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Sample records for cell biotherapeutics including

  1. Coupling of aggregation and immunogenicity in biotherapeutics: T- and B-cell immune epitopes may contain aggregation-prone regions.

    Science.gov (United States)

    Kumar, Sandeep; Singh, Satish K; Wang, Xiaoling; Rup, Bonita; Gill, Davinder

    2011-05-01

    Biotherapeutics, including recombinant or plasma-derived human proteins and antibody-based molecules, have emerged as an important class of pharmaceuticals. Aggregation and immunogenicity are among the major bottlenecks during discovery and development of biotherapeutics. Computational tools that can predict aggregation prone regions as well as T- and B-cell immune epitopes from protein sequence and structure have become available recently. Here, we describe a potential coupling between aggregation and immunogenicity: T-cell and B-cell immune epitopes in therapeutic proteins may contain aggregation-prone regions. The details of biological mechanisms behind this observation remain to be understood. However, our observation opens up an exciting potential for rational design of de-immunized novel, as well as follow on biotherapeutics with reduced aggregation propensity.

  2. Quantitative intracellular flux modeling and applications in biotherapeutic development and production using CHO cell cultures.

    Science.gov (United States)

    Huang, Zhuangrong; Lee, Dong-Yup; Yoon, Seongkyu

    2017-12-01

    Chinese hamster ovary (CHO) cells have been widely used for producing many recombinant therapeutic proteins. Constraint-based modeling, such as flux balance analysis (FBA) and metabolic flux analysis (MFA), has been developing rapidly for the quantification of intracellular metabolic flux distribution at a systematic level. Such methods would produce detailed maps of flows through metabolic networks, which contribute significantly to better understanding of metabolism in cells. Although these approaches have been extensively established in microbial systems, their application to mammalian cells is sparse. This review brings together the recent development of constraint-based models and their applications in CHO cells. The further development of constraint-based modeling approaches driven by multi-omics datasets is discussed, and a framework of potential modeling application in cell culture engineering is proposed. Improved cell culture system understanding will enable robust developments in cell line and bioprocess engineering thus accelerating consistent process quality control in biopharmaceutical manufacturing. © 2017 Wiley Periodicals, Inc.

  3. Investigation of Genipin Cross-Linked Microcapsule for Oral Delivery of Live Bacterial Cells and Other Biotherapeutics: Preparation and In Vitro Analysis in Simulated Human Gastrointestinal Model

    Directory of Open Access Journals (Sweden)

    Hongmei Chen

    2010-01-01

    Full Text Available Oral therapy utilizing engineered microorganisms has shown promise in the treatment of many diseases. By microencapsulation, viable cells can overcome the harsh gastrointestinal (GI environment and secrete needed therapeutics into the gut. These engineered cells should be encased without escaping into the GI tract for safety concerns, thus robust microcapsule membrane is requisite. This paper examined the GI performance of a novel microcapsule membrane using a dynamic simulated human GI model. Results showed that the genipin cross-linked alginate-chitosan (GCAC microcapsules possessed strong resistance to structural disintegration in the simulated GI environment. Leakage of encapsulated high molecular weight dextran, a model material to be protected during the simulated GI transit, was negligible over 72 h of exposure, in contrast to considerable leakage of dextran from the non-cross-linked counterparts. These microcapsules did not alter the microflora and enzymatic activities in the simulated human colonic media. This study suggested the potential of the GCAC microcapsules for oral delivery of live microorganisms and other biotherapeutics.

  4. Application of CFD in Bioprocessing: Separation of mammalian cells using disc stack centrifuge during production of biotherapeutics.

    Science.gov (United States)

    Shekhawat, Lalita Kanwar; Sarkar, Jayati; Gupta, Rachit; Hadpe, Sandeep; Rathore, Anurag S

    2018-02-10

    Centrifugation continues to be one of the most commonly used unit operations for achieving efficient harvest of the product from the mammalian cell culture broth during production of therapeutic monoclonal antibodies (mAbs). Since the mammalian cells are known to be shear sensitive, optimal performance of the centrifuge requires a balance between productivity and shear. In this study, Computational Fluid Dynamics (CFD) has been successfully used as a tool to facilitate efficient optimization. Multiphase Eulerian-Eulerian model coupled with Gidaspow drag model along with Eulerian-Eulerian k-ε mixture turbulence model have been used to quantify the complex hydrodynamics of the centrifuge and thus evaluate the turbulent stresses generated by the centrifugal forces. An empirical model has been developed by statistical analysis of experimentally observed cell lysis data as a function of turbulent stresses. An operating window that offers the optimal balance between high productivity, high separation efficiency, and low cell damage has been identified by use of CFD modeling. Copyright © 2017 Elsevier B.V. All rights reserved.

  5. Molecular characterization of gluten hydrolysing Bacillus sp. and their efficacy and biotherapeutic potential as probiotics using Caco-2 cell line.

    Science.gov (United States)

    Rashmi, B S; Gayathri, D

    2017-09-01

    To isolate and characterize indigenous gluten hydrolysing bacteria from wheat sourdough and curd samples and further evaluation of their probiotic potentiality. Indigenous gluten hydrolysing isolates GS 33, GS 143, GS 181 and GS 188 were identified as Bacillus sp. by molecular-typing methods and studied extensively for their functional and probiotic attributes. All the tested isolates could survive at pH 2 and toxicity of 0·3% bile and also exhibited cell surface hydrophobicity and autoaggregation phenotype. The isolates were adhered strongly to Caco-2 cells and coaggregated with Escherichia coli MTCC 433 and Listeria monocytogenes MTCC 1143 preventing pathogen invasion into Caco-2 cells in vitro. In addition, the minimum inhibitory concentration of selected antibiotics for all the investigated gluten hydrolysing isolates was within the breakpoint values as recommended by the European Food Safety Authority. The indigenous high intensity gluten hydrolysing bacteria exhibited high resistance to gastric and pancreatic stress and possessed antibacterial, aggregation, adhesion and pathogen exclusion properties, and as a potential probiotics, either alone or in consortium would be useful in the development of gluten-free wheat foods. Exploring new indigenous gluten hydrolysing bacteria from wheat sourdough and curd samples would be beneficial in developing gluten-free wheat foods using potential indigenous probiotics. © 2017 The Society for Applied Microbiology.

  6. Immunogenicity to Biotherapeutics – the role of Anti-drug Immune complexes

    Directory of Open Access Journals (Sweden)

    Murli eKrishna

    2016-02-01

    Full Text Available AbstractBiologic molecules are increasingly becoming a part of the therapeutics portfolio that has been either recently approved for marketing or those that are in the pipeline of several biotech and pharmaceutical companies. This is largely based on their ability to be highly specific relative to small molecules. However by virtue of being a large protein, and having a complex structure with structural variability arising from production using recombinant gene technology in cell lines, such therapeutics run the risk of being recognized as foreign by a host immune system. Given the range of immune mediated adverse effects that have been documented to biologic drugs thus far, including infusion reactions, and the evolving therapeutic platforms in the pipeline that engineer different functional modules in a biotherapeutic, it is critical to understand the interplay of the adaptive and innate immune responses, the pathophysiology of immunogenicity to biologic drugs in instances where there have been immune mediated adverse clinical sequelae and address technical approaches for their laboratory evaluation. The current paradigm in immunogenicity evaluation has a tiered approach to the detection and characterization of anti-drug antibodies (ADAs elicited in vivo to a biotherapeutic; alongside with the structural, biophysical and molecular information of the therapeutic, these analytical assessments form the core of the immunogenicity risk assessment. However many of the immune mediated adverse effects attributed to ADAs require the formation of a drug/ADA immune complex intermediate (ICs that can have a variety of downstream effects. This review will focus on the activation of potential immunopathological pathways arising as a consequence of circulating as well as cell surface bound drug bearing-ICs, risk factors that are either intrinsic to the therapeutic molecule or to the host which might predispose to IC mediated effects, and review the recent

  7. 77 FR 9947 - Guidance for Industry: Early Clinical Trials With Live Biotherapeutic Products: Chemistry...

    Science.gov (United States)

    2012-02-21

    ...] Guidance for Industry: Early Clinical Trials With Live Biotherapeutic Products: Chemistry, Manufacturing... ``Guidance for Industry: Early Clinical Trials With Live Biotherapeutic Products: Chemistry, Manufacturing... for Industry: Early Clinical Trials With Live Biotherapeutic Products: Chemistry, Manufacturing, and...

  8. Elaborating European Pharmacopoeia monographs for biotherapeutic proteins using substances from a single source.

    Science.gov (United States)

    Buda, M; Wicks, S; Charton, E

    2016-01-01

    For more than twenty years, the European Pharmacopoeia (Ph. Eur.) monographs for biotherapeutic proteins have been elaborated using the multisource approach (Procedure 1), which has led to robust quality standards for many of the first-generation biotherapeutics. In 2008, the Ph. Eur. opened up the way towards an alternative mechanism for the elaboration of monographs (Procedure 4-BIO pilot phase), which is applied to substances still under patent protection, based on a close collaboration with the Innovator company, to ensure a harmonised global standard and strengthen the quality of the upcoming products. This article describes the lessons learned during the P4-BIO pilot phase and addresses the current thinking on monograph elaboration in the field of biotherapeutics. Case studies are described to illustrate the standardisation challenges associated with the complexity of biotherapeutics and of analytical procedures, as well as the approaches that help ensure expectations are met when setting monograph specifications and allow for compatibility with the development of biosimilars. Emphasis is put on monograph flexibility, notably by including tests that measure process-dependent microheterogeneity (e.g. glycosylation) in the Production section of the monograph. The European Pharmacopoeia successfully concluded the pilot phase of the P4-BIO during its 156 th session on 22-23 November 2016.

  9. Electrochemical cell structure including an ionomeric barrier

    Science.gov (United States)

    Lambert, Timothy N.; Hibbs, Michael

    2017-06-20

    An apparatus includes an electrochemical half-cell comprising: an electrolyte, an anode; and an ionomeric barrier positioned between the electrolyte and the anode. The anode may comprise a multi-electron vanadium phosphorous alloy, such as VP.sub.x, wherein x is 1-5. The electrochemical half-cell is configured to oxidize the vanadium and phosphorous alloy to release electrons. A method of mitigating corrosion in an electrochemical cell includes disposing an ionomeric barrier in a path of electrolyte or ion flow to an anode and mitigating anion accumulation on the surface of the anode.

  10. Biotherapeutic effects of probiotic bacteria on candidiasis in immunodeficient mice.

    Science.gov (United States)

    Wagner, R D; Pierson, C; Warner, T; Dohnalek, M; Farmer, J; Roberts, L; Hilty, M; Balish, E

    1997-10-01

    Four species of probiotic bacteria were assessed for their capacities to protect athymic bg/bg-nu/nu and euthymic bg/bg-nu/+ mice from mucosal and systemic candidiasis. Each bacterial species and Candida albicans colonized the gastrointestinal tracts of both strains of mice. The presence of probiotic bacteria (Lactobacillus acidophilus, Lactobacillus reuteri, Lactobacillus casei GG, or Bifidobacterium animalis) in the gastrointestinal tracts prolonged the survival of adult and neonatal bg/bg-nu/nu mice compared to that of isogenic mice colonized with C. albicans alone. The incidence of systemic candidiasis in bg/bg-nu/nu mice was significantly reduced by each of the four probiotic bacterial species. The numbers of C. albicans present in the alimentary tracts of euthymic bg/bg-nu/+ mice were significantly reduced by L. casei GG and B. animalis. None of the probiotic bacteria species completely prevented mucosal candidiasis, but B. animalis reduced its incidence and severity. Probiotic bacteria also modulated antibody- and cell-mediated immune responses to C. albicans. The prolonged survival of mice, decreased severity of mucosal and systemic candidiasis, modulation of immune responses, decreased number of C. albicans in the alimentary tract, and reduced numbers of orogastric infections demonstrated not only that probiotic bacteria have biotherapeutic potential for prophylaxis against and therapy of this fungal disease but also that probiotic bacteria protect mice from candidiasis by a variety of immunologic (thymic and extrathymic) and nonimmunologic mechanisms in this model.

  11. Asymptomatic bacteriuria Escherichia coli are live biotherapeutics for UTI.

    Science.gov (United States)

    Rudick, Charles N; Taylor, Aisha K; Yaggie, Ryan E; Schaeffer, Anthony J; Klumpp, David J

    2014-01-01

    Urinary tract infections (UTI) account for approximately 8 million clinic visits annually with symptoms that include acute pelvic pain, dysuria, and irritative voiding. Empiric UTI management with antimicrobials is complicated by increasing antimicrobial resistance among uropathogens, but live biotherapeutics products (LBPs), such as asymptomatic bacteriuria (ASB) strains of E. coli, offer the potential to circumvent antimicrobial resistance. Here we evaluated ASB E. coli as LBPs, relative to ciprofloxacin, for efficacy against infection and visceral pain in a murine UTI model. Visceral pain was quantified as tactile allodynia of the pelvic region in response to mechanical stimulation with von Frey filaments. Whereas ciprofloxacin promoted clearance of uropathogenic E. coli (UPEC), it did not reduce pelvic tactile allodynia, a measure of visceral pain. In contrast, ASB E. coli administered intravesically or intravaginally provided comparable reduction of allodynia similar to intravesical lidocaine. Moreover, ASB E. coli were similarly effective against UTI allodynia induced by Proteus mirabilis, Enterococccus faecalis and Klebsiella pneumoniae. Therefore, ASB E. coli have anti-infective activity comparable to the current standard of care yet also provide superior analgesia. These studies suggest that ASB E. coli represent novel LBPs for UTI symptoms.

  12. Potential of probiotics as biotherapeutic agents targeting the innate ...

    African Journals Online (AJOL)

    Potential of probiotics as biotherapeutic agents targeting the innate immune system. ... Some of the positive effects of probiotics are: growth promotion of farm animals, protection of host from intestinal infections, alleviation of lactose intolerance, relief of constipation, anticarcinogenic effect, anticholesterolaemic effects, ...

  13. Sensitive and specific detection of the non-human sialic Acid N-glycolylneuraminic acid in human tissues and biotherapeutic products.

    Directory of Open Access Journals (Sweden)

    Sandra L Diaz

    Full Text Available Humans are genetically defective in synthesizing the common mammalian sialic acid N-glycolylneuraminic acid (Neu5Gc, but can metabolically incorporate it from dietary sources (particularly red meat and milk into glycoproteins and glycolipids of human tumors, fetuses and some normal tissues. Metabolic incorporation of Neu5Gc from animal-derived cells and medium components also results in variable contamination of molecules and cells intended for human therapies. These Neu5Gc-incorporation phenomena are practically significant, because normal humans can have high levels of circulating anti-Neu5Gc antibodies. Thus, there is need for the sensitive and specific detection of Neu5Gc in human tissues and biotherapeutic products. Unlike monoclonal antibodies that recognize Neu5Gc only in the context of underlying structures, chicken immunoglobulin Y (IgY polyclonal antibodies can recognize Neu5Gc in broader contexts. However, prior preparations of such antibodies (including our own suffered from some non-specificity, as well as some cross-reactivity with the human sialic acid N-acetylneuraminic acid (Neu5Ac.We have developed a novel affinity method utilizing sequential columns of immobilized human and chimpanzee serum sialoglycoproteins, followed by specific elution from the latter column by free Neu5Gc. The resulting mono-specific antibody shows no staining in tissues or cells from mice with a human-like defect in Neu5Gc production. It allows sensitive and specific detection of Neu5Gc in all underlying glycan structural contexts studied, and is applicable to immunohistochemical, enzyme-linked immunosorbent assay (ELISA, Western blot and flow cytometry analyses. Non-immune chicken IgY is used as a reliable negative control. We show that these approaches allow sensitive detection of Neu5Gc in human tissue samples and in some biotherapeutic products, and finally show an example of how Neu5Gc might be eliminated from such products, by using a human cell

  14. Sensitive and comprehensive analysis of O-glycosylation in biotherapeutics: a case study of novel erythropoiesis stimulating protein.

    Science.gov (United States)

    Kim, Unyong; Oh, Myung Jin; Seo, Youngsuk; Jeon, Yinae; Eom, Joon-Ho; An, Hyun Joo

    2017-09-01

    Glycosylation of recombinant human erythropoietins (rhEPOs) is significantly associated with drug's quality and potency. Thus, comprehensive characterization of glycosylation is vital to assess the biotherapeutic quality and establish the equivalency of biosimilar rhEPOs. However, current glycan analysis mainly focuses on the N-glycans due to the absence of analytical tools to liberate O-glycans with high sensitivity. We developed selective and sensitive method to profile native O-glycans on rhEPOs. O-glycosylation on rhEPO including O-acetylation on a sialic acid was comprehensively characterized. Details such as O-glycan structure and O-acetyl-modification site were obtained from tandem MS. This method may be applied to QC and batch analysis of not only rhEPOs but also other biotherapeutics bearing multiple O-glycosylations.

  15. Mapping the Pareto optimal design space for a functionally deimmunized biotherapeutic candidate.

    Science.gov (United States)

    Salvat, Regina S; Parker, Andrew S; Choi, Yoonjoo; Bailey-Kellogg, Chris; Griswold, Karl E

    2015-01-01

    The immunogenicity of biotherapeutics can bottleneck development pipelines and poses a barrier to widespread clinical application. As a result, there is a growing need for improved deimmunization technologies. We have recently described algorithms that simultaneously optimize proteins for both reduced T cell epitope content and high-level function. In silico analysis of this dual objective design space reveals that there is no single global optimum with respect to protein deimmunization. Instead, mutagenic epitope deletion yields a spectrum of designs that exhibit tradeoffs between immunogenic potential and molecular function. The leading edge of this design space is the Pareto frontier, i.e. the undominated variants for which no other single design exhibits better performance in both criteria. Here, the Pareto frontier of a therapeutic enzyme has been designed, constructed, and evaluated experimentally. Various measures of protein performance were found to map a functional sequence space that correlated well with computational predictions. These results represent the first systematic and rigorous assessment of the functional penalty that must be paid for pursuing progressively more deimmunized biotherapeutic candidates. Given this capacity to rapidly assess and design for tradeoffs between protein immunogenicity and functionality, these algorithms may prove useful in augmenting, accelerating, and de-risking experimental deimmunization efforts.

  16. Posttranslational Modifications and the Immunogenicity of Biotherapeutics

    Directory of Open Access Journals (Sweden)

    Roy Jefferis

    2016-01-01

    Full Text Available Whilst the amino acid sequence of a protein is determined by its gene sequence, the final structure and function are determined by posttranslational modifications (PTMs, including quality control (QC in the endoplasmic reticulum (ER and during passage through the Golgi apparatus. These processes are species and cell specific and challenge the biopharmaceutical industry when developing a production platform for the generation of recombinant biologic therapeutics. Proteins and glycoproteins are also subject to chemical modifications (CMs both in vivo and in vitro. The individual is naturally tolerant to molecular forms of self-molecules but nonself variants can provoke an immune response with the generation of anti-drug antibodies (ADA; aggregated forms can exhibit enhanced immunogenicity and QC procedures are developed to avoid or remove them. Monoclonal antibody therapeutics (mAbs are a special case because their purpose is to bind the target, with the formation of immune complexes (ICs, a particular form of aggregate. Such ICs may be removed by phagocytic cells that have antigen presenting capacity. These considerations may frustrate the possibility of ameliorating the immunogenicity of mAbs by rigorous exclusion of aggregates from drug product. Alternate strategies for inducing immunosuppression or tolerance are discussed.

  17. Photopolymerization Synthesis of Magnetic Nanoparticle Embedded Nanogels for Targeted Biotherapeutic Delivery

    Science.gov (United States)

    Denmark, Daniel J.

    Conventional therapeutic techniques treat the patient by delivering a biotherapeutic to the entire body rather than the target tissue. In the case of chemotherapy, the biotherapeutic is a drug that kills healthy and diseased cells indiscriminately which can lead to undesirable side effects. With targeted delivery, biotherapeutics can be delivered directly to the diseased tissue significantly reducing exposure to otherwise healthy tissue. Typical composite delivery devices are minimally composed of a stimuli responsive polymer, such as poly(N-isopropylacrylamide), allowing for triggered release when heated beyond approximately 32 °C, and magnetic nanoparticles which enable targeting as well as provide a mechanism for stimulus upon alternating magnetic field heating. Although more traditional methods, such as emulsion polymerization, have been used to realize these composite devices, the synthesis is problematic. Poisonous surfactants that are necessary to prevent agglomeration must be removed from the finished polymer, increasing the time and cost of the process. This study seeks to further explore non-toxic, biocompatible, non-residual, photochemical methods of creating stimuli responsive nanogels to advance the targeted biotherapeutic delivery field. Ultraviolet photopolymerization promises to be more efficient, while ensuring safety by using only biocompatible substances. The reactants selected for nanogel fabrication were N -isopropylacrylamide as monomer, methylene bisacrylamide as cross-linker, and Irgacure 2959 as ultraviolet photo-initiator. The superparamagnetic nanoparticles for encapsulation were approximately 10 nm in diameter and composed of magnetite to enable remote delivery and enhanced triggered release properties. Early investigations into the interactions of the polymer and nanoparticles employ a pioneering experimental setup, which allows for coincident turbidimetry and alternating magnetic field heating of an aqueous solution containing both

  18. Effect of biotherapeutics on antitoxin IgG in experimentally induced Clostridium difficile infection

    Directory of Open Access Journals (Sweden)

    S Kaur

    2012-01-01

    Full Text Available Purpose: Recurrent diarrhoea after successful treatment of primary Clostridium difficile associated disease (CDAD occurs due to bowel flora alterations and failure to mount an effective antibody response. Apart from antibiotics, risk factors include immunosuppressive and acid-suppressive drug administration. Biotherapeutics such as probiotic and epidermal growth factor (EGF may offer potential effective therapy for CDAD. Materials and Methods: The effect of biotherapeutics in mounting an antibody response against C. difficile toxins was studied in BALB/c mice challenged with C. difficile after pre-treatment with ampicillin, lansoprazole or cyclosporin. Sera from sacrificed animals were estimated for antitoxin IgG by enzyme linked immunosorbent assay. Results: Antitoxin IgG was significantly higher (P0.05 in animals in which C. difficile was given after pre-treatment with cyclosporin compared to those without any pre-treatment, or pre-treatment with antibiotic or lansoprazole. In inter-subgroup comparisons also significant anomaly in production of antitoxin IgG was found. The antitoxin IgG levels were raised in animals administered C. difficile after pre-treatment with ampicillin, but lower in animals administered cyclosporin. High levels of antitoxin IgG were also found in the serum samples of animals receiving lansoprazole and C. difficile. Conclusions: Probiotics showed their beneficial effect by boosting the immune response as seen by production of antitoxin IgG. Oral administration of EGF did not affect the immune response to C. difficile toxins as significant increase was not observed in the serum antitoxin IgG levels in any of the groups investigated.

  19. 75 FR 63188 - Draft Guidance for Industry: Early Clinical Trials With Live Biotherapeutic Products: Chemistry...

    Science.gov (United States)

    2010-10-14

    ...] Draft Guidance for Industry: Early Clinical Trials With Live Biotherapeutic Products: Chemistry...: Chemistry, Manufacturing, and Control Information'' dated September 2010. The draft guidance provides... Products: Chemistry, Manufacturing, and Control Information'' dated September 2010. The draft guidance...

  20. Reducing or Eliminating Polysorbate Induced Anaphylaxis and Unwanted Immunogenicity in Biotherapeutics

    Directory of Open Access Journals (Sweden)

    Edward Maggio

    2017-09-01

    Full Text Available The increasing use of biotherapeutics across a growing spectrum of neoplastic, autoimmune, and inflammatory diseases has resulted in a corresponding increase in hypersensitivity reactions. The origins of anaphylaxis are often attributed to undefined intrinsic properties of the biotherapeutic protein itself, ignoring the broader potential negative contributions of functional excipients, in particular polyoxyethylene containing surfactants such as polysorbate 80 and polysorbate 20 (Tween 80 and Tween 20. These surfactants allow biotherapeutics to meet the stringent challenges of extended shelf-life, increased solubility, protein aggregation prevention, reduced administration volume, and satisfactory reconstitution properties in the case of lyophilized biotherapeutics. The potential negative impact of certain functional excipients on product performance characteristics such as anaphylaxis and immunogenicity is often overlooked. While regulatory authorities understandably focus heavily on comparable efficacy in evaluating biosimilars, similar efficacy does not necessarily imply a similar safety profile between the originator and biosimilar products. Both unwanted immunogenicity and anaphylaxis do comprise major components of safety assessment, however, few if any attempts are made to differentiate drug-related from excipient-related anaphylaxis. Replacement of anaphylactogenic and immunogenic functional excipients with equally effective but safer alternatives will allow biotherapeutic developers to differentiate their biotherapeutic, biosimilar, or biobetter from the large number of nearly identical competitor products, simultaneously providing a substantial commercial benefit as well as critical clinical benefits for all concerned – patients, physicians, and third party payers.

  1. Immunogenicity of glycans on biotherapeutic drugs produced in plant expression systems—The taliglucerase alfa story

    Science.gov (United States)

    Rup, Bonita; Alon, Sari; Amit-Cohen, Bat-Chen; Brill Almon, Einat; Chertkoff, Raul; Rudd, Pauline M.

    2017-01-01

    Plants are a promising alternative for the production of biotherapeutics. Manufacturing in-planta adds plant specific glycans. To understand immunogenic potential of these glycans, we developed a validated method to detect plant specific glycan antibodies in human serum. Using this assay, low prevalence of pre-existing anti-plant glycan antibodies was found in healthy humans (13.5%) and in glucocerebrosidase-deficient Gaucher disease (GD) patients (5%). A low incidence (9% in naïve patient and none in treatment experienced patients) of induced anti-plant glycan antibodies was observed in GD patients after up to 30 months replacement therapy treatment with taliglucerase alfa, a version of human glucocerebrosidase produced in plant cells. Detailed evaluation of clinical safety and efficacy endpoints indicated that anti-plant glycan antibodies did not affect the safety or efficacy of taliglucerase alfa in patients. This study shows the benefit of using large scale human trials to evaluate the immunogenicity risk of plant derived glycans, and indicates no apparent risk related to anti-plant glycan antibodies. PMID:29088235

  2. Universal immunogenicity validation and assessment during early biotherapeutic development to support a green laboratory.

    Science.gov (United States)

    Bautista, Ami C; Zhou, Lei; Jawa, Vibha

    2013-10-01

    Immunogenicity support during nonclinical biotherapeutic development can be resource intensive if supported by conventional methodologies. A universal indirect species-specific immunoassay can eliminate the need for biotherapeutic-specific anti-drug antibody immunoassays without compromising quality. By implementing the R's of sustainability (reduce, reuse, rethink), conservation of resources and greener laboratory practices were achieved in this study. Statistical analysis across four biotherapeutics supported identification of consistent product performance standards (cut points, sensitivity and reference limits) and a streamlined universal anti-drug antibody immunoassay method implementation strategy. We propose an efficient, fit-for-purpose, scientifically and statistically supported nonclinical immunogenicity assessment strategy. Utilization of a universal method and streamlined validation, while retaining comparability to conventional immunoassays and meeting the industry recommended standards, provides environmental credits in the scientific laboratory. Collectively, individual reductions in critical material consumption, energy usage, waste and non-environment friendly consumables, such as plastic and paper, support a greener laboratory environment.

  3. Commercial-scale biotherapeutics manufacturing facility for plant-made pharmaceuticals.

    Science.gov (United States)

    Holtz, Barry R; Berquist, Brian R; Bennett, Lindsay D; Kommineni, Vally J M; Munigunti, Ranjith K; White, Earl L; Wilkerson, Don C; Wong, Kah-Yat I; Ly, Lan H; Marcel, Sylvain

    2015-10-01

    Rapid, large-scale manufacture of medical countermeasures can be uniquely met by the plant-made-pharmaceutical platform technology. As a participant in the Defense Advanced Research Projects Agency (DARPA) Blue Angel project, the Caliber Biotherapeutics facility was designed, constructed, commissioned and released a therapeutic target (H1N1 influenza subunit vaccine) in manufacturing facilities, with the capacity to process over 3500 kg of plant biomass per week in an automated multilevel growing environment using proprietary LED lighting. The facility can commission additional plant grow rooms that are already built to double this capacity. In addition to the commercial-scale manufacturing facility, a pilot production facility was designed based on the large-scale manufacturing specifications as a way to integrate product development and technology transfer. The primary research, development and manufacturing system employs vacuum-infiltrated Nicotiana benthamiana plants grown in a fully contained, hydroponic system for transient expression of recombinant proteins. This expression platform has been linked to a downstream process system, analytical characterization, and assessment of biological activity. This integrated approach has demonstrated rapid, high-quality production of therapeutic monoclonal antibody targets, including a panel of rituximab biosimilar/biobetter molecules and antiviral antibodies against influenza and dengue fever. © 2015 Society for Experimental Biology, Association of Applied Biologists and John Wiley & Sons Ltd.

  4. Electrolytes including fluorinated solvents for use in electrochemical cells

    Science.gov (United States)

    Tikhonov, Konstantin; Yip, Ka Ki; Lin, Tzu-Yuan

    2015-07-07

    Provided are electrochemical cells and electrolytes used to build such cells. The electrolytes include ion-supplying salts and fluorinated solvents capable of maintaining single phase solutions with the salts at between about -30.degree. C. to about 80.degree. C. The fluorinated solvents, such as fluorinated carbonates, fluorinated esters, and fluorinated esters, are less flammable than their non-fluorinated counterparts and increase safety characteristics of cells containing these solvents. The amount of fluorinated solvents in electrolytes may be between about 30% and 80% by weight not accounting weight of the salts. Fluorinated salts, such as fluoroalkyl-substituted LiPF.sub.6, fluoroalkyl-substituted LiBF.sub.4 salts, linear and cyclic imide salts as well as methide salts including fluorinated alkyl groups, may be used due to their solubility in the fluorinated solvents. In some embodiments, the electrolyte may also include a flame retardant, such as a phosphazene or, more specifically, a cyclic phosphazene and/or one or more ionic liquids.

  5. Mass spectrometric-based stable isotopic 2-aminobenzoic acid glycan mapping for rapid glycan screening of biotherapeutics.

    Science.gov (United States)

    Prien, Justin M; Prater, Bradley D; Qin, Qiang; Cockrill, Steven L

    2010-02-15

    Fast, sensitive, robust methods for "high-level" glycan screening are necessary during various stages of a biotherapeutic product's lifecycle, including clone selection, process changes, and quality control for lot release testing. Traditional glycan screening involves chromatographic or electrophoretic separation-based methods, and, although reproducible, these methods can be time-consuming. Even ultrahigh-performance chromatographic and microfluidic integrated LC/MS systems, which work on the tens of minute time scale, become lengthy when hundreds of samples are to be analyzed. Comparatively, a direct infusion mass spectrometry (MS)-based glycan screening method acquires data on a millisecond time scale, exhibits exquisite sensitivity and reproducibility, and is amenable to automated peak annotation. In addition, characterization of glycan species via sequential mass spectrometry can be performed simultaneously. Here, we demonstrate a quantitative high-throughput MS-based mapping approach using stable isotope 2-aminobenzoic acid (2-AA) for rapid "high-level" glycan screening.

  6. Identification of astrocytoma associated genes including cell surface markers

    International Nuclear Information System (INIS)

    Boon, Kathy; Edwards, Jennifer B; Eberhart, Charles G; Riggins, Gregory J

    2004-01-01

    Despite intense effort the treatment options for the invasive astrocytic tumors are still limited to surgery and radiation therapy, with chemotherapy showing little or no increase in survival. The generation of Serial Analysis of Gene Expression (SAGE) profiles is expected to aid in the identification of astrocytoma-associated genes and highly expressed cell surface genes as molecular therapeutic targets. SAGE tag counts can be easily added to public expression databases and quickly disseminated to research efforts worldwide. We generated and analyzed the SAGE transcription profiles of 25 primary grade II, III and IV astrocytomas [1]. These profiles were produced as part of the Cancer Genome Anatomy Project's SAGE Genie [2], and were used in an in silico search for candidate therapeutic targets by comparing astrocytoma to normal brain transcription. Real-time PCR and immunohistochemistry were used for the validation of selected candidate target genes in 2 independent sets of primary tumors. A restricted set of tumor-associated genes was identified for each grade that included genes not previously associated with astrocytomas (e.g. VCAM1, SMOC1, and thymidylate synthetase), with a high percentage of cell surface genes. Two genes with available antibodies, Aquaporin 1 and Topoisomerase 2A, showed protein expression consistent with transcript level predictions. This survey of transcription in malignant and normal brain tissues reveals a small subset of human genes that are activated in malignant astrocytomas. In addition to providing insights into pathway biology, we have revealed and quantified expression for a significant portion of cell surface and extra-cellular astrocytoma genes

  7. Aplasia versus pancytopenia, including the pure red cell variant

    African Journals Online (AJOL)

    to extend evaluation to the bone marrow and plasma while supplementary imaging ... B lood. Pluripotential stem cell. Early acting molecules, primarily interleukins .... options towards early immunohaematopoietic stem cell allogeneic transplantation. ... Chronic leukaemia, leukaemia, lymphomas; large granular lymphocytic ...

  8. Plasma Cell Neoplasms (Including Multiple Myeloma)—Patient Version

    Science.gov (United States)

    Plasma cell neoplasms occur when abnormal plasma cells form cancerous tumors. When there is only one tumor, the disease is called a plasmacytoma. When there are multiple tumors, it is called multiple myeloma. Start here to find information on plasma cell neoplasms treatment, research, and statistics.

  9. Toward best practices in data processing and analysis for intact biotherapeutics by MS in quantitative bioanalysis.

    Science.gov (United States)

    Kellie, John F; Kehler, Jonathan R; Karlinsey, Molly Z; Summerfield, Scott G

    2017-12-01

    Typically, quantitation of biotherapeutics from biological matrices by LC-MS is based on a surrogate peptide approach to determine molecule concentration. Recent efforts have focused on quantitation of the intact protein molecules or larger mass subunits of monoclonal antibodies. To date, there has been limited guidance for large or intact protein mass quantitation for quantitative bioanalysis. Intact- and subunit-level analyses of biotherapeutics from biological matrices are performed at 12-25 kDa mass range with quantitation data presented. Linearity, bias and other metrics are presented along with recommendations made on the viability of existing quantitation approaches. This communication is intended to start a discussion around intact protein data analysis and processing, recognizing that other published contributions will be required.

  10. Flexible organic solar cells including efficiency enhancing grating structures

    DEFF Research Database (Denmark)

    Oliveira Hansen, Roana Melina de; Liu, Yinghui; Madsen, Morten

    2013-01-01

    , such as photolithography and electron-beam lithography, besides the steps required for the bulk-heterojunction organic solar cell fabrication. After the production steps, the solar cells on polyimide are peeled off the silicon support substrates, resulting in flexible devices containing nanostructures for light absorption......In this work, a new method for the fabrication of organic solar cells containing functional light-trapping nanostructures on flexible substrates is presented. Polyimide is spin-coated on silicon support substrates, enabling standard micro- and nanotechnology fabrication techniques...

  11. Flexible organic solar cells including efficiency enhancing grating structures

    International Nuclear Information System (INIS)

    De Oliveira Hansen, Roana Melina; Liu Yinghui; Madsen, Morten; Rubahn, Horst-Günter

    2013-01-01

    In this work, a new method for the fabrication of organic solar cells containing functional light-trapping nanostructures on flexible substrates is presented. Polyimide is spin-coated on silicon support substrates, enabling standard micro- and nanotechnology fabrication techniques, such as photolithography and electron-beam lithography, besides the steps required for the bulk-heterojunction organic solar cell fabrication. After the production steps, the solar cells on polyimide are peeled off the silicon support substrates, resulting in flexible devices containing nanostructures for light absorption enhancement. Since the solar cells avoid using brittle electrodes, the performance of the flexible devices is not affected by the peeling process. We have investigated three different nanostructured grating designs and conclude that gratings with a 500 nm pitch distance have the highest light-trapping efficiency for the selected active layer material (P3HT:PCBM), resulting in an enhancement of about 34% on the solar cell efficiency. The presented method can be applied to a large variety of flexible nanostructured devices in future applications. (paper)

  12. Inferring time derivatives including cell growth rates using Gaussian processes

    Science.gov (United States)

    Swain, Peter S.; Stevenson, Keiran; Leary, Allen; Montano-Gutierrez, Luis F.; Clark, Ivan B. N.; Vogel, Jackie; Pilizota, Teuta

    2016-12-01

    Often the time derivative of a measured variable is of as much interest as the variable itself. For a growing population of biological cells, for example, the population's growth rate is typically more important than its size. Here we introduce a non-parametric method to infer first and second time derivatives as a function of time from time-series data. Our approach is based on Gaussian processes and applies to a wide range of data. In tests, the method is at least as accurate as others, but has several advantages: it estimates errors both in the inference and in any summary statistics, such as lag times, and allows interpolation with the corresponding error estimation. As illustrations, we infer growth rates of microbial cells, the rate of assembly of an amyloid fibril and both the speed and acceleration of two separating spindle pole bodies. Our algorithm should thus be broadly applicable.

  13. A Consensus Genome-scale Reconstruction of Chinese Hamster Ovary Cell Metabolism

    KAUST Repository

    Hefzi, Hooman; Ang, Kok  Siong; Hanscho, Michael; Bordbar, Aarash; Ruckerbauer, David; Lakshmanan, Meiyappan; Orellana, Camila  A.; Baycin-Hizal, Deniz; Huang, Yingxiang; Ley, Daniel; Martinez, Veronica  S.; Kyriakopoulos, Sarantos; Jimé nez, Natalia  E.; Zielinski, Daniel  C.; Quek, Lake-Ee; Wulff, Tune; Arnsdorf, Johnny; Li, Shangzhong; Lee, Jae  Seong; Paglia, Giuseppe; Loira, Nicolas; Spahn, Philipp  N.; Pedersen, Lasse  E.; Gutierrez, Jahir  M.; King, Zachary  A.; Lund, Anne  Mathilde; Nagarajan, Harish; Thomas, Alex; Abdel-Haleem, Alyaa M.; Zanghellini, Juergen; Kildegaard, Helene  F.; Voldborg, Bjø rn  G.; Gerdtzen, Ziomara  P.; Betenbaugh, Michael  J.; Palsson, Bernhard  O.; Andersen, Mikael  R.; Nielsen, Lars  K.; Borth, Nicole; Lee, Dong-Yup; Lewis, Nathan  E.

    2016-01-01

    Chinese hamster ovary (CHO) cells dominate biotherapeutic protein production and are widely used in mammalian cell line engineering research. To elucidate metabolic bottlenecks in protein production and to guide cell engineering and bioprocess

  14. A Consensus Genome-scale Reconstruction of Chinese Hamster Ovary Cell Metabolism

    DEFF Research Database (Denmark)

    Hefzi, Hooman; Ang, Kok Siong; Hanscho, Michael

    2016-01-01

    Chinese hamster ovary (CHO) cells dominate biotherapeutic protein production and are widely used in mammalian cell line engineering research. To elucidate metabolic bottlenecks in protein production and to guide cell engineering and bioprocess optimization, we reconstructed the metabolic pathways...

  15. Cholesterol-Lowering Probiotics as Potential Biotherapeutics for Metabolic Diseases

    Directory of Open Access Journals (Sweden)

    Manoj Kumar

    2012-01-01

    Full Text Available Cardiovascular diseases are one of the major causes of deaths in adults in the western world. Elevated levels of certain blood lipids have been reported to be the principal cause of cardiovascular disease and other disabilities in developed countries. Several animal and clinical trials have shown a positive association between cholesterol levels and the risks of coronary heart disease. Current dietary strategies for the prevention of cardiovascular disease advocate adherence to low-fat/low-saturated-fat diets. Although there is no doubt that, in experimental conditions, low-fat diets offer an effective means of reducing blood cholesterol concentrations on a population basis, these appear to be less effective, largely due to poor compliance, attributed to low palatability and acceptability of these diets to the consumers. Due to the low consumer compliance, attempts have been made to identify other dietary components that can reduce blood cholesterol levels. Supplementation of diet with fermented dairy products or lactic acid bacteria containing dairy products has shown the potential to reduce serum cholesterol levels. Various approaches have been used to alleviate this issue, including the use of probiotics, especially Bifidobacterium spp. and Lactobacillus spp.. Probiotics, the living microorganisms that confer health benefits on the host when administered in adequate amounts, have received much attention on their proclaimed health benefits which include improvement in lactose intolerance, increase in natural resistance to infectious disease in gastrointestinal tract, suppression of cancer, antidiabetic, reduction in serum cholesterol level, and improved digestion. In addition, there are numerous reports on cholesterol removal ability of probiotics and their hypocholesterolemic effects. Several possible mechanisms for cholesterol removal by probiotics are assimilation of cholesterol by growing cells, binding of cholesterol to cellular surface

  16. Global Foot-and-Mouth Disease Research Update and Gap Analysis: 5 - Biotherapeutics and Disinfectants.

    Science.gov (United States)

    Robinson, L; Knight-Jones, T J D; Charleston, B; Rodriguez, L L; Gay, C G; Sumption, K J; Vosloo, W

    2016-06-01

    We assessed knowledge gaps in foot-and-mouth disease (FMD) research. Findings are reported in a series of papers, and in this article, we consider biotherapeutics and disinfectants. The study took the form of a literature review (2011-2015) combined with research updates collected in 2014 from 33 institutes from across the world. Findings were used to identify priority areas for future FMD research. While vaccines will remain the key immunological intervention used against FMD virus (FMDV) for the foreseeable future, it takes a few days for the immune system to respond to vaccination. In an outbreak situation, protection could potentially be provided during this period by the application of rapid, short-acting biotherapeutics, aiming either to stimulate a non-specific antiviral state in the animal or to specifically inhibit a part of the viral life cycle. Certain antiviral cytokines have been shown to promote rapid protection against FMD; however, the effects of different immune-modulators appear to vary across species in ways and for reasons that are not yet understood. Major barriers to the effective incorporation of biotherapeutics into control strategies are cost, limited understanding of their effect on subsequent immune responses to vaccines and uncertainty about their potential impact if used for disease containment. Recent research has highlighted the importance of environmental contamination in FMDV transmission. Effective disinfectants for FMDV have long been available, but research is being conducted to further develop methods for quantitatively evaluating their performance under field, or near-field, conditions. During outbreaks in South Korea in 2010 there was public concern about potential environmental contamination after the mass use of disinfectant and mass burial of culled stock; this should be considered during outbreak contingency planning. © 2016 Blackwell Verlag GmbH.

  17. Modeling of Pem Fuel Cell Systems Including Controls and Reforming Effects for Hybrid Automotive Applications

    National Research Council Canada - National Science Library

    Boettner, Daisie

    2001-01-01

    .... This study develops models for a stand-alone Proton Exchange Membrane (PEM) fuel cell stack, a direct-hydrogen fuel cell system including auxiliaries, and a methanol reforming fuel cell system for integration into a vehicle performance simulator...

  18. Impact of product-related factors on immunogenicity of biotherapeutics.

    Science.gov (United States)

    Singh, Satish Kumar

    2011-02-01

    All protein therapeutics have the potential to be immunogenic. Several factors, including patient characteristics, disease state, and the therapy itself, influence the generation of an immune response. Product-related factors such as the molecule design, the expression system, post-translational modifications, impurities, contaminants, formulation and excipients, container, closure, as well as degradation products are all implicated. However, a critical examination of the available data shows that clear unequivocal evidence for the impact of these latter factors on clinical immunogenicity is lacking. No report could be found that clearly deconvolutes the clinical impact of the product attributes on patient susceptibility. Aggregation carries the greatest concern as a risk factor for immunogenicity, but the impact of aggregates is likely to depend on their structure as well as on the functionality (e.g., immunostimulatory or immunomodulatory) of the therapeutic. Preclinical studies are not yet capable of assessing the clinically relevant immunogenicity potential of these product-related factors. Simply addressing these risk factors as part of product development will not eliminate immunogenicity. Minimization of immunogenicity has to begin at the molecule design stage by reducing or eliminating antigenic epitopes and building in favorable physical and chemical properties. Copyright © 2010 Wiley-Liss, Inc.

  19. Laboratory automation of high-quality and efficient ligand-binding assays for biotherapeutic drug development.

    Science.gov (United States)

    Wang, Jin; Patel, Vimal; Burns, Daniel; Laycock, John; Pandya, Kinnari; Tsoi, Jennifer; DeSilva, Binodh; Ma, Mark; Lee, Jean

    2013-07-01

    Regulated bioanalytical laboratories that run ligand-binding assays in support of biotherapeutics development face ever-increasing demand to support more projects with increased efficiency. Laboratory automation is a tool that has the potential to improve both quality and efficiency in a bioanalytical laboratory. The success of laboratory automation requires thoughtful evaluation of program needs and fit-for-purpose strategies, followed by pragmatic implementation plans and continuous user support. In this article, we present the development of fit-for-purpose automation of total walk-away and flexible modular modes. We shared the sustaining experience of vendor collaboration and team work to educate, promote and track the use of automation. The implementation of laboratory automation improves assay performance, data quality, process efficiency and method transfer to CRO in a regulated bioanalytical laboratory environment.

  20. Plasma Cell Neoplasms (Including Multiple Myeloma)—Health Professional Version

    Science.gov (United States)

    There are several types of plasma cell neoplasms, including monoclonal gammopathy of undetermined significance (MGUS), isolated plasmacytoma of the bone, extramedullary plasmacytoma, and multiple myeloma. Find evidence-based information on plasma cell neoplasms treatment, research, and statistics.

  1. Potencial bioterapêutico dos probióticos nas parasitoses intestinais Probiotics as potential biotherapeutic agents targeting intestinal parasites

    Directory of Open Access Journals (Sweden)

    Teresa Cristina Goulart de Oliveira-Sequeira

    2008-12-01

    Full Text Available Probióticos são microrganismos vivos que, se administrados em quantidades adequadas, promovem benefícios à saúde do homem e dos animais. O crescente interesse nos probióticos fundamenta-se em estudos clínicos nos quais a administração desses organismos foi avaliada na prevenção e no tratamento de desordens intestinais e sistêmicas. Os potenciais mecanismos de ação desses microrganismos incluem a exclusão competitiva, a produção de metabólitos com atividade antimicrobiana e a modulação da resposta imune. Em algumas circunstâncias clínicas específicas, os benefícios produzidos por esses microrganismos foram amplamente documentados, enquanto que em outras os resultados são contraditórios. No presente artigo de revisão, os probióticos foram abordados considerando-se o potencial bioterapêutico desses microrganismos nas parasitoses intestinais.Probiotics are live microorganisms which, when administered in adequate amounts, beneficially affect the general health status of man and animal. The great interest in probiotic microganisms is based on evidences from clinical studies indicating benefits in the prevention or treatment of a broad spectrum of gastrointestinal and systemic disorders. The potential mechanisms by which probiotics beneficially affect health include strengthening of the intestinal barrier, modulation of the immune response, and antagonism of pathogens either by the production of antimicrobial compounds or through competition for mucosal binding sites. In some specific clinical circumstances, there is clear evidence of benefit whereas in others, the results are dubious and important questions remaining unanswered. The aim of this review article is to focus probiotics on their potential as biotherapeutic agents against intestinal parasites.

  2. Advances in the theory and application of BSF cells. [including electrical resistivity and photovoltaic cells

    Science.gov (United States)

    Mandelkorn, J.; Lamneck, J. H.

    1975-01-01

    The characteristics and behavior of p(+), p solar cells were investigated. The p(+), p cells were made by the removal of the n(+) surface layers from n(+), p p(+), BSF cells followed by application of a suitable contact to the resultant p(+), p structures. The open circuit voltage of p(+), p cells was found to increase with increasing 'p' bulk resistivity. The measured open circuit velocity-temperature coefficients were positive and increased with increasing resistivity. An outline of prior limitations in solar cell design is presented, and the removal of these limitations through use of BSF effects is pointed out. The study of BSF effects made feasible production of very thin high efficiency silicon cells as well as high resistivity-high efficiency cells, two desirable types of silicon cells which were previously impossible to make.

  3. Solar cells, structures including organometallic halide perovskite monocrystalline films, and methods of preparation thereof

    KAUST Repository

    Bakr, Osman; Peng, Wei; Wang, Lingfei

    2017-01-01

    Embodiments of the present disclosure provide for solar cells including an organometallic halide perovskite monocrystalline film (see fig. 1.1B), other devices including the organometallic halide perovskite monocrystalline film, methods of making

  4. A newly isolated probiotic Enterococcus faecalis strain from vagina microbiota enhances apoptosis of human cancer cells.

    Science.gov (United States)

    Nami, Y; Abdullah, N; Haghshenas, B; Radiah, D; Rosli, R; Yari Khosroushahi, A

    2014-08-01

    This study aimed to describe probiotic properties and bio-therapeutic effects of newly isolated Enterococcus faecalis from the human vaginal tract. The Enterococcus faecalis strain was originally isolated from the vaginal microbiota of Iranian women and was molecularly identified using 16SrDNA gene sequencing. Some biochemical methodologies were preliminarily used to characterize the probiotic potential of Ent. faecalis, including antibiotic susceptibility, antimicrobial activity, as well as acid and bile resistance. The bio-therapeutic effects of this strain's secreted metabolites on four human cancer cell lines (AGS, HeLa, MCF-7 and HT-29) and one normal cell line (HUVEC) were evaluated by cytotoxicity assay and apoptosis scrutiny. The characterization results demonstrated into the isolated bacteria strain revealed probiotic properties, such as antibiotic susceptibility, antimicrobial activity and resistance under conditions similar to those in the gastrointestinal tract. Results of bio-therapeutic efficacy assessments illustrated acceptable apoptotic effects on four human cancer cell lines and negligible side effects on assayed normal cell line. Our findings revealed that the apoptotic effect of secreted metabolites mainly depended on proteins secreted by Ent. faecalis on different cancer cells. These proteins can induce the apoptosis of cancer cells. The metabolites produced by this vaginal Ent. faecalis strain can be used as alternative pharmaceutical compounds with promising therapeutic indices because they are not cytotoxic to normal mammalian cells. Accordingly, the physicochemical, structural and functional properties of the secreted anticancer substances should be further investigated before using them as anticancer therapeutics. This study aim to screen total bacterial secreted metabolites as a wealthy source to find the new active compounds to introduce as anticancer therapeutics in the future. © 2014 The Society for Applied Microbiology.

  5. Glycoengineering of CHO Cells to Improve Product Quality.

    Science.gov (United States)

    Wang, Qiong; Yin, Bojiao; Chung, Cheng-Yu; Betenbaugh, Michael J

    2017-01-01

    Chinese hamster ovary (CHO) cells represent the predominant platform in biopharmaceutical industry for the production of recombinant biotherapeutic proteins, especially glycoproteins. These glycoproteins include oligosaccharide or glycan attachments that represent one of the principal components dictating product quality. Especially important are the N-glycan attachments present on many recombinant glycoproteins of commercial interest. Furthermore, altering the glycan composition can be used to modulate the production quality of a recombinant biotherapeutic from CHO and other mammalian hosts. This review first describes the glycosylation network in mammalian cells and compares the glycosylation patterns between CHO and human cells. Next genetic strategies used in CHO cells to modulate the sialylation patterns through overexpression of sialyltransfereases and other glycosyltransferases are summarized. In addition, other approaches to alter sialylation including manipulation of sialic acid biosynthetic pathways and inhibition of sialidases are described. Finally, this review also covers other strategies such as the glycosylation site insertion and manipulation of glycan heterogeneity to produce desired glycoforms for diverse biotechnology applications.

  6. Polysorbates 20 and 80 used in the formulation of protein biotherapeutics: structure and degradation pathways.

    Science.gov (United States)

    Kerwin, Bruce A

    2008-08-01

    Polysorbates 20 and 80 (Tween 20 and Tween 80) are used in the formulation of biotherapeutic products for both preventing surface adsorption and as stabilizers against protein aggregation. The polysorbates are amphipathic, nonionic surfactants composed of fatty acid esters of polyoxyethylene sorbitan being polyoxyethylene sorbitan monolaurate for polysorbate 20 and polyoxyethylene sorbitan monooleate for polysorbate 80. The polysorbates used in the formulation of biopharmaceuticals are mixtures of different fatty acid esters with the monolaurate fraction of polysorbate 20 making up only 40-60% of the mixture and the monooleate fraction of polysorbate 80 making up >58% of the mixture. The polysorbates undergo autooxidation, cleavage at the ethylene oxide subunits and hydrolysis of the fatty acid ester bond. Autooxidation results in hydroperoxide formation, side-chain cleavage and eventually formation of short chain acids such as formic acid all of which could influence the stability of a biopharmaceutical product. Oxidation of the fatty acid moiety while well described in the literature has not been specifically investigated for polysorbate. This review focuses on the chemical structure of the polysorbates, factors influencing micelle formation and factors and excipients influencing stability and degradation of the polyoxyethylene and fatty acid ester linkages.

  7. Radiosensitization effect by combination with paclitaxel in vivo, including the effect on intratumor quiescent cells

    International Nuclear Information System (INIS)

    Masunaga, Shin-ichiro; Ono, Koji; Suzuki, Minoru; Nishimura, Yasumasa; Kinashi, Yuko; Takagaki, Masao; Hori, Hitoshi; Nagasawa, Hideko; Uto, Yoshihiro; Tsuchiya, Izumi; Sadahiro, Sotaro; Murayama, Chieko

    2001-01-01

    Purpose: To evaluate the radiosensitization effect on solid tumors upon combination treatment with paclitaxel (TXL), including the effect on intratumor quiescent (Q) cells. Methods and Materials: Mice bearing SCC VII or EL4 solid tumors received 5-bromo-2'-deoxyuridine (BrdU) continuously for 5 days to label all proliferating (P) cells. The mice then received γ-irradiation with or without tirapazamine (TPZ) at various time points after TXL administration. Another group of mice received a series of test doses of γ-rays while alive or after tumor clamping to obtain hypoxic fractions (HFs) in the tumors at various time points after TXL administration. Immediately after irradiation, the tumor cells were isolated and incubated with a cytokinesis blocker. The micronucleus (MN) frequency in cells without BrdU labeling (Q cells) was determined using immunofluorescence staining for BrdU. Meanwhile, 6 h after irradiation, the tumor cells were isolated from the solid tumors in another group of mice, and the apoptosis frequency in Q cells was also determined with immunofluorescence staining for BrdU. The MN and apoptosis frequency in total (P+Q) tumor cells were determined from the tumors that were not pretreated with BrdU. For the measurement of the HFs, the MN or apoptosis frequency of Q cells was then used to calculate the surviving fraction of Q cells from the regression line for the relationship between the MN or apoptosis frequency and the surviving fraction of total tumor cells. Results: In both SCC VII and EL4 tumors, maximum values of mitotic index (MI) and apoptosis frequency were observed 9 and 24 h after TXL administration, respectively. However, on the whole, the apoptosis frequency for SCC VII was very low. γ-Irradiation 9 h after TXL administration induced significant radiosensitization effects on the total cells of both tumors. Irradiation at 60 h had a more significant effect on total cells of EL4 tumor, but no significant effect on total cells of SCC VII

  8. Solar cells, structures including organometallic halide perovskite monocrystalline films, and methods of preparation thereof

    KAUST Repository

    Bakr, Osman M.

    2017-03-02

    Embodiments of the present disclosure provide for solar cells including an organometallic halide perovskite monocrystalline film (see fig. 1.1B), other devices including the organometallic halide perovskite monocrystalline film, methods of making organometallic halide perovskite monocrystalline film, and the like.

  9. Photoelectrochemical cell including Ga(Sb.sub.x)N.sub.1-x semiconductor electrode

    Science.gov (United States)

    Menon, Madhu; Sheetz, Michael; Sunkara, Mahendra Kumar; Pendyala, Chandrashekhar; Sunkara, Swathi; Jasinski, Jacek B.

    2017-09-05

    The composition of matter comprising Ga(Sb.sub.x)N.sub.1-x where x=0.01 to 0.06 is characterized by a band gap between 2.4 and 1.7 eV. A semiconductor device includes a semiconductor layer of that composition. A photoelectric cell includes that semiconductor device.

  10. Fabrication of contacts for silicon solar cells including printing burn through layers

    Science.gov (United States)

    Ginley, David S; Kaydanova, Tatiana; Miedaner, Alexander; Curtis, Calvin J; Van Hest, Marinus Franciscus Antonius Maria

    2014-06-24

    A method for fabricating a contact (240) for a solar cell (200). The method includes providing a solar cell substrate (210) with a surface that is covered or includes an antireflective coating (220). For example, the substrate (210) may be positioned adjacent or proximate to an outlet of an inkjet printer (712) or other deposition device. The method continues with forming a burn through layer (230) on the coating (220) by depositing a metal oxide precursor (e.g., using an inkjet or other non-contact printing method to print or apply a volume of liquid or solution containing the precursor). The method includes forming a contact layer (240) comprising silver over or on the burn through layer (230), and then annealing is performed to electrically connect the contact layer (240) to the surface of the solar cell substrate (210) through a portion of the burn through layer (230) and the coating (220).

  11. Canine ovarian neoplasms: a clinicopathologic study of 71 cases, including histology of 12 granulosa cell tumors.

    Science.gov (United States)

    Patnaik, A K; Greenlee, P G

    1987-11-01

    In a retrospective study of 71 primary ovarian tumors in the dog, epithelial tumors (46%) were more common than sex cord stromal (34%) and germ cell tumors (20%). There were more adenocarcinomas (64%) than adenomas. Sex cord stromal tumors were equally divided into Sertoli-Leydig (12/24) and granulosa cell tumors (12/24). There were equal numbers (7/14) of dysgerminomas and teratomas among the germ cell tumors. Most teratomas (6/7) were malignant. Most granulosa cell tumors were solid; two were mostly cystic. Patterns included sheets of round and ovoid to spindle-shaped cells separated by thin, fibrovascular stroma; neoplastic cells formed rosettes or Call-Exner bodies. In some areas, neoplastic cells were in cords or columns and formed cyst-like structures. Four granulosa cell tumors were macrofollicular, having cysts lined with granulosa cells. Median ages of dogs with different ovarian neoplasms were similar; all were more than 10 years old, except the dogs with teratoma (mean age, 4 years). Most neoplasms were unilateral (84%), except the Sertoli-Leydig cell tumors, many of which were bilateral (36%). Size of ovarian neoplasms varied (2 cm3 to 15,000 cm3). Twenty-nine percent of neoplasms metastasized; adenocarcinomas (48%) and malignant teratomas (50%) had the highest rates, and distant metastasis was more common in malignant teratoma. Endometrial hyperplasia was in 67% of the dogs; it was most common in dogs with sex cord stromal tumors (95%). Uterine malignancy was not seen in dogs with granulosa cell tumors, although hyperplasia endometrium was in all dogs with this tumor. Cysts in the contralateral ovaries were most common in dogs with sex cord stromal tumors.

  12. Universal cell frame for high-pressure water electrolyzer and electrolyzer including the same

    Science.gov (United States)

    Schmitt, Edwin W.; Norman, Timothy J.

    2013-01-08

    Universal cell frame generic for use as an anode frame and as a cathode frame in a water electrolyzer. According to one embodiment, the universal cell frame includes a unitary annular member having a central opening. Four trios of transverse openings are provided in the annular member, each trio being spaced apart by about 90 degrees. A plurality of internal radial passageways fluidly interconnect the central opening and each of the transverse openings of two diametrically-opposed trios of openings, the other two trios of openings lacking corresponding radial passageways. Sealing ribs are provided on the top and bottom surfaces of the annular member. The present invention is also directed at a water electrolyzer that includes two such cell frames, one being used as the anode frame and the other being used as the cathode frame, the cathode frame being rotated 90 degrees relative to the anode frame.

  13. Simulation of E. coli gene regulation including overlapping cell cycles, growth, division, time delays and noise.

    Directory of Open Access Journals (Sweden)

    Ruoyu Luo

    Full Text Available Due to the complexity of biological systems, simulation of biological networks is necessary but sometimes complicated. The classic stochastic simulation algorithm (SSA by Gillespie and its modified versions are widely used to simulate the stochastic dynamics of biochemical reaction systems. However, it has remained a challenge to implement accurate and efficient simulation algorithms for general reaction schemes in growing cells. Here, we present a modeling and simulation tool, called 'GeneCircuits', which is specifically developed to simulate gene-regulation in exponentially growing bacterial cells (such as E. coli with overlapping cell cycles. Our tool integrates three specific features of these cells that are not generally included in SSA tools: 1 the time delay between the regulation and synthesis of proteins that is due to transcription and translation processes; 2 cell cycle-dependent periodic changes of gene dosage; and 3 variations in the propensities of chemical reactions that have time-dependent reaction rates as a consequence of volume expansion and cell division. We give three biologically relevant examples to illustrate the use of our simulation tool in quantitative studies of systems biology and synthetic biology.

  14. Pediatric littoral cell angioma of the spleen: multimodality imaging including diffusion-weighted imaging

    Energy Technology Data Exchange (ETDEWEB)

    Ertan, Gulhan; Tekes, Aylin; Huisman, Thierry A.G.M. [Johns Hopkins Hospital, Division of Pediatric Radiology, Department of Radiology and Radiological Science, Baltimore, MD (United States); Mitchell, Sally [Johns Hopkins Hospital, Division of Cardiovascular and Interventional Radiology, Department of Radiology and Radiological Science, Baltimore (United States); Keefer, Jeffrey [Johns Hopkins Hospital, Division of Pediatric Hematology, Department of Pediatrics, Baltimore, MD (United States)

    2009-10-15

    Littoral cell angioma (LCA) is a rare primary splenic vascular tumor originating from littoral cells lining the splenic red pulp sinuses. LCAs are rarely seen in children. We present the US, CT, and MRI findings including diffusion-weighted imaging (DWI) in a 2-year-old boy with histologically proven LCA. Previous studies on liver lesions have shown that DWI allows differentiation of vascular tumors from primary neoplasms and metastatic disease. The current case indicates that increased ADC values within the splenic lesions suggest a vascular etiology, which might help narrow the differential diagnosis. (orig.)

  15. Pediatric littoral cell angioma of the spleen: multimodality imaging including diffusion-weighted imaging

    International Nuclear Information System (INIS)

    Ertan, Gulhan; Tekes, Aylin; Huisman, Thierry A.G.M.; Mitchell, Sally; Keefer, Jeffrey

    2009-01-01

    Littoral cell angioma (LCA) is a rare primary splenic vascular tumor originating from littoral cells lining the splenic red pulp sinuses. LCAs are rarely seen in children. We present the US, CT, and MRI findings including diffusion-weighted imaging (DWI) in a 2-year-old boy with histologically proven LCA. Previous studies on liver lesions have shown that DWI allows differentiation of vascular tumors from primary neoplasms and metastatic disease. The current case indicates that increased ADC values within the splenic lesions suggest a vascular etiology, which might help narrow the differential diagnosis. (orig.)

  16. Photovoltaic cell electrical heating system for removing snow on panel including verification.

    Science.gov (United States)

    Weiss, Agnes; Weiss, Helmut

    2017-11-16

    Small photovoltaic plants in private ownership are typically rated at 5 kW (peak). The panels are mounted on roofs at a decline angle of 20° to 45°. In winter time, a dense layer of snow at a width of e.g., 10 cm keeps off solar radiation from the photovoltaic cells for weeks under continental climate conditions. Practically, no energy is produced over the time of snow coverage. Only until outside air temperature has risen high enough for a rather long-time interval to allow partial melting of snow; the snow layer rushes down in an avalanche. Following this proposal, snow removal can be arranged electrically at an extremely positive energy balance in a fast way. A photovoltaic cell is a large junction area diode inside with a threshold voltage of about 0.6 to 0.7 V (depending on temperature). This forward voltage drop created by an externally driven current through the modules can be efficiently used to provide well-distributed heat dissipation at the cell and further on at the glass surface of the whole panel. The adhesion of snow on glass is widely reduced through this heating in case a thin water film can be produced by this external short time heating. Laboratory experiments provided a temperature increase through rated panel current of more than 10 °C within about 10 min. This heating can initiate the avalanche for snow removal on intention as described before provided the clamping effect on snow at the edge of the panel frame is overcome by an additional heating foil. Basics of internal cell heat production, heating thermal effects in time course, thermographic measurements on temperature distribution, power circuit opportunities including battery storage elements and snow-removal under practical conditions are described.

  17. A generic template for automated bioanalytical ligand-binding assays using modular robotic scripts in support of discovery biotherapeutic programs.

    Science.gov (United States)

    Duo, Jia; Dong, Huijin; DeSilva, Binodh; Zhang, Yan J

    2013-07-01

    Sample dilution and reagent pipetting are time-consuming steps in ligand-binding assays (LBAs). Traditional automation-assisted LBAs use assay-specific scripts that require labor-intensive script writing and user training. Five major script modules were developed on Tecan Freedom EVO liquid handling software to facilitate the automated sample preparation and LBA procedure: sample dilution, sample minimum required dilution, standard/QC minimum required dilution, standard/QC/sample addition, and reagent addition. The modular design of automation scripts allowed the users to assemble an automated assay with minimal script modification. The application of the template was demonstrated in three LBAs to support discovery biotherapeutic programs. The results demonstrated that the modular scripts provided the flexibility in adapting to various LBA formats and the significant time saving in script writing and scientist training. Data generated by the automated process were comparable to those by manual process while the bioanalytical productivity was significantly improved using the modular robotic scripts.

  18. Plasma Cell Neoplasms (Including Multiple Myeloma) Treatment (PDQ®)—Patient Version

    Science.gov (United States)

    Plasma cell neoplasms occur when abnormal plasma cells or myeloma cells form tumors in the bones or soft tissues of the body. Multiple myeloma, plasmacytoma, lymphoplasmacytic lymphoma, and monoclonal gammopathy of undetermined significance (MGUS) are different types of plasma cell neoplasms. Find out about risk factors, symptoms, diagnostic tests, prognosis, and treatment for these diseases.

  19. Analysis of electronic models for solar cells including energy resolved defect densities

    Energy Technology Data Exchange (ETDEWEB)

    Glitzky, Annegret

    2010-07-01

    We introduce an electronic model for solar cells including energy resolved defect densities. The resulting drift-diffusion model corresponds to a generalized van Roosbroeck system with additional source terms coupled with ODEs containing space and energy as parameters for all defect densities. The system has to be considered in heterostructures and with mixed boundary conditions from device simulation. We give a weak formulation of the problem. If the boundary data and the sources are compatible with thermodynamic equilibrium the free energy along solutions decays monotonously. In other cases it may be increasing, but we estimate its growth. We establish boundedness and uniqueness results and prove the existence of a weak solution. This is done by considering a regularized problem, showing its solvability and the boundedness of its solutions independent of the regularization level. (orig.)

  20. Development method of Hybrid Energy Storage System, including PEM fuel cell and a battery

    International Nuclear Information System (INIS)

    Ustinov, A; Khayrullina, A; Khmelik, M; Sveshnikova, A; Borzenko, V

    2016-01-01

    Development of fuel cell (FC) and hydrogen metal-hydride storage (MH) technologies continuously demonstrate higher efficiency rates and higher safety, as hydrogen is stored at low pressures of about 2 bar in a bounded state. A combination of a FC/MH system with an electrolyser, powered with a renewable source, allows creation of an almost fully autonomous power system, which could potentially replace a diesel-generator as a back-up power supply. However, the system must be extended with an electro-chemical battery to start-up the FC and compensate the electric load when FC fails to deliver the necessary power. Present paper delivers the results of experimental and theoretical investigation of a hybrid energy system, including a proton exchange membrane (PEM) FC, MH- accumulator and an electro-chemical battery, development methodology for such systems and the modelling of different battery types, using hardware-in-the-loop approach. The economic efficiency of the proposed solution is discussed using an example of power supply of a real town of Batamai in Russia. (paper)

  1. Development method of Hybrid Energy Storage System, including PEM fuel cell and a battery

    Science.gov (United States)

    Ustinov, A.; Khayrullina, A.; Borzenko, V.; Khmelik, M.; Sveshnikova, A.

    2016-09-01

    Development of fuel cell (FC) and hydrogen metal-hydride storage (MH) technologies continuously demonstrate higher efficiency rates and higher safety, as hydrogen is stored at low pressures of about 2 bar in a bounded state. A combination of a FC/MH system with an electrolyser, powered with a renewable source, allows creation of an almost fully autonomous power system, which could potentially replace a diesel-generator as a back-up power supply. However, the system must be extended with an electro-chemical battery to start-up the FC and compensate the electric load when FC fails to deliver the necessary power. Present paper delivers the results of experimental and theoretical investigation of a hybrid energy system, including a proton exchange membrane (PEM) FC, MH- accumulator and an electro-chemical battery, development methodology for such systems and the modelling of different battery types, using hardware-in-the-loop approach. The economic efficiency of the proposed solution is discussed using an example of power supply of a real town of Batamai in Russia.

  2. A practical algorithm for optimal operation management of distribution network including fuel cell power plants

    Energy Technology Data Exchange (ETDEWEB)

    Niknam, Taher; Meymand, Hamed Zeinoddini; Nayeripour, Majid [Electrical and Electronic Engineering Department, Shiraz University of Technology, Shiraz (Iran)

    2010-08-15

    Fuel cell power plants (FCPPs) have been taken into a great deal of consideration in recent years. The continuing growth of the power demand together with environmental constraints is increasing interest to use FCPPs in power system. Since FCPPs are usually connected to distribution network, the effect of FCPPs on distribution network is more than other sections of power system. One of the most important issues in distribution networks is optimal operation management (OOM) which can be affected by FCPPs. This paper proposes a new approach for optimal operation management of distribution networks including FCCPs. In the article, we consider the total electrical energy losses, the total electrical energy cost and the total emission as the objective functions which should be minimized. Whereas the optimal operation in distribution networks has a nonlinear mixed integer optimization problem, the optimal solution could be obtained through an evolutionary method. We use a new evolutionary algorithm based on Fuzzy Adaptive Particle Swarm Optimization (FAPSO) to solve the optimal operation problem and compare this method with Genetic Algorithm (GA), Particle Swarm Optimization (PSO), Differential Evolution (DE), Ant Colony Optimization (ACO) and Tabu Search (TS) over two distribution test feeders. (author)

  3. Inactivation of Ricin Toxin by Nanosecond Pulsed Electric Fields Including Evidences from Cell and Animal Toxicity

    Science.gov (United States)

    Wei, Kai; Li, Wei; Gao, Shan; Ji, Bin; Zang, Yating; Su, Bo; Wang, Kaile; Yao, Maosheng; Zhang, Jue; Wang, Jinglin

    2016-01-01

    Ricin is one of the most toxic and easily produced plant protein toxin extracted from the castor oil plant, and it has been classified as a chemical warfare agent. Here, nanosecond pulsed electric fields (nsPEFs) at 30 kV/cm (pulse durations: 10 ns, 100 ns, and 300 ns) were applied to inactivating ricin up to 4.2 μg/mL. To investigate the efficacy, cells and mice were tested against the ricin treated by the nsPEFs via direct intraperitoneal injection and inhalation exposure. Results showed that nsPEFs treatments can effectively reduce the toxicity of the ricin. Without the nsPEFs treatment, 100% of mice were killed upon the 4 μg ricin injection on the first day, however 40% of the mice survived the ricin treated by the nsPEFs. Compared to injection, inhalation exposure even with higher ricin dose required longer time to observe mice fatality. Pathological observations revealed damages to heart, lung, kidney, and stomach after the ricin exposure, more pronounced for lung and kidney including severe bleeding. Sodium dodecyl sulfate polyacrylamide gel electrophoresis(SDS-PAGE) and circular dichroism (CD) analyses revealed that although the primary structure of ricin was not altered, its secondary structures (beta-sheet and beta-turn) underwent transition upon the nsPEFs treatment. PMID:26728251

  4. Insect biofuel cells using trehalose included in insect hemolymph leading to an insect-mountable biofuel cell.

    Science.gov (United States)

    Shoji, Kan; Akiyama, Yoshitake; Suzuki, Masato; Hoshino, Takayuki; Nakamura, Nobuhumi; Ohno, Hiroyuki; Morishima, Keisuke

    2012-12-01

    In this paper, an insect biofuel cell (BFC) using trehalose included in insect hemolymph was developed. The insect BFC is based on trehalase and glucose oxidase (GOD) reaction systems which oxidize β-glucose obtained by hydrolyzing trehalose. First, we confirmed by LC-MS that a sufficient amount of trehalose was present in the cockroach hemolymph (CHL). The maximum power density obtained using the insect BFC was 6.07 μW/cm(2). The power output was kept more than 10 % for 2.5 h by protecting the electrodes with a dialysis membrane. Furthermore, the maximum power density was increased to 10.5 μW/cm(2) by using an air diffusion cathode. Finally, we succeeded in driving a melody integrated circuit (IC) and a piezo speaker by connecting five insect BFCs in series. The results indicate that the insect BFC is a promising insect-mountable battery to power environmental monitoring micro-tools.

  5. Hardware-in-the-loop vehicle system including dynamic fuel cell model

    Energy Technology Data Exchange (ETDEWEB)

    Lemes, Z.; Lenhart, T.; Braun, M.; Maencher, H. [MAGNUM Automatisierungstechnik GmbH, Darmstadt (Germany)

    2005-07-01

    In order to reduce costs and accelerate the development of fuel cells and systems the usage of hardware-in-the-loop (HIL) testing and dynamic modelling opens new possibilities. The dynamic model of a proton exchange membrane fuel cell (PEMFC) together with a vehicle model is used to carry out a comprehensive system investigation, which allows designing and optimising the behaviour of the components and the entire fuel cell system. The set-up of a HIL system enables real time interaction between the selected hardware and the model. (orig.)

  6. The role of ECToolbox software in evaluating bio-therapeutic effect on acute myocardial infarct of pig modal

    International Nuclear Information System (INIS)

    Zou Renjian; Meng Shu; Fu Hongliang; Wu Jingchuan; Wang Hui

    2009-01-01

    Objective: The aim of this study was to estimate the role of ECToolbox software in evaluating the bio-therapeutic effect on acute myocardial infarction of pig model by angiopoietin-related protein 2 (Ad. ARP2). Methods: Sixteen acute myocardial infarction pigs were divided into groups A and B. Group A was intra-myocardial injected with Ad. ARP2 gene and group B was control with intra-myocardial injected of saline. Gated myocardial perfusion imaging was performed one and four weeks after the injection. To evaluate the bio-therapeutic effect, data was acquired and analyzed qualitatively and quantitatively with ECToolbox to observe the territory, extent and severity of myocardial defect. SPSS 10.0 was used for the statistical analysis. By applying the scoring system for each segment of the 20-segments model to the myocardial perfusion images, a mean score could be derived. Comparisons for the data of one and four weeks after the injection in the same group were made with the paired t-test, and for the data of different groups were made with t-test. Results: (1) The mean score of ischemic lateral wall was 1.99±0.85 and 1.71±0.85 respectively at one and four weeks after the injection. The mean score of ischemic inferior wall was 1.86±0.67 and 1.65±0.73 respectively. (2) The radioactivity ratios of defect area to the whole left ventricle in the first week and the fourth week were 25.75±7.16 and 31.57±5.64 on the short axis (t=3.83, P<0.01), 30.55±4.80 and 36.03± 6.27 on the vertical long axis (t=3.71, P<0.01), 25.03±2.65 and 27.42±3.48 on horizontal long axis (t= 2.88, P<0.01). (3) Polar maps showed myocardial defect extent of the fourth week was smaller than that of the first week. The percentage of defect area to the whole left ventricle in the first and fourth week was (16.58±5.78)% and (12.66±4.90)%. (4) Mean left ventricular eject fraction (LVEF) of group A was (43.99±5.96)% and (61.03±8.74)% respectively after one and four weeks. Conclusions: Bio

  7. HLA-DRB1*16-restricted recognition of myeloid cells, including CD34+ CML progenitor cells

    NARCIS (Netherlands)

    Ebeling, Saskia B.; Ivanov, Roman; Hol, Samantha; Aarts, Tineke I.; Hagenbeek, Anton; Verdonck, Leo F.; Petersen, Eefke J.

    2003-01-01

    The therapeutic effect of a human leucocyte antigen (HLA)-identical allogeneic stem cell transplantation (allo-SCT) for the treatment of haematological malignancies is mediated partly by the allogeneic T cells that are administered together with the stem cell graft. Chronic myeloid leukaemia (CML)

  8. Development of Microencapsulation Delivery System for Long-Term Preservation of Probiotics as Biotherapeutics Agent

    Science.gov (United States)

    Solanki, Himanshu K.; Pawar, Dipak D.; Shah, Dushyant A.; Prajapati, Vipul D.; Jani, Girish K.; Mulla, Akil M.; Thakar, Prachi M.

    2013-01-01

    The administration of probiotic bacteria for health benefit has rapidly expanded in recent years, with a global market worth $32.6 billion predicted by 2014. The oral administration of most of the probiotics results in the lack of ability to survive in a high proportion of the harsh conditions of acidity and bile concentration commonly encountered in the gastrointestinal tract of humans. Providing probiotic living cells with a physical barrier against adverse environmental conditions is therefore an approach currently receiving considerable interest. Probiotic encapsulation technology has the potential to protect microorganisms and to deliver them into the gut. However, there are still many challenges to overcome with respect to the microencapsulation process and the conditions prevailing in the gut. This review focuses mainly on the methodological approach of probiotic encapsulation including biomaterials selection and choice of appropriate technology in detailed manner. PMID:24027760

  9. Subretinal Pigment Epithelial Deposition of Drusen Components Including Hydroxyapatite in a Primary Cell Culture Model.

    Science.gov (United States)

    Pilgrim, Matthew G; Lengyel, Imre; Lanzirotti, Antonio; Newville, Matt; Fearn, Sarah; Emri, Eszter; Knowles, Jonathan C; Messinger, Jeffrey D; Read, Russell W; Guidry, Clyde; Curcio, Christine A

    2017-02-01

    Extracellular deposits containing hydroxyapatite, lipids, proteins, and trace metals that form between the basal lamina of the RPE and the inner collagenous layer of Bruch's membrane are hallmarks of early AMD. We examined whether cultured RPE cells could produce extracellular deposits containing all of these molecular components. Retinal pigment epithelium cells isolated from freshly enucleated porcine eyes were cultured on Transwell membranes for up to 6 months. Deposit composition and structure were characterized using light, fluorescence, and electron microscopy; synchrotron x-ray diffraction and x-ray fluorescence; secondary ion mass spectroscopy; and immunohistochemistry. Apparently functional primary RPE cells, when cultured on 10-μm-thick inserts with 0.4-μm-diameter pores, can produce sub-RPE deposits that contain hydroxyapatite, lipids, proteins, and trace elements, without outer segment supplementation, by 12 weeks. The data suggest that sub-RPE deposit formation is initiated, and probably regulated, by the RPE, as well as the loss of permeability of the Bruch's membrane and choriocapillaris complex associated with age and early AMD. This cell culture model of early AMD lesions provides a novel system for testing new therapeutic interventions against sub-RPE deposit formation, an event occurring well in advance of the onset of vision loss.

  10. Fabrication of Polymer Solar Cells Using Aqueous Processing for All Layers Including the Metal Back Electrode

    DEFF Research Database (Denmark)

    Søndergaard, Roar; Helgesen, Martin; Jørgensen, Mikkel

    2011-01-01

    The challenges of printing all layers in polymer solar cells from aqueous solution are met by design of inks for the electron-, hole-, active-, and metallic back electrode-layers. The conversion of each layer to an insoluble state after printing enables multilayer formation from the same solvent...

  11. Thermodynamic Modeling and Dispatch of Distributed Energy Technologies including Fuel Cell -- Gas Turbine Hybrids

    Science.gov (United States)

    McLarty, Dustin Fogle

    Distributed energy systems are a promising means by which to reduce both emissions and costs. Continuous generators must be responsive and highly efficiency to support building dynamics and intermittent on-site renewable power. Fuel cell -- gas turbine hybrids (FC/GT) are fuel-flexible generators capable of ultra-high efficiency, ultra-low emissions, and rapid power response. This work undertakes a detailed study of the electrochemistry, chemistry and mechanical dynamics governing the complex interaction between the individual systems in such a highly coupled hybrid arrangement. The mechanisms leading to the compressor stall/surge phenomena are studied for the increased risk posed to particular hybrid configurations. A novel fuel cell modeling method introduced captures various spatial resolutions, flow geometries, stack configurations and novel heat transfer pathways. Several promising hybrid configurations are analyzed throughout the work and a sensitivity analysis of seven design parameters is conducted. A simple estimating method is introduced for the combined system efficiency of a fuel cell and a turbine using component performance specifications. Existing solid oxide fuel cell technology is capable of hybrid efficiencies greater than 75% (LHV) operating on natural gas, and existing molten carbonate systems greater than 70% (LHV). A dynamic model is calibrated to accurately capture the physical coupling of a FC/GT demonstrator tested at UC Irvine. The 2900 hour experiment highlighted the sensitivity to small perturbations and a need for additional control development. Further sensitivity studies outlined the responsiveness and limits of different control approaches. The capability for substantial turn-down and load following through speed control and flow bypass with minimal impact on internal fuel cell thermal distribution is particularly promising to meet local demands or provide dispatchable support for renewable power. Advanced control and dispatch

  12. A review of cell-scale multiphase flow modeling, including water management, in polymer electrolyte fuel cells

    International Nuclear Information System (INIS)

    Andersson, M.; Beale, S.B.; Espinoza, M.; Wu, Z.; Lehnert, W.

    2016-01-01

    on the transport processes inside the porous GDL are extensively discussed. The selection of a computational approach, for the two-phase flow within a GDL or GC, for example, should be based on the computational resources available, concerns about time and scale (microscale, cell scale, stack scale or system scale), as well as accuracy requirements. One important feature, included in some computational approaches, is the possibility to track the front between the liquid and the gas phases. To build a PEFC model, one must make a large number of assumptions. Some assumptions have a negligible effect on the results and reliability of the model. However, other assumptions may significantly affect the result. It is strongly recommended in any modeling paper to clearly state the assumptions being implemented, for others to be able to judge the work. It is important to note that a large fraction of the expressions that presently are used to describe the transport processes inside PEFC GDLs were originally developed to describe significantly different systems, such as sand or rocks. Moreover, the flow pattern maps and pressure drop correlations of two phase flow in micro channels may not be applicable for GCs due to one side wall being porous, with the resulting interaction between the GDL and GC.

  13. Cancer risks related to low-level RF/MW exposures, including cell phones.

    Science.gov (United States)

    Szmigielski, Stanislaw

    2013-09-01

    For years, radiofrequency (RF) and microwave (MW) radiations have been applied in the modern world. The rapidly increasing use of cellular phones called recent attention to the possible health risks of RF/MW exposures. In 2011, a group of international experts organized by IARC (International Agency for Research on Cancer in Lyon) concluded that RF/MW radiations should be listed as a possible carcinogen (group 2B) for humans. Three meta-analyses of case-control studies have concluded that using cell phones for more than ten years was associated with an increase in the overall risk of developing a brain tumor. The Interphone Study, the largest health-related case-control international study of use of cell phones and head and neck tumors, showed no statistically significant increases in brain cancers related to higher amounts of cell phone use, but excess risk in a small subgroup of more heavily exposed users associated with latency and laterality was reported. So far, the published studies do not show that mobile phones could for sure increase the risk of cancer. This conclusion is based on the lack of a solid biological mechanism, and the fact that brain cancer rates are not going up significantly. However, all of the studies so far have weaknesses, which make it impossible to entirely rule out a risk. Mobile phones are still a new technology and there is little evidence about effects of long-term use. For this reason, bioelectromagnetic experts advise application of a precautionary resources. It suggests that if people want to use a cell phone, they can choose to minimize their exposure by keeping calls short and preferably using hand-held sets. It also advises discouraging children from making non essential calls as well as also keeping their calls short.

  14. Reduced Toxicity Fuel Satellite Propulsion System Including Fuel Cell Reformer with Alcohols Such as Methanol

    Science.gov (United States)

    Schneider, Steven J. (Inventor)

    2001-01-01

    A reduced toxicity fuel satellite propulsion system including a reduced toxicity propellant supply for consumption in an axial class thruster and an ACS class thruster. The system includes suitable valves and conduits for supplying the reduced toxicity propellant to the ACS decomposing element of an ACS thruster. The ACS decomposing element is operative to decompose the reduced toxicity propellant into hot propulsive gases. In addition the system includes suitable valves and conduits for supplying the reduced toxicity propellant to an axial decomposing element of the axial thruster. The axial decomposing element is operative to decompose the reduced toxicity propellant into hot gases. The system further includes suitable valves and conduits for supplying a second propellant to a combustion chamber of the axial thruster, whereby the hot gases and the second propellant auto-ignite and begin the combustion process for producing thrust.

  15. Consensus for nonmelanoma skin cancer treatment: basal cell carcinoma, including a cost analysis of treatment methods.

    Science.gov (United States)

    Kauvar, Arielle N B; Cronin, Terrence; Roenigk, Randall; Hruza, George; Bennett, Richard

    2015-05-01

    Basal cell carcinoma (BCC) is the most common cancer in the US population affecting approximately 2.8 million people per year. Basal cell carcinomas are usually slow-growing and rarely metastasize, but they do cause localized tissue destruction, compromised function, and cosmetic disfigurement. To provide clinicians with guidelines for the management of BCC based on evidence from a comprehensive literature review, and consensus among the authors. An extensive review of the medical literature was conducted to evaluate the optimal treatment methods for cutaneous BCC, taking into consideration cure rates, recurrence rates, aesthetic and functional outcomes, and cost-effectiveness of the procedures. Surgical approaches provide the best outcomes for BCCs. Mohs micrographic surgery provides the highest cure rates while maximizing tissue preservation, maintenance of function, and cosmesis. Mohs micrographic surgery is an efficient and cost-effective procedure and remains the treatment of choice for high-risk BCCs and for those in cosmetically sensitive locations. Nonsurgical modalities may be used for low-risk BCCs when surgery is contraindicated or impractical, but the cure rates are lower.

  16. Early lymphocyte recovery as a predictor of outcome, including relapse, after hematopoieticstem cell transplantation

    Directory of Open Access Journals (Sweden)

    Juliane Morando

    2012-01-01

    Full Text Available BACKGROUND: Despite advances in the treatment of acute leukemia, many patients need to undergo hematopoietic stem cell transplantation. Recent studies show that early lymphocyte recovery may be a predictor of relapse and survival in these patients. OBJECTIVE: To analyze the influence of lymphocyte recovery on Days +30 and +100 post-transplant on the occurrence of relapse and survival. METHODS: A descriptive, retrospective study was performed of 137 under 21-year-old patients who were submitted to hematopoietic stem cell transplantation for acute leukemia between 1995 and 2008. A lymphocyte count 0.3 x 10(9/L were considered adequate. Lymphocyte recovery was also analyzed on Day +100 with < 0.75 x 10(9/Land < 0.75 x 10(9/L being considered inadequate and adequate lymphocyte recovery, respectively. RESULTS: There was no significant difference in the occurrence of relapse between patients with inadequate and adequate lymphocyte recovery on Day +30 post-transplant. However, the transplant-related mortality was significantly higher in patients with inadequate recovery on Day +30. Patients with inadequate lymphocyte recovery on Day +30 had worse overall survival and relapse-free survival than patients with adequate recovery. There was no significant difference in the occurrence of infections and acute or chronic graft-versus-host disease. Patients with inadequate lymphocyte recovery on Day +100 had worse overall survival and relapse-free survival and a higher cumulative incidence of relapse. CONCLUSION: The evaluation of lymphocyte recovery on Day +30 is not a good predictor of relapse after transplant however patients with inadequate lymphocyte recovery had worse overall survival and relapse-free survival. Inadequate lymphocyte recovery on Day +100 is correlated with higher cumulative relapse as well as lower overall survival and relapse-free survival.

  17. Method of preparing a negative electrode including lithium alloy for use within a secondary electrochemical cell

    Science.gov (United States)

    Tomczuk, Zygmunt; Olszanski, Theodore W.; Battles, James E.

    1977-03-08

    A negative electrode that includes a lithium alloy as active material is prepared by briefly submerging a porous, electrically conductive substrate within a melt of the alloy. Prior to solidification, excess melt can be removed by vibrating or otherwise manipulating the filled substrate to expose interstitial surfaces. Electrodes of such as solid lithium-aluminum filled within a substrate of metal foam are provided.

  18. Model-based analysis of N-glycosylation in Chinese hamster ovary cells

    DEFF Research Database (Denmark)

    Krambeck, Frederick J.; Bennun, Sandra V; Andersen, Mikael Rørdam

    2017-01-01

    The Chinese hamster ovary (CHO) cell is the gold standard for manufacturing of glycosylated recombinant proteins for production of biotherapeutics. The similarity of its glycosylation patterns to the human versions enable the products of this cell line favorable pharmacokinetic properties and lower...

  19. Microencapsulation for the Therapeutic Delivery of Drugs, Live Mammalian and Bacterial Cells, and Other Biopharmaceutics: Current Status and Future Directions

    Directory of Open Access Journals (Sweden)

    Catherine Tomaro-Duchesneau

    2013-01-01

    Full Text Available Microencapsulation is a technology that has shown significant promise in biotherapeutics, and other applications. It has been proven useful in the immobilization of drugs, live mammalian and bacterial cells and other cells, and other biopharmaceutics molecules, as it can provide material structuration, protection of the enclosed product, and controlled release of the encapsulated contents, all of which can ensure efficient and safe therapeutic effects. This paper is a comprehensive review of microencapsulation and its latest developments in the field. It provides a comprehensive overview of the technology and primary goals of microencapsulation and discusses various processes and techniques involved in microencapsulation including physical, chemical, physicochemical, and other methods involved. It also summarizes the state-of-the-art successes of microencapsulation, specifically with regard to the encapsulation of microorganisms, mammalian cells, drugs, and other biopharmaceutics in various diseases. The limitations and future directions of microencapsulation technologies are also discussed.

  20. Microencapsulation for the Therapeutic Delivery of Drugs, Live Mammalian and Bacterial Cells, and Other Biopharmaceutics: Current Status and Future Directions

    Science.gov (United States)

    Saha, Shyamali; Malhotra, Meenakshi; Kahouli, Imen; Prakash, Satya

    2013-01-01

    Microencapsulation is a technology that has shown significant promise in biotherapeutics, and other applications. It has been proven useful in the immobilization of drugs, live mammalian and bacterial cells and other cells, and other biopharmaceutics molecules, as it can provide material structuration, protection of the enclosed product, and controlled release of the encapsulated contents, all of which can ensure efficient and safe therapeutic effects. This paper is a comprehensive review of microencapsulation and its latest developments in the field. It provides a comprehensive overview of the technology and primary goals of microencapsulation and discusses various processes and techniques involved in microencapsulation including physical, chemical, physicochemical, and other methods involved. It also summarizes the state-of-the-art successes of microencapsulation, specifically with regard to the encapsulation of microorganisms, mammalian cells, drugs, and other biopharmaceutics in various diseases. The limitations and future directions of microencapsulation technologies are also discussed. PMID:26555963

  1. Evaluation of pre-existing antibody presence as a risk factor for posttreatment anti-drug antibody induction: analysis of human clinical study data for multiple biotherapeutics.

    Science.gov (United States)

    Xue, Li; Rup, Bonita

    2013-07-01

    Biotherapeutic-reactive antibodies in treatment-naïve subjects (i.e., pre-existing antibodies) have been commonly detected during clinical immunogenicity assessments; however information on pre-existing antibody prevalence, physiological effects, and impact on posttreatment anti-drug antibody (ADA) induction remains limited. In this analysis, pre-existing antibody prevalence and impact on posttreatment ADA induction were determined using ADA data from 12 biotherapeutics analyzed in 32 clinical studies. Approximately half (58%) of the biotherapeutics were associated with some level of pre-existing antibodies and 67% of those were associated with posttreatment ADA induction. Across all studies, 5.6% of study subjects demonstrated presence of pre-existing antibodies, among which, 17% of the individual subjects had posttreatment increases in their ADA titers while 16% had decreased titers and 67% had no change in titers. However, in studies conducted in the rheumatoid arthritis (RA) population, 14.8% of RA patients were associated with pre-existing antibodies and 30% of those had posttreatment titer increases. The results suggest that in most study subjects, pre-existing antibodies pose a low risk for posttreatment ADA induction. That said, the high risk of induction implicated for RA patients, primarily observed in treatments evaluating novel antibody-based constructs, indicates that further understanding of the contribution of product and disease-specific factors is needed. Cross-industry efforts to collect and analyze a larger data set would enhance understanding of the prevalence, nature, and physiological consequences of pre-existing antibodies, better inform the immunogenicity risk profiles of products associated with these antibodies and lead to better fit-for-purpose immunogenicity management and mitigation strategies.

  2. Dynamic model of a micro-tubular solid oxide fuel cell stack including an integrated cooling system

    Science.gov (United States)

    Hering, Martin; Brouwer, Jacob; Winkler, Wolfgang

    2017-02-01

    A novel dynamic micro-tubular solid oxide fuel cell (MT-SOFC) and stack model including an integrated cooling system is developed using a quasi three-dimensional, spatially resolved, transient thermodynamic, physical and electrochemical model that accounts for the complex geometrical relations between the cells and cooling-tubes. The modeling approach includes a simplified tubular geometry and stack design including an integrated cooling structure, detailed pressure drop and gas property calculations, the electrical and physical constraints of the stack design that determine the current, as well as control strategies for the temperature. Moreover, an advanced heat transfer balance with detailed radiative heat transfer between the cells and the integrated cooling-tubes, convective heat transfer between the gas flows and the surrounding structures and conductive heat transfer between the solid structures inside of the stack, is included. The detailed model can be used as a design basis for the novel MT-SOFC stack assembly including an integrated cooling system, as well as for the development of a dynamic system control strategy. The evaluated best-case design achieves very high electrical efficiency between around 75 and 55% in the entire power density range between 50 and 550 mW /cm2 due to the novel stack design comprising an integrated cooling structure.

  3. Electrolyte for a lithium/thionyl chloride electric cell, a method of preparing said electrolyte and an electric cell which includes said electrolyte

    Energy Technology Data Exchange (ETDEWEB)

    Gabano, J.

    1983-03-01

    An electrolyte for an electric cell whose negative active material is constituted by lithium and whose positive active material is constituted by thionyl chloride. The electrolyte contains at least one solvent and at least one solute, said solvent being thionyl chloride and said solute being chosen from the group which includes lithium tetrachloroaluminate and lithium hexachloroantimonate. According to the invention said electrolyte further includes a complex chosen from the group which includes AlCl/sub 3/,SO/sub 2/ and SbCl/sub 5/,SO/sub 2/. The voltage rise of electric cells which include such an electrolyte takes negligible time.

  4. 76 FR 33298 - Grifols, S.A. and Talecris Biotherapeutics Holdings Corp.; Analysis of Agreement Containing...

    Science.gov (United States)

    2011-06-08

    ... consent agreement, and the allegations in the complaint. An electronic copy of the full text of the... Kedrion S.p.A. (``Kedrion''); (ii) divest plasma collection centers to Kedrion; (iii) divest to Kedrion Talecris' Koate DVI plasma-derived Factor VIII (``pdFVIII'') business, including the Koate brand name, in...

  5. Analysis of myelomonocytic leukemic differentiation by a cell surface marker panel including a fucose-binding lectin from Lotus tetragonolobus.

    Science.gov (United States)

    Elias, L; Van Epps, D E

    1984-06-01

    The fucose-binding lectin from Lotus tetragonolobus ( FBL -L) has been previously shown to bind specifically to normal cells of the myeloid and monocytic lineages. The purpose of this study was to explore the utility of fluoresceinated FBL -L as a leukemia differentiation marker in conjunction with a panel of other frequently used surface markers (Fc receptor, HLA-DR, OKM1, and antimonocyte antibody). FBL -L reacted with leukemic cells in 8/9 cases of clinically recognized acute myeloid leukemia, including myeloid blast crisis of chronic granulocytic leukemia, 3/3 cases of chronic phase chronic myelogenous leukemia, and in 2/7 cases of clinically undifferentiated acute leukemia. Correlations were noted between reactivity with FBL -L, and DR and Fc receptor expression. Among continuous cell lines, FBL -L bound with high intensity to a majority of HL-60 and U937 cells. The less well differentiated myeloblast cell lines, KG-1, KG1a , and HL-60 blast II, exhibited less FBL -L binding than HL-60 and U937. A moderate proportion of K562 cells exhibited low level binding of FBL -L. Several lymphoblastic cell lines exhibited a pattern of low intensity binding that was distinguishable from the high intensity binding pattern of the myeloblastic lines. FBL -L reactivity of U937 was enhanced by induction of differentiation with leukocyte conditioned medium, but not dimethylsulfoxide. Such treatments induced contrasting patterns of change of HL-60 and U937 when labeled with OKM1, alpha-Mono, and HLA-DR. These studies demonstrate the application of FBL -L to analysis and quantitation of myelomonocytic leukemic differentiation.

  6. Adipogenic differentiation by adipose-derived stem cells harvested from GFP transgenic mice - including relationship of sex differences

    International Nuclear Information System (INIS)

    Ogawa, Rei; Mizuno, Hiroshi; Watanabe, Atsushi; Migita, Makoto; Hyakusoku, Hiko; Shimada, Takashi

    2004-01-01

    We have previously demonstrated that adipose-derived stromal cells (ASCs) as well as bone marrow-derived stromal cells (BSCs) differentiate into a variety of cell lineages both in vitro and in vivo. Both types are considered to include mesenchymal stem cells. Taking advantage of homogeneously marked cells from green fluorescent protein (GFP) transgenic mice, we have also previously reported the plasticity of BSCs and ASCs. In this study, we focused on adipogenic differentiation in vitro by ASCs harvested from GFP transgenic mice. Moreover, preadipocytes and mature adipocytes were harvested at the same time, and the cells were cultured to compare them with ASCs. Inguinal fat pads from GFP transgenic mice were used for the isolation of ASCs, preadipocytes, and mature adipocytes. After expansion to three passages of ASCs, the cells were incubated in an adipogenic medium for two weeks. Adipogenic differentiation of ASCs was assessed by Oil Red O staining and the expression of the adipocyte specific peroxisome proliferative activated receptor γ2 (PPAR-γ2) gene. These ASCs stained positively, and expression of PPAR-γ2 was detected. Moreover, we also tried to characterize the influence of sex differences on the adipogenic differentiation of ASCs harvested from both male and female mice. This was assessed by the expression levels of the PPAR-γ2 gene using real-time PCR. The results showed that the expression levels of ASCs harvested from female mice were a maximum of 2.89 times greater than those harvested from male mice. This suggests that the adipogenic differentiation of ASCs is closely related to sex differences

  7. Impact of cell lines included in enterovirus isolation protocol on perception of nonpolio enterovirus species C diversity.

    Science.gov (United States)

    Adeniji, Johnson Adekunle; Faleye, Temitope Oluwasegun Cephas

    2014-10-01

    There has been under-reporting of nonpolio enterovirus species Cs (NPESCs) in Nigeria despite the fact that most isolates recovered from the Nigerian vaccine derived poliovirus serotype 2 (VDPV2) outbreak were recombinants with nonstructural region of NPESC origin. It has been suggested that cell lines included in enterovirus isolation protocols might account for this phenomenon and this study examined this suggestion. Fifteen environmental samples concentrated previously and analysed using L20B and RD cell lines as part of the poliovirus environmental surveillance (ES) program in Nigeria were randomly selected and inoculated into two cell lines (MCF-7 and LLC-MK2). Isolates were identified as enteroviruses and species C members using different RT-PCR assays, culture in L20B cell line and sequencing of partial VP1. Forty-eight (48) isolates were recovered from the 15 samples, 47 (97.9%) of which were enteroviruses. Of the enteroviruses, 32 (68.1%) belonged to enterovirus species C (EC) of which 19 (40.4%) were polioviruses and 13 (27.7%) were NPESC members. All 13 NPESC isolates were recovered on MCF-7. Results of the study show that NPESCs are circulating in Nigeria and their under-reporting was due to the combination of cell lines used for enterovirus isolation in previous reports. Copyright © 2014 Elsevier B.V. All rights reserved.

  8. Myeloid-derived suppressor cells in murine AIDS inhibit B-cell responses in part via soluble mediators including reactive oxygen and nitrogen species, and TGF-β

    Energy Technology Data Exchange (ETDEWEB)

    Rastad, Jessica L. [Department of Microbiology and Immunology, Geisel School of Medicine at Dartmouth, Lebanon, NH 03756 (United States); Green, William R., E-mail: William.R.Green@dartmouth.edu [Department of Microbiology and Immunology, Geisel School of Medicine at Dartmouth, Lebanon, NH 03756 (United States); Norris Cotton Cancer Center, Geisel School of Medicine at Dartmouth, Lebanon, NH 03756 (United States)

    2016-12-15

    Monocytic myeloid-derived suppressor cells (M-MDSCs) were increased during LP-BM5 retroviral infection, and were capable of suppressing not only T-cell, but also B-cell responses. In addition to previously demonstrating iNOS- and VISTA-dependent M-MDSC mechanisms, in this paper, we detail how M-MDSCs utilized soluble mediators, including the reactive oxygen and nitrogen species superoxide, peroxynitrite, and nitric oxide, and TGF-β, to suppress B cells in a predominantly contact-independent manner. Suppression was independent of cysteine-depletion and hydrogen peroxide production. When two major mechanisms of suppression (iNOS and VISTA) were eliminated in double knockout mice, M-MDSCs from LP-BM5-infected mice were able to compensate using other, soluble mechanisms in order to maintain suppression of B cells. The IL-10 producing regulatory B-cell compartment was among the targets of M-MDSC-mediated suppression. -- Highlights: •LP-BM5-expanded M-MDSCs utilized soluble mediators nitric oxide, superoxide, peroxynitrite, and TGF-β to suppress B cells. •When two major mechanisms of suppression were eliminated through knockouts, M-MDSCs maintained suppression. •M-MDSCs from LP-BM5-infected mice decreased proliferation of IL-10 producing regulatory B cells.

  9. Myeloid-derived suppressor cells in murine AIDS inhibit B-cell responses in part via soluble mediators including reactive oxygen and nitrogen species, and TGF-β

    International Nuclear Information System (INIS)

    Rastad, Jessica L.; Green, William R.

    2016-01-01

    Monocytic myeloid-derived suppressor cells (M-MDSCs) were increased during LP-BM5 retroviral infection, and were capable of suppressing not only T-cell, but also B-cell responses. In addition to previously demonstrating iNOS- and VISTA-dependent M-MDSC mechanisms, in this paper, we detail how M-MDSCs utilized soluble mediators, including the reactive oxygen and nitrogen species superoxide, peroxynitrite, and nitric oxide, and TGF-β, to suppress B cells in a predominantly contact-independent manner. Suppression was independent of cysteine-depletion and hydrogen peroxide production. When two major mechanisms of suppression (iNOS and VISTA) were eliminated in double knockout mice, M-MDSCs from LP-BM5-infected mice were able to compensate using other, soluble mechanisms in order to maintain suppression of B cells. The IL-10 producing regulatory B-cell compartment was among the targets of M-MDSC-mediated suppression. -- Highlights: •LP-BM5-expanded M-MDSCs utilized soluble mediators nitric oxide, superoxide, peroxynitrite, and TGF-β to suppress B cells. •When two major mechanisms of suppression were eliminated through knockouts, M-MDSCs maintained suppression. •M-MDSCs from LP-BM5-infected mice decreased proliferation of IL-10 producing regulatory B cells.

  10. The cell death factor, cell wall elicitor of rice blast fungus (Magnaporthe grisea) causes metabolic alterations including GABA shunt in rice cultured cells

    OpenAIRE

    Takahashi, Hideyuki; Matsumura, Hideo; Kawai-Yamada, Maki; Uchimiya, Hirofumi

    2008-01-01

    An elicitor derived from the cell wall of rice blast fungus (Magnaporthe grisea) causes cell death in suspension cultured cells of rice (Oryza sativa L.). To elucidate the role of M. grisea elicitor on metabolic pathway of rice cells, we performed metabolite profiling using capillary electrophoresis-mass spectrometry (CE/MS). Treatment with M. grisea elicitor increased the amounts of antioxidants and free amino acids and decreased the amount of metabolites in the tricarboxylic acid (TCA) cycl...

  11. Low Frequencies of Autoimmunity-Associated PTPN22 Polymorphisms in MODY Patients, Including Those Transiently Expressing Islet Cell Autoantibodies.

    Science.gov (United States)

    Heneberg, Petr; Malá, Milena; Yorifuji, Tohru; Gat-Yablonski, Galia; Lebenthal, Yael; Tajima, Toshihiro; Nogaroto, Viviane; Rypáčková, Blanka; Kocková, Lucie; Urbanová, Jana; Anděl, Michal

    2015-01-01

    The protein tyrosine phosphatase nonreceptor type 22 (PTPN22) gene encodes lymphoid tyrosine phosphatase (LYP), which is expressed primarily in lymphoid tissues. The functional but geographically highly variable PTPN22 single-nucleotide polymorphisms (SNPs), particularly c.1858C>T, contribute to the onset and progression of autoimmunity-associated diseases and facilitate the expression of disease-associated autoantibodies. In Central Europe, 17-25% of patients with monogenic diabetes (maturity-onset diabetes of the young, MODY) transiently express islet cell autoantibodies. We addressed the links between the functional and geographically variable PTPN22 SNPs with MODY manifestation and the expression of islet cell autoantibodies in 276 MODY patients who originated from four regions (the Czech Republic, Israel, Japan and Brazil). The frequency of PTPN22 polymorphisms in the MODY patients was similar to those in geographically matched healthy populations, with the exception of c.788G>A, the minor allele frequency of which was significantly elevated in the Czech hepatocyte nuclear factor 1-α (HNF1A) MODY patients [odds ratio (OR) 4.8, 95% confidence interval (CI) 2.2-10.7] and the Brazilian MODY patients (OR 8.4, 95% CI 1.8-39.1). A barely significant increase in the c.788G>A minor allele was also detected in the islet cell autoantibody-positive Czech MODY patients. However, c.788A behaves as a loss-of-function mutant in T cells, and thus protects against autoimmunity. MODY patients (including islet cell autoantibody-positive cases) do not display any increase in autoimmunity-associated PTPN22 alleles. The absence of autoimmunity-associated PTPN22 alleles was also demonstrated in latent autoimmune diabetes in adults, which suggests that the slow kinetics of the onset of autoantibodies is subject to a regulation that is different from that experienced in type 1 diabetes and other autoimmune disorders. © 2015 S. Karger AG, Basel.

  12. The primary immune response to Vaccinia virus vaccination includes cells with a distinct cytotoxic effector CD4 T-cell phenotype.

    Science.gov (United States)

    Munier, C Mee Ling; van Bockel, David; Bailey, Michelle; Ip, Susanna; Xu, Yin; Alcantara, Sheilajen; Liu, Sue Min; Denyer, Gareth; Kaplan, Warren; Suzuki, Kazuo; Croft, Nathan; Purcell, Anthony; Tscharke, David; Cooper, David A; Kent, Stephen J; Zaunders, John J; Kelleher, Anthony D

    2016-10-17

    Smallpox was eradicated by a global program of inoculation with Vaccinia virus (VV). Robust VV-specific CD4 T-cell responses during primary infection are likely essential to controlling VV replication. Although there is increasing interest in cytolytic CD4 T-cells across many viral infections, the importance of these cells during acute VV infection is unclear. We undertook a detailed functional and genetic characterization of CD4 T-cells during acute VV-infection of humans. VV-specific T-cells were identified by up-regulation of activation markers directly ex vivo and through cytokine and co-stimulatory molecule expression. At day-13-post primary inoculation with VV, CD38highCD45RO+ CD4 T-cells were purified by cell sorting, RNA isolated and analysed by microarray. Differential expression of up-regulated genes in activated CD4 T-cells was confirmed at the mRNA and protein levels. We compared analyses of VV-specific CD4 T-cells to studies on 12 subjects with primary HIV infection (PHI). VV-specific T-cells lines were established from PBMCs collected post vaccination and checked for cytotoxicity potential. A median 11.9% CD4 T-cells were CD38highCD45RO+ at day-13 post-VV inoculation, compared to 3.0% prior and 10.4% during PHI. Activated CD4 T-cells had an up-regulation of genes related to cytolytic function, including granzymes K and A, perforin, granulysin, TIA-1, and Rab27a. No difference was seen between CD4 T-cell expression of perforin or TIA-1 to VV and PHI, however granzyme k was more dominant in the VV response. At 25:1 effector to target ratio, two VV-specific T-cell lines exhibited 62% and 30% cytotoxicity respectively and CD107a degranulation. We show for the first time that CD4 CTL are prominent in the early response to VV. Understanding the role of CD4 CTL in the generation of an effective anti-viral memory may help develop more effective vaccines for diseases such as HIV. Crown Copyright © 2016. Published by Elsevier Ltd. All rights reserved.

  13. Adult Mouse DRG Explant and Dissociated Cell Models to Investigate Neuroplasticity and Responses to Environmental Insults Including Viral Infection.

    Science.gov (United States)

    Fornaro, Michele; Sharthiya, Harsh; Tiwari, Vaibhav

    2018-03-09

    This protocol describes an ex vivo model of mouse-derived dorsal root ganglia (DRG) explant and in vitro DRG-derived co-culture of dissociated sensory neurons and glial satellite cells. These are useful and versatile models to investigate a variety of biological responses associated with physiological and pathological conditions of the peripheral nervous system (PNS) ranging from neuron-glial interaction, neuroplasticity, neuroinflammation, and viral infection. The usage of DRG explant is scientifically advantageous compared to simplistic single cells models for multiple reasons. For instance, as an organotypic culture, the DRG explant allows ex vivo transfer of an entire neuronal network including the extracellular microenvironment that play a significant role in all the neuronal and glial functions. Further, DRG explants can also be maintained ex vivo for several days and the culture conditions can be perturbed as desired. In addition, the harvested DRG can be further dissociated into an in vitro co-culture of primary sensory neurons and satellite glial cells to investigate neuronal-glial interaction, neuritogenesis, axonal cone interaction with the extracellular microenvironment, and more general, any aspect associated with the neuronal metabolism. Therefore, the DRG-explant system offers a great deal of flexibility to study a wide array of events related to biological, physiological, and pathological conditions in a cost-effective manner.

  14. Merkel Cell Carcinomas Arising in Autoimmune Disease Affected Patients Treated with Biologic Drugs, Including Anti-TNF.

    Science.gov (United States)

    Rotondo, John Charles; Bononi, Ilaria; Puozzo, Andrea; Govoni, Marcello; Foschi, Valentina; Lanza, Giovanni; Gafà, Roberta; Gaboriaud, Pauline; Touzé, Françoise Antoine; Selvatici, Rita; Martini, Fernanda; Tognon, Mauro

    2017-07-15

    Purpose: The purpose of this investigation was to characterize Merkel cell carcinomas (MCC) arisen in patients affected by autoimmune diseases and treated with biologic drugs. Experimental Design: Serum samples from patients with MCC were analyzed for the presence and titer of antibodies against antigens of the oncogenic Merkel cell polyomavirus (MCPyV). IgG antibodies against the viral oncoproteins large T (LT) and small T (ST) antigens and the viral capsid protein-1 were analyzed by indirect ELISA. Viral antigens were recombinant LT/ST and virus-like particles (VLP), respectively. MCPyV DNA sequences were studied using PCR methods in MCC tissues and in peripheral blood mononuclear cells (PBMC). Immunohistochemical (IHC) analyses were carried out in MCC tissues to reveal MCPyV LT oncoprotein. Results: MCPyV DNA sequences identified in MCC tissues showed 100% homology with the European MKL-1 strain. PBMCs from patients tested MCPyV-negative. Viral DNA loads in the three MCC tissues were in the 0.1 to 30 copy/cell range. IgG antibodies against LT/ST were detected in patients 1 and 3, whereas patient 2 did not react to the MCPyV LT/ST antigen. Sera from the three patients with MCC contained IgG antibodies against MCPyV VP1. MCC tissues tested MCPyV LT-antigen-positive in IHC assays, with strong LT expression with diffuse nuclear localization. Normal tissues tested MCPyV LT-negative when employed as control. Conclusions: We investigated three new MCCs in patients affected by rheumatologic diseases treated with biologic drugs, including TNF. A possible cause-effect relationship between pharmacologic immunosuppressive treatment and MCC onset is suggested. Indeed, MCC is associated with MCPyV LT oncoprotein activity. Clin Cancer Res; 23(14); 3929-34. ©2017 AACR . ©2017 American Association for Cancer Research.

  15. Renal Cell Carcinoma With Chromosome 6p Amplification Including the TFEB Gene: A Novel Mechanism of Tumor Pathogenesis?

    Science.gov (United States)

    Williamson, Sean R; Grignon, David J; Cheng, Liang; Favazza, Laura; Gondim, Dibson D; Carskadon, Shannon; Gupta, Nilesh S; Chitale, Dhananjay A; Kalyana-Sundaram, Shanker; Palanisamy, Nallasivam

    2017-03-01

    Amplification of chromosome 6p has been implicated in aggressive behavior in several cancers, but has not been characterized in renal cell carcinoma (RCC). We identified 9 renal tumors with amplification of chromosome 6p including the TFEB gene, 3 by fluorescence in situ hybridization, and 6 from the Cancer Genome Atlas (TCGA) databases. Patients' ages were 28 to 78 years (median, 61 y). Most tumors were high stage (7/9 pT3a, 2/9 pN1). Using immunohistochemistry, 2/4 were positive for melanocytic markers and cathepsin K. Novel TFEB fusions were reported by TCGA in 2; however, due to a small composition of fusion transcripts compared with full-length transcripts (0.5/174 and 3.3/132 FPKM), we hypothesize that these represent secondary fusions due to amplification. Five specimens (4 TCGA, 1 fluorescence in situ hybridization) had concurrent chromosome 3p copy number loss or VHL deletion. However, these did not resemble clear cell RCC, had negative carbonic anhydrase IX labeling, lacked VHL mutation, and had papillary or unclassified histology (2/4 had gain of chromosome 7 or 17). One tumor each had somatic FH mutation and SMARCB1 mutation. Chromosome 6p amplification including TFEB is a previously unrecognized cytogenetic alteration in RCC, associated with heterogenous tubulopapillary eosinophilic and clear cell histology. The combined constellation of features does not fit cleanly into an existing tumor category (unclassified), most closely resembling papillary or translocation RCC. The tendency for high tumor stage, varied tubulopapillary morphology, and a subset with melanocytic marker positivity suggests the possibility of a unique tumor type, despite some variation in appearance and genetics.

  16. Evaluation of the Live Biotherapeutic Product, Asymptomatic Bacteriuria Escherichia coli 2-12, in Healthy Dogs and Dogs with Clinical Recurrent UTI.

    Science.gov (United States)

    Segev, G; Sykes, J E; Klumpp, D J; Schaeffer, A J; Antaki, E M; Byrne, B A; Yaggie, R E; Westropp, J L

    2018-01-01

    Antimicrobial resistance is an emerging problem. To investigate the safety and efficacy of a live biotherapeutic product, ASB E. coli 2-12 for UTI treatment. Six healthy research dogs; nine client-owned dogs with recurrent UTI. Prospective noncontrolled clinical trial. For safety data, research dogs were sedated, a urinary catheter was inserted into the bladder; 10 10 CFU/mL of ASB E. coli 2-12 was instilled. Urine was cultured on days 1, 3, and 8 post-instillation and dogs were observed for lower urinary tract signs (LUTS). For client-owned dogs, ASB E. coli 2-12 was instilled similarly and urine cultures analyzed on days 1, 7, and 14 days postinstillation. No LUTS were noted in any of the 6 research dogs after ASB E. coli 2-12 infusion. Pulse field gel electrophoresis (PFGE) studies confirmed the bacterial strains isolated matched that ASB E. coli 2-12 strain. Four of the nine client-owned dogs had complete or nearly complete clinical cures by day 14. Of these four dogs, 3 also had microbiologic cures at day 14; one of these dogs had subclinical bacteriuria (in addition to ASB E. coli 2-12). Three of these four dogs had ASB E. coli 2-12 isolated from their urine at day 14. With the exception of mild, temporary, self-limiting, hyporexia in two dogs on the day of biotherapeutic administration, there were no major adverse effects. These results suggest ASB E. coli 2-12 is safe and should be investigated in a larger controlled study evaluating clinical UTI in dogs. Copyright © 2017 The Authors. Journal of Veterinary Internal Medicine published by Wiley Periodicals, Inc. on behalf of the American College of Veterinary Internal Medicine.

  17. Size-dependent nonlinear bending of micro/nano-beams made of nanoporous biomaterials including a refined truncated cube cell

    Science.gov (United States)

    Sahmani, S.; Aghdam, M. M.

    2017-12-01

    Morphology and pore size plays an essential role in the mechanical properties as well as the associated biological capability of a porous structure made of biomaterials. The objective of the current study is to predict the Young's modulus and Poisson's ratio of nanoporous biomaterials including refined truncated cube cells based on a hyperbolic shear deformable beam model. Analytical relationships for the mechanical properties of nanoporous biomaterials are given as a function of the refined cell's dimensions. After that, the size dependency in the nonlinear bending behavior of micro/nano-beams made of such nanoporous biomaterials is analyzed using the nonlocal strain gradient elasticity theory. It is assumed that the micro/nano-beam has one movable end under axial compression in conjunction with a uniform distributed lateral load. The Galerkin method together with an improved perturbation technique is employed to propose explicit analytical expression for nonlocal strain gradient load-deflection curves of the micro/nano-beams made of nanoporous biomaterials subjected to uniform transverse distributed load. It is found that through increment of the pore size, the micro/nano-beam will undergo much more deflection corresponding to a specific distributed load due to the reduction in the stiffness of nanoporous biomaterial. This pattern is more prominent for lower value of applied axial compressive load at the free end of micro/nano-beam.

  18. Fabrication of Mediatorless/Membraneless Glucose/Oxygen Based Biofuel Cell using Biocatalysts Including Glucose Oxidase and Laccase Enzymes

    Science.gov (United States)

    Christwardana, Marcelinus; Kim, Ki Jae; Kwon, Yongchai

    2016-07-01

    Mediatorless and membraneless enzymatic biofuel cells (EBCs) employing new catalytic structure are fabricated. Regarding anodic catalyst, structure consisting of glucose oxidase (GOx), poly(ethylenimine) (PEI) and carbon nanotube (CNT) is considered, while three cathodic catalysts consist of glutaraldehyde (GA), laccase (Lac), PEI and CNT that are stacked together in different ways. Catalytic activities of the catalysts for glucose oxidation and oxygen reduction reactions (GOR and ORR) are evaluated. As a result, it is confirmed that the catalysts work well for promotion of GOR and ORR. In EBC tests, performances of EBCs including 150 μm-thick membrane are measured as references, while those of membraneless EBCs are measured depending on parameters like glucose flow rate, glucose concentration, distance between two electrodes and electrolyte pH. With the measurements, how the parameters affect EBC performance and their optimal conditions are determined. Based on that, best maximum power density (MPD) of membraneless EBC is 102 ± 5.1 μW · cm-2 with values of 0.5 cc · min-1 (glucose flow rate), 40 mM (glucose concentration), 1 mm (distance between electrodes) and pH 3. When membrane and membraneless EBCs are compared, MPD of the membraneless EBC that is run at the similar operating condition to EBC including membrane is speculated as about 134 μW · cm-2.

  19. Electrophysiological heterogeneity of pacemaker cells in the rabbit intercaval region, including the SA node: insights from recording multiple ion currents in each cell.

    Science.gov (United States)

    Monfredi, Oliver; Tsutsui, Kenta; Ziman, Bruce; Stern, Michael D; Lakatta, Edward G; Maltsev, Victor A

    2018-03-01

    Cardiac pacemaker cells, including cells of the sinoatrial node, are heterogeneous in size, morphology, and electrophysiological characteristics. The exact extent to which these cells differ electrophysiologically is unclear yet is critical to understanding their functioning. We examined major ionic currents in individual intercaval pacemaker cells (IPCs) sampled from the paracristal, intercaval region (including the sinoatrial node) that were spontaneously beating after enzymatic isolation from rabbit hearts. The beating rate was measured at baseline and after inhibition of the Ca 2+ pump with cyclopiazonic acid. Thereafter, in each cell, we consecutively measured the density of funny current ( I f ), delayed rectifier K + current ( I K ) (a surrogate of repolarization capacity), and L-type Ca 2+ current ( I Ca,L ) using whole cell patch clamp . The ionic current densities varied to a greater extent than previously appreciated, with some IPCs demonstrating very small or zero I f . The density of none of the currents was correlated with cell size, while I Ca,L and I f densities were related to baseline beating rates. I f density was correlated with I K density but not with that of I Ca,L . Inhibition of Ca 2+ cycling had a greater beating rate slowing effect in IPCs with lower I f densities. Our numerical model simulation indicated that 1) IPCs with small (or zero) I f or small I Ca,L can operate via a major contribution of Ca 2+ clock, 2) I f -Ca 2+ -clock interplay could be important for robust pacemaking function, and 3) coupled I f - I K function could regulate maximum diastolic potential. Thus, we have demonstrated marked electrophysiological heterogeneity of IPCs. This heterogeneity is manifested in basal beating rate and response to interference of Ca 2+ cycling, which is linked to I f . NEW & NOTEWORTHY In the present study, a hitherto unrecognized range of heterogeneity of ion currents in pacemaker cells from the intercaval region is demonstrated

  20. A Novel Technique to Follow Consequences of Exogenous Factors, Including Therapeutic Drugs, on Living Human Breast Epithelial Cells

    Science.gov (United States)

    1999-07-01

    and lipid vectors, are being tested. Concurrent with the development of procedures for live - cell imaging , we are examining the distribution of proteins...dimensional matrix. These studies have not yet begun. There are a number of procedures that must be developed and perfected in the live - cell imaging , as...components of the Wnt signaling pathway are too preliminary and require additional research prior to publication. (9) CONCLUSIONS Live cell imaging of

  1. Tumor cell anaplasia and multinucleation are predictors of disease recurrence in oropharyngeal squamous cell carcinoma, including among just the human papillomavirus-related cancers.

    Science.gov (United States)

    Lewis, James S; Scantlebury, Juliette B; Luo, Jingqin; Thorstad, Wade L

    2012-07-01

    Oropharyngeal squamous cell carcinoma (SCC) is frequently related to high risk human papillomavirus. This tumor expresses p16, frequently has a nonkeratinizing morphology, and has improved outcomes. Despite having a good prognosis, tumors can have focal or diffuse nuclear anaplasia or multinucleation, the significance of which is unknown. From a database of 270 oropharyngeal SCCs with known histologic typing (using our established system) and p16 immunohistochemistry, all surgically resected cases (149) were reviewed. Anaplasia was defined as any × 40 field with ≥ 3 tumor nuclei with diameters ≥ 5 lymphocyte nuclei (~25 μm), and multinucleation was defined as any × 40 field with ≥ 3 tumor cells with multiple nuclei. p16 was positive in 128 cases (85.9%), 64 cases (43.0%) showed anaplasia, and 71 (47.7%) showed multinucleation. Anaplasia and multinucleation were highly related (Panaplasia or multinucleation had worse overall, disease-specific, and disease-free survival (Panaplasia and multinucleation both predicted worse disease-specific survival (hazard ratio 9.9, P=0.04; and hazard ratio 11.9, P=0.02, respectively) independent of the other variables. In summary, among surgically resectable oropharyngeal SCC (including among just the p16-positive cohort), tumor cell anaplasia and multinucleation independently correlated with disease recurrence and poorer survival.

  2. Model of Organic Solar Cell Photocurrent Including the Effect of Charge Accumulation at Interfaces and Non-Uniform Carrier Generation

    DEFF Research Database (Denmark)

    Torto, Lorenzo; Cester, Andrea; Rizzo, Antonio

    2017-01-01

    We developed an improved model to fit the photocurrent density versus voltage in organic solar cells. The model has been validated by fitting data from P3HT:PCBM solar cells. Our model quantitatively accounts for the band bending near the electrodes caused by charge accumulation in the active layer...

  3. Slit-scanning technique using standard cell sorter instruments for analyzing and sorting nonacrocentric human chromosomes, including small ones

    NARCIS (Netherlands)

    Rens, W.; van Oven, C. H.; Stap, J.; Jakobs, M. E.; Aten, J. A.

    1994-01-01

    We have investigated the performance of two types of standard flow cell sorter instruments, a System 50 Cytofluorograph and a FACSTar PLUS cell sorter, for the on-line centromeric index (CI) analysis of human chromosomes. To optimize the results, we improved the detection efficiency for centromeres

  4. Molecular network including eIF1AX, RPS7, and 14-3-3γ regulates protein translation and cell proliferation in bovine mammary epithelial cells.

    Science.gov (United States)

    Yu, Cuiping; Luo, Chaochao; Qu, Bo; Khudhair, Nagam; Gu, Xinyu; Zang, Yanli; Wang, Chunmei; Zhang, Na; Li, Qingzhang; Gao, Xuejun

    2014-12-15

    14-3-3γ, an isoform of the 14-3-3 protein family, was proved to be a positive regulator of mTOR pathway. Here, we analyzed the function of 14-3-3γ in protein synthesis using bovine mammary epithelial cells (BMECs). We found that 14-3-3γ interacted with eIF1AX and RPS7 by 14-3-3γ coimmunoprecipitation (CoIP) and matrix-assisted laser desorption/ionization-time-of-flight/time-of-flight (MALDI-TOF/TOF) peptide mass fingerprinting analysis. These interactions of 14-3-3γ with eIF1AX and RPS7 were further confirmed by colocalization and fluorescence resonance energy transfer (FRET) analysis. We also found that methionine could promote protein synthesis and trigger the protein expression levels of 14-3-3γ, eIF1AX and RPS7. Analysis of overexpression and inhibition of 14-3-3γ confirmed that it positively affected the protein expression levels of eIF1AX, RPS7, Stat5 and mTOR pathway to promote protein synthesis and cell proliferation in BMECs. We further showed that overexpression of eIF1AX and RPS7 also triggered protein translation and cell proliferation. From these results, we conclude that molecular network including eIF1AX, RPS7, and 14-3-3γ regulates protein translation and cell proliferation in BMECs. Copyright © 2014 Elsevier Inc. All rights reserved.

  5. A multi-stage process including transient polyploidization and EMT precedes the emergence of chemoresistent ovarian carcinoma cells with a dedifferentiated and pro-inflammatory secretory phenotype.

    Science.gov (United States)

    Rohnalter, Verena; Roth, Katrin; Finkernagel, Florian; Adhikary, Till; Obert, Julia; Dorzweiler, Kristina; Bensberg, Maike; Müller-Brüsselbach, Sabine; Müller, Rolf

    2015-11-24

    DNA-damaging drugs induce a plethora of molecular and cellular alterations in tumor cells, but their interrelationship is largely obscure. Here, we show that carboplatin treatment of human ovarian carcinoma SKOV3 cells triggers an ordered sequence of events, which precedes the emergence of mitotic chemoresistant cells. The initial phase of cell death after initiation of carboplatin treatment is followed around day 14 by the emergence of a mixed cell population consisting of cycling, cell cycle-arrested and senescent cells. At this stage, giant cells make up >80% of the cell population, p21 (CDKN1A) in strongly induced, and cell numbers remain nearly static. Subsequently, cell death decreases, p21 expression drops to a low level and cell divisions increase, including regular mitoses of giant cells and depolyploidization by multi-daughter divisions. These events are accompanied by the upregulation of stemness markers and a pro-inflammatory secretory phenotype, peaking after approximately 14 days of treatment. At the same time the cells initiate epithelial to mesenchymal transition, which over the subsequent weeks continuously increases, concomitantly with the emergence of highly proliferative, migratory, dedifferentiated, pro-inflammatory and chemoresistant cells (SKOV3-R). These cells are anchorage-independent and grow in a 3D collagen matrix, while cells on day 14 do not survive under these conditions, indicating that SKOV3-R cells were generated thereafter by the multi-stage process described above. This process was essentially recapitulated with the ovarian carcinoma cell line IGROV-1. Our observations suggest that transitory cells characterized by polyploidy, features of stemness and a pro-inflammatory secretory phenotype contribute to the acquisition of chemoresistance.

  6. The alternatively-included 11a sequence modifies the effects of Mena on actin cytoskeletal organization and cell behavior.

    Science.gov (United States)

    Balsamo, Michele; Mondal, Chandrani; Carmona, Guillaume; McClain, Leslie M; Riquelme, Daisy N; Tadros, Jenny; Ma, Duan; Vasile, Eliza; Condeelis, John S; Lauffenburger, Douglas A; Gertler, Frank B

    2016-10-17

    During tumor progression, alternative splicing gives rise to different Mena protein isoforms. We analyzed how Mena11a, an isoform enriched in epithelia and epithelial-like cells, affects Mena-dependent regulation of actin dynamics and cell behavior. While other Mena isoforms promote actin polymerization and drive membrane protrusion, we find that Mena11a decreases actin polymerization and growth factor-stimulated membrane protrusion at lamellipodia. Ectopic Mena11a expression slows mesenchymal-like cell motility, while isoform-specific depletion of endogenous Mena11a in epithelial-like tumor cells perturbs cell:cell junctions and increases membrane protrusion and overall cell motility. Mena11a can dampen membrane protrusion and reduce actin polymerization in the absence of other Mena isoforms, indicating that it is not simply an inactive Mena isoform. We identify a phosphorylation site within 11a that is required for some Mena11a-specific functions. RNA-seq data analysis from patient cohorts demonstrates that the difference between mRNAs encoding constitutive Mena sequences and those containing the 11a exon correlates with metastasis in colorectal cancer, suggesting that 11a exon exclusion contributes to invasive phenotypes and leads to poor clinical outcomes.

  7. Industrial Production of Therapeutic Proteins: Cell Lines, Cell Culture, and Purification

    Science.gov (United States)

    Zhu, Marie M.; Mollet, Michael; Hubert, Rene S.

    The biotechnology and pharmaceutical industries have seen a recent surge in the development of biological drug products manufactured from engineered mammalian cell lines. Since the hugely successful launch of human tissue plasminogen activator in 1987 and erythropoietin in 1988, the biopharmaceutical market has grown immensely. Global sales in 2003 exceeded US 30 billion.1 Currently, a total of 108 biotherapeutics are approved and available to patients (Table 32.1). In addition, 324 medically related, biotechnology-derived medicines for nearly 150 diseases are in clinical trials or under review by the U.S. Food and Drug Administration.2 These biopharmaceutical candidates promise to bring more and better treatments to patients. Compared to small molecule drugs, biotherapeutics show exquisite specificity with fewer off-target interactions and improved safety profiles.

  8. Reserve, thin form-factor, hypochlorite-based cells for powering portable systems: Manufacture (including MEMS processes), performance and characterization

    Energy Technology Data Exchange (ETDEWEB)

    Cardenas-Valencia, Andres M.; Langebrake, Larry [Center for Ocean Technology, University of South Florida, 140 Seventh Ave. S., St. Petersburg, FL (United States); Biver, Carl J. [Center for Ocean Technology, University of South Florida, 140 Seventh Ave. S., St. Petersburg, FL (United States); Department of Chemical Engineering, University of South Florida, 4202 E. Fowler Ave. Tampa, FL (United States)

    2007-03-30

    This work focuses on fabrication routes and performance evaluation of thin form-factors, reserve cells, as a powering alternative for expendable and/or remotely operated systems. The catalytic decomposition of sodium hypochlorite solutions is revisited herein with two cost-effective anodes: zinc and aluminum. Aluminum, even though the most expensive of the utilized anodes, constituted cells with double the energy content (up to 55 Wh kg{sup -1}) than those fabricated with zinc. Even though the hypochlorite concentration in the solution limits the cells' operational life, attractive performances (1.0 V with a current of 10 mA) for the manufactured cells are obtained. It is shown that micro fabrication processes, allowing for close electrodes interspacing, provided high faradic and columbic efficiencies of up to 70 and 100%, respectively. Obtained specific energies (50-120 Wh kg{sup -1}) are in the same order of magnitude than batteries currently used for powering deployable systems. Experimental results show that a simple model that linearly relates over potentials and the electrical load, adequately describe all the cell designs. A mathematical model based on a kinetic-mechanistic scheme that relates the current output as a function of time agrees fairly well with results obtained activating cells with various concentrations of NaOCl solutions. (author)

  9. Cellular Components, Including Stem-Like Cells, of Preterm Mother's Mature Milk as Compared with Those in Her Colostrum: A Pilot Study.

    Science.gov (United States)

    Kaingade, Pankaj; Somasundaram, Indumathi; Sharma, Akshita; Patel, Darshan; Marappagounder, Dhanasekaran

    2017-09-01

    Whether the preterm mothers' mature milk retains the same cellular components as those in colostrum including stem-like cell, cell adhesion molecules, and immune cells. A total of five preterm mothers were recruited for the study having an average age of 30.2 years and gestational age of 29.8 weeks from the Pristine Women's Hospital, Kolhapur. Colostrum milk was collected within 2-5 days and matured milk was collected 20-30 days after delivery from the same mothers. Integral cellular components of 22 markers including stem cells, immune cells, and cell adhesion molecules were measured using flowcytometry. Preterm mature milk was found to possess higher expressions of hematopoietic stem cells, mesenchymal stem-like cells, immune cells, few cell adhesion molecules, and side population cells than colostrum. The increased level of these different cell components in mature milk may be important in the long-term preterm baby's health growth. Further similar research in a larger population of various gestational ages and lactation stages of preterm mothers is warranted to support these pilot findings.

  10. Fuel cell integral bundle assembly including ceramic open end seal and vertical and horizontal thermal expansion control

    Science.gov (United States)

    Zafred, Paolo R [Murrysville, PA; Gillett, James E [Greensburg, PA

    2012-04-24

    A plurality of integral bundle assemblies contain a top portion with an inlet fuel plenum and a bottom portion containing a base support, the base supports a dense, ceramic air exhaust manifold having four supporting legs, the manifold is below and connects to air feed tubes located in a recuperator zone, the air feed tubes passing into the center of inverted, tubular, elongated, hollow electrically connected solid oxide fuel cells having an open end above a combustion zone into which the air feed tubes pass and a closed end near the inlet fuel plenum, where the open end of the fuel cells rest upon and within a separate combination ceramic seal and bundle support contained in a ceramic support casting, where at least one flexible cushion ceramic band seal located between the recuperator and fuel cells protects and controls horizontal thermal expansion, and where the fuel cells operate in the fuel cell mode and where the base support and bottom ceramic air exhaust manifolds carry from 85% to all of the weight of the generator.

  11. Regulation of the proliferation of colon cancer cells by compounds that affect glycolysis, including 3-bromopyruvate, 2-deoxyglucose and biguanides.

    Science.gov (United States)

    Lea, Michael A; Qureshi, Mehreen S; Buxhoeveden, Michael; Gengel, Nicolette; Kleinschmit, Jessica; Desbordes, Charles

    2013-02-01

    In previous studies performed by our group, we observed that 2-deoxyglucose blocked the acidification of the medium used for culture of colon cancer cells caused by incubation with biguanides and it had an additive inhibitory effect on growth. In the present work, we found that 3-bromopyruvate can also prevent the lowering of pH caused by biguanide treatment. 3-Bromopyruvate inhibited colonic cancer cell proliferation, but the effect was not always additive to that of biguanides and an additive effect was more notable in combined treatment with 3-bromopyruvate and 2-deoxyglucose. The induction of alkaline phosphatase activity by butyrate was not consistently affected by combination with other agents that modified glucose metabolism. The drug combinations that were examined inhibited proliferation of wild-type and p53-null cells and affected colonic cancer lines with different growth rates.

  12. A recurrent germline BAP1 mutation and extension of the BAP1 tumor predisposition spectrum to include basal cell carcinoma

    DEFF Research Database (Denmark)

    Wadt, Karin Anna Wallentin; Aoude, L G; Johansson, P

    2015-01-01

    ) and mesothelioma, as previously reported for germline BAP1 mutations. However, mutation carriers from three new families, and one previously reported family, developed basal cell carcinoma (BCC), thus suggesting inclusion of BCC in the phenotypic spectrum of the BAP1 tumor syndrome. This notion is supported...

  13. Non-islet cell tumour-induced hypoglycaemia : a review of the literature including two new cases

    NARCIS (Netherlands)

    De Groot, Jan Willem B.; Rikhof, Bart; Van Doom, Jaap; Bilo, Henk J. G.; Alleman, Maarten A.; Honkoop, Aafke H.; Van der Graaf, Winette T. A.

    2007-01-01

    This review focuses on the tumour types and symptoms associated with non-islet cell tumour-induced hypoglycaemia (NICTH) as well as the pathogenesis, diagnosis and treatment of this rare paraneoplastic phenomenon. In addition, we report two illustrative cases of patients suffering from NICTH caused

  14. Stability enhancement of an atomic force microscope for long-term force measurement including cantilever modification for whole cell deformation

    Science.gov (United States)

    Weafer, P. P.; McGarry, J. P.; van Es, M. H.; Kilpatrick, J. I.; Ronan, W.; Nolan, D. R.; Jarvis, S. P.

    2012-09-01

    Atomic force microscopy (AFM) is widely used in the study of both morphology and mechanical properties of living cells under physiologically relevant conditions. However, quantitative experiments on timescales of minutes to hours are generally limited by thermal drift in the instrument, particularly in the vertical (z) direction. In addition, we demonstrate the necessity to remove all air-liquid interfaces within the system for measurements in liquid environments, which may otherwise result in perturbations in the measured deflection. These effects severely limit the use of AFM as a practical tool for the study of long-term cell behavior, where precise knowledge of the tip-sample distance is a crucial requirement. Here we present a readily implementable, cost effective method of minimizing z-drift and liquid instabilities by utilizing active temperature control combined with a customized fluid cell system. Long-term whole cell mechanical measurements were performed using this stabilized AFM by attaching a large sphere to a cantilever in order to approximate a parallel plate system. An extensive examination of the effects of sphere attachment on AFM data is presented. Profiling of cantilever bending during substrate indentation revealed that the optical lever assumption of free ended cantilevering is inappropriate when sphere constraining occurs, which applies an additional torque to the cantilevers "free" end. Here we present the steps required to accurately determine force-indentation measurements for such a scenario. Combining these readily implementable modifications, we demonstrate the ability to investigate long-term whole cell mechanics by performing strain controlled cyclic deformation of single osteoblasts.

  15. Cell-based delivery of oncolytic viruses: a new strategic alliance for a biological strike against cancer.

    Science.gov (United States)

    Power, Anthony T; Bell, John C

    2007-04-01

    Recent years have seen tremendous advances in the development of exquisitely targeted replicating virotherapeutics that can safely destroy malignant cells. Despite this promise, clinical advancement of this powerful and unique approach has been hindered by vulnerability to host defenses and inefficient systemic delivery. However, it now appears that delivery of oncolytic viruses within carrier cells may offer one solution to this critical problem. In this review, we compare the advantages and limitations of the numerous cell lineages that have been investigated as delivery platforms for viral therapeutics, and discuss examples showing how combined cell-virus biotherapeutics can be used to achieve synergistic gains in antitumor activity. Finally, we highlight avenues for future preclinical research that might be taken in order to refine cell-virus biotherapeutics in preparation for human trials.

  16. Evaluation of the anti-inflammatory actions of various functional food materials including glucosamine on synovial cells.

    Science.gov (United States)

    Yamagishi, Yoshie; Someya, Akimasa; Imai, Kensuke; Nagao, Junji; Nagaoka, Isao

    2017-08-01

    The anti-inflammatory actions of glucosamine (GlcN) on arthritic disorders involve the suppression of inflammatory mediator production from synovial cells. GlcN has also been reported to inhibit the activation of the p38 mitogen-activated protein kinase (MAPK) pathway. The present study aimed to determine the cooperative and anti‑inflammatory actions of functional food materials and evaluated the production of interleukin (IL)‑8 and phosphorylation of p38 MAPK in IL-1β-activated synovial cells, incubated with the combination of GlcN and various functional food materials containing L‑methionine (Met), undenatured type II collagen (UC‑II), chondroitin sulfate (CS), methylsulfonylmethane (MSM) and agaro-oligosaccharide (AO). The results indicated that Met, UC‑II, CS, MSM and AO slightly or moderately suppressed the IL-1β-stimulated IL‑8 production by human synovial MH7A cells. The same compounds further decreased the IL‑8 level lowered by GlcN. Similarly, they slightly suppressed the phosphorylation level of p38 MAPK and further reduced the phosphorylation level lowered by GlcN. These observations suggest a possibility that these functional food materials exert an anti‑inflammatory action (inhibition of IL‑8 production) in combination with GlcN by cooperatively suppressing the p38 MAPK signaling (phosphorylation).

  17. Mechanisms of growth inhibition of primary prostate epithelial cells following gamma irradiation or photodynamic therapy include senescence, necrosis, and autophagy, but not apoptosis

    International Nuclear Information System (INIS)

    Frame, Fiona M.; Savoie, Huguette; Bryden, Francesca; Giuntini, Francesca; Mann, Vincent M.; Simms, Matthew S.; Boyle, Ross W.; Maitland, Norman J.

    2015-01-01

    In comparison to more differentiated cells, prostate cancer stem-like cells are radioresistant, which could explain radio-recurrent prostate cancer. Improvement of radiotherapeutic efficacy may therefore require combination therapy. We have investigated the consequences of treating primary prostate epithelial cells with gamma irradiation and photodynamic therapy (PDT), both of which act through production of reactive oxygen species (ROS). Primary prostate epithelial cells were cultured from patient samples of benign prostatic hyperplasia and prostate cancer prior to treatment with PDT or gamma irradiation. Cell viability was measured using MTT and alamar blue assay, and cell recovery by colony-forming assays. Immunofluorescence of gamma-H2AX foci was used to quantify DNA damage, and autophagy and apoptosis were assessed using Western blots. Necrosis and senescence were measured by propidium iodide staining and beta-galactosidase staining, respectively. Both PDT and gamma irradiation reduced the colony-forming ability of primary prostate epithelial cells. PDT reduced the viability of all types of cells in the cultures, including stem-like cells and more differentiated cells. PDT induced necrosis and autophagy, whereas gamma irradiation induced senescence, but neither treatment induced apoptosis. PDT and gamma irradiation therefore inhibit cell growth by different mechanisms. We suggest these treatments would be suitable for use in combination as sequential treatments against prostate cancer

  18. Proteomic plasma membrane profiling reveals an essential role for gp96 in the cell surface expression of LDLR family members, including the LDL receptor and LRP6.

    Science.gov (United States)

    Weekes, Michael P; Antrobus, Robin; Talbot, Suzanne; Hör, Simon; Simecek, Nikol; Smith, Duncan L; Bloor, Stuart; Randow, Felix; Lehner, Paul J

    2012-03-02

    The endoplasmic reticulum chaperone gp96 is required for the cell surface expression of a narrow range of proteins, including toll-like receptors (TLRs) and integrins. To identify a more comprehensive repertoire of proteins whose cell surface expression is dependent on gp96, we developed plasma membrane profiling (PMP), a technique that combines SILAC labeling with selective cell surface aminooxy-biotinylation. This approach allowed us to compare the relative abundance of plasma membrane (PM) proteins on gp96-deficient versus gp96-reconstituted murine pre-B cells. Analysis of unfractionated tryptic peptides initially identified 113 PM proteins, which extended to 706 PM proteins using peptide prefractionation. We confirmed a requirement for gp96 in the cell surface expression of certain TLRs and integrins and found a marked decrease in cell surface expression of four members of the extended LDL receptor family (LDLR, LRP6, Sorl1 and LRP8) in the absence of gp96. Other novel gp96 client proteins included CD180/Ly86, important in the B-cell response to lipopolysaccharide. We highlight common structural motifs in these client proteins that may be recognized by gp96, including the beta-propeller and leucine-rich repeat. This study therefore identifies the extended LDL receptor family as an important new family of proteins whose cell surface expression is regulated by gp96.

  19. Increased frequency of CCR4+ and CCR6+ memory T-cells including CCR7+CD45RAmed very early memory cells in granulomatosis with polyangiitis (Wegener's)

    OpenAIRE

    Fagin, Ursula; Pitann, Silke; Gross, Wolfgang L; Lamprecht, Peter

    2012-01-01

    Introduction Chemokine receptors play an important role in mediating the recruitment of T cells to inflammatory sites. Previously, small proportions of circulating Th1-type CCR5+ and Th2-type CCR3+ cells have been shown in granulomatosis with polyangiitis (GPA). Wondering to what extent CCR4 and CCR6 expression could also be implicated in T cell recruitment to inflamed sites in GPA, we investigated the expression of CCR4 and CCR6 on T cells and its association with T cell diversity and polari...

  20. PREFACE: 9th International Fröhlich's Symposium: Electrodynamic Activity of Living Cells (Including Microtubule Coherent Modes and Cancer Cell Physics)

    Science.gov (United States)

    Cifra, Michal; Pokorný, Jirí; Kucera, Ondrej

    2011-12-01

    This volume contains papers presented at the International Fröhlich's Symposium entitled 'Electrodynamic Activity of Living Cells' (1-3 July 2011, Prague, Czech Republic). The Symposium was the 9th meeting devoted to physical processes in living matter organized in Prague since 1987. The hypothesis of oscillation systems in living cells featured by non-linear interaction between elastic and electrical polarization fields, non-linear interactions between the system and the heat bath leading to energy downconversion along the frequency scale, energy condensation in the lowest frequency mode and creation of a coherent state was formulated by H Fröhlich, founder of the theory of dielectric materials. He assumed that biological activity is based not only on biochemical but also on biophysical mechanisms and that their disturbances form basic links along the cancer transformation pathway. Fröhlich outlined general ideas of non-linear physical processes in biological systems. The downconversion and the elastic-polarization interactions should be connected in a unified theory and the solution based on comprehensive non-linear characteristics. Biochemical and genetic research of biological systems are highly developed and have disclosed a variety of cellular and subcellular structures, chemical reactions, molecular information transfer, and genetic code sequences - including their pathological development. Nevertheless, the cancer problem is still a big challenge. Warburg's discovery of suppressed oxidative metabolism in mitochondria in cancer cells suggested the essential role of physical mechanisms (but his discovery has remained without impact on cancer research and on the study of physical properties of biological systems for a long time). Mitochondria, the power plants of the cell, have several areas of activity-oxidative energy production is connected with the formation of a strong static electric field around them, water ordering, and liberation of non

  1. Accumulation of small heat shock proteins, including mitochondrial HSP22, induced by oxidative stress and adaptive response in tomato cells

    International Nuclear Information System (INIS)

    Banzet, N.; Richaud, C.; Deveaux, Y.; Kazmaier, M.; Gagnon, J.; Triantaphylides, C.

    1998-01-01

    Changes in gene expression, by application of H2O2, O2.- generating agents (methyl viologen, digitonin) and gamma irradiation to tomato suspension cultures, were investigated and compared to the well-described heat shock response. Two-dimensional gel protein mapping analyses gave the first indication that at least small heat shock proteins (smHSP) accumulated in response to application of H2O2 and gamma irradiation, but not to O2.- generating agents. While some proteins seemed to be induced specifically by each treatment, only part of the heat shock response was observed. On the basis of Northern hybridization experiments performed with four heterologous cDNA, corresponding to classes I-IV of pea smHSP, it could be concluded that significant amounts of class I and II smHSP mRNA are induced by H2O2 and by irradiation. Taken together, these results demonstrate that in plants some HSP genes are inducible by oxidative stresses, as in micro-organisms and other eukaryotic cells. HSP22, the main stress protein that accumulates following H2O2 action or gamma irradiation, was also purified. Sequence homology of amino terminal and internal sequences, and immunoreactivity with Chenopodium rubrum mitochondrial smHSP antibody, indicated that the protein belongs to the recently discovered class of plant mitochondrial smHSP. Heat shock or a mild H2O2 pretreatment was also shown to lead to plant cell protection against oxidative injury. Therefore, the synthesis of these stress proteins can be considered as an adaptive mechanism in which mitochondrial protection could be essential

  2. A constitutive model for the compressive response of metallic closed-cell foams including micro-inertia effects

    Directory of Open Access Journals (Sweden)

    Barthélémy Romain

    2015-01-01

    Full Text Available Metallic foams have known a keen interest in the last decades. Their ability to undergo very large deformations while transmitting low stress levels make them capable of performing functions of protective layers against intense loadings and of energy absorbers, for instance. The behaviour of metal foams varies considerably between quasi-static and dynamic regimes. Those differences can be linked to the strain-rate sensitivity of the skeleton material and to micro-inertial effects (induced by the crushing of the foam cells. In the present work, a micromechanical model has been developed to take into account micro-inertia effects on the macroscopic behaviour of closed-cell foams under dynamic loading conditions. The proposed modelling is based on the dynamic homogenisation procedure introduced by Molinari and Mercier (J. Mech. Phys. Solids 49 (2001 1497–1516. Within this framework, the macrostress is the sum of two terms. The first one is a static stress, that can be described with any existing model of metal foam. The second contribution is a dynamic stress related to micro-inertia effects. Considering an initially spherical shell as a Representative Volume Element (RVE of the foam material, a closed-form expression of the dynamic stress was obtained. The proposed modelling was applied to shock propagation in aluminium foams (it should however be noted that the present theory is not restricted to uniaxial deformation but can be applied to arbitrary loadings. From experimental data of the literature, it is observed that incorporating micro-inertia effects allows one to achieve a better description of the foam shock response. This indicates that micro-inertia may have a significant influence on the dynamic behaviour of metallic foams.

  3. R5-SHIV induces multiple defects in T cell function during early infection of rhesus macaques including accumulation of T reg cells in lymph nodes.

    Directory of Open Access Journals (Sweden)

    Michael Santosuosso

    2011-04-01

    Full Text Available HIV-1 is a pathogen that T cell responses fail to control. HIV-1gp120 is the surface viral envelope glycoprotein that interacts with CD4 T cells and mediates entry. HIV-1gp120 has been implicated in immune dysregulatory functions that may limit anti-HIV antigen-specific T cell responses. We hypothesized that in the context of early SHIV infection, immune dysregulation of antigen-specific T-effector cell and regulatory functions would be detectable and that these would be associated or correlated with measurable concentrations of HIV-1gp120 in lymphoid tissues.Rhesus macaques were intravaginally inoculated with a Clade C CCR5-tropic simian-human immunodeficiency virus, SHIV-1157ipd3N4. HIV-1gp120 levels, antigen-specificity, levels of apoptosis/anergy and frequency and function of Tregs were examined in lymph node and blood derived T cells at 5 and 12 weeks post inoculation.We observed reduced responses to Gag in CD4 and gp120 in CD8 lymph node-derived T cells compared to the peripheral blood at 5 weeks post-inoculation. Reduced antigen-specific responses were associated with higher levels of PD-1 on lymph node-derived CD4 T cells as compared to peripheral blood and uninfected lymph node-derived CD4 T cells. Lymph nodes contained increased numbers of Tregs as compared to peripheral blood, which positively correlated with gp120 levels; T regulatory cell depletion restored CD8 T cell responses to Gag but not to gp120. HIV gp120 was also able to induce T regulatory cell chemotaxis in a dose-dependent, CCR5-mediated manner. These studies contribute to our broader understanding of the ways in which HIV-1 dysregulates T cell function and localization during early infection.

  4. Biocatalyst including porous enzyme cluster composite immobilized by two-step crosslinking and its utilization as enzymatic biofuel cell

    Science.gov (United States)

    Chung, Yongjin; Christwardana, Marcelinus; Tannia, Daniel Chris; Kim, Ki Jae; Kwon, Yongchai

    2017-08-01

    An enzyme cluster composite (TPA/GOx) formed from glucose oxidase (GOx) and terephthalaldehyde (TPA) that is coated onto polyethyleneimine (PEI) and carbon nanotubes (CNTs) is suggested as a new catalyst ([(TPA/GOx)/PEI]/CNT). In this catalyst, TPA promotes inter-GOx links by crosslinking to form a large and porous structure, and the TPA/GOx composite is again crosslinked with PEI/CNT to increase the amount of immobilized GOx. Such a two-step crosslinking (i) increases electron transfer because of electron delocalization by π conjugation and (ii) reduces GOx denaturation because of the formation of strong chemical bonds while its porosity facilitates mass transfer. With these features, an enzymatic biofuel cell (EBC) employing the new catalyst is fabricated and induces an excellent maximum power density (1.62 ± 0.08 mW cm-2), while the catalytic activity of the [(TPA/GOx)/PEI]/CNT catalyst is outstanding. This is clear evidence that the two-step crosslinking and porous structure caused by adoption of the TPA/GOx composite affect the performance enhancement of EBC.

  5. Sensitivity of docetaxel-resistant MCF-7 breast cancer cells to microtubule-destabilizing agents including vinca alkaloids and colchicine-site binding agents.

    Directory of Open Access Journals (Sweden)

    Richard C Wang

    Full Text Available One of the main reasons for disease recurrence in the curative breast cancer treatment setting is the development of drug resistance. Microtubule targeted agents (MTAs are among the most commonly used drugs for the treatment of breaset cancer and therefore overcoming taxane resistance is of primary clinical importance. Our group has previously demonstrated that the microtubule dynamics of docetaxel-resistant MCF-7TXT cells are insensitivity to docetaxel due to the distinct expression profiles of β-tubulin isotypes in addition to the high expression of p-glycoprotein (ABCB1. In the present investigation we examined whether taxane-resistant breast cancer cells are more sensitive to microtubule destabilizing agents including vinca alkaloids and colchicine-site binding agents (CSBAs than the non-resistant cells.Two isogenic MCF-7 breast cancer cell lines were selected for resistance to docetaxel (MCF-7TXT and the wild type parental cell line (MCF-7CC to examine if taxane-resistant breast cancer cells are sensitive to microtubule-destabilizing agents including vinca alkaloids and CSBAs. Cytotoxicity assays, immunoblotting, indirect immunofluorescence and live imaging were used to study drug resistance, apoptosis, mitotic arrest, microtubule formation, and microtubule dynamics.MCF-7TXT cells were demonstrated to be cross resistant to vinca alkaloids, but were more sensitive to treatment with colchicine compared to parental non-resistant MCF-7CC cells. Cytotoxicity assays indicated that the IC50 of MCF-7TXT cell to vinorelbine and vinblastine was more than 6 and 3 times higher, respectively, than that of MCF-7CC cells. By contrast, the IC50 of MCF-7TXT cell for colchincine was 4 times lower than that of MCF-7CC cells. Indirect immunofluorescence showed that all MTAs induced the disorganization of microtubules and the chromatin morphology and interestingly each with a unique pattern. In terms of microtubule and chromain morphology, MCF-7TXT cells were

  6. Pleural fluid cell-free DNA integrity index to identify cytologically negative malignant pleural effusions including mesotheliomas

    International Nuclear Information System (INIS)

    Sriram, Krishna B; Courtney, Deborah; Yang, Ian A; Bowman, Rayleen V; Fong, Kwun M; Relan, Vandana; Clarke, Belinda E; Duhig, Edwina E; Windsor, Morgan N; Matar, Kevin S; Naidoo, Rishendran; Passmore, Linda; McCaul, Elizabeth

    2012-01-01

    The diagnosis of malignant pleural effusions (MPE) is often clinically challenging, especially if the cytology is negative for malignancy. DNA integrity index has been reported to be a marker of malignancy. The aim of this study was to evaluate the utility of pleural fluid DNA integrity index in the diagnosis of MPE. We studied 75 pleural fluid and matched serum samples from consecutive subjects. Pleural fluid and serum ALU DNA repeats [115bp, 247bp and 247bp/115bp ratio (DNA integrity index)] were assessed by real-time quantitative PCR. Pleural fluid and serum mesothelin levels were quantified using ELISA. Based on clinico-pathological evaluation, 52 subjects had MPE (including 16 mesotheliomas) and 23 had benign effusions. Pleural fluid DNA integrity index was higher in MPE compared with benign effusions (1.2 vs. 0.8; p<0.001). Cytology had a sensitivity of 55% in diagnosing MPE. If cytology and pleural fluid DNA integrity index were considered together, they exhibited 81% sensitivity and 87% specificity in distinguishing benign and malignant effusions. In cytology-negative pleural effusions (35 MPE and 28 benign effusions), elevated pleural fluid DNA integrity index had an 81% positive predictive value in detecting MPEs. In the detection of mesothelioma, at a specificity of 90%, pleural fluid DNA integrity index had similar sensitivity to pleural fluid and serum mesothelin (75% each respectively). Pleural fluid DNA integrity index is a promising diagnostic biomarker for identification of MPEs, including mesothelioma. This biomarker may be particularly useful in cases of MPE where pleural aspirate cytology is negative, and could guide the decision to undertake more invasive definitive testing. A prospective validation study is being undertaken to validate our findings and test the clinical utility of this biomarker for altering clinical practice

  7. The ethanol extract of Scutellaria baicalensis and the active compounds induce cell cycle arrest and apoptosis including upregulation of p53 and Bax in human lung cancer cells

    International Nuclear Information System (INIS)

    Gao Jiayu; Morgan, Winston A.; Sanchez-Medina, Alberto; Corcoran, Olivia

    2011-01-01

    Despite a lack of scientific authentication, Scutellaria baicalensis is clinically used in Chinese medicine as a traditional adjuvant to chemotherapy of lung cancer. In this study, cytotoxicity assays demonstrated that crude ethanolic extracts of S. baicalensis were selectively toxic to human lung cancer cell lines A549, SK-LU-1 and SK-MES-1 compared with normal human lung fibroblasts. The active compounds baicalin, baicalein and wogonin did not exhibit such selectivity. Following exposure to the crude extracts, cellular protein expression in the cancer cell lines was assessed using 2D gel electrophoresis coupled with MALDI-TOF-MS/Protein Fingerprinting. The altered protein expression indicated that cell growth arrest and apoptosis were potential mechanisms of cytotoxicity. These observations were supported by PI staining cell cycle analysis using flow cytometry and Annexin-V apoptotic analysis by fluorescence microscopy of cancer cells treated with the crude extract and pure active compounds. Moreover, specific immunoblotting identification showed the decreased expression of cyclin A results in the S phase arrest of A549 whereas the G 0 /G 1 phase arrest in SK-MES-1 cells results from the decreased expression of cyclin D1. Following treatment, increased expression in the cancer cells of key proteins related to the enhancement of apoptosis was observed for p53 and Bax. These results provide further insight into the molecular mechanisms underlying the clinical use of this herb as an adjuvant to lung cancer therapy. - Research highlights: → Scutellaria baicalensis is a clinical adjuvant to lung cancer chemotherapy in China. → Scutellaria ethanol extracts selectively toxic to A549, SK-LU-1 and SK-MES-1. → Baicalin, baicalein and wogonin were toxic to all lung cancer cell lines. → Proteomics identified increased p53 and BAX in response to Scutellaria extracts.

  8. Pediatric medulloblastoma xenografts including molecular subgroup 3 and CD133+ and CD15+ cells are sensitive to killing by oncolytic herpes simplex viruses.

    Science.gov (United States)

    Friedman, Gregory K; Moore, Blake P; Nan, Li; Kelly, Virginia M; Etminan, Tina; Langford, Catherine P; Xu, Hui; Han, Xiaosi; Markert, James M; Beierle, Elizabeth A; Gillespie, G Yancey

    2016-02-01

    Childhood medulloblastoma is associated with significant morbidity and mortality that is compounded by neurotoxicity for the developing brain caused by current therapies, including surgery, craniospinal radiation, and chemotherapy. Innate therapeutic resistance of some aggressive pediatric medulloblastoma has been attributed to a subpopulation of cells, termed cancer-initiating cells or cancer stemlike cells (CSCs), marked by the surface protein CD133 or CD15. Brain tumors characteristically contain areas of pathophysiologic hypoxia, which has been shown to drive the CSC phenotype leading to heightened invasiveness, angiogenesis, and metastasis. Novel therapies that target medulloblastoma CSCs are needed to improve outcomes and decrease toxicity. We hypothesized that oncolytic engineered herpes simplex virus (oHSV) therapy could effectively infect and kill pediatric medulloblastoma cells, including CSCs marked by CD133 or CD15. Using 4 human pediatric medulloblastoma xenografts, including 3 molecular subgroup 3 tumors, which portend worse patient outcomes, we determined the expression of CD133, CD15, and the primary HSV-1 entry molecule nectin-1 (CD111) by fluorescence activated cell sorting (FACS) analysis. Infectability and cytotoxicity of clinically relevant oHSVs (G207 and M002) were determined in vitro and in vivo by FACS, immunofluorescent staining, cytotoxicity assays, and murine survival studies. We demonstrate that hypoxia increased the CD133+ cell fraction, while having the opposite effect on CD15 expression. We established that all 4 xenografts, including the CSCs, expressed CD111 and were highly sensitive to killing by G207 or M002. Pediatric medulloblastoma, including Group 3 tumors, may be an excellent target for oHSV virotherapy, and a clinical trial in medulloblastoma is warranted. © The Author(s) 2015. Published by Oxford University Press on behalf of the Society for Neuro-Oncology. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.

  9. DSP30 and interleukin-2 as a mitotic stimulant in B-cell disorders including those with a low disease burden.

    Science.gov (United States)

    Dun, Karen A; Riley, Louise A; Diano, Giuseppe; Adams, Leanne B; Chiu, Eleanor; Sharma, Archna

    2018-05-01

    Chromosome abnormalities detected during cytogenetic investigations for B-cell malignancy offer prognostic information that can have wide ranging clinical impacts on patients. These impacts may include monitoring frequency, treatment type, and disease staging level. The use of the synthetic oligonucleotide DSP30 combined with interleukin 2 (IL2) has been described as an effective mitotic stimulant in B-cell disorders, not only in chronic lymphocytic leukemia (CLL) but also in a range of other B-cell malignancies. Here, we describe the comparison of two B-cell mitogens, lipopolysaccharide (LPS), and DSP30 combined with IL2 as mitogens in a range of common B-cell disorders excluding CLL. The results showed that DSP30/IL2 was an effective mitogen in mature B-cell disorders, revealing abnormal cytogenetic results in a range of B-cell malignancies. The abnormality rate increased when compared to the use of LPS to 64% (DSP30/IL2) from 14% (LPS). In a number of cases the disease burden was proportionally very low, less than 10% of white cells. In 37% of these cases, the DSP30 culture revealed abnormal results. Importantly, we also obtained abnormal conventional cytogenetics results in 3 bone marrow cases in which immunophenotyping showed an absence of an abnormal B-cell clone. In these cases, the cytogenetics results correlated with the provisional diagnosis and altered their staging level. The use of DSP30 and IL2 is recommended for use in many B-cell malignancies as an effective mitogen and their use has been shown to enable successful culture of the malignant clone, even at very low levels of disease. © 2018 Wiley Periodicals, Inc.

  10. Highly active antiretroviral therapy including protease inhibitors does not confer a unique CD4 cell benefit. The AVANTI and INCAS Study Groups.

    Science.gov (United States)

    2000-07-07

    To determine if triple combination therapy, particularly including HIV protease inhibitors (PI), confers an unique immunological benefit that is independent of reductions of plasma viral load (pVL). The correlation between changes from baseline in CD4 cell count and pVL was examined at all time points up to 52 weeks in three randomized clinical trials (AVANTI-2, AVANTI-3 and INCAS) that compared dual nucleoside therapy with triple combination therapy. Individual pVL and CD4 cell counts changes from baseline were entered into multivariate linear regression models for patients receiving double therapy and for those receiving triple therapy including a PI and/or a non-nucleoside reverse transcriptase inhibitor (NNRTI), and the null hypothesis was tested. After 52 weeks of therapy, the relationship between changes from baseline CD4 cell count and pVL was independent of whether patients were assigned double or triple therapy (P = 0.23 and 0.69 for intercept and slope, respectively), or whether patients were assigned triple therapy including a PI or triple therapy including an NNRTI (P = 0.92 and 0.95, respectively). Less than 5% of patients ever had 'discordant' increases in both CD4 cell count and pVL compared with baseline, and this proportion was unrelated to the class of therapy used. 'Discordant' decreases from baseline in both parameters were observed in up to 35% of individuals. The correlation between pVL and CD4 cell count changes from baseline improved over time on therapy, regardless of the therapeutic regimen involved. The data provide no evidence for a CD4 cell count benefit of highly active antiretroviral therapy (HAART) unique to triple therapy or PI-containing regimens.

  11. MiR-9 is overexpressed in spontaneous canine osteosarcoma and promotes a metastatic phenotype including invasion and migration in osteoblasts and osteosarcoma cell lines.

    Science.gov (United States)

    Fenger, Joelle M; Roberts, Ryan D; Iwenofu, O Hans; Bear, Misty D; Zhang, Xiaoli; Couto, Jason I; Modiano, Jaime F; Kisseberth, William C; London, Cheryl A

    2016-10-10

    alterations in numerous genes, including upregulation of GSN, an actin filament-severing protein involved in cytoskeletal remodeling. Lastly, stable downregulation of miR-9 in OS cell lines reduced GSN expression with a concomitant decrease in cell invasion and migration; concordantly, cells transduced with GSN shRNA demonstrated decreased invasive properties. Our findings demonstrate that miR-9 promotes a metastatic phenotype in normal canine osteoblasts and malignant OS cell lines, and that this is mediated in part by enhanced GSN expression. As such, miR-9 represents a novel target for therapeutic intervention in OS.

  12. Tumor Cell Anaplasia and Multinucleation Are Predictors of Disease Recurrence in Oropharyngeal Squamous Cell Carcinoma, Including Among Just the Human Papillomavirus-Related Cancers

    OpenAIRE

    Lewis, James S.; Scantlebury, Juliette B.; Luo, Jingqin; Thorstad, Wade L.

    2012-01-01

    Oropharyngeal squamous cell carcinoma (SCC) is frequently related to high risk human papillomavirus. This tumor expresses p16, frequently has a nonkeratinizing morphology, and has improved outcomes. Despite having a good prognosis, tumors can have focal or diffuse nuclear anaplasia or multinucleation, the significance of which is unknown. From a database of 270 oropharyngeal SCCs with known histologic typing (using our established system) and p16 immunohistochemistry, all su...

  13. Epigenetics targeted protein-vorinostat nanomedicine inducing apoptosis in heterogeneous population of primary acute myeloid leukemia cells including refractory and relapsed cases.

    Science.gov (United States)

    Chandran, Parwathy; Kavalakatt, Anu; Malarvizhi, Giridharan Loghanathan; Vasanthakumari, Divya Rani Vikraman Nair; Retnakumari, Archana Payickattu; Sidharthan, Neeraj; Pavithran, Keechilat; Nair, Shantikumar; Koyakutty, Manzoor

    2014-05-01

    Aberrant epigenetics play a key role in the onset and progression of acute myeloid leukemia (AML). Herein we report in silico modelling based development of a novel, protein-vorinostat nanomedicine exhibiting selective and superior anti-leukemic activity against heterogeneous population of AML patient samples (n=9), including refractory and relapsed cases, and three representative cell lines expressing CD34(+)/CD38(-) stem cell phenotype (KG-1a), promyelocytic phenotype (HL-60) and FLT3-ITD mutation (MV4-11). Nano-vorinostat having ~100nm size exhibited enhanced cellular uptake rendering significantly lower IC50 in AML cell lines and patient samples, and induced enhanced HDAC inhibition, oxidative injury, cell cycle arrest and apoptosis compared to free vorinostat. Most importantly, nanomedicine showed exceptional single-agent activity against the clonogenic proliferative capability of bone marrow derived leukemic progenitors, while remaining non-toxic to healthy bone marrow cells. Collectively, this epigenetics targeted nanomedicine appears to be a promising therapeutic strategy against various French-American-British (FAB) classes of AML. Through the use of a protein-vorinostat agent, exceptional single-agent activity was demonstrated against the clonogenic proliferative capability of bone marrow derived leukemic progenitors, while remaining non-toxic to healthy bone marrow cells. The studied epigenetics targeted nanomedicine approach is a promising therapeutic strategy against various French-American-British classes of acute myeloid leukemia. © 2014 Elsevier Inc. All rights reserved.

  14. Robust vaginal colonization of macaques with a novel vaginally disintegrating tablet containing a live biotherapeutic product to prevent HIV infection in women.

    Directory of Open Access Journals (Sweden)

    Laurel A Lagenaur

    Full Text Available MucoCept is a biotherapeutic for prevention of HIV-1 infection in women and contains a human, vaginal Lactobacillus jensenii that has been genetically enhanced to express the HIV-1 entry inhibitor, modified cyanovirin-N (mCV-N. The objective of this study was to develop a solid vaginal dosage form that supports sustained vaginal colonization of the MucoCept Lactobacillus at levels previously shown, with freshly prepared cultures, to protect macaques from SHIV infection and to test this formulation in a macaque vaginal colonization model. Vaginally disintegrating tablets were prepared by lyophilizing the formulated bacteria in tablet-shaped molds, then packaging in foil pouches with desiccant. Disintegration time, potency and stability of the tablets were assessed. For colonization, non-synchronized macaques were dosed vaginally with either one tablet or five tablets delivered over five days. Vaginal samples were obtained at three, 14, and 21 days post-dosing and cultured to determine Lactobacillus colonization levels. To confirm identity of the MucoCept Lactobacillus strain, genomic DNA was extracted from samples on days 14 and 21 and a strain-specific PCR was performed. Supernatants from bacteria were tested for the presence of the mCV-N protein by Western blot. The tablets were easy to handle, disintegrated within two minutes, potent (5.7x1011 CFU/g, and stable at 4°C and 25°C. Vaginal administration of the tablets to macaques resulted in colonization of the MucoCept Lactobacillus in 66% of macaques at 14 days post-dosing and 83% after 21 days. There was no significant difference in colonization levels for the one or five tablet dosing regimens (p=0.88 Day 14, p=0.99 Day 21. Strain-specific PCR confirmed the presence of the bacteria even in culture-negative macaques. Finally, the presence of mCV-N protein was confirmed by Western blot analysis using a specific anti-mCV-N antibody.

  15. Robust vaginal colonization of macaques with a novel vaginally disintegrating tablet containing a live biotherapeutic product to prevent HIV infection in women.

    Science.gov (United States)

    Lagenaur, Laurel A; Swedek, Iwona; Lee, Peter P; Parks, Thomas P

    2015-01-01

    MucoCept is a biotherapeutic for prevention of HIV-1 infection in women and contains a human, vaginal Lactobacillus jensenii that has been genetically enhanced to express the HIV-1 entry inhibitor, modified cyanovirin-N (mCV-N). The objective of this study was to develop a solid vaginal dosage form that supports sustained vaginal colonization of the MucoCept Lactobacillus at levels previously shown, with freshly prepared cultures, to protect macaques from SHIV infection and to test this formulation in a macaque vaginal colonization model. Vaginally disintegrating tablets were prepared by lyophilizing the formulated bacteria in tablet-shaped molds, then packaging in foil pouches with desiccant. Disintegration time, potency and stability of the tablets were assessed. For colonization, non-synchronized macaques were dosed vaginally with either one tablet or five tablets delivered over five days. Vaginal samples were obtained at three, 14, and 21 days post-dosing and cultured to determine Lactobacillus colonization levels. To confirm identity of the MucoCept Lactobacillus strain, genomic DNA was extracted from samples on days 14 and 21 and a strain-specific PCR was performed. Supernatants from bacteria were tested for the presence of the mCV-N protein by Western blot. The tablets were easy to handle, disintegrated within two minutes, potent (5.7x1011 CFU/g), and stable at 4°C and 25°C. Vaginal administration of the tablets to macaques resulted in colonization of the MucoCept Lactobacillus in 66% of macaques at 14 days post-dosing and 83% after 21 days. There was no significant difference in colonization levels for the one or five tablet dosing regimens (p=0.88 Day 14, p=0.99 Day 21). Strain-specific PCR confirmed the presence of the bacteria even in culture-negative macaques. Finally, the presence of mCV-N protein was confirmed by Western blot analysis using a specific anti-mCV-N antibody.

  16. Signal transduction profile of chemical sensitisers in dendritic cells: An endpoint to be included in a cell-based in vitro alternative approach to hazard identification?

    International Nuclear Information System (INIS)

    Neves, Bruno Miguel; Goncalo, Margarida; Figueiredo, Americo; Duarte, Carlos B.; Lopes, Maria Celeste; Cruz, Maria Teresa

    2011-01-01

    The development of non-animal testing methods for the assessment of skin sensitisation potential is an urgent challenge within the framework of existing and forthcoming legislation. Efforts have been made to replace current animal tests, but so far no alternative methods have been developed. It is widely recognised that alternatives to animal testing cannot be accomplished with a single approach, but rather will require the integration of results obtained from different in vitro and in silico assays. The argument subjacent to the development of in vitro dendritic cell (DC)-based assays is that sensitiser-induced changes in the DC phenotype can be differentiated from those induced by irritants. This assumption is derived from the unique capacity of DC to convert environmental signals encountered at the skin into a receptor expression pattern (MHC class II molecules, co-stimulatory molecules, chemokine receptors) and a soluble mediator release profile that will stimulate T lymphocytes. Since signal transduction cascades precede changes in surface marker expression and cytokine/chemokine secretion, these phenotypic modifications are a consequence of a signal transduction profile that is specifically triggered by sensitisers and not by irritants. A limited number of studies have addressed this subject and the present review attempts to summarise and highlight all of the signalling pathways modulated by skin sensitisers and irritants. Furthermore, we conclude this review by focusing on the most promising strategies suitable for inclusion into a cell-based in vitro alternative approach to hazard identification.

  17. Epigenetic profiling of cutaneous T-cell lymphoma: promoter hypermethylation of multiple tumor suppressor genes including BCL7a, PTPRG, and p73.

    Science.gov (United States)

    van Doorn, Remco; Zoutman, Willem H; Dijkman, Remco; de Menezes, Renee X; Commandeur, Suzan; Mulder, Aat A; van der Velden, Pieter A; Vermeer, Maarten H; Willemze, Rein; Yan, Pearlly S; Huang, Tim H; Tensen, Cornelis P

    2005-06-10

    To analyze the occurrence of promoter hypermethylation in primary cutaneous T-cell lymphoma (CTCL) on a genome-wide scale, focusing on epigenetic alterations with pathogenetic significance. DNA isolated from biopsy specimens of 28 patients with CTCL, including aggressive CTCL entities (transformed mycosis fungoides and CD30-negative large T-cell lymphoma) and an indolent entity (CD30-positive large T-cell lymphoma), were investigated. For genome-wide DNA methylation screening, differential methylation hybridization using CpG island microarrays was applied, which allows simultaneous detection of the methylation status of 8640 CpG islands. Bisulfite sequence analysis was applied for confirmation and detection of hypermethylation of eight selected tumor suppressor genes. The DNA methylation patterns of CTCLs emerging from differential methylation hybridization analysis included 35 CpG islands hypermethylated in at least four of the 28 studied CTCL samples when compared with benign T-cell samples. Hypermethylation of the putative tumor suppressor genes BCL7a (in 48% of CTCL samples), PTPRG (27%), and thrombospondin 4 (52%) was confirmed and demonstrated to be associated with transcriptional downregulation. BCL7a was hypermethylated at a higher frequency in aggressive (64%) than in indolent (14%) CTCL entities. In addition, the promoters of the selected tumor suppressor genes p73 (48%), p16 (33%), CHFR (19%), p15 (10%), and TMS1 (10%) were hypermethylated in CTCL. Malignant T cells of patients with CTCL display widespread promoter hypermethylation associated with inactivation of several tumor suppressor genes involved in DNA repair, cell cycle, and apoptosis signaling pathways. In view of this, CTCL may be amenable to treatment with demethylating agents.

  18. Enteric bacterial metabolites propionic and butyric acid modulate gene expression, including CREB-dependent catecholaminergic neurotransmission, in PC12 cells--possible relevance to autism spectrum disorders.

    Directory of Open Access Journals (Sweden)

    Bistra B Nankova

    Full Text Available Alterations in gut microbiome composition have an emerging role in health and disease including brain function and behavior. Short chain fatty acids (SCFA like propionic (PPA, and butyric acid (BA, which are present in diet and are fermentation products of many gastrointestinal bacteria, are showing increasing importance in host health, but also may be environmental contributors in neurodevelopmental disorders including autism spectrum disorders (ASD. Further to this we have shown SCFA administration to rodents over a variety of routes (intracerebroventricular, subcutaneous, intraperitoneal or developmental time periods can elicit behavioral, electrophysiological, neuropathological and biochemical effects consistent with findings in ASD patients. SCFA are capable of altering host gene expression, partly due to their histone deacetylase inhibitor activity. We have previously shown BA can regulate tyrosine hydroxylase (TH mRNA levels in a PC12 cell model. Since monoamine concentration is known to be elevated in the brain and blood of ASD patients and in many ASD animal models, we hypothesized that SCFA may directly influence brain monoaminergic pathways. When PC12 cells were transiently transfected with plasmids having a luciferase reporter gene under the control of the TH promoter, PPA was found to induce reporter gene activity over a wide concentration range. CREB transcription factor(s was necessary for the transcriptional activation of TH gene by PPA. At lower concentrations PPA also caused accumulation of TH mRNA and protein, indicative of increased cell capacity to produce catecholamines. PPA and BA induced broad alterations in gene expression including neurotransmitter systems, neuronal cell adhesion molecules, inflammation, oxidative stress, lipid metabolism and mitochondrial function, all of which have been implicated in ASD. In conclusion, our data are consistent with a molecular mechanism through which gut related environmental signals

  19. Orthogonal Assessment of Biotherapeutic Glycosylation: A Case Study Correlating N-Glycan Core Afucosylation of Herceptin with Mechanism of Action.

    Science.gov (United States)

    Upton, Rosie; Bell, Leonard; Guy, Colin; Caldwell, Paul; Estdale, Sian; Barran, Perdita E; Firth, David

    2016-10-18

    In the development of therapeutic antibodies and biosimilars, an appropriate biopharmaceutical CMC control strategy that connects critical quality attributes with mechanism of action should enable product assessment at an early stage of development in order to mitigate risk. Here we demonstrate a new analytical workflow using trastuzumab which comprises "middle-up" analysis using a combination of IdeS and the endoglycosidases EndoS and EndoS2 to comprehensively map the glycan content. Enzymatic cleavage between the two N-acetyl glucosamine residues of the chitobiose core of N-glycans significantly simplifies the oligosaccharide component enabling facile distinction of GlcNAc from GlcNAc with core fucose. This approach facilitates quantitative determination of total Fc-glycan core-afucosylation, which was in turn correlated with receptor binding affinity by surface plasmon resonance and in vitro ADCC potency with a cell based bioassay. The strategy also quantifies Fc-glycan occupancy and the relative contribution from high mannose glycans.

  20. A novel multimodal chromatography based single step purification process for efficient manufacturing of an E. coli based biotherapeutic protein product.

    Science.gov (United States)

    Bhambure, Rahul; Gupta, Darpan; Rathore, Anurag S

    2013-11-01

    Methionine oxidized, reduced and fMet forms of a native recombinant protein product are often the critical product variants which are associated with proteins expressed as bacterial inclusion bodies in E. coli. Such product variants differ from native protein in their structural and functional aspects, and may lead to loss of biological activity and immunogenic response in patients. This investigation focuses on evaluation of multimodal chromatography for selective removal of these product variants using recombinant human granulocyte colony stimulating factor (GCSF) as the model protein. Unique selectivity in separation of closely related product variants was obtained using combined pH and salt based elution gradients in hydrophobic charge induction chromatography. Simultaneous removal of process related impurities was also achieved in flow-through leading to single step purification process for the GCSF. Results indicate that the product recovery of up to 90.0% can be obtained with purity levels of greater than 99.0%. Binding the target protein at pHproduct variants using the combined pH and salt based elution gradient and removal of the host cell impurities in flow-through are the key novel features of the developed multimodal chromatographic purification step. Copyright © 2013 Elsevier B.V. All rights reserved.

  1. MiR-7 triggers cell cycle arrest at the G1/S transition by targeting multiple genes including Skp2 and Psme3.

    Directory of Open Access Journals (Sweden)

    Noelia Sanchez

    Full Text Available MiR-7 acts as a tumour suppressor in many cancers and abrogates proliferation of CHO cells in culture. In this study we demonstrate that miR-7 targets key regulators of the G1 to S phase transition, including Skp2 and Psme3, to promote increased levels of p27(KIP and temporary growth arrest of CHO cells in the G1 phase. Simultaneously, the down-regulation of DNA repair-specific proteins via miR-7 including Rad54L, and pro-apoptotic regulators such as p53, combined with the up-regulation of anti-apoptotic factors like p-Akt, promoted cell survival while arrested in G1. Thus miR-7 can co-ordinate the levels of multiple genes and proteins to influence G1 to S phase transition and the apoptotic response in order to maintain cellular homeostasis. This work provides further mechanistic insight into the role of miR-7 as a regulator of cell growth in times of cellular stress.

  2. In a patient with biclonal Waldenstrom macroglobulinemia only one clone expands in three-dimensional culture and includes putative cancer stem cells.

    Science.gov (United States)

    Kirshner, Julia; Thulien, Kyle J; Kriangkum, Jitra; Motz, Sarah; Belch, Andrew R; Pilarski, Linda M

    2011-02-01

    A small percentage of cases of Waldenstrom macroglobulinemia (WM) present with biclonality, defined here as the rearrangement of two distinct VDJ gene segments. Here we investigated the expansion of two clones from a patient with WM expressing molecularly detectable clonotypic gene rearrangements, one V(H)3 and one V(H)4. Biclonality was determined in blood and bone marrow mononuclear cells using real-time quantitative PCR (RQ-PCR). V(H)4 expressing cells but not V(H)3 expressing cells underwent clonal expansion in 3-D culture of reconstructed WM bone marrow. After 3-D culture, secondary culture in a colony forming unit assay, and RQ-PCR, only the V(H)4 clone was shown to harbor a subpopulation with characteristics of cancer stem cells, including proliferative quiescence, self-regeneration, and the ability to generate clonotypic progeny, suggesting that the V(H)4, but not the V(H)3, clone is clinically significant. Enrichment of potential WM stem cells in 3-D cultures holds promise for monitoring their response to treatment and for testing new therapies.

  3. Subvisible (2-100 μm) Particle Analysis During Biotherapeutic Drug Product Development: Part 1, Considerations and Strategy.

    Science.gov (United States)

    Narhi, Linda O; Corvari, Vincent; Ripple, Dean C; Afonina, Nataliya; Cecchini, Irene; Defelippis, Michael R; Garidel, Patrick; Herre, Andrea; Koulov, Atanas V; Lubiniecki, Tony; Mahler, Hanns-Christian; Mangiagalli, Paolo; Nesta, Douglas; Perez-Ramirez, Bernardo; Polozova, Alla; Rossi, Mara; Schmidt, Roland; Simler, Robert; Singh, Satish; Spitznagel, Thomas M; Weiskopf, Andrew; Wuchner, Klaus

    2015-06-01

    Measurement and characterization of subvisible particles (defined here as those ranging in size from 2 to 100 μm), including proteinaceous and nonproteinaceous particles, is an important part of every stage of protein therapeutic development. The tools used and the ways in which the information generated is applied depends on the particular product development stage, the amount of material, and the time available for the analysis. In order to compare results across laboratories and products, it is important to harmonize nomenclature, experimental protocols, data analysis, and interpretation. In this manuscript on perspectives on subvisible particles in protein therapeutic drug products, we focus on the tools available for detection, characterization, and quantification of these species and the strategy around their application. © 2015 Wiley Periodicals, Inc. and the American Pharmacists Association.

  4. Recognition of Core- and Polymerase-derived immunogenic peptides included in novel therapeutic vaccine by T cells from Chinese chronic hepatitis B patients.

    Science.gov (United States)

    Huang, D; Sansas, B; Jiang, J H; Gong, Q M; Jin, G D; Calais, V; Yu, D M; Zhu, M Y; Wei, D; Zhang, D H; Inchauspé, G; Zhang, X X; Zhu, R

    2017-11-01

    Chronic hepatitis B (CHB) is one of the major public health challenges in the world. Due to a strong interplay between specific T-cell immunity and elimination of hepatitis B virus (HBV), efforts to develop novel immunotherapeutics are gaining attention. TG1050, a novel immunotherapy, has shown efficacy in an animal study. To support the clinical development of TG1050 in China, specific immunity to the fusion antigens of TG1050 was assessed in Chinese patients. One hundred and thirty subjects were divided into three groups as CHB patients, HBV spontaneous resolvers, and CHB patients with HBsAg loss after antiviral treatment. HBV-specific T-cell responses to pools of HBV Core or Polymerase genotype D peptides included in TG1050 were evaluated. HBV Core- or Polymerase-specific cells were detected in peripheral blood mononuclear cells (PBMCs) from the different cohorts. The frequencies and intensities of HBV Core-specific immune responses were significantly lower in CHB patients than in HBsAg loss subjects. In CHB patients, a dominant pool derived from Polymerase (Pol1) was the most immunogenic. CHB patients with low viral loads (Core peptide pool. Overall, genotype D-derived peptides included in TG1050 could raise broad and functional T-cell responses in PBMCs from Chinese CHB patients infected with genotype B/C isolates. Core-specific immunogenic domains appeared as "hot spots" with the capacity to differentiate between CHB vs HBsAg loss subjects. These observations support the extended application and associated immune monitoring of TG1050 in China. © 2017 The Authors. Journal of Viral Hepatitis Published by John Wiley & Sons Ltd.

  5. MiR-9 is overexpressed in spontaneous canine osteosarcoma and promotes a metastatic phenotype including invasion and migration in osteoblasts and osteosarcoma cell lines

    International Nuclear Information System (INIS)

    Fenger, Joelle M.; Roberts, Ryan D.; Iwenofu, O. Hans; Bear, Misty D.; Zhang, Xiaoli; Couto, Jason I.; Modiano, Jaime F.; Kisseberth, William C.; London, Cheryl A.

    2016-01-01

    alterations in numerous genes, including upregulation of GSN, an actin filament-severing protein involved in cytoskeletal remodeling. Lastly, stable downregulation of miR-9 in OS cell lines reduced GSN expression with a concomitant decrease in cell invasion and migration; concordantly, cells transduced with GSN shRNA demonstrated decreased invasive properties. Our findings demonstrate that miR-9 promotes a metastatic phenotype in normal canine osteoblasts and malignant OS cell lines, and that this is mediated in part by enhanced GSN expression. As such, miR-9 represents a novel target for therapeutic intervention in OS. The online version of this article (doi:10.1186/s12885-016-2837-5) contains supplementary material, which is available to authorized users

  6. Investigation of the performance of fermentation processes using a mathematical model including effects of metabolic bottleneck and toxic product on cells.

    Science.gov (United States)

    Sriyudthsak, Kansuporn; Shiraishi, Fumihide

    2010-11-01

    A number of recent research studies have focused on theoretical and experimental investigation of a bottleneck in a metabolic reaction network. However, there is no study on how the bottleneck affects the performance of a fermentation process when a product is highly toxic and remarkably influences the growth and death of cells. The present work therefore studies the effect of bottleneck on product concentrations under different product toxicity conditions. A generalized bottleneck model in a fed-batch fermentation is constructed including both the bottleneck and the product influences on cell growth and death. The simulation result reveals that when the toxic product strongly influences the cell growth and death, the final product concentration is hardly changed even if the bottleneck is removed, whereas it is markedly changed by the degree of product toxicity. The performance of an ethanol fermentation process is also discussed as a case example to validate this result. In conclusion, when the product is highly toxic, one cannot expect a significant increase in the final product concentration even if removing the bottleneck; rather, it may be more effective to somehow protect the cells so that they can continuously produce the product. Copyright © 2010 Elsevier Inc. All rights reserved.

  7. Method Of Bonding A Metal Connection To An Electrode Including A Core Having A Fiber Or Foam Type Structure For An Electrochemical Cell, An

    Science.gov (United States)

    Loustau, Marie-Therese; Verhoog, Roelof; Precigout, Claude

    1996-09-24

    A method of bonding a metal connection to an electrode including a core having a fiber or foam-type structure for an electrochemical cell, in which method at least one metal strip is pressed against one edge of the core and is welded thereto under compression, wherein, at least in line with the region in which said strip is welded to the core, which is referred to as the "main core", a retaining core of a type analogous to that of the main core is disposed prior to the welding.

  8. Probiotics as oral health biotherapeutics.

    Science.gov (United States)

    Saha, Shyamali; Tomaro-Duchesneau, Catherine; Tabrizian, Maryam; Prakash, Satya

    2012-09-01

    Oral health is affected by its resident microorganisms. Three prominent oral disorders are dental caries, gingivitis and periodontitis, with the oral microbiota playing a key role in the initiation/progression of all three. Understanding the microbiota and the diseases they may cause is critical to the development of new therapeutics. This review is focused on probiotics for the prevention and/or treatment of oral diseases. This review describes the oral ecosystem and its correlation with oral health/disease. The pathogenesis and current prevention/treatment strategies of periodontal diseases (PD) and dental caries (DC) are depicted. An introduction of probiotics is followed by an analysis of their role in PD and DC, and their potential role(s) in oral health. Finally, a discussion ensues on the future research directions and limitations of probiotics for oral health. An effective oral probiotic formulation should contribute to the prevention/treatment of microbial diseases of the oral cavity. Understanding the oral microbiota's role in oral disease is important for the development of a therapeutic to prevent/treat dental diseases. However, investigations into clinical efficacy, delivery/dose optimization, mechanism(s) of action and other related parameters are yet to be fully explored. Keeping this in mind, investigations into oral probiotic therapies are proving promising.

  9. Biotherapeutics as alternatives to antibiotics

    Science.gov (United States)

    Increasing pressure to limit antibiotic use in agriculture is heightening the need for alternative methods to reduce the adverse effects of clinical and subclinical disease on livestock performance that are currently managed by in-feed antibiotic usage. Immunomodulators have long been sought as such...

  10. Mechanism of mucosal permeability enhancement of CriticalSorb® (Solutol® HS15) investigated In Vitro in cell cultures.

    OpenAIRE

    Shubber, Saif; Vllasaliu, Driton; Rauch, Cyril; Jordan, Faron; Illum, Lisbeth; Stolnik, Snjezana

    2015-01-01

    Purpose CriticalSorb?, with the principal component Solutol? HS15, is a novel mucosal drug delivery system demonstrated to improve the bioavailability of selected biotherapeutics. The intention of this study is to elucidate mechanism(s) responsible for the enhancement of trans-mucosal absorption of biological drugs by Solutol? HS15. Methods Micelle size and CMC of Solutol? HS15 were determined in biologically relevant media. Polarised airway Calu-3 cell layers were used to measure the permeab...

  11. Simulation and measurement of complete dye sensitised solar cells: including the influence of trapping, electrolyte, oxidised dyes and light intensity on steady state and transient device behaviour.

    Science.gov (United States)

    Barnes, Piers R F; Anderson, Assaf Y; Durrant, James R; O'Regan, Brian C

    2011-04-07

    A numerical model of the dye sensitised solar cell (DSSC) is used to assess the importance of different loss pathways under various operational conditions. Based on our current understanding, the simulation describes the processes of injection, regeneration, recombination and transport of electrons, oxidised dye molecules and electrolyte within complete devices to give both time dependent and independent descriptions of performance. The results indicate that the flux of electrons lost from the nanocrystalline TiO(2) film is typically at least twice as large under conditions equivalent to 1 sun relative to dark conditions at matched TiO(2) charge concentration. This is in agreement with experimental observations (Barnes et al. Phys. Chem. Chem. Phys. [DOI: 10.1039/c0cp01855d]). The simulated difference in recombination flux is shown to be due to variation in the concentration profile of electron accepting species in the TiO(2) pores between light and dark conditions and to recombination to oxidised dyes in the light. The model is able to easily incorporate non-ideal behaviour of a cell such as the variation of open circuit potential with light intensity and non-first order recombination of conduction band electrons. The time dependent simulations, described by the multiple trapping model of electron transport and recombination, show good agreement with both small and large transient photocurrent and photovoltage measurements at open circuit, including photovoltage rise measurements. The simulation of photovoltage rise also suggests the possibility of assessing the interfacial resistance between the TiO(2) and substrate. When cells with a short diffusion length relative to film thickness were modelled, the simulated small perturbation photocurrent transients at short circuit (but not open circuit) yielded significantly higher effective diffusion coefficients than expected from the mean concentration of electrons and the electrolyte in the cell. This implies that

  12. Optimizing Staining Protocols for Laser Microdissection of Specific Cell Types from the Testis Including Carcinoma In Situ

    DEFF Research Database (Denmark)

    Sonne, Si Brask; Dalgaard, Marlene D; Nielsen, John Erik

    2009-01-01

    Microarray and RT-PCR based methods are important tools for analysis of gene expression; however, in tissues containing many different cells types, such as the testis, characterization of gene expression in specific cell types can be severely hampered by noise from other cells. The laser microdis......Microarray and RT-PCR based methods are important tools for analysis of gene expression; however, in tissues containing many different cells types, such as the testis, characterization of gene expression in specific cell types can be severely hampered by noise from other cells. The laser...... protocols, and present two staining protocols for frozen sections, one for fast and specific staining of fetal germ cells, testicular carcinoma in situ cells, and other cells with embryonic stem cell-like properties that express the alkaline phosphatase, and one for specific staining of lipid droplet...

  13. Plant-based oral tolerance to hemophilia therapy employs a complex immune regulatory response including LAP+CD4+ T cells

    OpenAIRE

    Wang, Xiaomei; Su, Jin; Sherman, Alexandra; Rogers, Geoffrey L.; Liao, Gongxian; Hoffman, Brad E.; Leong, Kam W.; Terhorst, Cox; Daniell, Henry; Herzog, Roland W.

    2015-01-01

    Coadministering FIX orally and systemically induces tolerance via complex immune regulation, involving tolerogenic dendritic and T-cell subsets.Induced CD4+CD25−LAP+ regulatory T cells with increased IL-10 and TGF-β expression and CD4+CD25+ regulatory T cells suppress antibody formation against FIX.

  14. Predictive value of diffusion-weighted imaging without and with including contrast-enhanced magnetic resonance imaging in image analysis of head and neck squamous cell carcinoma

    Energy Technology Data Exchange (ETDEWEB)

    Noij, Daniel P., E-mail: d.noij@vumc.nl [Department of Radiology and Nuclear Medicine, VU University Medical Center, De Boelelaan 1117, Amsterdam, Noord-Holland (Netherlands); Pouwels, Petra J.W., E-mail: pjw.pouwels@vumc.nl [Department of Physics and Medical Technology, VU University Medical Center, De Boelelaan 1117, Amsterdam, Noord-Holland (Netherlands); Ljumanovic, Redina, E-mail: rljumanovic@adventh.org [Department of Radiology and Nuclear Medicine, VU University Medical Center, De Boelelaan 1117, Amsterdam, Noord-Holland (Netherlands); Knol, Dirk L., E-mail: dirklknol@gmail.com [Department of Epidemiology and Biostatistics, VU University Medical Center, De Boelelaan 1117, Amsterdam, Noord-Holland (Netherlands); Doornaert, Patricia, E-mail: p.doornaert@vumc.nl [Department of Radiation Oncology, VU University Medical Center, De Boelelaan 1117, Amsterdam, Noord-Holland (Netherlands); Bree, Remco de, E-mail: r.debree@vumc.nl [Department of Otolaryngology – Head and Neck Surgery, VU University Medical Center, De Boelelaan 1117, Amsterdam, Noord-Holland (Netherlands); Castelijns, Jonas A., E-mail: j.castelijns@vumc.nl [Department of Radiology and Nuclear Medicine, VU University Medical Center, De Boelelaan 1117, Amsterdam, Noord-Holland (Netherlands); Graaf, Pim de, E-mail: p.degraaf@vumc.nl [Department of Radiology and Nuclear Medicine, VU University Medical Center, De Boelelaan 1117, Amsterdam, Noord-Holland (Netherlands)

    2015-01-15

    Highlights: • Primary tumor volume and lymph node ADC1000 are predictors of survival. • CE-T1WI does not improve the prognostic capacity of DWI. • Using CE-T1WI for ROI placement results in lower interobserver agreement. - Abstract: Objectives: To assess disease-free survival (DFS) in head and neck squamous cell carcinoma (HNSCC) treated with (chemo)radiotherapy ([C]RT). Methods: Pretreatment MR-images of 78 patients were retrospectively studied. Apparent diffusion coefficients (ADC) were calculated with two sets of two b-values: 0–750 s/mm{sup 2} (ADC{sub 750}) and 0–1000 s/mm{sup 2} (ADC{sub 1000}). One observer assessed tumor volume on T1-WI. Two independent observers assessed ADC-values of primary tumor and largest lymph node in two sessions (i.e. without and with including CE-T1WI in image analysis). Interobserver and intersession agreement were assessed with intraclass correlation coefficients (ICC) separately for ADC{sub 750} and ADC{sub 1000}. Lesion volumes and ADC-values were related to DFS using Cox regression analysis. Results: Median follow-up was 18 months. Interobserver ICC was better without than with CE-T1WI (primary tumor: 0.92 and 0.75–0.83, respectively; lymph node: 0.81–0.83 and 0.61–0.64, respectively). Intersession ICC ranged from 0.84 to 0.89. With CE-T1WI, mean ADC-values of primary tumor and lymph node were higher at both b-values than without CE-T1WI (P < 0.001). Tumor volume (sensitivity: 73%; specificity: 57%) and lymph node ADC{sub 1000} (sensitivity: 71–79%; specificity: 77–79%) were independent significant predictors of DFS without and with including CE-T1WI (P < 0.05). Conclusions: Pretreatment primary tumor volume and lymph node ADC{sub 1000} were significant independent predictors of DFS in HNSCC treated with (C)RT. DFS could be predicted from ADC-values acquired without and with including CE-T1WI in image analysis. The inclusion of CE-T1WI did not result in significant improvements in the predictive value of

  15. Platyphylloside Isolated From Betula platyphylla Inhibit Adipocyte Differentiation and Induce Lipolysis Via Regulating Adipokines Including PPARγ in 3T3-L1 Cells

    Science.gov (United States)

    Lee, Mina; Sung, Sang Hyun

    2016-01-01

    Background: Obesity causes or aggravates many health problems, both independently and in association with several pathological disorders, including Type II diabetes, hypertension, atherosclerosis, and cancer. Therefore, we screened small compounds isolated from natural products for the development of anti-obesity drugs. Objective: The purpose of this study was to investigate the anti-adipogenic activities of platyphylloside, diarylheptanoid isolated from Betula platyphylla, which was selected based on the screening using 3T3-L1 cells. Materials and Methods: To evaluate the inhibition of adipocyte differentiation and lipolysis, lipid contents of BPP on were measured using Oil Red O staining in 3T3-L1 cells. The mRNA and protein expression levels of various adipokines were measured by Quantitative real-time PCR and Western blotting analysis, respectively. Results: Platyphylloside showed significant inhibitory activity on adipocyte differentiation in 3T3-L1 cells and suppressed adipocyte differentiation even in the presence of troglitazone, a PPARγ agonist. Platyphylloside might suppress adipocyte differentiation through PPARγ, C/EBPα, and SREBP1-induced adipogenesis, which is synergistically associated with downstream adipocyte-specific gene promoters such as aP2, FAS, SCD-1, LPL, and Adiponectin. In addition, platyphylloside affected lipolysis by down-regulating perilipin and HSL and up-regulating TNFα. Conclusion: Taken together, the results reveal that platyphylloside has anti-adipogenic activity and highlight its potential in the prevention and treatment of obesity. SUMMARY The extract of B. platyphylla bark and its isolate, BPP, had anti-adipogenic activity in 3T3-L1 cells via suppression of adipocyte differentiation from preadipocytes.Treatment with BPP significantly down-regulated the expression of PPARγ, C/EBP, C/EBPβ, C/EBPδ, SREBP1c, SCD-1, FAS, aP2 and LPL.BPP induced a lipolytic response in mature adipocytes via up-regulation krof TNFá and down

  16. Coating of Biomaterial Scaffolds with the Collagen-Mimetic Peptide GFOGER for Bone Defect Repair

    OpenAIRE

    Wojtowicz, Abigail M.; Shekaran, Asha; Oest, Megan E.; Dupont, Kenneth M.; Templeman, Kellie L.; Hutmacher, Dietmar W.; Guldberg, Robert E.; García, Andrés J.

    2009-01-01

    Healing large bone defects and non-unions remains a significant clinical problem. Current treatments, consisting of auto- and allografts, are limited by donor supply and morbidity, insufficient bioactivity and risk of infection. Biotherapeutics, including cells, genes and proteins, represent promising alternative therapies, but these strategies are limited by technical roadblocks to biotherapeutic delivery, cell sourcing, high cost, and regulatory hurdles. In the present study, the collagen-m...

  17. Whole-body-MR imaging including DWIBS in the work-up of patients with head and neck squamous cell carcinoma: A feasibility study

    Energy Technology Data Exchange (ETDEWEB)

    Noij, Daniel P., E-mail: d.noij@vumc.nl [Department of Radiology and Nuclear Medicine, VU University Medical Center, De Boelelaan 1117, PO Box 7057, 1007 MB Amsterdam (Netherlands); Boerhout, Els J., E-mail: e.boerhout@vumc.nl [Department of Radiology and Nuclear Medicine, VU University Medical Center, De Boelelaan 1117, PO Box 7057, 1007 MB Amsterdam (Netherlands); Pieters-van den Bos, Indra C., E-mail: i.pieters@vumc.nl [Department of Radiology and Nuclear Medicine, VU University Medical Center, De Boelelaan 1117, PO Box 7057, 1007 MB Amsterdam (Netherlands); Comans, Emile F., E-mail: efi.comans@vumc.nl [Department of Radiology and Nuclear Medicine, VU University Medical Center, De Boelelaan 1117, PO Box 7057, 1007 MB Amsterdam (Netherlands); Oprea-Lager, Daniela, E-mail: d.oprea-lager@vumc.nl [Department of Radiology and Nuclear Medicine, VU University Medical Center, De Boelelaan 1117, PO Box 7057, 1007 MB Amsterdam (Netherlands); Reinhard, Rinze, E-mail: r.reinhard@vumc.nl [Department of Radiology and Nuclear Medicine, VU University Medical Center, De Boelelaan 1117, PO Box 7057, 1007 MB Amsterdam (Netherlands); Hoekstra, Otto S., E-mail: os.hoekstra@vumc.nl [Department of Radiology and Nuclear Medicine, VU University Medical Center, De Boelelaan 1117, PO Box 7057, 1007 MB Amsterdam (Netherlands); Bree, Remco de, E-mail: r.debree@vumc.nl [Department Otolaryngology/Head and Neck Surgery, VU University Medical Center, De Boelelaan 1117, PO Box 7057, 1007 MB Amsterdam (Netherlands); Graaf, Pim de, E-mail: p.degraaf@vumc.nl [Department of Radiology and Nuclear Medicine, VU University Medical Center, De Boelelaan 1117, PO Box 7057, 1007 MB Amsterdam (Netherlands); Castelijns, Jonas A., E-mail: j.castelijns@vumc.nl [Department of Radiology and Nuclear Medicine, VU University Medical Center, De Boelelaan 1117, PO Box 7057, 1007 MB Amsterdam (Netherlands)

    2014-07-15

    Objectives: To assess the feasibility of whole-body magnetic resonance imaging (WB-MRI) including diffusion-weighted whole-body imaging with background-body-signal-suppression (DWIBS) for the evaluation of distant malignancies in head and neck squamous cell carcinoma (HNSCC); and to compare WB-MRI findings with {sup 18}F-fluorodeoxyglucose positron emission tomography/computed tomography ({sup 18}F-FDG-PET/CT) and chest-CT. Methods: Thirty-three patients with high risk for metastatic spread (26 males; range 48–79 years, mean age 63 ± 7.9 years (mean ± standard deviation) years) were prospectively included with a follow-up of six months. WB-MRI protocol included short-TI inversion recovery and T1-weighted sequences in the coronal plane and half-fourier acquisition single-shot turbo spin-echo T2 and contrast-enhanced-T1-weighted sequences in the axial plane. Axial DWIBS was reformatted in the coronal plane. Interobserver variability was assessed using weighted kappa and the proportion specific agreement (PA). Results: Two second primary tumors and one metastasis were detected on WB-MRI. WB-MRI yielded seven clinically indeterminate lesions which did not progress at follow-up. The metastasis and one second primary tumor were found when combining {sup 18}F-FDG-PET/CT and chest-CT findings. Interobserver variability for WB-MRI was κ = 0.91 with PA ranging from 0.82 to 1.00. For {sup 18}F-FDG-PET/CT κ could not be calculated due to a constant variable in the table and PA ranged from 0.40 to 0.99. Conclusions: Our WB-MRI protocol with DWIBS is feasible in the work-up of HNSCC patients for detection and characterization of distant pathology. WB-MRI can be complementary to {sup 18}F-FDG-PET/CT, especially in the detection of non {sup 18}F-FDG avid second primary tumors.

  18. Diagnostic terminology for urinary cytology reports including the new subcategories 'atypical urothelial cells of undetermined significance' (AUC-US) and 'cannot exclude high grade' (AUC-H).

    Science.gov (United States)

    Piaton, E; Decaussin-Petrucci, M; Mege-Lechevallier, F; Advenier, A-S; Devonec, M; Ruffion, A

    2014-02-01

    We studied whether atypical, non-superficial urothelial cells (AUC) could be separated into new subcategories including AUC 'of undetermined significance' (AUC-US) and 'cannot exclude high grade'' (AUC-H) in order to help to standardize urine cytopathology reports, as it is widely accepted in the Bethesda system for gynaecological cytopathology. We investigated whether AUC-US and AUC-H, defined by distinctive cytological criteria, might be separated with statistical significance according to actual diagnosis and follow-up data. A series of 534 cyto-histological comparisons taken in 139 patients, including 221 AUC at various steps of their clinical history was studied. There were 513 (96.1%) postcystoscopy and 469 (87.8%) ThinPrep® liquid-based specimens (95.9% and 89.1% of AUC cases, respectively). Patients viewed between 1999 and 2011 had histological control in a 0- to 6-months delay and were followed-up during an additional 5.9 ± 9.2 (0- to 56-) months period. The 221 AUC represented 0.8-2% of the specimens viewed during the study period. Among AUC-H cases, 70 out of 185 (37.8%) matched with high-grade lesions, compared with 3 of 38 (8.3%) of AUC-US cases (P = 0.0003). Conservatively treated patients with AUC-H more frequently developed high-grade lesions than those with AUC-US (54.1% versus 16.7%, P = 0.0007) with a 17.6-months mean delay. Nuclear hyperchromasia, a nuclear to cytoplasm (N/C) ratio > 0.7 and the combination of both were the more informative diagnostic criteria, all with P < 0.01. We conclude that the new subcategories could help to standardize urine cytopathology reports and contribute to the patient's management, provided it is validated by multicentric studies. © 2013 John Wiley & Sons Ltd.

  19. Tropism and Infectivity of Influenza Virus, Including Highly Pathogenic Avian H5N1 Virus, in Ferret Tracheal Differentiated Primary Epithelial Cell Cultures

    Science.gov (United States)

    Zeng, Hui; Goldsmith, Cynthia S.; Maines, Taronna R.; Belser, Jessica A.; Gustin, Kortney M.; Pekosz, Andrew; Zaki, Sherif R.; Katz, Jacqueline M.

    2013-01-01

    Tropism and adaptation of influenza viruses to new hosts is partly dependent on the distribution of the sialic acid (SA) receptors to which the viral hemagglutinin (HA) binds. Ferrets have been established as a valuable in vivo model of influenza virus pathogenesis and transmission because of similarities to humans in the distribution of HA receptors and in clinical signs of infection. In this study, we developed a ferret tracheal differentiated primary epithelial cell culture model that consisted of a layered epithelium structure with ciliated and nonciliated cells on its apical surface. We found that human-like (α2,6-linked) receptors predominated on ciliated cells, whereas avian-like (α2,3-linked) receptors, which were less abundant, were presented on nonciliated cells. When we compared the tropism and infectivity of three human (H1 and H3) and two avian (H1 and H5) influenza viruses, we observed that the human influenza viruses primarily infected ciliated cells and replicated efficiently, whereas a highly pathogenic avian H5N1 virus (A/Vietnam/1203/2004) replicated efficiently within nonciliated cells despite a low initial infection rate. Furthermore, compared to other influenza viruses tested, VN/1203 virus replicated more efficiently in cells isolated from the lower trachea and at a higher temperature (37°C) compared to a lower temperature (33°C). VN/1203 virus infection also induced higher levels of immune mediator genes and cell death, and virus was recovered from the basolateral side of the cell monolayer. This ferret tracheal differentiated primary epithelial cell culture system provides a valuable in vitro model for studying cellular tropism, infectivity, and the pathogenesis of influenza viruses. PMID:23255802

  20. HuB (elavl2 mRNA is restricted to the germ cells by post-transcriptional mechanisms including stabilisation of the message by DAZL.

    Directory of Open Access Journals (Sweden)

    Sophie E Wiszniak

    Full Text Available The ability of germ cells to carry out a gene regulatory program distinct from the surrounding somatic tissue, and their capacity to specify an entire new organism has made them a focus of many studies that seek to understand how specific regulatory mechanisms, particularly post-transcriptional mechanisms, contribute to cell fate. In zebrafish, germ cells are specified through the inheritance of cytoplasmic determinants, termed the germ plasm, which contains a number of maternal mRNAs and proteins. Investigation of several of these messages has revealed that the restricted localisation of these mRNAs to the germ plasm and subsequent germ cells is due to cis-acting sequence elements present in their 3'UTRs. Here we show that a member of the Hu family of RNA-binding proteins, HuB, is maternally provided in the zebrafish embryo and exhibits germ cell specific expression during embryogenesis. Restriction of HuB mRNA to the germ cells is dependent on a number of sequence elements in its 3'UTR, which act to degrade the mRNA in the soma and stabilise it in the germ cells. In addition, we show that the germ cell specific RNA-binding protein DAZL is able to promote HuB mRNA stability and translation in germ cells, and further demonstrate that these activities require a 30 nucleotide element in the 3'UTR. Our study suggests that DAZL specifically binds the HuB 3'UTR and protects the message from degradation and/or enhances HuB translation, leading to the germ cell specific expression of HuB protein.

  1. A pacemaker powered by an implantable biofuel cell operating under conditions mimicking the human blood circulatory system--battery not included.

    Science.gov (United States)

    Southcott, Mark; MacVittie, Kevin; Halámek, Jan; Halámková, Lenka; Jemison, William D; Lobel, Robert; Katz, Evgeny

    2013-05-07

    Biocatalytic electrodes made of buckypaper were modified with PQQ-dependent glucose dehydrogenase on the anode and with laccase on the cathode and were assembled in a flow biofuel cell filled with serum solution mimicking the human blood circulatory system. The biofuel cell generated an open circuitry voltage, Voc, of ca. 470 mV and a short circuitry current, Isc, of ca. 5 mA (a current density of 0.83 mA cm(-2)). The power generated by the implantable biofuel cell was used to activate a pacemaker connected to the cell via a charge pump and a DC-DC converter interface circuit to adjust the voltage produced by the biofuel cell to the value required by the pacemaker. The voltage-current dependencies were analyzed for the biofuel cell connected to an Ohmic load and to the electronic loads composed of the interface circuit, or the power converter, and the pacemaker to study their operation. The correct pacemaker operation was confirmed using a medical device - an implantable loop recorder. Sustainable operation of the pacemaker was achieved with the system closely mimicking human physiological conditions using a single biofuel cell. This first demonstration of the pacemaker activated by the physiologically produced electrical energy shows promise for future electronic implantable medical devices powered by electricity harvested from the human body.

  2. Plant-based oral tolerance to hemophilia therapy employs a complex immune regulatory response including LAP+CD4+ T cells.

    Science.gov (United States)

    Wang, Xiaomei; Su, Jin; Sherman, Alexandra; Rogers, Geoffrey L; Liao, Gongxian; Hoffman, Brad E; Leong, Kam W; Terhorst, Cox; Daniell, Henry; Herzog, Roland W

    2015-04-09

    Coagulation factor replacement therapy for the X-linked bleeding disorder hemophilia is severely complicated by antibody ("inhibitor") formation. We previously found that oral delivery to hemophilic mice of cholera toxin B subunit-coagulation factor fusion proteins expressed in chloroplasts of transgenic plants suppressed inhibitor formation directed against factors VIII and IX and anaphylaxis against factor IX (FIX). This observation and the relatively high concentration of antigen in the chloroplasts prompted us to evaluate the underlying tolerance mechanisms. The combination of oral delivery of bioencapsulated FIX and intravenous replacement therapy induced a complex, interleukin-10 (IL-10)-dependent, antigen-specific systemic immune suppression of pathogenic antibody formation (immunoglobulin [Ig] 1/inhibitors, IgE) in hemophilia B mice. Tolerance induction was also successful in preimmune mice but required prolonged oral delivery once replacement therapy was resumed. Orally delivered antigen, initially targeted to epithelial cells, was taken up by dendritic cells throughout the small intestine and additionally by F4/80(+) cells in the duodenum. Consistent with the immunomodulatory responses, frequencies of tolerogenic CD103(+) and plasmacytoid dendritic cells were increased. Ultimately, latency-associated peptide expressing CD4(+) regulatory T cells (CD4(+)CD25(-)LAP(+) cells with upregulated IL-10 and transforming growth factor-β (TGF-β) expression) as well as conventional CD4(+)CD25(+) regulatory T cells systemically suppressed anti-FIX responses. © 2015 by The American Society of Hematology.

  3. Treating cell culture media with UV irradiation against adventitious agents: minimal impact on CHO performance.

    Science.gov (United States)

    Yen, Sandi; Sokolenko, Stanislav; Manocha, Bhavik; Blondeel, Eric J M; Aucoin, Marc G; Patras, Ankit; Daynouri-Pancino, Farnaz; Sasges, Michael

    2014-01-01

    Sterility of cell culture media is an important concern in biotherapeutic processing. In large scale biotherapeutic production, a unit contamination of cell culture media can have costly effects. Ultraviolet (UV) irradiation is a sterilization method effective against bacteria and viruses while being non-thermal and non-adulterating in its mechanism of action. This makes UV irradiation attractive for use in sterilization of cell culture media. The objective of this study was to evaluate the effect of UV irradiation of cell culture media in terms of chemical composition and the ability to grow cell cultures in the treated media. The results showed that UV irradiation of commercial cell culture media at relevant disinfection doses impacted the chemical composition of the media with respect to several carboxylic acids, and to a minimal extent, amino acids. The cumulative effect of these changes, however, did not negatively influence the ability to culture Chinese Hamster Ovary cells, as evaluated by cell viability, growth rate, and protein titer measurements in simple batch growth compared with the same cells cultured in control media exposed to visible light. © 2014 The Authors. Published by Wiley Periodicals, Inc. on behalf of American Institute of Chemical Engineers.

  4. Immunofluorescence Microscopy and mRNA Analysis of Human Embryonic Stem Cells (hESCs) Including Primary Cilia Associated Signaling Pathways

    DEFF Research Database (Denmark)

    Vestergaard, Maj Linea; Awan, Aashir; Warzecha, Caroline Becker

    2016-01-01

    onto 16-well glass chambers, and continuing with the general IFM and qPCR anlysis. The techniques are illustrated with results on cellular localization of transcriptional factors and components of the Hedgehog, Wnt, PDGF, and TGFβ signaling pathways to primary cilia in stem cell maintenance......This chapter describes the procedures for immunofluorescence microscopy (IFM) and quantitative PCR (qPCR) analyses of human embryonic stem cells (hESCs) grown specifically under feeder-free conditions. A detailed protocol is provided outlining the steps from initially growing the cells, passaging...

  5. Design of the integration interface between the EU HCPB TBM and the ITER TBM port plug including hot cell operations for connection

    International Nuclear Information System (INIS)

    Neuberger, H.; Boccaccini, L.V.; Roccella, R.

    2007-01-01

    In the frame of the activities of the EU Breeder Blanket Programme and of the Test Blanket Working Group, the Helium Cooled Pebble Bed Test Blanket Module- (HCPB-TBM) System is developed. The TBM test schedule foresees four different campaigns for simulation of DEMO relevant conditions, campaign requires a dedicate TBM. Therefore a concept for TBM integration into ITER is designed with attention to simplify the mounting/dismounting operations. This paper presents the status of this concept with regard to the operations in hot cell required to install a new TBM into an equatorial TBM Port Plug (PP). This includes the establishment of the connection for the attachment, supply- and diagnostic lines in the environment of the interface (IF 1) between the TBM rear part and the PP backside shield. The connection of IF 1 has to be designed to cope with a temperature difference between TBM and PP (∝200 K) and the EM-loads during normal operation and disruption scenarios. The reference attachment concept based on shear keys and flexible cartridges is revised to cope with new conditions on the load and at the interface to the PP. According to the latest results of EM analysis, a radial component of the Maxwell forces (due to the ferromagnetic structural material) has been identified as an additional challenging load for the attachment. Furthermore, the replacing operations at IF 1 are influenced by the design of the PP; the recent ITER proposal based on a removable back side shield allows access to the IF 1 from the periphery after the frame of the PP surrounding the TBM is removed. As for the mechanical attachment, the tools and operations for connection of the TBM supply lines (Helium-, Purge- and measurement lines for different purpose depending on the test schedule) are strongly influenced by the restrictions to access IF 1, too. Dismantling of the frame would allow direct access to the interface by e.g. orbital welding tools. The concept for connection of the TBM

  6. The T Cell Response to Major Grass Allergens Is Regulated and Includes IL-10 Production in Atopic but Not in Non-Atopic Subjects

    DEFF Research Database (Denmark)

    Domdey, A.; Liu, A.; Millner, A.

    2010-01-01

    in allergen-specific responses. The aim was to determine whether major grass allergens induce production of suppressive cytokines in allergic and healthy subjects and to examine the inhibitory effect of these cytokines on allergic responses. Methods: Peripheral blood mononuclear cells (PBMCs) were isolated...... from healthy and grass-allergic donors and stimulated with the major grass allergens Phl p 1 or Phl p 5. The effects of endogenous IL-10 and/or TGF-beta on proliferation and cytokine production were determined by use of blocking antibodies. In addition, the number of CD4(+)CD25(+) T cells...... in PBMCs in the two groups, but fewer cells from atopic donors were CD4(+)CD25(+)CCR4(+) and more cells were CD4(+)CD25(+)CLA(+) compared to healthy donors. Conclusion: Allergen-specific responses of grass allergic patients but not in non-atopic subjects are influenced by regulatory cytokines produced...

  7. Numerical investigation of a double-junction a:SiGe thin-film solar cell including the multi-trench region

    International Nuclear Information System (INIS)

    Kacha, K.; Djeffal, F.; Ferhati, H.; Arar, D.; Meguellati, M.

    2015-01-01

    We present a new approach based on the multi-trench technique to improve the electrical performances, which are the fill factor and the electrical efficiency. The key idea behind this approach is to introduce a new multi-trench region in the intrinsic layer, in order to modulate the total resistance of the solar cell. Based on 2-D numerical investigation and optimization of amorphous SiGe double-junction (a-Si:H/a-SiGe:H) thin film solar cells, in the present paper numerical models of electrical and optical parameters are developed to explain the impact of the multi-trench technique on the improvement of the double-junction solar cell electrical behavior for high performance photovoltaic applications. In this context, electrical characteristics of the proposed design are analyzed and compared with conventional amorphous silicon double-junction thin-film solar cells. (paper)

  8. Phage T4 endonuclease V stimulates DNA repair replication in isolated nuclei from ultraviolet-irradiated human cells, including xeroderma pigmentosum fibroblasts

    International Nuclear Information System (INIS)

    Smith, C.A.; Hanawalt, P.C.

    1978-01-01

    The repair mode of DNA replication has been demonstrated in isolated nuclei from uv-irradiated human cells. Nuclei are incubated in a mixture containing [ 3 H]thymidine triphosphate and bromodeoxyuridine triphosphate in a 1:5 ratio. The 3 H at the density of parental DNA in alkaline CsCl density gradients is then a measure of repair. In nuclei prepared from WI38 cells 30 min after irradiation, repair replication is uv-dependent and proceeds at approximately the in vivo rate for 5 min. Repair replication is reduced in irradiated nuclei or in nuclei prepared immediately after irradiation. It is Mg 2+ -dependent and stimulated by added ATP and deoxyribonucleoside triphosphates. No repair replication is observed in nuclei from xeroderma pigmentosum (complementation group A) cells. However, upon addition of coliphage T4 endonuclease V, which specifically nicks DNA containing pyrimidine dimers, repair replication is observed in nuclei from irradiated xeroderma pigmentosum cells and is stimulated in WI38 nuclei. The reaction then persists for an hour and is dependent upon added ATP and deoxyribonucleoside triphosphates. The repair label is in stretches of roughly 35 nucleotides, as it is in intact cells. Added pancreatic DNase does not promote uv-dependent repair synthesis. Our results support the view that xeroderma pigmentosum (group A) cells are defective in the incision step of the DNA excision repair pathway, and demonstrate the utility of this system for probing DNA repair mechanisms

  9. Anti-Infective Activities of Lactobacillus Strains in the Human Intestinal Microbiota: from Probiotics to Gastrointestinal Anti-Infectious Biotherapeutic Agents

    Science.gov (United States)

    Liévin-Le Moal, Vanessa

    2014-01-01

    SUMMARY A vast and diverse array of microbial species displaying great phylogenic, genomic, and metabolic diversity have colonized the gastrointestinal tract. Resident microbes play a beneficial role by regulating the intestinal immune system, stimulating the maturation of host tissues, and playing a variety of roles in nutrition and in host resistance to gastric and enteric bacterial pathogens. The mechanisms by which the resident microbial species combat gastrointestinal pathogens are complex and include competitive metabolic interactions and the production of antimicrobial molecules. The human intestinal microbiota is a source from which Lactobacillus probiotic strains have often been isolated. Only six probiotic Lactobacillus strains isolated from human intestinal microbiota, i.e., L. rhamnosus GG, L. casei Shirota YIT9029, L. casei DN-114 001, L. johnsonii NCC 533, L. acidophilus LB, and L. reuteri DSM 17938, have been well characterized with regard to their potential antimicrobial effects against the major gastric and enteric bacterial pathogens and rotavirus. In this review, we describe the current knowledge concerning the experimental antibacterial activities, including antibiotic-like and cell-regulating activities, and therapeutic effects demonstrated in well-conducted, placebo-controlled, randomized clinical trials of these probiotic Lactobacillus strains. What is known about the antimicrobial activities supported by the molecules secreted by such probiotic Lactobacillus strains suggests that they constitute a promising new source for the development of innovative anti-infectious agents that act luminally and intracellularly in the gastrointestinal tract. PMID:24696432

  10. Animal cell cultures: recent achievements and perspectives in the production of biopharmaceuticals.

    Science.gov (United States)

    Butler, Michael

    2005-08-01

    There has been a rapid increase in the number and demand for approved biopharmaceuticals produced from animal cell culture processes over the last few years. In part, this has been due to the efficacy of several humanized monoclonal antibodies that are required at large doses for therapeutic use. There have also been several identifiable advances in animal cell technology that has enabled efficient biomanufacture of these products. Gene vector systems allow high specific protein expression and some minimize the undesirable process of gene silencing that may occur in prolonged culture. Characterization of cellular metabolism and physiology has enabled the design of fed-batch and perfusion bioreactor processes that has allowed a significant improvement in product yield, some of which are now approaching 5 g/L. Many of these processes are now being designed in serum-free and animal-component-free media to ensure that products are not contaminated with the adventitious agents found in bovine serum. There are several areas that can be identified that could lead to further improvement in cell culture systems. This includes the down-regulation of apoptosis to enable prolonged cell survival under potentially adverse conditions. The characterization of the critical parameters of glycosylation should enable process control to reduce the heterogeneity of glycoforms so that production processes are consistent. Further improvement may also be made by the identification of glycoforms with enhanced biological activity to enhance clinical efficacy. The ability to produce the ever-increasing number of biopharmaceuticals by animal cell culture is dependent on sufficient bioreactor capacity in the industry. A recent shortfall in available worldwide culture capacity has encouraged commercial activity in contract manufacturing operations. However, some analysts indicate that this still may not be enough and that future manufacturing demand may exceed production capacity as the number

  11. The T cell response to major grass allergens is regulated and includes IL-10 production in atopic but not in non-atopic subjects

    DEFF Research Database (Denmark)

    Domdey, A; Liu, A; Millner, A

    2010-01-01

    The incidence of allergic diseases is increasing in industrialized countries and the immunological mechanisms leading to tolerance or allergy are poorly understood. Cytokines with suppressive abilities and CD4(+)CD25(+) regulatory T cells have been suggested to play a central role in allergen-spe...

  12. Granular cell tumor of the oral cavity; a case series including a case of metachronous occurrence in the tongue and the lung

    NARCIS (Netherlands)

    van de Loo, S.; Thunissen, E.; Postmus, P.; van der Waal, I.

    2015-01-01

    The granular cell tumor (GCT) is a rare, benign tumor that most commonly occurs in the oral cavity, particularly in the anterior part of the tongue. In this study the experience with 16 patients with a GCT observed in a single Institution will be discussed. Although no radicality has been obtained

  13. Hybrid [{sup 18}F]-FDG PET/MRI including non-Gaussian diffusion-weighted imaging (DWI): Preliminary results in non-small cell lung cancer (NSCLC)

    Energy Technology Data Exchange (ETDEWEB)

    Heusch, Philipp [Univ Dusseldorf, Medical Faculty, Department of Diagnostic and Interventional Radiology, D-40225 Dusseldorf (Germany); Univ Duisburg-Essen, Medical Faculty, Department of Diagnostic and Interventional Radiology and Neuroradiology, D-45147 Essen (Germany); Köhler, Jens [Univ Duisburg-Essen, Medical Faculty, Department of Medical Oncology, D-45147 Essen (Germany); Wittsack, Hans-Joerg [Univ Dusseldorf, Medical Faculty, Department of Diagnostic and Interventional Radiology, D-40225 Dusseldorf (Germany); Heusner, Till A., E-mail: Heusner@med.uni-duesseldorf.de [Univ Dusseldorf, Medical Faculty, Department of Diagnostic and Interventional Radiology, D-40225 Dusseldorf (Germany); Buchbender, Christian [Univ Dusseldorf, Medical Faculty, Department of Diagnostic and Interventional Radiology, D-40225 Dusseldorf (Germany); Poeppel, Thorsten D. [Univ Duisburg-Essen, Medical Faculty, Department of Nuclear Medicine, D-45147 Essen (Germany); Nensa, Felix; Wetter, Axel [Univ Duisburg-Essen, Medical Faculty, Department of Diagnostic and Interventional Radiology and Neuroradiology, D-45147 Essen (Germany); Gauler, Thomas [Univ Duisburg-Essen, Medical Faculty, Department of Medical Oncology, D-45147 Essen (Germany); Hartung, Verena [Univ Duisburg-Essen, Medical Faculty, Department of Nuclear Medicine, D-45147 Essen (Germany); Lanzman, Rotem S. [Univ Dusseldorf, Medical Faculty, Department of Diagnostic and Interventional Radiology, D-40225 Dusseldorf (Germany)

    2013-11-01

    Purpose: To assess the feasibility of non-Gaussian DWI as part of a FDG-PET/MRI protocol in patients with histologically proven non-small cell lung cancer. Material and methods: 15 consecutive patients with histologically proven NSCLC (mean age 61 ± 11 years) were included in this study and underwent whole-body FDG-PET/MRI following whole-body FDG-PET/CT. As part of the whole-body FDG-PET/MRI protocol, an EPI-sequence with 5 b-values (0, 100, 500, 1000 and 2000 s/mm{sup 2}) was acquired for DWI of the thorax during free-breathing. Volume of interest (VOI) measurements were performed to determine the maximum and mean standardized uptake value (SUV{sub max}; SUV{sub mean}). A region of interest (ROI) was manually drawn around the tumor on b = 0 images and then transferred to the corresponding parameter maps to assess ADC{sub mono}, D{sub app} and K{sub app}. To assess the goodness of the mathematical fit R{sup 2} was calculated for monoexponential and non-Gaussian analysis. Spearman's correlation coefficients were calculated to compare SUV values and diffusion coefficients. A Student's t-test was performed to compare the monoexponential and non-Gaussian diffusion fitting (R{sup 2}). Results: T staging was equal between FDG-PET/CT and FDG-PET/MRI in 12 of 15 patients. For NSCLC, mean ADC{sub mono} was 2.11 ± 1.24 × 10{sup −3} mm{sup 2}/s, D{sub app} was 2.46 ± 1.29 × 10{sup −3} mm{sup 2}/s and mean K{sub app} was 0.70 ± 0.21. The non-Gaussian diffusion analysis (R{sup 2} = 0.98) provided a significantly better mathematical fitting to the DWI signal decay than the monoexponetial analysis (R{sup 2} = 0.96) (p < 0.001). SUV{sub max} and SUV{sub mean} of NSCLC was 13.5 ± 7.6 and 7.9 ± 4.3 for FDG-PET/MRI. ADC{sub mono} as well as D{sub app} exhibited a significant inverse correlation with the SUV{sub max} (ADC{sub mono}: R = −0.67; p < 0.01; D{sub app}: R = −0.69; p < 0.01) as well as with SUV{sub mean} assessed by FDG-PET/MRI (ADC{sub mono}: R

  14. SU-D-BRB-06: Treating Glioblastoma Multiforme (GBM) as a Chronic Disease: Implication of Temporal-Spatial Dose Fractionation Optimization Including Cancer Stem Cell Dynamics

    Energy Technology Data Exchange (ETDEWEB)

    Yu, V; Nguyen, D; Pajonk, F; Kaprealian, T; Kupelian, P; Steinberg, M; Low, D; Sheng, K [Department of Radiation Oncology, UCLA, Los Angeles, CA (United States)

    2015-06-15

    Purpose: To explore the feasibility of improving GBM treatment outcome with temporal-spatial dose optimization of an ordinary differential equation (ODE) that models the differentiation and distinct radiosensitivity between cancer stem cells (CSC) and differentiated cancer cells (DCC). Methods: The ODE was formulated into a non-convex optimization problem with the objective to minimize remaining total cancer cells 500 days from the onset of radiotherapy when the total cancer cell number was 3.5×10{sup 7}, while maintaining normal tissue biological effective dose (BED) of 100Gy resulted from standard prescription of 2Gyx30. Assuming spatially separated CSC and DCC, optimization was also performed to explore the potential benefit from dose-painting the two compartments. Dose escalation to a sub-cell-population in the GTV was also examined assuming that a 2 cm margin around the GTV allows sufficient dose drop-off to 100Gy BED. The recurrence time was determined as the time at which the total cancer cell number regrows to 10{sup 9} cells. Results: The recurrence time with variable fractional doses administered once per week, bi-week and month for one year were found to be 615, 593 and 570 days, superior to the standard-prescription recurrence time of 418 days. The optimal dose-fraction size progression for both uniform and dose-painting to the tumor is low and relatively constant in the beginning and gradually increases to more aggressive fractions at end of the treatment course. Dose escalation to BED of 200Gy to the whole tumor alongside with protracted weekly treatment was found to further delay recurrence to 733 days. Dose-painting of 200 and 500Gy BED to CSC on a year-long weekly schedule further extended recurrence to 736 and 1076 days, respectively. Conclusion: GBM treatment outcome can possibly be improved with a chronic treatment approach. Further dose escalation to the entire tumor or CSC targeted killing is needed to achieve total tumor control. This work

  15. MYR1-Dependent Effectors Are the Major Drivers of a Host Cell's Early Response to Toxoplasma, Including Counteracting MYR1-Independent Effects.

    Science.gov (United States)

    Naor, Adit; Panas, Michael W; Marino, Nicole; Coffey, Michael J; Tonkin, Christopher J; Boothroyd, John C

    2018-04-03

    The obligate intracellular parasite Toxoplasma gondii controls its host cell from within the parasitophorous vacuole (PV) by using a number of diverse effector proteins, a subset of which require the aspartyl protease 5 enzyme (ASP5) and/or the recently discovered MYR1 protein to cross the PV membrane. To examine the impact these effectors have in the context of the entirety of the host response to Toxoplasma , we used RNA-Seq to analyze the transcriptome expression profiles of human foreskin fibroblasts infected with wild-type RH (RH-WT), RHΔ myr1 , and RHΔ asp5 tachyzoites. Interestingly, the majority of the differentially regulated genes responding to Toxoplasma infection are MYR1 dependent. A subset of MYR1 responses were ASP5 independent, and MYR1 function did not require ASP5 cleavage, suggesting the export of some effectors requires only MYR1. Gene set enrichment analysis of MYR1-dependent host responses suggests an upregulation of E2F transcription factors and the cell cycle and a downregulation related to interferon signaling, among numerous others. Most surprisingly, "hidden" responses arising in RHΔ myr1 - but not RH-WT-infected host cells indicate counterbalancing actions of MYR1-dependent and -independent activities. The host genes and gene sets revealed here to be MYR1 dependent provide new insight into the parasite's ability to co-opt host cell functions. IMPORTANCE Toxoplasma gondii is unique in its ability to successfully invade and replicate in a broad range of host species and cells within those hosts. The complex interplay of effector proteins exported by Toxoplasma is key to its success in co-opting the host cell to create a favorable replicative niche. Here we show that a majority of the transcriptomic effects in tachyzoite-infected cells depend on the activity of a novel translocation system involving MYR1 and that the effectors delivered by this system are part of an intricate interplay of activators and suppressors. Removal of all MYR1

  16. Nanotechnology in stem cells research: advances and applications.

    Science.gov (United States)

    Deb, Kaushik Dilip; Griffith, May; Muinck, Ebo De; Rafat, Mehrdad

    2012-01-01

    Human beings suffer from a myriad of disorders caused by biochemical or biophysical alteration of physiological systems leading to organ failure. For a number of these conditions, stem cells and their enormous reparative potential may be the last hope for restoring function to these failing organ or tissue systems. To harness the potential of stem cells for biotherapeutic applications, we need to work at the size scale of molecules and processes that govern stem cells fate. Nanotechnology provides us with such capacity. Therefore, effective amalgamation of nanotechnology and stem cells - medical nanoscience or nanomedicine - offers immense benefits to the human race. The aim of this paper is to discuss the role and importance of nanotechnology in stem cell research by focusing on several important areas such as stem cell visualization and imaging, genetic modifications and reprogramming by gene delivery systems, creating stem cell niche, and similar therapeutic applications.

  17. Cellular Phone Towers, Cell tower locations as derived from various sources including the Department of Licenses and Inspections and the Department of Planning and Zoning., Published in 2010, 1:2400 (1in=200ft) scale, Howard County Government.

    Data.gov (United States)

    NSGIC Local Govt | GIS Inventory — Cellular Phone Towers dataset current as of 2010. Cell tower locations as derived from various sources including the Department of Licenses and Inspections and the...

  18. A model predictive control strategy for the space heating of a smart building including cogeneration of a fuel cell-electrolyzer system

    DEFF Research Database (Denmark)

    Sossan, Fabrizio; Bindner, Henrik W.; Madsen, Henrik

    2014-01-01

    The objective of this paper is to analyze the value of energy replacement in the context of demand response. Energy replacement is dened as the possibility of the consumer to choose the most convenient source for providing space heating to a smart building according to a dynamic electricity price....... In the proposed setup, heat is provided by conventional electric radiators and a combined heat and power generation system, composed by a fuel cell and an electrolyzer. The energy replacement strategy is formulated using model predictive control and mathematical models of the components involved. Simulations show...... that the predictive energy replacement strategy reduces the operating costs of the system and is able to provide a larger amount of regulating power to the grid. In the paper, we also develop a novel dynamic model of a PEM fuel cell suitable for micro-grid applications. The model is realized applying a grey...

  19. Preprotachykinin A is expressed by a distinct population of excitatory neurons in the mouse superficial spinal dorsal horn including cells that respond to noxious and pruritic stimuli.

    Science.gov (United States)

    Gutierrez-Mecinas, Maria; Bell, Andrew M; Marin, Alina; Taylor, Rebecca; Boyle, Kieran A; Furuta, Takahiro; Watanabe, Masahiko; Polgár, Erika; Todd, Andrew J

    2017-03-01

    The superficial dorsal horn, which is the main target for nociceptive and pruritoceptive primary afferents, contains a high density of excitatory interneurons. Our understanding of their roles in somatosensory processing has been restricted by the difficulty of distinguishing functional populations among these cells. We recently defined 3 nonoverlapping populations among the excitatory neurons, based on the expression of neurotensin, neurokinin B, and gastrin-releasing peptide. Here we identify and characterise another population: neurons that express the tachykinin peptide substance P. We show with immunocytochemistry that its precursor protein (preprotachykinin A, PPTA) can be detected in ∼14% of lamina I-II neurons, and these are concentrated in the outer part of lamina II. Over 80% of the PPTA-positive cells lack the transcription factor Pax2 (which determines an inhibitory phenotype), and these account for ∼15% of the excitatory neurons in this region. They are different from the neurotensin, neurokinin B, or gastrin-releasing peptide neurons, although many of them contain somatostatin, which is widely expressed among superficial dorsal horn excitatory interneurons. We show that many of these cells respond to noxious thermal and mechanical stimuli and to intradermal injection of pruritogens. Finally, we demonstrate that these cells can also be identified in a knock-in Cre mouse line (Tac1), although our findings suggest that there is an additional population of neurons that transiently express PPTA. This population of substance P-expressing excitatory neurons is likely to play an important role in the transmission of signals that are perceived as pain and itch.

  20. Consumption of Dairy Yogurt Containing Lactobacillus paracasei ssp. paracasei, Bifidobacterium animalis ssp. lactis and Heat-Treated Lactobacillus plantarum Improves Immune Function Including Natural Killer Cell Activity

    Science.gov (United States)

    Lee, Ayoung; Lee, Young Ju; Yoo, Hye Jin; Kim, Minkyung; Chang, Yeeun; Lee, Dong Seog; Lee, Jong Ho

    2017-01-01

    The aim of this study was to investigate the impact of consuming dairy yogurt containing Lactobacillus paracasei ssp. paracasei (L. paracasei), Bifidobacterium animalis ssp. lactis (B. lactis) and heat-treated Lactobacillus plantarum (L. plantarum) on immune function. A randomized, open-label, placebo-controlled study was conducted on 200 nondiabetic subjects. Over a twelve-week period, the test group consumed dairy yogurt containing probiotics each day, whereas the placebo group consumed milk. Natural killer (NK) cell activity, interleukin (IL)-12 and immunoglobulin (Ig) G1 levels were significantly increased in the test group at twelve weeks compared to baseline. Additionally, the test group had significantly greater increases in serum NK cell activity and interferon (IFN)-γ and IgG1 than placebo group. Daily consumption of dairy yogurt containing L. paracasei, B. lactis and heat-treated L. plantarum could be an effective option to improve immune function by enhancing NK cell function and IFN-γ concentration (ClinicalTrials.gov: NCT03051425). PMID:28561762

  1. Consumption of Dairy Yogurt Containing Lactobacillus paracasei ssp. paracasei, Bifidobacterium animalis ssp. lactis and Heat-Treated Lactobacillus plantarum Improves Immune Function Including Natural Killer Cell Activity

    Directory of Open Access Journals (Sweden)

    Ayoung Lee

    2017-05-01

    Full Text Available The aim of this study was to investigate the impact of consuming dairy yogurt containing Lactobacillus paracasei ssp. paracasei (L. paracasei, Bifidobacterium animalis ssp. lactis (B. lactis and heat-treated Lactobacillus plantarum (L. plantarum on immune function. A randomized, open-label, placebo-controlled study was conducted on 200 nondiabetic subjects. Over a twelve-week period, the test group consumed dairy yogurt containing probiotics each day, whereas the placebo group consumed milk. Natural killer (NK cell activity, interleukin (IL-12 and immunoglobulin (Ig G1 levels were significantly increased in the test group at twelve weeks compared to baseline. Additionally, the test group had significantly greater increases in serum NK cell activity and interferon (IFN-γ and IgG1 than placebo group. Daily consumption of dairy yogurt containing L. paracasei, B. lactis and heat-treated L. plantarum could be an effective option to improve immune function by enhancing NK cell function and IFN-γ concentration (ClinicalTrials.gov: NCT03051425.

  2. Consumption of Dairy Yogurt Containing Lactobacillus paracasei ssp. paracasei, Bifidobacterium animalis ssp. lactis and Heat-Treated Lactobacillus plantarum Improves Immune Function Including Natural Killer Cell Activity.

    Science.gov (United States)

    Lee, Ayoung; Lee, Young Ju; Yoo, Hye Jin; Kim, Minkyung; Chang, Yeeun; Lee, Dong Seog; Lee, Jong Ho

    2017-05-31

    The aim of this study was to investigate the impact of consuming dairy yogurt containing Lactobacillus paracasei ssp. paracasei ( L. paracasei ), Bifidobacterium animalis ssp. lactis ( B. lactis ) and heat-treated Lactobacillus plantarum ( L. plantarum ) on immune function. A randomized, open-label, placebo-controlled study was conducted on 200 nondiabetic subjects. Over a twelve-week period, the test group consumed dairy yogurt containing probiotics each day, whereas the placebo group consumed milk. Natural killer (NK) cell activity, interleukin (IL)-12 and immunoglobulin (Ig) G1 levels were significantly increased in the test group at twelve weeks compared to baseline. Additionally, the test group had significantly greater increases in serum NK cell activity and interferon (IFN)-γ and IgG1 than placebo group. Daily consumption of dairy yogurt containing L. paracasei , B. lactis and heat-treated L. plantarum could be an effective option to improve immune function by enhancing NK cell function and IFN-γ concentration (ClinicalTrials.gov: NCT03051425).

  3. Dynamic Regulation of a Cell Adhesion Protein Complex Including CADM1 by Combinatorial Analysis of FRAP with Exponential Curve-Fitting

    Science.gov (United States)

    Sakurai-Yageta, Mika; Maruyama, Tomoko; Suzuki, Takashi; Ichikawa, Kazuhisa; Murakami, Yoshinori

    2015-01-01

    Protein components of cell adhesion machinery show continuous renewal even in the static state of epithelial cells and participate in the formation and maintenance of normal epithelial architecture and tumor suppression. CADM1 is a tumor suppressor belonging to the immunoglobulin superfamily of cell adhesion molecule and forms a cell adhesion complex with an actin-binding protein, 4.1B, and a scaffold protein, MPP3, in the cytoplasm. Here, we investigate dynamic regulation of the CADM1-4.1B-MPP3 complex in mature cell adhesion by fluorescence recovery after photobleaching (FRAP) analysis. Traditional FRAP analysis were performed for relatively short period of around 10min. Here, thanks to recent advances in the sensitive laser detector systems, we examine FRAP of CADM1 complex for longer period of 60 min and analyze the recovery with exponential curve-fitting to distinguish the fractions with different diffusion constants. This approach reveals that the fluorescence recovery of CADM1 is fitted to a single exponential function with a time constant (τ) of approximately 16 min, whereas 4.1B and MPP3 are fitted to a double exponential function with two τs of approximately 40-60 sec and 16 min. The longer τ is similar to that of CADM1, suggesting that 4.1B and MPP3 have two distinct fractions, one forming a complex with CADM1 and the other present as a free pool. Fluorescence loss in photobleaching analysis supports the presence of a free pool of these proteins near the plasma membrane. Furthermore, double exponential fitting makes it possible to estimate the ratio of 4.1B and MPP3 present as a free pool and as a complex with CADM1 as approximately 3:2 and 3:1, respectively. Our analyses reveal a central role of CADM1 in stabilizing the complex with 4.1B and MPP3 and provide insight in the dynamics of adhesion complex formation. PMID:25780926

  4. Identification of a developmental gene expression signature, including HOX genes, for the normal human colonic crypt stem cell niche: overexpression of the signature parallels stem cell overpopulation during colon tumorigenesis.

    Science.gov (United States)

    Bhatlekar, Seema; Addya, Sankar; Salunek, Moreh; Orr, Christopher R; Surrey, Saul; McKenzie, Steven; Fields, Jeremy Z; Boman, Bruce M

    2014-01-15

    Our goal was to identify a unique gene expression signature for human colonic stem cells (SCs). Accordingly, we determined the gene expression pattern for a known SC-enriched region--the crypt bottom. Colonic crypts and isolated crypt subsections (top, middle, and bottom) were purified from fresh, normal, human, surgical specimens. We then used an innovative strategy that used two-color microarrays (∼18,500 genes) to compare gene expression in the crypt bottom with expression in the other crypt subsections (middle or top). Array results were validated by PCR and immunostaining. About 25% of genes analyzed were expressed in crypts: 88 preferentially in the bottom, 68 in the middle, and 131 in the top. Among genes upregulated in the bottom, ∼30% were classified as growth and/or developmental genes including several in the PI3 kinase pathway, a six-transmembrane protein STAMP1, and two homeobox (HOXA4, HOXD10) genes. qPCR and immunostaining validated that HOXA4 and HOXD10 are selectively expressed in the normal crypt bottom and are overexpressed in colon carcinomas (CRCs). Immunostaining showed that HOXA4 and HOXD10 are co-expressed with the SC markers CD166 and ALDH1 in cells at the normal crypt bottom, and the number of these co-expressing cells is increased in CRCs. Thus, our findings show that these two HOX genes are selectively expressed in colonic SCs and that HOX overexpression in CRCs parallels the SC overpopulation that occurs during CRC development. Our study suggests that developmental genes play key roles in the maintenance of normal SCs and crypt renewal, and contribute to the SC overpopulation that drives colon tumorigenesis.

  5. Cell culture isolation and sequence analysis of genetically diverse US porcine epidemic diarrhea virus strains including a novel strain with a large deletion in the spike gene.

    Science.gov (United States)

    Oka, Tomoichiro; Saif, Linda J; Marthaler, Douglas; Esseili, Malak A; Meulia, Tea; Lin, Chun-Ming; Vlasova, Anastasia N; Jung, Kwonil; Zhang, Yan; Wang, Qiuhong

    2014-10-10

    The highly contagious and deadly porcine epidemic diarrhea virus (PEDV) first appeared in the US in April 2013. Since then the virus has spread rapidly nationwide and to Canada and Mexico causing high mortality among nursing piglets and significant economic losses. Currently there are no efficacious preventive measures or therapeutic tools to control PEDV in the US. The isolation of PEDV in cell culture is the first step toward the development of an attenuated vaccine, to study the biology of PEDV and to develop in vitro PEDV immunoassays, inactivation assays and screen for PEDV antivirals. In this study, nine of 88 US PEDV strains were isolated successfully on Vero cells with supplemental trypsin and subjected to genomic sequence analysis. They differed genetically mainly in the N-terminal S protein region as follows: (1) strains (n=7) similar to the highly virulent US PEDV strains; (2) one similar to the reportedly US S INDEL PEDV strain; and (3) one novel strain most closely related to highly virulent US PEDV strains, but with a large (197aa) deletion in the S protein. Representative strains of these three genetic groups were passaged serially and grew to titers of ∼5-6log10 plaque forming units/mL. To our knowledge, this is the first report of the isolation in cell culture of an S INDEL PEDV strain and a PEDV strain with a large (197aa) deletion in the S protein. We also designed primer sets to detect these genetically diverse US PEDV strains. Copyright © 2014 Elsevier B.V. All rights reserved.

  6. Cryopreservation does not alter main characteristics of Good Manufacturing Process-grade human multipotent mesenchymal stromal cells including immunomodulating potential and lack of malignant transformation.

    Science.gov (United States)

    Luetzkendorf, Jana; Nerger, Katrin; Hering, Julian; Moegel, Angelika; Hoffmann, Katrin; Hoefers, Christiane; Mueller-Tidow, Carsten; Mueller, Lutz P

    2015-02-01

    The immunomodulating capacity of multipotent mesenchymal stromal cells (MSCs) qualifies them as a therapeutic tool in several diseases. However, repeated transplantation with products of reproducible characteristics may be required. This could be achieved with cryopreserved aliquots of Good Manufacturing Practice (GMP)-grade MSCs. However, the impact of cryopreservation on the characteristics of GMP-MSCs is ill defined. We produced fresh and cryopreserved MSCs from human donors with a xenogen-free GMP protocol. Immunogenicity and immunomodulating capacity were tested in co-culture with putative recipient-specific peripheral blood mononuclear cells (PBMCs). Risk of malignant transformation was assessed in vitro and in vivo. Cryopreservation had no impact on viability and consensus criteria of MSCs. In co-culture with PBMCs, MSCs showed low immunogenicity and suppressed mitogen-stimulated proliferation of PBMC irrespective of cryopreservation. Cytogenetic aberrations were not observed consistently in fresh and cryopreserved products, and no signs of malignant transformation occurred in functional assays. MSC products from an elderly pretreated donor showed reduced functional quality, but imminent failure of functional criteria could be detected by an increased population doubling time in early passages. This study is the first systematic analysis on cryopreservation of xenogen-free human bone marrow-derived GMP-MSCs. The data support that cryopreservation does not alter the characteristics of the cells and thus may allow the generation of products for serial transplantation. In addition, the protocol allowed early detection of MSC products with low functional capacity. Copyright © 2015 International Society for Cellular Therapy. Published by Elsevier Inc. All rights reserved.

  7. Endothelin-2/Vasoactive Intestinal Contractor: Regulation of Expression via Reactive Oxygen Species Induced by CoCl22, and Biological Activities Including Neurite Outgrowth in PC12 Cells

    Directory of Open Access Journals (Sweden)

    Eiichi Kotake-Nara

    2006-01-01

    Full Text Available This paper reviews the local hormone endothelin-2 (ET-2, or vasoactive intestinal contractor (VIC, a member of the vasoconstrictor ET peptide family, where ET-2 is the human orthologous peptide of the murine VIC. While ET-2/VIC gene expression has been observed in some normal tissues, ET-2 recently has been reported to act as a tumor marker and as a hypoxia-induced autocrine survival factor in tumor cells. A recently published study reported that the hypoxic mimetic agent CoCl2 at 200 µM increased expression of the ET-2/VIC gene, decreased expression of the ET-1 gene, and induced intracellular reactive oxygen species (ROS increase and neurite outgrowth in neuronal model PC12 cells. The ROS was generated by addition of CoCl2 to the culture medium, and the CoCl2-induced effects were completely inhibited by the antioxidant N-acetyl cysteine. Furthermore, interleukin-6 (IL-6 gene expression was up-regulated upon the differentiation induced by CoCl2. These results suggest that expression of ET-2/VIC and ET-1 mediated by CoCl2-induced ROS may be associated with neuronal differentiation through the regulation of IL-6 expression. CoCl2 acts as a pro-oxidant, as do Fe(II, III and Cu(II. However, some biological activities have been reported for CoCl2 that have not been observed for other metal salts such as FeCl3, CuSO4, and NiCl2. The characteristic actions of CoCl2 may be associated with the differentiation of PC12 cells. Further elucidation of the mechanism of neurite outgrowth and regulation of ET-2/VIC expression by CoCl2 may lead to the development of treatments for neuronal disorders.

  8. Pregnancy and live birth after follicle-stimulating hormone treatment for an infertile couple including a male affected by Sertoli cell-only syndrome

    Directory of Open Access Journals (Sweden)

    Paulis G

    2017-10-01

    Full Text Available Gianni Paulis,1,2 Luca Paulis,3 Gennaro Romano,4 Carmen Concas,5 Marika Di Sarno,5 Renata Pagano,5 Antonio Di Filippo,5 Maria Luisa Di Petrillo5 1Andrology Center, Regina Apostolorum Hospital, Rome, Italy; 2Department of Uro-Andrology, Castelfidardo Medical Team, Peyronie’s Disease Care Center, Rome, Italy; 3Section of Pharmacology and Research, Department of Uro-Andrology, Castelfidardo Medical Team, Peyronie’s Disease Care Center, Rome, Italy; 4Department of Urologic Oncology, Italian League Against Cancer, Avellino, Italy; 5Department of Reproductive Medicine and Biology, Caran Center, Caserta, Italy Abstract: In males with nonobstructive azoospermia, one of the main histopathologic patterns of the testis is Sertoli cell-only syndrome (SCOS, in which no germ cells are present and only Sertoli cells are contained in the seminiferous tubules. There is not any formal treatment for this pathological condition. However, several studies reported the possibility to perform testicular sperm extraction in patients with SCOS, although, according to some authors, sperm retrieval is possible only in the presence of focal spermatogenesis. We report the case of an infertile couple in whom the 30-year-old male was azoospermic. After the diagnosis, the patient underwent multiple bilateral testicular biopsies, which showed a histological pattern corresponding to SCOS. We administered a cycle of hormone stimulation followed by medically assisted procreation procedures to the male patient. Therefore, the male patient was treated with follicle-stimulating hormone gonadotropin for a total of 7 months (150 IU recombinant human follicle stimulating hormone three times per week. After carrying out a new multiple testicular sperm extraction, several spermatozoa were microscopically observed, and it was then possible to perform an intracytoplasmic sperm injection with subsequent embryo transfer of the blastocyst into the wife’s uterus, and so pregnancy was

  9. Insulin-induced inhibition of gluconeogenesis genes, including glutamic pyruvic transaminase 2, is associated with reduced histone acetylation in a human liver cell line.

    Science.gov (United States)

    Honma, Kazue; Kamikubo, Michiko; Mochizuki, Kazuki; Goda, Toshinao

    2017-06-01

    Hepatic glutamic pyruvic transaminase (GPT; also known as alanine aminotransferase) is a gluconeogenesis enzyme that catalyzes conversions between alanine and pyruvic acid. It is also used as a blood biomarker for hepatic damage. In this study, we investigated whether insulin regulates GPT expression, as it does for other gluconeogenesis genes, and if this involves the epigenetic modification of histone acetylation. Human liver-derived HepG2 cells were cultured with 0.5-100nM insulin for 8h, and the mRNA expression of GPT, glutamic-oxaloacetic transaminase (GOT), γ-glutamyltransferase (GGT), PCK1, G6PC and FBP1 was measured. We also investigated the extent of histone acetylation around these genes. Insulin suppressed the mRNA expression of gluconeogenesis genes (GPT2, GOT1, GOT2, GGT1, GGT2, G6PC, and PCK1) in HepG2 cells in a dose-dependent manner. mRNA levels of GPT2, but not GPT1, were decreased by insulin. Histone acetylation was also reduced around GPT2, G6PC, and PCK1 in response to insulin. The expression of GPT2 and other gluconeogenesis genes such as G6PC and PCK1 was suppressed by insulin, in association with decreases in histone H3 and H4 acetylation surrounding these genes. Copyright © 2017 Elsevier Inc. All rights reserved.

  10. Mathematical modeling of synthesis gas fueled electrochemistry and transport including H2/CO co-oxidation and surface diffusion in solid oxide fuel cell

    Science.gov (United States)

    Bao, Cheng; Jiang, Zeyi; Zhang, Xinxin

    2015-10-01

    Fuel flexibility is a significant advantage of solid oxide fuel cell (SOFC). A comprehensive macroscopic framework is proposed for synthesis gas (syngas) fueled electrochemistry and transport in SOFC anode with two main novelties, i.e. analytical H2/CO electrochemical co-oxidation, and correction of gas species concentration at triple phase boundary considering competitive absorption and surface diffusion. Staring from analytical approximation of the decoupled charge and mass transfer, we present analytical solutions of two defined variables, i.e. hydrogen current fraction and enhancement factor. Giving explicit answer (rather than case-by-case numerical calculation) on how many percent of the current output contributed by H2 or CO and on how great the water gas shift reaction plays role on, this approach establishes at the first time an adaptive superposition mechanism of H2-fuel and CO-fuel electrochemistry for syngas fuel. Based on the diffusion equivalent circuit model, assuming series-connected resistances of surface diffusion and bulk diffusion, the model predicts well at high fuel utilization by keeping fixed porosity/tortuosity ratio. The model has been validated by experimental polarization behaviors in a wide range of operation on a button cell for H2-H2O-CO-CO2-N2 fuel systems. The framework could be helpful to narrow the gap between macro-scale and meso-scale SOFC modeling.

  11. An Atypical Human Induced Pluripotent Stem Cell Line With a Complex, Stable, and Balanced Genomic Rearrangement Including a Large De Novo 1q Uniparental Disomy

    Science.gov (United States)

    Steichen, Clara; Maluenda, Jérôme; Tosca, Lucie; Luce, Eléanor; Pineau, Dominique; Dianat, Noushin; Hannoun, Zara; Tachdjian, Gérard; Melki, Judith

    2015-01-01

    Human induced pluripotent stem cells (hiPSCs) hold great promise for cell therapy through their use as vital tools for regenerative and personalized medicine. However, the genomic integrity of hiPSCs still raises some concern and is one of the barriers limiting their use in clinical applications. Numerous articles have reported the occurrence of aneuploidies, copy number variations, or single point mutations in hiPSCs, and nonintegrative reprogramming strategies have been developed to minimize the impact of the reprogramming process on the hiPSC genome. Here, we report the characterization of an hiPSC line generated by daily transfections of modified messenger RNAs, displaying several genomic abnormalities. Karyotype analysis showed a complex genomic rearrangement, which remained stable during long-term culture. Fluorescent in situ hybridization analyses were performed on the hiPSC line showing that this karyotype is balanced. Interestingly, single-nucleotide polymorphism analysis revealed the presence of a large 1q region of uniparental disomy (UPD), demonstrating for the first time that UPD can occur in a noncompensatory context during nonintegrative reprogramming of normal fibroblasts. PMID:25650439

  12. Hematopoietic stem cell transplantation activity worldwide in 2012 and a SWOT analysis of the Worldwide Network for Blood and Marrow Transplantation Group including the global survey.

    Science.gov (United States)

    Niederwieser, D; Baldomero, H; Szer, J; Gratwohl, M; Aljurf, M; Atsuta, Y; Bouzas, L F; Confer, D; Greinix, H; Horowitz, M; Iida, M; Lipton, J; Mohty, M; Novitzky, N; Nunez, J; Passweg, J; Pasquini, M C; Kodera, Y; Apperley, J; Seber, A; Gratwohl, A

    2016-06-01

    Data on 68 146 hematopoietic stem cell transplants (HSCTs) (53% autologous and 47% allogeneic) gathered by 1566 teams from 77 countries and reported through their regional transplant organizations were analyzed by main indication, donor type and stem cell source for the year 2012. With transplant rates ranging from 0.1 to 1001 per 10 million inhabitants, more HSCTs were registered from unrelated 16 433 donors than related 15 493 donors. Grafts were collected from peripheral blood (66%), bone marrow (24%; mainly non-malignant disorders) and cord blood (10%). Compared with 2006, an increase of 46% total (57% allogeneic and 38% autologous) was observed. Growth was due to an increase in reporting teams (18%) and median transplant activity/team (from 38 to 48 HSCTs/team). An increase of 167% was noted in mismatched/haploidentical family HSCT. A Strengths, Weaknesses, Opportunities, Threats (SWOT) analysis revealed the global perspective of WBMT to be its major strength and identified potential to be the key professional body for patients and authorities. The limited data collection remains its major weakness and threat. In conclusion, global HSCT grows over the years without plateauing (allogeneic>autologous) and at different rates in the four World Health Organization regions. Major increases were observed in allogeneic, haploidentical HSCT and, to a lesser extent, in cord blood transplantation.

  13. Hematopoietic Stem Cell Transplantation Activity Worldwide in 2012 and a SWOT Analysis of the Worldwide Network for Blood and Marrow Transplantation Group (WBMT) including the global survey

    Science.gov (United States)

    Niederwieser, Dietger; Baldomero, Helen; Szer, Jeff; Gratwohl, Michael; Aljurf, Mahmoud; Atsuta, Yoshiko; Bouzas, Luis Fernando; Confer, Dennis; Greinix, Hildegard; Horowitz, Mary; Iida, Minako; Lipton, Jeff; Mohty, Mohamad; Novitzky, Nicolas; Nunez, José; Passweg, Jakob; Pasquini, Marcelo C.; Kodera, Yoshihisa; Apperley, Jane; Seber, Adriana; Gratwohl, Alois

    2016-01-01

    Data on 68,146 hematopoietic stem cell transplants (HSCT) (53% autologous and 47% allogeneic) gathered by 1566 teams from 77 countries and reported through their regional transplant organizations were analyzed by main indication, donor type and stem cell source for the year 2012. With transplant rates ranging from 0.1 to 1001 per 10 million inhabitants, more HSCT were registered from unrelated 16,433 than related 15,493 donors. Grafts were collected from peripheral blood (66%), bone marrow (24%; mainly non-malignant disorders) and cord blood (10%). Compared to 2006, an increase of 46% total (57% allogeneic and 38% autologous) was observed. Growth was due to an increase in reporting teams (18%) and median transplant activity/team (from 38 to 48 HSCT/team). An increase of 67% was noted in mismatched/haploidentical family HSCT. A SWOT analysis revealed the global perspective of WBMT to be its major strength and identified potential to be the key professional body for patients and authorities. The limited data collection remains its major weakness and threat. In conclusion, global HSCT grows over the years without plateauing (allogeneic>autologous) and at different rates in the four WHO regions. Major increases were observed in allogeneic, haploidentical HSCT and, to a lesser extent, in cord blood. PMID:26901703

  14. Systematic aging of commercial LiFePO4|Graphite cylindrical cells including a theory explaining rise of capacity during aging

    Science.gov (United States)

    Lewerenz, Meinert; Münnix, Jens; Schmalstieg, Johannes; Käbitz, Stefan; Knips, Marcus; Sauer, Dirk Uwe

    2017-03-01

    The contribution introduces a new theory explaining the capacity increase that is often observed in early stages of life of lithium-ion batteries. This reversible and SOC-depending capacity rise is explained by the passive electrode effect in this work. The theory assumes a slow, compensating flow of active lithium between the passive and the active part of the anode, where the passive part represents the geometric excess anode with respect to the cathode. The theory is validated using a systematic test of 50 cylindrical 8 Ah LiFePO4|Graphite battery cells analyzed during cyclic and calendaric aging. The cyclic aging has been performed symmetrically at 40 °C cell temperature, varying current rates and DODs. The calendar aging is executed at three temperatures and up to four SOCs. The aging is dominated by capacity fade while the increase of internal resistance is hardly influenced. Surprisingly shallow cycling between 45 and 55% SOC shows stronger aging than aging at higher DOD and tests at 4 C exhibit less aging than aging at lower C-rates. Aging mechanisms at 60 °C seem to deviate from those at 40 °C or lower. The data of this aging matrix is used for further destructive and non-destructive characterization in future contributions.

  15. Characterization of Genotoxic Response to 15 Multiwalled Carbon Nanotubes with Variable Physicochemical Properties Including Surface Functionalizations in the FE1-Muta(TM) Mouse Lung Epithelial Cell Line

    DEFF Research Database (Denmark)

    Jackson, Petra; Kling, Kirsten; Jensen, Keld Alstrup

    2015-01-01

    Carbon nanotubes vary greatly in physicochemical properties. We compared cytotoxic and genotoxic response to 15 multiwalled carbon nanotubes (MWCNT) with varying physicochemical properties to identify drivers of toxic responses. The studied MWCNT included OECD Working Party on Manufactured...... Nanomaterials (WPMN) (NM-401, NM-402, and NM-403), materials (NRCWE-026 and MWCNT-XNRI-7), and three sets of surface-modified MWCNT grouped by physical characteristics (thin, thick, and short I-III, respectively). Each Groups I-III included pristine, hydroxylated and carboxylated MWCNT. Group III also included...... an amino-functionalized MWCNT. The level of surface functionalization of the MWCNT was low. The level and type of elemental impurities of the MWCNT varied by...

  16. Prognostic role of platelet to lymphocyte ratio in non-small cell lung cancers: A meta-analysis including 3,720 patients.

    Science.gov (United States)

    Zhao, Qing-Tao; Yuan, Zheng; Zhang, Hua; Zhang, Xiao-Peng; Wang, Hui-En; Wang, Zhi-Kang; Duan, Guo-Chen

    2016-07-01

    Platelet to lymphocyte ratio (PLR) was recently reported as a useful index in predicting the prognosis of lung cancer. However, the prognostic role of PLR in lung cancer remains controversial. The aim of this study was to evaluate the association between PLR and clinical outcome of lung cancer patients through a meta-analysis. Relevant literatures were retrieved from PubMed, Ovid, the Cochrane Library and Web of Science databases. Meta-analysis was performed using hazard ratio (HR) and 95% confidence intervals (CIs) as effect measures. A total of 5,314 patients from 13 studies were finally enrolled in the meta-analysis. The summary results showed that elevated PLR predicted poorer overall survival (OS) (HR: 1.526, 95%CI: 1.268-1.836, p analysis revealed that increased PLR was also associated with poor OS in NSCLC treated by surgical resection (HR: 1.884, 95%CI: 1.308-2.714, P 160 (HR: 1.842, 95%CI: 1.523-2.228, P  0.05) in patients with small cell lung cancer (SCLC).This meta-analysis result suggested that elevated PLR might be a predicative factor of poor prognosis for NSCLC patients. © 2016 UICC.

  17. Expression patterns of DLK1 and INSL3 identify stages of Leydig cell differentiation during normal development and in testicular pathologies, including testicular cancer and Klinefelter syndrome

    DEFF Research Database (Denmark)

    Lottrup, G; Nielsen, J E; Maroun, L L

    2014-01-01

    , and in the majority of LCs, it was mutually exclusive of DLK1. LIMITATIONS, REASONS FOR CAUTION: The number of samples was relatively small and no true normal adult controls were available. True stereology was not used for LC counting, instead LCs were counted in three fields of 0.5 µm(2) surface for each sample...... in adult men with testicular pathologies including testis cancer and Klinefelter syndrome. STUDY FUNDING/COMPETING INTERESTS: This work was funded by Rigshospitalet's research funds, the Danish Cancer Society and Kirsten and Freddy Johansen's foundation. The authors have no conflicts of interest....

  18. Radiochemotherapy including cisplatin alone versus cisplatin + 5-fluorouracil for locally advanced unresectable stage IV squamous cell carcinoma of the head and neck

    Energy Technology Data Exchange (ETDEWEB)

    Tribius, Silke; Kilic, Yasemin [Dept. of Radiation Oncology, Univ. Medical Center Hamburg-Eppendorf, Hamburg (Germany); Kronemann, Stefanie [Dept. of Radiation Oncology, Univ. Hospital Schleswig-Holstein, Campus Luebeck (Germany); Schroeder, Ursula [Dept. of Head and Neck Surgery, Univ. Hospital Schleswig-Holstein, Campus Luebeck (Germany); Hakim, Samer [Dept. of Oro-Maxillo-Facial Surgery, Univ. Hospital Schleswig-Holstein, Campus Luebeck (Germany); Schild, Steven E. [Dept. of Radiation Oncology, Mayo Clinic, Scottsdale, AZ (United States); Rades, Dirk [Dept. of Radiation Oncology, Univ. Medical Center Hamburg-Eppendorf, Hamburg (Germany); Dept. of Radiation Oncology, Univ. Hospital Schleswig-Holstein, Campus Luebeck (Germany)

    2009-10-15

    Background and purpose: the optimal radiochemotherapy regimen for advanced head-and-neck cancer is still debated. This nonrandomized study compares two cisplatin-based radiochemotherapy regimens in 128 patients with locally advanced unresectable stage IV squamous cell carcinoma of the head and neck (SCCHN). Patients and methods: concurrent chemotherapy consisted of either two courses cisplatin (20 mg/m{sup 2}/d1-5 + 29-33; n = 54) or two courses cisplatin (20 mg/m{sup 2}/d1-5 + 29-33) + 5-fluorouracil (5-FU; 600 mg/m{sup 2}/d1-5 + 29-33; n = 74). Results: at least one grade 3 toxicity occurred in 25 of 54 patients (46%) receiving cisplatin alone and in 52 of 74 patients (70%) receiving cisplatin + 5-FU. The latter regimen was particularly associated with increased rates of mucositis (p = 0.027) and acute skin toxicity (p = 0.001). Seven of 54 (13%) and 20 of 74 patients (27%) received only one chemotherapy course due to treatment-related acute toxicity. Late toxicity in terms of xerostomia, neck fibrosis, skin toxicity, and lymphedema was not significantly different. The 2-year locoregional control rates were 67% after cisplatin alone and 52% after cisplatin + 5-FU (p = 0.35). The metastases-free survival rates were 79% and 69%, respectively (p = 0.65), and the overall survival rates 70% and 51%, respectively (p = 0.10). On multivariate analysis, outcome was significantly associated with performance status, T-category, N-category, hemoglobin level prior to radiotherapy, and radiotherapy break > 1 week. Conclusion: two courses of fractionated cisplatin (20 mg/m{sup 2}/day) alone appear preferable, as this regimen resulted in similar outcome and late toxicity as two courses of cisplatin + 5-FU, but in significantly less acute toxicity. (orig.)

  19. 3D nuclear organization of telomeres in the Hodgkin cell lines U-HO1 and U-HO1-PTPN1: PTPN1 expression prevents the formation of very short telomeres including "t-stumps"

    Directory of Open Access Journals (Sweden)

    Lemieux Bruno

    2010-12-01

    Full Text Available Abstract Background In cancer cells the three-dimensional (3D telomere organization of interphase nuclei into a telomeric disk is heavily distorted and aggregates are found. In Hodgkin's lymphoma quantitative FISH (3D Q-FISH reveals a major impact of nuclear telomere dynamics during the transition form mononuclear Hodgkin (H to diagnostic multinuclear Reed-Sternberg (RS cells. In vitro and in vivo formation of RS-cells is associated with the increase of very short telomeres including "t-stumps", telomere loss, telomeric aggregate formation and the generation of "ghost nuclei". Results Here we analyze the 3D telomere dynamics by Q-FISH in the novel Hodgkin cell line U-HO1 and its non-receptor protein-tyrosine phosphatase N1 (PTPN1 stable transfectant U-HO1-PTPN1, derived from a primary refractory Hodgkin's lymphoma. Both cell lines show equally high telomerase activity but U-HO1-PTPN differs from U-HO1 by a three times longer doubling time, low STAT5A expression, accumulation of RS-cells (p As expected, multinuclear U-HO1-RS-cells and multinuclear U-HO1-PTPN1-RS-cells differ from their mononuclear H-precursors by their nuclear volume (p Conclusion Abundant RS-cells without additional very short telomeres including "t-stumps", high rate of apoptosis, but low STAT5A expression, are hallmarks of the U-HO1-PTPN1 cell line. These characteristics are independent of telomerase activity. Thus, PTPN1 induced dephosphorylation of STAT5 with consecutive lack of Akt/PKB activation and cellular arrest in G2, promoting induction of apoptosis, appears as a possible pathogenetic mechanism deserving further experimental investigation.

  20. Incidence of isolated nodal failure in non-small cell lung cancer patients included in a prospective study of the value of PET–CT

    International Nuclear Information System (INIS)

    Kolodziejczyk, Milena; Bujko, Krzysztof; Michalski, Wojciech; Kepka, Lucyna

    2012-01-01

    Purpose: Elective nodal irradiation (ENI) is not recommended in PET–CT-based radiotherapy for NSCLC despite a low level of evidence to support such guidelines. The aim of this investigation is to find out whether omitting ENI is safe. Materials and methods: Sixty-seven patients treated within a frame of a previously published prospective trial of the value of PET–CT were included in the analysis. Seventeen (25%) patients received ENI due to higher initial nodal involvement and in the remaining 50 patients (75%) with N0-N1 or single N2 disease ENI was omitted. Isolated nodal failure (INF) was recorded if relapse occurred in the initially uninvolved regional lymph node without previous or simultaneous local recurrence regardless of the status of distant metastases. Results: With a median follow-up of 32 months, the estimated 3-year overall survival was 42%, local progression-free interval was 55%, and distant metastases-free interval was 62%. Three patients developed INF; all had ENI omitted from treatment, giving a final result of three INFs in 50 (6%) patients treated without ENI. In this group of patients, the 3-year cause-specific cumulative incidence of INF was 6.4% (95% confidence interval: 0–17%). Conclusions: The omission of ENI appears to be not as safe as suggested by current recommendations.

  1. Incidence of isolated nodal failure in non-small cell lung cancer patients included in a prospective study of the value of PET-CT.

    Science.gov (United States)

    Kolodziejczyk, Milena; Bujko, Krzysztof; Michalski, Wojciech; Kepka, Lucyna

    2012-07-01

    Elective nodal irradiation (ENI) is not recommended in PET-CT-based radiotherapy for NSCLC despite a low level of evidence to support such guidelines. The aim of this investigation is to find out whether omitting ENI is safe. Sixty-seven patients treated within a frame of a previously published prospective trial of the value of PET-CT were included in the analysis. Seventeen (25%) patients received ENI due to higher initial nodal involvement and in the remaining 50 patients (75%) with N0-N1 or single N2 disease ENI was omitted. Isolated nodal failure (INF) was recorded if relapse occurred in the initially uninvolved regional lymph node without previous or simultaneous local recurrence regardless of the status of distant metastases. With a median follow-up of 32 months, the estimated 3-year overall survival was 42%, local progression-free interval was 55%, and distant metastases-free interval was 62%. Three patients developed INF; all had ENI omitted from treatment, giving a final result of three INFs in 50 (6%) patients treated without ENI. In this group of patients, the 3-year cause-specific cumulative incidence of INF was 6.4% (95% confidence interval: 0-17%). The omission of ENI appears to be not as safe as suggested by current recommendations. Copyright © 2012 Elsevier Ireland Ltd. All rights reserved.

  2. 4-IBP, a σ1 Receptor Agonist, Decreases the Migration of Human Cancer Cells, Including Glioblastoma Cells, In Vitro and Sensitizes Them In Vitro and In Vivo to Cytotoxic Insults of Proapoptotic and Proautophagic Drugs

    Directory of Open Access Journals (Sweden)

    Veronique Mégalizzi

    2007-05-01

    Full Text Available Although the molecular function of cr receptors has not been fully defined and the natural ligand(s is still not known, there is increasing evidence that these receptors and their ligands might play a significant role in cancer biology. 4-(N-tibenzylpiperidin-4-yl-4iodobenzamide (4-IBP, a selective σ1, agonist, has been used to investigate whether this compound is able to modify: 1 in vitro the migration and proliferation of human cancer cells; 2 in vitro the sensitivity of human glioblastoma cells to cytotoxic drugs; and 3 in vivo in orthotopic glioblastoma and non-small cell lung carcinoma (NSCLC models the survival of mice coadministered cytotoxic agents. 4-IBP has revealed weak anti proliferative effects on human U373-MG glioblastoma and C32 melanoma cells but induced marked concentration-dependent decreases in the growth of human A549 NSCLC and PC3 prostate cancer cells. The compound was also significantly antimigratory in all four cancer cell lines. This may result, at least in U373-MG cells, from modifications to the actin cytoskeleton. 4-IBP modified the sensitivity of U373-MG cells in vitro to proapoptotic lomustin and proautophagic temozolomide, and markedly decreased the expression of two proteins involved in drug resistance: glucosylceramide synthase and Rho guanine nucleotide dissociation inhibitor. In vivo, 4-IBP increased the antitumor effects of temozolomide and irinotecan in immunodeficient mice that were orthotopically grafted with invasive cancer cells.

  3. Development of a modified prognostic index for patients with aggressive adult T-cell leukemia-lymphoma aged 70 years or younger: possible risk-adapted management strategies including allogeneic transplantation.

    Science.gov (United States)

    Fuji, Shigeo; Yamaguchi, Takuhiro; Inoue, Yoshitaka; Utsunomiya, Atae; Moriuchi, Yukiyoshi; Uchimaru, Kaoru; Owatari, Satsuki; Miyagi, Takashi; Taguchi, Jun; Choi, Ilseung; Otsuka, Eiichi; Nakachi, Sawako; Yamamoto, Hisashi; Kurosawa, Saiko; Tobinai, Kensei; Fukuda, Takahiro

    2017-07-01

    Adult T-cell leukemia-lymphoma is a distinct type of peripheral T-cell lymphoma caused by human T-cell lymphotropic virus type I. Although allogeneic stem cell transplantation after chemotherapy is a recommended treatment option for patients with aggressive adult T-cell leukemia-lymphoma, there is no consensus about indications for allogeneic stem cell transplantation because there is no established risk stratification system for transplant eligible patients. We conducted a nationwide survey of patients with aggressive adult T-cell leukemia-lymphoma in order to construct a new, large database that includes 1,792 patients aged 70 years or younger with aggressive adult T-cell leukemia-lymphoma who were diagnosed between 2000 and 2013 and received intensive first-line chemotherapy. We randomly divided patients into two groups (training and validation sets). Acute type, poor performance status, high soluble interleukin-2 receptor levels (> 5,000 U/mL), high adjusted calcium levels (≥ 12 mg/dL), and high C-reactive protein levels (≥ 2.5 mg/dL) were independent adverse prognostic factors used in the training set. We used these five variables to divide patients into three risk groups. In the validation set, median overall survival for the low-, intermediate-, and high-risk groups was 626 days, 322 days, and 197 days, respectively. In the intermediate- and high-risk groups, transplanted recipients had significantly better overall survival than non-transplanted patients. We developed a promising new risk stratification system to identify patients aged 70 years or younger with aggressive adult T-cell leukemia-lymphoma who may benefit from upfront allogeneic stem cell transplantation. Prospective studies are warranted to confirm the benefit of this treatment strategy. Copyright© 2017 Ferrata Storti Foundation.

  4. Ribosome profiling-guided depletion of an mRNA increases cell growth rate and protein secretion

    DEFF Research Database (Denmark)

    Beuchert Kallehauge, Thomas; Li, Shangzhong; Pedersen, Lasse Ebdrup

    2017-01-01

    Recombinant protein production coopts the host cell machinery to provide high protein yields of industrial enzymes or biotherapeutics. However, since protein translation is energetically expensive and tightly controlled, it is unclear if highly expressed recombinant genes are translated as effici......Recombinant protein production coopts the host cell machinery to provide high protein yields of industrial enzymes or biotherapeutics. However, since protein translation is energetically expensive and tightly controlled, it is unclear if highly expressed recombinant genes are translated...... as efficiently as host genes. Furthermore, it is unclear how the high expression impacts global translation. Here, we present the first genome-wide view of protein translation in an IgG-producing CHO cell line, measured with ribosome profiling. Through this we found that our recombinant mRNAs were translated...... as efficiently as the host cell transcriptome, and sequestered up to 15% of the total ribosome occupancy. During cell culture, changes in recombinant mRNA translation were consistent with changes in transcription, demonstrating that transcript levels influence specific productivity. Using this information, we...

  5. Phenolic promiscuity in the cell nucleus--epigallocatechingallate (EGCG) and theaflavin-3,3'-digallate from green and black tea bind to model cell nuclear structures including histone proteins, double stranded DNA and telomeric quadruplex DNA.

    Science.gov (United States)

    Mikutis, Gediminas; Karaköse, Hande; Jaiswal, Rakesh; LeGresley, Adam; Islam, Tuhidul; Fernandez-Lahore, Marcelo; Kuhnert, Nikolai

    2013-02-01

    Flavanols from tea have been reported to accumulate in the cell nucleus in considerable concentrations. The nature of this phenomenon, which could provide novel approaches in understanding the well-known beneficial health effects of tea phenols, is investigated in this contribution. The interaction between epigallocatechin gallate (EGCG) from green tea and a selection of theaflavins from black tea with selected cell nuclear structures such as model histone proteins, double stranded DNA and quadruplex DNA was investigated using mass spectrometry, Circular Dichroism spectroscopy and fluorescent assays. The selected polyphenols were shown to display affinity to all of the selected cell nuclear structures, thereby demonstrating a degree of unexpected molecular promiscuity. Most interestingly theaflavin-digallate was shown to display the highest affinity to quadruplex DNA reported for any naturally occurring molecule reported so far. This finding has immediate implications in rationalising the chemopreventive effect of the tea beverage against cancer and possibly the role of tea phenolics as "life span essentials".

  6. New seismograph includes filters

    Energy Technology Data Exchange (ETDEWEB)

    1979-11-02

    The new Nimbus ES-1210 multichannel signal enhancement seismograph from EG and G geometrics has recently been redesigned to include multimode signal fillers on each amplifier. The ES-1210F is a shallow exploration seismograph for near subsurface exploration such as in depth-to-bedrock, geological hazard location, mineral exploration, and landslide investigations.

  7. Low-Intensity Ultrasound-Induced Anti-inflammatory Effects Are Mediated by Several New Mechanisms Including Gene Induction, Immunosuppressor Cell Promotion, and Enhancement of Exosome Biogenesis and Docking

    Directory of Open Access Journals (Sweden)

    Qian Yang

    2017-10-01

    Full Text Available Background: Low-intensity ultrasound (LIUS was shown to be beneficial in mitigating inflammation and facilitating tissue repair in various pathologies. Determination of the molecular mechanisms underlying the anti-inflammatory effects of LIUS allows to optimize this technique as a therapy for the treatment of malignancies and aseptic inflammatory disorders.Methods: We conducted cutting-edge database mining approaches to determine the anti-inflammatory mechanisms exerted by LIUS.Results: Our data revealed following interesting findings: (1 LIUS anti-inflammatory effects are mediated by upregulating anti-inflammatory gene expression; (2 LIUS induces the upregulation of the markers and master regulators of immunosuppressor cells including MDSCs (myeloid-derived suppressor cells, MSCs (mesenchymal stem cells, B1-B cells and Treg (regulatory T cells; (3 LIUS not only can be used as a therapeutic approach to deliver drugs packed in various structures such as nanobeads, nanospheres, polymer microspheres, and lipidosomes, but also can make use of natural membrane vesicles as small as exosomes derived from immunosuppressor cells as a novel mechanism to fulfill its anti-inflammatory effects; (4 LIUS upregulates the expression of extracellular vesicle/exosome biogenesis mediators and docking mediators; (5 Exosome-carried anti-inflammatory cytokines and anti-inflammatory microRNAs inhibit inflammation of target cells via multiple shared and specific pathways, suggesting exosome-mediated anti-inflammatory effect of LIUS feasible; and (6 LIUS-mediated physical effects on tissues may activate specific cellular sensors that activate downstream transcription factors and signaling pathways.Conclusions: Our results have provided novel insights into the mechanisms underlying anti-inflammatory effects of LIUS, and have provided guidance for the development of future novel therapeutic LIUS for cancers, inflammatory disorders, tissue regeneration and tissue repair.

  8. Analytic device including nanostructures

    KAUST Repository

    Di Fabrizio, Enzo M.; Fratalocchi, Andrea; Totero Gongora, Juan Sebastian; Coluccio, Maria Laura; Candeloro, Patrizio; Cuda, Gianni

    2015-01-01

    A device for detecting an analyte in a sample comprising: an array including a plurality of pixels, each pixel including a nanochain comprising: a first nanostructure, a second nanostructure, and a third nanostructure, wherein size of the first nanostructure is larger than that of the second nanostructure, and size of the second nanostructure is larger than that of the third nanostructure, and wherein the first nanostructure, the second nanostructure, and the third nanostructure are positioned on a substrate such that when the nanochain is excited by an energy, an optical field between the second nanostructure and the third nanostructure is stronger than an optical field between the first nanostructure and the second nanostructure, wherein the array is configured to receive a sample; and a detector arranged to collect spectral data from a plurality of pixels of the array.

  9. Saskatchewan resources. [including uranium

    Energy Technology Data Exchange (ETDEWEB)

    1979-09-01

    The production of chemicals and minerals for the chemical industry in Saskatchewan are featured, with some discussion of resource taxation. The commodities mentioned include potash, fatty amines, uranium, heavy oil, sodium sulfate, chlorine, sodium hydroxide, sodium chlorate and bentonite. Following the successful outcome of the Cluff Lake inquiry, the uranium industry is booming. Some developments and production figures for Gulf Minerals, Amok, Cenex and Eldorado are mentioned.

  10. Synergizing metabolic flux analysis and nucleotide sugar metabolism to understand the control of glycosylation of recombinant protein in CHO cells

    LENUS (Irish Health Repository)

    Burleigh, Susan C

    2011-10-18

    Abstract Background The glycosylation of recombinant proteins can be altered by a range of parameters including cellular metabolism, metabolic flux and the efficiency of the glycosylation process. We present an experimental set-up that allows determination of these key processes associated with the control of N-linked glycosylation of recombinant proteins. Results Chinese hamster ovary cells (CHO) were cultivated in shake flasks at 0 mM glutamine and displayed a reduced growth rate, glucose metabolism and a slower decrease in pH, when compared to other glutamine-supplemented cultures. The N-linked glycosylation of recombinant human chorionic gonadotrophin (HCG) was also altered under these conditions; the sialylation, fucosylation and antennarity decreased, while the proportion of neutral structures increased. A continuous culture set-up was subsequently used to understand the control of HCG glycosylation in the presence of varied glutamine concentrations; when glycolytic flux was reduced in the absence of glutamine, the glycosylation changes that were observed in shake flask culture were similarly detected. The intracellular content of UDP-GlcNAc was also reduced, which correlated with a decrease in sialylation and antennarity of the N-linked glycans attached to HCG. Conclusions The use of metabolic flux analysis illustrated a case of steady state multiplicity, where use of the same operating conditions at each steady state resulted in altered flux through glycolysis and the TCA cycle. This study clearly demonstrated that the control of glycoprotein microheterogeneity may be examined by use of a continuous culture system, metabolic flux analysis and assay of intracellular nucleotides. This system advances our knowledge of the relationship between metabolic flux and the glycosylation of biotherapeutics in CHO cells and will be of benefit to the bioprocessing industry.

  11. Being Included and Excluded

    DEFF Research Database (Denmark)

    Korzenevica, Marina

    2016-01-01

    Following the civil war of 1996–2006, there was a dramatic increase in the labor mobility of young men and the inclusion of young women in formal education, which led to the transformation of the political landscape of rural Nepal. Mobility and schooling represent a level of prestige that rural...... politics. It analyzes how formal education and mobility either challenge or reinforce traditional gendered norms which dictate a lowly position for young married women in the household and their absence from community politics. The article concludes that women are simultaneously excluded and included from...... community politics. On the one hand, their mobility and decision-making powers decrease with the increase in the labor mobility of men and their newly gained education is politically devalued when compared to the informal education that men gain through mobility, but on the other hand, schooling strengthens...

  12. Psoriatic arthritis management update - biotherapeutic options.

    LENUS (Irish Health Repository)

    Saber, Tajvur P

    2012-02-01

    Psoriatic arthritis (PsA) is a seronegative spondyloarthropathy (SpA) occurring in up to 30% of patients with psoriasis. It has a wide variation of annual incidence (median 6.4, range 0.1-3.1 per 10(5) people), based on analysis of 13 incidence and prevalence reviews published between 1987 and December 2006. Conventional treatments with antiinflammatory and disease modifying or antirheumatic drugs are not efficacious in all patients, in particular those with axial disease. This review examines new pharmacological developments in the treatment of PsA with a focus on biologic therapies.

  13. Fibroadenoma and phyllodes tumors of anogenital mammary-like glands: a series of 13 neoplasms in 12 cases, including mammary-type juvenile fibroadenoma, fibroadenoma with lactation changes, and neurofibromatosis-associated pseudoangiomatous stromal hyperplasia with multinucleated giant cells.

    Science.gov (United States)

    Kazakov, Dmitry V; Spagnolo, Dominic V; Stewart, Colin J; Thompson, Jane; Agaimy, Abbas; Magro, Gaetano; Bisceglia, Michele; Vazmitel, Marina; Kacerovska, Denisa; Kutzner, Heinz; Mukensnabl, Petr; Michal, Michal

    2010-01-01

    The authors present a series of 13 fibroepithelial neoplasms involving anogenital mammary-like glands, all occurring in 12 female patients, whose age at diagnosis ranged from 30 to 51 years (mean, 38 y; median, 42 y). All women presented with a solitary asymptomatic nodule in the vulva (n=8), perineum (n=2), or near the anus (n=2) ranging in size from 1.5 to 4.5 cm. Microscopically, 8 lesions were classified as fibroadenoma, and 5, including 1 recurrent tumor, as phyllodes tumor, of which 1 was benign and 4 low-grade malignant. In addition to conventional findings, we describe several hitherto unreported features including juvenile fibroadenoma-like proliferation, fibroadenoma with lactation change, and pseudoangiomatous stromal hyperplasia with multinucleated stromal giant cells in a patient with neurofibromatosis, type 1 all constituting potential diagnostic pitfalls, which are best averted by using the same approach to diagnosis as for their analogous mammary counterparts.

  14. Curative or pre-emptive adenovirus-specific T cell transfer from matched unrelated or third party haploidentical donors after HSCT, including UCB transplantations: a successful phase I/II multicenter clinical trial

    Directory of Open Access Journals (Sweden)

    Chongsheng Qian

    2017-05-01

    Full Text Available Abstract Background Allogeneic hematopoietic stem cell transplantation (HSCT, the most widely used potentially curable cellular immunotherapeutic approach in the treatment of hematological malignancies, is limited by life-threatening complications: graft versus host disease (GVHD and infections especially viral infections refractory to antiviral drugs. Adoptive transfer of virus-specific T cells is becoming an alternative treatment for infections following HSCT. We report here the results of a phase I/II multicenter study which includes a series of adenovirus-specific T cell (ADV-VST infusion either from the HSCT donor or from a third party haploidentical donor for patients transplanted with umbilical cord blood (UCB. Methods Fourteen patients were eligible and 11 patients received infusions of ADV-VST generated by interferon (IFN-γ-based immunomagnetic isolation from a leukapheresis from their original donor (42.9% or a third party haploidentical donor (57.1%. One patient resolved ADV infection before infusion, and ADV-VST could not reach release or infusion criteria for two patients. Two patients received cellular immunotherapy alone without antiviral drugs as a pre-emptive treatment. Results One patient with adenovirus infection and ten with adenovirus disease were infused with ADV-VST (mean 5.83 ± 8.23 × 103 CD3+IFN-γ+ cells/kg up to 9 months after transplantation. The 11 patients showed in vivo expansion of specific T cells up to 60 days post-infusion, associated with adenovirus load clearance in ten of the patients (91%. Neither de novo GVHD nor side effects were observed during the first month post-infusion, but GVHD reactivations occurred in three patients, irrespective of the type of leukapheresis donor. For two of these patients, GVHD reactivation was controlled by immunosuppressive treatment. Four patients died during follow-up, one due to refractory ADV disease. Conclusions Adoptive transfer of rapidly isolated ADV

  15. Microscale to manufacturing scale-up of cell-free cytokine production--a new approach for shortening protein production development timelines.

    Science.gov (United States)

    Zawada, James F; Yin, Gang; Steiner, Alexander R; Yang, Junhao; Naresh, Alpana; Roy, Sushmita M; Gold, Daniel S; Heinsohn, Henry G; Murray, Christopher J

    2011-07-01

    Engineering robust protein production and purification of correctly folded biotherapeutic proteins in cell-based systems is often challenging due to the requirements for maintaining complex cellular networks for cell viability and the need to develop associated downstream processes that reproducibly yield biopharmaceutical products with high product quality. Here, we present an alternative Escherichia coli-based open cell-free synthesis (OCFS) system that is optimized for predictable high-yield protein synthesis and folding at any scale with straightforward downstream purification processes. We describe how the linear scalability of OCFS allows rapid process optimization of parameters affecting extract activation, gene sequence optimization, and redox folding conditions for disulfide bond formation at microliter scales. Efficient and predictable high-level protein production can then be achieved using batch processes in standard bioreactors. We show how a fully bioactive protein produced by OCFS from optimized frozen extract can be purified directly using a streamlined purification process that yields a biologically active cytokine, human granulocyte-macrophage colony-stimulating factor, produced at titers of 700 mg/L in 10 h. These results represent a milestone for in vitro protein synthesis, with potential for the cGMP production of disulfide-bonded biotherapeutic proteins. Copyright © 2011 Wiley Periodicals, Inc.

  16. Phosphoproteome and transcription factor activity profiling identify actions of the anti-inflammatory agent UTL-5g in LPS stimulated RAW 264.7 cells including disrupting actin remodeling and STAT-3 activation.

    Science.gov (United States)

    Carruthers, Nicholas J; Stemmer, Paul M; Chen, Ben; Valeriote, Frederick; Gao, Xiaohua; Guatam, Subhash C; Shaw, Jiajiu

    2017-09-15

    UTL-5g is a novel small-molecule TNF-alpha modulator. It reduces cisplatin-induced side effects by protecting kidney, liver, and platelets, thereby increasing tolerance for cisplatin. UTL-5g also reduces radiation-induced acute liver toxicity. The mechanism of action for UTL-5g is not clear at the present time. A phosphoproteomic analysis to a depth of 4943 phosphopeptides and a luminescence-based transcription factor activity assay were used to provide complementary analyses of signaling events that were disrupted by UTL-5g in RAW 264.7 cells. Transcriptional activity downstream of the interferon gamma, IL-6, type 1 Interferon, TGF-β, PKC/Ca 2+ and the glucocorticoid receptor pathways were disrupted by UTL-5g. Phosphoproteomic analysis indicated that hyperphosphorylation of proteins involved in actin remodeling was suppressed by UTL-5g (gene set analysis, FDR 5g. This global characterization of UTL-5g activity in a macrophage cell line discovered that it disrupts selected aspects of LPS signaling including Stat3 activation and actin remodeling providing new insight on how UTL-5g acts to reduce cisplatin-induced side effects. Copyright © 2017 Elsevier B.V. All rights reserved.

  17. Histogram analysis parameters of dynamic contrast-enhanced magnetic resonance imaging can predict histopathological findings including proliferation potential, cellularity, and nucleic areas in head and neck squamous cell carcinoma.

    Science.gov (United States)

    Surov, Alexey; Meyer, Hans Jonas; Leifels, Leonard; Höhn, Anne-Kathrin; Richter, Cindy; Winter, Karsten

    2018-04-20

    Our purpose was to analyze possible associations between histogram analysis parameters of dynamic contrast-enhanced magnetic resonance imaging DCE MRI and histopathological findings like proliferation index, cell count and nucleic areas in head and neck squamous cell carcinoma (HNSCC). 30 patients (mean age 57.0 years) with primary HNSCC were included in the study. In every case, histogram analysis parameters of K trans , V e , and K ep were estimated using a mathlab based software. Tumor proliferation index, cell count, and nucleic areas were estimated on Ki 67 antigen stained specimens. Spearman's non-parametric rank sum correlation coefficients were calculated between DCE and different histopathological parameters. KI 67 correlated with K trans min ( p = -0.386, P = 0.043) and s K trans skewness ( p = 0.382, P = 0.045), V e min ( p = -0.473, P = 0.011), Ve entropy ( p = 0.424, P = 0.025), and K ep entropy ( p = 0.464, P = 0.013). Cell count correlated with K trans kurtosis ( p = 0.40, P = 0.034), V e entropy ( p = 0.475, P = 0.011). Total nucleic area correlated with V e max ( p = 0.386, P = 0.042) and V e entropy ( p = 0.411, P = 0.030). In G1/2 tumors, only K trans entropy correlated well with total ( P =0.78, P =0.013) and average nucleic areas ( p = 0.655, P = 0.006). In G3 tumors, KI 67 correlated with Ve min ( p = -0.552, P = 0.022) and V e entropy ( p = 0.524, P = 0.031). Ve max correlated with total nucleic area ( p = 0.483, P = 0.049). Kep max correlated with total area ( p = -0.51, P = 0.037), and K ep entropy with KI 67 ( p = 0.567, P = 0.018). We concluded that histogram-based parameters skewness, kurtosis and entropy of K trans , V e , and K ep can be used as markers for proliferation activity, cellularity and nucleic content in HNSCC. Tumor grading influences significantly associations between perfusion and histopathological parameters.

  18. Complementation of non-tumorigenicity of HPV18-positive cervical carcinoma cells involves differential mRNA expression of cellular genes including potential tumor suppressor genes on chromosome 11q13.

    Science.gov (United States)

    Kehrmann, Angela; Truong, Ha; Repenning, Antje; Boger, Regina; Klein-Hitpass, Ludger; Pascheberg, Ulrich; Beckmann, Alf; Opalka, Bertram; Kleine-Lowinski, Kerstin

    2013-01-01

    The fusion between human tumorigenic cells and normal human diploid fibroblasts results in non-tumorigenic hybrid cells, suggesting a dominant role for tumor suppressor genes in the generated hybrid cells. After long-term cultivation in vitro, tumorigenic segregants may arise. The loss of tumor suppressor genes on chromosome 11q13 has been postulated to be involved in the induction of the tumorigenic phenotype of human papillomavirus (HPV)18-positive cervical carcinoma cells and their derived tumorigenic hybrid cells after subcutaneous injection in immunocompromised mice. The aim of this study was the identification of novel cellular genes that may contribute to the suppression of the tumorigenic phenotype of non-tumorigenic hybrid cells in vivo. We used cDNA microarray technology to identify differentially expressed cellular genes in tumorigenic HPV18-positive hybrid and parental HeLa cells compared to non-tumorigenic HPV18-positive hybrid cells. We detected several as yet unknown cellular genes that play a role in cell differentiation, cell cycle progression, cell-cell communication, metastasis formation, angiogenesis, antigen presentation, and immune response. Apart from the known differentially expressed genes on 11q13 (e.g., phosphofurin acidic cluster sorting protein 1 (PACS1) and FOS ligand 1 (FOSL1 or Fra-1)), we detected novel differentially expressed cellular genes located within the tumor suppressor gene region (e.g., EGF-containing fibulin-like extracellular matrix protein 2 (EFEMP2) and leucine rich repeat containing 32 (LRRC32) (also known as glycoprotein-A repetitions predominant (GARP)) that may have potential tumor suppressor functions in this model system of non-tumorigenic and tumorigenic HeLa x fibroblast hybrid cells. Copyright © 2013 Elsevier Inc. All rights reserved.

  19. Multiple transcription factors directly regulate Hox gene lin-39 expression in ventral hypodermal cells of the C. elegans embryo and larva, including the hypodermal fate regulators LIN-26 and ELT-6.

    Science.gov (United States)

    Liu, Wan-Ju; Reece-Hoyes, John S; Walhout, Albertha J M; Eisenmann, David M

    2014-05-13

    Hox genes encode master regulators of regional fate specification during early metazoan development. Much is known about the initiation and regulation of Hox gene expression in Drosophila and vertebrates, but less is known in the non-arthropod invertebrate model system, C. elegans. The C. elegans Hox gene lin-39 is required for correct fate specification in the midbody region, including the Vulval Precursor Cells (VPCs). To better understand lin-39 regulation and function, we aimed to identify transcription factors necessary for lin-39 expression in the VPCs, and in particular sought factors that initiate lin-39 expression in the embryo. We used the yeast one-hybrid (Y1H) method to screen for factors that bound to 13 fragments from the lin-39 region: twelve fragments contained sequences conserved between C. elegans and two other nematode species, while one fragment was known to drive reporter gene expression in the early embryo in cells that generate the VPCs. Sixteen transcription factors that bind to eight lin-39 genomic fragments were identified in yeast, and we characterized several factors by verifying their physical interactions in vitro, and showing that reduction of their function leads to alterations in lin-39 levels and lin-39::GFP reporter expression in vivo. Three factors, the orphan nuclear hormone receptor NHR-43, the hypodermal fate regulator LIN-26, and the GATA factor ELT-6 positively regulate lin-39 expression in the embryonic precursors to the VPCs. In particular, ELT-6 interacts with an enhancer that drives GFP expression in the early embryo, and the ELT-6 site we identified is necessary for proper embryonic expression. These three factors, along with the factors ZTF-17, BED-3 and TBX-9, also positively regulate lin-39 expression in the larval VPCs. These results significantly expand the number of factors known to directly bind and regulate lin-39 expression, identify the first factors required for lin-39 expression in the embryo, and hint at a

  20. Global miRNA expression analysis of serous and clear cell ovarian carcinomas identifies differentially expressed miRNAs including miR-200c-3p as a prognostic marker

    International Nuclear Information System (INIS)

    Vilming Elgaaen, Bente; Olstad, Ole Kristoffer; Haug, Kari Bente Foss; Brusletto, Berit; Sandvik, Leiv; Staff, Anne Cathrine; Gautvik, Kaare M; Davidson, Ben

    2014-01-01

    Improved insight into the molecular characteristics of the different ovarian cancer subgroups is needed for developing a more individualized and optimized treatment regimen. The aim of this study was to a) identify differentially expressed miRNAs in high-grade serous ovarian carcinoma (HGSC), clear cell ovarian carcinoma (CCC) and ovarian surface epithelium (OSE), b) evaluate selected miRNAs for association with clinical parameters including survival and c) map miRNA-mRNA interactions. Differences in miRNA expression between HGSC, CCC and OSE were analyzed by global miRNA expression profiling (Affymetrix GeneChip miRNA 2.0 Arrays, n = 12, 9 and 9, respectively), validated by RT-qPCR (n = 35, 19 and 9, respectively), and evaluated for associations with clinical parameters. For HGSC, differentially expressed miRNAs were linked to differentially expressed mRNAs identified previously. Differentially expressed miRNAs (n = 78) between HGSC, CCC and OSE were identified (FDR < 0.01%), of which 18 were validated (p < 0.01) using RT-qPCR in an extended cohort. Compared with OSE, miR-205-5p was the most overexpressed miRNA in HGSC. miR-200 family members and miR-182-5p were the most overexpressed in HGSC and CCC compared with OSE, whereas miR-383 was the most underexpressed. miR-205-5p and miR-200 members target epithelial-mesenchymal transition (EMT) regulators, apparently being important in tumor progression. miR-509-3-5p, miR-509-5p, miR-509-3p and miR-510 were among the strongest differentiators between HGSC and CCC, all being significantly overexpressed in CCC compared with HGSC. High miR-200c-3p expression was associated with poor progression-free (p = 0.031) and overall (p = 0.026) survival in HGSC patients. Interacting miRNA and mRNA targets, including those of a TP53-related pathway presented previously, were identified in HGSC. Several miRNAs differentially expressed between HGSC, CCC and OSE have been identified, suggesting a carcinogenetic role for these mi

  1. A global RNA-seq-driven analysis of CHO host and production cell lines reveals distinct differential expression patterns of genes contributing to recombinant antibody glycosylation.

    Science.gov (United States)

    Könitzer, Jennifer D; Müller, Markus M; Leparc, Germán; Pauers, Martin; Bechmann, Jan; Schulz, Patrick; Schaub, Jochen; Enenkel, Barbara; Hildebrandt, Tobias; Hampel, Martin; Tolstrup, Anne B

    2015-09-01

    Boehringer Ingelheim uses two CHO-DG44 lines for manufacturing biotherapeutics, BI-HEX-1 and BI-HEX-2, which produce distinct cell type-specific antibody glycosylation patterns. A recently established CHO-K1 descended host, BI-HEX-K1, generates antibodies with glycosylation profiles differing from CHO-DG44. Manufacturing process development is significantly influenced by these unique profiles. To investigate the underlying glycosylation related gene expression, we leveraged our CHO host and production cell RNA-seqtranscriptomics and product quality database together with the CHO-K1 genome. We observed that each BI-HEX host and antibody producing cell line has a unique gene expression fingerprint. CHO-DG44 cells only transcribe Fut10, Gfpt2 and ST8Sia6 when expressing antibodies. BI-HEX-K1 cells express ST8Sia6 at host cell level. We detected a link between BI-HEX-1/BI-HEX-2 antibody galactosylation and mannosylation and the gene expression of the B4galt gene family and genes controlling mannose processing. Furthermore, we found major differences between the CHO-DG44 and CHO-K1 lineages in the expression of sialyl transferases and enzymes synthesizing sialic acid precursors, providing a rationale for the lack of immunogenic NeuGc/NGNA synthesis in CHO. Our study highlights the value of systems biotechnology to understand glycoprotein synthesis and product glycoprofiles. Such data improve future production clone selection and process development strategies for better steering of biotherapeutic product quality. Copyright © 2015 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

  2. Identification of novel candidate target genes, including EPHB3, MASP1 and SST at 3q26.2–q29 in squamous cell carcinoma of the lung

    International Nuclear Information System (INIS)

    Kang, Ji Un; Koo, Sun Hoe; Kwon, Kye Chul; Park, Jong Woo; Kim, Jin Man

    2009-01-01

    The underlying genetic alterations for squamous cell carcinoma (SCC) and adenocarcinoma (AC) carcinogenesis are largely unknown. High-resolution array- CGH was performed to identify the differences in the patterns of genomic imbalances between SCC and AC of non-small cell lung cancer (NSCLC). On a genome-wide profile, SCCs showed higher frequency of gains than ACs (p = 0.067). More specifically, statistically significant differences were observed across the histologic subtypes for gains at 2q14.2, 3q26.2–q29, 12p13.2–p13.33, and 19p13.3, as well as losses at 3p26.2–p26.3, 16p13.11, and 17p11.2 in SCC, and gains at 7q22.1 and losses at 15q22.2–q25.2 occurred in AC (P < 0.05). The most striking difference between SCC and AC was gains at the 3q26.2–q29, occurring in 86% (19/22) of SCCs, but in only 21% (3/14) of ACs. Many significant genes at the 3q26.2–q29 regions previously linked to a specific histology, such as EVI1,MDS1, PIK3CA and TP73L, were observed in SCC (P < 0.05). In addition, we identified the following possible target genes (> 30% of patients) at 3q26.2–q29: LOC389174 (3q26.2),KCNMB3 (3q26.32),EPHB3 (3q27.1), MASP1 and SST (3q27.3), LPP and FGF12 (3q28), and OPA1,KIAA022,LOC220729, LOC440996,LOC440997, and LOC440998 (3q29), all of which were significantly targeted in SCC (P < 0.05). Among these same genes, high-level amplifications were detected for the gene, EPHB3, at 3q27.1, and MASP1 and SST, at 3q27.3 (18, 18, and 14%, respectively). Quantitative real time PCR demonstrated array CGH detected potential candidate genes that were over expressed in SCCs. Using whole-genome array CGH, we have successfully identified significant differences and unique information of chromosomal signatures prevalent between the SCC and AC subtypes of NSCLC. The newly identified candidate target genes may prove to be highly attractive candidate molecular markers for the classification of NSCLC histologic subtypes, and could potentially contribute to the

  3. (including travel dates) Proposed itinerary

    Indian Academy of Sciences (India)

    Ashok

    31 July to 22 August 2012 (including travel dates). Proposed itinerary: Arrival in Bangalore on 1 August. 1-5 August: Bangalore, Karnataka. Suggested institutions: Indian Institute of Science, Bangalore. St Johns Medical College & Hospital, Bangalore. Jawaharlal Nehru Centre, Bangalore. 6-8 August: Chennai, TN.

  4. A 3.0-kb deletion including an erythroid cell-specific regulatory element in intron 1 of the ABO blood group gene in an individual with the Bm phenotype.

    Science.gov (United States)

    Sano, R; Kuboya, E; Nakajima, T; Takahashi, Y; Takahashi, K; Kubo, R; Kominato, Y; Takeshita, H; Yamao, H; Kishida, T; Isa, K; Ogasawara, K; Uchikawa, M

    2015-04-01

    We developed a sequence-specific primer PCR (SSP-PCR) for detection of a 5.8-kb deletion (B(m) 5.8) involving an erythroid cell-specific regulatory element in intron 1 of the ABO blood group gene. Using this SSP-PCR, we performed genetic analysis of 382 individuals with Bm or ABm. The 5.8-kb deletion was found in 380 individuals, and disruption of the GATA motif in the regulatory element was found in one individual. Furthermore, a novel 3.0-kb deletion involving the element (B(m) 3.0) was demonstrated in the remaining individual. Comparisons of single-nucleotide polymorphisms and microsatellites in intron 1 between B(m) 5.8 and B(m) 3.0 suggested that these deletions occurred independently. © 2014 International Society of Blood Transfusion.

  5. Theory including future not excluded

    DEFF Research Database (Denmark)

    Nagao, K.; Nielsen, H.B.

    2013-01-01

    We study a complex action theory (CAT) whose path runs over not only past but also future. We show that, if we regard a matrix element defined in terms of the future state at time T and the past state at time TA as an expectation value in the CAT, then we are allowed to have the Heisenberg equation......, Ehrenfest's theorem, and the conserved probability current density. In addition,we showthat the expectation value at the present time t of a future-included theory for large T - t and large t - T corresponds to that of a future-not-included theory with a proper inner product for large t - T. Hence, the CAT...

  6. The selective treatment of clinical mastitis based on on-farm culture results: II. Effects on lactation performance, including clinical mastitis recurrence, somatic cell count, milk production, and cow survival.

    Science.gov (United States)

    Lago, A; Godden, S M; Bey, R; Ruegg, P L; Leslie, K

    2011-09-01

    The objective of this multi-state, multi-herd clinical trial was to report on the efficacy of using an on-farm culture system to guide strategic treatment decisions in cows with clinical mastitis. The study was conducted in 8 commercial dairy farms ranging in size from 144 to 1,795 cows from Minnesota, Wisconsin, and Ontario, Canada. A total of 422 cows affected with mild or moderate clinical mastitis in 449 quarters were randomly assigned to either (1) a positive-control treatment program or (2) an on-farm culture-based treatment program. Quarter cases assigned to the positive-control group received immediate on-label intramammary treatment with cephapirin sodium. Quarters assigned to the culture-based treatment program were not treated until the results of on-farm culture were determined after 18 to 24h of incubation. Quarters in the culture-based treatment program that had gram-positive growth or a mixed infection were treated according to label instruction using intramammary cephapirin sodium. Quarters assigned to the culture-based treatment program that had gram-negative or no-growth did not receive intramammary therapy. It was already reported in a companion paper that the selective treatment of clinical mastitis based on on-farm culture results decreases antibiotic use by half and tends to decrease milk withholding time without affecting short-term clinical and bacteriological outcomes. The present article reports on long-term outcomes of the aforementioned study. No statistically significant differences existed between cases assigned to the positive-control program and cases assigned to the culture-based treatment program in risk and days for recurrence of clinical mastitis in the same quarter (35% and 78 d vs. 43% and 82 d), linear somatic cell count (4.2 vs. 4.4), daily milk production (30.0 vs. 30.7 kg), and risk and days for culling or death events (28% and 160 d vs. 32% and 137 d) for the rest of the lactation after enrollment of the clinical mastitis

  7. Identification and monitoring of host cell proteins by mass spectrometry combined with high performance immunochemistry testing.

    Directory of Open Access Journals (Sweden)

    Katrin Bomans

    Full Text Available Biotherapeutics are often produced in non-human host cells like Escherichia coli, yeast, and various mammalian cell lines. A major focus of any therapeutic protein purification process is to reduce host cell proteins to an acceptable low level. In this study, various E. coli host cell proteins were identified at different purifications steps by HPLC fractionation, SDS-PAGE analysis, and tryptic peptide mapping combined with online liquid chromatography mass spectrometry (LC-MS. However, no host cell proteins could be verified by direct LC-MS analysis of final drug substance material. In contrast, the application of affinity enrichment chromatography prior to comprehensive LC-MS was adequate to identify several low abundant host cell proteins at the final drug substance level. Bacterial alkaline phosphatase (BAP was identified as being the most abundant host cell protein at several purification steps. Thus, we firstly established two different assays for enzymatic and immunological BAP monitoring using the cobas® technology. By using this strategy we were able to demonstrate an almost complete removal of BAP enzymatic activity by the established therapeutic protein purification process. In summary, the impact of fermentation, purification, and formulation conditions on host cell protein removal and biological activity can be conducted by monitoring process-specific host cell proteins in a GMP-compatible and high-throughput (> 1000 samples/day manner.

  8. Device including a contact detector

    DEFF Research Database (Denmark)

    2011-01-01

    arms (12) may extend from the supporting body in co-planar relationship with the first surface. The plurality of cantilever arms (12) may extend substantially parallel to each other and each of the plurality of cantilever arms (12) may include an electrical conductive tip for contacting the area......The present invention relates to a probe for determining an electrical property of an area of a surface of a test sample, the probe is intended to be in a specific orientation relative to the test sample. The probe may comprise a supporting body defining a first surface. A plurality of cantilever...... of the test sample by movement of the probe relative to the surface of the test sample into the specific orientation.; The probe may further comprise a contact detector (14) extending from the supporting body arranged so as to contact the surface of the test sample prior to any one of the plurality...

  9. Neoclassical transport including collisional nonlinearity.

    Science.gov (United States)

    Candy, J; Belli, E A

    2011-06-10

    In the standard δf theory of neoclassical transport, the zeroth-order (Maxwellian) solution is obtained analytically via the solution of a nonlinear equation. The first-order correction δf is subsequently computed as the solution of a linear, inhomogeneous equation that includes the linearized Fokker-Planck collision operator. This equation admits analytic solutions only in extreme asymptotic limits (banana, plateau, Pfirsch-Schlüter), and so must be solved numerically for realistic plasma parameters. Recently, numerical codes have appeared which attempt to compute the total distribution f more accurately than in the standard ordering by retaining some nonlinear terms related to finite-orbit width, while simultaneously reusing some form of the linearized collision operator. In this work we show that higher-order corrections to the distribution function may be unphysical if collisional nonlinearities are ignored.

  10. Three-dimensional imaging of absolute blood flow velocity and blood vessel position under low blood flow velocity based on Doppler signal information included in scattered light from red blood cells

    Science.gov (United States)

    Kyoden, Tomoaki; Akiguchi, Shunsuke; Tajiri, Tomoki; Andoh, Tsugunobu; Hachiga, Tadashi

    2017-11-01

    The development of a system for in vivo visualization of occluded distal blood vessels for diabetic patients is the main target of our research. We herein describe two-beam multipoint laser Doppler velocimetry (MLDV), which measures the instantaneous multipoint flow velocity and can be used to observe the blood flow velocity in peripheral blood vessels. By including a motorized stage to shift the measurement points horizontally and in the depth direction while measuring the velocity, the path of the blood vessel in the skin could be observed using blood flow velocity in three-dimensional space. The relationship of the signal power density between the blood vessel and the surrounding tissues was shown and helped us identify the position of the blood vessel. Two-beam MLDV can be used to simultaneously determine the absolute blood flow velocity distribution and identify the blood vessel position in skin.

  11. The Budget Impact of Including Necitumumab on the Formulary for First-Line Treatment of Metastatic Squamous Non-Small Cell Lung Cancer: U.S. Commercial Payer and Medicare Perspectives.

    Science.gov (United States)

    Bly, Christopher A; Molife, Cliff; Brown, Jacqueline; Tawney, Mahesh K; Carter, Gebra Cuyun; Cinfio, Frank N; Klein, Robert W

    2018-06-01

    Necitumumab (Neci) was the first biologic approved by the FDA for use in combination with gemcitabine and cisplatin (Neci + GCis) in first-line treatment of metastatic squamous non-small cell lung cancer (msqNSCLC). The potential financial impact on a health plan of adding Neci + GCis to drug formularies may be important to value-based decision makers in the United States, given ever-tightening budget constraints. To estimate the budget impact of introducing Neci + GCis for first-line treatment of msqNSCLC from U.S. commercial and Medicare payer perspectives. The budget impact model estimates the costs of msqNSCLC before and after adoption of Neci + GCis in hypothetical U.S. commercial and Medicare health plans over a 3-year time horizon. The eligible patient population was estimated from U.S. epidemiology statistics. Clinical data were obtained from randomized clinical trials, U.S. prescribing information, and clinical guidelines. Market share projections were based on market research data. Cost data were obtained from online sources and published literature. The incremental aggregate annual health plan, per-patient-per-year (PPPY), and per-member-per-month (PMPM) costs were estimated in 2015 U.S. dollars. One-way sensitivity analyses were conducted to assess the effect of model parameters on results. In a hypothetical 1,000,000-member commercial health plan with an estimated population of 30 msqNSCLC patients receiving first-line chemotherapy, the introduction of Neci + GCis at an initial market share of approximately 5% had an overall year 1 incremental budget impact of $88,394 ($3,177 PPPY, $0.007 PMPM), representing a 2.9% cost increase and reaching $304,079 ($10,397 PPPY, $0.025 PMPM) or a 7.4% cost increase at a market share of 14.7% in year 3. This increase in total costs was largely attributable to Neci drug costs and, in part, due to longer survival and treatment duration for patients treated with Neci+GCis. Overall, treatment costs increased by $81

  12. Methods for Using Small Non-Coding RNAs to Improve Recombinant Protein Expression in Mammalian Cells

    Directory of Open Access Journals (Sweden)

    Sarah Inwood

    2018-01-01

    Full Text Available The ability to produce recombinant proteins by utilizing different “cell factories” revolutionized the biotherapeutic and pharmaceutical industry. Chinese hamster ovary (CHO cells are the dominant industrial producer, especially for antibodies. Human embryonic kidney cells (HEK, while not being as widely used as CHO cells, are used where CHO cells are unable to meet the needs for expression, such as growth factors. Therefore, improving recombinant protein expression from mammalian cells is a priority, and continuing effort is being devoted to this topic. Non-coding RNAs are RNA segments that are not translated into a protein and often have a regulatory role. Since their discovery, major progress has been made towards understanding their functions. Non-coding RNA has been investigated extensively in relation to disease, especially cancer, and recently they have also been used as a method for engineering cells to improve their protein expression capability. In this review, we provide information about methods used to identify non-coding RNAs with the potential of improving recombinant protein expression in mammalian cell lines.

  13. A Consensus Genome-scale Reconstruction of Chinese Hamster Ovary Cell Metabolism

    KAUST Repository

    Hefzi, Hooman

    2016-11-23

    Chinese hamster ovary (CHO) cells dominate biotherapeutic protein production and are widely used in mammalian cell line engineering research. To elucidate metabolic bottlenecks in protein production and to guide cell engineering and bioprocess optimization, we reconstructed the metabolic pathways in CHO and associated them with >1,700 genes in the Cricetulus griseus genome. The genome-scale metabolic model based on this reconstruction, iCHO1766, and cell-line-specific models for CHO-K1, CHO-S, and CHO-DG44 cells provide the biochemical basis of growth and recombinant protein production. The models accurately predict growth phenotypes and known auxotrophies in CHO cells. With the models, we quantify the protein synthesis capacity of CHO cells and demonstrate that common bioprocess treatments, such as histone deacetylase inhibitors, inefficiently increase product yield. However, our simulations show that the metabolic resources in CHO are more than three times more efficiently utilized for growth or recombinant protein synthesis following targeted efforts to engineer the CHO secretory pathway. This model will further accelerate CHO cell engineering and help optimize bioprocesses.

  14. Priming anticancer active specific immunotherapy with dendritic cells.

    Science.gov (United States)

    Mocellin, Simone

    2005-06-01

    Dendritic cells (DCs) probably represent the most powerful naturally occurring immunological adjuvant for anticancer vaccines. However, the initial enthusiasm for DC-based vaccines is being tempered by clinical results not meeting expectations. The partial failure of current vaccine formulations is explained by the extraordinary complexity of the immune system, which makes the task of exploiting the potential of such a biotherapeutic approach highly challenging. Clinical findings obtained in humans so far indicate that the immune system can be actively polarized against malignant cells by means of DC-based active specific immunotherapy, and that in some cases this is associated with tumor regression. This implies that under some unique circumstances, the naturally 'dormant' immune effectors can actually be employed as endogenous weapons against malignant cells. Only the thorough understanding of DC biology and tumor-host immune system interactions will allow researchers to reproduce, in a larger set of patients, the cellular/molecular conditions leading to an effective immune-mediated eradication of cancer.

  15. Treatment Option Overview (Plasma Cell Neoplasms Including Multiple Myeloma)

    Science.gov (United States)

    ... factors affect prognosis (chance of recovery) and treatment options. The prognosis (chance of recovery ) depends on the ... going up even though treatment is given. Treatment Option Overview Key Points There are different types of ...

  16. Calculation of Dancoff correction for cylindrical cells including void

    International Nuclear Information System (INIS)

    Lima, C.P.B.; Martinez, A.S.

    1989-01-01

    This paper presents a method developed to the calculation of an analytical expression to the Dancoff Correction for fuel rods surrounded by air gaps. The Dancoff Correction has an important role in the calculation of the multigroup constants. The approximated expression obtained to the Dancoff Correction may be used in the available methods for the multigroup constants calculation, based in its simple and precise form. (author) [pt

  17. Stages of Plasma Cell Neoplasms (Including Multiple Myeloma)

    Science.gov (United States)

    ... cancer treatment is also called biotherapy or immunotherapy. Immunomodulators are a type of biologic therapy. Thalidomide , lenalidomide , and pomalidomide are immunomodulators used to treat multiple myeloma and other plasma ...

  18. Treatment Options for Plasma Cell Neoplasms (Including Multiple Myeloma)

    Science.gov (United States)

    ... cancer treatment is also called biotherapy or immunotherapy. Immunomodulators are a type of biologic therapy. Thalidomide , lenalidomide , and pomalidomide are immunomodulators used to treat multiple myeloma and other plasma ...

  19. Assessing the survival of MRC5 and a549 cell lines upon exposure to pyruvic Acid, sodium citrate and sodium bicarbonate - biomed 2013.

    Science.gov (United States)

    Farah, Ibrahim O; Lewis, Veshell L; Ayensu, Wellington K; Cameron, Joseph A

    2013-01-01

    Lung cancer is among the most prevalent and deadly cancers in United States. In general, cancer cells are known to exhibit higher rates of glycolysis in comparison to normal cells. In attempting to exploit this unique cancer-dependent ATP generation phenomenon, it was our hypothesis that upon exposure to organic inhibitors of glycolysis, cancer cells would not survive normally and that their growth and viability would be vastly decreased; essential glycolytic ATP production will be exhausted to the point of collapsing energy utilization. Furthermore, we hypothesize that no negative effect would be seen with exposures to organic inhibitors for normal lung cells. The human lung fibroblast MRC-5 and the human A549 alveolar epithelial cell lines were used as in vitro models of normal lung and lung cancers respectively. Using standard methods, both cell lines were maintained and exposed to pyruvic acid, sodium citrate and sodium bicarbonate reagents at concentration levels ranging from 31.3-2,000 µg/ml in 96 well plates in quadruplets and experiments repeated at least three times using MTT, and cell counting (T4 Cellometer) assays as well as phase-contrast photo-imaging for parallel morphological displays of any changes in the course of their vitality and metabolic activities. Our results indicate that exposure of both cell lines to these organics resulted in concentration dependent cell destruction/cell survival depending on the cell line exposed. Pyruvic acid, sodium citrate and sodium bicarbonate showed statistically significant (pcancer biotherapeutics.

  20. Cellular Phone Towers, Cell towers developed for Appraiser's Department in 2003. Location was based upon parcel centroids, and corrected to orthophotography. Probably includes towers other than cell towers (uncertain). Not published., Published in 2003, 1:1200 (1in=100ft) scale, Sedgwick County Government.

    Data.gov (United States)

    NSGIC Local Govt | GIS Inventory — Cellular Phone Towers dataset current as of 2003. Cell towers developed for Appraiser's Department in 2003. Location was based upon parcel centroids, and corrected...

  1. Generation and characterization of the first immortalized alpaca cell line suitable for diagnostic and immunization studies.

    Directory of Open Access Journals (Sweden)

    Valentina Franceschi

    Full Text Available Raising of alpacas as exotic livestock for wool and meat production and as companion animals is growing in importance in the United States, Europe and Australia. Furthermore the alpaca, as well as the rest of the camelids, possesses the peculiarity of producing single-chain antibodies from which nanobodies can be generated. Nanobodies, due to their structural simplicity and reduced size, are very versatile in terms of manipulation and bio-therapeutic exploitation. In fact the biotech companies involved in nanobody production and application continue to grow in number and size. Hence, the development of reagents and tools to assist in the further growth of this new scientific and entrepreneurial reality is becoming a necessity. These are needed mainly to address alpaca disease diagnosis and prophylaxis, and to develop alpaca immunization strategies for nanobody generation. For instance an immortalized alpaca cell line would be extremely valuable. In the present work the first stabilized alpaca cell line from alpaca skin stromal cells (ASSCs was generated and characterized. This cell line was shown to be suitable for replication of viruses bovine herpesvirus-1, bovine viral diarrhea virus and caprine herpesvirus-1 and the endocellular parasite Neospora caninum. Moreover ASSCs were easy to transfect and transduce by several methods. These two latter characteristics are extremely useful when recombinant antigens need to be produced in a host homologous system. This work could be considered as a starting point for the expansion of the biotechnologies linked to alpaca farming and industry.

  2. Advanced process monitoring and feedback control to enhance cell culture process production and robustness.

    Science.gov (United States)

    Zhang, An; Tsang, Valerie Liu; Moore, Brandon; Shen, Vivian; Huang, Yao-Ming; Kshirsagar, Rashmi; Ryll, Thomas

    2015-12-01

    It is a common practice in biotherapeutic manufacturing to define a fixed-volume feed strategy for nutrient feeds, based on historical cell demand. However, once the feed volumes are defined, they are inflexible to batch-to-batch variations in cell growth and physiology and can lead to inconsistent productivity and product quality. In an effort to control critical quality attributes and to apply process analytical technology (PAT), a fully automated cell culture feedback control system has been explored in three different applications. The first study illustrates that frequent monitoring and automatically controlling the complex feed based on a surrogate (glutamate) level improved protein production. More importantly, the resulting feed strategy was translated into a manufacturing-friendly manual feed strategy without impact on product quality. The second study demonstrates the improved process robustness of an automated feed strategy based on online bio-capacitance measurements for cell growth. In the third study, glucose and lactate concentrations were measured online and were used to automatically control the glucose feed, which in turn changed lactate metabolism. These studies suggest that the auto-feedback control system has the potential to significantly increase productivity and improve robustness in manufacturing, with the goal of ensuring process performance and product quality consistency. © 2015 Wiley Periodicals, Inc.

  3. Monitoring Quality of Biotherapeutic Products Using Multivariate Data Analysis.

    Science.gov (United States)

    Rathore, Anurag S; Pathak, Mili; Jain, Renu; Jadaun, Gaurav Pratap Singh

    2016-07-01

    Monitoring the quality of pharmaceutical products is a global challenge, heightened by the implications of letting subquality drugs come to the market on public safety. Regulatory agencies do their due diligence at the time of approval as per their prescribed regulations. However, product quality needs to be monitored post-approval as well to ensure patient safety throughout the product life cycle. This is particularly complicated for biotechnology-based therapeutics where seemingly minor changes in process and/or raw material attributes have been shown to have a significant effect on clinical safety and efficacy of the product. This article provides a perspective on the topic of monitoring the quality of biotech therapeutics. In the backdrop of challenges faced by the regulatory agencies, the potential use of multivariate data analysis as a tool for effective monitoring has been proposed. Case studies using data from several insulin biosimilars have been used to illustrate the key concepts.

  4. Patent holdings of US biotherapeutic companies in major markets.

    Science.gov (United States)

    Sebastian, Teena E; Yerram, Chandra Bindu; Saberwal, Gayatri

    2009-05-01

    In previous studies we examined the (United States, US) patent holdings of 109 largely North American biotech companies developing therapeutics that, in particular, have an interest in discovery stage science. There appears little correlation between the number of patents and the number of products of individual companies. Here we quantified and compared the 103 US-headquartered companies' patent holdings in Australia, Canada, Europe, Japan and the US. The companies demonstrate variable and surprising patterns of patent holdings across these countries or regions. For most companies, patent holdings are not in proportion to the importance of the country as a biotech or pharma market. These results have implications for the patenting strategies of small biotech companies involved in drug discovery.

  5. Solid-state nuclear magnetic resonance (NMR) spectroscopy of human immunodeficiency virus gp41 protein that includes the fusion peptide: NMR detection of recombinant Fgp41 in inclusion bodies in whole bacterial cells and structural characterization of purified and membrane-associated Fgp41.

    Science.gov (United States)

    Vogel, Erica P; Curtis-Fisk, Jaime; Young, Kaitlin M; Weliky, David P

    2011-11-22

    Human immunodeficiency virus (HIV) infection of a host cell begins with fusion of the HIV and host cell membranes and is mediated by the gp41 protein, a single-pass integral membrane protein of HIV. The 175 N-terminal residues make up the ectodomain that lies outside the virus. This work describes the production and characterization of an ectodomain construct containing the 154 N-terminal gp41 residues, including the fusion peptide (FP) that binds to target cell membranes. The Fgp41 sequence was derived from one of the African clade A strains of HIV-1 that have been less studied than European/North American clade B strains. Fgp41 expression at a level of ~100 mg/L of culture was evidenced by an approach that included amino acid type (13)CO and (15)N labeling of recombinant protein and solid-state NMR (SSNMR) spectroscopy of lyophilized whole cells. The approach did not require any protein solubilization or purification and may be a general approach for detection of recombinant protein. The purified Fgp41 yield was ~5 mg/L of culture. SSNMR spectra of membrane-associated Fgp41 showed high helicity for the residues C-terminal of the FP. This was consistent with a "six-helix bundle" (SHB) structure that is the final gp41 state during membrane fusion. This observation and negligible Fgp41-induced vesicle fusion supported a function for SHB gp41 of membrane stabilization and fusion arrest. SSNMR spectra of residues in the membrane-associated FP provided evidence of a mixture of molecular populations with either helical or β-sheet FP conformation. These and earlier SSNMR data strongly support the existence of these populations in the SHB state of membrane-associated gp41. © 2011 American Chemical Society

  6. Experimental and in silico modelling analyses of the gene expression pathway for recombinant antibody and by-product production in NS0 cell lines.

    Science.gov (United States)

    Mead, Emma J; Chiverton, Lesley M; Spurgeon, Sarah K; Martin, Elaine B; Montague, Gary A; Smales, C Mark; von der Haar, Tobias

    2012-01-01

    Monoclonal antibodies are commercially important, high value biotherapeutic drugs used in the treatment of a variety of diseases. These complex molecules consist of two heavy chain and two light chain polypeptides covalently linked by disulphide bonds. They are usually expressed as recombinant proteins from cultured mammalian cells, which are capable of correctly modifying, folding and assembling the polypeptide chains into the native quaternary structure. Such recombinant cell lines often vary in the amounts of product produced and in the heterogeneity of the secreted products. The biological mechanisms of this variation are not fully defined. Here we have utilised experimental and modelling strategies to characterise and define the biology underpinning product heterogeneity in cell lines exhibiting varying antibody expression levels, and then experimentally validated these models. In undertaking these studies we applied and validated biochemical (rate-constant based) and engineering (nonlinear) models of antibody expression to experimental data from four NS0 cell lines with different IgG4 secretion rates. The models predict that export of the full antibody and its fragments are intrinsically linked, and cannot therefore be manipulated individually at the level of the secretory machinery. Instead, the models highlight strategies for the manipulation at the precursor species level to increase recombinant protein yields in both high and low producing cell lines. The models also highlight cell line specific limitations in the antibody expression pathway.

  7. Anticarcinogenic properties of medium chain fatty acids on human colorectal, skin and breast cancer cells in vitro.

    Science.gov (United States)

    Narayanan, Amoolya; Baskaran, Sangeetha Ananda; Amalaradjou, Mary Anne Roshni; Venkitanarayanan, Kumar

    2015-03-05

    Colorectal cancer, breast cancer and skin cancer are commonly-reported cancer types in the U.S. Although radiation and chemotherapy are routinely used to treat cancer, they produce side effects in patients. Additionally, resistance to chemotherapeutic drugs has been noticed in cancers. Thus, there is a need for effective and safe bioprophylactics and biotherapeutics in cancer therapy. The medicinal value of goat milk has been recognized for centuries and is primarily attributed to three fatty acids, namely capric, caprylic and caproic acids. This research investigates the anticancer property of these fatty acids on human colorectal, skin and mammary gland cancer cells. The cancer cells were treated with various concentrations of fatty acids for 48 h, and cell viability was monitored by the 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) reduction assay. Additionally, real-time quantitative PCR (RT-qPCR) was performed to elucidate the potential anti-cancer mechanisms of the three fatty acids under investigation. Capric, caprylic and caproic acids reduced cancer cell viability by 70% to 90% (p acids in an appropriate in vivo model.

  8. Contribution to the systemic study of energetic systems including electrochemical devices: Bond Graph formalism applied to modelling fuel cells, lithium-ion batteries and sun-racer; Contribution a l'etude systemique de dispositifs energetiques a composants electrochimiques. Formalisme Bond Graph applique aux piles a combustible, accumulateurs lithium-ion, vehicule solaire

    Energy Technology Data Exchange (ETDEWEB)

    Saisset, R.

    2004-04-01

    This thesis is a contribution to the study of electric power conversion systems including electrochemical devices. A systemic approach draws advantage of the unified Bond Graph formalism in order to model every component as well as the whole system. A state of the art of electrochemical devices for decentralized electric energy generation and storage put emphasis on common phenomena with the aim of developing 'system oriented' generic models. Solid Oxide and Proton Exchange Fuel Cells (SOFC, PEMFC), as well as Lithium Ion batteries, have been modelled through an efficient work with electrochemistry specialists. These models involve an explicit representation, at a macroscopic level, of conversion and irreversible phenomena linked to the chemical reaction and coupled together both in the hydraulic, chemical, thermodynamic, electric and thermal fields. These models are used to study the modularity of the components, particularly the electric and thermal imbalances in the series and parallel fuel cells associations. The systemic approach is also applied to the study of architectures and energy management of electric power generating units involving PEMFC and battery or super-capacitors storage. Different working conditions for the fuel cells are defined and studied, consisting in either voltage or current or power imposed by means of the storage and static converters environment. Identification of parameters and working tests are performed on specially developed test benches so as to validate theoretical results. At last, the method is applied to study a 'sun-racer', an original complex system with embedded photovoltaic generator, electrochemical storage and brush-less wheel motor, wholly modelled in order to compare various energy management onboard the solar vehicle 'Solelhada'. (author)

  9. Coumarin-gold nanoparticle bioconjugates: preparation, antioxidant, and cytotoxic effects against MCF-7 breast cancer cells

    Science.gov (United States)

    Mahendran, Gokila; Ponnuchamy, Kumar

    2018-05-01

    In recent, the conjugation of gold nanoparticles (AuNPs) with biomolecules has shown great potential especially in disease diagnostics and treatment. Taking this in account, we report the methodology involved in the conjugation of coumarin onto the surface of citrate-capped AuNPs by a simple in situ method. Herein, we systematically performed UV-Vis spectroscopy, transmission electron microscopy, dynamic light scattering, and zeta potential measurements to characterize citrate-capped AuNPs and bioconjugates. Our results demonstrate in-depth surface chemistry of bioconjugates with improved surface plasmon resonance (529 nm), morphology (near spherical shape), hydrodynamic diameter (25.3 nm) as well as surface charge (- 35 mV). Furthermore, the bioconjugates displayed dose-dependent response in scavenging free radicals and exhibited cytotoxicity against MCF-7 breast cancer cell lines. In addition, phase-contrast microscopic analysis revealed that bioconjugates promote apoptosis in cancer cells in a time-dependent manner. Overall, we ascertain the fact that this kind of bioconjugation of AuNPs with coumarin further enhances the efficacy of inorganic nanomaterials and thus make them a better bio-therapeutic candidate.

  10. 42 CFR 410.100 - Included services.

    Science.gov (United States)

    2010-10-01

    ... service; however, maintenance therapy itself is not covered as part of these services. (c) Occupational... increase respiratory function, such as graded activity services; these services include physiologic... rehabilitation plan of treatment, including physical therapy services, occupational therapy services, speech...

  11. Static, Lightweight Includes Resolution for PHP

    NARCIS (Netherlands)

    M.A. Hills (Mark); P. Klint (Paul); J.J. Vinju (Jurgen)

    2014-01-01

    htmlabstractDynamic languages include a number of features that are challenging to model properly in static analysis tools. In PHP, one of these features is the include expression, where an arbitrary expression provides the path of the file to include at runtime. In this paper we present two

  12. Article Including Environmental Barrier Coating System

    Science.gov (United States)

    Lee, Kang N. (Inventor)

    2015-01-01

    An enhanced environmental barrier coating for a silicon containing substrate. The enhanced barrier coating may include a bond coat doped with at least one of an alkali metal oxide and an alkali earth metal oxide. The enhanced barrier coating may include a composite mullite bond coat including BSAS and another distinct second phase oxide applied over said surface.

  13. Rare thoracic cancers, including peritoneum mesothelioma

    NARCIS (Netherlands)

    Siesling, Sabine; van der Zwan, Jan Maarten; Izarzugaza, Isabel; Jaal, Jana; Treasure, Tom; Foschi, Roberto; Ricardi, Umberto; Groen, Harry; Tavilla, Andrea; Ardanaz, Eva

    Rare thoracic cancers include those of the trachea, thymus and mesothelioma (including peritoneum mesothelioma). The aim of this study was to describe the incidence, prevalence and survival of rare thoracic tumours using a large database, which includes cancer patients diagnosed from 1978 to 2002,

  14. Rare thoracic cancers, including peritoneum mesothelioma

    NARCIS (Netherlands)

    Siesling, Sabine; Zwan, J.M.V.D.; Izarzugaza, I.; Jaal, J.; Treasure, T.; Foschi, R.; Ricardi, U.; Groen, H.; Tavilla, A.; Ardanaz, E.

    2012-01-01

    Rare thoracic cancers include those of the trachea, thymus and mesothelioma (including peritoneum mesothelioma). The aim of this study was to describe the incidence, prevalence and survival of rare thoracic tumours using a large database, which includes cancer patients diagnosed from 1978 to 2002,

  15. Mechanism of mucosal permeability enhancement of CriticalSorb® (Solutol® HS15) investigated in vitro in cell cultures.

    Science.gov (United States)

    Shubber, Saif; Vllasaliu, Driton; Rauch, Cyril; Jordan, Faron; Illum, Lisbeth; Stolnik, Snjezana

    2015-02-01

    CriticalSorb™, with the principal component Solutol® HS15, is a novel mucosal drug delivery system demonstrated to improve the bioavailability of selected biotherapeutics. The intention of this study is to elucidate mechanism(s) responsible for the enhancement of trans-mucosal absorption of biological drugs by Solutol® HS15. Micelle size and CMC of Solutol® HS15 were determined in biologically relevant media. Polarised airway Calu-3 cell layers were used to measure the permeability of a panel of biological drugs, and to assess changes in TEER, tight junction and F-actin morphology. The rate of cell endocytosis was measured in vitro in the presence of Solutol® HS15 using a membrane probe, FM 2-10. This work initially confirms surfactant-like behaviour of Solutol® HS15 in aqueous media, while subsequent experiments demonstrate that the effect of Solutol® HS15 on epithelial tight junctions is different from a 'classical' tight junction opening agent and illustrate the effect of Solutol® HS15 on the cell membrane (endocytosis rate) and F-actin cytoskeleton. Solutol® HS15 is the principle component of CriticalSorb™ that has shown an enhancement in permeability of medium sized biological drugs across epithelia. This study suggests that its mechanism of action arises primarily from effects on the cell membrane and consequent impacts on the cell cytoskeleton in terms of actin organisation and tight junction opening.

  16. Diseases of the abdomen including the pelvis

    International Nuclear Information System (INIS)

    Kido, C.; Tanaka, H.

    1983-01-01

    This book discusses the following diseases: fatty liver; cystic disease of the liver; liver abscess; liver cirrhosis; hepatic hemangioma; cholelithiasis; primary liver cancer; cholangioma; cancer of the common bile duct; pancreatic cyst; pancreatic calculi; chronic pancreatitis; pancreatic pseudocyst; chronic pancreatitis: pancreatic fatty degeneration; cancer of the pancreas; nonfunctioning kidney: chalk kidney; polycystic kidney; perirenal calcified abscess; renal infarct; cancer of the renal pelvis; adrenal pheochromocytoma; adenoma of the adrenal cortex; leiomyosarcoma of the stomach; malignant mesothelioma; intraperitoneal abscess; perityphlic abscess; retroperitoneal reticulum cell sarcoma; and retroperitoneal cyst

  17. Births and deaths including fetal deaths

    Data.gov (United States)

    U.S. Department of Health & Human Services — Access to a variety of United States birth and death files including fetal deaths: Birth Files, 1968-2009; 1995-2005; Fetal death file, 1982-2005; Mortality files,...

  18. Including Indigenous Minorities in Decision-Making

    DEFF Research Database (Denmark)

    Pristed Nielsen, Helene

    Based on theories of public sphere participation and deliberative democracy, this book presents empirical results from a study of experiences with including Aboriginal and Maori groups in political decision-making in respectively Western Australia and New Zealand......Based on theories of public sphere participation and deliberative democracy, this book presents empirical results from a study of experiences with including Aboriginal and Maori groups in political decision-making in respectively Western Australia and New Zealand...

  19. Gas storage materials, including hydrogen storage materials

    Science.gov (United States)

    Mohtadi, Rana F; Wicks, George G; Heung, Leung K; Nakamura, Kenji

    2013-02-19

    A material for the storage and release of gases comprises a plurality of hollow elements, each hollow element comprising a porous wall enclosing an interior cavity, the interior cavity including structures of a solid-state storage material. In particular examples, the storage material is a hydrogen storage material such as a solid state hydride. An improved method for forming such materials includes the solution diffusion of a storage material solution through a porous wall of a hollow element into an interior cavity.

  20. An Integrated Biochemistry Laboratory, Including Molecular Modeling

    Science.gov (United States)

    Hall, Adele J. Wolfson Mona L.; Branham, Thomas R.

    1996-11-01

    for lysozyme activity and a colorimetric one for protein concentration. Familiarity with the assays is reinforced by an independently designed project to modify a variable in one of these assays. The assay for lysozyme activity is that of Shugar (6), based on hydrolysis of a cell-wall suspension from the bacterium Micrococcus lysodeikticus, a substrate that is particularly sensitive to lysozyme. As the cell walls are broken down by the enzyme, the turbidity of the sample decreases. This decrease can be conveniently measured by following the decrease in absorbance at a wavelength of 450 nm, using a spectrophotometer or other device for measuring light scattering. The Bradford method (7), a standard assay, is used to determine protein concentration. Using the data from both lysozyme activity assays and protein concentration assays, students can calculate the specific activity for commercial lysozyme and an egg- white solution. These calculations clearly demonstrate the increase in specific activity with increasing purity, since the purified (commercial) preparation has a specific activity approximately 20-fold higher than that of the crude egg-white solution. Lysozyme Purification by Ion-Exchange Chromatography (5 weeks) As suggested by Strang (8), students can design a rational purification of lysozyme using ion-exchange chromatography when presented with information on the isoelectric point of the enzyme and the properties of ion- exchange resins. One week is spent discussing protein purification and the relative advantages and disadvantages of different resins. Each group has a choice of anion-exchange (DEAE) or cation-exchange (CM) resins. Because lysozyme is positively charged below a pH of 11, it will not be adsorbed to an anion-exchange resin, but will be adsorbed to the cation-exchange resin. Therefore, for the cation-exchange protocols, there are further options for methods of collecting and eluting the desired protein. A purification table, including

  1. Electric Power Monthly, August 1990. [Glossary included

    Energy Technology Data Exchange (ETDEWEB)

    1990-11-29

    The Electric Power Monthly (EPM) presents monthly summaries of electric utility statistics at the national, Census division, and State level. The purpose of this publication is to provide energy decisionmakers with accurate and timely information that may be used in forming various perspectives on electric issues that lie ahead. Data includes generation by energy source (coal, oil, gas, hydroelectric, and nuclear); generation by region; consumption of fossil fuels for power generation; sales of electric power, cost data; and unusual occurrences. A glossary is included.

  2. Isolators Including Main Spring Linear Guide Systems

    Science.gov (United States)

    Goold, Ryan (Inventor); Buchele, Paul (Inventor); Hindle, Timothy (Inventor); Ruebsamen, Dale Thomas (Inventor)

    2017-01-01

    Embodiments of isolators, such as three parameter isolators, including a main spring linear guide system are provided. In one embodiment, the isolator includes first and second opposing end portions, a main spring mechanically coupled between the first and second end portions, and a linear guide system extending from the first end portion, across the main spring, and toward the second end portion. The linear guide system expands and contracts in conjunction with deflection of the main spring along the working axis, while restricting displacement and rotation of the main spring along first and second axes orthogonal to the working axis.

  3. 28 CFR 20.32 - Includable offenses.

    Science.gov (United States)

    2010-07-01

    ... Exchange of Criminal History Record Information § 20.32 Includable offenses. (a) Criminal history record... vehicular manslaughter, driving under the influence of drugs or liquor, and hit and run), when unaccompanied by a § 20.32(a) offense. These exclusions may not be applicable to criminal history records...

  4. Including Students with Visual Impairments: Softball

    Science.gov (United States)

    Brian, Ali; Haegele, Justin A.

    2014-01-01

    Research has shown that while students with visual impairments are likely to be included in general physical education programs, they may not be as active as their typically developing peers. This article provides ideas for equipment modifications and game-like progressions for one popular physical education unit, softball. The purpose of these…

  5. Extending flood damage assessment methodology to include ...

    African Journals Online (AJOL)

    Optimal and sustainable flood plain management, including flood control, can only be achieved when the impacts of flood control measures are considered for both the man-made and natural environments, and the sociological aspects are fully considered. Until now, methods/models developed to determine the influences ...

  6. BIOLOGIC AND ECONOMIC EFFECTS OF INCLUDING DIFFERENT ...

    African Journals Online (AJOL)

    The biologic and economic effects of including three agro-industrial by-products as ingredients in turkey poult diets were investigated using 48 turkey poults in a completely randomised design experiment. Diets were formulated to contain the three by-products – wheat offal, rice husk and palm kernel meal, each at 20% level ...

  7. Including Children Dependent on Ventilators in School.

    Science.gov (United States)

    Levine, Jack M.

    1996-01-01

    Guidelines for including ventilator-dependent children in school are offered, based on experience with six such students at a New York State school. Guidelines stress adherence to the medical management plan, the school-family partnership, roles of the social worker and psychologist, orientation, transportation, classroom issues, and steps toward…

  8. Photoactive devices including porphyrinoids with coordinating additives

    Science.gov (United States)

    Forrest, Stephen R; Zimmerman, Jeramy; Yu, Eric K; Thompson, Mark E; Trinh, Cong; Whited, Matthew; Diev, Vlacheslav

    2015-05-12

    Coordinating additives are included in porphyrinoid-based materials to promote intermolecular organization and improve one or more photoelectric characteristics of the materials. The coordinating additives are selected from fullerene compounds and organic compounds having free electron pairs. Combinations of different coordinating additives can be used to tailor the characteristic properties of such porphyrinoid-based materials, including porphyrin oligomers. Bidentate ligands are one type of coordinating additive that can form coordination bonds with a central metal ion of two different porphyrinoid compounds to promote porphyrinoid alignment and/or pi-stacking. The coordinating additives can shift the absorption spectrum of a photoactive material toward higher wavelengths, increase the external quantum efficiency of the material, or both.

  9. Electric power monthly, September 1990. [Glossary included

    Energy Technology Data Exchange (ETDEWEB)

    1990-12-17

    The purpose of this report is to provide energy decision makers with accurate and timely information that may be used in forming various perspectives on electric issues. The power plants considered include coal, petroleum, natural gas, hydroelectric, and nuclear power plants. Data are presented for power generation, fuel consumption, fuel receipts and cost, sales of electricity, and unusual occurrences at power plants. Data are compared at the national, Census division, and state levels. 4 figs., 52 tabs. (CK)

  10. Nuclear reactor shield including magnesium oxide

    International Nuclear Information System (INIS)

    Rouse, C.A.; Simnad, M.T.

    1981-01-01

    An improvement is described for nuclear reactor shielding of a type used in reactor applications involving significant amounts of fast neutron flux. The reactor shielding includes means providing structural support, neutron moderator material, neutron absorber material and other components, wherein at least a portion of the neutron moderator material is magnesium in the form of magnesium oxide either alone or in combination with other moderator materials such as graphite and iron

  11. Model for safety reports including descriptive examples

    International Nuclear Information System (INIS)

    1995-12-01

    Several safety reports will be produced in the process of planning and constructing the system for disposal of high-level radioactive waste in Sweden. The present report gives a model, with detailed examples, of how these reports should be organized and what steps they should include. In the near future safety reports will deal with the encapsulation plant and the repository. Later reports will treat operation of the handling systems and the repository

  12. Jet-calculus approach including coherence effects

    International Nuclear Information System (INIS)

    Jones, L.M.; Migneron, R.; Narayanan, K.S.S.

    1987-01-01

    We show how integrodifferential equations typical of jet calculus can be combined with an averaging procedure to obtain jet-calculus-based results including the Mueller interference graphs. Results in longitudinal-momentum fraction x for physical quantities are higher at intermediate x and lower at large x than with the conventional ''incoherent'' jet calculus. These results resemble those of Marchesini and Webber, who used a Monte Carlo approach based on the same dynamics

  13. [Renal patient's diet: Can fish be included?].

    Science.gov (United States)

    Castro González, M I; Maafs Rodríguez, A G; Galindo Gómez, C

    2012-01-01

    Medical and nutritional treatment for renal disease, now a major public health issue, is highly complicated. Nutritional therapy must seek to retard renal dysfunction, maintain an optimal nutritional status and prevent the development of underlying pathologies. To analyze ten fish species to identify those that, because of their low phosphorus content, high biological value protein and elevated n-3 fatty acids EPA and DHA, could be included in renal patient's diet. The following fish species (Litte tunny, Red drum, Spotted eagleray, Escolar, Swordfish, Big-scale pomfret, Cortez flounder, Largemouth blackbass, Periche mojarra, Florida Pompano) were analyzed according to the AOAC and Keller techniques to determine their protein, phosphorus, sodium, potassium, cholesterol, vitamins D(3) and E, and n-3 EPA+DHA content. These results were used to calculate relations between nutrients. The protein in the analyzed species ranged from 16.5 g/100 g of fillet (Largemouth black bass) to 27.2 g/100 g (Red drum); the lowest phosphorus value was 28.6 mg/100 g (Periche mojarra) and the highest 216.3 mg/100 g (Spotted eagle ray). 80% of the fish presented > 100 mg EPA + DHA in 100 g of fillet. By its Phosphorus/gProtein ratio, Escolar and Swordfish could not be included in the renal diet; Little tunny, Escolar, Big-scale pomfret, Largemouth black-bass, Periche mojarra and Florida Pompano presented a lower Phosphorus/EPA + DHA ratio. Florida pompano is the most recommended specie for renal patients, due to its optimal nutrient relations. However, all analyzed species, except Escolar and Swordfish, could be included in renal diets.

  14. MOS modeling hierarchy including radiation effects

    International Nuclear Information System (INIS)

    Alexander, D.R.; Turfler, R.M.

    1975-01-01

    A hierarchy of modeling procedures has been developed for MOS transistors, circuit blocks, and integrated circuits which include the effects of total dose radiation and photocurrent response. The models were developed for use with the SCEPTRE circuit analysis program, but the techniques are suitable for other modern computer aided analysis programs. The modeling hierarchy permits the designer or analyst to select the level of modeling complexity consistent with circuit size, parametric information, and accuracy requirements. Improvements have been made in the implementation of important second order effects in the transistor MOS model, in the definition of MOS building block models, and in the development of composite terminal models for MOS integrated circuits

  15. Drug delivery device including electrolytic pump

    KAUST Repository

    Foulds, Ian G.; Buttner, Ulrich; Yi, Ying

    2016-01-01

    Systems and methods are provided for a drug delivery device and use of the device for drug delivery. In various aspects, the drug delivery device combines a “solid drug in reservoir” (SDR) system with an electrolytic pump. In various aspects an improved electrolytic pump is provided including, in particular, an improved electrolytic pump for use with a drug delivery device, for example an implantable drug delivery device. A catalytic reformer can be incorporated in a periodically pulsed electrolytic pump to provide stable pumping performance and reduced actuation cycle.

  16. Drug delivery device including electrolytic pump

    KAUST Repository

    Foulds, Ian G.

    2016-03-31

    Systems and methods are provided for a drug delivery device and use of the device for drug delivery. In various aspects, the drug delivery device combines a “solid drug in reservoir” (SDR) system with an electrolytic pump. In various aspects an improved electrolytic pump is provided including, in particular, an improved electrolytic pump for use with a drug delivery device, for example an implantable drug delivery device. A catalytic reformer can be incorporated in a periodically pulsed electrolytic pump to provide stable pumping performance and reduced actuation cycle.

  17. Energy principle with included boundary conditions

    International Nuclear Information System (INIS)

    Lehnert, B.

    1994-01-01

    Earlier comments by the author on the limitations of the classical form of the extended energy principle are supported by a complementary analysis on the potential energy change arising from free-boundary displacements of a magnetically confined plasma. In the final formulation of the extended principle, restricted displacements, satisfying pressure continuity by means of plasma volume currents in a thin boundary layer, are replaced by unrestricted (arbitrary) displacements which can give rise to induced surface currents. It is found that these currents contribute to the change in potential energy, and that their contribution is not taken into account by such a formulation. A general expression is further given for surface currents induced by arbitrary displacements. The expression is used to reformulate the energy principle for the class of displacements which satisfy all necessary boundary conditions, including that of the pressure balance. This makes a minimization procedure of the potential energy possible, for the class of all physically relevant test functions which include the constraints imposed by the boundary conditions. Such a procedure is also consistent with a corresponding variational calculus. (Author)

  18. Aerosol simulation including chemical and nuclear reactions

    International Nuclear Information System (INIS)

    Marwil, E.S.; Lemmon, E.C.

    1985-01-01

    The numerical simulation of aerosol transport, including the effects of chemical and nuclear reactions presents a challenging dynamic accounting problem. Particles of different sizes agglomerate and settle out due to various mechanisms, such as diffusion, diffusiophoresis, thermophoresis, gravitational settling, turbulent acceleration, and centrifugal acceleration. Particles also change size, due to the condensation and evaporation of materials on the particle. Heterogeneous chemical reactions occur at the interface between a particle and the suspending medium, or a surface and the gas in the aerosol. Homogeneous chemical reactions occur within the aersol suspending medium, within a particle, and on a surface. These reactions may include a phase change. Nuclear reactions occur in all locations. These spontaneous transmutations from one element form to another occur at greatly varying rates and may result in phase or chemical changes which complicate the accounting process. This paper presents an approach for inclusion of these effects on the transport of aerosols. The accounting system is very complex and results in a large set of stiff ordinary differential equations (ODEs). The techniques for numerical solution of these ODEs require special attention to achieve their solution in an efficient and affordable manner. 4 refs

  19. Addressing Stillbirth in India Must Include Men.

    Science.gov (United States)

    Roberts, Lisa; Montgomery, Susanne; Ganesh, Gayatri; Kaur, Harinder Pal; Singh, Ratan

    2017-07-01

    Millennium Development Goal 4, to reduce child mortality, can only be achieved by reducing stillbirths globally. A confluence of medical and sociocultural factors contribute to the high stillbirth rates in India. The psychosocial aftermath of stillbirth is a well-documented public health problem, though less is known of the experience for men, particularly outside of the Western context. Therefore, men's perceptions and knowledge regarding reproductive health, as well as maternal-child health are important. Key informant interviews (n = 5) were analyzed and 28 structured interviews were conducted using a survey based on qualitative themes. Qualitative themes included men's dual burden and right to medical and reproductive decision making power. Wives were discouraged from expressing grief and pushed to conceive again. If not successful, particularly if a son was not conceived, a second wife was considered a solution. Quantitative data revealed that men with a history of stillbirths had greater anxiety and depression, perceived less social support, but had more egalitarian views towards women than men without stillbirth experience. At the same time fathers of stillbirths were more likely to be emotionally or physically abusive. Predictors of mental health, attitudes towards women, and perceived support are discussed. Patriarchal societal values, son preference, deficient women's autonomy, and sex-selective abortion perpetuate the risk for future poor infant outcomes, including stillbirth, and compounds the already higher risk of stillbirth for males. Grief interventions should explore and take into account men's perceptions, attitudes, and behaviors towards reproductive decision making.

  20. Including gauge corrections to thermal leptogenesis

    Energy Technology Data Exchange (ETDEWEB)

    Huetig, Janine

    2013-05-17

    This thesis provides the first approach of a systematic inclusion of gauge corrections to leading order to the ansatz of thermal leptogenesis. We have derived a complete expression for the integrated lepton number matrix including all resummations needed. For this purpose, a new class of diagram has been invented, namely the cylindrical diagram, which allows diverse investigations into the topic of leptogenesis such as the case of resonant leptogenesis. After a brief introduction of the topic of the baryon asymmetry in the universe and a discussion of its most promising solutions as well as their advantages and disadvantages, we have presented our framework of thermal leptogenesis. An effective model was described as well as the associated Feynman rules. The basis for using nonequilibrium quantum field theory has been built in chapter 3. At first, the main definitions have been presented for equilibrium thermal field theory, afterwards we have discussed the Kadanoff-Baym equations for systems out of equilibrium using the example of the Majorana neutrino. The equations have also been solved in the context of leptogenesis in chapter 4. Since gauge corrections play a crucial role throughout this thesis, we have also repeated the naive ansatz by replacing the free equilibrium propagator by propagators including thermal damping rates due to the Standard Model damping widths for lepton and Higgs fields. It is shown that this leads to a comparable result to the solutions of the Boltzmann equations for thermal leptogenesis. Thus it becomes obvious that Standard Model corrections are not negligible for thermal leptogenesis and therefore need to be included systematically from first principles. In order to achieve this we have started discussing the calculation of ladder rung diagrams for Majorana neutrinos using the HTL and the CTL approach in chapter 5. All gauge corrections are included in this framework and thus it has become the basis for the following considerations

  1. Including gauge corrections to thermal leptogenesis

    International Nuclear Information System (INIS)

    Huetig, Janine

    2013-01-01

    This thesis provides the first approach of a systematic inclusion of gauge corrections to leading order to the ansatz of thermal leptogenesis. We have derived a complete expression for the integrated lepton number matrix including all resummations needed. For this purpose, a new class of diagram has been invented, namely the cylindrical diagram, which allows diverse investigations into the topic of leptogenesis such as the case of resonant leptogenesis. After a brief introduction of the topic of the baryon asymmetry in the universe and a discussion of its most promising solutions as well as their advantages and disadvantages, we have presented our framework of thermal leptogenesis. An effective model was described as well as the associated Feynman rules. The basis for using nonequilibrium quantum field theory has been built in chapter 3. At first, the main definitions have been presented for equilibrium thermal field theory, afterwards we have discussed the Kadanoff-Baym equations for systems out of equilibrium using the example of the Majorana neutrino. The equations have also been solved in the context of leptogenesis in chapter 4. Since gauge corrections play a crucial role throughout this thesis, we have also repeated the naive ansatz by replacing the free equilibrium propagator by propagators including thermal damping rates due to the Standard Model damping widths for lepton and Higgs fields. It is shown that this leads to a comparable result to the solutions of the Boltzmann equations for thermal leptogenesis. Thus it becomes obvious that Standard Model corrections are not negligible for thermal leptogenesis and therefore need to be included systematically from first principles. In order to achieve this we have started discussing the calculation of ladder rung diagrams for Majorana neutrinos using the HTL and the CTL approach in chapter 5. All gauge corrections are included in this framework and thus it has become the basis for the following considerations

  2. The surgery of peripheral nerves (including tumors)

    DEFF Research Database (Denmark)

    Fugleholm, Kåre

    2013-01-01

    Surgical pathology of the peripheral nervous system includes traumatic injury, entrapment syndromes, and tumors. The recent significant advances in the understanding of the pathophysiology and cellular biology of peripheral nerve degeneration and regeneration has yet to be translated into improved...... surgical techniques and better outcome after peripheral nerve injury. Decision making in peripheral nerve surgery continues to be a complex challenge, where the mechanism of injury, repeated clinical evaluation, neuroradiological and neurophysiological examination, and detailed knowledge of the peripheral...... nervous system response to injury are prerequisite to obtain the best possible outcome. Surgery continues to be the primary treatment modality for peripheral nerve tumors and advances in adjuvant oncological treatment has improved outcome after malignant peripheral nerve tumors. The present chapter...

  3. AMS at the ANU including biomedical applications

    Energy Technology Data Exchange (ETDEWEB)

    Fifield, L K; Allan, G L; Cresswell, R G; Ophel, T R [Australian National Univ., Canberra, ACT (Australia); King, S J; Day, J P [Manchester Univ. (United Kingdom). Dept. of Chemistry

    1994-12-31

    An extensive accelerator mass spectrometry program has been conducted on the 14UD accelerator at the Australian National University since 1986. In the two years since the previous conference, the research program has expanded significantly to include biomedical applications of {sup 26}Al and studies of landform evolution using isotopes produced in situ in surface rocks by cosmic ray bombardment. The system is now used for the measurement of {sup 10}Be, {sup 14}C, {sup 26}Al, {sup 36}Cl, {sup 59}Ni and {sup 129}I, and research is being undertaken in hydrology, environmental geochemistry, archaeology and biomedicine. On the technical side, a new test system has permitted the successful off-line development of a high-intensity ion source. A new injection line to the 14UD has been established and the new source is now in position and providing beams to the accelerator. 4 refs.

  4. AMS at the ANU including biomedical applications

    Energy Technology Data Exchange (ETDEWEB)

    Fifield, L.K.; Allan, G.L.; Cresswell, R.G.; Ophel, T.R. [Australian National Univ., Canberra, ACT (Australia); King, S.J.; Day, J.P. [Manchester Univ. (United Kingdom). Dept. of Chemistry

    1993-12-31

    An extensive accelerator mass spectrometry program has been conducted on the 14UD accelerator at the Australian National University since 1986. In the two years since the previous conference, the research program has expanded significantly to include biomedical applications of {sup 26}Al and studies of landform evolution using isotopes produced in situ in surface rocks by cosmic ray bombardment. The system is now used for the measurement of {sup 10}Be, {sup 14}C, {sup 26}Al, {sup 36}Cl, {sup 59}Ni and {sup 129}I, and research is being undertaken in hydrology, environmental geochemistry, archaeology and biomedicine. On the technical side, a new test system has permitted the successful off-line development of a high-intensity ion source. A new injection line to the 14UD has been established and the new source is now in position and providing beams to the accelerator. 4 refs.

  5. CERN Technical Training: LABVIEW courses include RADE

    CERN Multimedia

    HR Department

    2009-01-01

    The contents of the "LabView Basic I" and "LabView Intermediate II" courses have recently been changed to include, respectively, an introduction to and expert training in the Rapid Application Development Environment (RADE). RADE is a LabView-based application developed at CERN to integrate LabView in the accelerator and experiment control infrastructure. It is a suitable solution to developing expert tools, machine development analysis and independent test facilities. The course names have also been changed to "LabVIEW Basics I with RADE Introduction" and "LabVIEW Intermediate II with Advanced RADE Application". " LabVIEW Basics I with RADE Introduction" is designed for: Users preparing to develop applications using LabVIEW, or NI Developer Suite; users and technical managers evaluating LabVIEW or NI Developer Suite in purchasing decisions; users pursuing the Certified LabVIEW Developer certification. The course pr...

  6. CERN Technical Training: LABVIEW courses include RADE

    CERN Multimedia

    HR Department

    2009-01-01

    The contents of the "LabView Basic I" and "LabView Intermediate II" courses have recently been changed to include, respectively, an introduction to and expert training in the Rapid Application Development Environment (RADE). RADE is a LabView-based application developed at CERN to integrate LabView in the accelerator and experiment control infrastructure. It is a suitable solution to developing expert tools, machine development analysis and independent test facilities. The course names have also been changed to "LabVIEW Basics I with RADE Introduction" and "LabVIEW Intermediate II with Advanced RADE Application". " LabVIEW Basics I with RADE Introduction" is designed for: Users preparing to develop applications using LabVIEW, or NI Developer Suite; users and technical managers evaluating LabVIEW or NI Developer Suite in purchasing decisions; users pursuing the Certified LabVIEW Developer certification. The course prepares participants to develop test and measurement, da...

  7. CERN Technical Training: LABVIEW courses include RADE

    CERN Multimedia

    HR Department

    2009-01-01

    The contents of "LabView Basic I" and "LabView Intermediate II" trainings have been recently changed to include, respectively, an introduction and an expert training on the Rapid Application Development Environment (RADE). RADE is a LabView-based application developed at CERN to integrate LabView in the accelerator and experiment control infrastructure. It is a suitable solution to develop expert tools, machine development analysis and independent test facilities. The course names have also been changed to "LabVIEW Basics I with RADE Introduction" and "LabVIEW Intermediate II with Advanced RADE Application". " LabVIEW Basics I with RADE Introduction" is designed for: Users preparing to develop applications using LabVIEW, or NI Developer Suite; users and technical managers evaluating LabVIEW or NI Developer Suite in purchasing decisions; users pursuing the Certified LabVIEW Developer certification. The course prepare...

  8. Critical point anomalies include expansion shock waves

    Energy Technology Data Exchange (ETDEWEB)

    Nannan, N. R., E-mail: ryan.nannan@uvs.edu [Mechanical Engineering Discipline, Anton de Kom University of Suriname, Leysweg 86, PO Box 9212, Paramaribo, Suriname and Process and Energy Department, Delft University of Technology, Leeghwaterstraat 44, 2628 CA Delft (Netherlands); Guardone, A., E-mail: alberto.guardone@polimi.it [Department of Aerospace Science and Technology, Politecnico di Milano, Via La Masa 34, 20156 Milano (Italy); Colonna, P., E-mail: p.colonna@tudelft.nl [Propulsion and Power, Delft University of Technology, Kluyverweg 1, 2629 HS Delft (Netherlands)

    2014-02-15

    From first-principle fluid dynamics, complemented by a rigorous state equation accounting for critical anomalies, we discovered that expansion shock waves may occur in the vicinity of the liquid-vapor critical point in the two-phase region. Due to universality of near-critical thermodynamics, the result is valid for any common pure fluid in which molecular interactions are only short-range, namely, for so-called 3-dimensional Ising-like systems, and under the assumption of thermodynamic equilibrium. In addition to rarefaction shock waves, diverse non-classical effects are admissible, including composite compressive shock-fan-shock waves, due to the change of sign of the fundamental derivative of gasdynamics.

  9. CLIC expands to include the Southern Hemisphere

    CERN Multimedia

    Roberto Cantoni

    2010-01-01

    Australia has recently joined the CLIC collaboration: the enlargement will bring new expertise and resources to the project, and is especially welcome in the wake of CERN budget redistributions following the recent adoption of the Medium Term Plan.   The countries involved in CLIC collaboration With the signing of a Memorandum of Understanding on 26 August 2010, the ACAS network (Australian Collaboration for Accelerator Science) became the 40th member of in the multilateral CLIC collaboration making Australia the 22nd country to join the collaboration. “The new MoU was signed by the ACAS network, which includes the Australian Synchrotron and the University of Melbourne”, explains Jean-Pierre Delahaye, CLIC Study Leader. “Thanks to their expertise, the Australian institutes will contribute greatly to the CLIC damping rings and the two-beam test modules." Institutes from any country wishing to join the CLIC collaboration are invited to assume responsibility o...

  10. Should Broca's area include Brodmann area 47?

    Science.gov (United States)

    Ardila, Alfredo; Bernal, Byron; Rosselli, Monica

    2017-02-01

    Understanding brain organization of speech production has been a principal goal of neuroscience. Historically, brain speech production has been associated with so-called Broca’s area (Brodmann area –BA- 44 and 45), however, modern neuroimaging developments suggest speech production is associated with networks rather than with areas. The purpose of this paper was to analyze the connectivity of BA47 ( pars orbitalis) in relation to language . A meta-analysis was conducted to assess the language network in which BA47 is involved. The Brainmap database was used. Twenty papers corresponding to 29 experimental conditions with a total of 373 subjects were included. Our results suggest that BA47 participates in a “frontal language production system” (or extended Broca’s system). The BA47  connectivity found is also concordant with a minor role in language semantics. BA47 plays a central role in the language production system.

  11. Musculoskeletal ultrasound including definitions for ultrasonographic pathology

    DEFF Research Database (Denmark)

    Wakefield, RJ; Balint, PV; Szkudlarek, Marcin

    2005-01-01

    Ultrasound (US) has great potential as an outcome in rheumatoid arthritis trials for detecting bone erosions, synovitis, tendon disease, and enthesopathy. It has a number of distinct advantages over magnetic resonance imaging, including good patient tolerability and ability to scan multiple joints...... in a short period of time. However, there are scarce data regarding its validity, reproducibility, and responsiveness to change, making interpretation and comparison of studies difficult. In particular, there are limited data describing standardized scanning methodology and standardized definitions of US...... pathologies. This article presents the first report from the OMERACT ultrasound special interest group, which has compared US against the criteria of the OMERACT filter. Also proposed for the first time are consensus US definitions for common pathological lesions seen in patients with inflammatory arthritis....

  12. Grand unified models including extra Z bosons

    International Nuclear Information System (INIS)

    Li Tiezhong

    1989-01-01

    The grand unified theories (GUT) of the simple Lie groups including extra Z bosons are discussed. Under authors's hypothesis there are only SU 5+m SO 6+4n and E 6 groups. The general discussion of SU 5+m is given, then the SU 6 and SU 7 are considered. In SU 6 the 15+6 * +6 * fermion representations are used, which are not same as others in fermion content, Yukawa coupling and broken scales. A conception of clans of particles, which are not families, is suggested. These clans consist of extra Z bosons and the corresponding fermions of the scale. The all of fermions in the clans are down quarks except for the standard model which consists of Z bosons and 15 fermions, therefore, the spectrum of the hadrons which are composed of these down quarks are different from hadrons at present

  13. Including climate change in energy investment decisions

    International Nuclear Information System (INIS)

    Ybema, J.R.; Boonekamp, P.G.M.; Smit, J.T.J.

    1995-08-01

    To properly take climate change into account in the analysis of energy investment decisions, it is required to apply decision analysis methods that are capable of considering the specific characteristics of climate change (large uncertainties, long term horizon). Such decision analysis methods do exist. They can explicitly include evolving uncertainties, multi-stage decisions, cumulative effects and risk averse attitudes. Various methods are considered in this report and two of these methods have been selected: hedging calculations and sensitivity analysis. These methods are applied to illustrative examples, and its limitations are discussed. The examples are (1a) space heating and hot water for new houses from a private investor perspective and (1b) as example (1a) but from a government perspective, (2) electricity production with an integrated coal gasification combined cycle (ICGCC) with or without CO 2 removal, and (3) national energy strategy to hedge for climate change. 9 figs., 21 tabs., 42 refs., 1 appendix

  14. Education Program on Fossil Resources Including Coal

    Science.gov (United States)

    Usami, Masahiro

    Fossil fuels including coal play a key role as crucial energies in contributing to economic development in Asia. On the other hand, its limited quantity and the environmental problems causing from its usage have become a serious global issue and a countermeasure to solve such problems is very much demanded. Along with the pursuit of sustainable development, environmentally-friendly use of highly efficient fossil resources should be therefore, accompanied. Kyushu-university‧s sophisticated research through long years of accumulated experience on the fossil resources and environmental sectors together with the advanced large-scale commercial and empirical equipments will enable us to foster cooperative research and provide internship program for the future researchers. Then, this program is executed as a consignment business from the Ministry of Economy, Trade and Industry from 2007 fiscal year to 2009 fiscal year. The lecture that uses the textbooks developed by this program is scheduled to be started a course in fiscal year 2010.

  15. Analysis of Smart Composite Structures Including Debonding

    Science.gov (United States)

    Chattopadhyay, Aditi; Seeley, Charles E.

    1997-01-01

    Smart composite structures with distributed sensors and actuators have the capability to actively respond to a changing environment while offering significant weight savings and additional passive controllability through ply tailoring. Piezoelectric sensing and actuation of composite laminates is the most promising concept due to the static and dynamic control capabilities. Essential to the implementation of these smart composites are the development of accurate and efficient modeling techniques and experimental validation. This research addresses each of these important topics. A refined higher order theory is developed to model composite structures with surface bonded or embedded piezoelectric transducers. These transducers are used as both sensors and actuators for closed loop control. The theory accurately captures the transverse shear deformation through the thickness of the smart composite laminate while satisfying stress free boundary conditions on the free surfaces. The theory is extended to include the effect of debonding at the actuator-laminate interface. The developed analytical model is implemented using the finite element method utilizing an induced strain approach for computational efficiency. This allows general laminate geometries and boundary conditions to be analyzed. The state space control equations are developed to allow flexibility in the design of the control system. Circuit concepts are also discussed. Static and dynamic results of smart composite structures, obtained using the higher order theory, are correlated with available analytical data. Comparisons, including debonded laminates, are also made with a general purpose finite element code and available experimental data. Overall, very good agreement is observed. Convergence of the finite element implementation of the higher order theory is shown with exact solutions. Additional results demonstrate the utility of the developed theory to study piezoelectric actuation of composite

  16. Zγ production at NNLO including anomalous couplings

    Science.gov (United States)

    Campbell, John M.; Neumann, Tobias; Williams, Ciaran

    2017-11-01

    In this paper we present a next-to-next-to-leading order (NNLO) QCD calculation of the processes pp → l + l -γ and pp\\to ν \\overline{ν}γ that we have implemented in MCFM. Our calculation includes QCD corrections at NNLO both for the Standard Model (SM) and additionally in the presence of Zγγ and ZZγ anomalous couplings. We compare our implementation, obtained using the jettiness slicing approach, with a previous SM calculation and find broad agreement. Focusing on the sensitivity of our results to the slicing parameter, we show that using our setup we are able to compute NNLO cross sections with numerical uncertainties of about 0.1%, which is small compared to residual scale uncertainties of a few percent. We study potential improvements using two different jettiness definitions and the inclusion of power corrections. At √{s}=13 TeV we present phenomenological results and consider Zγ as a background to H → Zγ production. We find that, with typical cuts, the inclusion of NNLO corrections represents a small effect and loosens the extraction of limits on anomalous couplings by about 10%.

  17. Alternating phase focussing including space charge

    International Nuclear Information System (INIS)

    Cheng, W.H.; Gluckstern, R.L.

    1992-01-01

    Longitudinal stability can be obtained in a non-relativistic drift tube accelerator by traversing each gap as the rf accelerating field rises. However, the rising accelerating field leads to a transverse defocusing force which is usually overcome by magnetic focussing inside the drift tubes. The radio frequency quadrupole is one way of providing simultaneous longitudinal and transverse focusing without the use of magnets. One can also avoid the use of magnets by traversing alternate gaps between drift tubes as the field is rising and falling, thus providing an alternation of focussing and defocusing forces in both the longitudinal and transverse directions. The stable longitudinal phase space area is quite small, but recent efforts suggest that alternating phase focussing (APF) may permit low velocity acceleration of currents in the 100-300 ma range. This paper presents a study of the parameter space and a test of crude analytic predictions by adapting the code PARMILA, which includes space charge, to APF. 6 refs., 3 figs

  18. Probabilistic production simulation including CHP plants

    Energy Technology Data Exchange (ETDEWEB)

    Larsen, H.V.; Palsson, H.; Ravn, H.F.

    1997-04-01

    A probabilistic production simulation method is presented for an energy system containing combined heat and power plants. The method permits incorporation of stochastic failures (forced outages) of the plants and is well suited for analysis of the dimensioning of the system, that is, for finding the appropriate types and capacities of production plants in relation to expansion planning. The method is in the tradition of similar approaches for the analysis of power systems, based on the load duration curve. The present method extends on this by considering a two-dimensional load duration curve where the two dimensions represent heat and power. The method permits the analysis of a combined heat and power system which includes all the basic relevant types of plants, viz., condensing plants, back pressure plants, extraction plants and heat plants. The focus of the method is on the situation where the heat side has priority. This implies that on the power side there may be imbalances between demand and production. The method permits quantification of the expected power overflow, the expected unserviced power demand, and the expected unserviced heat demand. It is shown that a discretization method as well as double Fourier series may be applied in algorithms based on the method. (au) 1 tab., 28 ills., 21 refs.

  19. Langevin simulations of QCD, including fermions

    International Nuclear Information System (INIS)

    Kronfeld, A.S.

    1986-02-01

    We encounter critical slow down in updating when xi/a -> infinite and in matrix inversion (needed to include fermions) when msub(q)a -> 0. A simulation that purports to solve QCD numerically will encounter these limits, so to face the challenge in the title of this workshop, we must cure the disease of critical slow down. Physically, this critical slow down is due to the reluctance of changes at short distances to propagate to large distances. Numerically, the stability of an algorithm at short wavelengths requires a (moderately) small step size; critical slow down occurs when the effective long wavelength step size becomes tiny. The remedy for this disease is an algorithm that propagates signals quickly throughout the system; i.e. one whose effective step size is not reduced for the long wavelength conponents of the fields. (Here the effective ''step size'' is essentially an inverse decorrelation time.) To do so one must resolve various wavelengths of the system and modify the dynamics (in CPU time) of the simulation so that all modes evolve at roughly the same rate. This can be achieved by introducing Fourier transforms. I show how to implement Fourier acceleration for Langevin updating and for conjugate gradient matrix inversion. The crucial feature of these algorithms that lends them to Fourier acceleration is that they update the lattice globally; hence the Fourier transforms are computed once per sweep rather than once per hit. (orig./HSI)

  20. SEEPAGE MODEL FOR PA INCLUDING DRIFT COLLAPSE

    International Nuclear Information System (INIS)

    C. Tsang

    2004-01-01

    The purpose of this report is to document the predictions and analyses performed using the seepage model for performance assessment (SMPA) for both the Topopah Spring middle nonlithophysal (Tptpmn) and lower lithophysal (Tptpll) lithostratigraphic units at Yucca Mountain, Nevada. Look-up tables of seepage flow rates into a drift (and their uncertainty) are generated by performing numerical simulations with the seepage model for many combinations of the three most important seepage-relevant parameters: the fracture permeability, the capillary-strength parameter 1/a, and the percolation flux. The percolation flux values chosen take into account flow focusing effects, which are evaluated based on a flow-focusing model. Moreover, multiple realizations of the underlying stochastic permeability field are conducted. Selected sensitivity studies are performed, including the effects of an alternative drift geometry representing a partially collapsed drift from an independent drift-degradation analysis (BSC 2004 [DIRS 166107]). The intended purpose of the seepage model is to provide results of drift-scale seepage rates under a series of parameters and scenarios in support of the Total System Performance Assessment for License Application (TSPA-LA). The SMPA is intended for the evaluation of drift-scale seepage rates under the full range of parameter values for three parameters found to be key (fracture permeability, the van Genuchten 1/a parameter, and percolation flux) and drift degradation shape scenarios in support of the TSPA-LA during the period of compliance for postclosure performance [Technical Work Plan for: Performance Assessment Unsaturated Zone (BSC 2002 [DIRS 160819], Section I-4-2-1)]. The flow-focusing model in the Topopah Spring welded (TSw) unit is intended to provide an estimate of flow focusing factors (FFFs) that (1) bridge the gap between the mountain-scale and drift-scale models, and (2) account for variability in local percolation flux due to

  1. Photovoltaic Cells

    OpenAIRE

    Karolis Kiela

    2012-01-01

    The article deals with an overview of photovoltaic cells that are currently manufactured and those being developed, including one or several p-n junction, organic and dye-sensitized cells using quantum dots. The paper describes the advantages and disadvantages of various photovoltaic cells, identifies the main parameters, explains the main reasons for the losses that may occur in photovoltaic cells and looks at the ways to minimize them.Article in Lithuanian

  2. Ionic liquids, electrolyte solutions including the ionic liquids, and energy storage devices including the ionic liquids

    Science.gov (United States)

    Gering, Kevin L.; Harrup, Mason K.; Rollins, Harry W.

    2015-12-08

    An ionic liquid including a phosphazene compound that has a plurality of phosphorus-nitrogen units and at least one pendant group bonded to each phosphorus atom of the plurality of phosphorus-nitrogen units. One pendant group of the at least one pendant group comprises a positively charged pendant group. Additional embodiments of ionic liquids are disclosed, as are electrolyte solutions and energy storage devices including the embodiments of the ionic liquid.

  3. Catalyst support structure, catalyst including the structure, reactor including a catalyst, and methods of forming same

    Science.gov (United States)

    Van Norman, Staci A.; Aston, Victoria J.; Weimer, Alan W.

    2017-05-09

    Structures, catalysts, and reactors suitable for use for a variety of applications, including gas-to-liquid and coal-to-liquid processes and methods of forming the structures, catalysts, and reactors are disclosed. The catalyst material can be deposited onto an inner wall of a microtubular reactor and/or onto porous tungsten support structures using atomic layer deposition techniques.

  4. The physics of semiconductors an introduction including nanophysics and applications

    CERN Document Server

    Grundmann, Marius

    2016-01-01

    The 3rd edition of this successful textbook contains ample material for a comprehensive upper-level undergraduate or beginning graduate course, guiding readers to the point where they can choose a special topic and begin supervised research. The textbook provides a balance between essential aspects of solid-state and semiconductor physics, on the one hand, and the principles of various semiconductor devices and their applications in electronic and photonic devices, on the other. It highlights many practical aspects of semiconductors such as alloys, strain, heterostructures, nanostructures, that are necessary in modern semiconductor research but typically omitted in textbooks. Coverage also includes additional advanced topics, such as Bragg mirrors, resonators, polarized and magnetic semiconductors, nanowires, quantum dots, multi-junction solar cells, thin film transistors, carbon-based nanostructures and transparent conductive oxides. The text derives explicit formulas for many results to support better under...

  5. Launch Lock Assemblies Including Axial Gap Amplification Devices and Spacecraft Isolation Systems Including the Same

    Science.gov (United States)

    Barber, Tim Daniel (Inventor); Hindle, Timothy (Inventor); Young, Ken (Inventor); Davis, Torey (Inventor)

    2014-01-01

    Embodiments of a launch lock assembly are provided, as are embodiments of a spacecraft isolation system including one or more launch lock assemblies. In one embodiment, the launch lock assembly includes first and second mount pieces, a releasable clamp device, and an axial gap amplification device. The releasable clamp device normally maintains the first and second mount pieces in clamped engagement; and, when actuated, releases the first and second mount pieces from clamped engagement to allow relative axial motion there between. The axial gap amplification device normally residing in a blocking position wherein the gap amplification device obstructs relative axial motion between the first and second mount pieces. The axial gap amplification device moves into a non-blocking position when the first and second mount pieces are released from clamped engagement to increase the range of axial motion between the first and second mount pieces.

  6. Integrated circuit cell library

    Science.gov (United States)

    Whitaker, Sterling R. (Inventor); Miles, Lowell H. (Inventor)

    2005-01-01

    According to the invention, an ASIC cell library for use in creation of custom integrated circuits is disclosed. The ASIC cell library includes some first cells and some second cells. Each of the second cells includes two or more kernel cells. The ASIC cell library is at least 5% comprised of second cells. In various embodiments, the ASIC cell library could be 10% or more, 20% or more, 30% or more, 40% or more, 50% or more, 60% or more, 70% or more, 80% or more, 90% or more, or 95% or more comprised of second cells.

  7. Electrolyte solutions including a phosphoranimine compound, and energy storage devices including same

    Science.gov (United States)

    Klaehn, John R.; Dufek, Eric J.; Rollins, Harry W.; Harrup, Mason K.; Gering, Kevin L.

    2017-09-12

    An electrolyte solution comprising at least one phosphoranimine compound and a metal salt. The at least one phosphoranimine compound comprises a compound of the chemical structure ##STR00001## where X is an organosilyl group or a tert-butyl group and each of R.sup.1, R.sup.2, and R.sup.3 is independently selected from the group consisting of an alkyl group, an aryl group, an alkoxy group, or an aryloxy group. An energy storage device including the electrolyte solution is also disclosed.

  8. Exclusive queueing model including the choice of service windows

    Science.gov (United States)

    Tanaka, Masahiro; Yanagisawa, Daichi; Nishinari, Katsuhiro

    2018-01-01

    In a queueing system involving multiple service windows, choice behavior is a significant concern. This paper incorporates the choice of service windows into a queueing model with a floor represented by discrete cells. We contrived a logit-based choice algorithm for agents considering the numbers of agents and the distances to all service windows. Simulations were conducted with various parameters of agent choice preference for these two elements and for different floor configurations, including the floor length and the number of service windows. We investigated the model from the viewpoint of transit times and entrance block rates. The influences of the parameters on these factors were surveyed in detail and we determined that there are optimum floor lengths that minimize the transit times. In addition, we observed that the transit times were determined almost entirely by the entrance block rates. The results of the presented model are relevant to understanding queueing systems including the choice of service windows and can be employed to optimize facility design and floor management.

  9. Pancreatic islet cell tumor

    Science.gov (United States)

    ... cell tumors; Islet of Langerhans tumor; Neuroendocrine tumors; Peptic ulcer - islet cell tumor; Hypoglycemia - islet cell tumor ... stomach acid. Symptoms may include: Abdominal pain Diarrhea ... and small bowel Vomiting blood (occasionally) Glucagonomas make ...

  10. Kinetic models of gene expression including non-coding RNAs

    Energy Technology Data Exchange (ETDEWEB)

    Zhdanov, Vladimir P., E-mail: zhdanov@catalysis.r

    2011-03-15

    In cells, genes are transcribed into mRNAs, and the latter are translated into proteins. Due to the feedbacks between these processes, the kinetics of gene expression may be complex even in the simplest genetic networks. The corresponding models have already been reviewed in the literature. A new avenue in this field is related to the recognition that the conventional scenario of gene expression is fully applicable only to prokaryotes whose genomes consist of tightly packed protein-coding sequences. In eukaryotic cells, in contrast, such sequences are relatively rare, and the rest of the genome includes numerous transcript units representing non-coding RNAs (ncRNAs). During the past decade, it has become clear that such RNAs play a crucial role in gene expression and accordingly influence a multitude of cellular processes both in the normal state and during diseases. The numerous biological functions of ncRNAs are based primarily on their abilities to silence genes via pairing with a target mRNA and subsequently preventing its translation or facilitating degradation of the mRNA-ncRNA complex. Many other abilities of ncRNAs have been discovered as well. Our review is focused on the available kinetic models describing the mRNA, ncRNA and protein interplay. In particular, we systematically present the simplest models without kinetic feedbacks, models containing feedbacks and predicting bistability and oscillations in simple genetic networks, and models describing the effect of ncRNAs on complex genetic networks. Mathematically, the presentation is based primarily on temporal mean-field kinetic equations. The stochastic and spatio-temporal effects are also briefly discussed.

  11. Transient performance of integrated SOFC system including spatial temperature control

    OpenAIRE

    Mueller, F; Fardadi, M; Shaffer, B; Brouwer, J; Jabbari, F

    2010-01-01

    Spatial temperature feedback control has been developed for a simulated integrated non-pressurized simple cycle solid oxide fuel cell (SOFC) system. The fuel cell spatial temperature feedback controller is based on (1) feed-forward set-points that minimize temperature variation in the fuel cell electrode-electrolyte solid temperature profile for the system operating power range, and (2) decentralized proportional-integral based feedback to maintain the fuel cell spatial temperature profile du...

  12. Hydromechanical modeling of clay rock including fracture damage

    Science.gov (United States)

    Asahina, D.; Houseworth, J. E.; Birkholzer, J. T.

    2012-12-01

    Argillaceous rock typically acts as a flow barrier, but under certain conditions significant and potentially conductive fractures may be present. Fracture formation is well-known to occur in the vicinity of underground excavations in a region known as the excavation disturbed zone. Such problems are of particular importance for low-permeability, mechanically weak rock such as clays and shales because fractures can be relatively transient as a result of fracture self-sealing processes. Perhaps not as well appreciated is the fact that natural fractures can form in argillaceous rock as a result of hydraulic overpressure caused by phenomena such as disequlibrium compaction, changes in tectonic stress, and mineral dehydration. Overpressure conditions can cause hydraulic fracturing if the fluid pressure leads to tensile effective stresses that exceed the tensile strength of the material. Quantitative modeling of this type of process requires coupling between hydrogeologic processes and geomechanical processes including fracture initiation and propagation. Here we present a computational method for three-dimensional, hydromechanical coupled processes including fracture damage. Fractures are represented as discrete features in a fracture network that interact with a porous rock matrix. Fracture configurations are mapped onto an unstructured, three-dimensonal, Voronoi grid, which is based on a random set of spatial points. Discrete fracture networks (DFN) are represented by the connections of the edges of a Voronoi cells. This methodology has the advantage that fractures can be more easily introduced in response to coupled hydro-mechanical processes and generally eliminates several potential issues associated with the geometry of DFN and numerical gridding. A geomechanical and fracture-damage model is developed here using the Rigid-Body-Spring-Network (RBSN) numerical method. The hydrogelogic and geomechanical models share the same geometrical information from a 3D Voronoi

  13. Magnetic properties of nickel halide hydrates including deuteration effects

    Energy Technology Data Exchange (ETDEWEB)

    DeFotis, G.C., E-mail: gxdefo@wm.edu [Chemistry Department, College of William & Mary, Williamsburg, VA, 23187 United States (United States); Van Dongen, M.J.; Hampton, A.S.; Komatsu, C.H.; Trowell, K.T.; Havas, K.C.; Davis, C.M.; DeSanto, C.L. [Chemistry Department, College of William & Mary, Williamsburg, VA, 23187 United States (United States); Hays, K.; Wagner, M.J. [Chemistry Department, George Washington University, Washington, DC, 20052 United States (United States)

    2017-01-01

    Magnetic measurements on variously hydrated nickel chlorides and bromides, including deuterated forms, are reported. Results include locations and sizes of susceptibility maxima, T{sub max} and χ{sub max}, ordering temperatures T{sub c}, Curie constants and Weiss theta in the paramagnetic regime, and primary and secondary exchange interactions from analysis of low temperature data. For the latter a 2D Heisenberg model augmented by interlayer exchange in a mean-field approximation is applied. Magnetization data to 16 kG as a function of temperature show curvature and hysteresis characteristics quite system dependent. For four materials high field magnetization data to 70 kG at 2.00 K are also obtained. Comparison is made with theoretical relations for spin-1 models. Trends are apparent, primarily that T{sub max} of each bromide hydrate is less than for the corresponding chloride, and that for a given halide nD{sub 2}O (n=1 or 2) deuterates exhibit lesser T{sub max} than do nH{sub 2}O hydrates. A monoclinic unit cell determined from powder X-ray diffraction data on NiBr{sub 2}·2D{sub 2}O is different from and slightly larger than that of NiBr{sub 2}·2H{sub 2}O. This provides some rationale for the difference in magnetic properties between these. - Highlights: • The magnetism of Ni(II) chloride and bromide dihydrates and monohydrates is studied. • Effects of replacing H{sub 2}O by D{sub 2}O are examined for both hydration states and both halides. • Exchange interactions in bromides are weaker than in corresponding chlorides. • Exchange interactions are weaker in D{sub 2}O than in corresponding H{sub 2}O containing systems. • The unit cell of NiBr{sub 2}·2D{sub 2}O is different from and slightly larger than that of NiBr{sub 2}·2H{sub 2}O.

  14. Human Cell Line-Derived Monoclonal IgA Antibodies for Cancer Immunotherapy

    Directory of Open Access Journals (Sweden)

    Felix Hart

    2017-05-01

    Full Text Available IgA antibodies have great potential to improve the functional diversity of current IgG antibody-based cancer immunotherapy options. However, IgA production and purification is not well established, which can at least in part be attributed to the more complex glycosylation as compared to IgG antibodies. IgA antibodies possess up to five N-glycosylation sites within their constant region of the heavy chain as compared to one site for IgG antibodies. The human GlycoExpress expression system was developed to produce biotherapeutics with optimized glycosylation and used here to generate a panel of IgA isotype antibodies directed against targets for solid (TA-mucin 1, Her2, EGFR, Thomsen–Friedenreich and hematological (CD20 cancer indications. The feasibility of good manufacturing practice was shown by the production of 11 g IgA within 35 days in a one liter perfusion bioreactor, and IgA antibodies in high purity were obtained after purification. The monoclonal IgA antibodies possessed a high sialylation degree, and no non-human glycan structures were detected. Kinetic analysis revealed increased avidity antigen binding for IgA dimers as compared to monomeric antibodies. The IgA antibodies exhibited potent Fab- and Fc-mediated functionalities against cancer cell lines, whereby especially granulocytes are recruited. Therefore, for patients who do not sufficiently benefit from therapeutic IgG antibodies, IgA antibodies may complement current regiment options and represent a promising strategy for cancer immunotherapy. In conclusion, a panel of novel biofunctional IgA antibodies with human glycosylation was successfully generated.

  15. Growth inhibition of thyroid follicular cell-derived cancers by the opioid growth factor (OGF) - opioid growth factor receptor (OGFr) axis

    International Nuclear Information System (INIS)

    McLaughlin, Patricia J; Zagon, Ian S; Park, Sunny S; Conway, Andrea; Donahue, Renee N; Goldenberg, David

    2009-01-01

    as recorded by BrdU incorporation was depressed by 28% in OGF-treated cultures compared to those exposed to sterile water. The OGF-OGFr axis was detected and functional in PTC (KTC-1) and FTC (WRO 82-1) cell lines. These data suggest that OGF and OGFr are present in follicular-derived thyroid cancers, and that OGF serves in a tonically active inhibitory manner to maintain homeostasis of cell proliferation. These results may provide a biotherapeutic strategy in the treatment of these cancers

  16. Designing proteins for therapeutic applications.

    Science.gov (United States)

    Lazar, Greg A; Marshall, Shannon A; Plecs, Joseph J; Mayo, Stephen L; Desjarlais, John R

    2003-08-01

    Protein design is becoming an increasingly useful tool for optimizing protein drugs and creating novel biotherapeutics. Recent progress includes the engineering of monoclonal antibodies, cytokines, enzymes and viral fusion inhibitors.

  17. Estratégias de tratamento da leucemia linfóide crônica recidivada ou resistente incluindo o transplante de célula progenitora hematopoiética Strategies of treatment for relapsed or resistant chronic lymphocytic leukemia including to hematopoietic progenitor cell transplantation

    Directory of Open Access Journals (Sweden)

    Cármino A. Souza

    2005-12-01

    pacientes com doador HLA idêntico, preferentemente mais jovens (Despite much progress in therapy, chronic lymphocytic leukemia, the most common leukemia in the Western world, remains incurable. The use of fludarabine alone or associated to cyclophosphamide and/or mitoxantrone or doxorubicin improved the objective response, including complete response (also molecular and the progression- and relapse-free-survival. Several authors have suggested the introduction of monoclonal antibodies in order to improve the results. Despite that, all treated patients will further relapse or progress and salvage treatment should be used. In the present state-of-the art, salvage treatment is similar to those used as front line therapy. Indeed the criteria to start treatment are the same as defined by NCI for the front line therapy. Fludarabine alone or associated should be the therapy of choice for relapsed patients also for those previously treated with fludarabine. The use of monoclonal antibodies particularly rituximab is a good option although this procedure has not been considered as the standard therapy until now. Alemtuzumab is a very efficient monoclonal antibody and promotes significant benefits in clinical and hematological responses also in heavily treated or fludarabine refractory patients. The HPCT has limited indication due to the risks of high dose therapy in elderly patients. Autologous HPCT may be used specifically in young patients, if possible in complete remission, in order to improve the progression- or disease-free-survival. Conventional or with reduced intensity allogeneic HPCT may be used in patients presenting with a sibling donor particularly those under 60 years old, in fludarabine refractory patients or in patients presenting with unfavorable cytogenetics (17p-, with a curative objective.

  18. Gastric stem cells and gastric cancer stem cells

    OpenAIRE

    Han, Myoung-Eun; Oh, Sae-Ock

    2013-01-01

    The gastric epithelium is continuously regenerated by gastric stem cells, which give rise to various kinds of daughter cells, including parietal cells, chief cells, surface mucous cells, mucous neck cells, and enteroendocrine cells. The self-renewal and differentiation of gastric stem cells need delicate regulation to maintain the normal physiology of the stomach. Recently, it was hypothesized that cancer stem cells drive the cancer growth and metastasis. In contrast to conventional clonal ev...

  19. Skin Cancer (Including Melanoma)—Health Professional Version

    Science.gov (United States)

    Basal cell carcinoma and squamous cell carcinoma are referred to as nonmelanoma skin cancers. Melanoma is a malignant tumor of melanocytes, which make the melanin. Find evidence-based information on skin cancer treatment, causes and prevention, screening, research, genetics, and statistics.

  20. Skin Cancer (Including Melanoma)—Patient Version

    Science.gov (United States)

    Skin cancer is the most common type of cancer. The main types of skin cancer are squamous cell carcinoma, basal cell carcinoma, and melanoma. Most deaths from skin cancer are caused by melanoma. Start here to find information on skin cancer treatment, causes and prevention, screening, research, and statistics.

  1. iPSCs: A Minireview from Bench to Bed, including Organoids and the CRISPR System

    Directory of Open Access Journals (Sweden)

    Andrés Javier Orqueda

    2016-01-01

    Full Text Available When Dolly the sheep was born, the first probe into an adult mammalian genome traveling back in time and generating a whole new animal appeared. Ten years later, the reprogramming process became a defined method of producing induced pluripotent stem cells (iPSCs through the overexpression of four transcription factors. iPSCs are capable of originating virtually all types of cells and tissues, including a whole new animal. The reprogramming strategies based on patient-derived cells should make the development of clinical applications of cell based therapy much more straightforward. Here, we analyze the current state, opportunities, and challenges of iPSCs from bench to bed, including organoids and the CRISPR system.

  2. Method for pulse control in a laser including a stimulated brillouin scattering mirror system

    Science.gov (United States)

    Dane, C. Brent; Hackel, Lloyd; Harris, Fritz B.

    2007-10-23

    A laser system, such as a master oscillator/power amplifier system, comprises a gain medium and a stimulated Brillouin scattering SBS mirror system. The SBS mirror system includes an in situ filtered SBS medium that comprises a compound having a small negative non-linear index of refraction, such as a perfluoro compound. An SBS relay telescope having a telescope focal point includes a baffle at the telescope focal point which blocks off angle beams. A beam splitter is placed between the SBS mirror system and the SBS relay telescope, directing a fraction of the beam to an alternate beam path for an alignment fiducial. The SBS mirror system has a collimated SBS cell and a focused SBS cell. An adjustable attenuator is placed between the collimated SBS cell and the focused SBS cell, by which pulse width of the reflected beam can be adjusted.

  3. 76 FR 61749 - SpectraWatt, Inc. Including On-Site Leased Workers From Kelly Services Hopewell Junction, NY...

    Science.gov (United States)

    2011-10-05

    ... to the production of solar cells for their application in solar panels. The worker group includes on..., during the period of investigation, imports of articles like or directly competitive with solar cells produced by the subject firm have increased, and that the increased imports of solar cells (or like or...

  4. Key Factors in Planning a Sustainable Energy Future Including Hydrogen and Fuel Cells

    Science.gov (United States)

    Hedstrom, Lars; Saxe, Maria; Folkesson, Anders; Wallmark, Cecilia; Haraldsson, Kristina; Bryngelsson, Marten; Alvfors, Per

    2006-01-01

    In this article, a number of future energy visions, especially those basing the energy systems on hydrogen, are discussed. Some often missing comparisons between alternatives, from a sustainability perspective, are identified and then performed for energy storage, energy transportation, and energy use in vehicles. It is shown that it is important…

  5. Cell control report

    CERN Document Server

    2013-01-01

    Please note this is a Short Discount publication. This extensive report provides an essential overview of cells and their use as factory automation building blocks. The following issues are discussed in depth: Cell integration Cell software and standards Future technologies applied to cells Plus Cell control applications including: - rotary parts manufacturing - diesel engine component development - general cell control development at the General Electric Corporation - a vendor list.

  6. Tuft (caveolated) cells in two human colon carcinoma cell lines.

    OpenAIRE

    Barkla, D. H.; Whitehead, R. H.; Foster, H.; Tutton, P. J.

    1988-01-01

    The presence of an unusual cell type in two human colon carcinoma cell lines is reported. The cells show the same morphology as "tuft" (caveolated) cells present in normal gastrointestinal epithelium. Tuft cells were seen in cell line LIM 1863 growing in vitro and in human colon carcinoma cell line LIM 2210 growing as subcutaneous solid tumour xenografts in nude mice. Characteristic morphologic features of tuft cells included a wide base, narrow apex and a tuft of long microvilli projecting f...

  7. High-efficiency photovoltaic technology including thermoelectric generation

    Science.gov (United States)

    Fisac, Miguel; Villasevil, Francesc X.; López, Antonio M.

    2014-04-01

    Nowadays, photovoltaic solar energy is a clean and reliable source for producing electric power. Most photovoltaic systems have been designed and built up for use in applications with low power requirements. The efficiency of solar cells is quite low, obtaining best results in monocrystalline silicon structures, with an efficiency of about 18%. When temperature rises, photovoltaic cell efficiency decreases, given that the short-circuit current is slightly increased, and the open-circuit voltage, fill factor and power output are reduced. To ensure that this does not affect performance, this paper describes how to interconnect photovoltaic and thermoelectric technology into a single structure. The temperature gradient in the solar panel is used to supply thermoelectric cells, which generate electricity, achieving a positive contribution to the total balance of the complete system.

  8. Dictionary of scientific units including dimensionless numbers and scales

    National Research Council Canada - National Science Library

    Jerrard, H.G; McNeill, D.B

    1992-01-01

    .... The text includes the most recently accepted values of all units. Several disciplines, which have in the past employed few scientific principles and the dictionary has been extended to include examples of these.

  9. Should Relational Aggression Be Included in DSM-V?

    Science.gov (United States)

    Keenan, Kate; Coyne, Claire; Lahey, Benjamin B.

    2008-01-01

    The study examines whether relational aggression should be included in DSM-V disruptive behavior disorders. The results conclude that some additional information is gathered from assessing relational aggression but not enough to be included in DSM-V.

  10. Partially ionized plasmas including the third symposium on uranium plasmas

    Energy Technology Data Exchange (ETDEWEB)

    Krishnan, M. [ed.

    1976-09-01

    Separate abstracts are included for 28 papers on electrically generated plasmas, fission generated plasmas, nuclear pumped lasers, gaseous fuel reactor research, and applications. Five papers have been previously abstracted and included in ERA.

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

    Science.gov (United States)

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

    2016-01-01

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

  12. 48 CFR 536.213-371 - Bids that include options.

    Science.gov (United States)

    2010-10-01

    ... 48 Federal Acquisition Regulations System 4 2010-10-01 2010-10-01 false Bids that include options... Contracting for Construction 536.213-371 Bids that include options. (a) Subject to the limitations in paragraph (c) of this section, you may include options in contracts if it is in the Government's interest...

  13. 29 CFR 780.616 - Operations included in raising livestock.

    Science.gov (United States)

    2010-07-01

    ... 29 Labor 3 2010-07-01 2010-07-01 false Operations included in raising livestock. 780.616 Section... Employment in Agriculture and Livestock Auction Operations Under the Section 13(b)(13) Exemption Requirements for Exemption § 780.616 Operations included in raising livestock. Raising livestock includes such...

  14. A Call to Include Severe Combined Immunodeficiency in Newborn Screening Program

    Directory of Open Access Journals (Sweden)

    Raz Somech

    2014-01-01

    Full Text Available Quantification of the T cell receptor excision circles (TRECs has recently emerged as a useful non-invasive clinical and research tool to investigate thymic activity. It allows the identification of T cell production by the thymus. Quantification of TREC copies has recently been implemented as the preferred test to screen neonates with severe combined immunodeficiency (SCID or significant lymphopenia. Neonatal genetic screening for SCID is highly important in countries with high rates of consanguinous marriages, such as Israel, and can be used for early diagnosis, enabling prompt therapeutic intervention that will save lives and improve the outcome of these patients. TREC measurement is also applicable in clinical settings where T cell immunity is involved, including any T cell immunodeficiencies, HIV infection, the aging process, autoimmune diseases, and immune reconstitution after bone marrow transplantation.

  15. Cell-Based Therapy

    Directory of Open Access Journals (Sweden)

    Masaaki Kitada

    2012-01-01

    Full Text Available Cell transplantation is a strategy with great potential for the treatment of Parkinson's disease, and many types of stem cells, including neural stem cells and embryonic stem cells, are considered candidates for transplantation therapy. Mesenchymal stem cells are a great therapeutic cell source because they are easy accessible and can be expanded from patients or donor mesenchymal tissues without posing serious ethical and technical problems. They have trophic effects for protecting damaged tissues as well as differentiation ability to generate a broad spectrum of cells, including dopamine neurons, which contribute to the replenishment of lost cells in Parkinson's disease. This paper focuses mainly on the potential of mesenchymal stem cells as a therapeutic cell source and discusses their potential clinical application in Parkinson's disease.

  16. Fuel cells

    International Nuclear Information System (INIS)

    Niederdoeckl, J.

    2001-01-01

    Europe has at present big hopes on the fuel cells technology, in comparison with other energy conversion technologies, this technology has important advantages, for example: high efficiency, very low pollution and parallel use of electric and thermal energy. Preliminary works for fuel cells developing and its commercial exploitation are at full speed; until now the European Union has invested approx. 1.7 billion Schillings, 60 relevant projects are being executed. The Austrian industry is interested in applying this technique to drives, thermal power stations and the miniature fuel cells as replacement of batteries in electronic products (Notebooks, mobile telephones, etc.). A general description of the historic development of fuel cells including the main types is given as well as what is the situation in Austria. (nevyjel)

  17. 76 FR 61741 - Bmc Software, Inc. Including On-Site Leased Workers From COMSYS ITS Including Remote Workers...

    Science.gov (United States)

    2011-10-05

    ... DEPARTMENT OF LABOR Employment and Training Administration [TA-W-74,540] Bmc Software, Inc... November 23, 2010, applicable to workers of BMC Software, Inc., including on-site leased workers from... BMC Software, inc., including on-site leased workers from Comsys ITS, and including remote workers...

  18. Parenteral nutrition including polyamine under experimental irradiation of the abdomen

    International Nuclear Information System (INIS)

    Moroz, B.B.; Fedorovskij, L.L.; Lyashchenko, Yu.N.

    1982-01-01

    White rats-males were used in experiments. Irradiation dose of abdomen area is 13.5 Gy (1400 R). Parenteral nutrition using aminoacid preparation of polyamine affects favourably during radiation damage resulted from local irradiation of abdomen area. This was manifested in weakening of gastroenteric syndrom, reduction of 3.5 day death of animals and increase of their 30 day survival rate, intensification of recovery processes in small intestine, decrease of cell devastation in bone marrow

  19. Biotherapeutics as alternatives to antibiotics: Effects of adenoviral delivered cytokines on innate and adaptive immunity

    Science.gov (United States)

    Acceptable alternatives to the use of antibiotics in food animal practice need to be explored. The use of immunomodulators is a promising area for therapeutic, prophylactic, and metaphylactic use to prevent and combat infectious disease during periods of peak disease incidence. We developed a method...

  20. 26 CFR 1.1013-1 - Property included in inventory.

    Science.gov (United States)

    2010-04-01

    ... 26 Internal Revenue 11 2010-04-01 2010-04-01 true Property included in inventory. 1.1013-1 Section... inventory. The basis of property required to be included in inventory is the last inventory value of such property in the hands of the taxpayer. The requirements with respect to the valuation of an inventory are...

  1. 31 CFR 103.51 - Dollars as including foreign currency.

    Science.gov (United States)

    2010-07-01

    ... RECORDKEEPING AND REPORTING OF CURRENCY AND FOREIGN TRANSACTIONS General Provisions § 103.51 Dollars as including foreign currency. Wherever in this part an amount is stated in dollars, it shall be deemed to mean... 31 Money and Finance: Treasury 1 2010-07-01 2010-07-01 false Dollars as including foreign currency...

  2. Microfluidic devices and methods including porous polymer monoliths

    Science.gov (United States)

    Hatch, Anson V; Sommer, Gregory J; Singh, Anup K; Wang, Ying-Chih; Abhyankar, Vinay V

    2014-04-22

    Microfluidic devices and methods including porous polymer monoliths are described. Polymerization techniques may be used to generate porous polymer monoliths having pores defined by a liquid component of a fluid mixture. The fluid mixture may contain iniferters and the resulting porous polymer monolith may include surfaces terminated with iniferter species. Capture molecules may then be grafted to the monolith pores.

  3. 7 CFR 1437.303 - Aquaculture, including ornamental fish.

    Science.gov (United States)

    2010-01-01

    ... 7 Agriculture 10 2010-01-01 2010-01-01 false Aquaculture, including ornamental fish. 1437.303... ASSISTANCE PROGRAM Determining Coverage Using Value § 1437.303 Aquaculture, including ornamental fish. (a... human consumption as determined by CCC. (2) Fish raised as feed for other fish that are consumed by...

  4. Solar Energy Education. Reader, Part II. Sun story. [Includes glossary

    Energy Technology Data Exchange (ETDEWEB)

    1981-05-01

    Magazine articles which focus on the subject of solar energy are presented. The booklet prepared is the second of a four part series of the Solar Energy Reader. Excerpts from the magazines include the history of solar energy, mythology and tales, and selected poetry on the sun. A glossary of energy related terms is included. (BCS)

  5. A framework for including family health spillovers in economic evaluation

    NARCIS (Netherlands)

    H. Al-Janabi (Hareth); N.J.A. van Exel (Job); W.B.F. Brouwer (Werner); J. Coast (Joanna)

    2016-01-01

    textabstractHealth care interventions may affect the health of patients' family networks. It has been suggested that these health spillovers? should be included in economic evaluation, but there is not a systematic method for doing this. In this article, we develop a framework for including health

  6. Articles which include chevron film cooling holes, and related processes

    Science.gov (United States)

    Bunker, Ronald Scott; Lacy, Benjamin Paul

    2014-12-09

    An article is described, including an inner surface which can be exposed to a first fluid; an inlet; and an outer surface spaced from the inner surface, which can be exposed to a hotter second fluid. The article further includes at least one row or other pattern of passage holes. Each passage hole includes an inlet bore extending through the substrate from the inlet at the inner surface to a passage hole-exit proximate to the outer surface, with the inlet bore terminating in a chevron outlet adjacent the hole-exit. The chevron outlet includes a pair of wing troughs having a common surface region between them. The common surface region includes a valley which is adjacent the hole-exit; and a plateau adjacent the valley. The article can be an airfoil. Related methods for preparing the passage holes are also described.

  7. [Saccharomyces boulardii modulates dendritic cell properties and intestinal microbiota disruption after antibiotic treatment].

    Science.gov (United States)

    Collignon, A; Sandré, C; Barc, M-C

    2010-09-01

    Saccharomyces boulardii is a non-pathogenic yeast with biotherapeutic properties that has been used successfully to prevent and to treat various infectious and antibiotic-associated diarrheas. The intestinal microbiota is responsible for colonization resistance and immune response to pathogens but can be disrupted by antibiotics and lose its barrier effect. Dendritic cells (DCs) are professional antigen-presenting cells of the immune system with the ability to initiate a primary immune response or immune tolerance. In a human microbiota-associated mouse model, we evaluated the influence of S. boulardii on the composition of the microbiota and on the properties of dendritic cells in normal homeostatic conditions and after antibiotic-induced stress. The DCs were derived from splenic precursors. Membrane antigen expression and phagocytosis of FITC-latex beads by DCs were evaluated by flow cytometry. The molecular analysis of the microbiota was performed with fluorescence in situ hybridization (FISH) combined with flow cytometry or confocal microscopy using group specific 16S rRNA targeted probes. This evaluation was conducted during and after a 7-day oral treatment with amoxicillin-clavulanic acid alone and in combination with the administration of the yeast. The antibiotic treatment increased the phagocytic activity of DCs. Their antigen presenting function (MHC class II antigen and CD 86 costimulatory molecule membrane expression) was up-regulated. This reflects a functional activation of DCs. In the presence of S. boulardii, the modification of membrane antigen expression was down regulated. To correlate these modifications to the microbiota disruption, we analyzed in parallel the composition of the intestinal microbiota. As previously shown, the amoxicillin-clavulanic acid treatment, both alone and with S. boulardii, did not quantitatively alter the total microbiota. In contrast, after one day of the antibiotic treatment the Clostridium coccoides group decreased

  8. Molten carbonate fuel cell

    Science.gov (United States)

    Kaun, T.D.; Smith, J.L.

    1986-07-08

    A molten electrolyte fuel cell is disclosed with an array of stacked cells and cell enclosures isolating each cell except for access to gas manifolds for the supply of fuel or oxidant gas or the removal of waste gas. The cell enclosures collectively provide an enclosure for the array and effectively avoid the problems of electrolyte migration and the previous need for compression of stack components. The fuel cell further includes an inner housing about and in cooperation with the array enclosure to provide a manifold system with isolated chambers for the supply and removal of gases. An external insulated housing about the inner housing provides thermal isolation to the cell components.

  9. Electric drive systems including smoothing capacitor cooling devices and systems

    Energy Technology Data Exchange (ETDEWEB)

    Dede, Ercan Mehmet; Zhou, Feng

    2017-02-28

    An electric drive system includes a smoothing capacitor including at least one terminal, a bus bar electrically coupled to the at least one terminal, a thermoelectric device including a first side and a second side positioned opposite the first side, where the first side is thermally coupled to at least one of the at least one terminal and the bus bar, and a cooling element thermally coupled to the second side of the thermoelectric device, where the cooling element dissipates heat from the thermoelectric device.

  10. Engineering stem cell niches in bioreactors

    OpenAIRE

    Liu, Meimei; Liu, Ning; Zang, Ru; Li, Yan; Yang, Shang-Tian

    2013-01-01

    Stem cells, including embryonic stem cells, induced pluripotent stem cells, mesenchymal stem cells and amniotic fluid stem cells have the potential to be expanded and differentiated into various cell types in the body. Efficient differentiation of stem cells with the desired tissue-specific function is critical for stem cell-based cell therapy, tissue engineering, drug discovery and disease modeling. Bioreactors provide a great platform to regulate the stem cell microenvironment, known as “ni...

  11. Stem Cells

    Science.gov (United States)

    Stem cells are cells with the potential to develop into many different types of cells in the body. ... the body. There are two main types of stem cells: embryonic stem cells and adult stem cells. Stem ...

  12. Diabetes Nutrition: Including Sweets in Your Meal Plan

    Science.gov (United States)

    Diabetes nutrition: Including sweets in your meal plan Diabetes nutrition focuses on healthy foods, but sweets aren't necessarily ... your meal plan. By Mayo Clinic Staff Diabetes nutrition focuses on healthy foods. But you can eat ...

  13. Initiation devices, initiation systems including initiation devices and related methods

    Energy Technology Data Exchange (ETDEWEB)

    Daniels, Michael A.; Condit, Reston A.; Rasmussen, Nikki; Wallace, Ronald S.

    2018-04-10

    Initiation devices may include at least one substrate, an initiation element positioned on a first side of the at least one substrate, and a spark gap electrically coupled to the initiation element and positioned on a second side of the at least one substrate. Initiation devices may include a plurality of substrates where at least one substrate of the plurality of substrates is electrically connected to at least one adjacent substrate of the plurality of substrates with at least one via extending through the at least one substrate. Initiation systems may include such initiation devices. Methods of igniting energetic materials include passing a current through a spark gap formed on at least one substrate of the initiation device, passing the current through at least one via formed through the at least one substrate, and passing the current through an explosive bridge wire of the initiation device.

  14. Chronic Obstructive Pulmonary Disease (COPD) Includes: Chronic Bronchitis and Emphysema

    Science.gov (United States)

    ... Submit Button NCHS Home Chronic Obstructive Pulmonary Disease (COPD) Includes: Chronic Bronchitis and Emphysema Recommend on Facebook ... Percent of visits to office-based physicians with COPD indicated on the medical record: 3.2% Source: ...

  15. Including estimates of the future in today's financial statements

    OpenAIRE

    Mary Barth

    2006-01-01

    This paper explains why the question is how, not if, today's financial statements should include estimates of the future. Including such estimates is not new, but their use is increasing. This increase results primarily because standard setters believe asset and liability measures that reflect current economic conditions and up-to-date expectations of the future will result in more useful information for making economic decisions, which is the objective of financial reporting. This is why sta...

  16. 75 FR 16513 - B&C Corporation, JR Engineering Division, Including B&C Distribution Center, Including On-Site...

    Science.gov (United States)

    2010-04-01

    ... Engineering Division, Including B&C Distribution Center, Including On-Site Leased Workers From B&C Services... occurred during the relevant time period at the B&C Distribution Center, Inc. of the B&C Corporation, JR Engineering Division, Barberton, Ohio. The B&C Distribution Center provides distribution and logistical...

  17. Quantitative imaging of epithelial cell scattering identifies specific inhibitors of cell motility and cell-cell dissociation

    NARCIS (Netherlands)

    Loerke, D.; le Duc, Q.; Blonk, I.; Kerstens, A.; Spanjaard, E.; Machacek, M.; Danuser, G.; de Rooij, J.

    2012-01-01

    The scattering of cultured epithelial cells in response to hepatocyte growth factor (HGF) is a model system that recapitulates key features of metastatic cell behavior in vitro, including disruption of cell-cell adhesions and induction of cell migration. We have developed image analysis tools that

  18. Perspective on a Modified Developmental and Reproductive Toxicity Testing Strategy for Cancer Immunotherapy.

    Science.gov (United States)

    Prell, Rodney A; Halpern, Wendy G; Rao, Gautham K

    2016-05-01

    The intent of cancer immunotherapy (CIT) is to generate and enhance T-cell responses against tumors. The tumor microenvironment establishes several inhibitory pathways that lead to suppression of the local immune response, which is permissive for tumor growth. The efficacy of different CITs, alone and in combination, stems from reinvigorating the tumor immune response via several mechanisms, including costimulatory agonists, checkpoint inhibitors, and vaccines. However, immune responses to other antigens (self and foreign) may also be enhanced, resulting in potentially undesired effects. In outbred mammalian pregnancies, the fetus expresses paternally derived alloantigens that are recognized as foreign by the maternal immune system. If unchecked or enhanced, maternal immunity to these alloantigens represents a developmental and reproductive risk and thus is a general liability for cancer immunotherapeutic molecules. We propose a tiered approach to confirm this mechanistic reproductive liability for CIT molecules. A rodent allopregnancy model is based on breeding 2 different strains of mice so that paternally derived alloantigens are expressed by the fetus. When tested with a cross-reactive biotherapeutic, small molecule drug, or surrogate molecule, this model should reveal on-target reproductive liabilities if the pathway is involved in maintaining pregnancy. Alternatively, allopregnancy models with genetically modified mice can be interrogated for exquisitely specific biotherapeutics with restricted species reactivity. The allopregnancy model represents a relatively straightforward approach to confirm an expected on-target reproductive risk for CIT molecules. For biotherapeutics, it could potentially replace more complex developmental and reproductive toxicity testing in nonhuman primates when a pregnancy hazard is confirmed or expected. © The Author(s) 2016.

  19. Single-cell sequencing in stem cell biology.

    Science.gov (United States)

    Wen, Lu; Tang, Fuchou

    2016-04-15

    Cell-to-cell variation and heterogeneity are fundamental and intrinsic characteristics of stem cell populations, but these differences are masked when bulk cells are used for omic analysis. Single-cell sequencing technologies serve as powerful tools to dissect cellular heterogeneity comprehensively and to identify distinct phenotypic cell types, even within a 'homogeneous' stem cell population. These technologies, including single-cell genome, epigenome, and transcriptome sequencing technologies, have been developing rapidly in recent years. The application of these methods to different types of stem cells, including pluripotent stem cells and tissue-specific stem cells, has led to exciting new findings in the stem cell field. In this review, we discuss the recent progress as well as future perspectives in the methodologies and applications of single-cell omic sequencing technologies.

  20. [Origin of sennosides in health teas including Malva leaves].

    Science.gov (United States)

    Kojima, T; Kishi, M; Sekita, S; Satake, M

    2001-06-01

    The aim of this study is to clarify whether sennosides are contained in the leaf of Malva verticillata L., and then to clarify the source of sennosides in health teas including malva leaves. The identification and determination of sennosides were performed with thin layer chromatography and high performance liquid chromatography. The leaf of Malva verticillata L. did not contain sennosides A or B and could be easily distinguished from senna leaf. Our previous report showed that sennosides are contained in weight-reducing herbal teas including malva leaves, and that senna leaf is a herbal component in some teas. Furthermore, in 10 samples of health tea including malva leaves that were bought last year, the smallest amount of sennosides was 6.1 mg/bag, and all health teas including malva leaves contained the leaf and midrib of senna. We suggest that sennosides A and B are not contained in the leaf of Malva verticillata L., and that the sennosides in health teas including malva leaves are not derived from malva leaf but from senna leaf.

  1. Classical mechanics including an introduction to the theory of elasticity

    CERN Document Server

    Hentschke, Reinhard

    2017-01-01

    This textbook teaches classical mechanics as one of the foundations of physics. It describes the mechanical stability and motion in physical systems ranging from the molecular to the galactic scale. Aside from the standard topics of mechanics in the physics curriculum, this book includes an introduction to the theory of elasticity and its use in selected modern engineering applications, e.g. dynamic mechanical analysis of viscoelastic materials. The text also covers many aspects of numerical mechanics, ranging from the solution of ordinary differential equations, including molecular dynamics simulation of many particle systems, to the finite element method. Attendant Mathematica programs or parts thereof are provided in conjunction with selected examples. Numerous links allow the reader to connect to related subjects and research topics. Among others this includes statistical mechanics (separate chapter), quantum mechanics, space flight, galactic dynamics, friction, and vibration spectroscopy. An introductory...

  2. Internet addiction neuroscientific approaches and therapeutical implications including smartphone addiction

    CERN Document Server

    Reuter, Martin

    2017-01-01

    The second edition of this successful book provides further and in-depth insight into theoretical models dealing with Internet addiction, as well as includes new therapeutical approaches. The editors also broach the emerging topic of smartphone addiction. This book combines a scholarly introduction with state-of-the-art research in the characterization of Internet addiction. It is intended for a broad audience including scientists, students and practitioners. The first part of the book contains an introduction to Internet addiction and their pathogenesis. The second part of the book is dedicated to an in-depth review of neuroscientific findings which cover studies using a variety of biological techniques including brain imaging and molecular genetics. The third part of the book focuses on therapeutic interventions for Internet addiction. The fourth part of the present book is an extension to the first edition and deals with a new emerging potential disorder related to Internet addiction – smartphone addicti...

  3. Ceramic substrate including thin film multilayer surface conductor

    Science.gov (United States)

    Wolf, Joseph Ambrose; Peterson, Kenneth A.

    2017-05-09

    A ceramic substrate comprises a plurality of ceramic sheets, a plurality of inner conductive layers, a plurality of vias, and an upper conductive layer. The ceramic sheets are stacked one on top of another and include a top ceramic sheet. The inner conductive layers include electrically conductive material that forms electrically conductive features on an upper surface of each ceramic sheet excluding the top ceramic sheet. The vias are formed in each of the ceramic sheets with each via being filled with electrically conductive material. The upper conductive layer includes electrically conductive material that forms electrically conductive features on an upper surface of the top ceramic sheet. The upper conductive layer is constructed from a stack of four sublayers. A first sublayer is formed from titanium. A second sublayer is formed from copper. A third sublayer is formed from platinum. A fourth sublayer is formed from gold.

  4. Tunable cavity resonator including a plurality of MEMS beams

    Science.gov (United States)

    Peroulis, Dimitrios; Fruehling, Adam; Small, Joshua Azariah; Liu, Xiaoguang; Irshad, Wasim; Arif, Muhammad Shoaib

    2015-10-20

    A tunable cavity resonator includes a substrate, a cap structure, and a tuning assembly. The cap structure extends from the substrate, and at least one of the substrate and the cap structure defines a resonator cavity. The tuning assembly is positioned at least partially within the resonator cavity. The tuning assembly includes a plurality of fixed-fixed MEMS beams configured for controllable movement relative to the substrate between an activated position and a deactivated position in order to tune a resonant frequency of the tunable cavity resonator.

  5. Meta-structure and tunable optical device including the same

    Science.gov (United States)

    Han, Seunghoon; Papadakis, Georgia Theano; Atwater, Harry

    2017-12-26

    A meta-structure and a tunable optical device including the same are provided. The meta-structure includes a plurality of metal layers spaced apart from one another, an active layer spaced apart from the plurality of metal layers and having a carrier concentration that is tuned according to an electric signal applied to the active layer and the plurality of metal layers, and a plurality of dielectric layers spaced apart from one another and each having one surface contacting a metal layer among the plurality of metal layers and another surface contacting the active layer.

  6. EC6 safety enhancement - including impact of Fukushima lessons learned

    Energy Technology Data Exchange (ETDEWEB)

    Yu, S.; Zemdegs, R.; Boyle, S.; Soulard, M., E-mail: stephen.yu@candu.com [Candu Energy Inc., Mississauga, Ontario (Canada)

    2012-09-15

    The Enhanced CANDU 6 (EC6) is the new Generation III CANDU reactor design that meets the most up to date regulatory requirements and customer expectations. EC6 builds on the proven high performance design inch as the Qinshan CANDU 6 units and has made improvements to safety and operational performance, and has incorporated extensive operational feedback including Fukushima. The Fukushima Dai-ichi March 11, 2011 event has demonstrated the importance of defence-in-depth considerations for beyond-design basis events, including severe accidents. The EC6 design is based on the defence-in-depth principles and provides further design features that address the lessons learned from Fukushima. (author)

  7. Solar Energy Education. Renewable energy: a background text. [Includes glossary

    Energy Technology Data Exchange (ETDEWEB)

    1985-01-01

    Some of the most common forms of renewable energy are presented in this textbook for students. The topics include solar energy, wind power hydroelectric power, biomass ocean thermal energy, and tidal and geothermal energy. The main emphasis of the text is on the sun and the solar energy that it yields. Discussions on the sun's composition and the relationship between the earth, sun and atmosphere are provided. Insolation, active and passive solar systems, and solar collectors are the subtopics included under solar energy. (BCS)

  8. Methods of producing adsorption media including a metal oxide

    Science.gov (United States)

    Mann, Nicholas R; Tranter, Troy J

    2014-03-04

    Methods of producing a metal oxide are disclosed. The method comprises dissolving a metal salt in a reaction solvent to form a metal salt/reaction solvent solution. The metal salt is converted to a metal oxide and a caustic solution is added to the metal oxide/reaction solvent solution to adjust the pH of the metal oxide/reaction solvent solution to less than approximately 7.0. The metal oxide is precipitated and recovered. A method of producing adsorption media including the metal oxide is also disclosed, as is a precursor of an active component including particles of a metal oxide.

  9. Calculation of Permeability inside the Basket including one Fuel Assembly

    Energy Technology Data Exchange (ETDEWEB)

    Yu, Seung Hwan; Bang, Kyung Sik; Lee, Ju an; Choi, Woo Seok [KAERI, Daejeon (Korea, Republic of)

    2016-05-15

    In general, the porous media model and the effective thermal conductivity were used to simply the fuel assembly. The methods of calculating permeability were compared considering the flow inside a basket which includes a nuclear fuel. Detailed fuel assembly was a computational modeling and the flow characteristics were investigated. The flow inside the basket which included a fuel assembly is analyzed by CFD. As the height of the fuel assembly increases, the pressure drop linearly increased. The inertia resistance could be neglected. Three methods to calculate the permeability were compared. The permeability by the friction factor is 50% less than the permeability by wall shear stress and pressure drop.

  10. Epithelial cell polarity, stem cells and cancer

    DEFF Research Database (Denmark)

    Martin-Belmonte, Fernando; Perez-Moreno, Mirna

    2011-01-01

    , deregulation of adhesion and polarity proteins can cause misoriented cell divisions and increased self-renewal of adult epithelial stem cells. In this Review, we highlight some advances in the understanding of how loss of epithelial cell polarity contributes to tumorigenesis.......After years of extensive scientific discovery much has been learned about the networks that regulate epithelial homeostasis. Loss of expression or functional activity of cell adhesion and cell polarity proteins (including the PAR, crumbs (CRB) and scribble (SCRIB) complexes) is intricately related...

  11. Relationship between potential aggregation-prone regions and HLA-DR-binding T-cell immune epitopes: implications for rational design of novel and follow-on therapeutic antibodies.

    Science.gov (United States)

    Kumar, Sandeep; Mitchell, Mark A; Rup, Bonita; Singh, Satish K

    2012-08-01

    Aggregation and unwanted immunogenicity are hurdles to avoid in successful commercial development of antibody-based therapeutics. In this article, the relationship between aggregation-prone regions (APRs), capable of forming cross-β motifs/amyloid fibrils, and major histocompatibility complex class II-restricted human leukocyte antigen (HLA)-DR-binding T-cell immune epitopes (TcIEs) is analyzed using amino acid sequences of 25 therapeutic antibodies, 55 TcIEs recognized by T-regulatory cells (tregitopes), 1000 randomly generated 15-residue-long peptides, 2257 human self-TcIEs (autoantigens), and 11 peptides in HLA-peptide cocrystal structures. Sequence analyses from these diverse sources consistently show a high level of correlation between APRs and TcIEs: approximately one-third of TcIEs contain APRs, but the majority of APRs occur within TcIE regions (TcIERs). Tregitopes also contain APRs. Most APR-containing TcIERs can bind multiple HLA-DR alleles, suggesting that aggregation-driven adverse immune responses could impact a broad segment of patient population. This article has identified common molecular sequence-structure loci that potentially contribute toward both manufacturability and safety profiles of the therapeutic antibodies, thereby laying a foundation for simultaneous optimization of these attributes in novel and follow-on candidates. Incidence of APRs within TcIERs is not special to biotherapeutics, self-TcIEs from human proteins, involved in various diseases, also contain predicted APRs and experimentally proven amyloid-fibril-forming peptide sequence portions. Copyright © 2012 Wiley Periodicals, Inc.

  12. A Reconstruction Approach to High-Order Schemes Including Discontinuous Galerkin for Diffusion

    Science.gov (United States)

    Huynh, H. T.

    2009-01-01

    We introduce a new approach to high-order accuracy for the numerical solution of diffusion problems by solving the equations in differential form using a reconstruction technique. The approach has the advantages of simplicity and economy. It results in several new high-order methods including a simplified version of discontinuous Galerkin (DG). It also leads to new definitions of common value and common gradient quantities at each interface shared by the two adjacent cells. In addition, the new approach clarifies the relations among the various choices of new and existing common quantities. Fourier stability and accuracy analyses are carried out for the resulting schemes. Extensions to the case of quadrilateral meshes are obtained via tensor products. For the two-point boundary value problem (steady state), it is shown that these schemes, which include most popular DG methods, yield exact common interface quantities as well as exact cell average solutions for nearly all cases.

  13. Mammalian Cell Culture Simplified.

    Science.gov (United States)

    Moss, Robert; Solomon, Sondra

    1991-01-01

    A tissue culture experiment that does not require elaborate equipment and that can be used to teach sterile technique, the principles of animal cell line maintenance, and the concept of cell growth curves is described. The differences between cancerous and normal cells can be highlighted. The procedure is included. (KR)

  14. 36 CFR 1254.94 - What must my request include?

    Science.gov (United States)

    2010-07-01

    ... includes the following elements: (1) Record group number or agency of origin or, for donated historical... volume in number of pages or cubic feet. (b) The estimated amount of time (work-days) that the microfilm... who would require training (see § 1254.108(b)). (c) The number and a description of the equipment that...

  15. 20 CFR 404.1013 - Included-excluded rule.

    Science.gov (United States)

    2010-04-01

    ... least one-half of your time in the pay period is in covered work. If you spend most of your time in a... 20 Employees' Benefits 2 2010-04-01 2010-04-01 false Included-excluded rule. 404.1013 Section 404.1013 Employees' Benefits SOCIAL SECURITY ADMINISTRATION FEDERAL OLD-AGE, SURVIVORS AND DISABILITY...

  16. Including Critical Thinking and Problem Solving in Physical Education

    Science.gov (United States)

    Pill, Shane; SueSee, Brendan

    2017-01-01

    Many physical education curriculum frameworks include statements about the inclusion of critical inquiry processes and the development of creativity and problem-solving skills. The learning environment created by physical education can encourage or limit the application and development of the learners' cognitive resources for critical and creative…

  17. Modelling a linear PM motor including magnetic saturation

    NARCIS (Netherlands)

    Polinder, H.; Slootweg, J.G.; Compter, J.C.; Hoeijmakers, M.J.

    2002-01-01

    The use of linear permanent-magnet (PM) actuators increases in a wide variety of applications because of the high force density, robustness and accuracy. The paper describes the modelling of a linear PM motor applied in, for example, wafer steppers, including magnetic saturation. This is important

  18. Sexually transmitted infections, including HIV, in the Netherlands in 2006

    NARCIS (Netherlands)

    MG van Veen; FDH Koedijk; IVF van der Broek; ELM Op de Coul; IM de Boer; AI van Sighem; MAB van der Sande; soa-centra; Stichting HIV Monitoring; EPI/Cib

    2007-01-01

    The nationally covered low threshold STI centres offering STI care targeted at high risk groups, provide surveillance data to monitor national trends in STI, including HIV. In 2006, chlamydia remained the most commonly diagnosed bacterial STI in the Netherlands in the STI centres, in spite of

  19. 40 CFR 1502.14 - Alternatives including the proposed action.

    Science.gov (United States)

    2010-07-01

    ... impacts of the proposal and the alternatives in comparative form, thus sharply defining the issues and... action so that reviewers may evaluate their comparative merits. (c) Include reasonable alternatives not... identify such alternative in the final statement unless another law prohibits the expression of such a...

  20. 31 CFR 306.87 - Partnerships (including nominee partnerships).

    Science.gov (United States)

    2010-07-01

    ... (including nominee partnerships). An assignment of a security registered in the name of or assigned to a... appropriate for winding up partnership affairs. In those cases where assignments by or in behalf of all... dissolution. Upon voluntary dissolution, for any jurisdiction where a general partner may not act in winding...

  1. 10 CFR 905.11 - What must an IRP include?

    Science.gov (United States)

    2010-01-01

    ..., energy conservation and efficiency, cogeneration and district heating and cooling applications, and..., consumer preferences, environmental impacts, demand or energy impacts, implementation issues, revenue... 10 Energy 4 2010-01-01 2010-01-01 false What must an IRP include? 905.11 Section 905.11 Energy...

  2. Smart Antenna Skins, including Conformal Array, MMICs and Applications

    NARCIS (Netherlands)

    Bogaart, F.L.M. van den

    2000-01-01

    Low-cost technologies are presented for future space-borne and airborne SAR systems. These technologies include state-of-the art highly integrated circuits to miniaturise front-end, solutions to lower-cost interconnection technologies, new beamforming aspects and new architectures. The MMICs address

  3. LTRACK: Beam-transport calculation including wakefield effects

    International Nuclear Information System (INIS)

    Chan, K.C.D.; Cooper, R.K.

    1988-01-01

    LTRACK is a first-order beam-transport code that includes wakefield effects up to quadrupole modes. This paper will introduce the readers to this computer code by describing the history, the method of calculations, and a brief summary of the input/output information. Future plans for the code will also be described

  4. Towards a general framework for including noise impacts in LCA

    NARCIS (Netherlands)

    Cucurachi, Stefano; Heijungs, Reinout; Ohlau, Katrin

    Purpose Several damages have been associated with the exposure of human beings to noise. These include auditory effects, i.e., hearing impairment, but also non-auditory physiological ones such as hypertension and ischemic heart disease, or psychological ones such as annoyance, depression, sleep

  5. 30 CFR 250.1007 - What to include in applications.

    Science.gov (United States)

    2010-07-01

    ... features and other pertinent data including area, lease, and block designations; water depths; route...) submitted for a pipeline right-of-way shall bear a signed certificate upon its face by the engineer who made... additional design precautions you took to enable the pipeline to withstand the effects of water currents...

  6. cDNA encoding a polypeptide including a hevein sequence

    Energy Technology Data Exchange (ETDEWEB)

    Raikhel, N.V.; Broekaert, W.F.; Namhai Chua; Kush, A.

    1993-02-16

    A cDNA clone (HEV1) encoding hevein was isolated via polymerase chain reaction (PCR) using mixed oligonucleotides corresponding to two regions of hevein as primers and a Hevea brasiliensis latex cDNA library as a template. HEV1 is 1,018 nucleotides long and includes an open reading frame of 204 amino acids.

  7. Synthetic pulse radar including a microprocessor based controller

    International Nuclear Information System (INIS)

    Fowler, J.C.; Rubin, L.A.; Still, W.L.

    1980-01-01

    This invention relates to pulse radar detection of targets in extended media, including natural phenomena such as oil, coal and ore deposits within the earth. In particular, this invention relates to a pulse radar system employing a synthetic pulse formed from a fourier spectrum of frequencies generated and detected by a digitally controlled transmitter and receiver circuits

  8. Methodological challenges when doing research that includes ethnic minorities

    DEFF Research Database (Denmark)

    Morville, Anne-Le; Erlandsson, Lena-Karin

    2016-01-01

    minorities are included. Method: A thorough literature search yielded 21 articles obtained from the scientific databases PubMed, Cinahl, Web of Science and PsychInfo. Analysis followed Arksey and O’Malley’s framework for scoping reviews, applying content analysis. Results: The results showed methodological...

  9. Including patients’ perspectives in patient information leaflets: A polyocular approach

    DEFF Research Database (Denmark)

    Fage-Butler, Antoinette Mary

    2013-01-01

    Existing research reveals that patients’ perspectives are missing from mandatory patient information leaflets (PILs). At the same time, there is overwhelming consensus that they should be included in this genre, and a corresponding need for potential approaches to tackle this problem. This paper ...

  10. Prototype solar heating and cooling systems including potable hot water

    Science.gov (United States)

    1978-01-01

    Progress is reviewed in the development, delivery, and support of two prototype solar heating and cooling systems including potable hot water. The system consisted of the following subsystems: collector, auxiliary heating, potable hot water, storage, control, transport, and government-furnished site data acquisition.

  11. A Guide to Running a Recycling Project. [Includes Recycling Handbook].

    Science.gov (United States)

    Oregon Recycling Information and Organizing Network, Portland.

    This guide, designed for both students and adults, is intended for individuals who feel they might be interested in establishing a recycling depot. The guide includes such pertinent information as deciding how to set up a depot, markets and transportation, preparation of materials, where to place the depot and when to operate it, publicity and…

  12. 25 CFR 20.403 - What do protective services include?

    Science.gov (United States)

    2010-04-01

    ....403 Indians BUREAU OF INDIAN AFFAIRS, DEPARTMENT OF THE INTERIOR HUMAN SERVICES FINANCIAL ASSISTANCE AND SOCIAL SERVICES PROGRAMS Services to Children, Elderly, and Families § 20.403 What do protective services include? Protective services provided to a child, family or elderly person will be documented in...

  13. Unsteady panel method for complex configurations including wake modeling

    CSIR Research Space (South Africa)

    Van Zyl, Lourens H

    2008-01-01

    Full Text Available implementations of the DLM are however not very versatile in terms of geometries that can be modeled. The ZONA6 code offers a versatile surface panel body model including a separated wake model, but uses a pressure panel method for lifting surfaces. This paper...

  14. Interviewing Objects: Including Educational Technologies as Qualitative Research Participants

    Science.gov (United States)

    Adams, Catherine A.; Thompson, Terrie Lynn

    2011-01-01

    This article argues the importance of including significant technologies-in-use as key qualitative research participants when studying today's digitally enhanced learning environments. We gather a set of eight heuristics to assist qualitative researchers in "interviewing" technologies-in-use (or other relevant objects), drawing on concrete…

  15. Towards ligand docking including explicit interface water molecules.

    Directory of Open Access Journals (Sweden)

    Gordon Lemmon

    Full Text Available Small molecule docking predicts the interaction of a small molecule ligand with a protein at atomic-detail accuracy including position and conformation the ligand but also conformational changes of the protein upon ligand binding. While successful in the majority of cases, docking algorithms including RosettaLigand fail in some cases to predict the correct protein/ligand complex structure. In this study we show that simultaneous docking of explicit interface water molecules greatly improves Rosetta's ability to distinguish correct from incorrect ligand poses. This result holds true for both protein-centric water docking wherein waters are located relative to the protein binding site and ligand-centric water docking wherein waters move with the ligand during docking. Protein-centric docking is used to model 99 HIV-1 protease/protease inhibitor structures. We find protease inhibitor placement improving at a ratio of 9:1 when one critical interface water molecule is included in the docking simulation. Ligand-centric docking is applied to 341 structures from the CSAR benchmark of diverse protein/ligand complexes [1]. Across this diverse dataset we see up to 56% recovery of failed docking studies, when waters are included in the docking simulation.

  16. 25 CFR 20.308 - What does earned income include?

    Science.gov (United States)

    2010-04-01

    ... self-employment, total profit from a business enterprise (i.e., gross receipts less expenses incurred in producing the goods or services). Business expenses do not include depreciation, personal business and entertainment expenses, personal transportation, capital equipment purchases, or principal...

  17. Visual Impairments, "Including Blindness." NICHCY Disability Fact Sheet #13

    Science.gov (United States)

    National Dissemination Center for Children with Disabilities, 2012

    2012-01-01

    Vision is one of the five senses. Being able to see gives tremendous access to learning about the world around--people's faces and the subtleties of expression, what different things look like and how big they are, and the physical environments, including approaching hazards. When a child has a visual impairment, it is cause for immediate…

  18. Truck Drivers And Risk Of STDs Including HIV

    Directory of Open Access Journals (Sweden)

    Bansal R.K

    1995-01-01

    Full Text Available Research Question: Whether long distance truck drivers are at a higher risk of contracting and transmitting STDs including HIV? Objectives: i To study the degree of knowledge of HIV and AIDS among long- distance truck drivers. ii Assess their sexual behaviour including condom use. iii Explore their prevailing social influences and substance abuse patterns. iv Explore their treatment seeking bahaviour as regards STDs. v Deduce their risk of contracting and transmitting STDs including HIV. Study Design: Cross- sectional interview. Setting: Transport Nagar, Indore (M.P Participants: 210 senior drivers (First drivers and 210 junior drivers (Second drivers. Study Variables: Extra-Marital sexual intercourse, condom usage, past and present history of STDs, treatment and counseling, substance abuse, social â€" cultural milieu. Outcome Variables: Risk of contraction of STDs. Statistical Analysis: Univariate analysis. Results: 94% of the drivers were totally ignorant about AIDS. 82.9% and 43.8 % of the senior and junior drivers had a history of extra- marital sex and of these only 2 regularly used condoms. 13.8% and 3.3 % of the senior and junior drivers had a past or present history suggestive of STD infection. Alcohol and Opium were regularly used by them. Conclusion: The studied drivers are at a high risk of contracting and transmitting STDs including HIV.

  19. Including Students with Severe Disabilities in General Education Settings.

    Science.gov (United States)

    Wisniewski, Lech; Alper, Sandra

    1994-01-01

    This paper presents five systematic phases for bringing about successful regular education inclusion of students with severe disabilities. Phases include develop networks within the community, assess school and community resources, review strategies for integration, install strategies that lead to integration, and develop a system of feedback and…

  20. Simple suggestions for including vertical physics in oil spill models

    International Nuclear Information System (INIS)

    D'Asaro, Eric; University of Washington, Seatle, WA

    2001-01-01

    Current models of oil spills include no vertical physics. They neglect the effect of vertical water motions on the transport and concentration of floating oil. Some simple ways to introduce vertical physics are suggested here. The major suggestion is to routinely measure the density stratification of the upper ocean during oil spills in order to develop a database on the effect of stratification. (Author)

  1. 27 CFR 53.181 - Further manufacture included.

    Science.gov (United States)

    2010-04-01

    ... 27 Alcohol, Tobacco Products and Firearms 2 2010-04-01 2010-04-01 false Further manufacture... Further manufacture included. (a) In general. The payment of tax imposed by chapter 32 of the Code on the... of any use in further manufacture, or sale as part of a second manufactured article, described in...

  2. Human regulatory B cells control the TFH cell response.

    Science.gov (United States)

    Achour, Achouak; Simon, Quentin; Mohr, Audrey; Séité, Jean-François; Youinou, Pierre; Bendaoud, Boutahar; Ghedira, Ibtissem; Pers, Jacques-Olivier; Jamin, Christophe

    2017-07-01

    Follicular helper T (T FH ) cells support terminal B-cell differentiation. Human regulatory B (Breg) cells modulate cellular responses, but their control of T FH cell-dependent humoral immune responses is unknown. We sought to assess the role of Breg cells on T FH cell development and function. Human T cells were polyclonally stimulated in the presence of IL-12 and IL-21 to generate T FH cells. They were cocultured with B cells to induce their terminal differentiation. Breg cells were included in these cultures, and their effects were evaluated by using flow cytometry and ELISA. B-cell lymphoma 6, IL-21, inducible costimulator, CXCR5, and programmed cell death protein 1 (PD-1) expressions increased on stimulated human T cells, characterizing T FH cell maturation. In cocultures they differentiated B cells into CD138 + plasma and IgD - CD27 + memory cells and triggered immunoglobulin secretions. Breg cells obtained by Toll-like receptor 9 and CD40 activation of B cells prevented T FH cell development. Added to T FH cell and B-cell cocultures, they inhibited B-cell differentiation, impeded immunoglobulin secretions, and expanded Foxp3 + CXCR5 + PD-1 + follicular regulatory T cells. Breg cells modulated IL-21 receptor expressions on T FH cells and B cells, and their suppressive activities involved CD40, CD80, CD86, and intercellular adhesion molecule interactions and required production of IL-10 and TGF-β. Human Breg cells control T FH cell maturation, expand follicular regulatory T cells, and inhibit the T FH cell-mediated antibody secretion. These novel observations demonstrate a role for the Breg cell in germinal center reactions and suggest that deficient activities might impair the T FH cell-dependent control of humoral immunity and might lead to the development of aberrant autoimmune responses. Copyright © 2016 American Academy of Allergy, Asthma & Immunology. Published by Elsevier Inc. All rights reserved.

  3. A unified pathogenesis for kidney diseases, including genetic diseases and cancers, by the protein-homeostasis-system hypothesis.

    Science.gov (United States)

    Lee, Kyung-Yil

    2017-06-01

    Every cell of an organism is separated and protected by a cell membrane. It is proposed that harmony between intercellular communication and the health of an organism is controlled by a system, designated the protein-homeostasis-system (PHS). Kidneys consist of a variety of types of renal cells, each with its own characteristic cell-receptor interactions and producing characteristic proteins. A functional union of these renal cells can be determined by various renal function tests, and harmonious intercellular communication is essential for the healthy state of the host. Injury to a kind of renal cells can impair renal function and induce an imbalance in total body health. Every acute or chronic renal disease has unknown etiologic substances that are responsible for renal cell injury at the molecular level. The immune/repair system of the host should control the etiologic substances acting against renal cells; if this system fails, the disease progresses to end stage renal disease. Each renal disease has its characteristic pathologic lesions where immune cells and immune proteins, such as immunoglobulins and complements, are infiltrated. These immune cells and immune proteins may control the etiologic substances involved in renal pathologic lesions. Also, genetic renal diseases and cancers may originate from a protein deficiency or malfunctioning protein under the PHS. A unified pathogenesis for renal diseases, including acute glomerulonephritis, idiopathic nephrotic syndrome, immunoglobulin A nephropathy, genetic renal diseases such as Alport syndrome, and malignancies such as Wilms tumor and renal cell carcinoma, is proposed using the PHS hypothesis.

  4. Energy storage device including a redox-enhanced electrolyte

    Science.gov (United States)

    Stucky, Galen; Evanko, Brian; Parker, Nicholas; Vonlanthen, David; Auston, David; Boettcher, Shannon; Chun, Sang-Eun; Ji, Xiulei; Wang, Bao; Wang, Xingfeng; Chandrabose, Raghu Subash

    2017-08-08

    An electrical double layer capacitor (EDLC) energy storage device is provided that includes at least two electrodes and a redox-enhanced electrolyte including two redox couples such that there is a different one of the redox couples for each of the electrodes. When charged, the charge is stored in Faradaic reactions with the at least two redox couples in the electrolyte and in a double-layer capacitance of a porous carbon material that comprises at least one of the electrodes, and a self-discharge of the energy storage device is mitigated by at least one of electrostatic attraction, adsorption, physisorption, and chemisorption of a redox couple onto the porous carbon material.

  5. Progressive IRP Models for Power Resources Including EPP

    Directory of Open Access Journals (Sweden)

    Yiping Zhu

    2017-01-01

    Full Text Available In the view of optimizing regional power supply and demand, the paper makes effective planning scheduling of supply and demand side resources including energy efficiency power plant (EPP, to achieve the target of benefit, cost, and environmental constraints. In order to highlight the characteristics of different supply and demand resources in economic, environmental, and carbon constraints, three planning models with progressive constraints are constructed. Results of three models by the same example show that the best solutions to different models are different. The planning model including EPP has obvious advantages considering pollutant and carbon emission constraints, which confirms the advantages of low cost and emissions of EPP. The construction of progressive IRP models for power resources considering EPP has a certain reference value for guiding the planning and layout of EPP within other power resources and achieving cost and environmental objectives.

  6. 3D integrated HYDRA simulations of hohlraums including fill tubes

    Science.gov (United States)

    Marinak, M. M.; Milovich, J.; Hammel, B. A.; Macphee, A. G.; Smalyuk, V. A.; Kerbel, G. D.; Sepke, S.; Patel, M. V.

    2017-10-01

    Measurements of fill tube perturbations from hydro growth radiography (HGR) experiments on the National Ignition Facility show spoke perturbations in the ablator radiating from the base of the tube. These correspond to the shadow of the 10 μm diameter glass fill tube cast by hot spots at early time. We present 3D integrated HYDRA simulations of these experiments which include the fill tube. Meshing techniques are described which were employed to resolve the fill tube structure and associated perturbations in the simulations. We examine the extent to which the specific illumination geometry necessary to accommodate a backlighter in the HGR experiment contributes to the spoke pattern. Simulations presented include high resolution calculations run on the Trinity machine operated by the Alliance for Computing at Extreme Scale (ACES) partnership. This work was performed under the auspices of the Lawrence Livermore National Security, LLC, (LLNS) under Contract No. DE-AC52-07NA27344.

  7. Management of radioactive waste from reprocessing including disposal aspects

    International Nuclear Information System (INIS)

    Malherbe, J.

    1991-01-01

    Based on a hypothetical scenario including a reactor park of 20 GWe consisting of Pressurised-Water-Reactors with a resulting annual production of 600 tonnes of heavy metal of spent fuel, all aspects of management of resulting wastes are studied. Waste streams from reprocessing include gaseous and liquid effluents, and a number of solid conditioned waste types. Disposal of waste is supposed to be performed either in a near-surface engineered repository, as long as the content of alpha-emitting radionuclides is low enough, and in a deep geological granite formation. After having estimated quantities, cost and radiological consequences, the sensitivity of results to modification in reactor park size, burn-up and the introduction of mixed-oxide fuel (MOX) is evaluated

  8. Improving the strength of amalgams by including steel fibers

    Energy Technology Data Exchange (ETDEWEB)

    Cochran, Calvin T. [Hendrix College, Conway, AR 72032 (United States); Van Hoose, James R. [Siemens, Orlando, FL 32826 (United States); McGill, Preston B. [Marshall Space Flight Center, EM20, Huntsville, AL 35812 (United States); Grugel, Richard N., E-mail: richard.n.grugel@nasa.gov [Marshall Space Flight Center, EM30, Huntsville, AL 35812 (United States)

    2012-05-30

    Highlights: Black-Right-Pointing-Pointer A room temperature liquid Ga-In alloy was successfully substituted for mercury. Black-Right-Pointing-Pointer Physically sound amalgams with included steel fibers can be made. Black-Right-Pointing-Pointer A small volume fraction inclusion of fibers increased strength by {approx}20%. - Abstract: Mercury amalgams, due to their material properties, are widely and successfully used in dental practice. They are, however, also well recognized as having poor tensile strength. With the possibility of expanding amalgam applications it is demonstrated that tensile strength can be increased some 20% by including a small amount of steel fibers. Furthermore, it is shown that mercury can be replaced with a room temperature liquid gallium-indium alloy. Processing, microstructures, and mechanical test results of these novel amalgams are presented and discussed in view of means to further improve their properties.

  9. Microfluidic System Simulation Including the Electro-Viscous Effect

    Science.gov (United States)

    Rojas, Eileen; Chen, C. P.; Majumdar, Alok

    2007-01-01

    This paper describes a practical approach using a general purpose lumped-parameter computer program, GFSSP (Generalized Fluid System Simulation Program) for calculating flow distribution in a network of micro-channels including electro-viscous effects due to the existence of electrical double layer (EDL). In this study, an empirical formulation for calculating an effective viscosity of ionic solutions based on dimensional analysis is described to account for surface charge and bulk fluid conductivity, which give rise to electro-viscous effect in microfluidics network. Two dimensional slit micro flow data was used to determine the model coefficients. Geometry effect is then included through a Poiseuille number correlation in GFSSP. The bi-power model was used to calculate flow distribution of isotropically etched straight channel and T-junction microflows involving ionic solutions. Performance of the proposed model is assessed against experimental test data.

  10. Including investment risk in large-scale power market models

    DEFF Research Database (Denmark)

    Lemming, Jørgen Kjærgaard; Meibom, P.

    2003-01-01

    Long-term energy market models can be used to examine investments in production technologies, however, with market liberalisation it is crucial that such models include investment risks and investor behaviour. This paper analyses how the effect of investment risk on production technology selection...... can be included in large-scale partial equilibrium models of the power market. The analyses are divided into a part about risk measures appropriate for power market investors and a more technical part about the combination of a risk-adjustment model and a partial-equilibrium model. To illustrate...... the analyses quantitatively, a framework based on an iterative interaction between the equilibrium model and a separate risk-adjustment module was constructed. To illustrate the features of the proposed modelling approach we examined how uncertainty in demand and variable costs affects the optimal choice...

  11. Suddenly included: cultural differences in experiencing re-inclusion.

    Science.gov (United States)

    Pfundmair, Michaela; Graupmann, Verena; Du, Hongfei; Frey, Dieter; Aydin, Nilüfer

    2015-03-01

    In the current research, we examined whether re-inclusion (i.e. the change from a previous state of exclusion to a new state of inclusion) was perceived differently by people with individualistic and collectivistic cultural backgrounds. Individualists (German and Austrian participants) but not collectivists (Chinese participants) experienced re-inclusion differently than continued inclusion: While collectivistic participants did not differentiate between both kinds of inclusion, individualistic participants showed reduced fulfilment of their psychological needs under re-inclusion compared to continued inclusion. The results moreover revealed that only participants from individualistic cultures expressed more feelings of exclusion when re-included than when continually included. These exclusionary feelings partially mediated the relationship between the different states of inclusion and basic need fulfilment. © 2014 International Union of Psychological Science.

  12. MODEL OF THE TOKAMAK EDGE DENSITY PEDESTAL INCLUDING DIFFUSIVE NEUTRALS

    International Nuclear Information System (INIS)

    BURRELL, K.H.

    2003-01-01

    OAK-B135 Several previous analytic models of the tokamak edge density pedestal have been based on diffusive transport of plasma plus free-streaming of neutrals. This latter neutral model includes only the effect of ionization and neglects charge exchange. The present work models the edge density pedestal using diffusive transport for both the plasma and the neutrals. In contrast to the free-streaming model, a diffusion model for the neutrals includes the effect of both charge exchange and ionization and is valid when charge exchange is the dominant interaction. Surprisingly, the functional forms for the electron and neutral density profiles from the present calculation are identical to the results of the previous analytic models. There are some differences in the detailed definition of various parameters in the solution. For experimentally relevant cases where ionization and charge exchange rate are comparable, both models predict approximately the same width for the edge density pedestal

  13. Positron scattering by atomic hydrogen including positronium formation

    International Nuclear Information System (INIS)

    Higgins, K.; Burke, P.G.

    1993-01-01

    Positron scattering by atomic hydrogen including positronium formation has been formulated using the R-matrix method and a general computer code written. Partial wave elastic and ground state positronium formation cross sections have been calculated for L ≤ 6 using a six-state approximation which includes the ground state and the 2s and 2p pseudostates of both hydrogen and positronium. The elastic scattering results obtained are in good agreement with those derived from a highly accurate calculation based upon the intermediate energy R-matrix approach. As in a previous coupled-channel static calculation, resonance effects are observed at intermediate energies in the S-wave positronium formation cross section. However, in the present results, the dominant resonance arises in the P-wave cross sections at an energy of 2.73 Ryd and with a width of 0.19 Ryd. (author)

  14. XFEL OSCILLATOR SIMULATION INCLUDING ANGLE-DEPENDENT CRYSTAL REFLECTIVITY

    International Nuclear Information System (INIS)

    Fawley, William; Lindberg, Ryan; Kim, K.-J.; Shvyd'ko, Yuri

    2010-01-01

    The oscillator package within the GINGER FEL simulation code has now been extended to include angle-dependent reflectivity properties of Bragg crystals. Previously, the package was modified to include frequencydependent reflectivity in order to model x-ray FEL oscillators from start-up from shot noise through to saturation. We present a summary of the algorithms used for modeling the crystal reflectivity and radiation propagation outside the undulator, discussing various numerical issues relevant to the domain of high Fresnel number and efficient Hankel transforms. We give some sample XFEL-O simulation results obtained with the angle-dependent reflectivity model, with particular attention directed to the longitudinal and transverse coherence of the radiation output.

  15. QCD Reggeon field theory for every day: Pomeron loops included

    International Nuclear Information System (INIS)

    Altinoluk, Tolga; Kovner, Alex; Peressutti, Javier; Lublinsky, Michael

    2009-01-01

    We derive the evolution equation for hadronic scattering amplitude at high energy. Our derivation includes the nonlinear effects of finite partonic density in the hadronic wave function as well as the effect of multiple scatterings for scattering on dense hadronic target. It thus includes Pomeron loops. It is based on the evolution of the hadronic wave function derived in /cite{foam}. The kernel of the evolution equation defines the second quantized Hamiltonian of the QCD Reggeon Field Theory, H RFT beyond the limits considered so far. The two previously known limits of the evolution: dilute target (JIMWLK limit) and dilute projectile (KLWMIJ limit) are recovered directly from our final result. The Hamiltonian H RFT is applicable for the evolution of scattering amplitude for arbitrarily dense hadronic projectiles/targets - from 'dipole-dipole' to 'nucleus-nucleus' scattering processes.

  16. The Physics of Semiconductors An Introduction Including Devices and Nanophysics

    CERN Document Server

    Grundmann, Marius

    2006-01-01

    The Physics of Semiconductors provides material for a comprehensive upper-level-undergrauate and graduate course on the subject, guiding readers to the point where they can choose a special topic and begin supervised research. The textbook provides a balance between essential aspects of solid-state and semiconductor physics, on the one hand, and the principles of various semiconductor devices and their applications in electronic and photonic devices, on the other. It highlights many practical aspects of semiconductors such as alloys, strain, heterostructures, nanostructures, that are necessary in modern semiconductor research but typically omitted in textbooks. For the interested reader some additional advanced topics are included, such as Bragg mirrors, resonators, polarized and magnetic semiconductors are included. Also supplied are explicit formulas for many results, to support better understanding. The Physics of Semiconductors requires little or no prior knowledge of solid-state physics and evolved from ...

  17. Smart Farming: Including Rights Holders for Responsible Agricultural Innovation

    OpenAIRE

    Kelly Bronson

    2018-01-01

    This article draws on the literature of responsible innovation to suggest concrete processes for including rights holders in the “smart” agricultural revolution. It first draws upon historical agricultural research in Canada to highlight how productivist values drove seed innovations with particular consequences for the distribution of power in the food system. Next, the article uses document analysis to suggest that a similar value framework is motivating public investment in smart farming i...

  18. Aggregated Demand Modelling Including Distributed Generation, Storage and Demand Response

    OpenAIRE

    Marzooghi, Hesamoddin; Hill, David J.; Verbic, Gregor

    2014-01-01

    It is anticipated that penetration of renewable energy sources (RESs) in power systems will increase further in the next decades mainly due to environmental issues. In the long term of several decades, which we refer to in terms of the future grid (FG), balancing between supply and demand will become dependent on demand actions including demand response (DR) and energy storage. So far, FG feasibility studies have not considered these new demand-side developments for modelling future demand. I...

  19. Stochastic modelling of two-phase flows including phase change

    International Nuclear Information System (INIS)

    Hurisse, O.; Minier, J.P.

    2011-01-01

    Stochastic modelling has already been developed and applied for single-phase flows and incompressible two-phase flows. In this article, we propose an extension of this modelling approach to two-phase flows including phase change (e.g. for steam-water flows). Two aspects are emphasised: a stochastic model accounting for phase transition and a modelling constraint which arises from volume conservation. To illustrate the whole approach, some remarks are eventually proposed for two-fluid models. (authors)

  20. Production, control and utilization of radioisotopes including radiopharmaceuticals

    International Nuclear Information System (INIS)

    Muenze, R.

    1985-05-01

    From April 29th to May 5th, 1984 27 participants from 21 developing countries stayed within an IAEA Study Tour ('Production, Control and Utilization of Radioisotopes including Radiopharmaceuticals') in the GDR. In the CINR, Rossendorf the reactor, the cyclotron, the technological centre as well as the animal test laboratory were visited. The participants were made familiar by 10 papers with the development, production and control of radiopharmaceuticals in the CINR, Rossendorf. (author)

  1. Reliability evaluation of containments including soil-structure interaction

    International Nuclear Information System (INIS)

    Pires, J.; Hwang, H.; Reich, M.

    1985-12-01

    Soil-structure interaction effects on the reliability assessment of containment structures are examined. The probability-based method for reliability evaluation of nuclear structures developed at Brookhaven National Laboratory is extended to include soil-structure interaction effects. In this method, reliability of structures is expressed in terms of limit state probabilities. Furthermore, random vibration theory is utilized to calculate limit state probabilities under random seismic loads. Earthquake ground motion is modeled by a segment of a zero-mean, stationary, filtered Gaussian white noise random process, represented by its power spectrum. All possible seismic hazards at a site, represented by a hazard curve, are also included in the analysis. The soil-foundation system is represented by a rigid surface foundation on an elastic halfspace. Random and other uncertainties in the strength properties of the structure, in the stiffness and internal damping of the soil, are also included in the analysis. Finally, a realistic reinforced concrete containment is analyzed to demonstrate the application of the method. For this containment, the soil-structure interaction effects on; (1) limit state probabilities, (2) structural fragility curves, (3) floor response spectra with probabilistic content, and (4) correlation coefficients for total acceleration response at specified structural locations, are examined in detail. 25 refs., 21 figs., 12 tabs

  2. A Framework for Including Family Health Spillovers in Economic Evaluation.

    Science.gov (United States)

    Al-Janabi, Hareth; van Exel, Job; Brouwer, Werner; Coast, Joanna

    2016-02-01

    Health care interventions may affect the health of patients' family networks. It has been suggested that these "health spillovers" should be included in economic evaluation, but there is not a systematic method for doing this. In this article, we develop a framework for including health spillovers in economic evaluation. We focus on extra-welfarist economic evaluations where the objective is to maximize health benefits from a health care budget (the "health care perspective"). Our framework involves adapting the conventional cost-effectiveness decision rule to include 2 multiplier effects to internalize the spillover effects. These multiplier effects express the ratio of total health effects (for patients and their family networks) to patient health effects. One multiplier effect is specified for health benefit generated from providing a new intervention, one for health benefit displaced by funding this intervention. We show that using multiplier effects to internalize health spillovers could change the optimal funding decisions and generate additional health benefits to society. © The Author(s) 2015.

  3. Assessment of pancreas cells

    Science.gov (United States)

    Vanoss, C. J.

    1978-01-01

    Pancreatic islets were obtained from guinea pig pancreas by the collagenase method and kept alive in tissue culture prior to further studies. Pancreas cell morphology was studied by standard histochemical techniques using light microscopy. Preparative vertical electrophoresis-levitation of dispersed fetal guinea pig pancreas cells was conducted in phosphate buffer containing a heavy water (D20) gradient which does not cause clumping of cells or alter the osmolarity of the buffers. The faster migrating fractions tended to be enriched in beta-cell content. Alpha and delta cells were found to some degree in most fractions. A histogram showing the cell count distribution is included.

  4. The COG database: an updated version includes eukaryotes

    Directory of Open Access Journals (Sweden)

    Sverdlov Alexander V

    2003-09-01

    Full Text Available Abstract Background The availability of multiple, essentially complete genome sequences of prokaryotes and eukaryotes spurred both the demand and the opportunity for the construction of an evolutionary classification of genes from these genomes. Such a classification system based on orthologous relationships between genes appears to be a natural framework for comparative genomics and should facilitate both functional annotation of genomes and large-scale evolutionary studies. Results We describe here a major update of the previously developed system for delineation of Clusters of Orthologous Groups of proteins (COGs from the sequenced genomes of prokaryotes and unicellular eukaryotes and the construction of clusters of predicted orthologs for 7 eukaryotic genomes, which we named KOGs after eukaryotic orthologous groups. The COG collection currently consists of 138,458 proteins, which form 4873 COGs and comprise 75% of the 185,505 (predicted proteins encoded in 66 genomes of unicellular organisms. The eukaryotic orthologous groups (KOGs include proteins from 7 eukaryotic genomes: three animals (the nematode Caenorhabditis elegans, the fruit fly Drosophila melanogaster and Homo sapiens, one plant, Arabidopsis thaliana, two fungi (Saccharomyces cerevisiae and Schizosaccharomyces pombe, and the intracellular microsporidian parasite Encephalitozoon cuniculi. The current KOG set consists of 4852 clusters of orthologs, which include 59,838 proteins, or ~54% of the analyzed eukaryotic 110,655 gene products. Compared to the coverage of the prokaryotic genomes with COGs, a considerably smaller fraction of eukaryotic genes could be included into the KOGs; addition of new eukaryotic genomes is expected to result in substantial increase in the coverage of eukaryotic genomes with KOGs. Examination of the phyletic patterns of KOGs reveals a conserved core represented in all analyzed species and consisting of ~20% of the KOG set. This conserved portion of the

  5. The role of chemical engineering in medicinal research including Alzheimer's.

    Science.gov (United States)

    Kontogeorgis, Georgios M

    2015-01-01

    Various disciplines of chemical engineering, especially thermodynamics and kinetics, play an important role in medicinal research and this has been particularly recognized during the last 10-15 years (von Stockar and van der Wielen, J Biotechnol 59:25, 1997; Prausnitz, Fluid Phase Equilib 53:439, 1989; Prausnitz, Pure Appl Chem 79:1435, 2007; Dey and Prausnitz, Ind Eng Chem Res 50:3, 2011; Prausnitz, J Chem Thermodynamics 35:21, 2003; Tsivintzelis et al. AIChE J 55:756, 2009). It is expected that during the twenty-first century chemical engineering and especially thermodynamics can contribute as significantly to the life sciences development as it has been done with the oil and gas and chemical sectors in the twentieth century. Moreover, it has during the recent years recognized that thermodynamics can help in understanding diseases like human cataract, sickle-cell anemia, Creuzfeldt-Jacob ("mad cow" disease), and Alzheimer's which are connected to "protein aggregation." Several articles in the Perspectives section of prominent chemical engineering journals have addressed this issue (Hall, AIChE J 54:1956, 2008; Vekilov, AIChE J 54:2508, 2008). This work reviews recent applications of thermodynamics (and other areas of chemical engineering) first in drug development and then in the understanding of the mechanism of Alzheimer's and similar diseases.

  6. A fast and robust hepatocyte quantification algorithm including vein processing

    Directory of Open Access Journals (Sweden)

    Homeyer André

    2010-03-01

    Full Text Available Abstract Background Quantification of different types of cells is often needed for analysis of histological images. In our project, we compute the relative number of proliferating hepatocytes for the evaluation of the regeneration process after partial hepatectomy in normal rat livers. Results Our presented automatic approach for hepatocyte (HC quantification is suitable for the analysis of an entire digitized histological section given in form of a series of images. It is the main part of an automatic hepatocyte quantification tool that allows for the computation of the ratio between the number of proliferating HC-nuclei and the total number of all HC-nuclei for a series of images in one processing run. The processing pipeline allows us to obtain desired and valuable results for a wide range of images with different properties without additional parameter adjustment. Comparing the obtained segmentation results with a manually retrieved segmentation mask which is considered to be the ground truth, we achieve results with sensitivity above 90% and false positive fraction below 15%. Conclusions The proposed automatic procedure gives results with high sensitivity and low false positive fraction and can be applied to process entire stained sections.

  7. Global anthropogenic emissions of particulate matter including black carbon

    Science.gov (United States)

    Klimont, Zbigniew; Kupiainen, Kaarle; Heyes, Chris; Purohit, Pallav; Cofala, Janusz; Rafaj, Peter; Borken-Kleefeld, Jens; Schöpp, Wolfgang

    2017-07-01

    This paper presents a comprehensive assessment of historical (1990-2010) global anthropogenic particulate matter (PM) emissions including the consistent and harmonized calculation of mass-based size distribution (PM1, PM2. 5, PM10), as well as primary carbonaceous aerosols including black carbon (BC) and organic carbon (OC). The estimates were developed with the integrated assessment model GAINS, where source- and region-specific technology characteristics are explicitly included. This assessment includes a number of previously unaccounted or often misallocated emission sources, i.e. kerosene lamps, gas flaring, diesel generators, refuse burning; some of them were reported in the past for selected regions or in the context of a particular pollutant or sector but not included as part of a total estimate. Spatially, emissions were calculated for 172 source regions (as well as international shipping), presented for 25 global regions, and allocated to 0.5° × 0.5° longitude-latitude grids. No independent estimates of emissions from forest fires and savannah burning are provided and neither windblown dust nor unpaved roads emissions are included. We estimate that global emissions of PM have not changed significantly between 1990 and 2010, showing a strong decoupling from the global increase in energy consumption and, consequently, CO2 emissions, but there are significantly different regional trends, with a particularly strong increase in East Asia and Africa and a strong decline in Europe, North America, and the Pacific region. This in turn resulted in important changes in the spatial pattern of PM burden, e.g. European, North American, and Pacific contributions to global emissions dropped from nearly 30 % in 1990 to well below 15 % in 2010, while Asia's contribution grew from just over 50 % to nearly two-thirds of the global total in 2010. For all PM species considered, Asian sources represented over 60 % of the global anthropogenic total, and residential combustion

  8. Global anthropogenic emissions of particulate matter including black carbon

    Directory of Open Access Journals (Sweden)

    Z. Klimont

    2017-07-01

    Full Text Available This paper presents a comprehensive assessment of historical (1990–2010 global anthropogenic particulate matter (PM emissions including the consistent and harmonized calculation of mass-based size distribution (PM1, PM2. 5, PM10, as well as primary carbonaceous aerosols including black carbon (BC and organic carbon (OC. The estimates were developed with the integrated assessment model GAINS, where source- and region-specific technology characteristics are explicitly included. This assessment includes a number of previously unaccounted or often misallocated emission sources, i.e. kerosene lamps, gas flaring, diesel generators, refuse burning; some of them were reported in the past for selected regions or in the context of a particular pollutant or sector but not included as part of a total estimate. Spatially, emissions were calculated for 172 source regions (as well as international shipping, presented for 25 global regions, and allocated to 0.5°  ×  0.5° longitude–latitude grids. No independent estimates of emissions from forest fires and savannah burning are provided and neither windblown dust nor unpaved roads emissions are included. We estimate that global emissions of PM have not changed significantly between 1990 and 2010, showing a strong decoupling from the global increase in energy consumption and, consequently, CO2 emissions, but there are significantly different regional trends, with a particularly strong increase in East Asia and Africa and a strong decline in Europe, North America, and the Pacific region. This in turn resulted in important changes in the spatial pattern of PM burden, e.g. European, North American, and Pacific contributions to global emissions dropped from nearly 30 % in 1990 to well below 15 % in 2010, while Asia's contribution grew from just over 50 % to nearly two-thirds of the global total in 2010. For all PM species considered, Asian sources represented over 60 % of the global

  9. Dental pulp stem cells

    DEFF Research Database (Denmark)

    Ashri, N. Y.; Ajlan, S. A.; Aldahmash, Abdullah M.

    2015-01-01

    scaffold, and guided through signaling molecules. Dental pulp stem cells have been used in an increasing number of studies in dental tissue engineering. Those cells show mesenchymal (stromal) stem cell-like properties including self-renewal and multilineage differentiation potentials, aside from...... an updated review on dental pulp stem cells and their applications in periodontal regeneration, in combination with different scaffolds and growth factors....

  10. Increased voltage photovoltaic cell

    Science.gov (United States)

    Ross, B.; Bickler, D. B.; Gallagher, B. D. (Inventor)

    1985-01-01

    A photovoltaic cell, such as a solar cell, is provided which has a higher output voltage than prior cells. The improved cell includes a substrate of doped silicon, a first layer of silicon disposed on the substrate and having opposite doping, and a second layer of silicon carbide disposed on the first layer. The silicon carbide preferably has the same type of doping as the first layer.

  11. Phenotypes in defined genotypes including siblings with Usher syndrome.

    Science.gov (United States)

    Malm, Eva; Ponjavic, Vesna; Möller, Claes; Kimberling, William J; Andréasson, Sten

    2011-06-01

    To characterize visual function in defined genotypes including siblings with Usher syndrome. Thirteen patients with phenotypically different subtypes of Usher syndrome, including 3 families with affected siblings, were selected. Genetic analysis and ophthalmological examinations including visual fields, full-field electroretinography (ERG), multifocal electroretinography (mf ERG), and optical coherence tomography (OCT) were assessed. The patients' degree of visual handicap was evaluated by a questionnaire (ADL). Twelve of thirteen patients were genotyped as Usher 1B, 1D, 1F, 2A, 2C or 3A. In 12 of 13 patients examined with ERG the 30 Hz flickering light response revealed remaining cone function. In 3 of the patients with Usher type 1 mf ERG demonstrated a specific pattern, with a sharp distinction between the area with reduced function and the central area with remaining macular function and normal peak time. OCT demonstrated loss of foveal depression with distortion of the foveal architecture in the macula in all patients. The foveal thickness ranged from 159 to 384 µm and was not correlated to retinal function. Three siblings shared the same mutation for Usher 2C but in contrast to previous reports regarding this genotype, 1 of them diverged in phenotype with substantially normal visual fields, almost normal OCT and mf ERG findings, and only moderately reduced rod and cone function according to ERG. Evaluation of visual function comprising both the severity of the rod cone degeneration and the function in the macular region confirm phenotypical heterogeneity within siblings and between different genotypes of Usher syndrome.

  12. Fabrication of SWCNT-Ag nanoparticle hybrid included self-assemblies for antibacterial applications.

    Directory of Open Access Journals (Sweden)

    Sayanti Brahmachari

    Full Text Available The present article reports the development of soft nanohybrids comprising of single walled carbon nanotube (SWCNT included silver nanoparticles (AgNPs having superior antibacterial property. In this regard aqueous dispersing agent of carbon nanotube (CNT containing a silver ion reducing unit was synthesised by the inclusion of tryptophan and tyrosine within the backbone of the amphiphile. The dispersions were characterized spectroscopically and microscopically using TEM, AFM and Raman spectroscopy. The nanotube-nanoparticle conjugates were prepared by the in situ photoreduction of AgNO3. The phenolate residue and the indole moieties of tyrosine and tryptophan, respectively reduces the sliver ion as well as acts as stabilizing agents for the synthesized AgNPs. The nanohybrids were characterized using TEM and AFM. The antibacterial activity of the nanohybrids was studied against Gram-positive (Bacillus subtilis and Micrococcus luteus and Gram-negative bacteria (Escherichia coli and Klebsiella aerogenes. The SWCNT dispersions showed moderate killing ability (40-60% against Gram-positive bacteria however no antibacterial activity was observed against the Gram negative ones. Interestingly, the developed SWCNT-amphiphile-AgNP nanohybrids exhibited significant killing ability (∼90% against all bacteria. Importantly, the cell viability of these newly developed self-assemblies was checked towards chinese hamster ovarian cells and high cell viability was observed after 24 h of incubation. This specific killing of bacterial cells may have been achieved due to the presence of higher -SH containing proteins in the cell walls of the bacteria. The developed nanohybrids were subsequently infused into tissue engineering scaffold agar-gelatin films and the films similarly showed bactericidal activity towards both kinds of bacterial strains while allowing normal growth of eukaryotic cells on the surface of the films.

  13. Developing HYDMN code to include the transient of MNSR

    International Nuclear Information System (INIS)

    Al-Barhoum, M.

    2000-11-01

    A description of the programs added to HYDMN code (a code for thermal-hydraulic steady state of MNSR) to include the transient of the same MNSR is presented. The code asks the initial conditions for the power (in k W) and the cold initial core inlet temperature (in degrees centigrade). A time-dependent study of the coolant inlet and outlet temperature, its speed, pool and tank temperatures is done for MNSR in general and for the Syrian MNSR in particular. The study solves the differential equations taken from reference (1) by using some numerical methods found in reference (3). The code becomes this way independent of any external information source. (Author)

  14. Modification of SKYSHINE-III to include cask array shadowing

    Energy Technology Data Exchange (ETDEWEB)

    Hertel, N.E. [Georgia Institute of Technology, Atlanta, GA (United States); Pfeifer, H.J. [NAC International, Norcross, GA (United States); Napolitano, D.G. [NISYS Corporation, Duluth, GA (United States)

    2000-03-01

    The NAC International version of SKYSHINE-III has been expanded to represent the radiation emissions from ISFSI (Interim Spent Fuel Storage Installations) dry storage casks using surface source descriptions. In addition, this modification includes a shadow shielding algorithm of the casks in the array. The resultant code is a flexible design tool which can be used to rapidly assess the impact of various cask loadings and arrangements. An example of its use in calculating dose rates for a 10x8 cask array is presented. (author)

  15. Composite material including nanocrystals and methods of making

    Science.gov (United States)

    Bawendi, Moungi G.; Sundar, Vikram C.

    2010-04-06

    Temperature-sensing compositions can include an inorganic material, such as a semiconductor nanocrystal. The nanocrystal can be a dependable and accurate indicator of temperature. The intensity of emission of the nanocrystal varies with temperature and can be highly sensitive to surface temperature. The nanocrystals can be processed with a binder to form a matrix, which can be varied by altering the chemical nature of the surface of the nanocrystal. A nanocrystal with a compatibilizing outer layer can be incorporated into a coating formulation and retain its temperature sensitive emissive properties.

  16. Endoscopic Management of Vascular Sinonasal Tumors, Including Angiofibroma.

    Science.gov (United States)

    Snyderman, Carl H; Pant, Harshita

    2016-06-01

    The greatest challenge in the surgical treatment of angiofibromas is dealing with the hypervascularity of these tumors. Staging systems that take into account the vascularity of the tumor may be more prognostic. A variety of treatment strategies are used to deal with the vascularity of angiofibromas, including preoperative embolization, segmentation of the tumor into vascular territories, use of hemostatic tools, and staging of surgery. Even large angiofibromas with intracranial extension and residual vascularity can be successfully managed by a skull base team using endoscopic techniques. Copyright © 2016 Elsevier Inc. All rights reserved.

  17. Solution of neutron slowing down equation including multiple inelastic scattering

    International Nuclear Information System (INIS)

    El-Wakil, S.A.; Saad, A.E.

    1977-01-01

    The present work is devoted the presentation of an analytical method for the calculation of elastically and inelastically slowed down neutrons in an infinite non absorbing homogeneous medium. On the basis of the Central limit theory (CLT) and the integral transform technique the slowing down equation including inelastic scattering in terms of the Green function of elastic scattering is solved. The Green function is decomposed according to the number of collisions. A formula for the flux at any lethargy O (u) after any number of collisions is derived. An equation for the asymptotic flux is also obtained

  18. cDNA encoding a polypeptide including a hevein sequence

    Energy Technology Data Exchange (ETDEWEB)

    Raikhel, Natasha V. (Okemos, MI); Broekaert, Willem F. (Dilbeek, BE); Chua, Nam-Hai (Scarsdale, NY); Kush, Anil (New York, NY)

    1993-02-16

    A cDNA clone (HEV1) encoding hevein was isolated via polymerase chain reaction (PCR) using mixed oligonucleotides corresponding to two regions of hevein as primers and a Hevea brasiliensis latex cDNA library as a template. HEV1 is 1018 nucleotides long and includes an open reading frame of 204 amino acids. The deduced amino acid sequence contains a pu GOVERNMENT RIGHTS This application was funded under Department of Energy Contract DE-AC02-76ER01338. The U.S. Government has certain rights under this application and any patent issuing thereon.

  19. Smart Farming: Including Rights Holders for Responsible Agricultural Innovation

    Directory of Open Access Journals (Sweden)

    Kelly Bronson

    2018-02-01

    Full Text Available This article draws on the literature of responsible innovation to suggest concrete processes for including rights holders in the “smart” agricultural revolution. It first draws upon historical agricultural research in Canada to highlight how productivist values drove seed innovations with particular consequences for the distribution of power in the food system. Next, the article uses document analysis to suggest that a similar value framework is motivating public investment in smart farming innovations. The article is of interest to smart farming’s decision makers (from farmers to governance actors and a broader audience – anyone interested in engendering equity through innovation-led societal transitions.

  20. Clinton administration budget includes mixed bag for science

    Science.gov (United States)

    Showstack, Randy

    The $1,766 trillion federal budget proposal that the Clinton Administration rolled out on February 1—which promises to protect Social Security and Medicare and work within mandated budget caps—generally provides favorable news for federally funded science research and development.Within the 17% ($592 billion) of the federal budget earmarked for discretionary spending, the Administration's budget proposal increases funding for nondefense research and development for the seventh year in a row. This includes increased funding for a number of science accounts and money for a series of new science initiatives.

  1. Retinal stem cells and potential cell transplantation treatments

    Directory of Open Access Journals (Sweden)

    Tai-Chi Lin

    2014-11-01

    Full Text Available The retina, histologically composed of ten delicate layers, is responsible for light perception and relaying electrochemical signals to the secondary neurons and visual cortex. Retinal disease is one of the leading clinical causes of severe vision loss, including age-related macular degeneration, Stargardt's disease, and retinitis pigmentosa. As a result of the discovery of various somatic stem cells, advances in exploring the identities of embryonic stem cells, and the development of induced pluripotent stem cells, cell transplantation treatment for retinal diseases is currently attracting much attention. The sources of stem cells for retinal regeneration include endogenous retinal stem cells (e.g., neuronal stem cells, Müller cells, and retinal stem cells from the ciliary marginal zone and exogenous stem cells (e.g., bone mesenchymal stem cells, adipose-derived stem cells, embryonic stem cells, and induced pluripotent stem cells. The success of cell transplantation treatment depends mainly on the cell source, the timing of cell harvesting, the protocol of cell induction/transplantation, and the microenvironment of the recipient's retina. This review summarizes the different sources of stem cells for regeneration treatment in retinal diseases and surveys the more recent achievements in animal studies and clinical trials. Future directions and challenges in stem cell transplantation are also discussed.

  2. TOOLS TO INCLUDE BLIND STUDENTS IN SCHOOL BUILDING PERFORMANCE ASSESSMENTS

    Directory of Open Access Journals (Sweden)

    Tania Pietzschke Abate

    2016-05-01

    Full Text Available This article discusses the design of data collection instruments that include the opinions of blind students, in accordance with the principles of Universal Design (UD. The aim of this study is to understand the importance of adapting data collection instruments for the inclusion of disabled persons in field research in Architecture and Design, among other fields. The data collection instruments developed were a play interview with a tactile map and a 3D survey with the use of tactile models. These instruments sought to assess the school environment experienced by blind students. The study involved students from the early years of a school for the blind who had not yet mastered the Braille system. The participation of these students was evaluated. A multidisciplinary team consisting of architects, designers, educators, and psychologists lent support to the study. The results showed that the data collection instruments adapted to blind students were successful in making the group of authors examine questions regarding UD. An analysis of the participatory phase showed that the limitations resulting from blindness determine the specificities in the adaptation and implementation process of the instruments in schools. Practical recommendations for future studies related to instruments in the UD thematic are presented. This approach is in line with the global trend of including disabled persons in society based on these users’ opinions concerning what was designed by architects and designers.

  3. Kabuki syndrome: expanding the phenotype to include microphthalmia and anophthalmia.

    Science.gov (United States)

    McVeigh, Terri P; Banka, Siddharth; Reardon, William

    2015-10-01

    Kabuki syndrome is a rare genetic malformation syndrome that is characterized by distinct facies, structural defects and intellectual disability. Kabuki syndrome may be caused by mutations in one of two histone methyltransferase genes: KMT2D and KDM6A. We describe a male child of nonconsanguineous Irish parents presenting with multiple malformations, including bilateral extreme microphthalmia; cleft palate; congenital diaphragmatic hernia; duplex kidney; as well as facial features of Kabuki syndrome, including interrupted eyebrows and lower lid ectropion. A de-novo germline mutation in KMT2D was identified. Whole-exome sequencing failed to reveal mutations in any of the known microphthalmia/anopthalmia genes. We also identified four other patients with Kabuki syndrome and microphthalmia. We postulate that Kabuki syndrome may produce this type of ocular phenotype as a result of extensive interaction between KMT2D, WAR complex proteins and PAXIP1. Children presenting with microphthalmia/anophthalmia should be examined closely for other signs of Kabuki syndrome, especially at an age where the facial gestalt might be less readily appreciable.

  4. Risk Factors for Breast Cancer, Including Occupational Exposures

    Directory of Open Access Journals (Sweden)

    Elisabete Weiderpass

    2011-03-01

    Full Text Available The knowledge on the etiology of breast cancer has advanced substantially in recent years, and several etiological factors are now firmly established. However, very few new discoveries have been made in relation to occupational risk factors. The International Agency for Research on Cancer has evaluated over 900 different exposures or agents to-date to determine whether they are carcinogenic to humans. These evaluations are published as a series of Monographs (www.iarc.fr. For breast cancer the following substances have been classified as “carcinogenic to humans” (Group 1: alcoholic beverages, exposure to diethylstilbestrol, estrogen-progestogen contraceptives, estrogen-progestogen hormone replacement therapy and exposure to X-radiation and gamma-radiation (in special populations such as atomic bomb survivors, medical patients, and in-utero exposure. Ethylene oxide is also classified as a Group 1 carcinogen, although the evidence for carcinogenicity in epidemiologic studies, and specifically for the human breast, is limited. The classification “probably carcinogenic to humans” (Group 2A includes estrogen hormone replacement therapy, tobacco smoking, and shift work involving circadian disruption, including work as a flight attendant. If the association between shift work and breast cancer, the most common female cancer, is confirmed, shift work could become the leading cause of occupational cancer in women.

  5. Proposal to Include Electrical Energy in the Industrial Return Statistics

    CERN Document Server

    2003-01-01

    At its 108th session on the 20 June 1997, the Council approved the Report of the Finance Committee Working Group on the Review of CERN Purchasing Policy and Procedures. Among other topics, the report recommended the inclusion of utility supplies in the calculation of the return statistics as soon as the relevant markets were deregulated, without reaching a consensus on the exact method of calculation. At its 296th meeting on the 18 June 2003, the Finance Committee approved a proposal to award a contract for the supply of electrical energy (CERN/FC/4693). The purpose of the proposal in this document is to clarify the way electrical energy will be included in future calculations of the return statistics. The Finance Committee is invited: 1. to agree that the full cost to CERN of electrical energy (excluding the cost of transport) be included in the Industrial Service return statistics; 2. to recommend that the Council approves the corresponding amendment to the Financial Rules set out in section 2 of this docum...

  6. Impact of a pain protocol including hypnosis in major burns.

    Science.gov (United States)

    Berger, Mette M; Davadant, Maryse; Marin, Christian; Wasserfallen, Jean-Blaise; Pinget, Christophe; Maravic, Philippe; Koch, Nathalie; Raffoul, Wassim; Chiolero, René L

    2010-08-01

    Pain is a major issue after burns even when large doses of opioids are prescribed. The study focused on the impact of a pain protocol using hypnosis on pain intensity, anxiety, clinical course, and costs. All patients admitted to the ICU, aged >18 years, with an ICU stay >24h, accepting to try hypnosis, and treated according to standardized pain protocol were included. Pain was scaled on the Visual Analog Scale (VAS) (mean of daily multiple recordings), and basal and procedural opioid doses were recorded. Clinical outcome and economical data were retrieved from hospital charts and information system, respectively. Treated patients were matched with controls for sex, age, and the burned surface area. Forty patients were admitted from 2006 to 2007: 17 met exclusion criteria, leaving 23 patients, who were matched with 23 historical controls. Altogether patients were 36+/-14 years old and burned 27+/-15%BSA. The first hypnosis session was performed after a median of 9 days. The protocol resulted in the early delivery of higher opioid doses/24h (ppatient. A pain protocol including hypnosis reduced pain intensity, improved opioid efficiency, reduced anxiety, improved wound outcome while reducing costs. The protocol guided use of opioids improved patient care without side effects, while hypnosis had significant psychological benefits.

  7. Study on 'Tannix' an absorbent for heavy metals including uranium

    International Nuclear Information System (INIS)

    Nakamura, Yasuo

    1997-01-01

    To treat radioactive wastes including uranium and transuranic elements such as plutonium, americium etc., development of an absorbent which can be used to absorb and isolate these elements without producing secondary wastes after treatment was attempted. And an absorbent has been successfully developed by polymerizing tannin, a natural product. It is known that tannin binds heavy metals including uranium resulting to produce their precipitates. There are some reports suggesting its absorption ability for uranium. However, tannin has not been used to isolate a heavy metal from a solution because it is soluble in water. Here, insolubilization of tannin was attempted and a manufacturing method for a gelatinized insoluble tannin named as ''Tannix'' was established. Wattle tannin extracted from Mimosa pudica produced in Africa was dissolved in an alkaline solution and gelatinized by heating after the addition of formalin. Thus obtained insoluble tannin was used after crushing and sieving. This product, ''Tannix'' was able to absorb more than 99% of uranium in the waste. And the absorbed Tannin could be degraded by incineration even at a low temperature, leaving only uranium, but not producing any secondary product. (M.N.)

  8. Global Analysis of Solar Neutrino Oscillations Including SNO CC Measurement

    CERN Document Server

    Bahcall, J N; Peña-Garay, C; Bahcall, John N; Peña-Garay, Carlos

    2001-01-01

    For active and sterile neutrinos, we present the globally allowed solutions for two neutrino oscillations. We include the SNO CC measurement and all other relevant solar neutrino and reactor data. Five active neutrino oscillation solutions (LMA, LOW, SMA, VAC, and Just So2) are currently allowed at 3 sigma; three sterile neutrino solutions (Just So2, SMA, and VAC) are allowed at 3 sigma. The goodness of fit is satisfactory for all eight solutions. We also investigate the robustness of the allowed solutions by carrying out global analyses with and without: 1) imposing solar model constraints on the 8B neutrino flux, 2) including the Super-Kamiokande spectral energy distribution and day-night data, 3) using an enhanced CC cross section for deuterium (due to radiative corrections), and 4) a optimistic, hypothetical reduction by a factor of three of the error of the SNO CC rate. For every analysis strategy used in this paper, the most favored solutions all involve large mixing angles: LMA, LOW, or VAC. The favore...

  9. Numerical optimization of conical flow waveriders including detailed viscous effects

    Science.gov (United States)

    Bowcutt, Kevin G.; Anderson, John D., Jr.; Capriotti, Diego

    1987-01-01

    A family of optimized hypersonic waveriders is generated and studied wherein detailed viscous effects are included within the optimization process itself. This is in contrast to previous optimized waverider work, wherein purely inviscid flow is used to obtain the waverider shapes. For the present waveriders, the undersurface is a streamsurface of an inviscid conical flowfield, the upper surface is a streamsurface of the inviscid flow over a tapered cylinder (calculated by the axisymmetric method of characteristics), and the viscous effects are treated by integral solutions of the boundary layer equations. Transition from laminar to turbulent flow is included within the viscous calculations. The optimization is carried out using a nonlinear simplex method. The resulting family of viscous hypersonic waveriders yields predicted high values of lift/drag, high enough to break the L/D barrier based on experience with other hypersonic configurations. Moreover, the numerical optimization process for the viscous waveriders results in distinctly different shapes compared to previous work with inviscid-designed waveriders. Also, the fine details of the viscous solution, such as how the shear stress is distributed over the surface, and the location of transition, are crucial to the details of the resulting waverider geometry. Finally, the moment coefficient variations and heat transfer distributions associated with the viscous optimized waveriders are studied.

  10. Control rod calibration including the rod coupling effect

    International Nuclear Information System (INIS)

    Szilard, R.; Nelson, G.W.

    1984-01-01

    In a reactor containing more than one control rod, which includes all reactors licensed in the United States, there will be a 'coupling' or 'shadowing' of control rod flux at the location of a control rod as a result of the flux depression caused by another control rod. It was decided to investigate this phenomenon further, and eventually to put calibration table data or formulae in a small computer in the control room, so once could insert the positions of the three control rods and receive the excess reactivity without referring to separate tables. For this to be accomplished, a 'three control- rod reactivity function' would be used which would include the flux coupling between the rods. The function is design and measured data was fitted into it to determine the calibration constants. The input data for fitting the trial functions consisted of 254 data points, each consisting of the position of the reg, shim, and transient rods, and the total excess reactivity. (About 200 of these points were 'critical balance points', that is the rod positions for which reactor was critical, and the remainder were determined by positive period measurements.) Although this may be unrealistic from a physical viewpoint, the function derived gave a very accurate recalculation of the input data, and thus would faithfully give the excess reactivity for any possible combination of the locations of the three control rods. The next step, incorporation of the three-rod function into the minicomputer, will be pursued in the summer and fall of 1984

  11. Study on `Tannix` an absorbent for heavy metals including uranium

    Energy Technology Data Exchange (ETDEWEB)

    Nakamura, Yasuo [Mitsubishi Nuclear Fuel Co. Ltd., Tokyo (Japan)

    1997-09-01

    To treat radioactive wastes including uranium and transuranic elements such as plutonium, americium etc., development of an absorbent which can be used to absorb and isolate these elements without producing secondary wastes after treatment was attempted. And an absorbent has been successfully developed by polymerizing tannin, a natural product. It is known that tannin binds heavy metals including uranium resulting to produce their precipitates. There are some reports suggesting its absorption ability for uranium. However, tannin has not been used to isolate a heavy metal from a solution because it is soluble in water. Here, insolubilization of tannin was attempted and a manufacturing method for a gelatinized insoluble tannin named as ``Tannix`` was established. Wattle tannin extracted from Mimosa pudica produced in Africa was dissolved in an alkaline solution and gelatinized by heating after the addition of formalin. Thus obtained insoluble tannin was used after crushing and sieving. This product, ``Tannix`` was able to absorb more than 99% of uranium in the waste. And the absorbed Tannin could be degraded by incineration even at a low temperature, leaving only uranium, but not producing any secondary product. (M.N.)

  12. Community Assessment Tool for Public Health Emergencies Including Pandemic Influenza

    Energy Technology Data Exchange (ETDEWEB)

    ORAU' s Oak Ridge Institute for Science Education (HCTT-CHE)

    2011-04-14

    The Community Assessment Tool (CAT) for Public Health Emergencies Including Pandemic Influenza (hereafter referred to as the CAT) was developed as a result of feedback received from several communities. These communities participated in workshops focused on influenza pandemic planning and response. The 2008 through 2011 workshops were sponsored by the Centers for Disease Control and Prevention (CDC). Feedback during those workshops indicated the need for a tool that a community can use to assess its readiness for a disaster - readiness from a total healthcare perspective, not just hospitals, but the whole healthcare system. The CAT intends to do just that - help strengthen existing preparedness plans by allowing the healthcare system and other agencies to work together during an influenza pandemic. It helps reveal each core agency partners (sectors) capabilities and resources, and highlights cases of the same vendors being used for resource supplies (e.g., personal protective equipment [PPE] and oxygen) by the partners (e.g., public health departments, clinics, or hospitals). The CAT also addresses gaps in the community's capabilities or potential shortages in resources. This tool has been reviewed by a variety of key subject matter experts from federal, state, and local agencies and organizations. It also has been piloted with various communities that consist of different population sizes, to include large urban to small rural communities.

  13. The Diversification Benefits of Including Carbon Assets in Financial Portfolios

    Directory of Open Access Journals (Sweden)

    Yinpeng Zhang

    2017-03-01

    Full Text Available Carbon allowances traded in the EU-Emission Trading Scheme (EU-ETS were initially designed as an economic motivation for efficiently curbing greenhouse as emissions, but now it mimics quite a few characteristics of financial assets, and have now been used as a candidate product in building financial portfolios. In this study, we examine the time-varying correlations between carbon allowance prices with other financial indices, during the third phase of EU-ETS. The results show that, at the beginning of this period, carbon price was still strongly corrected with other financial indices. However, this connection was weakened over time. Given the relative independence of carbon assets from other financial assets, we argue for the diversification benefits of including carbon assets in financial portfolios, and building such portfolios, respectively, with the traditional global minimum variance (GMV strategy, the mean-variance-OGARCH (MV-OGARCH strategy, and the dynamic conditional correlation (DCC strategy. It is shown that the portfolio built with the MV-OGARCH strategy far out-performs the others and that including carbon assets in financial portfolios does help reduce investment risks.

  14. Nonlinear equilibrium in Tokamaks including convective terms and viscosity

    International Nuclear Information System (INIS)

    Martin, P.; Castro, E.; Puerta, J.

    2003-01-01

    MHD equilibrium in tokamaks becomes very complex, when the non-linear convective term and viscosity are included in the momentum equation. In order to simplify the analysis, each new term has been separated in type gradient terms and vorticity depending terms. For the special case in which the vorticity vanishes, an extended Grad-Shafranov type equation can be obtained. However now the magnetic surface is not isobars or current surfaces as in the usual Grad-Shafranov treatment. The non-linear convective terms introduces gradient of Bernoulli type kinetic terms . Montgomery and other authors have shown the importance of the viscosity terms in tokamaks [1,2], here the treatment is carried out for the equilibrium condition, including generalized tokamaks coordinates recently described [3], which simplify the equilibrium analysis. Calculation of the new isobar surfaces is difficult and some computation have been carried out elsewhere for some particular cases [3]. Here, our analysis is extended discussing how the toroidal current density, plasma pressure and toroidal field are modified across the midplane because of the new terms (convective and viscous). New calculations and computations are also presented. (Author)

  15. Free vibration of elastically supported thin cylinders including gyroscopic effects

    CSIR Research Space (South Africa)

    Loveday, PW

    1998-10-29

    Full Text Available [ The equations D[R[ 747723 JSV 106:2 "Issue# MS 1560 VIBRATION OF THIN CYLINDERS 442 required for this procedure\\ including the gyroscopic terms\\ are included in Appendix A[ The displacement functions can then be written as follows] W"x# C0 cosh a0xa C1 sinh a0... xa C2 cos g1xa C3 sin g1xa epx:a0C4 cos qxa C5 sin qxa 1 e px:a0C6 cos qxa C7 sin qxa 1 "6a# V"x# A0C0 cosh a0xa A0C1 sinh a0xa A2C2 cos g1xa A2C3 sin g1xa epx:a$"A4C4 A5C5# cos qxa "A4C5 A5C4# sin qxa % e px:a$"A4C6 A5C7# cos...

  16. Fuel cell cassette with compliant seal

    Science.gov (United States)

    Karl, Haltiner, Jr. J.; Anthony, Derose J.; Klotzbach, Darasack C.; Schneider, Jonathan R.

    2017-11-07

    A fuel cell cassette for forming a fuel cell stack along a fuel cell axis includes a cell retainer, a plate positioned axially to the cell retainer and defining a space axially with the cell retainer, and a fuel cell having an anode layer and a cathode layer separated by an electrolyte layer. The outer perimeter of the fuel cell is positioned in the space between the plate and the cell retainer, thereby retaining the fuel cell and defining a cavity between the cell retainer, the fuel cell, and the plate. The fuel cell cassette also includes a seal disposed within the cavity for sealing the edge of the fuel cell. The seal is compliant at operational temperatures of the fuel cell, thereby allowing lateral expansion and contraction of the fuel cell within the cavity while maintaining sealing at the edge of the fuel cell.

  17. Nephrin regulates lamellipodia formation by assembling a protein complex that includes Ship2, filamin and lamellipodin.

    Directory of Open Access Journals (Sweden)

    Madhusudan Venkatareddy

    Full Text Available Actin dynamics has emerged at the forefront of podocyte biology. Slit diaphragm junctional adhesion protein Nephrin is necessary for development of the podocyte morphology and transduces phosphorylation-dependent signals that regulate cytoskeletal dynamics. The present study extends our understanding of Nephrin function by showing in cultured podocytes that Nephrin activation induced actin dynamics is necessary for lamellipodia formation. Upon activation Nephrin recruits and regulates a protein complex that includes Ship2 (SH2 domain containing 5' inositol phosphatase, Filamin and Lamellipodin, proteins important in regulation of actin and focal adhesion dynamics, as well as lamellipodia formation. Using the previously described CD16-Nephrin clustering system, Nephrin ligation or activation resulted in phosphorylation of the actin crosslinking protein Filamin in a p21 activated kinase dependent manner. Nephrin activation in cell culture results in formation of lamellipodia, a process that requires specialized actin dynamics at the leading edge of the cell along with focal adhesion turnover. In the CD16-Nephrin clustering model, Nephrin ligation resulted in abnormal morphology of actin tails in human podocytes when Ship2, Filamin or Lamellipodin were individually knocked down. We also observed decreased lamellipodia formation and cell migration in these knock down cells. These data provide evidence that Nephrin not only initiates actin polymerization but also assembles a protein complex that is necessary to regulate the architecture of the generated actin filament network and focal adhesion dynamics.

  18. Fuel cell system with interconnect

    Science.gov (United States)

    Goettler, Richard; Liu, Zhien

    2017-12-12

    The present invention includes a fuel cell system having a plurality of adjacent electrochemical cells formed of an anode layer, a cathode layer spaced apart from the anode layer, and an electrolyte layer disposed between the anode layer and the cathode layer. The fuel cell system also includes at least one interconnect, the interconnect being structured to conduct free electrons between adjacent electrochemical cells. Each interconnect includes a primary conductor embedded within the electrolyte layer and structured to conduct the free electrons.

  19. Aerodynamic analysis of the Darrieus rotor including secondary effects

    Science.gov (United States)

    Paraschivoiu, I.; Delclaux, F.; Fraunie, P.; Beguier, C.

    1983-10-01

    An aerodynamic analysis is made of two variants of the two-actuator-disk theory for modeling the Darrieus wind turbine. The double-multiple-streamtube model with constant and variable interference factors, including secondary effects, is examined for a Darrieus rotor. The influence of the secondary effects, namely, the blade geometry and profile type, the rotating tower, and the presence of struts and aerodynamic spoilers, is relatively significant, especially at high tip-speed ratios. Variation of the induced velocity as a function of the azimuthal angle allows a more accurate calculation of the aerodynamic loads on the downwind zone of the rotor with respect to the assumed constant interference factors. The theoretical results were compared with available experimental data for the Magdalen Islands wind turbine and Sandia-type machines (straight-line/circular-arc shape).

  20. Simulations of tokamak disruptions including self-consistent temperature evolution

    International Nuclear Information System (INIS)

    Bondeson, A.

    1986-01-01

    Three-dimensional simulations of tokamaks have been carried out, including self-consistent temperature evolution with a highly anisotropic thermal conductivity. The simulations extend over the transport time-scale and address the question of how disruptive current profiles arise at low-q or high-density operation. Sharply defined disruptive events are triggered by the m/n=2/1 resistive tearing mode, which is mainly affected by local current gradients near the q=2 surface. If the global current gradient between q=2 and q=1 is sufficiently steep, the m=2 mode starts a shock which accelerates towards the q=1 surface, leaving stochastic fields, a flattened temperature profile and turbulent plasma behind it. For slightly weaker global current gradients, a shock may form, but it will dissipate before reaching q=1 and may lead to repetitive minidisruptions which flatten the temperature profile in a region inside the q=2 surface. (author)

  1. Two-dimensional analysis of motion artifacts, including flow effects

    International Nuclear Information System (INIS)

    Litt, A.M.; Brody, A.S.; Spangler, R.A.; Scott, P.D.

    1990-01-01

    The effects of motion on magnetic resonance images have been theoretically analyzed for the case of a point-like object in simple harmonic motion and for other one-dimensional trajectories. The authors of this paper extend this analysis to a generalized two-dimensional magnetization with an arbitrary motion trajectory. The authors provide specific solutions for the clinically relevant cases of the cross-sections of cylindrical objects in the body, such as the aorta, which has a roughly one-dimensional, simple harmonic motion during respiration. By extending the solution to include inhomogeneous magnetizations, the authors present a model which allows the effects of motion artifacts and flow artifacts to be analyzed simultaneously

  2. Thermodynamic analysis of a Stirling engine including regenerator dead volume

    Energy Technology Data Exchange (ETDEWEB)

    Puech, Pascal; Tishkova, Victoria [Universite de Toulouse, UPS, CNRS, CEMES, 29 rue Jeanne Marvig, F-31055 Toulouse (France)

    2011-02-15

    This paper provides a theoretical investigation on the thermodynamic analysis of a Stirling engine with linear and sinusoidal variations of the volume. The regenerator in a Stirling engine is an internal heat exchanger allowing to reach high efficiency. We used an isothermal model to analyse the net work and the heat stored in the regenerator during a complete cycle. We show that the engine efficiency with perfect regeneration doesn't depend on the regenerator dead volume but this dead volume strongly amplifies the imperfect regeneration effect. An analytical expression to estimate the improvement due to the regenerator has been proposed including the combined effects of dead volume and imperfect regeneration. This could be used at the very preliminary stage of the engine design process. (author)

  3. A Case for Including Transactions in OpenMP

    Energy Technology Data Exchange (ETDEWEB)

    Wong, M; Bihari, B L; de Supinski, B R; Wu, P; Michael, M; Liu, Y; Chen, W

    2010-01-25

    Transactional Memory (TM) has received significant attention recently as a mechanism to reduce the complexity of shared memory programming. We explore the potential of TM to improve OpenMP applications. We combine a software TM (STM) system to support transactions with an OpenMP implementation to start thread teams and provide task and loop-level parallelization. We apply this system to two application scenarios that reflect realistic TM use cases. Our results with this system demonstrate that even with the relatively high overheads of STM, transactions can outperform OpenMP critical sections by 10%. Overall, our study demonstrates that extending OpenMP to include transactions would ease programming effort while allowing improved performance.

  4. Update on antiplatelet agents, including MATCH, CHARISMA, and ESPRIT.

    Science.gov (United States)

    Skliut, Maryna; Jamieson, Dara G

    2008-02-01

    Despite recent advances in the acute treatment of stroke, prevention and risk factor modification remain the mainstays of management for patients with ischemic stroke and transient ischemic attack. The majority of noncardioembolic ischemic strokes are atherothrombotic, presumed to be associated with the activation and aggregation of platelets. Antiplatelet medications have been shown to be effective in the secondary prevention of stroke of presumed arterial origin, both as monotherapy and in combination. Among combination of antiplatelet agents, aspirin plus extended-release dipyridamole has demonstrated statistically significant additive benefit over monotherapy with each agent. Clopidogrel plus aspirin does not prevent recurrent ischemic stroke over each component individually, and the combination increases the risk of hemorrhagic side effects. This article reviews the most recent studies on antiplatelet medications, including the combination of aspirin and clopidogrel or extended-release dipyridamole, and discusses some of the controversies that still exist with the use of antiplatelet agents.

  5. Mathematics of flexible risers including pressure and internal flow affects

    Energy Technology Data Exchange (ETDEWEB)

    Seyed, F.B. (John Brown Engineers and Constructors Ltd., London (GB)); Patel, M.H. (University Coll., London (GB). Dept. of Mechanical Engineering)

    1992-01-01

    Derivations are presented for calculation of pressure and internal flow induced forces on flexible risers and other curved pipes using a mathematically rigorous approach. Approximate and exact methods are presented for calculation of pressure forces on straight and curved pipes in two dimensions. The mathematical identity of these equations with those for effective tension is illustrated. The force arising from the flow of an internal fluid of constant density is then calculated and combined with those for pressure forces in derivation of the catenary equations including pressure and internal flow terms. It is shown that internal flow contributes a new term to the expression for effective tension. These governing equations are then reduced for the specific cases of simple catenary, steep-S, lazy-S, steep-wave and lazy-wave risers. In each case, the solution method has been presented and the governing equilibrium and geometric compatability conditions cited. (author).

  6. Property transfer assessments should include radon gas testing

    International Nuclear Information System (INIS)

    Nardi, M.A.

    1992-01-01

    There are two emerging influences that will require radon gas testing as part of many property transfers and most environmental assessments. These requirements come from lending regulators and state legislatures and affect single family, multifamily, and commercial properties. Fannie Mae and others have developed environmental investigation guidelines for protection from long term legal liabilities in the purchase of environmentally contaminated real estate. These guidelines include radon gas testing for many properties. Several states have enacted laws that require environmental disclosure forms be prepared to ensure that the parties involved in certain real estate transactions are aware of the environmental liabilities that may come with the transfer of property. Indiana has recently enacted legislation that would require the disclosure of the presence of radon gas on many commercial real estate transactions. With more banks and state governments following this trend, radon gas testing should be performed during all property transfers and environmental assessments to protect the parties involved from any long term legal liabilities

  7. Environmental site assessments should include radon gas testing

    International Nuclear Information System (INIS)

    Nardi, M.A.

    1991-01-01

    There are two emerging influences that will require radon gas testing as part of many property transfers and most site assessments. These requirements come from lending regulators and state legislatures. Fannie Mae and others have developed environmental investigation guidelines for the purchase of environmentally contaminated real estate. These guidelines include radon gas testing for many properties. Several states have enacted laws that require environmental disclosure forms be prepared to ensure that the parties involved in certain real estate transactions are aware of the environmental liabilities that may come with the transfer of property. Indiana has recently enacted legislation that would require the disclosure of the presence of radon gas on many commercial real estate transactions. With more lenders and state governments likely to follow this trend, radon gas testing should be performed during all property transfers and site assessment to protect the parties involved from any legal liabilities

  8. Neutrinos from Cosmic Accelerators including Magnetic Field and Flavor Effects

    Directory of Open Access Journals (Sweden)

    Walter Winter

    2012-01-01

    Full Text Available We review the particle physics ingredients affecting the normalization, shape, and flavor composition of astrophysical neutrinos fluxes, such as different production modes, magnetic field effects on the secondaries (muons, pions, and kaons, and flavor mixing, where we focus on pγ interactions. We also discuss the interplay with neutrino propagation and detection, including the possibility to detect flavor and its application in particle physics, and the use of the Glashow resonance to discriminate pγ from pp interactions in the source. We illustrate the implications on fluxes and flavor composition with two different models: (1 the target photon spectrum is dominated by synchrotron emission of coaccelerated electrons and (2 the target photon spectrum follows the observed photon spectrum of gamma-ray bursts. In the latter case, the multimessenger extrapolation from the gamma-ray fluence to the expected neutrino flux is highlighted.

  9. Unification of all elementary-particle forces including gravity

    International Nuclear Information System (INIS)

    Terazawa, Hidezumi; Chikashige, Yuichi; Matsuki, Takayuki; Akama, Keiichi.

    1978-07-01

    A unified model of the Nambu-Jona-Lasinio type for all elementary-particle forces including gravity is reviewed in some detail. Starting with a nonlinear fermion Lagrangian of the Heisenberg type and imposing the massless conditions of Bjorken on vector auxiliary fields, on effective Lagrangian is constructed, which combines the unified SU (2) x U (1) gauge theory of Weinberg and Salam for the weak and electromagnetic interactions of leptons and quarks and the Yang-Mills gauge theory of color SU (3) for the strong interaction of quarks. The photon, the weak vector bosons, and the physical Higgs scalar appear as collective excitations of lepton-antilepton or quark-antiquark pairs while the color-octet gluons appear as those of quark-antiquark pairs. The most important results of this unified model are presented. The Weinberg angle and the gluon coupling constant are determined, and the masses of the weak vector bosons are predicted. (Yoshimori, M.)

  10. OPAL Central Detector (Including vertex, jet and Z chambers)

    CERN Multimedia

    OPAL was one of the four experiments installed at the LEP particle accelerator from 1989 - 2000. OPAL's central tracking system consists of (in order of increasing radius) a silicon microvertex detector, a vertex detector, a jet chamber, and z-chambers. All the tracking detectors work by observing the ionization of atoms by charged particles passing by: when the atoms are ionized, electrons are knocked out of their atomic orbitals, and are then able to move freely in the detector. These ionization electrons are detected in the different parts of the tracking system. (This piece includes the vertex, jet and Z chambers) In the picture above, the central detector is the piece being removed to the right.

  11. Loan Products Included in the Offer of Commercial Banks

    Directory of Open Access Journals (Sweden)

    Vasile Dedu

    2009-04-01

    Full Text Available A bank loan is the main form of economical credit. It is for corporate activities – for medium and big companies and for retail activities – for small companies and individuals. The conditions for credit mainly depend on the quality of customers, it means their ability to perform a profitable activity and to be able to pay back the credits. For reasons which are mainly connected to marketing, bank practice has developed a large range of credit names, trying to emphasize some of the parts of the products or to take profit of some competition advantages in relation with customers’ products. We are trying to include the offer of bank loans in a typology which takes into account the law, the bank field rules and the main technical features of the offered products.

  12. The Photoconversion of Phytochrome Includes an Unproductive Shunt Reaction Pathway.

    Science.gov (United States)

    Buhrke, David; Kuhlmann, Uwe; Michael, Norbert; Hildebrandt, Peter

    2018-03-05

    Phytochromes are modular bimodal photoswitches that control gene expression for morphogenetic processes in plants. These functions are triggered by photoinduced conversions between the inactive and active states of the photosensory module, denoted as Pr and Pfr, respectively. In the present time-resolved resonance Raman spectroscopic study of bacterial representatives of this photoreceptor family, we demonstrate that these phototransformations do not represent linear processes but include a branching reaction back to the initial state, prior to (de)activation of the output module. Thus, only a fraction of the photoreceptors undergoing the phototransformations can initiate the downstream signaling process, consistent with phytochrome's function as a sensor for more durable changes of light conditions. © 2018 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim.

  13. Modeling Electric Double-Layers Including Chemical Reaction Effects

    DEFF Research Database (Denmark)

    Paz-Garcia, Juan Manuel; Johannesson, Björn; Ottosen, Lisbeth M.

    2014-01-01

    A physicochemical and numerical model for the transient formation of an electric double-layer between an electrolyte and a chemically-active flat surface is presented, based on a finite elements integration of the nonlinear Nernst-Planck-Poisson model including chemical reactions. The model works...... for symmetric and asymmetric multi-species electrolytes and is not limited to a range of surface potentials. Numerical simulations are presented, for the case of a CaCO3 electrolyte solution in contact with a surface with rate-controlled protonation/deprotonation reactions. The surface charge and potential...... are determined by the surface reactions, and therefore they depends on the bulk solution composition and concentration...

  14. PROPERTIES AND MICROSTRUCTURE OF CEMENT PASTE INCLUDING RECYCLED CONCRETE POWDER

    Directory of Open Access Journals (Sweden)

    Jaroslav Topič

    2017-02-01

    Full Text Available The disposal and further recycling of concrete is being investigated worldwide, because the issue of complete recycling has not yet been fully resolved. A fundamental difficulty faced by researchers is the reuse of the recycled concrete fines which are very small (< 1 mm. Currently, full recycling of such waste fine fractions is highly energy intensive and resulting in production of CO2. Because of this, the only recycling methods that can be considered as sustainable and environmentally friendly are those which involve recycled concrete powder (RCP in its raw form. This article investigates the performance of RCP with the grain size < 0.25 mm as a potential binder replacement, and also as a microfiller in cement-based composites. Here, the RCP properties are assessed, including how mechanical properties and the microstructure are influenced by increasing the amount of the RCP in a cement paste (≤ 25 wt%.

  15. Hydraulic engine valve actuation system including independent feedback control

    Science.gov (United States)

    Marriott, Craig D

    2013-06-04

    A hydraulic valve actuation assembly may include a housing, a piston, a supply control valve, a closing control valve, and an opening control valve. The housing may define a first fluid chamber, a second fluid chamber, and a third fluid chamber. The piston may be axially secured to an engine valve and located within the first, second and third fluid chambers. The supply control valve may control a hydraulic fluid supply to the piston. The closing control valve may be located between the supply control valve and the second fluid chamber and may control fluid flow from the second fluid chamber to the supply control valve. The opening control valve may be located between the supply control valve and the second fluid chamber and may control fluid flow from the supply control valve to the second fluid chamber.

  16. Relativistic bound state approach to fundamental forces including gravitation

    Directory of Open Access Journals (Sweden)

    Morsch H.P.

    2012-06-01

    Full Text Available To describe the structure of particle bound states of nature, a relativistic bound state formalism is presented, which requires a Lagrangian including scalar coupling of two boson fields. The underlying mechanisms are quite complex and require an interplay of overlapping boson fields and fermion-antifermion production. This gives rise to two potentials, a boson-exchange potential and one identified with the long sought confinement potential in hadrons. With minimal requirements, two elementary massless fermions (quantons - with and without charge - and one gauge boson, hadrons and leptons but also atoms and gravitational systems are described by bound states with electric and magnetic coupling between the charges and spins of quantons. No need is found for colour, Higgs-coupling and supersymmetry.

  17. Dynamic Analysis of Wind Turbines Including Soil-Structure Interaction

    DEFF Research Database (Denmark)

    Harte, M.; Basu, B.; Nielsen, Søren R.K.

    2012-01-01

    This paper investigates the along-wind forced vibration response of an onshore wind turbine. The study includes the dynamic interaction effects between the foundation and the underlying soil, as softer soils can influence the dynamic response of wind turbines. A Multi-Degree-of-Freedom (MDOF......) horizontal axes onshore wind turbine model is developed for dynamic analysis using an Euler–Lagrangian approach. The model is comprised of a rotor blade system, a nacelle and a flexible tower connected to a foundation system using a substructuring approach. The rotor blade system consists of three rotating...... for displacement of the turbine system are obtained and the modal frequencies of the combined turbine-foundation system are estimated. Simulations are presented for the MDOF turbine structure subjected to wind loading for different soil stiffness conditions. Steady state and turbulent wind loading, developed using...

  18. Double-photoionization of helium including quadrupole radiation effects

    Energy Technology Data Exchange (ETDEWEB)

    Colgan, James [Los Alamos National Laboratory; Ludlow, J A [AUBURN UNIV; Lee, Teck - Ghee [AUBURN UNIV; Pindzola, M S [AUBURN UNIV; Robicheaux, F [AUBURN UNIV

    2009-01-01

    Non-perturbative time-dependent close-coupling calculations are carried out for the double photoionization of helium including both dipole and quadrupole radiation effects. At a photon energy of 800 eV, accessible at CUlTent synchrotron light sources, the quadrupole interaction contributes around 6% to the total integral double photoionization cross section. The pure quadrupole single energy differential cross section shows a local maxima at equal energy sharing, as opposed to the minimum found in the pure dipole single energy differential cross section. The sum of the pure dipole and pure quadrupole single energy differentials is insensitive to non-dipole effects at 800 eV. However, the triple differential cross section at equal energy sharing of the two ejected electrons shows strong non-dipole effects due to the quadrupole interaction that may be experimentally observable.

  19. Extensions of MAD Version 8 to Include Beam Acceleration

    International Nuclear Information System (INIS)

    Raubenheimer, Tor O

    2000-01-01

    In this paper, the authors describe modifications to MAD version 8.23 to include linear accelerator cavities and beam acceleration. An additional energy variable has been added which is modified as the beam passes through LCAV elements (linear accelerator cavities) and can be used as a constraint in matching commands. The calculation of the beta functions and phase advance is consistent with that in other codes that treat acceleration such as TRANSPORT or DIMAD. These modifications allow this version of MAD to be used for the design and modeling of linacs and the authors present examples from the Next Linear Collider design as well as a muon acceleration complex. The code is available from CERN or SLAC

  20. Ball Screw Actuator Including a Compliant Ball Screw Stop

    Science.gov (United States)

    Wingett, Paul T. (Inventor); Hanlon, Casey (Inventor)

    2017-01-01

    An actuator includes a ball nut, a ball screw, and a ball screw stop. The ball nut is adapted to receive an input torque and in response rotates and supplies a drive force. The ball screw extends through the ball nut and has a first end and a second end. The ball screw receives the drive force from the ball nut and in response selectively translates between a retract position and a extend position. The ball screw stop is mounted on the ball screw proximate the first end to translate therewith. The ball screw stop engages the ball nut when the ball screw is in the extend position, translates, with compliance, a predetermined distance toward the first end upon engaging the ball nut, and prevents further rotation of the ball screw upon translating the predetermined distance.

  1. Actuator assembly including a single axis of rotation locking member

    Science.gov (United States)

    Quitmeyer, James N.; Benson, Dwayne M.; Geck, Kellan P.

    2009-12-08

    An actuator assembly including an actuator housing assembly and a single axis of rotation locking member fixedly attached to a portion of the actuator housing assembly and an external mounting structure. The single axis of rotation locking member restricting rotational movement of the actuator housing assembly about at least one axis. The single axis of rotation locking member is coupled at a first end to the actuator housing assembly about a Y axis and at a 90.degree. angle to an X and Z axis providing rotation of the actuator housing assembly about the Y axis. The single axis of rotation locking member is coupled at a second end to a mounting structure, and more particularly a mounting pin, about an X axis and at a 90.degree. angle to a Y and Z axis providing rotation of the actuator housing assembly about the X axis. The actuator assembly is thereby restricted from rotation about the Z axis.

  2. Ball Screw Actuator Including an Axial Soft Stop

    Science.gov (United States)

    Wingett, Paul T. (Inventor); Forrest, Steven Talbert (Inventor); Abel, Steve (Inventor); Woessner, George (Inventor); Hanlon, Casey (Inventor)

    2016-01-01

    An actuator includes an actuator housing, a ball screw, and an axial soft stop assembly. The ball screw extends through the actuator housing and has a first end and a second end. The ball screw is coupled to receive a drive force and is configured, upon receipt of the drive force, to selectively move in a retract direction and an extend direction. The axial soft stop assembly is disposed within the actuator housing. The axial soft stop assembly is configured to be selectively engaged by the ball screw and, upon being engaged thereby, to translate, with compliance, a predetermined distance in the extend direction, and to prevent further movement of the ball screw upon translating the predetermined distance.

  3. Ball Screw Actuator Including a Stop with an Integral Guide

    Science.gov (United States)

    Wingett, Paul T. (Inventor); Perek, John (Inventor); Geck, Kellan (Inventor)

    2015-01-01

    An actuator includes a housing assembly, a ball nut, a ball screw, and a ball screw stop. The ball nut is rotationally mounted in the housing assembly, is adapted to receive an input torque, and is configured, upon receipt thereof, to rotate and supply a drive force. The ball screw is mounted within the housing assembly and extends through the ball nut. The ball screw has a first end and a second end, and is coupled to receive the drive force from the ball nut. The ball screw is configured, upon receipt of the drive force, to selectively translate between a stow position and a deploy position. The ball screw stop is mounted on the ball screw to translate therewith and is configured to at selectively engage the housing assembly while the ball screw is translating, and engage the ball nut when the ball screw is in the deploy position.

  4. Dispersion in thermal plasma including arbitrary degeneracy and quantum recoil

    International Nuclear Information System (INIS)

    Mushtaq, A.; Melrose, D.B.

    2012-01-01

    The longitudinal response function for a thermal electron gas was calculated including two quantum effects exactly, degeneracy and the quantum recoil. The Fermi-Dirac distribution was expanded in powers of a parameter that is small in the non-degenerate limit and the response function was evaluated in terms of the conventional plasma dispersion function to arbitrary order in this parameter. The infinite sum was performed in terms of poly logarithms in the long-wavelength and quasi-static limits, giving results that apply for arbitrary degeneracy. The results were applied to the dispersion relations for Langmuir waves and to screening, reproducing known results in the non-degenerate and completely degenerate limits], and generalizing them to arbitrary degeneracy. The occupation number for the completely degenerate limit is shown. The importance of the results regarding to semiconductor plasmas were highlighted. (orig./A.B.)

  5. Optimage central organised image quality control including statistics and reporting

    International Nuclear Information System (INIS)

    Jahnen, A.; Schilz, C.; Shannoun, F.; Schreiner, A.; Hermen, J.; Moll, C.

    2008-01-01

    Quality control of medical imaging systems is performed using dedicated phantoms. As the imaging systems are more and more digital, adequate image processing methods might help to save evaluation time and to receive objective results. The developed software package OPTIMAGE is focusing on this with a central approach: On one hand, OPTIMAGE provides a framework, which includes functions like database integration, DICOM data sources, multilingual user interface and image processing functionality. On the other hand, the test methods are implemented using modules which are able to process the images automatically for the common imaging systems. The integration of statistics and reporting into this environment is paramount: This is the only way to provide these functions in an interactive, user-friendly way. These features enable the users to discover degradation in performance quickly and document performed measurements easily. (authors)

  6. One-dimensional central-force problem, including radiation reaction

    International Nuclear Information System (INIS)

    Kasher, J.C.

    1976-01-01

    Two equal masses of equal charge magnitude (either attractive or repulsive) are held a certain distance apart for their entire past history. AT t = 0 one of them is either started from rest or given an initial velocity toward or away from the other charge. When the Dirac radiation-reaction force is included in the force equation, our Taylor-series numerical calculations lead to two types of nonphysical results for both the attractive and repulsive cases. In the attractive case, the moving charge either stops and moves back out to infinity, or violates energy conservation as it nears collision with the fixed charge. For the repulsive charges, the moving particle either eventually approaches and collides with the fixed one, or violates energy conservation as it goes out to infinity. These results lead us to conclude that the Lorentz-Dirac equation is not valid for the one-dimensional central-force problem

  7. PASCAL for engineers: A course including OMEGASOFT PASCAL for microcomputers

    International Nuclear Information System (INIS)

    Tausch, L.A.

    1985-01-01

    These are the notes of a PASCAL course for controls engineers at CERN. The course starts with 'Standard Pascal' and includes OMEGASOFT Pascal, a powerful extension of Pascal towards real-time and systems applications. It demonstrates how a language such as Pascal, with adequate extensions for systems programming and embedded microprocessor-driven systems, can substantially increase the productivity of programmers and the reliability of their products. Also enhanced will be the legibility of the programs and their maintainability, since programming in Pascal automatically leads to autodocumentation. Simple examples show how OMEGASOFT-PASCAL can be used for efficient programming of embedded systems for real-time data acquisition and control using the MC6809 microprocessor. (orig.)

  8. Strategies for replacement of obsolete equipment - including reverse engineering

    International Nuclear Information System (INIS)

    Irish, C.S.

    2000-01-01

    The presentation shall detail the challenges facing nuclear power plants with the replacement of obsolete equipment and the strategies used to overcome those challenges. The presentation will outline the common equipment types which are either obsolete or are becoming obsolete, with a focus on safety related components. The four options of the obsolete equipment replacement philosophy will be presented with replacement examples from each of the options shown for discussion purposes. Detailed examples from each of the four obsolete equipment replacement options of: commercially available equivalent component; modification of a commercial available component; reverse engineering of the original component; and finally, design changes using a new component, shall be presented to evaluate the advantages and disadvantages of each option. The presentation will include the technical challenges, cost and schedule concerns for each of the four options. Emphasis will be placed on the technological challenges associated with replacing old and obsolete equipment. The following is a bullet list of the challenges which will be discussed: Missing, misleading or no information on the original component; Acquiring information from the original equipment manufacturer and the plant; Using a sample component for the replacement evaluation and or reverse engineering; and Reverse engineering old equipment with newly available discrete components. The presentation will include the equivalency documentation using the EPRI guidelines when replacing an original component with a different yet form, fit and functional equivalent component. The presentation will conclude with a discussion of the advantages and disadvantages of the replacement of the obsolete component with a form, fit and functional equivalent component vs. the replacement of the original component with a new component with today's technology. (author)

  9. Including all voices in international data-sharing governance.

    Science.gov (United States)

    Kaye, Jane; Terry, Sharon F; Juengst, Eric; Coy, Sarah; Harris, Jennifer R; Chalmers, Don; Dove, Edward S; Budin-Ljøsne, Isabelle; Adebamowo, Clement; Ogbe, Emilomo; Bezuidenhout, Louise; Morrison, Michael; Minion, Joel T; Murtagh, Madeleine J; Minari, Jusaku; Teare, Harriet; Isasi, Rosario; Kato, Kazuto; Rial-Sebbag, Emmanuelle; Marshall, Patricia; Koenig, Barbara; Cambon-Thomsen, Anne

    2018-03-07

    Governments, funding bodies, institutions, and publishers have developed a number of strategies to encourage researchers to facilitate access to datasets. The rationale behind this approach is that this will bring a number of benefits and enable advances in healthcare and medicine by allowing the maximum returns from the investment in research, as well as reducing waste and promoting transparency. As this approach gains momentum, these data-sharing practices have implications for many kinds of research as they become standard practice across the world. The governance frameworks that have been developed to support biomedical research are not well equipped to deal with the complexities of international data sharing. This system is nationally based and is dependent upon expert committees for oversight and compliance, which has often led to piece-meal decision-making. This system tends to perpetuate inequalities by obscuring the contributions and the important role of different data providers along the data stream, whether they be low- or middle-income country researchers, patients, research participants, groups, or communities. As research and data-sharing activities are largely publicly funded, there is a strong moral argument for including the people who provide the data in decision-making and to develop governance systems for their continued participation. We recommend that governance of science becomes more transparent, representative, and responsive to the voices of many constituencies by conducting public consultations about data-sharing addressing issues of access and use; including all data providers in decision-making about the use and sharing of data along the whole of the data stream; and using digital technologies to encourage accessibility, transparency, and accountability. We anticipate that this approach could enhance the legitimacy of the research process, generate insights that may otherwise be overlooked or ignored, and help to bring valuable

  10. Terrorism cover in France for property damage including nuclear risks

    International Nuclear Information System (INIS)

    Stanislas, A.

    2004-01-01

    The obligation to include terrorism cover in all Property Damage policies issued on the French Market is ruled by an Act of 1986 and introduced under Section R 126-2 of the French Code of Insurance. This section stipulates that Property Damage policies must provide cover for damage resulting from acts of terrorism, with the same deductible and the same limit than that of the other damage covered in the policy. Soon after the dramatic events of September 11, 2001 in the United States and although reinsurers worldwide restricted their offer of capacities, French insurers recognized that they had to maintain this global cover for the benefit of their insurers. After difficult discussions between insurers, reinsurers, brokers, risk managers and representatives of the State, the creation of a new Pool, backed with a State guarantee, was decided in less than three months. Effective January 1, 2002 and called Gestion d'Assurance et de Reassurance des Risques Attentats et Actes de Terrorisme (GAREAT), the Pool offers a multiple layers stop-loss cover for Property Damage only, i.e. excluding TPL policies. Considering that nuclear risks should be treated in the same way as other industrial risks, it was decided that they would be covered by GAREAT as well. In the meantime, by a Decree of December 28, 2001 modifying Section R 126-2, a special provision, aiming at reducing the limit and thus the price of this cover, was introduced in the Code. The purpose of this paper is to expose the present situation applying through GAREAT and, after two years of operation to discuss future developments, including other sources of capacity for the coverage of acts of terrorism in nuclear risks insurance.(author)

  11. Internet interventions for chronic pain including headache: A systematic review

    Directory of Open Access Journals (Sweden)

    Monica Buhrman

    2016-05-01

    Full Text Available Chronic pain is a major health problem and behavioral based treatments have been shown to be effective. However, the availability of these kinds of treatments is scarce and internet-based treatments have been shown to be promising in this area. The objective of the present systematic review is to evaluate internet-based interventions for persons with chronic pain. The specific aims are to do an updated review with a broad inclusion of different chronic pain diagnoses and to assess disability and pain and also measures of catastrophizing, depression and anxiety. A systematic search identified 891 studies and 22 trials were selected as eligible for review. Two of the selected trials included children/youth and five included individuals with chronic headache and/or migraine. The most frequently measured domain reflected in the primary outcomes was interference/disability, followed by catastrophizing. Result across the studies showed a number of beneficial effects. Twelve trials reported significant effects on disability/interference outcomes and pain intensity. Positive effects were also found on psychological variable such as catastrophizing, depression and anxiety. Several studies (n = 12 were assessed to have an unclear level of risk bias. The attrition levels ranged from 4% to 54% where the headache trials had the highest drop-out levels. However, findings suggest that internet-based treatments based on cognitive behavioural therapy (CBT are efficacious measured with different outcome variables. Results are in line with trials in clinical settings. Meta-analytic statistics were calculated for interference/disability, pain intensity, catastrophizing and mood ratings. Results showed that the effect size for interference/disability was Hedge's g = −0.39, for pain intensity Hedge's g = −0.33, for catastrophizing Hedge's g = −0.49 and for mood variables (depression Hedge's g = −0.26.

  12. Strategies for replacement of obsolete equipment, including reverse engineering

    International Nuclear Information System (INIS)

    Irish, C.S.

    2003-01-01

    The presentation shall detail the challenges facing nuclear power plants with the replacement of obsolete equipment and the strategies used to overcome those challenges. The presentation will outline the common equipment types which are either obsolete or are becoming obsolete, with a focus on safety related components. The four options of the obsolete equipment replacement philosophy will be presented with replacement examples from each of the options shown for discussion purposes. Detailed examples from each of the four obsolete equipment replacement options of, (1) commercially available equivalent component, (2) modification of a commercial available component, (3) reverse engineering of the original component and finally (4) design changes using a new component, shall be presented to evaluate the advantages and disadvantages of each option. The presentation will include the technical challenges, cost and schedule concerns for each of the four options. Emphasis will be placed on the technological challenges associated with replacing old and obsolete equipment. The following is a bullet list of the challenges which will be discussed: 1) Missing, misleading or no information on the original component. 2) Acquiring information from the original equipment manufacturer and the plant. 3) Using a sample component for the replacement evaluation and or reverse engineering. 4) Reverse engineering old equipment with newly available discrete components. The presentation will include the equivalency documentation using the EPRI guidelines when replacing an original component with a different yet form, fit and functional equivalent component. The presentation will conclude with a discussion of the advantages and disadvantages of the replacement of the obsolete component with a form, fit and functional equivalent component vs. the replacement of the original component with a new component with today's technology. (author)

  13. Including a learner with physical disabilities: stressful for teachers?

    Directory of Open Access Journals (Sweden)

    I. Eloff

    2002-08-01

    Full Text Available Learners with physical disabilities have been entering mainstream schools for some years now. Whereas early research on inclusive education necessitated a strong focus on the needs of the learners, there has also been a recent interest in the role of the teachers in inclusive education. By adopting constructivism as the paradigm for inquiry a study was undertaken to establish the stress factors for teachers who have to include a learner with a physical disability in their mainstream classes. The rationale for the study is threefold: i Learners with physical disabilities are entering mainstream schools increasingly, ii it is often assumed that inclusive education is too stressful for teachers to cope with, and iii related research has shown that increased contact with individuals with disabilities has a positive effect on attitudes towards individuals with disabilities. In accordance with the dialectical methodology of constructivism, the Teacher Stress and Coping Questionnaire and in-depth interviews were utilised to establish the stress factors and the extent of the stress factors that may be present. The aim of the constructivist inquiry process is to promote understanding and reconstruction. In this article the quantitative results indicate overall low or non-existent levels of stress in teachers who have to include a learner with a physical disability, and the results therefore contribute to our understanding of this situation. The qualitative results reconstruct the meanings that these teachers attach to the inclusion of a learner with a physical disability and reveal some albeit limited concerns about the communication processes between parents and teachers and a perceived lack of pre-service training.

  14. Extending Vulnerability Assessment to Include Life Stages Considerations.

    Science.gov (United States)

    Hodgson, Emma E; Essington, Timothy E; Kaplan, Isaac C

    2016-01-01

    Species are experiencing a suite of novel stressors from anthropogenic activities that have impacts at multiple scales. Vulnerability assessment is one tool to evaluate the likely impacts that these stressors pose to species so that high-vulnerability cases can be identified and prioritized for monitoring, protection, or mitigation. Commonly used semi-quantitative methods lack a framework to explicitly account for differences in exposure to stressors and organism responses across life stages. Here we propose a modification to commonly used spatial vulnerability assessment methods that includes such an approach, using ocean acidification in the California Current as an illustrative case study. Life stage considerations were included by assessing vulnerability of each life stage to ocean acidification and were used to estimate population vulnerability in two ways. We set population vulnerability equal to: (1) the maximum stage vulnerability and (2) a weighted mean across all stages, with weights calculated using Lefkovitch matrix models. Vulnerability was found to vary across life stages for the six species explored in this case study: two krill-Euphausia pacifica and Thysanoessa spinifera, pteropod-Limacina helicina, pink shrimp-Pandalus jordani, Dungeness crab-Metacarcinus magister and Pacific hake-Merluccius productus. The maximum vulnerability estimates ranged from larval to subadult and adult stages with no consistent stage having maximum vulnerability across species. Similarly, integrated vulnerability metrics varied greatly across species. A comparison showed that some species had vulnerabilities that were similar between the two metrics, while other species' vulnerabilities varied substantially between the two metrics. These differences primarily resulted from cases where the most vulnerable stage had a low relative weight. We compare these methods and explore circumstances where each method may be appropriate.

  15. Optimizing cell viability in droplet-based cell deposition

    NARCIS (Netherlands)

    Hendriks, Jan; Visser, C.W.; Henke, S.J.; Leijten, Jeroen Christianus Hermanus; Saris, Daniël B.F.; Sun, Chao; Lohse, Detlef; Karperien, Hermanus Bernardus Johannes

    2015-01-01

    Biofabrication commonly involves the use of liquid droplets to transport cells to the printed structure. However, the viability of the cells after impact is poorly controlled and understood, hampering applications including cell spraying, inkjet bioprinting, and laser-assisted cell transfer. Here,

  16. Universal health coverage in 'One ASEAN': are migrants included?

    Science.gov (United States)

    Guinto, Ramon Lorenzo Luis R; Curran, Ufara Zuwasti; Suphanchaimat, Rapeepong; Pocock, Nicola S

    2015-01-01

    As the Association of South East Asian Nations (ASEAN) gears toward full regional integration by 2015, the cross-border mobility of workers and citizens at large is expected to further intensify in the coming years. While ASEAN member countries have already signed the Declaration on the Protection and Promotion of the Rights of Migrant Workers, the health rights of migrants still need to be addressed, especially with ongoing universal health coverage (UHC) reforms in most ASEAN countries. This paper seeks to examine the inclusion of migrants in the UHC systems of five ASEAN countries which exhibit diverse migration profiles and are currently undergoing varying stages of UHC development. A scoping review of current migration trends and policies as well as ongoing UHC developments and migrant inclusion in UHC in Indonesia, Malaysia, Philippines, Singapore, and Thailand was conducted. In general, all five countries, whether receiving or sending, have schemes that cover migrants to varying extents. Thailand even allows undocumented migrants to opt into its Compulsory Migrant Health Insurance scheme, while Malaysia and Singapore are still yet to consider including migrants in their government-run UHC systems. In terms of predominantly sending countries, the Philippines's social health insurance provides outbound migrants with portable insurance yet with limited benefits, while Indonesia still needs to strengthen the implementation of its compulsory migrant insurance which has a health insurance component. Overall, the five ASEAN countries continue to face implementation challenges, and will need to improve on their UHC design in order to ensure genuine inclusion of migrants, including undocumented migrants. However, such reforms will require strong political decisions from agencies outside the health sector that govern migration and labor policies. Furthermore, countries must engage in multilateral and bilateral dialogue as they redefine UHC beyond the basis of

  17. Mechanical behaviour of cracked welded structures including mismatch effect

    International Nuclear Information System (INIS)

    Hornet, P.

    2002-01-01

    The most important parameters for predicting more precisely the fracture behaviour of welded structures have been identified. In particular, the plasticity development at the crack tip in the ligament appeared as a major parameter to evaluate the yield load of such a complex structure. In this way defect assessments procedures have been developed or modified to take into account the mismatch effect that is to say the mechanical properties of the different material constituting the weld joint. This paper is a synthesis of the work done in the past at Electricite de France on this topic in regards with other work done in France or around the World. The most important parameters which control the plasticity development at the crack tip and so mainly influence the fracture behaviour of welded structures are underlined: the mismatch ratio (weld to base metal yield strength ratio), the mismatch ratio (weld to base metal yield strength ratio), the ligament size and the weld width. Moreover, commonly used fracture toughness testing procedures developed in case of homogeneous specimens cannot be used in a straight forward manner and so has to be modified to take into account the mismatch effect. Number or defect assessment procedures taking into account the mismatch effect by considering the yield load of the welded structure are shortly described. Then, the 'Equivalent Material Method' developed at EDF which allows a good prediction of the applied J-Integral at the crack tip is more detailed. This procedure includes not only both weld and base metal yield strength, the structure geometry, the crack size and the weld dimension using the yield load of the real structures but also includes the effect of both weld and base metal strain hardening exponents. Some validations of this method are proposed. Finally, the ability of finite element modelling to predict the behaviour of such welded structures is demonstrated by modelling real experiments: crack located in the middle of

  18. Designing monitoring programs for chemicals of emerging concern in potable reuse ⋯ What to include and what not to include?

    KAUST Repository

    Drewes, Jorg; Anderson, Paul D.; Denslow, Nancy D.; Olivieri, Adam W.; Schlenk, Daniel K.; Snyder, Shane A.; Maruya, Keith

    2012-01-01

    This study discussed a proposed process to prioritize chemicals for reclaimed water monitoring programs, selection of analytical methods required for their quantification, toxicological relevance of chemicals of emerging concern regarding human health, and related issues. Given that thousands of chemicals are potentially present in reclaimed water and that information about those chemicals is rapidly evolving, a transparent, science-based framework was developed to guide prioritization of which compounds of emerging concern (CECs) should be included in reclaimed water monitoring programs. The recommended framework includes four steps: (1) compile environmental concentrations (e.g., measured environmental concentration or MEC) of CECs in the source water for reuse projects; (2) develop a monitoring trigger level (MTL) for each of these compounds (or groups thereof) based on toxicological relevance; (3) compare the environmental concentration (e.g., MEC) to the MTL; CECs with a MEC/MTL ratio greater than 1 should be prioritized for monitoring, compounds with a ratio less than '1' should only be considered if they represent viable treatment process performance indicators; and (4) screen the priority list to ensure that a commercially available robust analytical method is available for that compound. © IWA Publishing 2013.

  19. Designing monitoring programs for chemicals of emerging concern in potable reuse--what to include and what not to include?

    Science.gov (United States)

    Drewes, J E; Anderson, P; Denslow, N; Olivieri, A; Schlenk, D; Snyder, S A; Maruya, K A

    2013-01-01

    This study discussed a proposed process to prioritize chemicals for reclaimed water monitoring programs, selection of analytical methods required for their quantification, toxicological relevance of chemicals of emerging concern regarding human health, and related issues. Given that thousands of chemicals are potentially present in reclaimed water and that information about those chemicals is rapidly evolving, a transparent, science-based framework was developed to guide prioritization of which compounds of emerging concern (CECs) should be included in reclaimed water monitoring programs. The recommended framework includes four steps: (1) compile environmental concentrations (e.g., measured environmental concentration or MEC) of CECs in the source water for reuse projects; (2) develop a monitoring trigger level (MTL) for each of these compounds (or groups thereof) based on toxicological relevance; (3) compare the environmental concentration (e.g., MEC) to the MTL; CECs with a MEC/MTL ratio greater than 1 should be prioritized for monitoring, compounds with a ratio less than '1' should only be considered if they represent viable treatment process performance indicators; and (4) screen the priority list to ensure that a commercially available robust analytical method is available for that compound.

  20. Designing monitoring programs for chemicals of emerging concern in potable reuse ⋯ What to include and what not to include?

    KAUST Repository

    Drewes, Jorg

    2012-11-01

    This study discussed a proposed process to prioritize chemicals for reclaimed water monitoring programs, selection of analytical methods required for their quantification, toxicological relevance of chemicals of emerging concern regarding human health, and related issues. Given that thousands of chemicals are potentially present in reclaimed water and that information about those chemicals is rapidly evolving, a transparent, science-based framework was developed to guide prioritization of which compounds of emerging concern (CECs) should be included in reclaimed water monitoring programs. The recommended framework includes four steps: (1) compile environmental concentrations (e.g., measured environmental concentration or MEC) of CECs in the source water for reuse projects; (2) develop a monitoring trigger level (MTL) for each of these compounds (or groups thereof) based on toxicological relevance; (3) compare the environmental concentration (e.g., MEC) to the MTL; CECs with a MEC/MTL ratio greater than 1 should be prioritized for monitoring, compounds with a ratio less than \\'1\\' should only be considered if they represent viable treatment process performance indicators; and (4) screen the priority list to ensure that a commercially available robust analytical method is available for that compound. © IWA Publishing 2013.