions is discussed. Analytic fits and graphicmore » displays for these data are given for the Ft. St. Vrain and GASSAR models.« less

Autocrine Regulation of UVA-Induced IL-6 Production via Release of ATP and Activation of P2Y Receptors

PubMed Central

Kawano, Ayumi; Kadomatsu, Remi; Ono, Miyu; Kojima, Shuji; Tsukimoto, Mitsutoshi; Sakamoto, Hikaru

2015-01-01

Extracellular nucleotides, such as ATP, are released from cells in response to various stimuli and act as intercellular signaling molecules through activation of P2 receptors. Exposure to the ultraviolet radiation A (UVA) component of sunlight causes molecular and cellular damage, and in this study, we investigated the involvement of extracellular nucleotides and P2 receptors in the UVA-induced cellular response. Human keratinocyte-derived HaCaT cells were irradiated with a single dose of UVA (2.5 J/cm2), and ATP release and interleukin (IL)-6 production were measured. ATP was released from cells in response to UVA irradiation, and the release was blocked by pretreatment with inhibitors of gap junction hemichannels or P2X7 receptor antagonist. IL-6 production was increased after UVA irradiation, and this increase was inhibited by ecto-nucleotidase or by antagonists of P2Y11 or P2Y13 receptor. These results suggest that UVA-induced IL-6 production is mediated by release of ATP through hemichannels and P2X7 receptor, followed by activation of P2Y11 and P2Y13 receptors. Interestingly, P2Y11 and P2Y13 were associated with the same pattern of IL-6 production, though they trigger different intracellular signaling cascades: Ca2+-dependent and PI3K-dependent, respectively. Thus, IL-6 production in response to UVA-induced ATP release involves at least two distinct pathways, mediated by activation of P2Y11 and P2Y13 receptors. PMID:26030257

In vivo predictive release methods for medicated chewing gums.

PubMed

Gajendran, Jayachandar; Kraemer, Johannes; Langguth, Peter

2012-10-01

Understanding the performance of a drug product in vivo plays a key role in the development of meaningful in vitro drug release methodology. In case of functional chewing gums, the mode and the mechanism of release and the site of application differ significantly from other conventional solid oral dosage forms and require a special consideration to extract meaningful information from clinical studies. In the current study, suitable drug release methodology was developed to predict the in vivo performance of an investigated chewing gum product. Different parameters of the drug release testing apparatus described in the Ph. Eur. and Pharmeuropa were evaluated. Drug release data indicate that the parameters, chewing distance, chewing frequency and twisting motion, affect the drug release. Higher drug release was observed when the frequency was changed from 40 chews/min to 60 chews/min for apparatus A and B, as was the case for the twisting motion when changed from 20º to 40º for apparatus B. As far as the chewing distance is concerned, the release rate was in the following order; apparatus A: 0.3 mm > 0.5 mm > 0.7 mm; apparatus B: 1.4 mm > 1.6 mm > 1.8 mm. A suitable apparatus set-up for in vitro release testing was identified. The method will be useful for the establishment of in vitro in vivo correlations (IVIVC) for medicated chewing gums. Interchangeability of the apparatus for a product is not generally recommended without prior knowledge of the performance of the product, as the construction and principle of operation for the apparatus differ considerably. Copyright © 2012 John Wiley & Sons, Ltd.

Primary system fission product release and transport: A state-of-the-art report to the committee on the safety of nuclear installations

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

Wright, A.L.

This report presents a summary of the status of research activities associated with fission product behavior (release and transport) under severe accident conditions within the primary systems of water-moderated and water-cooled nuclear reactors. For each of the areas of fission product release and fission product transport, the report summarizes relevant information on important phenomena, major experiments performed, relevant computer models and codes, comparisons of computer code calculations with experimental results, and general conclusions on the overall state of the art. Finally, the report provides an assessment of the overall importance and knowledge of primary system release and transport phenomena andmore » presents major conclusions on the state of the art.« less

High wettability of liquid caesium iodine with solid uranium dioxide.

PubMed

Kurosaki, Ken; Suzuki, Masanori; Uno, Masayoshi; Ishii, Hiroto; Kumagai, Masaya; Anada, Keito; Murakami, Yukihiro; Ohishi, Yuji; Muta, Hiroaki; Tanaka, Toshihiro; Yamanaka, Shinsuke

2017-09-13

In March 2011, the Fukushima Daiichi Nuclear Power Plant accident caused nuclear fuel to melt and the release of high-volatility fission products into the environment. Caesium and iodine caused environmental contamination and public exposure. Certain fission-product behaviours remain unclear. We found experimentally that liquid CsI disperses extremely favourably toward solid UO 2 , exhibiting a contact angle approaching zero. We further observed the presence of CsI several tens of micrometres below the surface of the solid UO 2 sample, which would be caused by the infiltration of pores network by liquid CsI. Thus, volatile fission products released from molten nuclear fuels with complex internal composition and external structure migrate or evaporate to varying extents, depending on the nature of the solid-liquid interface and the fuel material surface, which becomes the pathway for the released fission products. Introducing the concept of the wettability of liquid chemical species of fission products in contact with solid fuels enabled developing accurate behavioural assessments of volatile fission products released by nuclear fuel.

High Performance Computing Modernization Program Kerberos Throughput Test Report

DTIC Science & Technology

2017-10-26

functionality as Kerberos plugins. The pre -release production kit was used in these tests to compare against the current release kit. YubiKey support...HPCMP Kerberos Throughput Test Report 3 2. THROUGHPUT TESTING 2.1 Testing Components Throughput testing was done to determine the benefits of the pre ...both the current release kit and the pre -release production kit for a total of 378 individual tests in order to note any improvements. Based on work

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.

Influence of drug property and product design on in vitro-in vivo correlation of complex modified-release dosage forms.

PubMed

Qiu, Yihong; Li, Xia; Duan, John Z

2014-02-01

The present study examines how drug's inherent properties and product design influence the evaluation and applications of in vitro-in vivo correlation (IVIVC) for modified-release (MR) dosage forms consisting of extended-release (ER) and immediate-release (IR) components with bimodal drug release. Three analgesic drugs were used as model compounds, and simulations of in vivo pharmacokinetic profiles were conducted using different release rates of the ER component and various IR percentages. Plasma concentration-time profiles exhibiting a wide range of tmax and maximum observed plasma concentration (Cmax) were obtained from superposition of the simulated IR and ER profiles based on a linear IVIVC. It was found that depending on the drug and dosage form design, direct use of the superposed IR and ER data for IVIVC modeling and prediction may (1) be acceptable within errors, (2) become unreliable and less meaningful because of the confounding effect from the non-negligible IR contribution to Cmax, or (3) be meaningless because of the insensitivity of Cmax to release rate change of the ER component. Therefore, understanding the drug, design and drug release characteristics of the product is essential for assessing the validity, accuracy, and reliability of IVIVC of complex MR products obtained via directly modeling of in vivo data. © 2013 Wiley Periodicals, Inc. and the American Pharmacists Association.

Recent Developments on Microencapsulation for Autonomous Corrosion Protection

NASA Technical Reports Server (NTRS)

Calle, Luz M.; Li, Wenyan; Buhrow, Jerry W.; Fitzpatrick, Lilliana; Jolley, Scott T.; Surma, Jan M.; Pearman, Benjamin P.; Zhang, Xuejun

2014-01-01

This work concerns recent progress in the development of a multifunctional smart coating based on microencapsulation for the autonomous control of corrosion. Microencapsulation allows the incorporation of desired corrosion control functionalities, such as early corrosion detection and inhibition through corrosion controlled release of corrosion indicators and inhibitors, as well as self-healing agent release when mechanical damage occurs.While proof-of-concept results have been reported previously, more recent efforts have been concentrated in technical developments to improve coating compatibility, synthesis procedure scalability, as well as fine tuning the release property of encapsulated active agents.

Explanatory Supplement to the WISE All-Sky Release Products

NASA Technical Reports Server (NTRS)

2012-01-01

The Wide-field Infrared Survey Explorer (WISE; Wright et al. 2010) surveyed the entire sky at 3.4, 4.6, 12 and 22 microns in 2010, achieving 5-sigma point source sensitivities per band better than 0.08, 0.11, 1 and 6 mJy in unconfused regions on the ecliptic. The WISE All-Sky Data Release, conducted on March 14, 2012, incorporates all data taken during the full cryogenic mission phase, 7 January 2010 to 6 August 20l0,that were processed with improved calibrations and reduction algorithms. Release data products include: (1) an Atlas of 18,240 match-filtered, calibrated and coadded image sets; (2) a Source Catalog containing positions and four-band photometry for over 563 million objects, and (3) an Explanatory Supplement. Ancillary products include a Reject Table that contains 284 million detections that were not selected for the Source Catalog because they are low signal-to-noise ratio or spurious detections of image artifacts, an archive of over 1.5 million sets of calibrated WISE Single-exposure images, and a database of 9.4 billion source extractions from those single images, and moving object tracklets identified by the NEOWISE program (Mainzer et aI. 2011). The WISE All-Sky Data Release products supersede those from the WISE Preliminary Data Release (Cutri et al. 2011). The Explanatory Supplement to the WISE All-Sky Data Release Products is a general guide for users of the WISE data. The Supplement contains an overview of the WISE mission, facilities, and operations, a detailed description of WISE data processing algorithms, a guide to the content and formals of the image and tabular data products, and cautionary notes that describe known limitations of the All-Sky Release products. Instructions for accessing the WISE data products via the services of the NASA/IPAC Infrared Science Archive are provided. The Supplement also provides analyses of the achieved sky coverage, photometric and astrometric characteristics and completeness and reliability of the All-Sky Release data products. The WISE All-Sky Release Explanatory Supplement is an on-line document that is updated frequently to provide the most current information for users of the WISE data products. The Explanatory Supplement is maintained at: http://wise2.ipac.caltech.edu/docs/release/allsky/expsup/index.html WISE is a joint project of the University of California, Los Angeles and the Jet Propulsion Laboratory/California Institute of Technology, funded by the National Aeronautics and Space Administration. NEOWISE is a project of the Jet Propulsion Laboratory/California Institute of Technology, funded by the Planetary Science Division of the National Aeronautics and Space Administration.

9 CFR 113.8 - In vitro tests for serial release.

Code of Federal Regulations, 2011 CFR

2011-01-01

... 9 Animals and Animal Products 1 2011-01-01 2011-01-01 false In vitro tests for serial release. 113... REQUIREMENTS Applicability § 113.8 In vitro tests for serial release. (a) Master Seed which has been established as pure, safe, and immunogenic shall be used for preparing seed for production as specified in the...

Nitrogen, phosphorus, calcium, and magnesium applied individually or as a slow release or controlled release fertilizer increase growth

USDA-ARS?s Scientific Manuscript database

The U.S. Environmental Protection Agency (USEPA) has restricted concentrated animal feeding operation(CAFO) release of waste products into U.S. waters. These waste products must be disposed of using best management practices. Most of the waste is spread on cropland, but some operations have found ot...

Kinetic release of hydrogen peroxide from different whitening products.

PubMed

da Silva Marques, Duarte Nuno; Silveira, Joao Miguel; Marques, Joana Rita; Amaral, Joao Almeida; Guilherme, Nuno Marques; da Mata, António Duarte

2012-01-01

The objective of this in vitro study was to evaluate the kinetics of hydrogen peroxide (HP) release from five different bleaching products: VivaStyle® 10% fitted tray gel, VivaStyle® 30% in-office bleaching gel, VivaStyle® Paint-On Plus paint-on bleaching varnish, Opalescence PF® 10% carbamide peroxide gel and Trèswhite Supreme™ 10% HP gel. Each product was firstly titrated for its HP content by a described method. HP release kinetics was assessed by a modified spectrophotometric technique. One sample t test was performed to test for differences between the manufacturers' claimed HP concentrations and the titrated HP content in the whitening products. Analysis of variance plus Tamhane's post hoc tests and Pearson correlation analysis were used as appropriate. Values of P < 0.05 were taken as significant. Titrated HP revealed an increased content when compared to the manufacturer's specifications for all the products tested (P < 0.05), although only products from one manufacturer produced significantly higher results. All products presented a significant (P < 0.05) and sustained release of HP. However, the product with paint-on cellulose-based matrix resulted in significantly (P < 0.05) faster kinetics when compared to other products tested. These results are consistent with manufacturers' reduced recommended application times. The results of this study suggest that modifying the matrix composition may be a viable alternative to HP concentration increase, since this may result in faster release kinetics without exposure to high HP concentrations.

[Batch release of immunoglobulin and monoclonal antibody products].

PubMed

Gross, S

2014-10-01

The Paul-Ehrlich Institute (PEI) is an independent institution of the Federal Republic of Germany responsible for performing official experimental batch testing of sera. The institute decides about the release of each batch and performs experimental research in the field. The experimental quality control ensures the potency of the product and also the absence of harmful impurities. For release of an immunoglobulin batch the marketing authorization holder has to submit the documentation of the manufacture and the results of quality control measures together with samples of the batch to the PEI. Experimental testing is performed according to the approved specifications regarding the efficacy and safety. Since implementation of the 15th German drug law amendment, the source of antibody is not defined anymore. According to § 32 German drug law, all batches of sera need to be released by an official control laboratory. Sera are medicinal products, which contain antibodies, antibody fragments or fusion proteins with a functional antibody portion. Therefore, all batches of monoclonal antibodies and derivatives must also be released by the PEI and the marketing authorization holder has to submit a batch release application. Under certain circumstances a waiver for certain products can be issued with regard to batch release. The conditions for such a waiver apply to the majority of monoclonal antibodies.

4 CFR 81.5 - Records originating outside GAO, records of interviews, or records involving work in progress.

Code of Federal Regulations, 2010 CFR

2010-01-01

... 4 Accounts 1 2010-01-01 2010-01-01 false Records originating outside GAO, records of interviews... GAO, records of interviews, or records involving work in progress. (a) It is the policy of GAO not to... to the release of a record of interview created by GAO in connection with an audit, evaluation, or...

An Exploration of Progression Rates of Widening Participation Students on to an Integrated Master of Engineering

ERIC Educational Resources Information Center

Humphries-Smith, Tania; Hunt, Clive

2017-01-01

This paper reports on an investigation into the potential to widen participation to Higher Education provided by a flexible learning MEng Engineering. The MEng is part of an integrated programme that provides progression routes from a traditional day release Apprenticeship, through HNC, FdEng at a Further Education College to a flexible learning…

Delivery of drugs bound to erythrocytes: new avenues for an old intravascular carrier

PubMed Central

Villa, Carlos H; Pan, Daniel C; Zaitsev, Sergei; Cines, Douglas B; Siegel, Donald L; Muzykantov, Vladimir R

2015-01-01

For several decades, researchers have used erythrocytes for drug delivery of a wide variety of therapeutics in order to improve their pharmacokinetics, biodistribution, controlled release and pharmacodynamics. Approaches include encapsulation of drugs within erythrocytes, as well as coupling of drugs onto the red cell surface. This review focuses on the latter approach, and examines the delivery of red blood cell (RBC)-surface-bound anti-inflammatory, anti-thrombotic and anti-microbial agents, as well as RBC carriage of nanoparticles. Herein, we discuss the progress that has been made in surface loading approaches, and address in depth the issues relevant to surface loading of RBC, including intrinsic features of erythrocyte membranes, immune considerations, potential surface targets and techniques for the production of affinity ligands. PMID:26228773

Helminths in the gastrointestinal tract as modulators of immunity and pathology.

PubMed

Varyani, Fumi; Fleming, John O; Maizels, Rick M

2017-06-01

Helminth parasites are highly prevalent in many low- and middle-income countries, in which inflammatory bowel disease and other immunopathologies are less frequent than in the developed world. Many of the most common helminths establish themselves in the gastrointestinal tract and can exert counter-inflammatory influences on the host immune system. For these reasons, interest has arisen as to how parasites may ameliorate intestinal inflammation and whether these organisms, or products they release, could offer future therapies for immune disorders. In this review, we discuss interactions between helminth parasites and the mucosal immune system, as well as the progress being made toward identifying mechanisms and molecular mediators through which it may be possible to attenuate pathology in the intestinal tract. Copyright © 2017 the American Physiological Society.

Role of anti-inflammatory adipokines in obesity-related diseases.

PubMed

Ohashi, Koji; Shibata, Rei; Murohara, Toyoaki; Ouchi, Noriyuki

2014-07-01

Obesity results in many health complications. Accumulating evidence indicates that the obese state is characterized by chronic low-grade inflammation, thereby leading to the initiation and progression of obesity-related disorders such as type 2 diabetes, hypertension, cardiovascular disease, and atherosclerosis. Fat tissue releases numerous bioactive molecules, called adipokines, which affect whole-body homeostasis. Most adipokines are proinflammatory, whereas a small number of anti-inflammatory adipokines including adiponectin exert beneficial actions on obese complications. The dysregulated production of adipokines seen in obesity is linked to the pathogenesis of various disease processes. In this review we focus on the role of the anti-inflammatory adipokines that are of current interest in the setting of obesity-linked metabolic and cardiovascular diseases. Copyright © 2014 Elsevier Ltd. All rights reserved.

Fundamental Study of Disposition and Release of Methane in a Shale Gas Reservoir

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

Wang, Yifeng; Xiong, Yongliang; Criscenti, Louise J.

The recent boom in shale gas production through hydrofracturing has reshaped the energy production landscape in the United States. Wellbore production rates vary greatly among the wells within a single field and decline rapidly with time, thus bring up a serious concern with the sustainability of shale gas production. Shale gas production starts with creating a fracture network by injecting a pressurized fluid in a wellbore. The induced fractures are then held open by proppant particles. During production, gas releases from the mudstone matrix, migrates to nearby fractures, and ultimately reaches a production wellbore. Given the relatively high permeability ofmore » the induced fractures, gas release and migration in low-permeability shale matrix is likely to be a limiting step for long-term wellbore production. Therefore, a clear understanding of the underlying mechanisms of methane disposition and release in shale matrix is crucial for the development of new technologies to maximize gas production and recovery. Shale is a natural nanocomposite material with distinct characteristics of nanometer-scale pore sizes, extremely low permeability, high clay contents, significant amounts of organic carbon, and large spatial heterogeneities. Our work has shown that nanopore confinement plays an important role in methane disposition and release in shale matrix. Using molecular simulations, we show that methane release in nanoporous kerogen matrix is characterized by fast release of pressurized free gas (accounting for ~ 30 - 47% recovery) followed by slow release of adsorbed gas as the gas pressure decreases. The first stage is driven by the gas pressure gradient while the second stage is controlled by gas desorption and diffusion. The long-term production decline appears controlled by the second stage of gas release. We further show that diffusion of all methane in nanoporous kerogen behaves differently from the bulk phase, with much smaller diffusion coefficients. The MD simulations also indicate that a significant fraction (3 - 35%) of methane deposited in kerogen can potentially become trapped in isolated nanopores and thus not recoverable. We have successfully established experimental capabilities for measuring gas sorption and desorption on shale and model materials under a wide range of physical and chemical conditions. Both low and high pressure measurements show significant sorption of CH 4 and CO 2 onto clays, implying that methane adsorbed on clay minerals could contribute a significant portion of gas-in-place in an unconventional reservoir. We have also studied the potential impact of the interaction of shale with hydrofracking fluid on gas sorption. We have found that the CH 4-CO 2 sorption capacity for the reacted sample is systematically lower (by a factor of ~2) than that for the unreacted (raw) sample. This difference in sorption capacity may result from a mineralogical or surface chemistry change of the shale sample induced by fluid-rock interaction. Our results shed a new light on mechanistic understanding gas release and production decline in unconventional reservoirs.« less

46 CFR 160.170-15 - Production inspections, tests, quality control, and conformance of release mechanisms.

Code of Federal Regulations, 2014 CFR

2014-10-01

... 46 Shipping 6 2014-10-01 2014-10-01 false Production inspections, tests, quality control, and..., quality control, and conformance of release mechanisms. (a) Unless the Commandant directs otherwise, an... prescribe additional production tests and inspections necessary to maintain quality control and to monitor...

46 CFR 160.133-15 - Production inspections, tests, quality control, and conformance of release mechanisms.

Code of Federal Regulations, 2012 CFR

2012-10-01

... 46 Shipping 6 2012-10-01 2012-10-01 false Production inspections, tests, quality control, and..., tests, quality control, and conformance of release mechanisms. (a) Unless the Commandant directs.... The Commandant may prescribe additional production tests and inspections necessary to maintain quality...

46 CFR 160.170-15 - Production inspections, tests, quality control, and conformance of release mechanisms.

Code of Federal Regulations, 2012 CFR

2012-10-01

... 46 Shipping 6 2012-10-01 2012-10-01 false Production inspections, tests, quality control, and..., quality control, and conformance of release mechanisms. (a) Unless the Commandant directs otherwise, an... prescribe additional production tests and inspections necessary to maintain quality control and to monitor...

46 CFR 160.133-15 - Production inspections, tests, quality control, and conformance of release mechanisms.

Code of Federal Regulations, 2014 CFR

2014-10-01

... 46 Shipping 6 2014-10-01 2014-10-01 false Production inspections, tests, quality control, and..., quality control, and conformance of release mechanisms. (a) Unless the Commandant directs otherwise, an... prescribe additional production tests and inspections necessary to maintain quality control and to monitor...

46 CFR 160.133-15 - Production inspections, tests, quality control, and conformance of release mechanisms.

Code of Federal Regulations, 2013 CFR

2013-10-01

... 46 Shipping 6 2013-10-01 2013-10-01 false Production inspections, tests, quality control, and..., tests, quality control, and conformance of release mechanisms. (a) Unless the Commandant directs.... The Commandant may prescribe additional production tests and inspections necessary to maintain quality...

46 CFR 160.170-15 - Production inspections, tests, quality control, and conformance of release mechanisms.

Code of Federal Regulations, 2013 CFR

2013-10-01

... 46 Shipping 6 2013-10-01 2013-10-01 false Production inspections, tests, quality control, and..., quality control, and conformance of release mechanisms. (a) Unless the Commandant directs otherwise, an... prescribe additional production tests and inspections necessary to maintain quality control and to monitor...

75 FR 8970 - Guidance for Industry on Submission of Documentation in Applications for Parametric Release of...

Federal Register 2010, 2011, 2012, 2013, 2014

2010-02-26

... Veterinary Drug Products Terminally Sterilized by Moist Heat Processes; Availability AGENCY: Food and Drug... Release of Human and Veterinary Drug Products Terminally Sterilized by Moist Heat Processes.'' This... for sterile products terminally sterilized by moist heat when submitting a new drug application (NDA...

Gastrin-releasing peptide in human nasal mucosa.

PubMed

Baraniuk, J N; Lundgren, J D; Goff, J; Peden, D; Merida, M; Shelhamer, J; Kaliner, M

1990-04-01

Gastrin-releasing peptide (GRP), the 27 amino acid mammalian form of bombesin, was studied in human inferior turbinate nasal mucosa. The GRP content of the mucosa measured by radioimmunoassay was 0.60 +/- 0.25 pmol/g tissue (n = 9 patients; mean +/- SEM). GRP-immunoreactive nerves detected by the immunogold method of indirect immunohistochemistry were found predominantly in small muscular arteries, arterioles, venous sinusoids, and between submucosal gland acini. 125I-GRP binding sites determined by autoradiography were exclusively and specifically localized to nasal epithelium and submucosal glands. There was no binding to vessels. The effects of GRP on submucosal gland product release were studied in short-term explant culture. GRP (10 microM) significantly stimulated the release of the serous cell-specific product lactoferrin, and [3H]glucosamine-labeled glycoconjugates which are products of epithelial goblet cells and submucosal gland cells. These observations indicate that GRP released from nerve fibers probably acts on glandular GRP receptors to induce glycoconjugate release from submucosal glands and epithelium and lactoferrin release from serous cells, but that GRP would probably not affect vascular permeability.

Production of endogenous pyrogen.

PubMed

Dinarello, C A

1979-01-01

The production and release of endogenous pyrogen by the host is the first step in the pathogenesis of fever. Endogenous pyrogen is a low-molecular-weight protein released from phagocytic leukocytes in response to several substances of diverse nature. Some of these agents stimulate production of endogenous pyrogen because they are toxic; others act as antigens and interact with either antibody or sensitized lymphocytes in order to induce its production. Some tumors of macrophage origin produce the molecule spontaneously. Whatever the mechanism involved, endogenous pyrogen is synthesized following transcription of new DNA and translation of mRNA into new protein. Once synthesis is completed, the molecule is released without significant intracellular storage. Recent evidence suggests that following release, molecular aggregates form which are biologically active. In its monomer form, endogenous pyrogen is a potent fever-producing substance and mediates fever by its action on the thermoregulatory center.

Microiontophoretic release of drugs from micropipettes

PubMed Central

Clarke, G.; Hill, R. G.; Simmonds, M. A.

1973-01-01

1. The use of 24Na+ of high specific activity allowed its iontophoretic release from multibarrelled glass micropipettes to be followed over short periods with low currents. 2. When a negative retaining current was passed to reduce diffusional efflux between the periods of positive current expulsion of 24Na+, the rate of release of 24Na+ during the expulsion period progressively increased during the first minute before becoming constant. 3. The currents employed were similar to those normally used to regulate the microiontophoretic release of potent drugs such as γ-aminobutyric acid. It is therefore concluded that, during the usual period of response to such drugs, the rate of release of drug is not constant but increasing. 4. The implications of these observations for the construction of microiontophoretic dose-response relationships is discussed. PMID:4724187

Mapping Microbial Carbon Substrate Utilization Across Permafrost Thaw

NASA Astrophysics Data System (ADS)

Anderson, D.; Rich, V. I.; Hodgkins, S. B.; Tfaily, M.; Chanton, J.

2014-12-01

Permafrost thaw is likely to create a substantial positive feedback to climate warming, as previously frozen carbon becomes bioavailable and is released to the atmosphere. Microbes mediate this release, while also consuming "new" carbon from plant inputs and middle-aged soil carbon pools in the seasonally-thawed active layer overlying permafrost. This carbon consumption releases carbon dioxide (CO2) and methane (CH4), both potent greenhouse gases. To investigate microbial carbon cycling in this changing habitat, we examined how microbial communities' carbon substrate degradation changes along a natural permafrost thaw gradient in Stordalen Mire (68.35°N, 19.05°E), northern Sweden. At this location, intermediate thaw creates Sphagnum moss-dominated bogs, while complete thaw results in Eriophorum sedge-dominated fens. The progression of thaw results in increasing organic matter lability (Hodgkins et al, 2014), shifting microbial community composition (Mondav & Woodcroft et al 2014), and changing carbon gas emissions (McCalley et al, in review). However, the inter-relationship of the first two in producing the third remains unclear. We analyzed microbial carbon substrate utilization in the intermediate-thaw and full-thaw sites by two incubation-based methods. We used Biolog EcoPlates, which contain 31 ecologically relevant carbon substrates and a colorimetric marker of their consumption, and into which we added a soil liquid suspension. In addition, we performed mason-jar incubations of peat with carbon substrate amendments and measured CH4 and CO2 emissions. Preliminary Biolog Ecoplate incubations showed that intermediate-thaw features responded faster and more strongly overall to a wide range of substrates relative to the full-thaw features. Preliminary mason jar incubations showed that acetate amendment elicited the greatest response increase in CH4 production and the second greatest increase in CO2 production relative to the controls, in samples from both habitats. In addition, the lowest CH4 and CO2 production was seen in amendments of sphagnum acid. It is important to understand the carbon substrate utilization occurring at these initial and advanced thaw features to speculate the degree to which various carbon inputs are being metabolized to produce the observed gas emissions.

An accountability evaluation for the industry's responsible use of brand mascots and licensed media characters to market a healthy diet to American children.

PubMed

Kraak, V I; Story, M

2015-06-01

Corporate strategies that target children are controversial given the link between food marketing and childhood obesity. This case study explored diverse stakeholders' accountability expectations and actions for industry policies and practices that used popular cartoon brand mascots and media characters to promote food products to American children. We reviewed five electronic databases and Internet sources between January 2000 and January 2015. Evidence (n = 90) was selected based upon the Institute of Medicine's LEAD principles (i.e. locate, evaluate, assemble evidence to inform decisions) and organized into two tables: peer-reviewed articles, books and grey-literature reports (n = 34); and media stories, news releases and public testimony (n = 56). A four-step accountability framework was used to evaluate accountability structures. The results showed that moderate progress was achieved by stakeholders to take and share the account, limited progress to hold industry and government to account, and limited progress to strengthen accountability structures. Between 2006 and 2015, the U.S. Children's Food and Beverage Advertising Initiative lacked clear policies for companies to use brand mascots and media characters on food packages, in merchandising, and as toy giveaways and premiums. Government, industry and civil society can substantially strengthen their accountability for these food marketing practices to ensure healthy food environments for children. © 2015 World Obesity.

Deep-release of Epon 828 epoxy from the shock-driven reaction product phase

NASA Astrophysics Data System (ADS)

Lang, John; Fredenburg, Anthony; Coe, Joshua; Dattelbaum, Dana

2017-06-01

A challenge in improving equations-of-state (EOS) for polymers and their product phase is the lack of off-Hugoniot data. Here, we describe a novel experimental approach for obtaining release pathways along isentropes from the shocked products. A series of gas-gun experiments was conducted to obtain release isentropes of the products for 70/30 wt% Epon 828 epoxy resin/Jeffamine T-403 curing agent. Thin epoxy flyers backed by a low-density syntactic foam were impacted into LiF windows at up to 6.3 mm/ μs, creating stresses in excess of those required for reaction ( 25 GPa). Following a sustained shock input, a rarefaction fan from the back of the thin flyer reduced the pressure in the epoxy products along a release isentrope. Optical velocimetry (PDV) was used to measure the particle velocity at the epoxy/LiF interface. Numerical simulations using several different EOS describing the reactant-to-product transformation were conducted, and the results were compared with measured wave profiles. The best agreement with experiment was obtained using separate tabular EOS for the polymer ``reactant'' (e.g. epoxy) and product mixture, suggesting the transition to the products is irreversible.

Biotic and abiotic processes controlling water chemistry during snowmelt at rabbit ears pass, Rocky Mountains, Colorado, U.S.A.

USGS Publications Warehouse

Peters, N.E.; Leavesley, G.H.

1995-01-01

The chemical composition of snowmelt, groundwater, and streamwater was monitored during the spring of 1991 and 1992 in a 200-ha subalpine catchment on the western flank of the Rocky Mountains near Steamboat Springs, Colorado. Most of the snowmelt occurred during a one-month period annually that began in mid-May 1991 and mid-April 1992. The average water quality characteristics of individual sampling sites (meltwater, streamwater, and groundwater) were similar in 1991 and 1992. The major ions in meltwater were differentially eluted from the snowpack, and meltwater was dominated by Ca2+, SO4/2-, and NO3/-. Groundwater and streamwater were dominated by weathering products, including Ca2+, HCO3/- (measured as alkalinity), and SiO2, and their concentrations decreased as snowmelt progressed. One well had extremely high NO3/- concentrations, which were balanced by Ca2+ concentrations. For this well, hydrogen ion was hypothesized to be generated from nitrification in overlying soils, and subsequently exchanged with other cations, particularly Ca2+. Solute concentrations in streamwater also decreased as snowmelt progressed. Variations in groundwater levels and solute concentrations indicate thai most of the meltwater traveled through the surficial materials. A mass balance for 1992 indicated that the watershed retained H+, NH4/+, NO3/-, SO4/2- and Cl- and was the primary source of base cations and other weathering products. Proportionally more SO4/2- was deposited with the unusually high summer rainfall in 1992 compared to that released from snowmelt, whereas NO3/- was higher in snowmelt and Cl- was the same. The sum of snowmelt and rainfall could account for greater than 90% of the H+ and NH4/+ retained by the watershed and greater than 50% of the NO3/-.The chemical composition of snowmelt, groundwater, and streamwater was monitored during the spring of 1991 and 1992 in a 200-ha subalpine catchment on the western flank of the Rocky Mountains near Steamboat Springs, Colorado. The major ions in meltwater were differentially eluted from the snowpack, and meltwater was dominated by Ca2+, SO42-, and NO3-. Groundwater and streamwater were dominated by weathering products and their concentrations decreased as snowmelt progressed. Solute concentrations in streamwater also decreased as snowmelt progressed. A mass balance for 1992 showed that the watershed retained H+, NH4+, NO3-, SO42- and Cl- and was the primary source of base cations and other weathering products.

Oxidative dissolution of pyrite surfaces by hexavalent chromium: Surface site saturation and surface renewal

NASA Astrophysics Data System (ADS)

Graham, Andrew M.; Bouwer, Edward J.

2012-04-01

In-situ reduction of toxic Cr(VI) to nontoxic Cr(III) represents an important natural attenuation process for Cr(VI)-impacted environments. This study investigates the stoichiometry and kinetics of Cr(VI) reduction by pyrite, a reduced iron-sulfur mineral ubiquitous in recent estuarine and marine sediments. Pyrite suspensions at surface loadings of 0.28-2.10 m2/L (typical of estuarine or marine sediments) were capable of completely reducing 7-120 μM Cr(VI) on the timescale of minutes to days, with the time to reaction completion decreasing with increasing pyrite loading, decreasing initial Cr(VI) concentration, and decreasing suspension pH. Analysis of metal species (Cr and Fe) and sulfur species in solution and at the mineral surface indicated that Cr(VI) oxidatively dissolved the pyrite surface, releasing ferrous iron and sulfate into solution as the reaction progressed. Surface disulfide groups were postulated as the Cr(VI)-reactive surface entity. Net production or consumption of aqueous Fe(II) was shown to depend upon the relative rates of proton-promoted Fe(II) release, Fe(II) release due to oxidative dissolution of pyrite in the presence of Cr(VI), and Fe(II) consumption due to homogeneous reaction with Cr(VI). Kinetics of Cr(VI) reduction by pyrite displayed a biphasic pattern, and the time to reaction completion increased dramatically with increasing initial Cr(VI) concentration. Rapid Cr(VI) removal occurred early in the reaction progress, attributable to Cr(VI) loss under an adsorption-limited regime. Slow, approximately zero-order, Cr(VI) removal occurred over the bulk of the time courses, and corresponded to Cr(VI) removal under surface site saturation conditions. Stoichiometric Cr(VI) reduction was able to proceed under surface site limited conditions owing to regeneration of reactive surface sites following desorption/dissolution of oxidized surface products, as demonstrated in repeat Cr(VI)-spiking experiments. The role of surface passivation was evaluated by comparing rates of Cr(VI) reduction in the presence and absence of the Cr(III)-complexing agent citrate. While citrate addition significantly enhanced Cr(III) solubility, rates of Cr(VI) reduction were only marginally accelerated, suggesting that Cr(OH)3(s) coatings did not completely block access of Cr(VI) to reactive surface sites on pyrite. Given the rapid rates of Cr(VI) reduction with pyrite under pH and surface coverage conditions typical of natural environments, we propose that Cr(VI) reduction by pyrite be considered in fate and transport models for Cr in contaminated sediments.

Pharmacological characterisation of CR6086, a potent prostaglandin E2 receptor 4 antagonist, as a new potential disease-modifying anti-rheumatic drug.

PubMed

Caselli, Gianfranco; Bonazzi, Albino; Lanza, Marco; Ferrari, Flora; Maggioni, Daniele; Ferioli, Cristian; Giambelli, Roberto; Comi, Eleonora; Zerbi, Silvia; Perrella, Marco; Letari, Ornella; Di Luccio, Elena; Colovic, Milena; Persiani, Stefano; Zanelli, Tiziano; Mennuni, Laura; Piepoli, Tiziana; Rovati, Lucio Claudio

2018-03-01

Prostaglandin E 2 (PGE 2 ) acts via its EP4 receptor as a cytokine amplifier (e.g., interleukin [IL]-6) and induces the differentiation and expansion of inflammatory T-helper (Th) lymphocytes. These mechanisms play a key role in the onset and progression of rheumatoid arthritis (RA). We present the pharmacological characterisation of CR6086, a novel EP4 receptor antagonist, and provide evidence for its potential as a disease-modifying anti-rheumatic drug (DMARD). CR6086 affinity and pharmacodynamics were studied in EP4-expressing HEK293 cells by radioligand binding and cyclic adenosine monophosphate (cAMP) production, respectively. In immune cells, IL-6 and vascular endothelial growth factor (VEGF) expression were analysed by RT-PCR, and IL-23 and IL-17 release were measured by enzyme-linked immunosorbent assay (ELISA). In collagen-induced arthritis (CIA) models, rats or mice were immunised with bovine collagen type II. Drugs were administered orally (etanercept and methotrexate intraperitoneally) starting at disease onset. Arthritis progression was evaluated by oedema, clinical score and histopathology. Anti-collagen II immunoglobulin G antibodies were measured by ELISA. CR6086 showed selectivity and high affinity for the human EP4 receptor (K i = 16.6 nM) and functioned as a pure antagonist (half-maximal inhibitory concentration, 22 nM) on PGE 2 -stimulated cAMP production. In models of human immune cells in culture, CR6086 reduced key cytokine players of RA (IL-6 and VEGF expression in macrophages, IL-23 release from dendritic cells, IL-17 release from Th17 cells). In the CIA model of RA in rats and mice, CR6086 significantly improved all features of arthritis: severity, histology, inflammation and pain. In rats, CR6086 was better than the selective cyclooxygenase-2 inhibitor rofecoxib and at least as effective as the Janus kinase inhibitor tofacitinib. In mice, CR6086 and the biologic DMARD etanercept were highly effective, whereas the non-steroidal anti-inflammatory drug naproxen was ineffective. Importantly, in a study of CR6086/methotrexate, combined treatment greatly improved the effect of a fully immunosuppressive dose of methotrexate. CR6086 is a novel, potent EP4 antagonist showing favourable immunomodulatory properties, striking DMARD effects in rodents, and anti-inflammatory activity targeted to immune-mediated inflammatory diseases and distinct from the general effects of cyclooxygenase inhibitors. These results support the clinical development of CR6086, both as a stand-alone DMARD and as a combination therapy with methotrexate. The proof-of-concept trial in patients with RA is ongoing.

RIP1-mediated mitochondrial dysfunction and ROS production contributed to tumor necrosis factor alpha-induced L929 cell necroptosis and autophagy.

PubMed

Ye, Yuan-Chao; Wang, Hong-Ju; Yu, Lu; Tashiro, Shin-Ichi; Onodera, Satoshi; Ikejima, Takashi

2012-12-01

Tumor necrosis factor alpha (TNFα) induces necroptosis and autophagy; however, the detailed molecular mechanism is not fully understood. In this study, we found that TNFα administration caused mitochondrial dysfunction and reactive oxygen species (ROS) production, which led to necroptosis and autophagy in murine fibrosarcoma L929 cells. Notably, the RIP1 (serine-threonine kinase receptor-interacting protein 1, a main adaptor protein of necroptosis) specific inhibitor necrostatin-1 (Nec-1) recovered mitochondrial dysfunction and ROS production due to TNFα administration. Moreover, pan-caspase inhibitor z-VAD-fmk (zVAD) increased RIP1 expression and exacerbated TNFα-induced mitochondrial dysfunction and ROS production, indicating that RIP1 led to mitochondrial dysfunction and ROS production. In addition, cytochrome c release from mitochondria was accompanied with TNFα administration, and Nec-1 blocked the release of cytochrome c upon TNFα administration, while zVAD enhanced the release. These further suggested that RIP1 induced mitochondrial dysfunction accompanied with cytochrome c release. Furthermore, autophagy inhibitor 3-methyladenine (3MA) did not affect RIP1 expression as well as mitochondrial dysfunction and ROS production. Together with our previous publication that autophagy was a downstream consequence of necroptosis, we concluded that TNFα induced mitochondrial dysfunction accompanied with ROS production and cytochrome c release via RIP1, leading to necroptosis and resulting autophagic cell death. Copyright © 2012 Elsevier B.V. All rights reserved.

Antibiotic-induced bacterial killing stimulates tumor necrosis factor-alpha release in whole blood.

PubMed

Arditi, M; Kabat, W; Yogev, R

1993-01-01

Rapid lysis of gram-negative bacteria is associated with considerable release of free endotoxin. Production of tumor necrosis factor (TNF) from adult whole blood ex vivo in response to bacterial products generated during antibiotic killing of Haemophilus influenzae type b (Hib) was investigated. Heparinized whole blood released TNF in a dose-dependent fashion in response to purified lipooligosaccharide of Hib. Bacteria (10(4)-10(7) cfu/mL) were placed into a Transwell filter insert (0.1 microns) and incubated with whole blood in the presence of various antibiotics. Exposure to ceftriaxone resulted in significantly greater release of TNF during killing of Hib than did exposure to imipenem, despite similar degrees of bacterial killing at 6 h. Polymyxin B inhibited the ceftriaxone-induced TNF release by 97%-99%, indicating that free endotoxin was the predominant stimulus for the increase in TNF release in this system. These observations suggest that ceftriaxone-induced killing of Hib results in bacterial cell wall products that are more proinflammatory than those produced by imipenem.

[Immune mechanisms of the active ingredients of Chinese medicinal herbs for chronic prostatitis].

PubMed

Wang, Hao; Zhou, Yu-chun; Xue, Jian-guo

2016-01-01

Chronic prostatitis is a common male disease, and its pathogenesis is not yet clear. Most scholars believe that oxidative stress and immune imbalance are the keys to the occurrence and progression of chronic prostatitis. Currently immunotherapy of chronic prostatitis remains in the exploratory stage. This article relates the active ingredients of 5 Chinese medicinal herbs (total glucosides of paeony, tripterigium wilfordii polglycosidium, curcumin, geniposide, and quercetin) for the treatment of chronic prostatitis and their possible action mechanisms as follows: 1) inhibiting the immune response and activation and proliferation of T-cells, and adjusting the proportion of Th1/Th2 cells; 2) upregulating the expression of Treg and enhancing the patient's tolerability; 3) suppressing the activation of the NF-kB factor, reducing the release of iNOS, and further decreasing the release of NO, IL-2 and other inflammatory cytokines, which contribute to the suppression of the immune response; 4) inhibiting the production of such chemokines as MCP-1 and MIP-1α in order to reduce their induction of inflammatory response. Studies on the immune mechanisms of Chinese medicinal herbs in the treatment of chronic prostatitis are clinically valuable for the development of new drugs for this disease.

Processing of mammalian preprogastrin-releasing peptide.

PubMed

Reeve, J R; Cuttitta, F; Vigna, S R; Shively, J E; Walsh, J H

1988-01-01

The processing of preprogastrin-releasing peptide in mammalian tissues and in cultured cells takes place at discrete sites (Figure 6). Signal peptidase cleaves away the signal peptide from the amino terminus of gastrin-releasing peptide. An exopeptidase activity may remove dipeptides from the amino terminus. The amidation site (not shown in Fig. 6; see Fig. 2) has the same general sequence (Gly-Lys-Lys) seen for other amidated peptides. Cleavage after single basic residues yields gene-related products from Form I or II preproGRP. A unique non-basic cleavage yields a gene-related product from Form III preproGRP. The processing that occurs to form GRP, GRP, and GRP gene-related peptides is shown in Figure 7. ProGRP is cleaved by a series of enzymes to form GRP with an amidated carboxyl-terminal methionine (indicated by an asterisk in Fig. 7). GRP is cleaved to form the decapeptide GRP. The carboxyl-terminal flanking peptides of all three mRNA translation products are cleaved to form several gastrin-releasing peptide gene-related products. Knowledge of the processing of gastrin-releasing peptide and its gene-related products will allow synthesis of duplicates of the stored forms of these peptides, which can then be used for biological testing.

High resolution monitoring system for IRE stack releases.

PubMed

Deconninck, B; De Lellis, C

2013-11-01

The main activity of IRE (Institute for Radio-Element) is radioisotope production of bulk (99)Mo and (131)I for medical application (diagnosis and therapy). Those isotopes are chemically extracted from HEU (High Enriched Uranium) targets activated in reactors. During this process, fission products are released from the targets, including noble gases isotopes (Xe and Kr). Like any nuclear plant, IRE has release limits which are given by the Belgium authority and moreover IRE is in the process of continuously reducing the level of its releases. To achieve this mission, the need of an accurate tool is necessary and IRE has developed a specific monitoring system using a high resolution detector in order to identify and accurately estimate its gaseous releases. This system has a continuous air sampling system in the plant main stack. The sampled gases cross charcoal cartridges where they are slowed down and concentrated for higher detection efficiency. In front of those cartridges is installed an HPGe detector with a detection chain connected to a specific analysis system allowing on-line spectrum analysis. Each isotope can be separately followed without interferences, especially during the production process where high activity can be released. Due to its conception, the system also allows to measure iodine isotopes by integration on the charcoal cartridges. This device is of great help for accurately estimate IRE releases and to help for understanding specific releases and their origin in the production or maintenance process. Copyright © 2013 Elsevier Ltd. All rights reserved.

Modeling the Dynamics and Export of Dissolved Organic Matter in the Northeastern U.S. Continental Shelf

NASA Technical Reports Server (NTRS)

Druon, J.N.; Mannino, A.; Signorini, Sergio R.; McClain, Charles R.; Friedrichs, M.; Wilkin, J.; Fennel, K.

2009-01-01

Continental shelves are believed to play a major role in carbon cycling due to their high productivity. Particulate organic carbon (POC) burial has been included in models as a carbon sink, but we show here that seasonally produced dissolved organic carbon (DOC) on the shelf can be exported to the open ocean by horizontal transport at similar rates (1-2 mol C/sq m/yr) in the southern U.S. Mid-Atlantic Bight (MAB). The dissolved organic matter (DOM) model imbedded in a coupled circulation-biogeochemical model reveals a double dynamics: the progressive release of dissolved organic nitrogen (DON) in the upper layer during summer increases the regenerated primary production by 30 to 300%, which, in turns ; enhances the DOC production mainly from phytoplankton exudation in the upper layer and solubilization of particulate organic matter (POM) deeper in the water column. This analysis suggests that DOM is a key element for better representing the ecosystem functioning and organic fluxes in models because DOM (1) is a major organic pool directly related to primary production, (2) decouples partially the carbon and nitrogen cycles (through carbon excess uptake, POM solubilization and DOM mineralization) and (3) is intimately linked to the residence time of water masses for its distribution and export.

HEAVY AND THERMAL OIL RECOVERY PRODUCTION MECHANISMS

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

Anthony R. Kovscek

2003-04-01

This technical progress report describes work performed from January 1 through March 31, 2003 for the project ''Heavy and Thermal Oil Recovery Production Mechanisms,'' DE-FC26-00BC15311. In this project, a broad spectrum of research is undertaken related to thermal and heavy-oil recovery. The research tools and techniques span from pore-level imaging of multiphase fluid flow to definition of reservoir-scale features through streamline-based history matching techniques. During this period, previous analysis of experimental data regarding multidimensional imbibition to obtain shape factors appropriate for dual-porosity simulation was verified by comparison among analytic, dual-porosity simulation, and fine-grid simulation. We continued to study the mechanismsmore » by which oil is produced from fractured porous media at high pressure and high temperature. Temperature has a beneficial effect on recovery and reduces residual oil saturation. A new experiment was conducted on diatomite core. Significantly, we show that elevated temperature induces fines release in sandstone cores and this behavior may be linked to wettability. Our work in the area of primary production of heavy oil continues with field cores and crude oil. On the topic of reservoir definition, work continued on developing techniques that integrate production history into reservoir models using streamline-based properties.« less

The HST Frontier Fields: High-Level Science Data Products for the First 4 Completed Clusters, and Latest Data on the Remaining Clusters

NASA Astrophysics Data System (ADS)

Koekemoer, Anton M.; Mack, Jennifer; Lotz, Jennifer; Anderson, Jay; Avila, Roberto J.; Barker, Elizabeth A.; Borncamp, David; Gunning, Heather C.; Hilbert, Bryan; Khandrika, Harish G.; Lucas, Ray A.; Ogaz, Sara; Porterfield, Blair; Grogin, Norman A.; Robberto, Massimo; Flanagan, Kathryn; Mountain, Matt; HST Frontier Fields Team

2016-01-01

The Hubble Space Telescope Frontier Fields program is a large Director's Discretionary program of 840 orbits, to obtain ultra-deep observations of six strong lensing clusters of galaxies, together with parallel deep blank fields, making use of the strong lensing amplification by these clusters of distant background galaxies to detect the faintest galaxies currently observable in the high-redshift universe. The first four of these clusters are now complete, namely Abell 2744, MACS J0416.1-2403, MACS J0717.5+3745 and MACS J1149.5+2223, with each of these having been observed over two epochs, to a total depth of 140 orbits on the main cluster and an associated parallel field, using ACS (F435W, F606W, F814W) and WFC3/IR (F105W, F125W, F140W, F160W). The remaining two clusters, Abell 370 and Abell S1063, are currently in progress. Full sets of high-level science products have been generated for all these clusters by the team at STScI, including a total of 24 separate cumulative-depth data releases during each epoch, as well as full-depth version 1.0 releases at the end of each completed epoch. These products include all the full-depth distortion-corrected mosaics and associated products for each cluster, which are science-ready to facilitate the construction of lensing models as well as enabling a wide range of other science projects. Many improvements beyond default calibration for ACS and WFC3/IR are implemented in these data products, including corrections for persistence, time-variable sky, and low-level dark current residuals, as well as improvements in astrometric alignment to achieve milliarcsecond-level accuracy. The resulting high-level science products are delivered via the Mikulski Archive for Space Telescopes (MAST) to the community on a rapid timescale to enable the widest scientific use of these data, as well as ensuring a public legacy dataset of the highest possible quality that is of lasting value to the entire community.

Steady and transient fluid shear stress stimulate NO release in osteoblasts through distinct biochemical pathways

NASA Technical Reports Server (NTRS)

McAllister, T. N.; Frangos, J. A.

1999-01-01

Fluid flow has been shown to be a potent stimulus in osteoblasts and osteocytes and may therefore play an important role in load-induced bone remodeling. The objective of this study was to investigate the characteristics of flow-activated pathways. Previously we reported that fluid flow stimulates rapid and continuous release of nitric oxide (NO) in primary rat calvarial osteoblasts. Here we demonstrate that flow-induced NO release is mediated by shear stress and that this response is distinctly biphasic. Transients in shear stress associated with the onset of flow stimulated a burst in NO production (8.2 nmol/mg of protein/h), while steady flow stimulated sustained NO production (2.2 nmol/mg of protein/h). Both G-protein inhibition and calcium chelation abolished the burst phase but had no effect on sustained production. Activation of G-proteins stimulated dose-dependent NO release in static cultures of both calvarial osteoblasts and UMR-106 osteoblast-like cells. Pertussis toxin had no effect on NO release. Calcium ionophore stimulated low levels of NO production within 15 minutes but had no effect on sustained production. Taken together, these data suggest that fluid shear stress stimulates NO release by two distinct pathways: a G-protein and calcium-dependent phase sensitive to flow transients, and a G-protein and calcium-independent pathway stimulated by sustained flow.

Depositional processes in large-scale debris-flow experiments

USGS Publications Warehouse

Major, J.J.

1997-01-01

This study examines the depositional process and characteristics of deposits of large-scale experimental debris flows (to 15 m3) composed of mixtures of gravel (to 32 mm), sand, and mud. The experiments were performed using a 95-m-long, 2-m-wide debris-flow flume that slopes 31??. Following release, experimental debris flows invariably developed numerous shallow (???10 cm deep) surges. Sediment transported by surges accumulated abruptly on a 3?? runout slope at the mouth of the flume. Deposits developed in a complex manner through a combination of shoving forward and shouldering aside previously deposited debris and through progressive vertical accretion. Progressive accretion by the experimental flows is contrary to commonly assumed en masse sedimentation by debris flows. Despite progressive sediment emplacement, deposits were composed of unstratified accumulations of generally unsorted debris; hence massively textured, poorly sorted debris-flow deposits are not emplaced uniquely en masse. The depositional process was recorded mainly by deposit morphology and surface texture and was not faithfully registered by interior sedimentary texture; homogeneous internal textures could be misinterpreted as the result of en masse emplacement by a single surge. Deposition of sediment by similar, yet separate, debris flows produced a homogenous, massively textured composite deposit having little stratigraphic distinction. Similar deposit characteristics and textures are observed in natural debris-flow deposits. Experimental production of massively textured deposits by progressive sediment accretion limits interpretations that can be drawn from deposit characteristics and casts doubt on methods of estimating flow properties from deposit thickness or from relations between particle size and bed thickness.

Effect of ether glycerol lipids on interleukin-1β release and experimental autoimmune encephalomyelitis.

PubMed

Boomkamp, Stephanie D; Byun, Hoe-Sup; Ubhi, Satvir; Jiang, Hui-Rong; Pyne, Susan; Bittman, Robert; Pyne, Nigel J

2016-01-01

We have assessed the effect of two ether glycerol lipids, 77-6 ((2S, 3R)-4-(Tetradecyloxy)-2-amino-1,3-butanediol) and 56-5 ((S)-2-Amino-3-O-hexadecyl-1-propanol), which are substrates for sphingosine kinases, on inflammatory responses. Treatment of differentiated U937 macrophage-like cells with 77-6 but not 56-5 enhanced IL-1β release; either alone or in the presence of LPS. The stimulatory effect of sphingosine or 77-6 on LPS-stimulated IL-1β release was reduced by pretreatment of cells with the caspase-1 inhibitor, Ac-YVAD-CHO, thereby indicating a role for the inflammasome. The enhancement of LPS-stimulated IL-1β release in response to sphingosine, but not 77-6, was reduced by pretreatment of cells with the cathepsin B inhibitor, CA074Me, indicating a role for lysosomal destabilization in the effect of sphingosine. Administration of 56-5 to mice increased disease progression in an experimental autoimmune encephalomyelitis model and this was associated with a considerable increase in the infiltration of CD4(+) T-cells, CD11b(+) monocytes and F4/80(+) macrophages in the spinal cord. 56-5 and 77-6 were without effect on the degradation of myc-tagged sphingosine 1-phosphate 1 receptor in CCL39 cells. Therefore, the effect of 56-5 on EAE disease progression is likely to be independent of the inflammasome or the sphingosine 1-phosphate 1 receptor. However, 56-5 is chemically similar to platelet activating factor and the exacerbation of EAE disease progression might be linked to platelet activating factor receptor signaling. Copyright © 2015 Elsevier Ireland Ltd. All rights reserved.

Roles of type II thioesterases and their application for secondary metabolite yield improvement.

PubMed

Kotowska, Magdalena; Pawlik, Krzysztof

2014-09-01

A large number of antibiotics and other industrially important microbial secondary metabolites are synthesized by polyketide synthases (PKSs) and nonribosomal peptide synthetases (NRPSs). These multienzymatic complexes provide an enormous flexibility in formation of diverse chemical structures from simple substrates, such as carboxylic acids and amino acids. Modular PKSs and NRPSs, often referred to as megasynthases, have brought about a special interest due to the colinearity between enzymatic domains in the proteins working as an "assembly line" and the chain elongation and modification steps. Extensive efforts toward modified compound biosynthesis by changing organization of PKS and NRPS domains in a combinatorial manner laid good grounds for rational design of new structures and their controllable biosynthesis as proposed by the synthetic biology approach. Despite undeniable progress made in this field, the yield of such "unnatural" natural products is often not satisfactory. Here, we focus on type II thioesterases (TEIIs)--discrete hydrolytic enzymes often encoded within PKS and NRPS gene clusters which can be used to enhance product yield. We review diverse roles of TEIIs (removal of aberrant residues blocking the megasynthase, participation in substrate selection, intermediate, and product release) and discuss their application in new biosynthetic systems utilizing PKS and NRPS parts.

A bibliometric analysis of scientific production on atypical antipsychotic drugs from Italy

PubMed

López-Muñoz, Francisco; De Berardis, Domenico; Fornaro, Michele; Vellante, Federica; di Giannantonio, Massimo; Povedano-Montero, Francisco J; Póveda Fernández-Martín, Maria; Rubio, Gabriel; Álamo, Cecilio

2017-01-01

A bibliometric study of peer-reviewed scientific publications on atypical antipsychotic drugs (AADs) from Italy is herein presented. We selected the documents from Scopus database. We applied several bibliometric indicators of production and dispersion, including Price’s Law about the increase of scientific literature, and Bradford’s Law. We also calculated the participation index across different countries. The bibliometric data have also been correlated with some social and health data sourcing in Italy, such as total per capita expenditure on health and gross domestic expenditure. A total of 2949 original documents were published within the period 1972-2015. Our results state fulfilment of Price’s Law, with scientific production showing exponential growth (r=0.901, as against an r=0.838 after linear adjustment). The drugs most widely studied were clozapine (257 documents), risperidone (179), and olanzapine (172). Stratification into Bradford zones yielded a nucleus represented by the Journal of Clinical Psychopharmacology and Rivista di Psichiatria (58 articles, each one). A total of 1091 different journals were evaluated. The publications on AADs in Italy have undergone exponential growth over the studied period, which is in line with the progressively burgeoning on novel AAD releases. No evidence of saturation point was observed.

Drug Delivery of the Future: Chasing the Invisible Gorilla

PubMed Central

Park, Kinam

2015-01-01

For more than 60 years drug delivery systems have produced numerous controlled release formulations helping patients improve compliance and maximize the drug efficacy. Development of new controlled drug delivery systems was very productive during the period 1950-1980. The productivity, as measured by the number of clinically used formulations, dropped significantly during 1980-2010. This reduced productivity needs to be understood so that the future development of drug delivery systems can be accelerated and prolific again. This requires critical evaluation of the current drug delivery field, so that the factors inhibiting rapid progress can be identified and resolved. The current drug delivery field is faced with an invisible gorilla syndrome, i.e., seeing a gorilla when it is not present and missing a gorilla when it actually exists. Overcoming this syndrome requires a new way of thinking, questioning the status quo. Advances in drug delivery technologies occur by an evolutionary process, and thus, the more trials and errors lead to faster advances. The drug delivery area needs to nurture the environment where vastly different ideas can be tested, and all data, positive or negative, need to be exchanged freely as they have equal importance. PMID:26519857

Effects of Controlled Release Fertilizer on the Post-Production Performance of Impatiens Wallerana

USDA-ARS?s Scientific Manuscript database

Controlled release fertilizers (CRF) in production systems have been known to reduce environmental contamination. However, there is a lot to be explored as per its use in bedding plant production. Bedding plant growers have not adapted CRF use because there is little information about its use and ...

27 CFR 41.85 - Release from customs custody of imported tobacco articles.

Code of Federal Regulations, 2010 CFR

2010-04-01

..., cigarette papers, and cigarettes tubes, which are not put up in packages, i.e., not placed by the... TOBACCO PRODUCTS, CIGARETTE PAPERS AND TUBES, AND PROCESSED TOBACCO Tobacco Products and Cigarette Papers... Products and Cigarette Papers and Tubes Without Payment of Tax Or Certain Duty § 41.85 Release from customs...

CALIOP V4 Level 1 Product Release

Atmospheric Science Data Center

2014-11-13

CALIOP V4 Level 1 Product Release Thursday, November 13, 2014 The Atmospheric Science Data Center (ASDC) at NASA Langley Research Center in collaboration with the CALIPSO ... and peer-reviewed approach.   The version 3.x (3.01, 3.02 and 3.30) CALIOP Level 1 data product will continue to be generated ...

27 CFR 41.85 - Release from customs custody of imported tobacco articles.

Code of Federal Regulations, 2012 CFR

2012-04-01

... TOBACCO PRODUCTS, CIGARETTE PAPERS AND TUBES, AND PROCESSED TOBACCO Tobacco Products and Cigarette Papers... Products and Cigarette Papers and Tubes Without Payment of Tax Or Certain Duty § 41.85 Release from customs..., cigarette papers, and cigarettes tubes, which are not put up in packages, i.e., not placed by the...

27 CFR 41.85 - Release from customs custody of imported tobacco articles.

Code of Federal Regulations, 2013 CFR

2013-04-01

..., cigarette papers, and cigarettes tubes, which are not put up in packages, i.e., not placed by the... TOBACCO PRODUCTS, CIGARETTE PAPERS AND TUBES, AND PROCESSED TOBACCO Tobacco Products and Cigarette Papers... Products and Cigarette Papers and Tubes Without Payment of Tax Or Certain Duty § 41.85 Release from customs...

27 CFR 41.85 - Release from customs custody of imported tobacco articles.

Code of Federal Regulations, 2011 CFR

2011-04-01

..., cigarette papers, and cigarettes tubes, which are not put up in packages, i.e., not placed by the... TOBACCO PRODUCTS, CIGARETTE PAPERS AND TUBES, AND PROCESSED TOBACCO Tobacco Products and Cigarette Papers... Products and Cigarette Papers and Tubes Without Payment of Tax Or Certain Duty § 41.85 Release from customs...

19 CFR 12.8 - Inspection; bond; release.

Code of Federal Regulations, 2011 CFR

2011-04-01

... TREASURY SPECIAL CLASSES OF MERCHANDISE Meat and Meat-Food Products § 12.8 Inspection; bond; release. (a) All imported meat and meat-food products offered for entry into the United States are subject to the..., et seq.). The term “meat and meat-food products,” for the purpose of this section, shall include any...

Marine Mammals and Noise-Progress Since 1995

DTIC Science & Technology

2015-09-30

1 DISTRIBUTION STATEMENT A. Approved for public release; distribution is unlimited. Marine Mammals & Noise - Progress Since 1995 Christine...Erbe Centre for Marine Science & Technology Curtin University GPO Box U1987 Perth, WA 6845, Australia phone: +61-8-9266 7380 email: c.erbe...effects of underwater noise on marine mammals has grown steadily over the last few decades. Results and information are scattered across the peer

EPIRUS-NET: A Wireless Health Telematics Network in Greece

DTIC Science & Technology

2001-10-25

has also to be made. The system is represented of three basic layers: the database layer, the middleware and the Hospital Daily Progress Anamnesis ... Anamnesis . The Encounter entry is uniquely identified by the incremental ID, IID, attribute. Each encounter entry is associated with a clinical...the main entities of the system (Hospital, Patient, Anamnesis , Encounter, Clinical Examination, Daily Progress, Examination, Release Ticket), along

Quantum Manybody Physics with Rydberg Polaritons

DTIC Science & Technology

2016-06-22

report, such as final, technical, interim, memorandum, master’s thesis, progress, quarterly, research , special, group study, etc. 3. DATES COVERED...for public release. Over the course of this grant, we have seen tremendous progress, both theoretically and experimentally , in our control of photonic...shown in multiple stages of construction at left and below, spans three optical tables in two rooms: One for the experimental control system

The role of HFE genotype in macrophage phenotype.

PubMed

Nixon, Anne M; Neely, Elizabeth; Simpson, Ian A; Connor, James R

2018-02-01

Iron regulation is essential for cellular energy production. Loss of cellular iron homeostasis has critical implications for both normal function and disease progression. The H63D variant of the HFE gene is the most common gene variant in Caucasians. The resulting mutant protein alters cellular iron homeostasis and is associated with a number of neurological diseases and cancer. In the brain, microglial and infiltrating macrophages are critical to maintaining iron homeostasis and modulating inflammation associated with the pathogenic process in multiple diseases. This study addresses whether HFE genotype affects macrophage function and the implications of these findings for disease processes. Bone marrow macrophages were isolated from wildtype and H67D HFE knock-in mice. The H67D gene variant in mice is the human equivalent of the H63D variant. Upon differentiation, the macrophages were used to analyze iron regulatory proteins, cellular iron release, migration, phagocytosis, and cytokine expression. The results of this study demonstrate that the H67D HFE genotype significantly impacts a number of critical macrophage functions. Specifically, fundamental activities such as proliferation in response to iron exposure, L-ferritin expression in response to iron loading, secretion of BMP6 and cytokines, and migration and phagocytic activity were all found to be impacted by genotype. Furthermore, we demonstrated that exposure to apo-Tf (iron-poor transferrin) can increase the release of iron from macrophages. In normal conditions, 70% of circulating transferrin is unsaturated. Therefore, the ability of apo-Tf to induce iron release could be a major regulatory mechanism for iron release from macrophages. These studies demonstrate that the HFE genotype impacts fundamental components of macrophage phenotype that could alter their role in degenerative and reparative processes in neurodegenerative disorders.

Discovery and characterization of natural products that act as pheromones in fish.

PubMed

Li, Ke; Buchinger, Tyler J; Li, Weiming

2018-06-20

Covering: up to 2018 Fish use a diverse collection of molecules to communicate with conspecifics. Since Karlson and Lüscher termed these molecules 'pheromones', chemists and biologists have joined efforts to characterize their structures and functions. In particular, the understanding of insect pheromones developed at a rapid pace, set, in part, by the use of bioassay-guided fractionation and natural product chemistry. Research on vertebrate pheromones, however, has progressed more slowly. Initially, biologists characterized fish pheromones by screening commercially available compounds suspected to act as pheromones based upon their physiological function. Such biology-driven screening has proven a productive approach to studying pheromones in fish. However, the many functions of fish pheromones and diverse metabolites that fish release make predicting pheromone identity difficult and necessitate approaches led by chemistry. Indeed, the few cases in which pheromone identification was led by natural product chemistry indicated novel or otherwise unpredicted compounds act as pheromones. Here, we provide a brief review of the approaches to identifying pheromones, placing particular emphasis on the promise of using natural product chemistry together with assays of biological activity. Several case studies illustrate bioassay-guided fractionation as an approach to pheromone identification in fish and the unexpected diversity of pheromone structures discovered by natural product chemistry. With recent advances in natural product chemistry, bioassay-guided fractionation is likely to unveil an even broader collection of pheromone structures and enable research that spans across disciplines.

Homocysteine Is an Oncometabolite in Breast Cancer, Which Promotes Tumor Progression and Metastasis

DTIC Science & Technology

2017-01-01

January 2017 TYPE OF REPORT: Annual PREPARED FOR: U.S. Army Medical Research and Materiel Command Fort Detrick, Maryland 21702-5012 DISTRIBUTION ...STATEMENT: Approved for Public Release; Distribution Unlimited The views, opinions and/or findings contained in this report are those of the author(s...SPONSOR/MONITOR’S REPORT NUMBER(S) 12. DISTRIBUTION / AVAILABILITY STATEMENT Approved for Public Release; Distribution Unlimited 13. SUPPLEMENTARY

Advanced Glycation End Products: Association with the Pathogenesis of Diseases and the Current Therapeutic Advances.

PubMed

Ajith, Thekkuttuparambil A; Vinodkumar, Puzhikunathu

2016-01-01

Advanced glycation end products (AGE) such as N-ε-carboxy-ethyl-lysine (CEL), N-ε-carboxy-methyl-lysine (CML), imidazolone, methyl-glyoxal-lysine dimer (MOLD), glyoxal-lysine dimer (GOLD), pyrraline and pentosidine have been imparted in the development and worsening of complications of diabetes. They are also involved in atherosclerosis, normal aging process, arthritis, cancer and progression of age-related neurodegenerative diseases like Alzheimer`s disease. Endogenously, they are formed by nonenzymatic glycation by aldoses/ketoses to form intermediate precursor that were slowly converted into AGE. A positive correlation was observed with the level of AGEs formation and progression of the diseases. Exogenously, they formed in foods when they were cooked at very high temperature. AGEs can interact with the cell surface receptors of AGE (RAGE) to release cytokines, free radicals as well as directly modify the extracellular matrix and action of hormones. Hence, the mechanism of AGE association with pathogenesis of diseases can be ascribed mainly to the generated cytokines and free radicals. Second type of receptors such as AGE receptor-1, 2 and 3 were more specific and involved in their detoxification and clearance. Therapeutic agents were used to inhibit AGEs formation, traps the reactive carbonyl intermediate precursors, interfering with Amadori`s products, cross-link breaker and low molecular weight inhibitors of RAGE had been described as well. Despite the several therapeutic agents described so far, none of them have proven to be recommended for clinical use. Furthermore, no methods or standard units were accepted universally to measure AGEs are existing. This review discusses AGEs formation, association with diseases and therapeutic agents to alleviate them.

The Driving Magnetic Field and Reconnection in CME/Flare Eruptions and Coronal Jets

NASA Technical Reports Server (NTRS)

Moore, Ronald L.

2010-01-01

Signatures of reconnection in major CME (coronal mass ejection)/flare eruptions and in coronal X-ray jets are illustrated and interpreted. The signatures are magnetic field lines and their feet that brighten in flare emission. CME/flare eruptions are magnetic explosions in which: 1. The field that erupts is initially a closed arcade. 2. At eruption onset, most of the free magnetic energy to be released is not stored in field bracketing a current sheet, but in sheared field in the core of the arcade. 3. The sheared core field erupts by a process that from its start or soon after involves fast "tether-cutting" reconnection at an initially small current sheet low in the sheared core field. If the arcade has oppositely-directed field over it, the eruption process from its start or soon after also involves fast "breakout" reconnection at an initially small current sheet between the arcade and the overarching field. These aspects are shown by the small area of the bright field lines and foot-point flare ribbons in the onset of the eruption. 4. At either small current sheet, the fast reconnection progressively unleashes the erupting core field to erupt with progressively greater force. In turn, the erupting core field drives the current sheet to become progressively larger and to undergo progressively greater fast reconnection in the explosive phase of the eruption, and the flare arcade and ribbons grow to become comparable to the pre-eruption arcade in lateral extent. In coronal X-ray jets: 1. The magnetic energy released in the jet is built up by the emergence of a magnetic arcade into surrounding unipolar "open" field. 2. A simple jet is produced when a burst of reconnection occurs at the current sheet between the arcade and the open field. This produces a bright reconnection jet and a bright reconnection arcade that are both much smaller in diameter that the driving arcade. 3. A more complex jet is produced when the arcade has a sheared core field and undergoes an ejective eruption in the manner of a miniature CME/flare eruption. The jet is then a combination of a miniature CME and the products of more widely distributed reconnection of the erupting arcade with the open field than in simple jets.

Mast cells and fibroblasts work in concert to aggravate pulmonary fibrosis: role of transmembrane SCF and the PAR-2/PKC-α/Raf-1/p44/42 signaling pathway.

PubMed

Wygrecka, Malgorzata; Dahal, Bhola K; Kosanovic, Djuro; Petersen, Frank; Taborski, Brigitte; von Gerlach, Susanne; Didiasova, Miroslava; Zakrzewicz, Dariusz; Preissner, Klaus T; Schermuly, Ralph T; Markart, Philipp

2013-06-01

Mast cell (MC) accumulation has been demonstrated in the lungs of idiopathic pulmonary fibrosis (IPF) patients. Mediators released from MCs may regulate tissue remodeling processes, thereby contributing to IPF pathogenesis. We investigated the role of MC-fibroblast interaction in the progression of lung fibrosis. Increased numbers of activated MCs, in close proximity to fibroblast foci and alveolar type II cells, were observed in IPF lungs. Correspondingly elevated tryptase levels were detected in IPF lung tissue samples. Coculture of human lung MCs with human lung fibroblasts (HLFs) induced MC activation, as evinced by tryptase release, and stimulated HLF proliferation; IPF HLFs exhibited a significantly higher growth rate, compared with control. Tryptase stimulated HLF growth in a PAR-2/PKC-α/Raf-1/p44/42-dependent manner and potentiated extracellular matrix production, but independent of PKC-α, Raf-1, and p44/42 activities. Proproliferative properties of tryptase were attenuated by knockdown or pharmacological inhibition of PAR-2, PKC-α, Raf-1, or p44/42. Expression of transmembrane SCF, but not soluble SCF, was elevated in IPF lung tissue and in fibroblasts isolated from IPF lungs. Coculture of IPF HLFs with MCs enhanced MC survival and proliferation. These effects were cell-contact dependent and could be inhibited by application of anti-SCF antibody or CD117 inhibitor. Thus, fibroblasts and MCs appear to work in concert to perpetuate fibrotic processes and so contribute to lung fibrosis progression. Copyright © 2013 American Society for Investigative Pathology. Published by Elsevier Inc. All rights reserved.

Dopamine, 6-hydroxydopamine, iron, and dioxygen--their mutual interactions and possible implication in the development of Parkinson's disease.

PubMed

Linert, W; Herlinger, E; Jameson, R F; Kienzl, E; Jellinger, K; Youdim, M B

1996-08-23

The reactions of dopamine (1-amino-2-(3,4-dihydroxyphenyl)-ethane, DA), 5-hydroxydopamine (5-OHDA), and 6-hydroxydopamine (6-OHDA), with molecular oxygen-with and without the addition of catalytic amounts of iron(III) and other metal ions-have been studied and the implication of these results with respect to the chemistry involved in the progress of Parkinson's disease is discussed. In the presence of O2 DA reacts spontaneously without the necessity of metal-ion catalysis under the production of stoichiometric amounts of H2O2, to form initially pink dopaminochrome, which is not stable and reacts further (without the consumption of dioxygen) to form the insoluble polymeric material known as 'melanine'. DA reacts with iron(III) yielding an intermediate 1:1 complex, which decomposes releasing Fe(II) and the semiquinone, which reacts further under involvement of both Fe(III) and dioxygen. 6-OHDA reacts without showing the necessity of such an intermediate, and it is shown to be able to release iron as Fe(II) from ferritine. On the other hand, it is shown (in vitro) that Fe(II) reacts in a Fenton type reaction with DA and the present H2O2 producing 5-OHDA and especially 6-OHDA. Based on these mutual interacting reactions a mechanism for the initiation and progress of Parkinson's disease is suggested. The catalytic effects of some other transition-metal ions are presented and an explanation for the peculiarly toxic effects of manganese(II) is put forward. Finally, a possible reason for the effect that nicotine has in the mitigation of Parkinson's disease is discussed.

Accelerated in-vitro release testing methods for extended-release parenteral dosage forms.

PubMed

Shen, Jie; Burgess, Diane J

2012-07-01

This review highlights current methods and strategies for accelerated in-vitro drug release testing of extended-release parenteral dosage forms such as polymeric microparticulate systems, lipid microparticulate systems, in-situ depot-forming systems and implants. Extended-release parenteral dosage forms are typically designed to maintain the effective drug concentration over periods of weeks, months or even years. Consequently, 'real-time' in-vitro release tests for these dosage forms are often run over a long time period. Accelerated in-vitro release methods can provide rapid evaluation and therefore are desirable for quality control purposes. To this end, different accelerated in-vitro release methods using United States Pharmacopeia (USP) apparatus have been developed. Different mechanisms of accelerating drug release from extended-release parenteral dosage forms, along with the accelerated in-vitro release testing methods currently employed are discussed. Accelerated in-vitro release testing methods with good discriminatory ability are critical for quality control of extended-release parenteral products. Methods that can be used in the development of in-vitro-in-vivo correlation (IVIVC) are desirable; however, for complex parenteral products this may not always be achievable. © 2012 The Authors. JPP © 2012 Royal Pharmaceutical Society.

Accelerated in vitro release testing methods for extended release parenteral dosage forms

PubMed Central

Shen, Jie; Burgess, Diane J.

2012-01-01

Objectives This review highlights current methods and strategies for accelerated in vitro drug release testing of extended release parenteral dosage forms such as polymeric microparticulate systems, lipid microparticulate systems, in situ depot-forming systems, and implants. Key findings Extended release parenteral dosage forms are typically designed to maintain the effective drug concentration over periods of weeks, months or even years. Consequently, “real-time” in vitro release tests for these dosage forms are often run over a long time period. Accelerated in vitro release methods can provide rapid evaluation and therefore are desirable for quality control purposes. To this end, different accelerated in vitro release methods using United States Pharmacopoeia (USP) apparatus have been developed. Different mechanisms of accelerating drug release from extended release parenteral dosage forms, along with the accelerated in vitro release testing methods currently employed are discussed. Conclusions Accelerated in vitro release testing methods with good discriminatory ability are critical for quality control of extended release parenteral products. Methods that can be used in the development of in vitro-in vivo correlation (IVIVC) are desirable, however for complex parenteral products this may not always be achievable. PMID:22686344

ICP-MS analysis of fission product diffusion in graphite for High-Temperature Gas-Cooled Reactors

NASA Astrophysics Data System (ADS)

Carter, Lukas M.

Release of radioactive fission products from nuclear fuel during normal reactor operation or in accident scenarios is a fundamental safety concern. Of paramount importance are the understanding and elucidation of mechanisms of chemical interaction, nuclear interaction, and transport phenomena involving fission products. Worldwide efforts to reduce fossil fuel dependence coupled with an increasing overall energy demand have generated renewed enthusiasm toward nuclear power technologies, and as such, these mechanisms continue to be the subjects of vigorous research. High-Temperature Gas-Cooled Reactors (HTGRs or VHTRs) remain one of the most promising candidates for the next generation of nuclear power reactors. An extant knowledge gap specific to HTGR technology derives from an incomplete understanding of fission product transport in major core materials under HTGR operational conditions. Our specific interest in the current work is diffusion in reactor graphite. Development of methods for analysis of diffusion of multiple fission products is key to providing accurate models for fission product release from HTGR core components and the reactor as a whole. In the present work, a specialized diffusion cell has been developed and constructed to facilitate real-time diffusion measurements via ICP-MS. The cell utilizes a helium gas-jet system which transports diffusing fission products to the mass spectrometer using carbon nanoparticles. The setup was designed to replicate conditions present in a functioning HTGR, and can be configured for real-time release or permeation measurements of single or multiple fission products from graphite or other core materials. In the present work, we have analyzed release rates of cesium in graphite grades IG-110, NBG-18, and a commercial grade of graphite, as well as release of iodine in IG-110. Additionally we have investigated infusion of graphite samples with Cs, I, Sr, Ag, and other surrogate fission products for use in release or profile measurements of diffusion coefficients.

Development and validation of a new dynamic computer-controlled model of the human stomach and small intestine.

PubMed

Guerra, Aurélie; Denis, Sylvain; le Goff, Olivier; Sicardi, Vincent; François, Olivier; Yao, Anne-Françoise; Garrait, Ghislain; Manzi, Aimé Pacifique; Beyssac, Eric; Alric, Monique; Blanquet-Diot, Stéphanie

2016-06-01

For ethical, regulatory, and economic reasons, in vitro human digestion models are increasingly used as an alternative to in vivo assays. This study aims to present the new Engineered Stomach and small INtestine (ESIN) model and its validation for pharmaceutical applications. This dynamic computer-controlled system reproduces, according to in vivo data, the complex physiology of the human stomach and small intestine, including pH, transit times, chyme mixing, digestive secretions, and passive absorption of digestion products. Its innovative design allows a progressive meal intake and the differential gastric emptying of solids and liquids. The pharmaceutical behavior of two model drugs (paracetamol immediate release form and theophylline sustained release tablet) was studied in ESIN during liquid digestion. The results were compared to those found with a classical compendial method (paddle apparatus) and in human volunteers. Paracetamol and theophylline tablets showed similar absorption profiles in ESIN and in healthy subjects. For theophylline, a level A in vitro-in vivo correlation could be established between the results obtained in ESIN and in humans. Interestingly, using a pharmaceutical basket, the swelling and erosion of the theophylline sustained release form was followed during transit throughout ESIN. ESIN emerges as a relevant tool for pharmaceutical studies but once further validated may find many other applications in nutritional, toxicological, and microbiological fields. Biotechnol. Bioeng. 2016;113: 1325-1335. © 2015 Wiley Periodicals, Inc. © 2015 Wiley Periodicals, Inc.

Kinetic modeling of light limitation and sulfur deprivation effects in the induction of hydrogen production with Chlamydomonas reinhardtii: Part I. Model development and parameter identification.

PubMed

Fouchard, Swanny; Pruvost, Jérémy; Degrenne, Benoit; Titica, Mariana; Legrand, Jack

2009-01-01

Chlamydomonas reinhardtii is a green microalga capable of turning its metabolism towards H2 production under specific conditions. However this H2 production, narrowly linked to the photosynthetic process, results from complex metabolic reactions highly dependent on the environmental conditions of the cells. A kinetic model has been developed to relate culture evolution from standard photosynthetic growth to H2 producing cells. It represents transition in sulfur-deprived conditions, known to lead to H2 production in Chlamydomonas reinhardtii, and the two main processes then induced which are an over-accumulation of intracellular starch and a progressive reduction of PSII activity for anoxia achievement. Because these phenomena are directly linked to the photosynthetic growth, two kinetic models were associated, the first (one) introducing light dependency (Haldane type model associated to a radiative light transfer model), the second (one) making growth a function of available sulfur amount under extracellular and intracellular forms (Droop formulation). The model parameters identification was realized from experimental data obtained with especially designed experiments and a sensitivity analysis of the model to its parameters was also conducted. Model behavior was finally studied showing interdependency between light transfer conditions, photosynthetic growth, sulfate uptake, photosynthetic activity and O2 release, during transition from oxygenic growth to anoxic H2 production conditions.

Reported implementation lessons from a national quality improvement initiative; Productive Ward: Releasing Time to Care™. A qualitative, ward-based team perspective.

PubMed

White, Mark; Butterworth, Tony; Wells, John S G

2017-10-01

To explore the experiences of participants involved in the implementation of the Productive Ward: Releasing Time to Care™ initiative in Ireland, identifying key implementation lessons. A large-scale quality improvement programme Productive Ward: Releasing Time to Care™ was introduced nationwide into Ireland in 2011. We captured accounts from ward-based teams in an implementation phase during 2013-14 to explore their experiences. Semi-structured, in-depth interviews with a purposive sample of 24 members of ward-based teams from nine sites involved in the second national phase of the initiative were conducted. Interviews were analysed and coded under themes, using a seven-stage iterative process. The predominant theme identified was associated with the implementation and management of the initiative and included: project management; training; preparation; information and communication; and participant's negative experiences. The most prominent challenge reported related to other competing clinical priorities. Despite the structured approach of Productive Ward: Releasing Time to Care™, it appears that overstretched and busy clinical environments struggle to provide the right climate and context for ward-based teams to engage and interact actively with quality improvement tools, methods and activities. Findings highlight five key aspects of implementation and management that will help facilitate successful adoption of large-scale, ward-based quality improvement programmes such as Productive Ward: Releasing Time to Care™. Utilising pre-existing implementation or quality frameworks to assess each ward/unit for 'readiness' prior to commencing a quality improvement intervention such as Productive Ward: Releasing Time to Care™ should be considered. © 2017 John Wiley & Sons Ltd.

A comparative study of TiN and TiC: Oxidation resistance and retention of xenon at high temperature and under degraded vacuum

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

Gavarini, S.; Bes, R.; Millard-Pinard, N.

2011-01-01

Dense TiN and TiC samples were prepared by hot pressing using micrometric powders. Xenon species (simulating rare gas fission products) were then implanted into the ceramics. The samples were annealed for 1 h at 1500 deg. C under several degraded vacuums with P{sub O{sub 2}} varying from 10{sup -6} to 2x10{sup -4} mbars. The oxidation resistance of the samples and their retention properties with respect to preimplanted xenon species were analyzed using scanning electron microscopy, grazing incidence x-ray diffraction, Rutherford backscattering spectrometry, and nuclear backscattering spectrometry. Results indicate that TiC is resistant to oxidation and does not release xenon formore » P{sub O{sub 2{<=}}}6x10{sup -6} mbars. When P{sub O{sub 2}} increases, geometric oxide crystallites appear at the surface depending on the orientation and size of TiC grains. These oxide phases are Ti{sub 2}O{sub 3}, Ti{sub 3}O{sub 5}, and TiO{sub 2}. Apparition of oxide crystallites is associated with the beginning of xenon release. TiC surface is completely covered by the oxide phases at P{sub O{sub 2}}=2x10{sup -4} mbars up to a depth of 3 {mu}m and the xenon is then completely released. For TiN samples, the results show a progressive apparition of oxide crystallites (Ti{sub 3}O{sub 5} mainly) at the surface when P{sub O{sub 2}} increases. The presence of the oxide crystallites is also directly correlated with xenon release, the more oxide crystallites are growing the more xenon is released. TiN surface is completely covered by an oxide layer at P{sub O{sub 2}}=2x10{sup -4} mbars up to 1 {mu}m. A correlation between the initial fine microstructure of TiN and the properties of the growing layer is suggested.« less

Rab3-GAP controls the progression of synaptic homeostasis at a late stage of vesicle release.

PubMed

Müller, Martin; Pym, Edward C G; Tong, Amy; Davis, Graeme W

2011-02-24

Homeostatic signaling systems stabilize neural function through the modulation of neurotransmitter receptor abundance, ion channel density, and presynaptic neurotransmitter release. Molecular mechanisms that drive these changes are being unveiled. In theory, molecular mechanisms may also exist to oppose the induction or expression of homeostatic plasticity, but these mechanisms have yet to be explored. In an ongoing electrophysiology-based genetic screen, we have tested 162 new mutations for genes involved in homeostatic signaling at the Drosophila NMJ. This screen identified a mutation in the rab3-GAP gene. We show that Rab3-GAP is necessary for the induction and expression of synaptic homeostasis. We then provide evidence that Rab3-GAP relieves an opposing influence on homeostasis that is catalyzed by Rab3 and which is independent of any change in NMJ anatomy. These data define roles for Rab3-GAP and Rab3 in synaptic homeostasis and uncover a mechanism, acting at a late stage of vesicle release, that opposes the progression of homeostatic plasticity. Copyright © 2011 Elsevier Inc. All rights reserved.

CALIPSO IIR L1 V2-00 Release Announcement

Atmospheric Science Data Center

2017-07-12

... products will continue to be generated and provided to the public. There is no expedited version of the V2.00 IIR Level 1 planned for this release.   Information about this data product, including data availability, user ...

Impacts of CERCLA Release Notification Requirements on Transportation of Products Containing Hazardous Substances

DOT National Transportation Integrated Search

1986-08-01

In order to determine the regulatory burden imposed by CERCLA release-notification requirements on shippers and carriers handling products containing hazardous substances, eight shippers and seven carriers were interviewed in depth during the summer ...

EMMPRIN/CD147-encriched membrane vesicles released from malignant human testicular germ cells increase MMP production through tumor-stroma interaction.

PubMed

Milia-Argeiti, Eleni; Mourah, Samia; Vallée, Benoit; Huet, Eric; Karamanos, Nikos K; Theocharis, Achilleas D; Menashi, Suzanne

2014-08-01

Elevated levels of EMMPRIN/CD147 in cancer tissues have been correlated with tumor progression but the regulation of its expression is not yet understood. Here, the regulation of EMMPRIN expression was investigated in testicular germ cell tumor (TGCTs) cell lines. EMMPRIN expression in seminoma JKT-1 and embryonal carcinoma NT2/D1 cell lines was determined by Western blot, immunofluorescence and qRT-PCR. Membrane vesicles (MVs) secreted from these cells, treated or not with EMMPRIN siRNA, were isolated by differential centrifugations of their conditioned medium. MMP-2 was analyzed by zymography and qRT-PCR. The more aggressive embryonic carcinoma NT2/D1 cells expressed more EMMPRIN mRNA than the seminoma JKT-1 cells, but surprisingly contained less EMMPRIN protein, as determined by immunoblotting and immunostaining. The protein/mRNA discrepancy was not due to accelerated protein degradation in NT2/D1 cells, but by the secretion of EMMPRIN within MVs, as the vesicles released from NT2/D1 contained considerably more EMMPRIN than those released from JKT-1. EMMPRIN-containing MVs obtained from NT2/D1, but not from EMMPRIN-siRNA treated NT2/D1, increased MMP-2 production in fibroblasts to a greater extent than those from JKT-1 cells. The data presented show that the more aggressive embryonic carcinoma cells synthesize more EMMPRIN than seminoma cells, but which they preferentially target to secreted MVs, unlike seminoma cells which retain EMMPRIN within the cell membrane. This cellular event points to a mechanism by which EMMPRIN expressed by malignant testicular cells can exert its MMP inducing effect on distant cells within the tumor microenvironment to promote tumor invasion. This article is part of a Special Issue entitled Matrix-mediated cell behaviour and properties. Copyright © 2014 Elsevier B.V. All rights reserved.

Crocodile choline from Crocodylus siamensis induces apoptosis of human gastric cancer.

PubMed

Mao, Xiao-Mei; Fu, Qi-Rui; Li, Hua-Liang; Zheng, Ya-Hui; Chen, Shu-Ming; Hu, Xin-Yi; Chen, Qing-Xi; Chen, Qiong-Hua

2017-03-01

Crocodile choline, an active compound isolated from Crocodylus siamensis, was found to exert potent anti-cancer activities against human gastric cancer cells in vitro and in vivo. Our study revealed that crocodile choline led to cell cycle arrest at the G2/M phase through attenuating the expressions of cyclins, Cyclin B1, and CDK-1. Furthermore, crocodile choline accelerated apoptosis through the mitochondrial apoptotic pathway with the decrease in mitochondrial membrane potential, the increase in reactive oxygen species production and Bax/Bcl-2 ratio, and the activation of caspase-3 along with the release of cytochrome c. In addition, this study, for the first time, shows that Notch pathway is remarkably deregulated by crocodile choline. The combination of crocodile choline and Notch1 short interfering RNA led to dramatically increased cytotoxicity than observed with either agent alone. Notch1 short interfering RNA sensitized and potentiated the capability of crocodile choline to suppress the cell progression and invasion of gastric cancer. Taken together, these data suggested that crocodile choline was a potent progression inhibitor of gastric cancer cells, which was correlated with mitochondrial apoptotic pathway and Notch pathway. Combining Notch1 inhibitors with crocodile choline might represent a novel approach for gastric cancer.

Air oxidation of Zircaloy-4 in the 600-1000 °C temperature range: Modeling for ASTEC code application

NASA Astrophysics Data System (ADS)

Coindreau, O.; Duriez, C.; Ederli, S.

2010-10-01

Progress in the treatment of air oxidation of zirconium in severe accident (SA) codes are required for a reliable analysis of severe accidents involving air ingress. Air oxidation of zirconium can actually lead to accelerated core degradation and increased fission product release, especially for the highly-radiotoxic ruthenium. This paper presents a model to simulate air oxidation kinetics of Zircaloy-4 in the 600-1000 °C temperature range. It is based on available experimental data, including separate-effect experiments performed at IRSN and at Forschungszentrum Karlsruhe. The kinetic transition, named "breakaway", from a diffusion-controlled regime to an accelerated oxidation is taken into account in the modeling via a critical mass gain parameter. The progressive propagation of the locally initiated breakaway is modeled by a linear increase in oxidation rate with time. Finally, when breakaway propagation is completed, the oxidation rate stabilizes and the kinetics is modeled by a linear law. This new modeling is integrated in the severe accident code ASTEC, jointly developed by IRSN and GRS. Model predictions and experimental data from thermogravimetric results show good agreement for different air flow rates and for slow temperature transient conditions.

Coalition releases declaration for healthy and productive oceans

NASA Astrophysics Data System (ADS)

Showstack, Randy

2012-06-01

Coalition releases declaration for healthy and productive oceans A coalition of 13 countries or federal agencies participating in a new Global Partnership for Oceans (GPO) indicated its support for a “Declaration for Healthy and Productive Oceans to Help Reduce Poverty” on 16 June, just prior to the Rio+20 conference in Rio de Janeiro, Brazil.

Carbon monoxide – physiology, detection and controlled release

PubMed Central

Heinemann, Stefan H.; Hoshi, Toshinori; Westerhausen, Matthias

2014-01-01

Carbon monoxide (CO) is increasingly recognized as a cell-signalling molecule akin to nitric oxide (NO). CO has attracted particular attention as a potential therapeutic agent because of its reported anti-hypertensive, anti-inflammatory and cell-protective effects. We discuss recent progress in identifying new effector systems and elucidating the mechanisms of action of CO on, e.g., ion channels, as well as the design of novel methods to monitor CO in cellular environments. We also report on recent developments in the area of CO-releasing molecules (CORMs) and materials for controlled CO application. Novel triggers for CO release, metal carbonyls and degradation mechanisms of CORMs, are highlighted. In addition, potential formulations of CORMs for targeted CO release are discussed. PMID:24556640

Studies on the mechanism of endogenous pyrogen production. III. Human blood monocytes.

PubMed

Bodel, P

1974-10-01

The characteristics of pyrogen production and release by human blood monocytes were investigated. A dose-response assay of monocyte pyrogen in rabbits indicated a linear relationship of temperature elevation to dose of pyrogen at lower doses. Monocytes did not contain pyrogen when first obtained, nor did they release it spontaneously even after 5 days of incubation in vitro. Pyrogen production was apparent 4 h after stimulation by endotoxin or phagocytosis, and continued for 24 h or more. Puromycin, an inhibitor of protein synthesis, prevented both initiation and continuation of pyrogen production and release. Pyrogen-containing supernates retained most pyrogenic activity during overnight incubation even in the presence of activated cells. Lymphocytes appeared to play no role in either initiation or continuation of pyrogen production in these studies.

Fusion pores and their control of neurotransmitter and hormone release

PubMed Central

Chang, Che-Wei; Chiang, Chung-Wei

2017-01-01

Ca2+-triggered exocytosis functions broadly in the secretion of chemical signals, enabling neurons to release neurotransmitters and endocrine cells to release hormones. The biological demands on this process can vary enormously. Although synapses often release neurotransmitter in a small fraction of a millisecond, hormone release can be orders of magnitude slower. Vesicles usually contain multiple signaling molecules that can be released selectively and conditionally. Cells are able to control the speed, concentration profile, and content selectivity of release by tuning and tailoring exocytosis to meet different biological demands. Much of this regulation depends on the fusion pore—the aqueous pathway by which molecules leave a vesicle and move out into the surrounding extracellular space. Studies of fusion pores have illuminated how cells regulate secretion. Furthermore, the formation and growth of fusion pores serve as a readout for the progress of exocytosis, thus revealing key kinetic stages that provide clues about the underlying mechanisms. Herein, we review the structure, composition, and dynamics of fusion pores and discuss the implications for molecular mechanisms as well as for the cellular regulation of neurotransmitter and hormone release. PMID:28167663

[Mechanisms of leukocyte formation of endogenous pyrogen].

PubMed

Rybakina, E G; Sorokin, A V

1982-06-01

A study was made of the kinetics of endogenous pyrogen production by rabbit blood and exudate leukocytes and possible role played by the products of activated leukocytes in autoregulation of the process. It was established that accumulation of endogenous pyrogen in the cell precedes its release by stimulated cells. Then the processes of active pyrogen formation and release gel interdependent: pyrogen formed releases from the cell; the lowering of pyrogen concentration in the cell is accompanied by the decrease of its content in the medium. No stimulating effect of the products activated during leukocyte inflammation on pyrogen formation by blood leukocytes was discovered.

Annual Coded Wire Tag Program; Missing Production Groups, 1996 Annual Report.

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

Pastor, Stephen M.

1997-01-01

In 1989 the Bonneville Power Administration (BPA) began funding the evaluation of production groups of juvenile anadromous fish not being coded-wire tagged for other programs. These groups were the ''Missing Production Groups''. Production fish released by the U.S. Fish and Wildlife Service (USFWS) without representative coded-wire tags during the 1980's are indicated as blank spaces on the survival graphs in this report. The objectives of the ''Missing Production Groups'' program are: (1) to estimate the total survival of each production group, (2) to estimate the contribution of each production group to various fisheries, and (3) to prepare an annual reportmore » for all USFWS hatcheries in the Columbia River basin. Coded-wire tag recovery information will be used to evaluate the relative success of individual brood stocks. This information can also be used by salmon harvest managers to develop plans to allow the harvest of excess hatchery fish while protecting threatened, endangered, or other stocks of concern. In order to meet these objectives, a minimum of one marked group of fish is necessary for each production release. The level of marking varies according to location, species, and age at release. In general, 50,000 fish are marked with a coded-wire tag (CWT) to represent each production release group at hatcheries below John Day Dam. More than 100,000 fish per group are usually marked at hatcheries above John Day Dam. All fish release information, including marked/unmarked ratios, is reported to the Pacific States Marine Fisheries Commission (PSMFC). Fish recovered in the various fisheries or at the hatcheries are sampled to recover coded-wire tags. This recovery information is also reported to PSMFC.« less

How MMPs Impact Bone Responses to Metastatic Prostate Cancer

DTIC Science & Technology

2009-02-01

STATEMENT Approved for Public Release; Distribution Unlimited 13. SUPPLEMENTARY NOTES 14. ABSTRACT Using an animal model of prostate tumor...prostate tumor progression in the bone since no difference in osteolytic or osteoblastic responses between wild type and MMP-9 deficient animals were...described as the ‘vicious cycle’ (4). Using an animal model of 4 tumor progression in the bone, we have previously identified a group of enzymes known as

A history of the 2014 Minute 319 environmental pulse flow asdocumented by field measurements and satellite imagery

USGS Publications Warehouse

Nelson, Steven M.; Ramirez-Hernandez, Jorge; Rodriguez-Burgeueno, J. Eliana; Milliken, Jeff; Kennedy, Jeffrey R.; Zamora-Arroyo, Francisco; Schlatter, Karen; Santiago-Serrano, Edith; Carrera-Villa, Edgar

2017-01-01

As provided in Minute 319 of the U.S.-Mexico Water Treaty of 1944, a pulse flow of approximately 132 million cubic meters (mcm) was released to the riparian corridor of the Colorado River Delta over an eight-week period that began March 23, 2014 and ended May 18, 2014. Peak flows were released in the early part of the pulse to simulate a spring flood, with approximately 101.7 mcm released at Morelos Dam on the U.S.-Mexico border. The remainder of the pulse flow water was released to the riparian corridor via Mexicali Valley irrigation spillway canals, with 20.9 mcm released at Km 27 Spillway (41 km below Morelos Dam) and 9.3 mcm released at Km 18 Spillway (78 km below Morelos Dam). We used sequential satellite images, overflights, ground observations, water discharge measurements, and automated temperature, river stage and water quality loggers to document and describe the progression of pulse flow water through the study area. The rate of advance of the wetted front was slowed by infiltration and high channel roughness as the pulse flow crossed more than 40 km of dry channel which was disconnected from underlying groundwater and partially overgrown with salt cedar. High lag time and significant attenuation of flow resulted in a changing hydrograph as the pulse flow progressed to the downstream delivery points; two peak flows occurred in some lower reaches. The pulse flow advanced more than 120 km downstream from Morelos Dam to reach the Colorado River estuary at the northern end of the Gulf of California.

Acute kidney injury is common with intravenous abuse of extended-release oral oxymorphone and delayed renal recovery rates are associated with increased KDIGO staging.

PubMed

Bonnecaze, Alex K; Wilson, Matthew Whitaker; Dharod, Ajay; Fletcher, Alison; Miller, P J

2017-08-12

Prescription opioid abuse poses a serious problem in the United States, representing 615 per 100,000 deaths annually. Extended-release oxymorphone (Opana-ER) is an oral opioid pain medication that has recently been found to cause thrombotic microangiopathy when intravenously abused. In this retrospective study, prevalence and outcomes of AKI among patients intravenously abusing extended-release oral oxymorphone were analyzed. A query of electronic medical records for "drug abuse" at an academic medical center during January 2012 to December 2015 was performed and yielded 2350 patients. Patients were further identified by documented intravenous abuse of extended-release oxymorphone. Patients were stratified based on multiple renal indices and outcomes. Potential confounders were also identified. 165 patients were found to have a documented history of intravenous abuse of extended-release oral oxymorphone. Prevalence of AKI in this population was a 47.8%. KDIGO stage-I patients consisted of 17.8% of patients with AKI, 40.5% were classified as KDIGO stage-II AKI, and 41.8% were classified as KDIGO stage-III AKI. Among patients with AKI, average age was found to be 37.5 years, 59.4% experienced renal recovery, 56.9% required intensive care unit admission, 13.9% progressed to end-stage renal disease (ESRD), and 7.6% expired during admission. Clinicians should be educated to help recognize intravenous abuse of extended-release oral oxymorphone and its associated effects. Our data suggests AKI is common in these patients; higher KDIGO staging appears to be associated with slower rates of renal recovery, increased comorbidities and progression to both CKD and ESRD. This article is protected by copyright. All rights reserved.

Release and repair of a ventral thoracic spinal cord herniation.

PubMed

McCormick, Paul C

2014-09-01

Ventral thoracic spinal cord herniation is a rare but increasingly recognized cause of progressive myelopathy. This video demonstrates the imaging characteristics and surgical techniques for release and reduction of the spinal cord herniation as well as primary repair and reinforcement of the ventral dural hernia defect through an extended posterior approach. An instrumented fusion was concomitantly performed. The video can be found here: http://youtu.be/6Pcokep6Tug.

Laser-Based Alkene Sensors for Shock Tube Kinetics

DTIC Science & Technology

2016-06-28

Approved OMB NO. 0704-0188 3. DATES COVERED (From - To) - Approved for Public Release; Distribution Unlimited UU UU UU UU 28-06- 2016 1-Jul-2014 31-Dec...and progress reports, suitable for public release. (x) Perfomance of the research effort was accomplished in a satisfactory manner and all other... public reporting burden for this collection of information is estimated to average 1 hour per response, including the time for reviewing instructions

Annual Progress Summary Report for Grant N00014-89-J-3073 (Massachusetts General Hospital)

DTIC Science & Technology

1992-11-15

release of thromboxane and the subsequent pulmonary vasoconstriction and hypertension as well as the febrile response and leukopenia; 2) in-vitro...this mixture as measured by a decreased febrile response with a single temperature peak and a briefer leukopenia. However there was no reduc- tion of the...release and physiologically important acute pulmonary vasoconstriction and hypertension, as well as the sys- temic effects of a biphasic febrile response

PREFACE: 4th International Conference on Safe Production and Use of Nanomaterials (Nanosafe2014)

NASA Astrophysics Data System (ADS)

Tardif, F.; Damlencourt, J.-F.; Schuster, F.; Gaultier, V.

2015-05-01

This volume contains a collection of contributions presented at the 4th International Conference on Safe Production and Use of Nanomaterials (NANOSAFE 2014) held in Grenoble, France, from 18th to 20th November 2014. The issues of fast progress in the field of Nanosafety are up to the potential benefits that nanotechnology can bring to mankind. Making more efficient - more sustainable - easier to share mineral resources, increasing the yields of new energy technologies, enabling drugs that act selectively and locally are just few examples of the wide range of nanomaterial applications that currently benefit humanity. Nevertheless, the dynamic development of nanomaterials requires the adhesion from the general public who rightly demand major progresses in Nanosafety as a prerequisite. This is our exciting responsibility and challenge! Following the successful outcome of the three past international conferences on safe production and use of nanomaterials: Nanosafe 2008, 2010 and 2012, the organizing committee has the pleasure to welcoming you again to Minatec, Grenoble with some of the most famous specialists in the field. This year, two new topics have been added dealing with the "New Application of Nanomaterials" and "Nano-responsible Development" in addition to the usual issues addressed in previous Nanosafe conferences such as Expology, Detection and Characterization, Toxicology, Environmental Interactions, Nanomaterials Release, Life Cycle Analysis, Regulation and Standardization, Risk Management. The debates in 2012 proved highly successful so this formula has been kept in 2014 with 3 round tables: Nano-Responsible Development, Risks and Benefits for the Environment, Toxicology Progress. In this 4th edition, there were more than 330 registered participants from 28 different countries including 160 oral presentation covering the whole Nanosafety issues in 12 sessions, satellite workshops and round tables. This high number of participants makes this edition one of the most successful conference of the series. Finally, 2014 was for the organizing committee, a great year as we ramp up the Nano Safety "PNS" platform at Minatec, with a brand new building spread out over 2000 m2 of laboratories and more than 50 doctors and engineers dedicated to Nanosafety. F. Tardif, J-F. Damlencourt, F. Schuster and V. Gaultier

Kinetics of silver release from microfuel with taking into account the limited-solubility effect

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

Ivanov, A. S., E-mail: asi.kiae@gmail.com; Rusinkevich, A. A., E-mail: rusinkevich_andr@mail.ru

2014-12-15

The effect of a limited solubility of silver in silicon carbide on silver release from a microfuel with a TRISO coating is studied. It is shown that a limited solubility affects substantially both concentration profiles and silver release from a microfuel over a broad range of temperatures. A procedure is developed for obtaining fission-product concentration profiles in a microfuel and graphs representing the flow and integrated release of fission products on the basis of data from neutron-physics calculations and results obtained by calculating thermodynamics with the aid of the Ivtanthermo code and kinetics with the aid of the FP-Kinetics code.more » This procedure takes into account a limited solubility of fission products in protective coatings of microfuel.« less

Fission products and nuclear fuel behaviour under severe accident conditions part 3: Speciation of fission products in the VERDON-1 sample

NASA Astrophysics Data System (ADS)

Le Gall, C.; Geiger, E.; Gallais-During, A.; Pontillon, Y.; Lamontagne, J.; Hanus, E.; Ducros, G.

2017-11-01

Qualitative and quantitative analyses on the VERDON-1 sample made it possible to obtain valuable information on fission product behaviour in the fuel during the test. A promising methodology based on the quantitative results of post-test characterisations has been implemented to assess the release fraction of non γ-emitter fission products. The order of magnitude of the estimated release fractions for each fission product was consistent with their class of volatility.

Low VOC drying of lumber and wood panel products. Progress report Number 9 [January 1999

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

Yan, H.; Banerjee, S.; Conners, T.

1999-01-01

Results from a multi-year study show that a significant part of the extensive variability observed in oriented strand board (OSB) flake dryer emissions can be traced to physiological effects, and the rest can be attributed to handling and other factors. Low-headspace treatment of lumber was scaled up to the 50 kg level. The amount of turpentine collected was of the same magnitude as that released upon drying lumber. For the process to be economical, the wood must first be brought to about 95 C with steam, and then processed with RF. Attempts to remove VOCs from OSB through low-headspace bymore » placing a curtain over the wood failed because of leaks. A more rigid container will be required. RF-treatment does not alter the gas permeability of lumber.« less

Low VOC drying of lumber and wood panel products. Progress report Number 9

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

Yan, H.; Banerjee, S.; Conners, T.

1999-01-01

Results from a multi-year study show that a significant part of the extensive variability observed in oriented strand board (OSB) flake dryer emissions can be traced to physiological effects, and the rest can be attributed to handling and other factors. Low-headspace treatment of lumber was scaled up to the 50 kg level. The amount of turpentine collected was of the same magnitude as that released upon drying lumber. For the process to be economical, the wood must first be brought to about 95 C with steam, and then processed with RF. Attempts to remove VOCs from OSB through low-headspace bymore » placing a curtain over the wood failed because of leaks. A more rigid container will be required. RF-treatment does not alter the gas permeability of lumber.« less

Materials for lithium-ion battery safety.

PubMed

Liu, Kai; Liu, Yayuan; Lin, Dingchang; Pei, Allen; Cui, Yi

2018-06-01

Lithium-ion batteries (LIBs) are considered to be one of the most important energy storage technologies. As the energy density of batteries increases, battery safety becomes even more critical if the energy is released unintentionally. Accidents related to fires and explosions of LIBs occur frequently worldwide. Some have caused serious threats to human life and health and have led to numerous product recalls by manufacturers. These incidents are reminders that safety is a prerequisite for batteries, and serious issues need to be resolved before the future application of high-energy battery systems. This Review aims to summarize the fundamentals of the origins of LIB safety issues and highlight recent key progress in materials design to improve LIB safety. We anticipate that this Review will inspire further improvement in battery safety, especially for emerging LIBs with high-energy density.

Materials for lithium-ion battery safety

PubMed Central

Liu, Kai

2018-01-01

Lithium-ion batteries (LIBs) are considered to be one of the most important energy storage technologies. As the energy density of batteries increases, battery safety becomes even more critical if the energy is released unintentionally. Accidents related to fires and explosions of LIBs occur frequently worldwide. Some have caused serious threats to human life and health and have led to numerous product recalls by manufacturers. These incidents are reminders that safety is a prerequisite for batteries, and serious issues need to be resolved before the future application of high-energy battery systems. This Review aims to summarize the fundamentals of the origins of LIB safety issues and highlight recent key progress in materials design to improve LIB safety. We anticipate that this Review will inspire further improvement in battery safety, especially for emerging LIBs with high-energy density. PMID:29942858

Impact of room fragrance products on indoor air quality

NASA Astrophysics Data System (ADS)

Uhde, Erik; Schulz, Nicole

2015-04-01

Everyday life can no longer be imagined without fragrances and scented products. For the consumer, countless products exists which are solely or partly intended to give off a certain scent in sufficient concentrations to odorize a complete room. Sprays, diffusers and evaporators, scented candles and automatic devices for the distribution of fragrance liquids are typical examples of such products. If the consumer uses such products, his consent to the release of certain chemicals in his home can be implied, however, he may not know what kind of fragrance substances and solvents will be present in which concentrations. In this study, we determined the volatile emissions of a number of fragrance products in detail. Measurements were carried out under controlled conditions in test chambers. The products were tested in a passive (unused) and an active state, wherever applicable. Following a defined test protocol, the release of volatile organic compounds, ultrafine particles and NOx was monitored for each product. The potential for forming secondary organic aerosols under the influence of ozone was studied, and for a selection of products the long-term emission behavior was assessed. A remarkable variety of fragrance substances was found and more than 100 relevant compounds were identified and quantified. While it is the intended function of such products to release fragrance substances, also considerable amounts of non-odorous solvents and by-products were found to be released from several air fresheners. Emissions rates exceeding 2 mg/(unit*h) were measured for the five most common solvents.

Implications of alteration processes on radon emanation, radon production rate and W-Sn exploration in the Panasqueira ore district.

PubMed

Domingos, Filipa; Pereira, Alcides

2018-05-01

Alteration processes have strong impacts on the chemical and physical properties of rock masses. Because they can affect the contents and the distribution of U as well as enhance the permeability of the bedrock, they may lead to a significant increase of radon release to the environment. However, their influence on radon emanation and radon production rate has yet to be properly assessed. To investigate the impact of alteration processes on the radiological properties, samples were collected in the Panasqueira region under the influence of surface weathering, deuteric, hydrothermal and fault related alteration. Major and trace elements (U, Th), physical, and radiological properties were measured in metasedimentary and fault rocks. The degree of alteration and weathering progress were assessed through indices of alteration, porosity and bulk density. Overall, an increase of the radon emanation coefficient from (approximately) 0.1 to 0.4 and radon production rate (from 40 to over 160Bq·m -3 ·h -1 ) is observed with the progress of physicochemical alteration. Decoupling of physical and chemical alteration however implies both must be quantified towards a proper assessment of the degree of alteration. The behavior of radiogenic elements upon alteration is shown to be complex and contingent upon the alteration process. An atypical increase of radon emanation in the ore district due to U mobilization was caused by hydrothermal alteration. Because radon emanation is not dependent upon the pelitic nature of the metasedimentary rocks, it may thus become a proxy for W-Sn exploration. The dependency of radon production rate from the latter constrains its use for exploration. Nevertheless, it may provide a reliable estimation of the bedrock contribution to indoor radon concentrations. Higher indoor radon concentrations, hence, a higher risk of exposure to radon are expected in the ore district as well as within fault zones. Copyright © 2017 Elsevier B.V. All rights reserved.

Data summary report for fission product release test VI-6

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

Osborne, M.F.; Lorenz, R.A.; Travis, J.R.

Test VI-6 was the sixth test in the VI series conducted in the vertical furnace. The fuel specimen was a 15.2-cm-long section of a fuel rod from the BR3 reactor in Belgium. The fuel had experienced a burnup of {approximately}42 MWd/kg, with inert gas release during irradiation of {approximately}2%. The fuel specimen was heated in an induction furnace at 2300 K for 60 min, initially in hydrogen, then in a steam atmosphere. The released fission products were collected in three sequentially operated collection trains designed to facilitate sampling and analysis. The fission product inventories in the fuel were measured directlymore » by gamma-ray spectrometry, where possible, and were calculated by ORIGEN2. Integral releases were 75% for {sup 85}Kr, 67% for {sup 129}I, 64% for {sup 125}Sb, 80% for both {sup 134}Cs and {sup 137}Cs, 14% for {sup 154}Eu, 63% for Te, 32% for Ba, 13% for Mo, and 5.8% for Sr. Of the totals released from the fuel, 43% of the Cs, 32% of the Sb, and 98% of the Eu were deposited in the outlet end of the furnace. During the heatup in hydrogen, the Zircaloy cladding melted, ran down, and reacted with some of the UO{sub 2} and fission products, especially Te and Sb. The total mass released from the furnace to the collection system, including fission products, fuel, and structural materials, was 0.57 g, almost equally divided between thermal gradient tubes and filters. The release behaviors for the most volatile elements, Kr and Cs, were in good agreement with the ORNL Diffusion Model.« less

[The use of natural and synthetic hydrophilic polymers in the formulation of metformin hydrochloride tablets with different profile release].

PubMed

Kołodziejczyk, Michał Krzysztof; Kołodziejska, Justyna; Zgoda, Marian Mikołaj

2012-01-01

Metformin hydrochloride after buformin and phenformin belongs to the group of biguanid derivatives used as oral anti-diabetic drugs. The object of the study is the technological analysis and the potential effect of biodegradable macromolecular polymers on the technological and therapeutic parameters of oral anti-diabetic medicinal products with metformin hydrochloride: Siofor, Formetic, Glucophage, Metformax in doses of 500mg and 1000mg and Glucophage XR in a dose of 500 mg of modified release. Market therapeutic products containing 500 and 1000 mg of metformin hydrochloride in a normal formulation and 500 mg of metformin hydrochloride in a formulation of modified release were analyzed. Following research methods were used: technological analysis of tablets, study of disintegration time of tablets, evaluation of pharmaceutical availability of metformin hydrochloride from tested therapeutic products, mathematical and kinetic analysis of release profiles of metformin hydrochloride, statistical analysis of mean differences of release coefficients. The percentage of excipients in the XR formulation is higher and constitutes 50.5% of a tablet mass. However, in standard formulations the percentage is lower, between 5.5% and 12.76%. On the basis of the results of disintegration time studies, the analysed therapeutic products can be divided into two groups, regardless the dose. The first one are preparations with faster (not fast!) disintegration: Glucophage i Metformax. The second group are preparations with slower disintegration, more balanced in the aspect of a high dose of the biologically active substance: Formetic and Siofor. Products with a lower content of excipients (Metformax, Glucophage) disintegrate in a faster way. The disintegration rate of the products with a higher content of excipients (Formetic, Siofor) is slower. The appearance of metformin hydrochloride concentration in the gastrointestinal contents, balanced in time, caused by a slower disintegration-dissolving of a tablet, is conducive to the reduction of gastrointestinal side effects and better tolerance of the therapeutic product by a patient. The study on pharmaceutical availability indicated relevant kinetic differences between tested therapeutic products. They are particularly visible between standard formulations and the one with prolonged release (Glucophage XR500). Its release profile bears features of kinetics similar to zero-order reactions. Tested therapeutic products contain a large amount of the biologically active substance in relation to the content of excipients. A higher content of excipients in a single tablet mass distinguishes Siofor in comparison with Glucophage i Metformax. The excipients used in the formulations of tested preparations are comparable. A higher percentage of binding agents (HPMC, PVP) is observed, but there is a lack of typical disintegrants which results in a longer disintegration time up to 15 minutes. Siofor disintegrates at the same time as Formetic, but longer than Glucophage i Metformax. Considering the large content of the active substance and pharmacological properties of metformin hydrochloride, such a disintegration might have beneficial consequences, because the amount of the free active substance in the gastrointestinal tract will increase over the longer time period what will reduce the level of gastrointestinal side effects. The release profiles of metformin hydrochloride from tested therapeutic products are comparable. The Glucophage XR 500 formulation with the release kinetics of metformin hydrochloride similar to the zero-order kinetics is completely different from the others. The above is confirmed by the mathematical analysis of release profiles of metformin hydrochloride from tested preparations where equations of lines describing the release profile are characterized by similar values of correlation coefficients.

Sulfate-reducing bacteria release barium and radium from naturally occurring radioactive material in oil-field barite

USGS Publications Warehouse

Phillips, E.J.P.; Landa, E.R.; Kraemer, T.; Zielinski, R.

2001-01-01

Scale and sludge deposits formed during oil production can contain elevated levels of Ra, often coprecipitated with barium sulfate (barite). The potential for sulfate-reducing bacteria to release 226 Ra and Ba (a Ra analog) from oil-field barite was evaluated. The concentration of dissolved Ba increased when samples containing pipe scale, tank sludge, or oil-field brine pond sediment were incubated with sulfate-reducing bacteria Desulfovibrio sp., Str LZKI, isolated from an oil-field brine pond. However, Ba release was not stoichiometric with sulfide production in oil-field samples, and <0.1% of the Ba was released. Potential for the release of 226Ra was demonstrated, and the 226 Ra release associated with sulfate-reducing activity was predictable from the amount of Ba released. As with Ba, only a fraction of the 226Ra expected from the amount of sulfide produced was released, and most of the Ra remained associated with the solid material.

A refined method for calculating equivalent effective stratospheric chlorine

NASA Astrophysics Data System (ADS)

Engel, Andreas; Bönisch, Harald; Ostermöller, Jennifer; Chipperfield, Martyn P.; Dhomse, Sandip; Jöckel, Patrick

2018-01-01

Chlorine and bromine atoms lead to catalytic depletion of ozone in the stratosphere. Therefore the use and production of ozone-depleting substances (ODSs) containing chlorine and bromine is regulated by the Montreal Protocol to protect the ozone layer. Equivalent effective stratospheric chlorine (EESC) has been adopted as an appropriate metric to describe the combined effects of chlorine and bromine released from halocarbons on stratospheric ozone. Here we revisit the concept of calculating EESC. We derive a refined formulation of EESC based on an advanced concept of ODS propagation into the stratosphere and reactive halogen release. A new transit time distribution is introduced in which the age spectrum for an inert tracer is weighted with the release function for inorganic halogen from the source gases. This distribution is termed the release time distribution. We show that a much better agreement with inorganic halogen loading from the chemistry transport model TOMCAT is achieved compared with using the current formulation. The refined formulation shows EESC levels in the year 1980 for the mid-latitude lower stratosphere, which are significantly lower than previously calculated. The year 1980 is commonly used as a benchmark to which EESC must return in order to reach significant progress towards halogen and ozone recovery. Assuming that - under otherwise unchanged conditions - the EESC value must return to the same level in order for ozone to fully recover, we show that it will take more than 10 years longer than estimated in this region of the stratosphere with the current method for calculation of EESC. We also present a range of sensitivity studies to investigate the effect of changes and uncertainties in the fractional release factors and in the assumptions on the shape of the release time distributions. We further discuss the value of EESC as a proxy for future evolution of inorganic halogen loading under changing atmospheric dynamics using simulations from the EMAC model. We show that while the expected changes in stratospheric transport lead to significant differences between EESC and modelled inorganic halogen loading at constant mean age, EESC is a reasonable proxy for modelled inorganic halogen on a constant pressure level.

Environmental Releases in the Fuel Ethanol Industry

EPA Science Inventory

Corn ethanol is the largest produced alternate biofuel in the United States. More than 13 billion gallons of ethanol were produced in 2010. The projected corn ethanol production is 15 billion gallons by 2015. With increased production of ethanol, the environmental releases from e...

How polyamine synthesis inhibitors and cinnamic acid affect tropane alkaloid production.

PubMed

Marconi, Patricia L; Alvarez, María A; Pitta-Alvarez, Sandra I

2007-01-01

Hairy roots of Brugmansia candida produce the tropane alkaloids scopolamine and hyoscyamine. In an attempt to divert the carbon flux from competing pathways and thus enhance productivity, the polyamine biosynthesis inhibitors cyclohexylamine (CHA) and methylglyoxal-bis-guanylhydrazone (MGBG) and the phenylalanine-ammonia-lyase inhibitor cinnamic acid were used. CHA decreased the specific productivity of both alkaloids but increased significantly the release of scopolamine (approx 500%) when it was added in the mid-exponential phase. However, when CHA was added for only 48 h during the exponential phase, the specific productivity of both alkaloids increased (approx 200%), favoring scopolamine. Treatment with MGBG was detrimental to growth but promoted release into the medium of both alkaloids. However, when it was added for 48 h during the exponential phase, MGBG increased the specific productivity (approx 200%) and release (250- 1800%) of both alkaloids. Cinnamic acid alone also favored release but not specific productivity. When a combination of CHA or MGBG with cinnamic acid was used, the results obtained were approximately the same as with each polyamine biosynthesis inhibitor alone, although to a lesser extent. Regarding root morphology, CHA inhibited growth of primary roots and ramification. However, it had a positive effect on elongation of lateral roots.

Reduction of Tribocorrosion Products When using the Platform-Switching Concept.

PubMed

Alrabeah, G O; Knowles, J C; Petridis, H

2018-03-01

The reduced marginal bone loss observed when using the platform-switching concept may be the result of reduced amounts of tribocorrosion products released to the peri-implant tissues. Therefore, the purpose of this study was to compare the tribocorrosion product release from various platform-matched and platform-switched implant-abutment couplings under cyclic loading. Forty-eight titanium implants were coupled with pure titanium, gold alloy, cobalt-chrome alloy, and zirconia abutments forming either platform-switched or platform-matched groups ( n = 6). The specimens were subjected to cyclic occlusal forces in a wet acidic environment for 24 h followed by static aqueous immersion for 6 d. The amount of metal ions released was measured using inductively coupled plasma mass spectrometry. Microscopic evaluations were performed pre- and postimmersion under scanning electron microscope (SEM) equipped with energy-dispersive spectroscopy X-ray for corrosion assessment at the interface and wear particle characterization. All platform-switched groups showed less metal ion release compared with their platform-matched counterparts within each abutment material group ( P < 0.001). Implants connected to platform-matched cobalt-chrome abutments demonstrated the highest total mean metal ion release (218 ppb), while the least total mean ion release (11 ppb) was observed in the implants connected to platform-switched titanium abutments ( P ≤ 0.001). Titanium was released from all test groups, with its highest mean release (108 ppb) observed in the implants connected to platform-matched gold abutments ( P < 0.001). SEM images showed surface tribocorrosion features such as pitting and bands of fretting scars. Wear particles were mostly titanium, ranging from submicron to 48 µm in length. The platform-matched groups demonstrated a higher amount of metal ion release and more surface damage. These findings highlight the positive effect of the platform-switching concept in the reduction of tribocorrosion products released from dental implants, which consequently may minimize the adverse tissue reactions that lead to peri-implant bone loss.

Risk based In Vitro Performance Assessment of Extended Release Abuse Deterrent Formulations

PubMed Central

Xu, Xiaoming; Gupta, Abhay; Al-Ghabeish, Manar; Calderon, Silvia N.; Khan, Mansoor A.

2016-01-01

High strength extended release opioid products, which are indispensable tools in the management of pain, are associated with serious risks of unintentional and potentially fatal overdose, as well as of misuse and abuse that might lead to addiction. The issue of drug abuse becomes increasingly prominent when the dosage forms can be readily manipulated to release a high amount of opioid or to extract the drug in certain products or solvents. One approach to deter opioid drug abuse is by providing novel abuse deterrent formulations (ADF), with properties that may be viewed as barriers to abuse of the product. However, unlike regular extended release formulations, assessment of ADF technologies are challenging, in part due to the great variety of formulation designs available to achieve deterrence of abuse by oral, parenteral, nasal and respiratory routes. With limited prior history or literature information, and lack of compendial standards, evaluation and regulatory approval of these novel drug products become increasingly difficult. The present article describes a risk-based standardized in-vitro approach that can be utilized in general evaluation of abuse deterrent features for all ADF products. PMID:26784976

Preparation and properties of a double-coated slow-release NPK compound fertilizer with superabsorbent and water-retention.

PubMed

Wu, Lan; Liu, Mingzhu; Rui Liang

2008-02-01

A double-coated slow-release NPK compound fertilizer with superabsorbent and water-retention was prepared by crosslinked poly(acrylic acid)/diatomite - containing urea (the outer coating), chitosan (the inner coating), and water-soluble granular fertilizer NPK (the core). The effects of the amount of crosslinker, initiator, degree of neutralization of acrylic acid, initial monomer and diatomite concentration on water absorbency were investigated and optimized. The water absorbency of the product was 75 times its own weight if it was allowed to swell in tap water at room temperature for 2 h. Atomic absorption spectrophotometer and element analysis results showed that the product contained 8.47% potassium (shown by K(2)O), 8.51% phosphorus (shown by P(2)O(5)), and 15.77% nitrogen. We also investigated the water-retention property of the product and the slow release behavior of N, P and K in the product. This product with excellent slow release and water-retention capacity, being nontoxic in soil and environment-friendly, could be especially useful in agricultural and horticultural applications.

Insulin-secretagogue activity and cytoprotective role of the traditional antidiabetic plant Scoparia dulcis (Sweet Broomweed).

PubMed

Latha, Muniappan; Pari, Leelavinothan; Sitasawad, Sandhya; Bhonde, Ramesh

2004-09-03

Scoparia dulcis (Sweet Broomweed) has been documented as a traditional treatment of diabetes. The administration of an aqueous extract of Scoparia dulcis at a dose of 200 mg/kg body weight significantly decreased the blood glucose with significant increase in plasma insulin level in streptozotocin diabetic rats at the end of 15 days treatment. The insulin secretagogue action of Scoparia dulcis plant extract (SPEt) was further investigated using isolated pancreatic islets from mice. SPEt at a dose of 10 microg/ml evoked 6.0 fold stimulation of insulin secretion from isolated islets indicating its insulin secretagogue activity. In addition the effect of SPEt on streptozotocin induced cell death and nitric oxide (NO) in terms of nitrite production were also examined. SPEt protected against streptozotocin- mediated cytotoxicity (88%) and NO production in rat insulinoma cell line (RINm5F). Above results suggest the glucose lowering effect of SPEt to be associated with potentiation of insulin release from pancreatic islets. Our results revealed the possible therapeutic value of Scoparia dulcis for the better control, management and prevention of diabetes mellitus progression.

Human forearm metabolism during progressive starvation.

PubMed

Owen, O E; Reichard, G A

1971-07-01

Forearm muscle metabolism was studied in eight obese subjects after an overnight, 3 and 24 day fast. Arterio-deep-venous differences of oxygen, carbon dioxide, glucose, lactate, pyruvate, free fatty acids, acetoacetate, and beta-hydroxybutyrate with simultaneous forearm blood flow were measured. Rates of metabolite utilization and production were thus estimated. Oxygen consumption and lactate and pyruvate production remained relatively constant at each fasting period. Glucose, initially the major substrate consumed, showed decreased consumption after 3 and 24 days of fasting. Acetoacetate and beta-hydroxybutyrate consumption after an overnight fast was low. At 3 days of fasting with increased arterial concentrations of acetoactate and beta-hydroxybutyrate, consumption of these substrates rose dramatically. At 24 days of fasting, despite further elevation of arterial levels of acetoacetate and beta-hydroxybutyrate, the utilization of acetoacetate did not increase further and if anything decreased, while five out of eight subjects released beta-hydroxybutyrate across the forearm. Acetoacetate was preferentially extracted over beta-hydroxybutyrate. At 24 days of starvation, free fatty acids were the principal fuels extracted by forearm muscle; at this time there was a decreased glucose and also ketone-body consumption by skeletal muscle.

Environmental tobacco smoke exposure assessment

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

Guerin, M.R.

Environmental tobacco smoke (ETS) is the material released into the environment as tobacco products are smoked. Cigarettes, pipes, and cigars all produce ETS but the term has become all but synonymous with indoor air contamination by cigarette smoking. This is because cigarettes are by far the most commonly consumed tobacco product and because the principal human exposure occurs indoors. Exposure to ETS is variously termed as passive smoking, involuntary smoking, and as exposure to second-hand smoke. Considerable progress has been made toward a better understanding of ETS exposure. Strengths and limitations of various measures of exposure are better understood andmore » much data has been generated on the quantities of many ETS-constituents in many indoor environments. The properties of ETS, methods for its measurement in indoor air, and many results of field studies have recently been reviewed by the author. The recent EPA report includes a major treatment of exposure estimation including air concentrations, questionnaires, and biomarkers. This paper discusses approaches to exposure assessment and summarizes data on indoor air concentrations of ETS-constituents.« less

Study of the mode of action of a polygalacturonase from the phytopathogen Burkholderia cepacia

PubMed Central

Massa, Claudia; Clausen, Mads H.; Stojan, Jure; Lamba, Doriano; Campa, Cristiana

2007-01-01

We have recently isolated and heterologously expressed BcPeh28A, an endopolygalacturonase from the phytopathogenic Gram-negative bacterium Burkholderia cepacia. Endopolygalacturonases belong to glycoside hydrolase family 28 and are responsible for the hydrolysis of the non-esterified regions of pectins. The mode of action of BcPeh28A on different substrates has been investigated and its enzymatic mechanism elucidated. The hydrolysis of polygalacturonate indicates that BcPeh28A is a non-processive enzyme that releases oligomers with chain lengths ranging from two to eight. By inspection of product progression curves, a kinetic model has been generated and extensively tested. It has been used to derive the kinetic parameters that describe the time course of the formation of six predominant products. Moreover, an investigation of the enzymatic activity on shorter substrates that differ in their overall length and methylation patterns sheds light on the architecture of the BcPeh28A active site. Specifically the tolerance of individual sites towards methylated saccharide units was rationalized on the basis of the hydrolysis of hexagalacturonides with different methylation patterns. PMID:17627609

In-situ complex with by-product HCl and release chloride ions to dissolve aramid.

PubMed

Dai, Yu; Cheng, Zheng; Yuan, Yihao; Meng, Chenbo; Qin, Jiaqiang; Liu, Xiangyang

2018-06-20

Because of the strong hydrogen-bond interaction among macromolecular chains, addition of chloride salts is generally needed to offer Cl- ions for dissolution of aromatic polyamides. In this paper, poly-(benzimidazole-terephthalamide) which complexed with by-product HCl during polymerization (PABI-HCl) was prepared and imidazole compound as cosolvent was added into dimethylacetamide (DMAc) to dissolve PABI-HCl. Due to stronger affinity to protons, imidazole compound could in-situ complex with HCl of PABI-HCl and form imidazolium hydrochloride. Then imidazolium hydrochloride would ionize and produce much free Cl- ions which acted as stronger hydrogen-bond acceptor to disrupt interaction among macromolecular chains. As a result, solubility of PABI-HCl in DMAc was improved significantly in existence of small amount of imidazole compound. Moreover, DMAc-imidazole mixture was utlized for synthesis of different kinds of aramids and no precipitation was observed with progress of the reaction. So the mixture was suitable to be utlized as solvent for polymerization of aramid. © 2018 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

Detroit Research on Cancer Survivors Study

Cancer.gov

An NCI press release about the launch of the Detroit Research on Cancer Survivors (ROCS) study, which will look at factors affecting cancer progression, recurrence, mortality, and quality of life among African-American cancer survivors.

Mast cells mediate neutrophil recruitment during atherosclerotic plaque progression.

PubMed

Wezel, Anouk; Lagraauw, H Maxime; van der Velden, Daniël; de Jager, Saskia C A; Quax, Paul H A; Kuiper, Johan; Bot, Ilze

2015-08-01

Activated mast cells have been identified in the intima and perivascular tissue of human atherosclerotic plaques. As mast cells have been described to release a number of chemokines that mediate leukocyte fluxes, we propose that activated mast cells may play a pivotal role in leukocyte recruitment during atherosclerotic plaque progression. Systemic IgE-mediated mast cell activation in apoE(-/-)μMT mice resulted in an increase in atherosclerotic lesion size as compared to control mice, and interestingly, the number of neutrophils was highly increased in these lesions. In addition, peritoneal mast cell activation led to a massive neutrophil influx into the peritoneal cavity in C57Bl6 mice, whereas neutrophil numbers in mast cell deficient Kit(W(-sh)/W(-sh)) mice were not affected. Within the newly recruited neutrophil population, increased levels of CXCR2(+) and CXCR4(+) neutrophils were observed after mast cell activation. Indeed, mast cells were seen to contain and release CXCL1 and CXCL12, the ligands for CXCR2 and CXCR4. Intriguingly, peritoneal mast cell activation in combination with anti-CXCR2 receptor antagonist resulted in decreased neutrophil recruitment, thus establishing a prominent role for the CXCL1/CXCR2 axis in mast cell-mediated neutrophil recruitment. Our data suggest that chemokines, and in particular CXCL1, released from activated mast cells induce neutrophil recruitment to the site of inflammation, thereby aggravating the ongoing inflammatory response and thus affecting plaque progression and destabilization. Copyright © 2015 Elsevier Ireland Ltd. All rights reserved.

Decreased release of histamine and sulfidoleukotrienes by human peripheral blood leukocytes after wasp venom immunotherapy is partially due to induction of IL-10 and IFN-gamma production of T cells.

PubMed

Pierkes, M; Bellinghausen, I; Hultsch, T; Metz, G; Knop, J; Saloga, J

1999-02-01

Recent studies provide evidence that venom immunotherapy (VIT) alters the pattern of cytokine production by inducing an allergen-specific T-cell shift in cytokine expression from TH2 (IL-4, IL-5) to TH1 (IFN-gamma) cytokines and also inducing the production of IL-10. This study was carried out to analyze whether these changes in cytokine production of T cells already observed 1 week after the initiation of VIT in subjects with wasp venom allergy also influence the reactivity of effector cells, such as mast cells and basophils. All subjects included in this study had a history of severe systemic allergic reactions to wasp stings and positive skin test responses with venom and venom-specific IgE in the sera. Peripheral blood leukocytes were isolated before and after the initiation of VIT (rush therapy reaching a maintenance dose of 100 microg venom injected subcutaneously within 1 week) and preincubated with or without addition of IL-10, IFN-gamma, IL-10 + IFN-gamma, anti-IL-10, or anti-IFN-gamma. After stimulation with wasp venom, histamine and sulfidoleukotriene release were assessed by ELISA and compared with spontaneous release and total histamine content. After the induction of VIT, venom-induced absolute and relative histamine and sulfidoleukotriene release were reduced. This was at least partially due to the induction of IFN-gamma and IL-10 production, because (1) neutralization of IL-10 and IFN-gamma by mAbs partially restored the release after the initiation of VIT and (2) the addition of exogenous IFN-gamma and IL-10 caused a statistically significant diminution of the venom-induced histamine and sulfidoleukotriene release before VIT. Depletion of CD2(+) T cells also restored the releasability after VIT. These data indicate that T cells (producing IL-10 and IFN-gamma after VIT) play a key role for the inhibition of histamine and sulfidoleukotriene release of effector cells.

Study of soot production for double injections of n-dodecane in CI engine-like conditions

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

Moiz, Ahmed Abdul; Ameen, Muhsin M.; Lee, Seong-Young

Soot production mechanism in multiple injections is complex since it involves its dependence on turbulent interactions of constituting injections and their combustion progress. A concise study was performed in a constant-volume combustion vessel by considering a double injection scheme of 0.3 ms pilot injection, 0.5 ms dwell time and 1.2 ms main injection (nomenclature: 0.3/0.5/12 ms) with n-dodecane as fuel and replicating the thermodynamic operating condition of a compression ignition (CI) engine. Experimental ambient temperature variations of 900 K and 800 K were performed at 15% ambient oxygen level. Simultaneous planar laser-induced fluorescence (PUP) of formaldehyde and schlieren imaging techniquesmore » were employed to analyze the ignition and flame characteristics experimentally. These studies revealed almost similar heat release rates for a double injection at 900 K and 800 K ambient gas temperatures due to combustion of a longer main injection which is enhanced by pilot combustion event A lower soot production for 800 K ambient condition over 900 K case was observed, which was concluded to be due to its higher lift-off length which would allow for a leaner combustion of fuel-air mixtures. Numerical simulations were performed using a Large Eddy Simulation (LES) approach by extensively validating the 900 K double injection condition with respect to non-reacting vapor penetration profiles of both injections, reacting jet heat release rate and spatial as well as temporal (qualitative) soot production. As part of LES work, a dwell time variation of 0.65 ms (0.3/0.65/1.2 ms) was performed to reveal the sensitivity of soot production to variations in dwell time. It was observed numerically that marginally higher quasi steady lift-off length of the 0.3/0.65/1.2 ms injection causes increased entrainment of surrounding oxygen into the flame region. This leads to combustion of slightly leaner fuel-air mixture and hence relatively less soot when compared to a 0.3/0.5/1.2 ms injection. (C) 2016 The Combustion Institute. Published by Elsevier Inc All rights reserved.« less

A novel mechanism of vascular endothelial growth factor, leptin and transforming growth factor-beta2 sequestration in a subpopulation of human ovarian follicle cells.

PubMed

Antczak, M; Van Blerkom, J; Clark, A

1997-10-01

This study describes the occurrence of a highly specialized subpopulation of granulosa and cumulus oophorus cells that accumulate and sequester specific growth factors by a novel mechanism. These cells are characterized by multiple balloon-like processes tethered to the cell by means of a slender stalk of plasma membrane. Time-lapse analyses demonstrate that these tethered structures (TS) form in minutes and frequently detach from the cell with the bulbous portion remaining motile on the cell surface. Serial section reconstruction of transmission electron microscopic images shows a specific and stable intracellular organization in which an apparent secretory compartment composed of densely packed vacuoles, vesicles, and cisternae is separated by a thick filamentous network from a nuclear compartment containing mitochondria, polyribosomes, lipid inclusions, and rough-surfaced endoplasmic reticulum. Immunofluorescent analysis performed during the formation of these structures showed a progressive accumulation of vascular endothelial growth factor, leptin, and transforming growth factor-beta2 in the bulbous region. TS were identified in newly aspirated masses of granulosa and cumulus oophorus, and their production persists for months in culture. Observations of TS-forming cells made over several days of culture indicates that their production is episodic and factor release from these cells may be pulsatile. The findings suggest that a novel method of growth factor storage and release by an apparent apocrine-like mechanism occurs in the human ovarian follicle. The results are discussed with respect to possible roles in pre- and post-ovulatory follicular development.

Long-term stability study of Prussian blue-A quality assessment of water content and cyanide release.

PubMed

Mohammad, A; Yang, Y; Khan, M A; Faustino, P J

2015-02-01

Prussian blue, ferric hexacyanoferrate is approved for (oral) treatment of internal contamination with radioisotopes of cesium or thallium. Cyanide makes up 35-40% of Prussian blue's molecular composition; thus, cyanide may be released during transit through the digestive tract under physiological pH conditions. The purpose of this study is to assess the long-term stability of Prussian blue drug products and active pharmaceutical ingredients and its impact on cyanide release. The study involves the determination and comparison of the loss in water content and cyanide released from Prussian blue under pH conditions that bracket human physiological exposure. Test samples of active pharmaceutical ingredient and drug product were stored for 10 years at ambient temperatures that mimic warehouse storage conditions. Water loss from Prussian blue was measured using thermogravimetric analysis. An in vitro physiological pH model that brackets gastric exposure and gastrointestinal transit was utilized for cyanide release. Prussian blue was incubated in situ at pH: 1.0, 5.0, and 7.0 @ 37°C for 1-24 h. Cyanide was measured using a validated colorimetric method by UV-Vis spectroscopy. Although the water content (quality attribute) of Prussian blue active pharmaceutical ingredient and drug product decreased by about 10.5% and 13.8%, respectively, since 2003, the cyanide release remained comparable. At pH of 7.0 for 24 h cyanide released from active pharmaceutical ingredient-1 was 21.33 ± 1.76 μg/g in 2004, and 28.45 ± 3.15 μg/g in 2013; cyanide released from drug product-1 was 21.89 ± 0.56 μg/g in 2004, and 27.31 ± 5.78 μg/g in 2013. At gastric pH of 1.0 and upper gastrointestinal pH of 5.0, the data for active pharmaceutical ingredients and drug products were also comparable in 2013. The cyanide release is still pH-dependent and follows the same trend as observed in 2003 with minimum release at pH of 5.0 and maximal release at pH of 1.0. In summary, this is the long-term stability study of Prussian blue which correlates cyanide release to water loss. Cyanide released from Prussian blue was maximum at pH of 1.0 (47.47 μg/g) and minimum at pH of 5.0-7.0 (20.01 μg/g). Based on maximal dose, maximal residence time in stomach and intestine, the maximal cyanide released from Prussian blue is about 1.31 mg, which is far below the minimal lethal dose of cyanide of 50 mg, and therefore does not present a safety concern following long-term storage.

Organo-mineral fertilisers from glass-matrix and organic biomasses: a new way to release nutrients. A novel approach to fertilisation based on plant demand.

PubMed

Trinchera, Alessandra; Allegra, Maria; Rea, Elvira; Roccuzzo, Giancarlo; Rinaldi, Simona; Sequi, Paolo; Intrigliolo, Francesco

2011-10-01

A glass-matrix fertiliser (GMF), a by-product from ceramic industries, releases nutrients only in the presence of complexing solutions, similar to those exuded by plant roots. This ensures a slow release of nutrients over time, limiting the risk of their loss in the environment. With the aim to improve fertiliser performance, GMF was mixed with vine vinasse (DVV), pastazzo (a by-product of the citrus processing industry, PAS) or green compost (COMP) and nutrient release was evaluated by citric and chloridric acid extraction, at different concentrations. Theoretical and actual nutrients release were compared to evaluate possible synergistic effects due to the organic component added to the mineral fertiliser: phosphorus (+7.1%), K (+4.8%), Fe (+8.5%) and Zn (+5.5%) were released more efficiently by 2% citric acid from GMF + DVV, while Ca availability was increased (+5.3%) by 2% citric acid from GMF + PAS mixture. Both DVV and COMP increased by 12-18% the Fe release from GFM matrix. Organic biomasses added to GMF increased the release of some macro and micronutrients through an 'activation effect', which suggests the employment of these organo-mineral fertilisers also in short-cycle crops production. Moreover, the re-use of some agro-industrial organic residues gives another 'adding value' to this novel organo-mineral fertilfertilisers. Copyright © 2011 Society of Chemical Industry.

ENVIRONMENTAL RELEASE OF ASBESTOS/SUBSTITUTES FROM COMMERCIAL PRODUCTS USE AND DISPOSAL

EPA Science Inventory

For the first time, the release of respirable asbestos fibers has been quantified in terms of standard mechanical forces using widely accepted methodology and specified QA/QC procedures. Both fabrication of new products from asbestos containing materials and repair or removal of ...

Engineering multi-stage nanovectors for controlled degradation and tunable release kinetics

PubMed Central

Martinez, Jonathan O.; Chiappini, Ciro; Ziemys, Arturas; Faust, Ari M.; Kojic, Milos; Liu, Xuewu; Ferrari, Mauro; Tasciotti, Ennio

2013-01-01

Nanovectors hold substantial promise in abating the off-target effects of therapeutics by providing a means to selectively accumulate payloads at the target lesion, resulting in an increase in the therapeutic index. A sophisticated understanding of the factors that govern the degradation and release dynamics of these nanovectors is imperative to achieve these ambitious goals. In this work, we elucidate the relationship that exists between variations in pore size and the impact on the degradation, loading, and release of multistage nanovectors. Larger pored vectors displayed faster degradation and higher loading of nanoparticles, while exhibiting the slowest release rate. The degradation of these particles was characterized to occur in a multi-step progression where they initially decreased in size leaving the porous core isolated, while the pores gradually increased in size. Empirical loading and release studies of nanoparticles along with diffusion modeling revealed that this prolonged release was modulated by the penetration within the porous core of the vectors regulated by their pore size. PMID:23911070

Development and operations of the Astrophysics Data System

NASA Technical Reports Server (NTRS)

Murray, S. S.

1993-01-01

The main effort in October 1992 was for the development and of the Astrophysics Data System (ADS) 3.1 graphical interface (GUI) and the preparation for its release. The beta-release for the GUI was made available to the nodes for testing. Development of the Abstract Server progressed satisfactorily. A test version was prepared for the ADASS meeting. Another major effort was the preparation for the user and nodes meetings on 5 and 6 November and for the ADASS conference on 2-4 November. February 1993 was highlighted by the preparation for the update release and its associated problems. We have the okay from the Commerce Department to export ADS. Foreign users can now sign on and receive the software. The main event during June was the AAS meeting. In the summer, the project decided on a new release schedule. The next major release is scheduled for January 1994 and will include major architectural improvements. In late spring 1994, a major release will include the new networking software.

Rapid estimation of sugar release from winter wheat straw during bioethanol production using FTIR-photoacoustic spectroscopy

DOE PAGES

Bekiaris, Georgios; Lindedam, Jane; Peltre, Clément; ...

2015-06-18

Complexity and high cost are the main limitations for high-throughput screening methods for the estimation of the sugar release from plant materials during bioethanol production. In addition, it is important that we improve our understanding of the mechanisms by which different chemical components are affecting the degradability of plant material. In this study, Fourier transform infrared photoacoustic spectroscopy (FTIR-PAS) was combined with advanced chemometrics to develop calibration models predicting the amount of sugars released after pretreatment and enzymatic hydrolysis of wheat straw during bioethanol production, and the spectra were analysed to identify components associated with recalcitrance. A total of 1122more » wheat straw samples from nine different locations in Denmark and one location in the United Kingdom, spanning a large variation in genetic material and environmental conditions during growth, were analysed. The FTIR-PAS spectra of non-pretreated wheat straw were correlated with the measured sugar release, determined by a high-throughput pretreatment and enzymatic hydrolysis (HTPH) assay. A partial least square regression (PLSR) calibration model predicting the glucose and xylose release was developed. The interpretation of the regression coefficients revealed a positive correlation between the released glucose and xylose with easily hydrolysable compounds, such as amorphous cellulose and hemicellulose. Additionally, we observed a negative correlation with crystalline cellulose and lignin, which inhibits cellulose and hemicellulose hydrolysis. FTIR-PAS was used as a reliable method for the rapid estimation of sugar release during bioethanol production. The spectra revealed that lignin inhibited the hydrolysis of polysaccharides into monomers, while the crystallinity of cellulose retarded its hydrolysis into glucose. Amorphous cellulose and xylans were found to contribute significantly to the released amounts of glucose and xylose, respectively.« less

Rapid estimation of sugar release from winter wheat straw during bioethanol production using FTIR-photoacoustic spectroscopy

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

Bekiaris, Georgios; Lindedam, Jane; Peltre, Clément

Complexity and high cost are the main limitations for high-throughput screening methods for the estimation of the sugar release from plant materials during bioethanol production. In addition, it is important that we improve our understanding of the mechanisms by which different chemical components are affecting the degradability of plant material. In this study, Fourier transform infrared photoacoustic spectroscopy (FTIR-PAS) was combined with advanced chemometrics to develop calibration models predicting the amount of sugars released after pretreatment and enzymatic hydrolysis of wheat straw during bioethanol production, and the spectra were analysed to identify components associated with recalcitrance. A total of 1122more » wheat straw samples from nine different locations in Denmark and one location in the United Kingdom, spanning a large variation in genetic material and environmental conditions during growth, were analysed. The FTIR-PAS spectra of non-pretreated wheat straw were correlated with the measured sugar release, determined by a high-throughput pretreatment and enzymatic hydrolysis (HTPH) assay. A partial least square regression (PLSR) calibration model predicting the glucose and xylose release was developed. The interpretation of the regression coefficients revealed a positive correlation between the released glucose and xylose with easily hydrolysable compounds, such as amorphous cellulose and hemicellulose. Additionally, we observed a negative correlation with crystalline cellulose and lignin, which inhibits cellulose and hemicellulose hydrolysis. FTIR-PAS was used as a reliable method for the rapid estimation of sugar release during bioethanol production. The spectra revealed that lignin inhibited the hydrolysis of polysaccharides into monomers, while the crystallinity of cellulose retarded its hydrolysis into glucose. Amorphous cellulose and xylans were found to contribute significantly to the released amounts of glucose and xylose, respectively.« less

Metal release profiles of orthodontic bands, brackets, and wires: an in vitro study.

PubMed

Wendl, B; Wiltsche, H; Lankmayr, E; Winsauer, H; Walter, A; Muchitsch, A; Jakse, N; Wendl, M; Wendl, T

2017-11-01

The present study evaluated the temporal release of Co Cr, Mn, and Ni from the components of a typical orthodontic appliance during simulated orthodontic treatment. Several commercially available types of bands, brackets, and wires were exposed to an artificial saliva solution for at least 44 days and the metals released were quantified in regular intervals using inductively coupled plasma quadrupole mass spectrometry (ICP-MS, Elan DRC+, Perkin Elmer, USA). Corrosion products encountered on some products were investigated by a scanning electron microscope equipped with an energy dispersive X-ray microanalyzer (EDX). Bands released the largest quantities of Co, Cr, Mn, and Ni, followed by brackets and wires. Three different temporal metal release profiles were observed: (1) constant, though not necessarily linear release, (2) saturation (metal release stopped after a certain time), and (3) an intermediate release profile that showed signs of saturation without reaching saturation. These temporal metal liberation profiles were found to be strongly dependent on the individual test pieces. The corrosion products which developed on some of the bands after a 6-month immersion in artificial saliva and the different metal release profiles of the investigated bands were traced back to different attachments welded onto the bands. The use of constant release rates will clearly underestimate metal intake by the patient during the first couple of days and overestimate exposure during the remainder of the treatment which is usually several months long. While our data are consistent with heavy metal release by orthodontic materials at levels well below typical dietary intake, we nevertheless recommend the use of titanium brackets and replacement of the band with a tube in cases of severe Ni or Cr allergy.

Studies on the mechanism of endogenous pyrogen production. II. Role of cell products in the regulation of pyrogen release from blood leukocytes.

PubMed

Bodel, P

1974-09-01

Some characteristics of the process by which endogenous pyrogen (EP), the mediator of fever, is released from cells were examined by using human blood leukocytes incubated in vitro. Studies were designed to examine a possible role for leukocyte products, including EP, in the induction, augmentation, or suppression of pyrogen release by blood leukocytes. Products of stimulated leukocytes, including a partially purified preparation of EP, did not induce significant activation of nonstimulated cells. Also, no evidence was obtained that stimulated cell products either augment or inhibit pyrogen production by other stimulated cells. A feedback control of EP production was thus not observed. A crude preparation of EP, containing other products of activated cells, maintained its pyrogenicity when incubated at pH 7.4 but not at pH 5.0. These studies thus provide no support for hypothesized control mechanisms regulating production of EP by blood leukocytes. By contrast, local inactivation of EP at inflammatory sites may modify the amount of EP entering the blood, and hence fever.

Studies on the Mechanism of Endogenous Pyrogen Production II. Role of Cell Products in the Regulation of Pyrogen Release from Blood Leukocytes

PubMed Central

Bodel, Phyllis

1974-01-01

Some characteristics of the process by which endogenous pyrogen (EP), the mediator of fever, is released from cells were examined by using human blood leukocytes incubated in vitro. Studies were designed to examine a possible role for leukocyte products, including EP, in the induction, augmentation, or suppression of pyrogen release by blood leukocytes. Products of stimulated leukocytes, including a partially purified preparation of EP, did not induce significant activation of nonstimulated cells. Also, no evidence was obtained that stimulated cell products either augment or inhibit pyrogen production by other stimulated cells. A feedback control of EP production was thus not observed. A crude preparation of EP, containing other products of activated cells, maintained its pyrogenicity when incubated at pH 7.4 but not at pH 5.0. These studies thus provide no support for hypothesized control mechanisms regulating production of EP by blood leukocytes. By contrast, local inactivation of EP at inflammatory sites may modify the amount of EP entering the blood, and hence fever. PMID:4426696

Design evolution of a low shock release nut

NASA Technical Reports Server (NTRS)

Otth, D. H.; Gordon, W.

1976-01-01

Design improvements and detailed functional analyses are reviewed to trace the development of a pyroactuated release device with segmented thread design from its intermediate design into one that reduces the levels of shock spectra generated during its operation by 50%. Comparisons of shock output and internal load distribution are presented, along with descriptions of mechanical operation for both designs. Results also show the potential areas where design development activity can gain further progress in lowering actuation shock levels.

KSC-2011-1014

NASA Image and Video Library

2011-01-05

CAPE CANAVERAL, Fla. -- An endangered green sea turtle is released into the Mosquito Lagoon, which is part of Florida's Indian River. Workers with NASA's Kennedy Space Center, Innovative Health Applications and the Fish and Wildlife Conservation Commission rescued more than 300 turtles during this winter's frigid temperatures. Turtles that were stunned multiple times will be released in the Sebastian area of the Indian River, which often offers warmer water and could help prevent future stuns as winter progresses. NASA/Kim Shiflett

KSC-2011-1015

NASA Image and Video Library

2011-01-05

CAPE CANAVERAL, Fla. -- An endangered green sea turtle is released into the Mosquito Lagoon, which is part of Florida's Indian River. Workers with NASA's Kennedy Space Center, Innovative Health Applications and the Fish and Wildlife Conservation Commission rescued more than 300 turtles during this winter's frigid temperatures. Turtles that were stunned multiple times will be released in the Sebastian area of the Indian River, which often offers warmer water and could help prevent future stuns as winter progresses. NASA/Kim Shiflett

KSC-2011-1017

NASA Image and Video Library

2011-01-05

CAPE CANAVERAL, Fla. -- An endangered green sea turtle is released into the Mosquito Lagoon, which is part of Florida's Indian River. Workers with NASA's Kennedy Space Center, Innovative Health Applications and the Fish and Wildlife Conservation Commission rescued more than 300 turtles during this winter's frigid temperatures. Turtles that were stunned multiple times will be released in the Sebastian area of the Indian River, which often offers warmer water and could help prevent future stuns as winter progresses. NASA/Kim Shiflett

In vitro biocorrosion of Co-Cr-Mo implant alloy by macrophage cells.

PubMed

Lin, Hsin-Yi; Bumgardner, Joel D

2004-11-01

We hypothesized that macrophage cells and their released reactive chemical species (RCS) affect Co-Cr-Mo alloy's corrosion properties and that alloy corrosion products change macrophage cell behavior. A custom cell culture corrosion cell was used to evaluate how culture medium, cells, and RCS altered alloy corrosion in 3-day tests. Corrosion was evaluated by measuring total charge transfer at a constant potential using a potentiostat and metal ion release by atomic emission spectroscopy. Viability, proliferation, and NO (nitric oxide) and IL-1beta (interlukin-1beta) release were used to assess cellular response to alloy corrosion products. In the presence of activated cells, total charge transfers and Co ion release were the lowest (p < 0.05). This was attributed to an enhancement of the surface oxide by RCS. Cr and Mo release were not different between cells and activated cells. Low levels of metal ions did not affect cell viability, proliferation, or NO release, though IL-1beta released from the activated cells was higher on the alloy compared to the controls. These data support the hypothesis that macrophage cells and their RCS affect alloy corrosion. Changes in alloy corrosion by cells may be important to the development of host responses to the alloy and its corrosion products.

Preliminary results of post-irradiation examination of the AGR-1 TRISO fuel compacts

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

Paul Demkowicz; John Hunn; Robert Morris

2012-10-01

Five irradiated fuel compacts from the AGR-1 experiment have been examined in detail in order to assess in-pile fission product release behavior. Compacts were electrolytically deconsolidated and analyzed using the leach-burn-leach technique to measure fission product inventory in the compact matrix and identify any particles with a defective SiC layer. Loose particles were then gamma counted to measure the fission product inventory. One particle with a defective SiC layer was found in the five compacts examined. The fractional release of Ag 110m from the particles was significant. The total fraction of silver released from all the particles within a compactmore » ranged from 0-0.63 and individual particles within a single compact often exhibited a very wide range of silver release. The average fractional release of Eu-154 from all particles in a compact was 2.4×10-4—1.3×10-2, which is indicative of release through intact coatings. The fractional Cs-134 inventory in the compact matrix was <2×10-5 when all coatings remained intact, indicating good cesium retention. Approximately 1% of the palladium inventory was found in the compact matrix for two of the compacts, indicating significant release through intact coatings.« less

"MARK I" MEASUREMENT METHODOLOGY FOR POLLUTION PREVENTION PROGRESS OCCURRING AS A RESULT OF PRODUCT DECISIONS

EPA Science Inventory

A methodology for assessing progress in pollution prevention resulting from product redesign, reformulation or replacement is described. The method compares the pollution generated by the original product with that from the modified or replacement product, taking into account, if...

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.

Energy stress-induced lncRNA HAND2-AS1 represses HIF1α-mediated energy metabolism and inhibits osteosarcoma progression

PubMed Central

Kang, Yao; Zhu, Xiaojun; Xu, Yanyang; Tang, Qinglian; Huang, Zongwen; Zhao, Zhiqiang; Lu, Jinchang; Song, Guohui; Xu, Huaiyuan; Deng, Chuangzhong; Wang, Jin

2018-01-01

During recent years, long noncoding RNAs (lncRNAs) have been recognized as key regulators in the development and progression of human cancers, however, their roles in osteosarcoma metabolism are still not well understood. The present study aims to investigate the expression profiles and potential modulation of specific lncRNA(s) in osteosarcoma metabolism. The high-throughput Hiseq sequencing was performed to screen for abnormally expressed lncRNAs in osteosarcoma cells cultured under glucose starvation condition, and lncRNA HAND2-AS1 was eventually identified as one that was significantly up-regulated when compared with normal cultured cells. Mechanistic investigations indicated that knockdown of HAND2-AS1 abrogated the energy stress-induced effect on cell apoptosis and proliferation, and promoted osteosarcoma progression. Moreover, knockdown of HAND2-AS1 promoted glucose uptake, lactate production, and the expression level of a serious of enzymes that involved in energy metabolism. Subsequently, RNA pull-down and RNA immuneprecipitation revealed that, upon energy stress, HAND2-AS1 regulated osteosarcoma metabolism through sequestering FBP1 from binding to HIF1α, thereby releasing HIF1α expression and promoting the protein level. Taken together, our integrated approach reveals a regulatory mechanism by lncRNA HAND2-AS1 to control energy metabolism and tumor development in osteosarcoma. Thus, HAND2-AS1 may be a potential biomarker and therapeutic target for the repression of osteosarcoma metabolism. PMID:29637006

Postexposure prevention of progressive vaccinia in SCID mice treated with vaccinia immune globulin.

PubMed

Fisher, R W; Reed, J L; Snoy, P J; Mikolajczyk, M G; Bray, M; Scott, D E; Kennedy, M C

2011-01-01

A recently reported case of progressive vaccinia (PV) in an immunocompromised patient has refocused attention on this condition. Uniformly fatal prior to the licensure of vaccinia immune globulin (VIG) in 1978, PV was still fatal in about half of VIG-treated patients overall, with a greater mortality rate in infants and children. Additional therapies would be needed in the setting of a smallpox bioterror event, since mass vaccination following any variola virus release would inevitably result in exposure of immunocompromised people through vaccination or contact with vaccinees. Well-characterized animal models of disease can support the licensure of new products when human studies are not ethical or feasible, as in the case of PV. We chose vaccinia virus-scarified SCID mice to model PV. As in immunocompromised humans, vaccinia virus-scarified SCID animals develop enlarging primary lesions with minimal or no inflammation, eventual distal virus spread, and lethal outcomes if left untreated. Postexposure treatment with VIG slowed disease progression, caused local lesion regression, and resulted in the healthy survival of most of the mice for more than 120 days. Combination treatment with VIG and topical cidofovir also resulted in long-term disease-free survival of most of the animals, even when initiated 7 days postinfection. These results support the possibility that combination treatments may be effective in humans and support using this SCID model of PV to test new antibody therapies and combination therapies and to provide further insights into the pathogenesis and treatment of PV.

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.

Seed storage effects on germination for two forage kochia cultivars

USDA-ARS?s Scientific Manuscript database

The cultivar ‘Snowstorm’ forage kochia was released by the USDA-ARS in 2012. It is a synthetic cultivar selected for stature, forage production, and adaptation to semiarid environments. Similar to the earlier released (1984) ‘Immigrant’ cultivar it can increase rangeland productivity magnitudes when...

Longevity of controlled release fertilizer influences the growth of bedding Impatiens

USDA-ARS?s Scientific Manuscript database

Controlled-release fertilizers (CRF) have not been extensively used in floriculture production, perhaps due to lack of grower experience and research-based information with their use in herbaceous plant production. Any information about the correct use of CRF should increase growers’ confidence in ...

19 CFR 12.12 - Release under bond.

Code of Federal Regulations, 2010 CFR

2010-04-01

... SPECIAL CLASSES OF MERCHANDISE Plants and Plant Products § 12.12 Release under bond. Plants or plant products which require fumigation, disinfection, sterilization, or other treatment as a condition of entry... an inspector of the Department of Agriculture or returned to Customs custody when demanded by the...

Substance Flow Analysis of Mercury in China

NASA Astrophysics Data System (ADS)

Hui, L. M.; Wang, S.; Zhang, L.; Wang, F. Y.; Wu, Q. R.

2015-12-01

In previous studies, the emission of anthropogenic atmospheric Hg in China as well as single sector have been examined a lot. However, there might have been more Hg released as solid wastes rather than air. Hg stored in solid wastes may be released to air again when the solid wastes experience high temperature process or cause local pollution if the solid wastes are stacked casually for a long time. To trace the fate of Hg in China, this study developed the substance flow of Hg in 2010 covering all the sectors summarized in table 1. Below showed in Figure 1, the total Hg input is 2825t. The unintentional input of Hg, mined Hg, and recycled Hg account for 57%, 32% and 11% respectively. Figure 2 provides the detail information of substance flow of Hg. Byproducts from one sector may be used as raw materials of another, causing cross Hg flow between sectors. The Hg input of cement production is 303 t, of which 34% comes from coal and limestone, 33% comes from non-ferrous smelting, 23% comes from coal combustion, 7% comes from iron and steel production and 3% comes from mercury mining. Hg flowing to recycledHg production is 639 t, mainly from Hg contained in waste active carbon and mercuric chloride catalyst from VCM production and acid sludge from non-ferrous smelting. There are 20 t mercury flowing from spent mercury adding products to incineration. Figure1 and Figure 2 also show that 46% of the output Hg belongs to "Lagged release", which means this part of mercury might be released later. The "Lagged release" Hg includes 809 t Hg contained in stacked byproducts form coal combustion, non-ferrous smelting, iron and steel production, Al production, cement production and mercury mining, 161t Hg stored in the pipeline of VCM producing, 10 t Hg in fluorescent lamps that are in use and 314 t mercury stored in materials waiting to be handled with in recycled mercury plants. There is 112 t Hg stored in landfill and 129 t Hg exported abroad with the export of mercury adding products. Besides, 729t Hg is released to the environment, among which, 534 t is emitted to air, 129 t flows into water and 66 t is discharged to soil. To decrease the released mercury, the used mercury should be reduced firstly. On the one hand, large users like VCM production (the largest intentionally mercury user) should lower used mercury, on the other hand, mercury recycling should be enhanced.

TNF-alpha, but not IFN-gamma, regulates CCN2 (CTGF), collagen type I, and proliferation in mesangial cells: possible roles in the progression of renal fibrosis.

PubMed

Cooker, Laurinda A; Peterson, Darryl; Rambow, Joann; Riser, Melisa L; Riser, Rebecca E; Najmabadi, Feridoon; Brigstock, David; Riser, Bruce L

2007-07-01

Connective tissue growth factor (CCN2) is a profibrotic factor acting downstream and independently of TGF-beta to mediate renal fibrosis. Although inflammation is often involved in the initiation and/or progression of fibrosis, the role of inflammatory cytokines in regulation of glomerular CCN2 expression, cellular proliferation, and extracellular matrix accumulation is unknown. We studied two such cytokines, TNF-alpha and IFN-gamma, for their effects on cultured mesangial cells in the presence or absence of TGF-beta, as a model for progressive renal fibrosis. Short-term treatment with TNF-alpha, like TGF-beta, significantly increased secreted CCN2 per cell, but unlike TGF-beta inhibited cellular replication. TNF-alpha combined with TGF-beta further increased CCN2 secretion and mRNA levels and reduced proliferation. Surprisingly, however, TNF-alpha treatment decreased baseline collagen type I protein and mRNA levels and largely blocked their stimulation by TGF-beta. Long-term treatment with TGF-beta or TNF-alpha alone no longer increased CCN2 protein levels. However, the combination synergistically increased CCN2. IFN-gamma had no effect on either CCN2 or collagen activity and produced a mild inhibition of TGF-beta-induced collagen only at a high concentration (500 U/ml). In summary, we report a strong positive regulatory role for TNF-alpha, but not IFN-gamma, in CCN2 production and secretion, including that driven by TGF-beta. The stimulation of CCN2 release by TNF-alpha, unlike TGF-beta, is independent of cellular proliferation and not linked to increased collagen type I accumulation. This suggests that the paradigm of TGF-beta-driven CCN2 with subsequent collagen production may be overridden by an as yet undefined inhibitory mechanism acting either directly or indirectly on matrix metabolism.

The NASA/GEWEX Surface Radiation Budget Release 4 Integrated Product: An Assessment of Improvements in Algorithms and Inputs

NASA Astrophysics Data System (ADS)

Stackhouse, P. W., Jr.; Cox, S. J.; Mikovitz, J. C.; Zhang, T.; Gupta, S. K.

2016-12-01

The NASA/GEWEX Surface Radiation Budget (SRB) project produces, validates and analyzes shortwave and longwave surface and top of atmosphere radiative fluxes for the 1983-near present time period. The current release 3.0/3.1 consists of 1x1 degree radiative fluxes (available at gewex-srb.larc.nasa.gov) and is produced using the International Satellite Cloud Climatology Project (ISCCP) DX product for pixel level radiance and cloud information. This ISCCP DX product is subsampled to 30 km. ISCCP is currently recalibrating and reprocessing their entire data series, to be released as the H product series, with its highest resolution at 10km pixel resolution. The nine-fold increase in number of pixels will allow SRB to produce a higher resolution gridded product (e.g. 0.5 degree or higher), as well as the production of pixel-level fluxes. Other key input improvements include a detailed aerosol history using the Max Planck Institute Aerosol Climatology (MAC), temperature and moisture profiles from HIRS, and new topography, surface type, and snow/ice maps. Here we present results for the improved GEWEX Shortwave and Longwave algorithm (GSW and GLW) with new ISCCP data (for at least 5 years, 2005-2009), various other improved input data sets and incorporation of many additional internal SRB model improvements. We assess the radiative fluxes from new SRB products and contrast these at various resolutions. All these fluxes are compared to both surface measurements and to CERES SYN1Deg and EBAF data products for assessment of the effect of improvements. The SRB data produced will be released as part of the Release 4.0 Integrated Product that shares key input and output quantities with other GEWEX global products providing estimates of the Earth's global water and energy cycle (i.e., ISCCP, SeaFlux, LandFlux, NVAP, etc.).

Prolonged exposure of cortical neurons to oligomeric amyloid-β impairs NMDA receptor function via NADPH oxidase-mediated ROS production: protective effect of green tea (–)-epigallocatechin-3-gallate

PubMed Central

He, Yan; Cui, Jiankun; Lee, James C-M; Ding, Shinghua; Chalimoniuk, Malgorzata; Simonyi, Agnes; Sun, Albert Y; Gu, Zezong; Weisman∥, Gary A; Gibson Wood, W; Sun, Grace Y

2011-01-01

Excessive production of Aβ (amyloid β-peptide) has been shown to play an important role in the pathogenesis of AD (Alzheimer's disease). Although not yet well understood, aggregation of Aβ is known to cause toxicity to neurons. Our recent study demonstrated the ability for oligomeric Aβ to stimulate the production of ROS (reactive oxygen species) in neurons through an NMDA (N-methyl-d-aspartate)-dependent pathway. However, whether prolonged exposure of neurons to aggregated Aβ is associated with impairment of NMDA receptor function has not been extensively investigated. In the present study, we show that prolonged exposure of primary cortical neurons to Aβ oligomers caused mitochondrial dysfunction, an attenuation of NMDA receptor-mediated Ca2+ influx and inhibition of NMDA-induced AA (arachidonic acid) release. Mitochondrial dysfunction and the decrease in NMDA receptor activity due to oligomeric Aβ are associated with an increase in ROS production. Gp91ds-tat, a specific peptide inhibitor of NADPH oxidase, and Mn(III)-tetrakis(4-benzoic acid)-porphyrin chloride, an ROS scavenger, effectively abrogated Aβ-induced ROS production. Furthermore, Aβ-induced mitochondrial dysfunction, impairment of NMDA Ca2+ influx and ROS production were prevented by pre-treatment of neurons with EGCG [(−)-epigallocatechin-3-gallate], a major polyphenolic component of green tea. Taken together, these results support a role for NADPH oxidase-mediated ROS production in the cytotoxic effects of Aβ, and demonstrate the therapeutic potential of EGCG and other dietary polyphenols in delaying onset or retarding the progression of AD. PMID:21434871

Assessment of the pharmaceutical quality of marketed enteric coated pantoprazole sodium sesquihydrate products.

PubMed

Mostafa, Haitham F; Ibrahim, Mohamed A; Mahrous, Gamal M; Sakr, Adel

2011-04-01

Pantoprazole sodium sesquihydrate (PSS) is a proton pump inhibitor, used in acid-related disorders, like peptic ulcer and gastroesophageal reflux. Increasing the number of pantoprazole containing products in the market, raises questions of its efficacy and generic substitution. The pharmaceutical quality of 6 generic PSS enteric coated tablets in 2 local markets was assessed relative to the innovator product (pantozol®). Uniformity of dosage unit, disintegration and in vitro drug release were determined using United States pharmacopeia for delayed release tablets. The similarity factor (f2) was assessed using the FDA recommended approach (f2 similarity factor). The content uniformity of the innovator product was 98.39% of the labeled claim with RSD value of 1.08%, while the content of generic products ranged from 96.98% to 98.80% with RSD values of 1.24-2.19%. All the products showed no disintegration, cracks or swelling in 0.1 N HCl, except product 1, which showed complete disintegration after 20 min. However, the disintegration of all the products in phosphate buffer met USP requirements. Dissolution of tablets in 0.1 N HCl showed no drug release after 2 h except product 1 in which one tablet showed a drug release more than 10% at acid stage level A1. In addition, three tablets of this product showed dissolution of 45%, 48% and 69% at acid stage level A2. The similarity factor f2 of the products was between 71 and 74 indicating the similarity in dissolution profiles of all the products in accordance to FDA requirements, except product 1 in which f2 value was 18.67.

A MODEL FOR FISSION-GAS RELEASE FROM POROUS FUELS IN LOW-PERMEABILITY CONTAINERS

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

Prados, J.W.

1961-08-25

A simple mathematical model was developed to describe the steady-state release rate of gaseous fission products from porous ceramic fuels in low- permeability containers. The resulting equations are used to analyze experimental release rate results obtained from a UC/sub 2/-fueled graphite fuel body enclosed in a low-permeability impregnated graphite container. The relative release rates of the fission-product species Kr/sup 85m/, Kr/sup 88/, and Xe/sup 133/ were predicted with reasonable success. Absolute-rate predictions were not possible due to lack of information on true permeability and porosity profiles in the graphite container. (auth)

Current techniques in rice mill effluent treatment: Emerging opportunities for waste reuse and waste-to-energy conversion.

PubMed

Kumar, Anuj; Priyadarshinee, Rashmi; Roy, Abhishek; Dasgupta, Dalia; Mandal, Tamal

2016-12-01

Rice mills release huge volumes of wastewater and other by-products when processing paddy rice. The wastewater often contains toxic inorganic and organic contaminants which cause environmental damage when released. Accordingly, cost-effective techniques for removing contaminants are needed. This article reviews current processes for curbing pollution and also reusing and recycling waste products. Novel techniques exist for converting waste products into energy and value-added products. Copyright © 2016 Elsevier Ltd. All rights reserved.

Aspergillus-induced superoxide production by cystic fibrosis phagocytes is associated with disease severity.

PubMed

Brunel, Shan F; Willment, Janet A; Brown, Gordon D; Devereux, Graham; Warris, Adilia

2018-04-01

Aspergillus fumigatus infects up to 50% of cystic fibrosis (CF) patients and may play a role in progressive lung disease. As cystic fibrosis transmembrane conductance regulator is expressed in cells of the innate immune system, we hypothesised that impaired antifungal immune responses play a role in CF-related Aspergillus lung disease. Peripheral blood mononuclear cells, polymorphonuclear cells (PMN) and monocytes were isolated from blood samples taken from CF patients and healthy volunteers. Live-cell imaging and colorimetric assays were used to assess antifungal activity in vitro . Production of reactive oxygen species (ROS) was measured using luminol-induced chemiluminescence and was related to clinical metrics as collected by case report forms. CF phagocytes are as effective as those from healthy controls with regards to phagocytosis, killing and restricting germination of A. fumigatus conidia. ROS production by CF phagocytes was up to four-fold greater than healthy controls (p<0.05). This effect could not be replicated in healthy phagocytes by priming with lipopolysaccharide or serum from CF donors. Increased production of ROS against A. fumigatus by CF PMN was associated with an increased number of clinical exacerbations in the previous year (p=0.007) and reduced lung function (by forced expiratory volume in 1 s) (p=0.014). CF phagocytes mount an intrinsic exaggerated release of ROS upon A. fumigatus stimulation which is associated with clinical disease severity.

Aspergillus-induced superoxide production by cystic fibrosis phagocytes is associated with disease severity

PubMed Central

Brunel, Shan F.; Brown, Gordon D.; Devereux, Graham; Warris, Adilia

2018-01-01

Aspergillus fumigatus infects up to 50% of cystic fibrosis (CF) patients and may play a role in progressive lung disease. As cystic fibrosis transmembrane conductance regulator is expressed in cells of the innate immune system, we hypothesised that impaired antifungal immune responses play a role in CF-related Aspergillus lung disease. Peripheral blood mononuclear cells, polymorphonuclear cells (PMN) and monocytes were isolated from blood samples taken from CF patients and healthy volunteers. Live-cell imaging and colorimetric assays were used to assess antifungal activity in vitro. Production of reactive oxygen species (ROS) was measured using luminol-induced chemiluminescence and was related to clinical metrics as collected by case report forms. CF phagocytes are as effective as those from healthy controls with regards to phagocytosis, killing and restricting germination of A. fumigatus conidia. ROS production by CF phagocytes was up to four-fold greater than healthy controls (p<0.05). This effect could not be replicated in healthy phagocytes by priming with lipopolysaccharide or serum from CF donors. Increased production of ROS against A. fumigatus by CF PMN was associated with an increased number of clinical exacerbations in the previous year (p=0.007) and reduced lung function (by forced expiratory volume in 1 s) (p=0.014). CF phagocytes mount an intrinsic exaggerated release of ROS upon A. fumigatus stimulation which is associated with clinical disease severity. PMID:29651422

SAGEIII-ISS Data Release

Atmospheric Science Data Center

2017-11-15

... data has historically been used by the World Meteorological Organization to inform their periodic assessments of ozone depletion. These new ... follow a monthly release schedule.   SAGE III-ISS information is provided in the V5 Release Notes , Data Products User's ...

GLCF: Recent News

Science.gov Websites

global carbon cycle" is published in Nature Communications. October 2016 2015 Water Frequency Beta Release 2015 Water Frequency Beta Release The water frequency product for 2015 is now available via FTP and 2 data for improving our Tree and Water cover product. For more infomration about the project

CALIOP V4.10 L1 & L2 Release Announcement

Atmospheric Science Data Center

2016-11-14

... CALIPSO mission announces the release of new versions of its standard Level 1 and Level 2 lidar data products.  These products are ... essential ancillary data sets. The GTOPO30 Digital Elevation Model (DEM) used in V4.00 has been replaced by a substantially more accurate ...

10 CFR 1707.208 - Restrictions that apply to released records.

Code of Federal Regulations, 2014 CFR

2014-01-01

... 10 Energy 4 2014-01-01 2014-01-01 false Restrictions that apply to released records. 1707.208 Section 1707.208 Energy DEFENSE NUCLEAR FACILITIES SAFETY BOARD TESTIMONY BY DNFSB EMPLOYEES AND PRODUCTION OF OFFICIAL RECORDS IN LEGAL PROCEEDINGS Requests for Testimony and Production of Documents § 1707...

10 CFR 1707.208 - Restrictions that apply to released records.

Code of Federal Regulations, 2012 CFR

2012-01-01

... 10 Energy 4 2012-01-01 2012-01-01 false Restrictions that apply to released records. 1707.208 Section 1707.208 Energy DEFENSE NUCLEAR FACILITIES SAFETY BOARD TESTIMONY BY DNFSB EMPLOYEES AND PRODUCTION OF OFFICIAL RECORDS IN LEGAL PROCEEDINGS Requests for Testimony and Production of Documents § 1707...

10 CFR 1707.208 - Restrictions that apply to released records.

Code of Federal Regulations, 2011 CFR

2011-01-01

... 10 Energy 4 2011-01-01 2011-01-01 false Restrictions that apply to released records. 1707.208 Section 1707.208 Energy DEFENSE NUCLEAR FACILITIES SAFETY BOARD TESTIMONY BY DNFSB EMPLOYEES AND PRODUCTION OF OFFICIAL RECORDS IN LEGAL PROCEEDINGS Requests for Testimony and Production of Documents § 1707...

10 CFR 1707.208 - Restrictions that apply to released records.

Code of Federal Regulations, 2010 CFR

2010-01-01

... 10 Energy 4 2010-01-01 2010-01-01 false Restrictions that apply to released records. 1707.208 Section 1707.208 Energy DEFENSE NUCLEAR FACILITIES SAFETY BOARD TESTIMONY BY DNFSB EMPLOYEES AND PRODUCTION OF OFFICIAL RECORDS IN LEGAL PROCEEDINGS Requests for Testimony and Production of Documents § 1707...

10 CFR 1707.208 - Restrictions that apply to released records.

Code of Federal Regulations, 2013 CFR

2013-01-01

... 10 Energy 4 2013-01-01 2013-01-01 false Restrictions that apply to released records. 1707.208 Section 1707.208 Energy DEFENSE NUCLEAR FACILITIES SAFETY BOARD TESTIMONY BY DNFSB EMPLOYEES AND PRODUCTION OF OFFICIAL RECORDS IN LEGAL PROCEEDINGS Requests for Testimony and Production of Documents § 1707...

76 FR 10667 - Submission for OMB Review; Comment Request

Federal Register 2010, 2011, 2012, 2013, 2014

2011-02-25

... a currently approved collection. Title: Notice of Release of Tobacco Products, Cigarette Papers, or Cigarette Tubes. Form: TTB F 5200.11 Abstract: The form documents the release of tobacco products and cigarette papers and tubes from Customs custody, and return of such articles, to a manufacturer or export...

77 FR 41415 - Single-Ingredient, Immediate-Release Drug Products Containing Oxycodone for Oral Administration...

Federal Register 2010, 2011, 2012, 2013, 2014

2012-07-13

... INFORMATION CONTACT: Astrid Lopez-Goldberg, Center for Drug Evaluation and Research, Food and Drug... DEPARTMENT OF HEALTH AND HUMAN SERVICES Food and Drug Administration [Docket No. FDA-2012-N-0563] Single-Ingredient, Immediate-Release Drug Products Containing Oxycodone for Oral Administration and...

Foamy macrophages and the progression of the human TB granuloma

PubMed Central

Russell, David G.; Cardona, Pere-Joan; Kim, Mi-Jeong; Allain, Sophie; Altare, Frédéric

2009-01-01

The progression of tuberculosis from a latent, sub-clinical infection to active disease that culminates in transmission of infectious bacilli is determined locally at the level of the granuloma. This progression takes place even in the face of a robust immune response that, while it contains infection, is unable to eliminate the bacterium. The factors or environmental conditions that influence this progression remain to be determined. Recent advances have indicated that pathogen-induced dysregulation of host lipid synthesis and sequestration plays a critical role in this transition. The foamy macrophage appears to be a key player in both sustaining persistent bacteria and contributing to the tissue pathology that leads to cavitation and release of infectious bacilli. PMID:19692995

A physics-based model for the ionization of samarium by the MOSC chemical releases in the upper atmosphere

NASA Astrophysics Data System (ADS)

Bernhardt, Paul A.; Siefring, Carl L.; Briczinski, Stanley J.; Viggiano, Albert; Caton, Ronald G.; Pedersen, Todd R.; Holmes, Jeffrey M.; Ard, Shaun; Shuman, Nicholas; Groves, Keith M.

2017-05-01

Atomic samarium has been injected into the neutral atmosphere for production of electron clouds that modify the ionosphere. These electron clouds may be used as high-frequency radio wave reflectors or for control of the electrodynamics of the F region. A self-consistent model for the photochemical reactions of Samarium vapor cloud released into the upper atmosphere has been developed and compared with the Metal Oxide Space Cloud (MOSC) experimental observations. The release initially produces a dense plasma cloud that that is rapidly reduced by dissociative recombination and diffusive expansion. The spectral emissions from the release cover the ultraviolet to the near infrared band with contributions from solar fluorescence of the atomic, molecular, and ionized components of the artificial density cloud. Barium releases in sunlight are more efficient than Samarium releases in sunlight for production of dense ionization clouds. Samarium may be of interest for nighttime releases but the artificial electron cloud is limited by recombination with the samarium oxide ion.

The Food Contaminants Nivalenol and Deoxynivalenol Induce Inflammation in Intestinal Epithelial Cells by Regulating Reactive Oxygen Species Release.

PubMed

Adesso, Simona; Autore, Giuseppina; Quaroni, Andrea; Popolo, Ada; Severino, Lorella; Marzocco, Stefania

2017-12-11

Fusarium mycotoxins are fungal metabolites whose ability to affect cereal grains as multi-contaminants is progressively increasing. The trichothecene mycotoxins nivalenol (NIV) and deoxynivalenol (DON) are often found in almost all agricultural commodities worldwide. They are able to affect animal and human health, including at the intestinal level. In this study, NIV, both alone and in combination with DON, induced inflammation and increased the inflammatory response induced by lipopolysaccharide (LPS) plus Interferon-γ (IFN) in the non-tumorigenic intestinal epithelial cell line (IEC-6). The inflammatory response induced by NIV and DON involves tumor necrosis factor-α (TNF-α) production, inducible nitric oxide synthase (iNOS) and cyclooxygenase-2 (COX-2) expression, nitrotyrosine formation, reactive oxygen species (ROS) release, Nuclear Factor-κB (NF-κB), Nuclear factor (erythroid-derived 2)-like 2 (Nrf2) and inflammasome activation. The pro-inflammatory effect was strongly induced by NIV and by the mycotoxin mixture, when compared to DON alone. Mechanistic studies indicate a pivotal role for ROS in the observed pro-inflammatory effects induced by mycotoxins. In this study, the interactions between NIV and DON point out the importance of their food co-contamination, further highlighting the risk assessment process that is of growing concern.

Active corrosion protection performance of an epoxy coating applied on the mild steel modified with an eco-friendly sol-gel film impregnated with green corrosion inhibitor loaded nanocontainers

NASA Astrophysics Data System (ADS)

Izadi, M.; Shahrabi, T.; Ramezanzadeh, B.

2018-05-01

In this study the corrosion resistance, active protection, and cathodic disbonding performance of an epoxy coating were improved through surface modification of steel by a hybrid sol-gel system filled with green corrosion inhibitors loaded nanocontainer as intermediate layer on mild steel substrate. The green inhibitor loaded nanocontainers (GIN) were used to induce active inhibition performance in the protective coating system. The corrosion protection performance of the coated panels was investigated by electrochemical impedance spectroscopy (EIS), salt spray, and cathodic disbonding tests. It was observed that the corrosion inhibition performance of the coated mild steel panels was significantly improved by utilization of active multilayer coating system. The inhibitor release from nanocontainers at the epoxy-silane film/steel interface resulted in the anodic and cathodic reactions restriction, leading to the lower coating delamination from the substrate and corrosion products progress. Also, the active inhibition performance of the coating system was approved by electrochemical impedance spectroscopy (EIS), scanning electron microscopy (SEM), and energy dispersive X-ray (EDS) analysis on the panels with artificial defects. The inhibitive agents were released to the scratch region and blocked the active sites on the metal surface.

Low VOC drying of lumber and wood panel products. Progress report number 9

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

Hooda, U.; Banerjee, S.; Ingram, L.

1998-10-01

This project is based on the finding that brief microwave or RF-treatment of wood under low-headspace conditions leads to the release of VOCs. On occasion the authors have found that prolonged irradiation increases turpentine yield much more than anticipated from a simple mass balance; i.e., more pinene appeared to be released than was present in the wood in the first place. If taken at face value, this suggests that brief low-headspace irradiation removes VOCs, while prolonged exposure creates it. While seemingly improbable, this could follow if dielectric heating exposed regions of wood that were otherwise inaccessible to the solvent usedmore » for extraction (unlikely), or if the irradiation induced depolymerization of terpene dimers or higher polymers. In this report the authors attempt to identify the conditions that lead to this apparent enhancement of terpene yield, by constructing relationships between yield and irradiation parameters. The tentative conclusions are that this enhancement only occurs with relatively wet heartwood, and only under prolonged irradiation. An additional conclusion is that continuing analyses of twelve trees in the MSU forest confirm that the absence of a significant seasonal influence on turpentine content. An apparatus for permeability testing has been constructed, and work is underway.« less

Fifty Years of Research in ARDS. Cell-based Therapy for Acute Respiratory Distress Syndrome. Biology and Potential Therapeutic Value.

PubMed

Laffey, John G; Matthay, Michael A

2017-08-01

On the basis of several preclinical studies, cell-based therapy has emerged as a potential new therapeutic for acute respiratory distress syndrome (ARDS). Of the various cell-based therapy options, mesenchymal stem/stromal cells (MSCs) from bone marrow, adipose tissue, and umbilical cord have the most experimental data to support their potential efficacy for lung injury from both infectious and noninfectious causes. Mechanistically, MSCs exert their beneficial effects by release of paracrine factors, microvesicles, and transfer of mitochondria, all of which have antiinflammatory and pro-resolving effects on injured lung endothelium and alveolar epithelium, including enhancing the resolution of pulmonary edema by up-regulating sodium-dependent alveolar fluid clearance. MSCs also have antimicrobial effects mediated by release of antimicrobial factors and by up-regulating monocyte/macrophage phagocytosis. Phase 2a clinical trials to establish safety in ARDS are in progress, and two phase 1 trials did not report any serious adverse events. Several issues need further study, including: determining the optimal methods for large-scale production, reconstitution of cryopreserved cells for clinical use, defining cell potency assays, and determining the therapeutic potential of conditioned media derived from MSCs. Because ARDS is a heterogeneous syndrome, targeting MSCs to patients with ARDS with a more hyperinflammatory endotype may further enhance their potential for efficacy.

The Neuroglial Dialog Between Cannabinoids and Hemichannels

PubMed Central

Labra, Valeria C.; Santibáñez, Cristian A.; Gajardo-Gómez, Rosario; Díaz, Esteban F.; Gómez, Gonzalo I.; Orellana, Juan A.

2018-01-01

The formation of gap junctions was initially thought to be the central role of connexins, however, recent evidence had brought to light the high relevance of unopposed hemichannels as an independent mechanism for the selective release of biomolecules during physiological and pathological conditions. In the healthy brain, the physiological opening of astrocyte hemichannels modulates basal excitatory synaptic transmission. At the other end, the release of potentially neurotoxic compounds through astroglial hemichannels and pannexons has been insinuated as one of the functional alterations that negatively affect the progression of multiple brain diseases. Recent insights in this matter have suggested encannabinoids (eCBs) as molecules that could regulate the opening of these channels during diverse conditions. In this review, we discuss and hypothesize the possible interplay between the eCB system and the hemichannel/pannexon-mediated signaling in the inflamed brain and during event of synaptic plasticity. Most findings indicate that eCBs seem to counteract the activation of major neuroinflammatory pathways that lead to glia-mediated production of TNF-α and IL-1β, both well-known triggers of astroglial hemichannel opening. In contrast to the latter, in the normal brain, eCBs apparently elicit the Ca2+-activation of astrocyte hemichannels, which could have significant consequences on eCB-dependent synaptic plasticity. PMID:29662436

Transmutation effects on long-term Cs retention in phyllosilicate minerals from first principles.

PubMed

Sassi, Michel; Okumura, Masahiko; Machida, Masahiko; Rosso, Kevin M

2017-10-11

The accidental release and incorporation of radiocesium into soil minerals represents a massive environmental, technical and social challenge. Accurately forecasting the evolving distribution and fate of long- and medium-lived isotopes such as 137 Cs and 134 Cs over decadal time scales is essential. The cesium cation has long been modeled as a strongly and selectively sorbed species into clay mineral interlayers; however, because of the time scales involved by the radioisotopes half-lives, the effects of radioactive decay on Cs retention have been unknown. We report density functional theory (DFT) simulations of transmutation effects of radiocesium on long-term Cs retention in phlogopite. The calculations show that the progressive appearance of daughter product Ba 2+ is accompanied by a proportional increase in thermodynamic driving force to preferentially discharge remaining Cs, both radioactive and stable, back into aqueous solution. Based on thermodynamic analysis, the findings indicate that radiocesium transmutation provides a mean to weaken the binding of Cs in phyllosilicate minerals, therefore potentially involving a premature re-release of Cs back into the environment. In the case where radiogenic Ba 2+ ions accumulate in the mineral, collateral effects would ultimately be an increase in the overall interlayer binding energy and a lower resorption capacity.

Phytotoxicity, accumulation and transport of silver nanoparticles by Arabidopsis thaliana.

PubMed

Geisler-Lee, Jane; Wang, Qiang; Yao, Ying; Zhang, Wen; Geisler, Matt; Li, Kungang; Huang, Ying; Chen, Yongsheng; Kolmakov, Andrei; Ma, Xingmao

2013-05-01

The widespread availability of nano-enabled products in the global market may lead to the release of a substantial amount of engineered nanoparticles in the environment, which frequently display drastically different physiochemical properties than their bulk counterparts. The purpose of the study was to evaluate the impact of citrate-stabilised silver nanoparticles (AgNPs) on the plant Arabidopsis thaliana at three levels, physiological phytotoxicity, cellular accumulation and subcellular transport of AgNPs. The monodisperse AgNPs of three different sizes (20, 40 and 80 nm) aggregated into much larger sizes after mixing with quarter-strength Hoagland solution and became polydisperse. Immersion in AgNP suspension inhibited seedling root elongation and demonstrated a linear dose-response relationship within the tested concentration range. The phytotoxic effect of AgNPs could not be fully explained by the released silver ions. Plants exposed to AgNP suspensions bioaccumulated higher silver content than plants exposed to AgNO3 solutions (Ag(+) representative), indicating AgNP uptake by plants. AgNP toxicity was size and concentration dependent. AgNPs accumulated progressively in this sequence: border cells, root cap, columella and columella initials. AgNPs were apoplastically transported in the cell wall and found aggregated at plasmodesmata. In all the three levels studied, AgNP impacts differed from equivalent dosages of AgNO3.

In-vitro release and permeation studies of ketoconazole from optimized dermatological vehicles using powder, nanoparticles and solid dispersion forms of drug

NASA Astrophysics Data System (ADS)

Mohammed, Irfan A.

To optimize the clinical efficacy of Ketoconazole from an externally applied product, this project was undertaken to evaluate the drug release/permeation profile from various dermatological vehicles using regular powder, nanoparticles and solid dispersion forms with reduced level of drug. Nanoparticles of drug were prepared by wet media milling method using Polyvinylpyrrolidone (PVP-10K) as a stabilizer. The nanoparticles were in the size range of 250-300nm. Solid dispersion was prepared by solvent evaporation method using drug to PVP-10K at a weight ratio of (1:2). Formulations containing 1% w/w drug were developed using HPMC gel, Carbomer gel and a cationic cream as the vehicles. Penetration enhancers including propylene glycol (PG), dimethylsulfoxide (DMSO) and polyethylene glycol 400 (PEG-400) at various levels were evaluated. A commercial 2% w/w ketoconazole product was included as a control for comparison. Studies were carried out with Franz Diffusion Cells using cellulose membrane and human cadaver skin for two and six hour studies. Among the formulations evaluated, the general rank order of the drug release through the cellulose membrane was observed to be: HPMC gel base > Anionic gel base > Cationic gel base > Commercial product. The addition of penetration enhancers showed variable effects in all samples evaluated. However, the HPMC gel-based vehicle showed significant effect in enhancing the drug release in the presence of DMSO. The formulation containing 1% w/w ketoconazole and 20% w/w DMSO gave a maximum drug release of 20.21% when compared to only 1.60% from the commercial product. This represents a twelve fold increase in the release of ketoconazole from the formulation. Furthermore, when the optimum gel-based formulation containing 1% w/w ketoconazole was studied over an extended period of 6 hours, it gave 36.01% drug release from the sample formulation compared to only 2.00% from the commercial product. Finally, this formulation was selected to study for its drug release/permeation profile using the human cadaver skin as the diffusion barrier. Here, as expected, the drug release from both the formulations tested was significantly reduced due to the resistance posed by the skin. After 6 hours, the drug release form the commercial product was 0.17% when compared to 2.80% from the optimum formulation. Once again, this indicated that the experimental formulation exhibits superior drug release dynamics. The selected formulations were further evaluated for their in-vitro anti-fungal activities using yeast microorganisms. The results correlated to the in-vitro drug release profile, where HPMC based formulations exhibited a greater area of zone of inhibition for the growth of microorganisms when compared to diminutive area of zone of inhibition for the commercial product. The release data from all the samples were treated to calculate various physical parameters including: diffusion co-efficient, partition co-efficient, steady state flux and lag period etc. Interestingly, the values for the steady state flux and diffusion coefficient were found to be the highest from the optimum formulation and the values for the lag time and partition coefficient were observed to be the lowest. This supports the evidence that the drug from this formulation is readily diffusible to the skin at a steady rate after its application at the site. In-vitro drug diffusion studies and in-vitro anti-fungal studies proved useful in screening various dermatological formulations of ketoconazole compared to the commercial product containing 2% w/w drug. The HPMC based optimum formulation with reduced level of drug represents 15 folds increase through human cadaver skin and also exhibited augmented anti-fungal activity. This supports that by using an appropriate vehicle and proper incorporation of drug, one can optimize the drug release from topical formulation for maximum therapeutic effect.

GENIE Production Release 2.10.0

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

Alam, M.; Andreopoulos, C.; Athar, M.

2015-12-25

GENIE is a neutrino Monte Carlo event generator that simulates the primary interaction of a neutrino with a nuclear target, along with the subsequent propagation of the reaction products through the nuclear medium. It additionally contains libraries for fully-featured detector geometries and for managing various types of neutrino flux. This note details recent updates to GENIE, in particular, changes introduced into the newest production release, version 2.10.0.

Problematising the Pursuit of Progress in Mathematics Education

ERIC Educational Resources Information Center

Llewellyn, Anna

2016-01-01

In this article, I use a Foucauldian poststructural analysis to examine productions of progress within key discursive spaces of mathematics education. These sites of production are educational policy, mathematics education research and case studies of primary school student-teachers in England. From my analysis, I show how progress governs what is…

21 CFR 178.3860 - Release agents.

Code of Federal Regulations, 2010 CFR

2010-04-01

... 21 Food and Drugs 3 2010-04-01 2009-04-01 true Release agents. 178.3860 Section 178.3860 Food and... and Production Aids § 178.3860 Release agents. Substances listed in paragraph (b) of this section may be safely used as release agents in petroleum wax complying with § 178.3710 and in polymeric resins...

Effects of water temperature and substrate type on spore production and release in eastern Tubifex tubifex worms infected with Myxobolus cerebralis

USGS Publications Warehouse

Blazer, V.S.; Waldrop, T.B.; Schill, W.B.; Densmore, Christine L.; Smith, D.

2003-01-01

Eastern Tubifex tubifex worms were exposed to Myxobolus cerebralis spores at 9, 13, 17, and 20 C in 1-L jars that contained sand, mud, or leaf litter as substrata. Beginning 60 days after exposure, water from each jar was filtered daily and examined for the presence of waterborne triactinomyxon spores (TAMs). On discovering a single TAM from an experimental jar, 48 T. tubifex worms from that jar were placed individually into 24-well plates. Spores released from individual infected T. tubifex worms were quantified to determine the first day of TAM release from infected worms, the infection rate, the total number of TAMs released per worm, and the duration of release. No TAMs were found in any of the jars incubated at 20 C or in uninfected, control worms at any temperature. The total number of TAMs released by infected worms in mud and sand was highest at 13 C compared with other temperatures. Infection rates among individual worms increased with temperature between 9 and 17 C. Higher temperatures (up to 17 C) induced earlier TAM releases among infected worms, and substratum did not influence this production parameter. The average duration of TAM release decreased as the temperature increased from 9 to 17 C, and there was a significant effect of substratum in the groups maintained at 13 and 17 C. In all temperature treatments between 9 and 17 C, the duration of release was least in the worms maintained in leaf litter, as was the total number of TAMs released during the experimental period and the median number of TAMs per production day.

Dopamine Burden Triggers Neurodegeneration via Production and Release of TNF-α from Astrocytes in Minimal Hepatic Encephalopathy.

PubMed

Ding, Saidan; Wang, Weikan; Wang, Xuebao; Liang, Yong; Liu, Leping; Ye, Yiru; Yang, Jianjing; Gao, Hongchang; Zhuge, Qichuan

2016-10-01

Dopamine (DA)-induced learning and memory impairment is well documented in minimal hepatic encephalopathy (MHE), but the contribution of DA to neurodegeneration and the involved underlying mechanisms are not fully understood. In this study, the effect of DA on neuronal apoptosis was initially detected. The results showed that MHE/DA (10 μg)-treated rats displayed neuronal apoptosis. However, we found that DA (10 μM) treatment did not induce evident apoptosis in primary cultured neurons (PCNs) but did produce TNF-α in primary cultured astrocytes (PCAs). Furthermore, co-cultures between PCAs and PCNs exposed to DA exhibited increased astrocytic TNF-α levels and neuronal apoptosis compared with co-cultures exposed to the vehicle, indicating the attribution of the neuronal apoptosis to astrocytic TNF-α. We also demonstrated that DA enhanced TNF-α production from astrocytes by activation of the TLR4/MyD88/NF-κB pathway, and secreted astrocytic TNF-α-potentiated neuronal apoptosis through inactivation of the PI3K/Akt/mTOR pathway. Overall, the findings from this study suggest that DA stimulates substantial production and secretion of astrocytic TNF-α, consequently and indirectly triggering progressive neurodegeneration, resulting in cognitive decline and memory loss in MHE.

Involvement of CTGF, a hypertrophic chondrocyte-specific gene product, in tumor angiogenesis.

PubMed

Shimo, T; Nakanishi, T; Nishida, T; Asano, M; Sasaki, A; Kanyama, M; Kuboki, T; Matsumura, T; Takigawa, M

2001-01-01

Connective tissue growth factor (CTGF) is a potent secreted signaling factor which functions in multiple stages of angiogenesis. In the present study, we examined the role of CTGF in tumor angiogenesis and made the following observations: (1) Histological analysis of human breast cancer (MDA231) cell and human fibrosarcoma (HT1080) cell xenografts in BALB/c nude mice showed a high level of neovascularization. Human squamous cell carcinoma (A431) xenografts induced only a low level of neovascularization. (2) CTGF mRNA was strongly expressed in MDA231 and in HT1080 cells in vivo and in vitro, but not in A431 cells. (3) CTGF protein was markedly produced in MDA231 cells and HT1080 cells and secreted into culture medium, and its production was greater during phases of growth rather than confluency. (4) Production of CTGF in bovine aorta endothelial cells was induced by CTGF, VEGF, bFGF and TGF-beta. (5) Neovascularization induced by HT1080 cells or MDA231 cells on chicken chorioallantoic membrane was suppressed in the presence of neutralizing CTGF-specific polyclonal antibody. These results suggest that CTGF regulates progression in tumor angiogenesis and the release or secretion of CTGF from tumor cells is essential for the angiogenesis. Copyright 2001 S. Karger AG, Basel

Progress Against Prostate Cancer | NIH MedlinePlus the Magazine

MedlinePlus

... those diagnosed being 45 or older. What Is PSA? Prostate specific antigen, or PSA, is a substance produced by the prostate and released into the blood. PSA levels are often high in men with prostate ...

Fluid flow stimulates rapid and continuous release of nitric oxide in osteoblasts

NASA Technical Reports Server (NTRS)

Johnson, D. L.; McAllister, T. N.; Frangos, J. A.

1996-01-01

Interstitial fluid flow may mediate skeletal remodeling in response to mechanical loading. Because nitric oxide (NO) has been shown to be an osteoblast mitogen and inhibitor of osteoclastic resorption, we investigated and characterized the role of fluid shear on the release of NO in osteoblasts. Rat calvarial cells in a stationary culture produced undetectable levels of NO. Fluid shear stress (6 dyn/cm2) rapidly increased NO release rate to 9.8 nmol.h-1.mg protein-1 and sustained this production for 12 h of exposure to flow. Cytokine treatment also induced NO synthesis after a 12-h lag phase of zero production, followed by a production rate of 0.6 nmol.h-1.mg protein-1. Flow-induced NO production was blocked by the NO synthase (NOS) inhibitor NG-amino-L-arginine, but not by dexamethasone, which suggests that the flow stimulated a constitutive NOS isoform. This is the first time that a functional constitutively present NOS isoform has been identified in osteoblasts. Moreover, fluid flow represents the most potent stimulus of NO release in osteoblasts reported to date. Fluid flow-induced NO production may therefore play a primary role in bone maintenance and remodeling.

Greater absolute rates of N2O production and consumption with soil warming dwarf variations in denitrification enzyme temperature sensitivities across seasons

NASA Astrophysics Data System (ADS)

Tiemann, L. K.; Billings, S. A.

2010-12-01

Investigators appreciate the important role that nitrate (NO3-) and soil moisture availability can play in governing net N2O production from soils. However, a large knowledge gap remains surrounding the drivers of soil N2O consumption and the role of microbial adaptation to changing environmental conditions in governing both N2O production and consumption. Net N2O soil efflux can be correlated with temperature, but little is known about the influence of temperature on gross rates of N2O production vs. consumption. Further, we do not understand how microbial communities responsible for these processes adapt or acclimate to soil warming. To investigate whether temperature alters the denitrifier-mediated fate of NO3- lost via N2O or N2, and if any such effect changes across seasons, we incubated soil collected in three seasons at four temperatures with and without 15N-enriched nitrate for 26 hours. Incubations were conducted in an anaerobic environment flushed with helium to permit detection of N2O and N2, and those gases’ δ15N. Temperature positively influenced CO2 production resulting from anaerobic processes. Maximum values of net N2O production were positively influenced by incubation and seasonal temperature, and the maximum rate of net N2O production occurred relatively early at warmer incubation temperatures. We also observed greater N2O:N2 ratios early in the incubations at warmer incubation temperatures. Isotope data are consistent with these trends. For those soils receiving the 15N label, differences in δ15N2O between early and late in the incubations were increasingly negative, and differences in δ15N2 increasingly positive, as temperature increased. Q10 values for N2O production and consumption exhibited increasing similarities as seasons progressed, with June N2O production and consumption Q10 values being nearly identical. These data provide convincing evidence that: a) increasing temperatures can induce denitrifying communities to perform complete denitrification (i.e. consumption of gross N2O production into N2) to a greater degree, and permit release of a relatively smaller proportion of the nitrate they consumed as N2O; b) the suite of enzymes responsible for N2O production and the one enzyme responsible for its consumption exhibit differential temperature sensitivities in their production and expression during winter months, but the sensitivity of these processes converges during warmer seasons; c) in spite of the smaller proportion of NO3- released as N2O with warming, warming’s positive influence on the amount of NO3- transformed by denitrifying organisms resulted in far greater absolute quantities of N2O released with incubation and seasonal warming. Continuing work explores the influence that temperature may exert on the relative abundances of denitrifying populations and their gene expression, and links these microbial characteristics to denitrification processes with warming. These data signify the importance of understanding enzyme kinetics in concert with microbial adaptation and acclimation as a factor governing the net fluxes of N2O from soil vs. its transformation into N2 with warming.

Recent Developments on Autonomous Corrosion Protection Through Encapsulation

NASA Technical Reports Server (NTRS)

Li, W.; Buhrow, J. W.; Calle, L. M.; Gillis, M.; Blanton, M.; Hanna, J.; Rawlins, J.

2015-01-01

This paper concerns recent progress in the development of a multifunctional smart coating, based on microencapsulation, for the autonomous detection and control of corrosion. Microencapsulation has been validated and optimized to incorporate desired corrosion control functionalities, such as early corrosion detection and inhibition, through corrosion-initiated release of corrosion indicators and inhibitors, as well as self-healing agent release triggered by mechanical damage. While proof-of-concept results have been previously reported, more recent research and development efforts have concentrated on improving coating compatibility and synthesis procedure scalability, with a targeted goal of obtaining easily dispersible pigment-grade type microencapsulated materials. The recent progress has resulted in the development of pH-sensitive microparticles as a corrosion-triggered delivery system for corrosion indicators and inhibitors. The synthesis and early corrosion indication results obtained with coating formulations that incorporate these microparticles are reported. The early corrosion indicating results were obtained with color changing and with fluorescent indicators.

New Orleans' Resilience Story

NASA Astrophysics Data System (ADS)

Hebert, J.

2017-12-01

New Orleans has had unique experience in dealing with and recovering from major urban emergencies. From Hurricanes Katrina and Isaac to the Deepwater Horizon Oil Spill to the city's frequent boil water advisories, New Orleans has learned important lessons about what it takes to become a vibrant, resilient city that serves all its residents — particularly its most vulnerable. The city of New Orleans released its Resilience Strategy on August 28, 2015. On September 12, 2016, the city released its One-Year Progress Update, sharing its key milestones.

KSC-2011-1012

NASA Image and Video Library

2011-01-05

CAPE CANAVERAL, Fla. -- Karen Holloway, a biologist with Innovative Health Applications at NASA's Kennedy Space Center in Florida, prepares to release an endangered green sea turtle into the Mosquito Lagoon, which is part of Florida's Indian River. The turtle was one of more than 300 that were "stunned" during two cold snaps in December 2010. Turtles that were stunned multiple times will be released in the Sebastian area of the Indian River, which often offers warmer water and could help prevent future stuns as winter progresses. NASA/Kim Shiflett

KSC-2011-1013

NASA Image and Video Library

2011-01-05

CAPE CANAVERAL, Fla. -- Donna Oddy, a biologist with Innovative Health Applications at NASA's Kennedy Space Center in Florida, releases an endangered green sea turtle into the Mosquito Lagoon, which is part of Florida's Indian River. The turtle was one of more than 300 that were "stunned" during two cold snaps in December 2010. Turtles that were stunned multiple times will be released in the Sebastian area of the Indian River, which often offers warmer water and could help prevent future stuns as winter progresses. NASA/Kim Shiflett

KSC-2011-1011

NASA Image and Video Library

2011-01-05

CAPE CANAVERAL, Fla. -- Karen Holloway, a biologist with Innovative Health Applications at NASA's Kennedy Space Center in Florida, releases an endangered green sea turtle into the Mosquito Lagoon, which is part of Florida's Indian River. The turtle was one of more than 300 that were "stunned" during two cold snaps in December 2010. Turtles that were stunned multiple times will be released in the Sebastian area of the Indian River, which often offers warmer water and could help prevent future stuns as winter progresses. NASA/Kim Shiflett

Safety Precautions for Total Release Foggers

EPA Pesticide Factsheets

Total release foggers, also known as bug bombs, are pesticide products containing aerosol propellants that release their contents at once to fumigate an area. They can pose a hazard if used incorrectly. Find safety information and videos on this page.

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.

Linear Free Energy Correlations for Fission Product Release from the Fukushima-Daiichi Nuclear Accident

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

Abrecht, David G.; Schwantes, Jon M.

This paper extends the preliminary linear free energy correlations for radionuclide release performed by Schwantes, et al., following the Fukushima-Daiichi Nuclear Power Plant accident. Through evaluations of the molar fractionations of radionuclides deposited in the soil relative to modeled radionuclide inventories, we confirm the source of the radionuclides to be from active reactors rather than the spent fuel pool. Linear correlations of the form ln χ = -α (ΔG rxn°(T C))/(RT C)+β were obtained between the deposited concentration and the reduction potential of the fission product oxide species using multiple reduction schemes to calculate ΔG° rxn(T C). These models allowedmore » an estimate of the upper bound for the reactor temperatures of T C between 2130 K and 2220 K, providing insight into the limiting factors to vaporization and release of fission products during the reactor accident. Estimates of the release of medium-lived fission products 90Sr, 121mSn, 147Pm, 144Ce, 152Eu, 154Eu, 155Eu, 151Sm through atmospheric venting and releases during the first month following the accident were performed, and indicate large quantities of 90Sr and radioactive lanthanides were likely to remain in the damaged reactor cores.« less

Youth for Astronomy and Engineering - Engaging Local Families and Partners

NASA Astrophysics Data System (ADS)

Anderson, Tania; Eisenhamer, B.; Ryer, H.

2013-06-01

Youth for Astronomy and Engineering (YAE) is a program in the Space Telescope Science Institute’s Office of Public Outreach. It is designed to engage the local community in science, technology, engineering, and mathematics (STEM). This is accomplished through a series of yearly events such as astronomy and engineering clubs for students, family nights, and professional development for local educators. These events leverage SMD mission science to expose participants to the latest science discoveries (Hubble), new developments in space technology (James Webb), STEM career information, and activities that are representative of the work done by individuals in the astronomical and engineering fields. The YAE program helps provide a progression of opportunities for audiences by attracting and identifying highly-engaged individuals for participation in more intensive experiences. It also helps increase our impact by creating a network for piloting E/PO products and initiatives at the local level before nationwide release. This poster will highlight the YAE program.

Youth for Astronomy & Engineering Program: Engaging Local Families and Partners

NASA Astrophysics Data System (ADS)

Anderson, Tania; Eisenhamer, B.; Ryer, H.

2014-01-01

Youth for Astronomy and Engineering (YAE) is a program in the Space Telescope Science Institute's Office of Public Outreach. It is designed to engage the local community in science, technology, engineering, and mathematics (STEM). This is accomplished through a series of yearly events such as astronomy and engineering clubs for students, family nights, and professional development for local educators. These events leverage SMD mission science to expose participants to the latest science discoveries (Hubble), new developments in space technology (James Webb), STEM career information, and activities that are representative of the work done by individuals in the astronomical and engineering fields. The YAE program helps provide a progression of opportunities for audiences by attracting and identifying highly-engaged individuals for participation in more intensive experiences. It also helps increase our impact by creating a network for piloting E/PO products and initiatives at the local level before nationwide release. This poster will highlight the YAE program.

Emission of volatile organic compounds from petunia flowers is facilitated by an ABC transporter.

PubMed

Adebesin, Funmilayo; Widhalm, Joshua R; Boachon, Benoît; Lefèvre, François; Pierman, Baptiste; Lynch, Joseph H; Alam, Iftekhar; Junqueira, Bruna; Benke, Ryan; Ray, Shaunak; Porter, Justin A; Yanagisawa, Makoto; Wetzstein, Hazel Y; Morgan, John A; Boutry, Marc; Schuurink, Robert C; Dudareva, Natalia

2017-06-30

Plants synthesize a diversity of volatile molecules that are important for reproduction and defense, serve as practical products for humans, and influence atmospheric chemistry and climate. Despite progress in deciphering plant volatile biosynthesis, their release from the cell has been poorly understood. The default assumption has been that volatiles passively diffuse out of cells. By characterization of a Petunia hybrida adenosine triphosphate-binding cassette (ABC) transporter, PhABCG1, we demonstrate that passage of volatiles across the plasma membrane relies on active transport. PhABCG1 down-regulation by RNA interference results in decreased emission of volatiles, which accumulate to toxic levels in the plasma membrane. This study provides direct proof of a biologically mediated mechanism of volatile emission. Copyright © 2017 The Authors, some rights reserved; exclusive licensee American Association for the Advancement of Science. No claim to original U.S. Government Works.

Clinical-grade production of human mesenchymal stromal cells: occurrence of aneuploidy without transformation.

PubMed

Tarte, Karin; Gaillard, Julien; Lataillade, Jean-Jacques; Fouillard, Loic; Becker, Martine; Mossafa, Hossein; Tchirkov, Andrei; Rouard, Hélène; Henry, Catherine; Splingard, Marie; Dulong, Joelle; Monnier, Delphine; Gourmelon, Patrick; Gorin, Norbert-Claude; Sensebé, Luc

2010-02-25

Clinical-grade human mesenchymal stromal cells (MSCs) have been expanded in vitro for tissue engineering or immunoregulatory purposes without standardized culture conditions or release criteria. Although human MSCs show poor susceptibility for oncogenic transformation, 2 recent studies described their capacity to accumulate chromosomal instability and to give rise to carcinoma in immunocompromised mice after long-term culture. We thus investigated the immunologic and genetic features of MSCs expanded with fetal calf serum and fibroblast growth factor or with platelet lysate in 4 cell-therapy facilities during 2 multicenter clinical trials. Cultured MSCs showed a moderate expression of human leukocyte antigen-DR without alteration of their low immunogenicity or their immunomodulatory capacity. Moreover, some transient and donor-dependent recurring aneuploidy was detected in vitro, independently of the culture process. However, MSCs with or without chromosomal alterations showed progressive growth arrest and entered senescence without evidence of transformation either in vitro or in vivo.

Advances of blood cell-based drug delivery systems.

PubMed

Sun, Yanan; Su, Jing; Liu, Geyi; Chen, Jianjun; Zhang, Xiumei; Zhang, Ran; Jiang, Minhan; Qiu, Mingfeng

2017-01-01

Blood cells, including erythrocytes, leukocytes and platelets are used as drug carriers in a wide range of applications. They have many unique advantages such as long life-span in circulation (especially erythrocytes), target release capacities (especially platelets), and natural adhesive properties (leukocytes and platelets). These properties make blood cell based delivery systems, as well as their membrane-derived carriers, far superior to other drug delivery systems. Despite the advantages, the further development of blood cell-based delivery systems was hindered by limitations in the source, storage, and mass production. To overcome these problems, synthetic biomaterials that mimic blood cell and nanocrystallization of blood cells have been developed and may represent the future direction for blood cell membrane-based delivery systems. In this paper, we review recent progress of the rising blood cell-based drug delivery systems, and also discuss their challenges and future tendency of development. Copyright © 2016. Published by Elsevier B.V.

The Development of Boiler Pipes Used for 700°C A-USC-PP in China

NASA Astrophysics Data System (ADS)

Liu, Zhengdong; Bao, Hansheng; Xu, Songqian; Wang, Qijiang; Yang, Yujun; Zhang, Peng; Lei, Bingwang

This paper introduces the progress of boiler pipes used for the manufacturing of 700°C advanced ultra-super-critical (A-USC) fossil fuel power plants (PP) in China, with the emphasis on the detailed advancements of G115 and CN617 pipes, including technical exploration, industrial production and microstructure-property investigation. G115 is a novel ferritic heat resistant steels developed by CISRI, which is an impressive candidate material to make pipes for the temperature up to 650°C. CN617 is a recent modification of Inconel617B and the CN617 pipe with the dimension of Φ 460 × 80 mm was successfully manufactured in China. Some newly available data associated with above materials will be released. G115 and CN617 are imposing candidate materials for the manufacturing of 700°C advanced ultra-super-critical (A-USC) fossil fuel power plants (PP) in China.

The vaccines consistency approach project: an EPAA initiative.

PubMed

De Mattia, F; Hendriksen, C; Buchheit, K H; Chapsal, J M; Halder, M; Lambrigts, D; Redhead, K; Rommel, E; Scharton-Kersten, T; Sesardic, T; Viviani, L; Ragan, I

2015-01-01

The consistency approach for release testing of established vaccines promotes the use of in vitro, analytical, non-animal based systems allowing the monitoring of quality parameters during the whole production process. By using highly sensitive non-animal methods, the consistency approach has the potential to improve the quality of testing and to foster the 3Rs (replacement, refinement and reduction of animal use) for quality control of established vaccines. This concept offers an alternative to the current quality control strategy which often requires large numbers of laboratory animals. In order to facilitate the introduction of the consistency approach for established human and veterinary vaccine quality control, the European Partnership for Alternatives to Animal Testing (EPAA) initiated a project, the "Vaccines Consistency Approach Project", aiming at developing and validating the consistency approach with stakeholders from academia, regulators, OMCLs, EDQM, European Commission and industry. This report summarises progress since the project's inception.

Lactic acid alleviates stress: good for female genital tract homeostasis, bad for protection against malignancy.

PubMed

Witkin, Steven S

2018-05-01

Women are unique from all other mammals in that lactic acid is present at high levels in the vagina during their reproductive years. This dominance may have evolved in response to the unique human lifestyle and a need to optimally protect pregnant women and their fetuses from endogenous and exogenous insults. Lactic acid in the female genital tract inactivates potentially pathogenic bacteria and viruses, maximizes survival of vaginal epithelial cells, and inhibits inflammation that may be damaging to the developing fetus and maintenance of the pregnancy. In an analogous manner, lactic acid production facilitates survival of malignantly transformed cells, inhibits activation of immune cells, and prevents the release of pro-inflammatory mediators in response to tumor-specific antigens. Thus, the same stress-reducing properties of lactic acid that promote lower genital tract health facilitate malignant transformation and progression.

Unexpected dependence on pH of NO release from Paracoccus pantotrophus cytochrome cd1.

PubMed

Sam, Katharine A; Tolland, John D; Fairhurst, Shirley A; Higham, Christopher W; Lowe, David J; Thorneley, Roger N F; Allen, James W A; Ferguson, Stuart J

2008-07-11

A previous study of nitrite reduction by Paracoccus pantotrophus cytochrome cd(1) at pH 7.0 identified early reaction intermediates. The c-heme rapidly oxidised and nitrite was reduced to NO at the d(1)-heme. A slower equilibration of electrons followed, forming a stable complex assigned as 55% cFe(III)d(1)Fe(II)-NO and 45% cFe(II)d(1)Fe(II)-NO(+). No catalytically competent NO release was observed. Here we show that at pH 6.0, a significant proportion of the enzyme undergoes turnover and releases NO. An early intermediate, which was previously overlooked, is also identified; enzyme immediately following product release is a candidate. However, even at pH 6.0 a considerable fraction of the enzyme remains bound to NO so another component is required for full product release. The kinetically stable product formed at the end of the reaction differs significantly at pH 6.0 and 7.0, as does its rate of formation; thus the reaction is critically dependent on pH.

Impact of fruit texture on the release and perception of aroma compounds during in vivo consumption using fresh and processed mango fruits.

PubMed

Bonneau, Adeline; Boulanger, Renaud; Lebrun, Marc; Maraval, Isabelle; Valette, Jérémy; Guichard, Élisabeth; Gunata, Ziya

2018-01-15

Two fresh (fresh cubic pieces, fresh puree) and two dried (dried cubic pieces, dried powder) products were prepared from a homogenous mango fruit batch to obtain four samples differing in texture. The aromatic profiles were determined by SAFE extraction technique and GC-MS analysis. VOCs released during consumption were trapped by a retronasal aroma-trapping device (RATD) and analysed by GC-MS. Twenty-one terpenes and one ester were identified from the exhaled nose-space. They were amongst the major mango volatile compounds, 10 of which were already reported as being potential key flavour compounds in mango. The in vivo release of aroma compounds was affected by the matrix texture. The intact samples (fresh and dried cubic pieces) released significantly more aroma compounds than disintegrated samples (fresh puree, dried powder). The sensory descriptive analysis findings were in close agreement with the in vivo aroma release data regarding fresh products, in contrast to the dried products. Copyright © 2017 Elsevier Ltd. All rights reserved.

Production of extended release mini-tablets using directly compressible grades of HPMC.

PubMed

Mohamed, Faiezah A A; Roberts, Matthew; Seton, Linda; Ford, James L; Levina, Marina; Rajabi-Siahboomi, Ali R

2013-11-01

Hypromellose (HPMC) has been previously used to control drug release from mini-tablets. However, owing to poor flow, production of mini-tablets containing high HPMC levels is challenging. Directly compressible (DC) HPMC grades have been developed by Dow Chemical Company. To compare the properties of HPMC DC (METHOCEL™ K4M and K100M) with regular (REG) HPMC grades. Particle size distribution and flowability of HPMC REG and DC were evaluated. 3 mm mini-tablets, containing hydrocortisone or theophylline as model drugs and 40% w/w HPMC DC or REG were produced. Mini-tablets containing HPMC DC grades were manufactured using a rotary press simulator at forces between 2-4 kN and speeds of 5, 10, 15 or 20 rpm. Mini-tablets containing HPMC REG were produced manually. The improved flowability of HPMC DC grades, which have a narrower particle size distribution and larger particle sizes, meant that simulated large scale production of mini-tablets with good weight uniformity (CV 1.79-4.65%) was feasible. It was not possible to automatically manufacture mini-tablets containing HPMC REG due to the poor flowability of the formulations. Drug release from mini-tablets comprising HPMC DC and REG were comparable. Mini-tablets containing HPMC DC illustrated a higher tensile strength compared to mini-tablets made with HPMC REG. Mini-tablets produced with HPMC DC at different compression speeds had similar drug release profiles. Production of extended release mini-tablets was successfully achieved when HPMC DC was used. Drug release rate was not influenced by the different HPMC DC grades (K4M or K100M) or production speed.

Exosome platform for diagnosis and monitoring of traumatic brain injury

PubMed Central

Taylor, Douglas D.; Gercel-Taylor, Cicek

2014-01-01

We have previously demonstrated the release of membranous structures by cells into their extracellular environment, which are termed exosomes, microvesicles or extracellular vesicles depending on specific characteristics, including size, composition and biogenesis pathway. With activation, injury, stress, transformation or infection, cells express proteins and RNAs associated with the cellular responses to these events. The exosomes released by these cells can exhibit an array of proteins, lipids and nucleic acids linked to these physiologic events. This review focuses on exosomes associated with traumatic brain injury, which may be both diagnostic and a causative factor in the progression of the injury. Based on current data, exosomes play essential roles as conveyers of intercellular communication and mediators of many of the pathological conditions associated with development, progression and therapeutic failures and cellular stress in a variety of pathologic conditions. These extracellular vesicles express components responsible for angiogenesis promotion, stromal remodelling, signal pathway activation through growth factor/receptor transfer, chemoresistance, immunologic activation and genetic exchange. These circulating exosomes not only represent a central mediator of the pro-inflammatory microenvironment linked with secondary brain injury, but their presence in the peripheral circulation may serve as a surrogate for biopsies, enabling real-time diagnosis and monitoring of neurodegenerative progression. PMID:25135964

Microvesicles released from human renal cancer stem cells stimulate angiogenesis and formation of lung premetastatic niche.

PubMed

Grange, Cristina; Tapparo, Marta; Collino, Federica; Vitillo, Loriana; Damasco, Christian; Deregibus, Maria Chiara; Tetta, Ciro; Bussolati, Benedetta; Camussi, Giovanni

2011-08-01

Recent studies suggest that tumor-derived microvesicles (MV) act as a vehicle for exchange of genetic information between tumor and stromal cells, engendering a favorable microenvironment for cancer development. Within the tumor mass, all cell types may contribute to MV shedding, but specific contributions to tumor progression have yet to be established. Here we report that a subset of tumor-initiating cells expressing the mesenchymal stem cell marker CD105 in human renal cell carcinoma releases MVs that trigger angiogenesis and promote the formation of a premetastatic niche. MVs derived only from CD105-positive cancer stem cells conferred an activated angiogenic phenotype to normal human endothelial cells, stimulating their growth and vessel formation after in vivo implantation in immunocompromised severe combined immunodeficient (SCID) mice. Furthermore, treating SCID mice with MVs shed from CD105-positive cells greatly enhanced lung metastases induced by i.v. injection of renal carcinoma cells. Molecular characterization of CD105-positive MVs defines a set of proangiogenic mRNAs and microRNAs implicated in tumor progression and metastases. Our results define a specific source of cancer stem cell-derived MVs that contribute to triggering the angiogenic switch and coordinating metastatic diffusion during tumor progression.

Methane production and methanogen levels in steers that differ in residual gain

USDA-ARS?s Scientific Manuscript database

Methane gas released by cattle is a product of fermentation in the digestive tract. The two primary sites of methane fermentation in ruminants are the reticulum-rumen complex, and the cecum. Methane release from cattle represents a 2 to 12% loss of the energy intake. Reducing the proportion of fe...

Formation and Release Behavior of Iron Corrosion Products under the Influence of Bacterial Communities in a Simulated Water Distribution System

EPA Science Inventory

Understanding the effects of biofilm on the iron corrosion, iron release and associated corrosion by-products is critical for maintaining the water quality and the integrity of drinking water distribution system (DWDS). In this work, iron corrosion experiments under sterilized a...

27 CFR 41.85a - Release from customs custody of returned articles.

Code of Federal Regulations, 2012 CFR

2012-04-01

... PRODUCTS, CIGARETTE PAPERS AND TUBES, AND PROCESSED TOBACCO Tobacco Products and Cigarette Papers and Tubes... Cigarette Papers and Tubes Without Payment of Tax Or Certain Duty § 41.85a Release from customs custody of... warehouse proprietor. (b) Domestically produced cigarette papers and tubes (classifiable under item 9801.00...

Exposure to airborne engineered nanoparticles in the indoor environment

NASA Astrophysics Data System (ADS)

Vance, Marina E.; Marr, Linsey C.

2015-04-01

This literature review assesses the current state of knowledge about inhalation exposure to airborne, engineered nanoparticles in the indoor environment. We present principal exposure scenarios in indoor environments, complemented by analysis of the published literature and of an inventory of nanotechnology-enhanced consumer products. Of all products listed in the inventory, 10.8% (194 products) present the potential for aerosolization of nanomaterials and subsequent inhalation exposure during use or misuse. Among those, silver-containing products are the most prevalent (68 products). Roughly 50% of products would release wet aerosols and 50% would potentially release dry aerosols. Approximately 14% are cleaning products that can be broadly used in public indoor environments, where building occupants may be exposed. While a variety of nanomaterial compositions have been investigated in the limited number of published release and exposure studies, we identified a need for studies investigating nanofibers (beyond carbon nanotubes), nanofilms, nanoplatelets, and other emerging nanomaterials such as ceria and their nanocomposites. Finally, we provide recommendations for future research to advance the understanding of exposure to airborne nanomaterials indoors, such as studies into indoor chemistry of nanomaterials, better nanomaterial reporting and labeling in consumer products, and safer design of nanomaterial-containing consumer products.

Is the catalytic activity of triosephosphate isomerase fully optimized? An investigation based on maximization of entropy production.

PubMed

Bonačić Lošić, Željana; Donđivić, Tomislav; Juretić, Davor

2017-03-01

Triosephosphate isomerase (TIM) is often described as a fully evolved housekeeping enzyme with near-maximal possible reaction rate. The assumption that an enzyme is perfectly evolved has not been easy to confirm or refute. In this paper, we use maximization of entropy production within known constraints to examine this assumption by calculating steady-state cyclic flux, corresponding entropy production, and catalytic activity in a reversible four-state scheme of TIM functional states. The maximal entropy production (MaxEP) requirement for any of the first three transitions between TIM functional states leads to decreased total entropy production. Only the MaxEP requirement for the product (R-glyceraldehyde-3-phosphate) release step led to a 30% increase in enzyme activity, specificity constant k cat /K M , and overall entropy production. The product release step, due to the TIM molecular machine working in the physiological direction of glycolysis, has not been identified before as the rate-limiting step by using irreversible thermodynamics. Together with structural studies, our results open the possibility for finding amino acid substitutions leading to an increased frequency of loop six opening and product release.

Microcystin production by Microcystis aeruginosa exposed to different stages of herbivorous zooplankton.

PubMed

Jang, Min-Ho; Ha, Kyong; Takamura, Noriko

2008-04-01

Microcystin (MC) production by four monoclonal Microcystis aeruginosa strains was evaluated in response to infochemicals (indirect exposure) released from different stages of herbivorous zooplankton (neonate/juvenile and adult Daphnia magna and Moina macrocopa). The intracellular MC and extracellular MC concentrations were significantly different among the control and treatments with zooplankton culture media filtrates (p<0.05), and in most cases MC production was significantly higher (p<0.05) in strains exposed to infochemicals released from adult zooplankton rather than those of neonate/juvenile zooplankton in four strains of M. aeruginosa. Compared to intracellular MC (385.0-5598.6microg g(-1)DW), very low concentrations of extracellular MC (9.9-737.6microg ml(-1)) were released, but both showed similar temporal patterns over the course of the experiment. This result might be attributed to the fact that adult zooplankton produced more infochemical signals than equal numbers of smaller juveniles and neonates. It is the first study to provide evidence that MC production might be impacted by infochemicals released from different stages of zooplankton, mediated with physiological characteristics, body size, and feeding habits.

Anaerobic fermentation combined with low-temperature thermal pretreatment for phosphorus-accumulating granular sludge: Release of carbon source and phosphorus as well as hydrogen production potential.

PubMed

Zou, Jinte; Li, Yongmei

2016-10-01

Releases of organic compounds and phosphorus from phosphorus-accumulating granular sludge (PGS) and phosphorus-accumulating flocculent sludge (PFS) during low-temperature thermal pretreatment and anaerobic fermentation were investigated. Meanwhile, biogas production potential and microbial community structures were explored. The results indicate that much more soluble chemical oxygen demand (SCOD) and phosphorus were released from PGS than from PFS via low-temperature thermal pretreatment because of the higher extracellular polymeric substances (EPS) content in PGS and higher ratio of phosphorus reserved in EPS. Furthermore, PGS contains more anaerobes and dead cells, resulting in much higher SCOD and volatile fatty acids release from PGS than those from PFS during fermentation. PGS fermentation facilitated the n-butyric acid production, and PGS exhibited the hydrogen production potential during fermentation due to the presence of hydrogen-producing bacteria. Therefore, anaerobic fermentation combined with low-temperature thermal pretreatment can facilitate the recovery of carbon and phosphorus as well as producing hydrogen from PGS. Copyright © 2016 Elsevier Ltd. All rights reserved.

Does erosion progress differently on teeth already presenting clinical signs of erosive tooth wear than on sound teeth? An in vitro pilot trial.

PubMed

Carvalho, Thiago Saads; Baumann, Tommy; Lussi, Adrian

2016-07-07

Erosive tooth wear (ETW) is clinically characterized by a loss of tooth surface, and different enamel depths may have different susceptibility to demineralization. Therefore, the aim of this in vitro pilot study was to assess if the progression of erosive demineralization is faster on teeth already presenting signs of ETW when compared to originally sound teeth. We selected 23 central incisors: 14 were clinically sound (Sound) and 9 presented clinical signs of early erosive tooth wear (ETW-teeth). The teeth were embedded in resin, leaving an uncovered window of native enamel (6.69 ± 2.30 mm(2)) on the incisal half of the labial surface. We measured enamel surface reflection intensity (SRI) initially and after each consecutive erosive challenge (1 % citric acid, total of 4, 8, 12, 16, 20 and 24 min). Calcium released to the citric acid was measured with an atomic absorption spectrometer. We observed higher initial SRI values in ETW-teeth than in Sound teeth (p = 0.007). During in vitro erosive demineralization, we observed that erosion on originally Sound teeth progressed significantly slower (p = 0.033) than on ETW-teeth: SRI decreased by 75 % (from 100 to 25 %) on Sound teeth, and by 89 % (from 100 to 11 %) on ETW-teeth. Calcium release increased during erosion, but presented no significant differences (p = 0.643) between originally Sound (0.031 μmol/mm(2)) and ETW-teeth (0.032 μmol/mm(2)). There was satisfactory correlation between calcium release and rSRI values (r s  = -0.66). The optical reflectometer distinguished originally sound teeth from those with signs of ETW, and the results suggest that acid demineralization progresses differently on teeth already presenting clinical signs of ETW than on sound teeth.

Pyruvate oxidase of Streptococcus pneumoniae contributes to pneumolysin release.

PubMed

Bryant, Joseph C; Dabbs, Ridge C; Oswalt, Katie L; Brown, Lindsey R; Rosch, Jason W; Seo, Keun S; Donaldson, Janet R; McDaniel, Larry S; Thornton, Justin A

2016-11-09

Streptococcus pneumoniae is one of the leading causes of community acquired pneumonia and acute otitis media. Certain aspects of S. pneumoniae's virulence are dependent upon expression and release of the protein toxin pneumolysin (PLY) and upon the activity of the peroxide-producing enzyme, pyruvate oxidase (SpxB). We investigated the possible synergy of these two proteins and identified that release of PLY is enhanced by expression of SpxB prior to stationary phase growth. Mutants lacking the spxB gene were defective in PLY release and complementation of spxB restored PLY release. This was demonstrated by cytotoxic effects of sterile filtered supernatants upon epithelial cells and red blood cells. Additionally, peroxide production appeared to contribute to the mechanism of PLY release since a significant correlation was found between peroxide production and PLY release among a panel of clinical isolates. Exogenous addition of H 2 O 2 failed to induce PLY release and catalase supplementation prevented PLY release in some strains, indicating peroxide may exert its effect intracellularly or in a strain-dependent manner. SpxB expression did not trigger bacterial cell death or LytA-dependent autolysis, but did predispose cells to deoxycholate lysis. Here we demonstrate a novel link between spxB expression and PLY release. These findings link liberation of PLY toxin to oxygen availability and pneumococcal metabolism.

Recent Release of the ASTER Global DEM Product

NASA Astrophysics Data System (ADS)

Behnke, J.; Hall, A.; Meyer, D.; Sohre, T.; Doescher, C.

2009-12-01

On June 29th, the ASTER Global Digital Elevation Model (DEM) release was announced to the public and to a very eager audience. ASTER (Advanced Spaceborne Thermal Emission and Reflection Radiometer) is an imaging instrument flying on Terra, a satellite launched in December 1999 as part of NASA's Earth Observing System (EOS). ASTER is a cooperative effort between NASA, Japan's Ministry of Economy, Trade and Industry (METI) and Japan's Earth Remote Sensing Data Analysis Center (ERSDAC). On June 21, NASA Headquarters along with colleagues in Japan (METI) signed a plan for distribution of this product. The global digital elevation model of Earth is available online to users everywhere at no cost from NASA's Land Processes Distributed Active Archive Center (DAAC) located at Sioux Falls, SD. The DAAC is a joint project of NASA and the USGS and is a key component of NASA's EOSDIS. The new ASTER GDEM was created from nearly 1.3 million individual stereo-pair images acquired by the Japanese Advanced Spaceborne Thermal Emission and Reflection Radiometer (Aster) instrument aboard NASA’s Terra satellite. The ASTER elevation model was jointly developed by NASA and METI under contract to Sensor Information Laboratory Corp., Tsukuba, Japan. On June 29, the NASA press release was picked up quickly by numerous news organizations and online sites. Response to the product was incredible! The news of the release of the product was carried on websites across the globe, this fueled a tremendous response from users. Here are a few interesting metrics about the release: - over 41,000 unique visitors to website in first week following release - top countries in order were: US (approx. 20%), Germany, U.K., Brazil, Austria, Canada, Spain, Switzerland, Japan - approximately 29,000 visitors came to the news page in the first week and about 11,000 of these users downloaded the actual press release - by the end of August, over 2 Million ASTER GDEM files had been downloaded from the Land Processes DAAC This presentation covers the issues associated with the release of this very popular product, including issues raised by many of our users.

The "trapped fraction" and interfacial jumps of concentration in fission products release from coated fuel particles

NASA Astrophysics Data System (ADS)

Ivanov, A. S.; Rusinkevich, A. A.; Taran, M. D.

2018-01-01

The FP Kinetics computer code [1] designed for calculation of fission products release from HTGR coated fuel particles was modified to allow consideration of chemical bonding, effects of limited solubility and component concentration jumps at interfaces between coating layers. Curves of Cs release from coated particles calculated with the FP Kinetics and PARFUME [2] codes were compared. It has been found that the consideration of concentration jumps at silicon carbide layer interfaces allows giving an explanation of some experimental data on Cs release obtained from post-irradiation heating tests. The need to perform experiments for measurement of solubility limits in coating materials was noted.

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.

27 CFR 26.80 - Deferred payment of tax-release of spirits.

Code of Federal Regulations, 2010 CFR

2010-04-01

... indicate on TTB Form 5110.51. The revenue agent shall then execute his report of release on the TTB Form...-release of spirits. 26.80 Section 26.80 Alcohol, Tobacco Products and Firearms ALCOHOL AND TOBACCO TAX AND... tax—release of spirits. (a) Action by proprietor. Where the proprietor has furnished bond on TTB Form...

Furfural production from biomass pretreatment hydrolysate using vapor-releasing reactor system.

PubMed

Liu, Lu; Chang, Hou-Min; Jameel, Hasan; Park, Sunkyu

2018-03-01

Biomass hydrolysate from autohydrolysis pretreatment was used for furfural production considering it is in rich of xylose, xylo-oligomers, and other decomposition products from hemicellulose structure. By using the vapor-releasing reactor system, furfural was protected from degradation by separating it from the reaction media. The maximum furfural yield of 73% was achieved at 200 °C for biomass hydrolysate without the use of the catalyst. This is because the presence of organic acids such as acetic acid in hydrolysate functioned as a catalyst. According to the results in this study, biomass hydrolysate with a vapor-releasing system proves to be efficient for furfural production. The biorefinery process which allows the separation of xylose-rich autohydrolysate from other parts from biomass feedstock also improves the overall application of the biomass. Copyright © 2018 Elsevier Ltd. All rights reserved.

Building CHAOS: An Operating System for Livermore Linux Clusters

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

Garlick, J E; Dunlap, C M

2003-02-21

The Livermore Computing (LC) Linux Integration and Development Project (the Linux Project) produces and supports the Clustered High Availability Operating System (CHAOS), a cluster operating environment based on Red Hat Linux. Each CHAOS release begins with a set of requirements and ends with a formally tested, packaged, and documented release suitable for use on LC's production Linux clusters. One characteristic of CHAOS is that component software packages come from different sources under varying degrees of project control. Some are developed by the Linux Project, some are developed by other LC projects, some are external open source projects, and some aremore » commercial software packages. A challenge to the Linux Project is to adhere to release schedules and testing disciplines in a diverse, highly decentralized development environment. Communication channels are maintained for externally developed packages in order to obtain support, influence development decisions, and coordinate/understand release schedules. The Linux Project embraces open source by releasing locally developed packages under open source license, by collaborating with open source projects where mutually beneficial, and by preferring open source over proprietary software. Project members generally use open source development tools. The Linux Project requires system administrators and developers to work together to resolve problems that arise in production. This tight coupling of production and development is a key strategy for making a product that directly addresses LC's production requirements. It is another challenge to balance support and development activities in such a way that one does not overwhelm the other.« less

Potential scenarios for nanomaterial release and subsequent alteration in the environment.

PubMed

Nowack, Bernd; Ranville, James F; Diamond, Stephen; Gallego-Urrea, Julian A; Metcalfe, Chris; Rose, Jerome; Horne, Nina; Koelmans, Albert A; Klaine, Stephen J

2012-01-01

The risks associated with exposure to engineered nanomaterials (ENM) will be determined in part by the processes that control their environmental fate and transformation. These processes act not only on ENM that might be released directly into the environment, but more importantly also on ENM in consumer products and those that have been released from the product. The environmental fate and transformation are likely to differ significantly for each of these cases. The ENM released from actual direct use or from nanomaterial-containing products are much more relevant for ecotoxicological studies and risk assessment than pristine ENM. Released ENM may have a greater or lesser environmental impact than the starting materials, depending on the transformation reactions and the material. Almost nothing is known about the environmental behavior and the effects of released and transformed ENM, although these are the materials that are actually present in the environment. Further research is needed to determine whether the release and transformation processes result in a similar or more diverse set of ENM and ultimately how this affects environmental behavior. This article addresses these questions, using four hypothetical case studies that cover a wide range of ENM, their direct use or product applications, and their likely fate in the environment. Furthermore, a more definitive classification scheme for ENM should be adopted that reflects their surface condition, which is a result of both industrial and environmental processes acting on the ENM. The authors conclude that it is not possible to assess the risks associated with the use of ENM by investigating only the pristine form of the ENM, without considering alterations and transformation processes. Copyright © 2011 SETAC.

Identification of HNRNPK as Regulator of Hepatitis C Virus Particle Production

PubMed Central

Poenisch, Marion; Metz, Philippe; Blankenburg, Hagen; Ruggieri, Alessia; Lee, Ji-Young; Rupp, Daniel; Rebhan, Ilka; Diederich, Kathrin; Kaderali, Lars; Domingues, Francisco S.; Albrecht, Mario; Lohmann, Volker; Erfle, Holger; Bartenschlager, Ralf

2015-01-01

Hepatitis C virus (HCV) is a major cause of chronic liver disease affecting around 130 million people worldwide. While great progress has been made to define the principle steps of the viral life cycle, detailed knowledge how HCV interacts with its host cells is still limited. To overcome this limitation we conducted a comprehensive whole-virus RNA interference-based screen and identified 40 host dependency and 16 host restriction factors involved in HCV entry/replication or assembly/release. Of these factors, heterogeneous nuclear ribonucleoprotein K (HNRNPK) was found to suppress HCV particle production without affecting viral RNA replication. This suppression of virus production was specific to HCV, independent from assembly competence and genotype, and not found with the related Dengue virus. By using a knock-down rescue approach we identified the domains within HNRNPK required for suppression of HCV particle production. Importantly, HNRNPK was found to interact specifically with HCV RNA and this interaction was impaired by mutations that also reduced the ability to suppress HCV particle production. Finally, we found that in HCV-infected cells, subcellular distribution of HNRNPK was altered; the protein was recruited to sites in close proximity of lipid droplets and colocalized with core protein as well as HCV plus-strand RNA, which was not the case with HNRNPK variants unable to suppress HCV virion formation. These results suggest that HNRNPK might determine efficiency of HCV particle production by limiting the availability of viral RNA for incorporation into virions. This study adds a new function to HNRNPK that acts as central hub in the replication cycle of multiple other viruses. PMID:25569684

K+-induced alterations in airway muscle responsiveness to electrical field stimulation

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

Murlas, C.; Ehring, G.; Suszkiw, J.

1986-07-01

We investigated possible pre- and postsynaptic effects of K+-induced depolarization on ferret tracheal smooth muscle (TSM) responsiveness to cholinergic stimulation. To assess electromechanical activity, cell membrane potential (Em) and tension (Tm) were simultaneously recorded in buffer containing 6, 12, 18, or 24 mM K+ before and after electrical field stimulation (EFS) or exogenous acetylcholine (ACh). In 6 mM K+, Em was -58.1 +/- 1.0 mV (mean +/- SE). In 12 mM K+, Em was depolarized to -52.3 +/- 0.9 mV, basal Tm did not change, and both excitatory junctional potentials and contractile responses to EFS at short stimulus duration weremore » larger than in 6 mM K+. No such potentiation occurred at a higher K+, although resting Em and Tm increased progressively above 12 mM K+. The sensitivity of ferret TSM to exogenous ACh appeared unaffected by K+. To determine whether the hyperresponsiveness in 12 mM K+ was due, in part, to augmented ACh release from intramural airway nerves, experiments were done using TSM preparations incubated with (3H)choline to measure (3H)ACh release at rest and during EFS. Although resting (3H)ACh release increased progressively in higher K+, release evoked by EFS was maximal in 12 mM K+ and declined in higher concentrations. We conclude that small elevations in the extracellular K+ concentration augment responsiveness of the airways, by increasing the release of ACh both at rest and during EFS from intramural cholinergic nerve terminals. Larger increases in K+ appear to be inhibitory, possibly due to voltage-dependent effects that occur both pre- and postsynaptically.« less

Endangered Right Whales Enhance Primary Productivity in the Bay of Fundy

PubMed Central

Roman, Joe; Nevins, John; Altabet, Mark; Koopman, Heather; McCarthy, James

2016-01-01

Marine mammals have recently been documented as important facilitators of rapid and efficient nutrient recycling in coastal and offshore waters. Whales enhance phytoplankton nutrition by releasing fecal plumes near the surface after feeding and by migrating from highly productive, high-latitude feeding areas to low-latitude nutrient-poor calving areas. In this study, we measured NH4+ and PO43- release rates from the feces of North Atlantic right whales (Eubalaena glacialis), a highly endangered baleen whale. Samples for this species were primarily collected by locating aggregations of whales in surface-active groups (SAGs), which typically consist of a central female surrounded by males competing for sexual activity. When freshly collected feces were incubated in seawater, high initial rates of N release were generally observed, which decreased to near zero within 24 hours of sampling, a pattern that is consistent with the active role of gut microflora on fecal particles. We estimate that at least 10% of particulate N in whale feces becomes available as NH4+ within 24 hours of defecation. Phosphorous was also abundant in fecal samples: initial release rates of PO43- were higher than for NH4+, yielding low N/P nutrient ratios over the course of our experiments. The rate of PO43- release was thus more than sufficient to preclude the possibility that nitrogenous nutrients supplied by whales would lead to phytoplankton production limited by P availability. Phytoplankton growth experiments indicated that NH4+ released from whale feces enhance productivity, as would be expected, with no evidence that fecal metabolites suppress growth. Although North Atlantic right whales are currently rare (approximately 450 individuals), they once numbered about 14,000 and likely played a substantial role in recycling nutrients in areas where they gathered to feed and mate. Even though the NH4+ released from fresh whale fecal material is a small fraction of total whale fecal nitrogen, and recognizing the fact that the additional nitrogen released in whale urine would be difficult to measure in a field study, the results of this study support the idea that the distinctive isotopic signature of the released NH4+ could be used to provide a conservative estimate of the contribution of the whale pump to primary productivity in coastal regions where whales congregate. PMID:27331902

Endangered Right Whales Enhance Primary Productivity in the Bay of Fundy.

PubMed

Roman, Joe; Nevins, John; Altabet, Mark; Koopman, Heather; McCarthy, James

2016-01-01

Marine mammals have recently been documented as important facilitators of rapid and efficient nutrient recycling in coastal and offshore waters. Whales enhance phytoplankton nutrition by releasing fecal plumes near the surface after feeding and by migrating from highly productive, high-latitude feeding areas to low-latitude nutrient-poor calving areas. In this study, we measured NH4+ and PO43- release rates from the feces of North Atlantic right whales (Eubalaena glacialis), a highly endangered baleen whale. Samples for this species were primarily collected by locating aggregations of whales in surface-active groups (SAGs), which typically consist of a central female surrounded by males competing for sexual activity. When freshly collected feces were incubated in seawater, high initial rates of N release were generally observed, which decreased to near zero within 24 hours of sampling, a pattern that is consistent with the active role of gut microflora on fecal particles. We estimate that at least 10% of particulate N in whale feces becomes available as NH4+ within 24 hours of defecation. Phosphorous was also abundant in fecal samples: initial release rates of PO43- were higher than for NH4+, yielding low N/P nutrient ratios over the course of our experiments. The rate of PO43- release was thus more than sufficient to preclude the possibility that nitrogenous nutrients supplied by whales would lead to phytoplankton production limited by P availability. Phytoplankton growth experiments indicated that NH4+ released from whale feces enhance productivity, as would be expected, with no evidence that fecal metabolites suppress growth. Although North Atlantic right whales are currently rare (approximately 450 individuals), they once numbered about 14,000 and likely played a substantial role in recycling nutrients in areas where they gathered to feed and mate. Even though the NH4+ released from fresh whale fecal material is a small fraction of total whale fecal nitrogen, and recognizing the fact that the additional nitrogen released in whale urine would be difficult to measure in a field study, the results of this study support the idea that the distinctive isotopic signature of the released NH4+ could be used to provide a conservative estimate of the contribution of the whale pump to primary productivity in coastal regions where whales congregate.

New developments in the treatment of multiple myeloma - clinical utility of daratumumab.

PubMed

McEllistrim, Cian; Krawczyk, Janusz; O'Dwyer, Michael E

2017-01-01

Multiple myeloma is a clonal disorder of plasma cells that is currently considered incurable. CD38 is a 46 kDa type II transmembrane glycoprotein that is highly expressed on myeloma cells. Daratumumab is a first in-class human IgG1 monoclonal antibody that targets CD38, and has antimyeloma effects through several mechanisms. Single-agent trials show surprising activity in heavily pretreated myeloma patients. Trials in the relapsed setting, where daratumumab is added to lenalidomide and dexamethasone or bortezomib and dexamethasone, have demonstrated significantly improved progression-free survival with acceptable toxicity. In this review, we discuss the mechanism of action, pharmacology and pharmacokinetics of daratumumab and review the available clinical data in detail. We examine how daratumumab interferes with transfusion testing due to the expression of CD38 on the red blood cells, leading to potential difficulties releasing blood products. Daratumumab also affects disease assessments in multiple myeloma, including serum protein electrophoresis, immunofixation and flow cytometry. Strategies to mitigate these effects are discussed. The optimal use of daratumumab has yet to be decided, and several trials are ongoing in the relapsed and upfront setting. We discuss the potential upfront role of this exciting therapy, which has significant potential for increased minimal residual disease negativity and improved progression-free survival even in high-risk groups.

New developments in the treatment of multiple myeloma – clinical utility of daratumumab

PubMed Central

McEllistrim, Cian; Krawczyk, Janusz; O’Dwyer, Michael E

2017-01-01

Multiple myeloma is a clonal disorder of plasma cells that is currently considered incurable. CD38 is a 46 kDa type II transmembrane glycoprotein that is highly expressed on myeloma cells. Daratumumab is a first in-class human IgG1 monoclonal antibody that targets CD38, and has antimyeloma effects through several mechanisms. Single-agent trials show surprising activity in heavily pretreated myeloma patients. Trials in the relapsed setting, where daratumumab is added to lenalidomide and dexamethasone or bortezomib and dexamethasone, have demonstrated significantly improved progression-free survival with acceptable toxicity. In this review, we discuss the mechanism of action, pharmacology and pharmacokinetics of daratumumab and review the available clinical data in detail. We examine how daratumumab interferes with transfusion testing due to the expression of CD38 on the red blood cells, leading to potential difficulties releasing blood products. Daratumumab also affects disease assessments in multiple myeloma, including serum protein electrophoresis, immunofixation and flow cytometry. Strategies to mitigate these effects are discussed. The optimal use of daratumumab has yet to be decided, and several trials are ongoing in the relapsed and upfront setting. We discuss the potential upfront role of this exciting therapy, which has significant potential for increased minimal residual disease negativity and improved progression-free survival even in high-risk groups. PMID:28442888

The Tropical Rainfall Measuring Mission (TRMM) Progress Report

NASA Technical Reports Server (NTRS)

Simpson, Joanne; Meneghini, Robert; Kummerow, Christian D.; Meneghini, Robert; Hou, Arthur; Adler, Robert F.; Huffman, George; Barkstrom, Bruce; Wielicki, Bruce; Goodman, Steve

1999-01-01

Recognizing the importance of rain in the tropics and the accompanying latent heat release, NASA for the U.S. and NASDA for Japan have partnered in the design, construction and flight of an Earth Probe satellite to measure tropical rainfall and calculate the associated heating. Primary mission goals are 1) the understanding of crucial links in climate variability by the hydrological cycle, 2) improvement in the large-scale models of weather and climate 3) Improvement in understanding cloud ensembles and their impacts on larger scale circulations. The linkage with the tropical oceans and landmasses are also emphasized. The Tropical Rainfall Measuring Mission (TRMM) satellite was launched in November 1997 with fuel enough to obtain a four to five year data set of rainfall over the global tropics from 37'N to 37'S. This paper reports progress from launch date through the spring of 1999. The data system and its products and their access is described, as are the algorithms used to obtain the data. Some exciting early results from TRMM are described. Some important algorithm improvements are shown. These will be used in the first total data reprocessing, scheduled to be complete in early 2000. The reader is given information on how to access and use the data.

[Technological and pharmacotherapeutic properties of selected drugs with modified release of diclofenac sodium].

PubMed

Kołodziejczyk, Michał Krzysztof; Kołodziejska, Justyna; Zgoda, Marian Mikołaj

2012-01-01

Diclofenac and its sodium salt is one of the best-known and popular therapeutic agents from the group of NSAIDs used in medicine in many various pharmaceutical forms. Therapeutic products containing diclofenac sodium salt in doses of 100 mg and 75 mg with a qualitatively and quantitatively diversified share of excipients and a variable dosage form of the drug (solid capsules, tablets with modified release) were subjected to technological and pharmaceutical analysis. The effect of solid formulation components of polymer character making the core and the coating of the pharmaceutical form of therapeutic products on the disintegration time and pharmaceutical availability in pharmacopoeial receptor fluids was estimated. Market therapeutic products with diclofenac sodium in doses of 75 mg and 100 mg, technological analysis of the drug dosage form was conducted, disintegration time of solid oral dosage forms of the drug with diclofenac sodium salt was examined and research on pharmaceutical availability of diclofenac sodium salt from tested therapeutic products was conducted using the acid phase and the buffer phase according to the FP standards for delayed release enteral dosage forms. The experimental data was supplemented with the statistical analysis. There are three formulations in the form of solid capsules and one formulation in the form of a coated tablet. All therapeutic products bear features of a dosage form of modified release of diclofenac sodium salt, frequently of a delayed release formula in the duodenum or the small intestine with regard to the limitation of typical undesirable effects after taking NSAIDs. Considerable diversity between solid capsules and the tablet with modified release during disintegration or hydration and swelling has been observed. In the environment of a receptor fluid--purified water (pH = 7) the capsule Dicloberl retard disintegrates at the fastest rate in 5,49 minutes, and then in the order: DicloDuo 75 mg--8,13 minutes and Olfen 100 SR--11,27 minutes. The hydration degree of gelatin walls of capsules depends on the pH of the receptor fluid. The availability of diclofenac sodium salt in given receptor fluids confirms the fact of significant connection of clinical effectiveness of the tested pharmaceutical forms with the activity of hydrogen ions (pH) of the environment in which there are therapeutic products, and excipients used for making the pharmaceutical phase. Tested therapeutic products with diclofenac sodium salt are differentiated by the type of a dosage form. Dicloberl retard contains the minimally indispensable number of simple, commonly used excipients. The research on the disintegration time may only be related to the products Dicloberl retard, Olfen 100 SR and DicloDuo 75 mg treating it as the time of deformation and disintegration of a capsule. In all three types of receptor fluids, the capsule Dicloberl retard has the fastest disintegration rate. The "acid phase" demonstrated stability of the products with a slight dissolution of diclofenac sodium salt on the level 1,3-4,18% of the Q release coefficient. In the environment of artificial intestinal juice, Dicloberl retard is more effective releasing larger amounts of diclofenac sodium salt during 4 hours of exposition (differences from 10% to 14% of the Q release coefficient).

FY17Q4 Ristra project: Release Version 1.0 of a production toolkit

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

Hungerford, Aimee L.; Daniel, David John

2017-09-21

The Next Generation Code project will release Version 1.0 of a production toolkit for multi-physics application development on advanced architectures. Features of this toolkit will include remap and link utilities, control and state manager, setup, visualization and I/O, as well as support for a variety of mesh and particle data representations. Numerical physics packages that operate atop this foundational toolkit will be employed in a multi-physics demonstration problem and released to the community along with results from the demonstration.

A Productivity Measurement Model Application at an Aircraft Maintenance Facility.

DTIC Science & Technology

1980-12-01

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Inhibition of basal and stimulated release of endothelin-1 from guinea pig tracheal epithelial cells in culture by beta 2-adrenoceptor agonists and cyclic AMP enhancers.

PubMed

Yang, Quan; Battistini, Bruno; Pelletier, Stéphane; Sirois, Pierre

2007-10-01

The effects of cyclic AMP-related compounds and beta adrenoceptor agonists on the basal and lipopolysaccharide (LPS)-stimulated release of endothelin-1 (ET-1) from guinea-pig tracheal epithelial cells (GPTEpCs) in culture were studied. Forskolin (a potent activator of adenylyl cyclase), 8-bromo-cyclic AMP (a cyclic AMP analogue), salbutamol and salmeterol (two beta 2-adrenoceptor agonists), were used to increase cyclic AMP levels. Cultured GPTEpCs released ET-1 continuously over a 24 h incubation period. The values reached 1,938 +/- 122 pg/mg of total cell proteins after 24 h. LPS (10 microg/ml) significantly stimulated the release of ET-1 by 1.6- to 1.8-fold, up to 1,262 +/- 56 pg/mg total cell proteins after an 8 h incubation period. Compound 8-bromo-cyclic AMP (10(-5), 10(-4) and 10(-3) M) reduced the basal release of ET-1 from GPTEpCs by up to 31% (P < 0.01) and the LPS stimulated release by up to 42% (P < 0.05), after an 8 h incubation period. Forskolin (10(-6), 10(-5) and 10(-4) M) also inhibited the basal release of ET-1 by up to 28% (P < 0.05) and LPS-stimulated release of ET-1 by up to 50% (P < 0.05), after an 8 h incubation period. At the concentration of 10(-5) M, forskolin increased cyclic AMP levels in GPTEpCs by 17-fold (P < 0.001) in the medium, 15 min after the beginning of the incubation. Salbutamol (10(-8) to 10(-6) M) had no effect on the basal production and release of ET-1 after 8 h. Conversely, this short acting beta 2-adrenoceptor agonist significantly reduced LPS-mediated increase of ET-1 production by up to 55% (P < 0.05) after an 8 h incubation period. Salmeterol (10(-9) M to 10(-5) M) inhibited basal and LPS-stimulated production and release of ET-1 after an 8 h incubation period (between 44 and 51%, P < 0.01). Both salbutamol and salmeterol (10(-6) M) increase cyclic AMP levels by five- and twofold, respectively (P < 0.05). In summary, these observations indicate that beta 2-adrenoceptor agonists or cyclic AMP enhancers can modulate both basal and more markedly, the enhanced production of ET-1 from LPS-activated guinea pig airway EpCs. In addition, these compounds increase cyclic AMP levels in the cells. It is suggested that there is a correlation between cyclic AMP increase and inhibition of ET-1 release by guinea pig airway EpCs. Since ET-1 production was shown to be elevated in asthmatic subjects and in patients suffering from other inflammatory lung disorders, the inhibition of its production by beta adrenoceptor agonists, such as salbutamol and salmeterol, could be added to their therapeutical benefits.

Review and Oversight of the 1998 Reading Results of the National Assessment of Educational Progress (NAEP)--The Nation's Report Card. Hearing before the Subcommittee on Oversight and Investigations of the Committee on Education and the Workforce. United States House of Representatives, One Hundred Sixth Congress, First Session.

ERIC Educational Resources Information Center

Congress of the U.S., Washington, DC. House Committee on Education and the Workforce.

This document presents the transcript (and written statements) of a congressional hearing on the potential politicization of the National Assessment of Educational Progress (NAEP) and the trustworthiness of the scores that the states received during the 1998 reading assessment. It addresses whether Vice President Al Gore's "release" of…

Quantitative characterization of TiO2 nanoparticle release from textiles by conventional and single particle ICP-MS

NASA Astrophysics Data System (ADS)

Mackevica, Aiga; Olsson, Mikael Emil; Hansen, Steffen Foss

2018-01-01

TiO2 is ubiquitously present in a wide range of everyday items, both as an intentionally incorporated additive and naturally occurring constituent. It can be found in a wide range of consumer products, including personal care products, food contact materials, and textiles. Normal use of these products may lead to consumer and/or environmental exposure to TiO2, possibly in form of nanoparticles. The aim of this study is to perform a leaching test and apply state-of-the-art methods to investigate nano-TiO2 and total Ti release from five types of commercially available conventional textiles: table placemats, wet wipes, microfiber cloths, and two types of baby bodysuits, with Ti contents ranging from 2.63 to 1448 μg/g. Released particle analysis was performed using conventional and single particle inductively coupled plasma mass spectrometry (ICP-MS and spICP-MS), in conjunction with transmission electron microscopy (TEM), to measure total and particulate TiO2 release by mass and particle number, as well as size distribution. Less than 1% of the initial Ti content was released over 24 h of leaching, with the highest releases reaching 3.13 μg/g. The fraction of nano-TiO2 released varied among fabric types and represented 0-80% of total TiO2 release. Particle mode sizes were 50-75 nm, and TEM imaging revealed particles in sizes of 80-200 nm. This study highlights the importance of using a multi-method approach to obtain quantitative release data that is able to provide an indication regarding particle number, size distribution, and mass concentration, all of which can help in understanding the fate and exposure of nanoparticles.

NASA/GEWEX Surface Radiation Budget: First Results From The Release 4 GEWEX Integrated Data Products

NASA Astrophysics Data System (ADS)

Stackhouse, Paul; Cox, Stephen; Gupta, Shashi; Mikovitz, J. Colleen; zhang, taiping

2016-04-01

The NASA/GEWEX Surface Radiation Budget (SRB) project produces shortwave and longwave surface and top of atmosphere radiative fluxes for the 1983-near present time period. Spatial resolution is 1 degree. The current release 3 (available at gewex-srb.larc.nasa.gov) uses the International Satellite Cloud Climatology Project (ISCCP) DX product for pixel level radiance and cloud information. This product is subsampled to 30 km. ISCCP is currently recalibrating and recomputing their entire data series, to be released as the H product, at 10km resolution. The ninefold increase in pixel number should help improve the RMS of the existing products and allow for future higher resolution SRB gridded product (e.g. 0.5 degree). In addition to the input data improvements, several important algorithm improvements have been made. Most notable has been the adaptation of Angular Distribution Models (ADMs) from CERES to improve the initial calculation of shortwave TOA fluxes, from which the surface flux calculations follow. Other key input improvements include a detailed aerosol history using the Max Planck Institut Aerosol Climatology (MAC), temperature and moisture profiles from HIRS, and new topography, surface type, and snow/ice. Here we present results for the improved GEWEX Shortwave and Longwave algorithm (GSW and GLW) with new ISCCP data, the various other improved input data sets and the incorporation of many additional internal SRB model improvements. As of the time of abstract submission, results from 2007 have been produced with ISCCP H availability the limiting factor. More SRB data will be produced as ISCCP reprocessing continues. The SRB data produced will be released as part of the Release 4.0 Integrated Product, recognizing the interdependence of the radiative fluxes with other GEWEX products providing estimates of the Earth's global water and energy cycle (I.e., ISCCP, SeaFlux, LandFlux, NVAP, etc.).

Electrochemical capture and release of carbon dioxide

DOE PAGES

Rheinhardt, Joseph H.; Singh, Poonam; Tarakeshwar, Pilarisetty; ...

2017-01-18

Understanding the chemistry of carbon dioxide is key to affecting changes in atmospheric concentrations. One area of intense interest is CO 2 capture in chemically reversible cycles relevant to carbon capture technologies. Most CO 2 capture methods involve thermal cycles in which a nucleophilic agent captures CO 2 from impure gas streams (e.g., flue gas), followed by a thermal process in which pure CO 2 is released. Several reviews have detailed progress in these approaches. A less explored strategy uses electrochemical cycles to capture CO 2 and release it in pure form. These cycles typically rely on electrochemical generation ofmore » nucleophiles that attack CO 2 at the electrophilic carbon atom, forming a CO 2 adduct. Then, CO 2 is released in pure form via a subsequent electrochemical step. In this Perspective, we describe electrochemical cycles for CO 2 capture and release, emphasizing electrogenerated nucleophiles. As a result, we also discuss some advantages and disadvantages inherent in this general approach.« less

Development of modified-release dosage forms containing loratadine and pseudoephedrine sulfate.

PubMed

Sznitowska, Małgorzata; Cal, Krzysztof; Kupiec, Katarzyna

2004-12-01

Pseudoephedrine sulfate (PES) is a short-acting sympathomimetic amine and decongestant. Loratadine (L) is a long-acting antihistamine, H1 blocker. These drugs administered together provide relief from a whole range of rhinitis (hay fever) symptoms. Combination of both drugs is available in the form of sugar-coated modified-release tablets Clarinase (Schering-Plough). In this product, 5 mg of L and 60 mg of PES is present in the sugar-coating layer ready for an immediate release, and the rest of PES (60 mg) is incorporated in the extended-release core of the tablet. This enables fast as well as prolonged release of PES over 6-8 h. Because the sugar coating technologies are troublesome and rarely used nowadays, the aim of this study was to develop alternative oral dosage forms containing L (5 mg) and PES (120 mg). It was assumed that, similarly to the original product, the total dose of L and the half dose of PES should be released during 1 h and the remaining dose of PES ought to be gradually released for up to 8 h.

Large Scale PEM Electrolysis to Enable Renewable Hydrogen Fuel Production

DTIC Science & Technology

2010-02-10

PEM Fuel Cell Anode + -Cathode e- e- e- e- Electric load...BOP system. • Enables new product launch (C- Series) Proton PEM cell stack for UK Vanguard subs 18UNCLASSIFIED: Dist A. Approved for public release...UNCLASSIFIED: Dist A. Approved for public release “Large Scale PEM Electrolysis to Enable Renewable Hydrogen Fuel Production” Alternative Energy

Automatic Generation of Just-in-Time Online Assessments from Software Design Models

ERIC Educational Resources Information Center

Zualkernan, Imran A.; El-Naaj, Salim Abou; Papadopoulos, Maria; Al-Amoudi, Budoor K.; Matthews, Charles E.

2009-01-01

Computer software is pervasive in today's society. The rate at which new versions of computer software products are released is phenomenal when compared to the release rate of new products in traditional industries such as aircraft building. This rapid rate of change can partially explain why most certifications in the software industry are…

A comparison of human chorionic gonadotropin and luteinizing hormone releasing hormone on the induction of spermiation and amplexus in the American toad (Anaxyrus americanus).

PubMed

Kouba, Andrew J; delBarco-Trillo, Javier; Vance, Carrie K; Milam, Callie; Carr, Meghan

2012-08-20

Captive breeding programs for endangered amphibian species often utilize exogenous hormones for species that are difficult to breed. The purpose of our study was to compare the efficacy of two different hormones at various concentrations on sperm production, quantity and quality over time in order to optimize assisted breeding. Male American toads (Anaxyrus americanus) were divided into three separate treatment groups, with animals in each group rotated through different concentrations of luteinizing hormone releasing hormone analog (LHRH; 0.1, 1.0, 4.0 and 32 micrograms/toad), human chorionic gonadotropin (hCG; 50, 100, 200, and 300 IU), or the control over 24 hours. We evaluated the number of males that respond by producing spermic urine, the sperm concentration, percent motility, and quality of forward progression. We also evaluated the effects of hCG and LHRH on reproductive behavior as assessed by amplexus. Data were analyzed using the Generalized Estimating Equations incorporating repeated measures over time and including the main effects of treatment and time, and the treatment by time interaction. The hormone hCG was significantly more effective at stimulating spermiation in male Anaxyrus americanus than LHRH and showed a dose-dependent response in the number of animals producing sperm. At the most effective hCG dose (300 IU), 100% of the male toads produced sperm, compared to only 35% for the best LHRH dose tested (4.0 micrograms). In addition to having a greater number of responders (P < 0.05), the 300 IU hCG treatment group had a much higher average sperm concentration (P < 0.05) than the treatment group receiving 4.0 micrograms LHRH. In contrast, these two treatments did not result in significant differences in sperm motility or quality of forward progressive motility. However, more males went into amplexus when treated with LHRH vs. hCG (90% vs. 75%) by nine hours post-administration. There is a clear dichotomy between the two hormones' physiological responses on gamete production and stimulation of amplexus. Understanding how these two hormones influence physiology and reproductive behaviors in amphibians will have direct bearing on establishing similar breeding protocols for endangered species.